bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparative Study of Samarium-153-Ethylenediaminetetramethylene Phosphonic Acid with Pamidronate Disodium in the Treatment of Patients with Painful Metastatic Bone Cancer
Authors: Wang Rong Fu , Zhang Chun Li , Zhu Shou Li , Zhu Mei 
Published: April 2003

<i>Objective:</i> To assess the therapeutic efficacy and toxicity of samarium-153-ethylenediaminetetramethylene phosphonic acid <sup>(153</sup>Sm-EDTMP) and pamidronate disodium in patients with painful metastatic bone cancer. <i>Subjects and Methods:</i> Eighteen patients with histopathologically confirmed malignancy and multifocal bone metastases were randomized into two equal groups of 9 patients each. Group A was treated with <sup>153</sup>Sm-EDTMP, while group B was treated with pamidronate disodium. The pain score for each patient was recorded before and after therapy using visual analogue scales that graded both the intensity and frequency of the bone pain. Therapeutic response was classified as inefficient, mild, effective and excellent. <i>Results:</i> Pain score in each group prior to therapy was more than 6. In group A, 2 (22.2%) and 7 (77.8%) cases showed mild and effective response, respectively. The therapeutic efficacy of <sup>153</sup>Sm-EDTMP was adjudged to be 77.8%. Transient myelosuppression was generally mild and reversible with white blood cells and platelets recovering after 6 weeks. In group B, palliative response in 4 cases (44.4%) was inefficient, in 1 case (11.1%) mild, in 3 cases (33.3%) effective and in 1 case (11.1%) excellent, with a therapeutic efficacy of 44.4% for pamidronate disodium. No hematological toxicity was noted. <i>Conclusion:</i> The data showed that the therapeutic efficacy of <sup>153</sup>Sm-EDTPM was higher than that of pamidronate disodium (for pain relief maintained more than 3 weeks) and its incidence of blood toxicity was also higher than that of pamidronate disodium.
Immunomodulatory Effects of IL-12 in Relation to the Pineal Endocrine Function in Metastatic Cancer Patients
Authors: Lissoni Paolo , Rovelli Franco , Giani Luisa , Fumagalli Luca , Mandalà Mario 
Published: April 2003

In addition to IL-2, IL-12 would constitute one of the most promising cytokines in the treatment of human neoplasms. IL-2 has been proven to induce in vitro and in vivo several evident changes in the secretion of cytokines and various other immunoinflammatory substances. In contrast, very litte data are available about the immune effects of IL-12 in humans. The present study was carried out to investigate the in vivo immunoinflammatory effects of IL-12 by analyzing the secretions of neopterin, soluble IL-2 receptor (SIL-2R), tumor necrosis factor α (TNF), IL-2 and IL-6 in relation to the neuroendocrine function of the pineal gland, which is one of the most important organs involved in neuroimmunomodulation. Pineal endocrine function was investigated by evaluating the whole daily urinary excretion of the main catabolite of its hormone melatonin, 6-sulfatoxymelatonin (6-MTS). The study was performed on metastatic renal cell cancer patients. Each course of IL-12 consisted of 1.25 µg/kg b.w. subcutaneously in the morning once a week for 3 consecutive weeks. The study evaluated 10 IL-12 courses. Mean serum levels of neopterin, SIL-2R and TNF significantly increased in response to IL-12, whereas no significant change occurred in IL-6 and IL-2 mean concentrations. Finally, 6-MTS urinary excretion was significantly reduced by IL-12 injection, particularly during the dark phase of the day. This preliminary study would suggest that IL-12 may induce important changes in the in vivo immunoinflammatory response. Moreover, IL-12 administration would suppress pineal endocrine activity, thus confirming its previously suggested involvement in the neuroimmunomodulatory processes. Because of the fundamental role of the pineal gland in neuroimmunomodulation, IL-12-induced immune variations could depend at least in part on its action at central neuroendocrine sites.
Micromolar A and B Blood Group Active Trisaccharides Abolish Human Complement Haemolytic Activity Assayed by Erythrocytes
Authors: Bakács Tibor , Szabó Miklós , Varga László , Mushens Rosey , Mehrishi Jitendra N. , Lutz Hans U. , Merry Tony H. , Tusnády Gábor 
Published: April 2003

