bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enantioselective chromatography and molecular modeling of novel aryloxyaminopropan‐2‐ols with the alkyl carbamate function
Authors: Navrátilová Hana , Opatřilová Radka , Kříž Zdeněk , Koča Jaroslav 
Published: February 2004

AbstractA series of different racemic aryloxyaminopropan‐2‐ol derivatives 1a‐d–3a‐d with potential β‐adrenergic blocking effects related to propanolol 4 and atenolol 5 was resolved by HPLC using Chiralcel OD‐H and Chiralpak AD as chiral stationary phases. Mobile phases consisted of a hexane/alcohol (propan‐2‐ol or ethanol) mixture doped with a modifier (DEA or TFA). The retention behavior of the compounds depended on the position of the carbamate attached to the aryloxy moiety and on the length of the alkyl residue in the carbamate. Enantiomers of the title compounds were baseline separated with the separation factors α and resolutions Rs varying in the range of 1.34–4.55 and 1.50–10.65, respectively. The chromatographic systems developed can be used for the determination of the enantiomeric purity of the title compounds. Molecular modelling using empirical molecular mechanics and ab initio quantum chemistry methods provided low‐energy structures in which sites of potential interactions responsible for retention behavior and chiral recognition could be identified. Chirality 16:139–146, 2004. © 2004 Wiley‐Liss, Inc.
A randomized controlled trial of darbepoetin alfa administered as a fixed or weight‐based dose using a front‐loading schedule in patients with anemia who have nonmyeloid malignancies
Authors: Hesketh Paul J. , Arena Francis , Patel Dhimant , Austin Matt , D'Avirro Paul , Rossi Gregory , Colowick Alan , Schwartzberg Lee 
Published: February 2004

AbstractBACKGROUNDThe effect of using fixed versus weight‐based doses for erythropoietic agents has not been reported previously. To investigate this issue, the authors conducted a randomized Phase II study of darbepoetin alfa administered as either a fixed dose or a weight‐based dose using an accelerated correction and maintenance dosing regimen (front‐loading).METHODSDuring the correction phase, patients with anemia (hemoglobin < 11.0 g/dL) who had nonmyeloid malignancies and who were receiving chemotherapy were given darbepoetin alfa at a fixed dose of 325μg (n = 122) or at a weight‐based dose of 4.5 μg/kg (n = 120) once weekly until they achieved a hemoglobin concentration ≥ 12.0 g/dL. Patients then received darbepoetin alfa (325 μg or 4.5 μg/kg) once every 3 weeks for the remainder of the 16‐week treatment period (maintenance phase).RESULTSDarbepoetin alfa resulted in high Kaplan–Meier rates of hematopoietic response (≥ 2 g/dL increase from the baseline level or a hemoglobin level ≥ 12 g/dL) in both the fixed‐dose group (86%; 95% confidence interval [95% CI], 78– 94%) and the weight‐based dose group (84%; 95% CI, 76–92%). The median time to hematopoietic response was 34 days (95% CI, 28–44 days) for the fixed‐dose group and 36 days (95% CI, 30–45 days) for the weight‐based dose group. Hemoglobin concentrations were maintained at target levels for up to 16 weeks in both groups. Darbepoetin alfa was well tolerated, and no clinically significant differences between fixed doses and weight‐based doses were observed.CONCLUSIONSDarbepoetin alfa was effective when administered as either a fixed dose or a weight‐based dose using a front‐loading approach to rapidly correct anemia and effectively maintain hemoglobin levels in patients with anemia who had malignant disease. Cancer 2004;100:859–68. © 2004 American Cancer Society.
Adjuvant therapy of osteosarcoma—A Phase II trial
Authors: Zalupski Mark M. , Rankin Cathryn , Ryan James R. , Lucas David R. , Muler Jeffrey , Lanier Keith S. , Budd George Thomas , Biermann J. Sybil , Meyers Frederick J. , Antman Karen 
Published: February 2004