<i>Background:</i> At present, there is really no satisfactory treatment of severe haemolytic transfusion reactions involving the ABO system other than the use of steroids that at best are palliative in their effects. In contrast, the use of micromolar concentrations of A or B blood group active trisaccharides that are inexpensive and readily available may prevent lysis by generating soluble immune complexes (ICs) that consume complement. The purpose of this study was to determine the total lytic activity of human serum and to estimate the extent to which trisaccharides can exhaust this capacity. <i>Methods:</i> We measured complement consumption by (ICs) formed between anti-blood group antibodies and A or B blood group active sugars on erythrocytes (solid phase) or soluble components carrying trisaccharides (fluid phase) in AB serum. A direct complement-mediated lysis (DCL) assay measured the solid-phase reaction and an indirect complement consumption assay (CCA) allowed determination of the fluid-phase reaction. In CCA, the residual lytic activity of AB serum was measured following preincubation with various ICs. <i>Results:</i> Based on over 4000 data points a new mathematical model of complement consumption was formulated. Its predictions deviated by less than 6% in DCL and 9% in CCA when compared with the experimentally accessible data. The new model describes the dynamics of complement consumption including the soluble phase of the reaction. <i>Conclusions:</i> The mathematical model extrapolation predicts that: (1) in undiluted human serum up to 40% of the physiological erythrocyte concentration could be lysed (when antibodies did not limit lysis); and (2) a 40 µ<i>M</i> (or less) concentration of blood group active trisaccharides per patient is sufficient to block the haemolytic complement activity.
Inhibition of Nitric Oxide Synthase Aggravates Cisplatin-Induced Nephrotoxicity: Effect of 2-Amino-4-Methylpyridine
Authors: Saad Sherif Y. , Najjar Tawfeeg A.O. , Daba Mohammed H. , Al-Rikabi Ammar C. 
Published: April 2003

<i>Background:</i> Nitric oxide (NO) has been shown to play a role in maintaining normal renal function. However, the role of NO in cisplatin (CDDP)-induced nephrotoxicity is still unclear. The aim of the present work was to examine the effect of the NO synthase (NOS) inhibitor, 2-amino-4-methylpyridine, on the severity of CDDP-induced nephrotoxicity. <i>Methods:</i> Male Wistar rats were divided into six groups. Three control groups received plain drinking water or water containing 1.5% <i>L</i>-arginine. One of the two groups receiving plain water was treated with an intraperitoneal injection of 2-amino-4-methylpyridine (1 mg/kg in normal saline), and the other two control groups were injected intraperitoneally with normal saline. Another three groups were treated in the same manner and injected with CDDP (6 mg/kg, i.p.). CDDP was injected 1 h after 2-amino-4-methylpyridine treatment. Rats were sacrificed 7 days after CDDP treatment, and serum as well as kidneys were isolated and analysed. <i>Results:</i> CDDP-treated rats showed increases in the kidney weight as a percentage of the total body weight and serum creatinine and urea levels and decreases in serum albumin and calcium levels. Also, CDDP treatment induced reductions in the kidney total nitrate/nitrite (NO<sub>x</sub>), reduced glutathione (GSH) and glutathione peroxidase activity (GSH-Px) levels and an increase in the kidney malondialdehyde (MDA) production level. In contrast, 2-amino-4-methylpyridine treatment 1 h prior to CDDP injection induced marked exacerbation of CDDP-induced nephrotoxicity, as manifested by severe aggravation of the indices of nephrotoxicity. Also, 2-amino-4-methylpyridine plus CDDP-treated rats showed exaggeration of the reduction in the kidney total NO<sub>x</sub> content and GSH-Px activity and elevation of the kidney platinum accumulation level with normalization of the kidney MDA production level and rebound in the kidney GSH content. Histopathologically, CDDP-treated rats showed marked interstitial nephritis, tubular atrophy and tubular necrosis. However, treatment with 2-amino-4-methylpyridine 1 h prior to CDDP injection revealed marked exacerbation of CDDP-induced histopathological changes. <i>Conclusions:</i> The present findings suggest that NO plays a role in CDDP-induced nephrotoxicity. Administration of 2-amino-4-methylpyridine, an NOS inhibitor, exacerbates CDDP-induced nephrotoxicity.
Chronic Renal Failure Leads to Reduced Flow-Dependent Dilation in Isolated Rat Skeletal Muscle Arterioles due to Lack of NO Mediation
Authors: Bagi Zsolt , Hamar Peter , Antus Balazs , Rosivall Laszlo , Koller Akos 
Published: April 2003

<i>Background:</i> Chronic renal failure (CRF) is frequently accompanied by systemic vascular alterations which further increase the morbidity and mortality of these patients. However, the nature and the underlying mechanisms of vascular dysfunction are not completely understood. We hypothesized that – in addition to other factors – CRF alters local vasomotor mechanisms that are intrinsic to the vascular wall. <i>Methods:</i> Changes in the diameter of isolated, pressurized (at 80 mm Hg) gracilis skeletal muscle arterioles (diameter approximately 150 µm) of female Wistar rats were investigated by videomicroscopy. Arteriolar responses to an increase in flow and vasoactive agents in partially nephrectomized (NX) and sham-operated (control) rats were compared. <i>Results:</i> In NX rats, serum creatinine and urine protein excretion were increased. Compared to controls, increases in intraluminal flow (from 0 to 40 µl/min) resulted in significantly reduced dilation in arterioles of NX rats (maximum: 32 ± 4 vs. 15 ± 4 µm, p < 0.05). Inhibition of nitric oxide (NO) synthesis with L-NAME reduced the dilation of control arterioles but did not affect responses of NX arterioles. Also, dilations in response to histamine were significantly reduced in arterioles from NX rats as compared to control rats. L-NAME significantly decreased histamine-induced dilations of control arterioles, but it did not affect responses of NX arterioles. Dilations in response to the NO donor sodium nitroprusside were also significantly decreased in NX arterioles as compared to responses of control vessels, whereas responses to adenosine and norepinephrine were not significantly different in the two groups. <i>Conclusions:</i> We conclude that in rat skeletal muscle arterioles, CRF induced by renal mass reduction alters the mechanosensitive and agonist-induced responses of peripheral arterioles, in part by interfering with NO-signaling mechanisms. These alterations could contribute to increased peripheral vascular resistance and further aggravate the cardiovascular complications in CRF.
Phase II Study of Troxacitabine (BCH-4556) in Patients With Advanced and/or Metastatic Renal Cell Carcinoma: A Trial of the National Cancer Institute of Canada-Clinical Trials Group
Authors: Townsley C.A. , Chi K. , Ernst D.S. , Belanger K. , Tannock I. , Bjarnason G.A. , Stewart D. , Goel R. , Ruether J.D. , Siu L.L. , Jolivet J. , McIntosh L. , Seymour L. , Moore M.J. 
Published: April 2003

Purpose: A multi-institution phase II study was undertaken by National Cancer Institute of Canada–Clinical Trials Group to evaluate the efficacy and toxicity of intravenous troxacitabine (Troxatyl; Shire Pharmaceuticals Plc, Laval, Quebec, Canada), in patients with renal cell carcinoma. Patients and Methods: Between June 1999 and March 2000, 35 patients (24 male) with a mean age of 60 years who had advanced and/or metastatic disease were treated with troxacitabine given as an intravenous infusion over 30 minutes at a dose of 10 mg/m2 intravenously, once every 3 weeks. Results: Of the 33 of 35 patients evaluable for response, there were two confirmed partial responses, 21 patients had stable disease (median duration, 4.4 months), and 10 patients had progressive disease. Eight patients remained stable for more than 6 months, of whom six remain free of progression. The most common drug-related nonhematologic toxicities observed were skin rash (77.1%), hand-foot syndrome (68.6%), alopecia (51.4%), fatigue (51.4%), and nausea (57.1%). Out of a total of 145 cycles of treatment, 98 were given without steroid premedication, whereas 47 cycles were given with steroid premedication. Without premedication, skin rash occurred in 37% of cycles compared with 26% when steroids were given prophylactically. Conclusion: Troxacitabine given at a dose of 10 mg/m2 once every 3 weeks was well tolerated in patients with metastatic renal cell cancer, with common toxicities being a moderate to severe granulocytopenia and skin rash. Steroid premedication may reduce the frequency and severity of the skin rash. Our current study suggests that the nucleoside analog troxacitabine may have modest activity against renal cell carcinoma; however, larger studies are required to confirm this.
Cadherin-13, a Mediator of Calcium-Dependent Cell-Cell Adhesion, Is Silenced by Methylation in Chronic Myeloid Leukemia and Correlates With Pretreatment Risk Profile and Cytogenetic Response to Interferon Alfa
Authors: Roman-Gomez Jose , Castillejo Juan A. , Jimenez Antonio , Cervantes Francisco , Boque Concepcion , Hermosin Lourdes , Leon Angel , Grañena Albert , Colomer Dolors , Heiniger Anabel , Torres Antonio 
Published: April 2003