AbstractBACKGROUNDThe objective of this study was to estimate the time to treatment failure and survival rate of the three‐drug combination of doxorubicin, cisplatin, and ifosfamide as primary and postoperative, adjunctive treatment for teenagers and adults with osteosarcoma (OS).METHODSSixty‐three eligible patients with nonmetastatic OS of the extremities were registered from 24 institutions from February, 1992 through December, 1996. Chemotherapy was comprised of doxorubicin at a dose of 75 mg/m2 and cisplatin at a dose of 120 mg/m2, alternating with doxorubicin at a dose of 50 mg/m2 and ifosfamide at a dose of 8 g/m2. Four cycles were given prior to surgical resection, and four cycles were given after surgery. Outcome measures included the time to treatment failure, overall survival, toxicity, and centralized assessment of tumor necrosis.RESULTSThirty‐one of 63 eligible patients died, for a 5‐year overall survival rate of 58% (95% confidence interval [95% CI], 46–71%). The median time to treatment failure was 19 months (95% CI, 12–41 months). A good pathologic response (≥ 90% necrosis) to neoadjuvant chemotherapy was observed in 48% of patients who underwent surgery. There was no correlation noted between response to neoadjuvant chemotherapy and patient outcome. Grade 4 hematologic toxicities were frequent (89%), although serious nonhematologic toxicities other than nausea and emesis were uncommon.CONCLUSIONSThe regimen and schedule used in the current study did not improve outcomes compared with prior trials of doxorubicin and cisplatin alone. New, more effective drugs are needed for the treatment of patients with OS. The identification and utilization of molecular markers to predict outcome and response to therapy would facilitate clinical management, limiting exposure to toxic therapies for patients with favorable molecular profiles and identifying those patients who may fail with current approaches as candidates for clinical trials. Cancer 2004;100:818–25. © 2004 American Cancer Society.
Quality of life and pain relief during treatment with calcitriol and docetaxel in symptomatic metastatic androgen‐independent prostate carcinoma
Authors: Beer Tomasz M. , Eilers Kristine M. , Garzotto Mark , Hsieh Yi‐Ching , Mori Motomi 
Published: February 2004

AbstractBACKGROUNDThe current study evaluated the analgesic activity and impact on quality of life (QOL) of a new chemotherapy regimen of calcitriol and docetaxel in men with androgen‐independent prostate carcinoma.METHODSAnalgesic response was defined as a 2‐point reduction on the Present Pain Intensity (PPI) scale (or compete relief if baseline PPI was 1) without an increase in analgesic use or a 50% decrease in analgesic medication use without an increase in pain, maintained for ≥ 4 weeks. Pain, pain medication consumption, and QOL (measured by the European Organization for Research and Treatment of Cancer QLQ‐C30) were evaluated every 4 weeks.RESULTSTreatment resulted in an analgesic response in 14 of 29 evaluable patients (48%; 95% confidence interval [95% CI], 30–67%). The median time to symptomatic progression in the 14 patients who met criteria for analgesic response was 41 weeks (95% CI, 26–56 weeks). Worsening in physical and role functioning, fatigue, appetite, and global health status and improvement in constipation were detected using the QLQ‐C30 QOL questionnaire.CONCLUSIONSSignificant analgesic activity was demonstrated, although worsening in several QOL domains was observed in a patient population with relatively low pain intensity (median PPI, 2). Cancer 2004;100:758–63. © 2004 American Cancer Society.
The natural history of incidentally detected small renal masses
Authors: Volpe Alessandro , Panzarella Tony , Rendon Ricardo A. , Haider Masoom A. , Kondylis Filippos I. , Jewett Michael A. S. 
Published: February 2004

AbstractBACKGROUNDThe incidence of renal cell carcinoma (RCC) is increasing, largely due to the widespread use of cross‐sectional imaging. Most renal tumors are detected incidentally as small, asymptomatic masses. To study their natural history, the authors prospectively followed a series of patients with this type of lesion who were unsuited for or refused surgery.METHODSTwenty‐nine patients with 32 masses that measured < 4 cm in greatest dimension (25 solid masses and 7 complex cystic masses) were studied. The primary outcome was tumor size, which was calculated as volume over time. All patients were followed with serial abdominal imaging, and each mass had at least three follow‐up measurements. The median follow‐up was 27.9 months (range, 5.3–143.0 months).RESULTSOverall, the average growth rate did not differ statistically from zero growth (P = 0.09; 95% confidence interval, − 0.005–0.2 cm per year) and was not associated with either initial size (P = 0.28) or mass type (P = 0.41). Seven masses (22%) reached 4 cm in greatest dimension after 12–85 months of follow‐up. Eight masses (25%) doubled their volumes within 12 months. Overall, 11 masses (34%) fulfilled 1 of these 2 criteria of rapid growth. Nine tumors were removed surgically after an average of 3.1 years of follow‐up because it was believed that they were growing fast. No patient had disease progression.CONCLUSIONSApproximately one‐third of small renal masses that are presumed RCCs grow if they are managed conservatively and are followed with serial imaging. The growth rate is slow or undetectable in the majority of patients. These observations raise the possibility of a period of initial observation in selected patients, particularly the elderly or infirm. Cancer 2004;100:738–45. © 2004 American Cancer Society.
Mammalian target of rapamycin inhibition as therapy for hematologic malignancies
Authors: Panwalkar Amit , Verstovsek Srdan , Giles Francis J. 
Published: February 2004

AbstractThe mammalian target of rapamycin (mTOR) is a downstream effector of the phosphatidylinositol 3‐kinase (PI3K)/Akt (protein kinase B) signaling pathway, which mediates cell survival and proliferation. mTOR regulates essential signal‐transduction pathways, is involved in the coupling of growth stimuli with cell cycle progression, and initiates mRNA translation in response to favorable nutrient environments. mTOR is involved in regulating many aspects of cell growth, including membrane traffic, protein degradation, protein kinase C signaling, ribosome biogenesis, and transcription. Because mTOR activates both the 40S ribosomal protein S6 kinase (p70s6k) and the eukaryotic initiation factor 4E‐binding protein 1, its inhibitors cause G1‐phase cell cycle arrest. Inhibitors of mTOR also prevent cyclin dependent kinase (CDK) activation, inhibit retinoblastoma protein phosphorylation, and accelerate the turnover of cyclin D1, leading to a deficiency of active CDK4/cyclin D1 complexes, all of which may help cause G1‐phase arrest. It is known that the phosphatase and tensin homologue tumor suppressor gene (PTEN) plays a major role in embryonic development, cell migration, and apoptosis. Malignancies with PTEN mutations, which are associated with constitutive activation of the PI3K/Akt pathway, are relatively resistant to apoptosis and may be particularly sensitive to mTOR inhibitors. Rapamycin analogs with relatively favorable pharmaceutical properties, including CCI‐779, RAD001, and AP23573, are under investigation in patients with hematologic malignancies. Cancer 2004;100:657–66. © 2004 American Cancer Society.
Clinical significance of bone marrow microinvolvement in nonsmall cell lung carcinoma
Authors: Hsu Chung‐Ping , Shai Sen‐Ei , Hsia Jiun‐Yi , Chen Chih‐Yi 
Published: February 2004

AbstractBACKGROUNDThe divergences in the clinical significance of bone marrow microinvolvement (BMM) in patients with nonsmall cell lung carcinoma (NSCLC) necessitated a long‐term large series study.METHODSBetween March 1997 and June 2001, the authors analyzed 212 bone marrow specimens (from the posterior iliac crest) taken from patients with NSCLC before surgery. The degree of tumor differentiation included well differentiated carcinoma in 12 Patients, moderately differentiated carcinoma in 112 Patients, and poorly differentiated carcinoma in 68 Patients. The pTNM staging (according the the criteria of the American Joint Committee on Cancer) included Stage IA in 8 patients, Stage IB in 70 patients, Stage IIB in 36 patients, Stage IIIA in 54 patients, Stage IIIB in 14 patients, and Stage IV in 10 patients. The specimens were evaluated by immunohistochemical staining with antihuman cytokeratin AE1/AE3, Ber‐EP4, and clone MNF116 mixed solution to detect the presence of malignant epithelial cells in the bone marrow.RESULTSPositive results were observed in 66 patients (34.4%). The occurrence of BMM was not found to be related to patient age, gender, cell type, or TNM status. The 5‐year disease‐free survival rates were 44.9% and 40.5% in BMM‐negative and BMM‐positive patients, respectively (P = 0.3797). The 5‐year cumulative survival rates were 43.5% and 44.0% in BMM‐negative and BMM‐positive patients, respectively (P = 0.4262). Multivariate analysis failed to demonstrate BMM as an independent prognostic factor (P = 0.1817).CONCLUSIONSThe results of the current study showed that although BMM was observed frequently in patients with NSCLC, regardless of tumor stage and pathologic types, its occurrence was not a good predictor of long‐term prognosis. Cancer 2004;100:794–800. © 2004 American Cancer Society.
Therapeutic efficacy of once‐daily oral administration of a Kunitz‐type protease inhibitor, bikunin, in a mouse model and in human cancer
Authors: Kobayashi Hiroshi , Yagyu Tatsuo , Inagaki Kiyokazu , Kondo Toshiharu , Suzuki Mika , Kanayama Naohiro , Terao Toshihiko 
Published: February 2004