Purpose: Cadherin-13 (CDH13) is a newly characterized cadherin molecule responsible for selective cell recognition and adhesion, the expression of which is decreased by methylation in a variety of human cancers, indicating that the CDH13 gene functions as a tumor suppressor gene. Although defective progenitor-stromal adhesion is a well-recognized feature of chronic myeloid leukemia (CML), the role of CDH13 abnormalities has not been evaluated in this disease. Patients and Methods: We examined the methylation status of the CDH13 promoter in 179 chronic phase (CP)-CML patients and in 52 advanced-phase samples and correlated it with mRNA expression using methylation-specific polymerase chain reaction (PCR) and reverse transcriptase PCR. Results: Aberrant de novo methylation of the CDH13 promoter region was observed in 99 (55%) of 179 of CP-CML patients, and 90 of the patients failed to express CDH13 mRNA (P < .0001). Advanced-stage samples (n = 52) showed concordant methylation results with their corresponding CP tumors, indicating that CDH13 methylation was not acquired during the course of the disease. Nevertheless, absence of CDH13 expression was more frequently observed among Sokal high-risk patients (P = .01) and was also independently associated with a shorter median progression-free survival time (P = .03) and poor cytogenetic response to interferon alfa treatment (P = .0001). Conclusion: Our data indicate that the silencing of CDH13 expression by aberrant promoter methylation occurs at an early stage in CML pathogenesis and probably influences the clinical behavior of the disease.
Randomized Phase I Trial of Recombinant Human Keratinocyte Growth Factor Plus Chemotherapy: Potential Role as Mucosal Protectant
Authors: Meropol Neal J. , Somer Robert A. , Gutheil John , Pelley Robert J. , Modiano Manuel R. , Rowinsky Eric K. , Rothenberg Mace L. , Redding Spencer W. , Serdar Cuneyt M. , Yao Bin , Heard Robert , Rosen Lee S. 
Published: April 2003

Purpose: To evaluate the safety of recombinant human keratinocyte growth factor (KGF) when administered with fluorouracil (FU) in patients with metastatic colorectal cancer. Patients and Methods: Patients (N = 81) received KGF by intravenous (IV) bolus on days 1 to 3, followed by FU 425 mg/m2/d IV bolus plus leucovorin 20 mg/m2/d IV on days 4 to 8. KGF dose levels were 1, 10, 20, 40, 60, and 80 μg/kg/d. A randomized, placebo-controlled design was employed (2:1 randomization of KGF to placebo). Oral mucositis was assessed by examination on days 1, 4, 8, 15, and 28. In addition, patients provided daily assessments of oral symptoms using a self-administered questionnaire. Results: Skin and oral events occurred in 13 of 18 patients (eight patients, grade 1; four patients, grade 2; and one patient, grade 3) treated with 60 and 80 μg/kg of KGF and three of 11 patients treated with 40 μg/kg (grade 1). These symptoms were dose limiting in three cases (ie, in two of 10 patients treated with 80 μg/kg and in one of eight patients treated with 60 μg/kg). The frequency of grade 2 to 4 mucositis was 43% in patients treated with KGF, compared with 67% in patients treated with placebo (P = .06). Patient self-assessments of oral pain and clinical assessments of mucositis showed good correlation (Kendall’s tau = 0.75). Conclusion: KGF is generally well tolerated when administered IV at doses up to 40 μg/kg/d for 3 days before a 5-day course of FU plus leucovorin. A clinically meaningful biologic effect was also suggested in that patients treated with the epithelial growth factor KGF had a lower rate of grade 2 to 4 mucositis than did patients treated with placebo.
Oxyanion Adsorptions by Mono-, Di-, and Triamino-Functionalized MCM-48
Authors: Yoshitake Hideaki , Yokoi Toshiyuki , Tatsumi Takashi 
Published: April 2003