AbstractBACKGROUNDBikunin, a Kunitz‐type protease inhibitor, specifically inhibits tumor invasion and metastasis.METHODSThe authors initially evaluated the therapeutic efficacy of once‐daily oral administration of different doses of bikunin against human ovarian carcinoma HRA cells growing in the peritonea of nude mice. For the in vivo studies, female 7‐week‐old nude mice were randomized to 1 of 4 groups: bikunin‐treated groups (n = 9 in each group) received 3, 10, or 30 μg/g body weight per day bikunin for 7 days via gastrointestinal gavage, and a control group (n = 9) received the vehicle solution (phosphate‐buffered saline) via gastrointestinal gavage. On Day 9, the abdominal cavity was examined by two observers who were blinded to treatment.RESULTSAfter oral administration, intact bikunin was detectable in mouse serum specimens at 3 and 6 hours. This was followed by a decline at 12 hours. The mice given bikunin at the highest dose level had a 40% decrease in tumor load. The highest uptake in the tumor was obtained with [125I]bikunin 12 hours postadministration. No effect on either food intake or body weight was observed in the treated versus sham groups. The current study was the first to report the potent activity of once‐daily oral administration of bikunin against ovarian carcinoma. Next, the authors performed a Phase I trial to determine the maximum‐tolerated dose (MTD) and safety of a once‐daily oral administration schedule. The indication was locally advanced uterine cervical carcinoma after definitive treatment. An escalating dose (3, 10, and 30 mg/kg per day) of bikunin was administered orally to nine patients for 7 days. There were no dose‐limiting toxicities and the MTD of the bikunin schedule was not defined. The authors also obtained preliminary data on its effect on urokinase‐type plasminogen activator expression at the highest dose level.CONCLUSIONSOnce‐daily oral administration of bikunin was found to be safe in humans and exhibited signs of biologic activity. Cancer 2004;100:869–77. © 2004 American Cancer Society.
Impact of hydroelectric power releases on the morphology and sedimentology of the bed of the Warche River (Belgium)
Authors: Assani A. A. , Petit F. 
Published: February 2004

AbstractThe Butgenbach dam on the Warche River was built in 1932 in order to maintain a sufﬁcient supply of water to the Robertville reservoir situated 7 km downstream, for the production of hydroelectricity. During winter months, releases are made almost every day from the Butgenbach dam. From a hydrological point of view, this has resulted in signiﬁcantly reducing the number of discharges that are higher than bankfull. Despite the reduction in peak discharge, there is a signiﬁcant increase in the number of efﬁcient discharges (0·6 bankfull). The impacts of these hydrological modiﬁcations on the bed morphology and sedimentology below the Butgenbach dam have been studied and the following geomorphological modiﬁcations have been identiﬁed: a doubling of the width of the channel in 45 years, a reduction in the number of rifﬂes and pools, an increase in the number of gravel bars and islets and an increase in bedrock outcrops in the channel. Moreover, the ﬁnest bed particles are mobilized by the almost daily releases, inducing a signiﬁcant increase in bed‐material size sorting. The reduction of sinuosity and the disappearance of bed differentiation and rifﬂe/pool sequences have produced a diminution of bed roughness and an increase of the competence of the river. Thus relatively small ﬂoods can remove the armoured layer. Copyright © 2003 John Wiley & Sons, Ltd.
Tilting neotectonics of the Guadiamar drainage basin, SW Spain
Authors: Salvany Josep M. 
Published: February 2004

AbstractThe Guadiamar river ﬂows from the southern Iberian Massif to the Guadalquivir foreland basin, SW Spain. Its drainage basin displays asymmetries in the stream network, the arrangement of alluvial terraces and the conﬁguration of the trunk river valley. The stream network asymmetry was studied using morphometric measures of transverse topographic sym‐metry, asymmetry factor and drainage basin shape. The alluvial terraces were studied through the lithologic logs of more than a hundred boreholes and ﬁeld mapping. The morphometric methods demonstrate a regional tectonic tilting toward the SSE, causing both the migration of the Guadiamar river toward the east and the migration of the Guadiamar tributaries toward the southwest. As a consequence of the Guadiamar river migration, an asymmetric valley developed, with a steep eastern margin caused by river dissection, and a gentle western margin where the main alluvial deposits are found. The ages obtained using the 14C analysis of samples from several alluvial deposits show that the river migration, and thus tilting, has occurred during the Holocene as well as earlier in the Quaternary. This interpretation revises the Guadiamar longitudinal fault assumed by previous studies. Copyright © 2003 John Wiley & Sons, Ltd.
Drainage basin sensitivity to tectonic and climatic forcing: implications of a stochastic model for the role of entrainment and erosion thresholds
Authors: Tucker Gregory E. 
Published: February 2004

AbstractLong‐term average rates of channel erosion and sediment transport depend on the frequency–magnitude characteristics of ﬂood ﬂows that exceed an erosion threshold. Using a Poisson model for rainfall and runoff, analytical solutions are developed for average rates of stream incision and sediment transport in the presence of such a threshold. Solutions are derived and numerically tested for three erosion/transport formulas: the Howard–Kerby shear‐stress incision model, the Bridge–Dominic sediment transport model, and a generic shear‐stress sediment transport model. Results imply that non‐linearity resulting from threshold effects can have a ﬁrst‐order impact on topography and patterns of dynamic response to tectonic and climate forcing. This non‐linearity becomes signiﬁcant when fewer than about half of ﬂood events are capable of detaching rock or sediment. Predicted morphology and uplift‐gradient scaling is more closely consistent with observations and laboratory experiments than conventional slope‐linear or shear‐linear erosion laws. These results imply that particle detachment thresholds are not details that can be conveniently ignored in long‐term landscape evolution models. Copyright © 2004 John Wiley & Sons, Ltd.
Estimation of debris‐flow magnitude in the Eastern Italian Alps
Authors: Marchi Lorenzo , D'Agostino Vincenzo 
Published: February 2004

AbstractThe estimation of debris‐ﬂow magnitude is an essential step in the assessment of debris‐ﬂow hazard. Although different methods have been developed for the assessment of debris‐ﬂow magnitude, this is still a difﬁcult task because of the complexity of ﬂow processes and the lack of data to test estimation procedures in many mountainous regions. Data on debris‐ﬂow magnitude from 127 basins in the Eastern Italian Alps have been collected from scientiﬁc and technical journals, technical reports, historical documents gathered from local archives, and ﬁeld surveys. These data were used to develop and test different predictive approaches, encompassing regression equations, geomorphological surveys and probabilistic analysis of time series. Regression techniques were used to correlate debris‐ﬂow magnitude to morphometric parameters and geological characteristics of the basins. Values of the channel debris yield rate (contribution per unit length of channel), proposed in the literature, were compared with data from the study area for identifying reference values for channel stretches of different morphological characteristics. Although limited to the few basins in which sufﬁcient data were available, the probabilistic analysis of time series of debris‐ﬂow magnitude provides indications about the relations between magnitude and frequency of debris ﬂows. Some observations about the capability and drawbacks of considered methods are presented and the combined use of different approaches for the estimation of debris‐ﬂow magnitude is suggested. Copyright © 2004 John Wiley & Sons, Ltd.
Landslide incidence zonation in the Rio Mendoza valley, Mendoza Province, Argentina
Authors: Moreiras Stella M. 
Published: February 2004

AbstractThis paper presents a landslide incidence zonation map showing the percentage of underlying material involved in mass‐movement processes in the Rio Mendoza valley, Argentina. The landslide incidence zonation map was derived from an inventory map of landslides and reveals that many areas of the Rio Mendoza valley are implicated in this kind of process. A correlation has been found between the occurrence of landslides, earthquakes, and rainfall. The relation between lithology and landslides is clear: areas covered by friable sedimentary and volcanic rocks of the Choiyoi Group are prone to debris ﬂows and complex landslides. The slope map has been ranked and a general relation between slope and type of event is shown. Falls commonly develop in high‐angle slopes. Copyright © 2004 John Wiley & Sons, Ltd.
A homodyne five‐port network analyzer operating in the W‐frequency band
Authors: Chahine S. Abou , Huyart B. 
Published: February 2004

AbstractThis paper presents a homodyne five‐port network analyzer operating at 94 GHz using a single five‐port junction. The homodyne detection is realized using a PIN diode amplitude modulator and an AC detection technique. The obtained results show that the system can operate at very low power with no need for detector linearization. The proposed system as well as the exact equations in the two operating modes—reflection and transmission—are described. New calibration procedures, with and without matched loads, are proposed for the two operating modes. Practical measurements, in reflection as well as in transmission, prove the validity and the high efficiency of the system. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 444–448, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20001