Abstract
MCM-48 is functionalized with mono-, di-, and triamino-silanes without destruction of the mesoporous structure in order to efficiently remove chromate and arsenate in aqueous solutions. The adsorption capacities achieved 160 and 182 mg/g-adsorbent for chromate and arsenate, respectively, when triamino-functionalized MCM-48 was applied. The diamino-functionalized MCM-48 adsorbed much larger amounts of chromate and arsenate: 119 and 122 mg/g-adsorbent, respectively, than did diamino-functionalized fumed silica: 79.3 and 90.7 mg/g-adsorbent. The superiority arose from the large surface area of functionalized MCM-48. At the adsorption saturation, no clear difference was found in oxyanion/N stoichiometries among the mono-, di-, and triamino-functionalized MCM-48. On the other hand, the distribution coefficient, Kd, depended on the kind of silane fixed on MCM-48. It exceeded 2 × 105 when the concentration of oxyanions was low. The adsorbent by triamino-silylation showed the largest Kd; it was three or ten times higher than that of the adsorbent by monoamino-silylation for arsenate and chromate adsorptions, respectively. Although the adsorption capacity of diamino-functionalized MCM-48 was reduced to be 47% at 50 °C, it still adsorbed a large amount of arsenate.
A Two-Echelon Repairable Inventory System with Stocking-Center-Dependent Depot Replenishment Lead Times
Authors: Wang Yunzeng , Cohen Morris A. , Zheng Yu-Sheng 
Published: April 2003

Consider a two-echelon repairable inventory system consisting of a central depot and multiple stocking centers. The centers provide parts replacement service to customers and replenish their inventory from the depot, following a one-for-one policy. The depot fills center replenishment orders on a first-come-first-serve basis. Defectives received at the centers are passed to the depot for repair and depot inventory replenishment. For this system, existing models (e.g., the METRIC model) usually assume that the depot replenishment lead times (DRLTs) are i.i.d., which however, does not fit well into the service parts logistics system that motivated this research. Because the DRLTs consist of the sum of repair times, defective return times, and transportation times, they are different across stocking centers, which are located globally. We study the impact of such center-dependent DRLTs on system performance. We derive probability distributions of the random delays at the depot experienced by center replenishment orders. We prove that a center with shorter DRLTs experiences shorter delays, and therefore, delivers better customer service. We show that for such systems, using the i.i.d. DRLT assumption introduces errors in estimating system performance. These errors become significant when both the demand rates and the depot planned inventory level are low.
Decision Support for a Housing Mobility Program Using a Multiobjective Optimization Model
Authors: Johnson Michael P. , Hurter Arthur P. 
Published: April 2003

As result of public housing reform and welfare reform, the operating environment of public housing authorities has changed significantly. Given these policy initiatives, housing mobility programs represent viable strategies for providing public housing residents with access to economically healthy, integrated neighborhoods. In this paper we present a decision support methodology to assist the design of housing mobility programs. This methodology incorporates economic models for estimating dollar-valued impacts associated with tenant relocation, and a multiobjective optimization model for generating alternative relocation schemes associated with various objective function weights. Using data for Lake County, Illinois and Chicago, we demonstrate that nondominated allocations represent significant trade-offs between dollar-valued and non-dollar-valued policy objectives; existing distributions of subsidized housing represent suboptimal solutions to the housing relocation problem; and increases in available rental housing can result in housing dispersion schemes that have positive net economic benefits relative to the status quo.
Interactive Multiobjective Group Decision Making with Interval Parameters
Authors: Xanthopulos Zaharias , Melachrinoudis Emanuel , Solomon Marius M. 
Published: April 2003

This paper proposes a new framework for the solution of interactive multiobjective group decision-making problems with interval parameters. Its novelty stems from a learning phase where decision makers (DMs) explore the structural characteristics of the specific Multiple Criteria Decision Making (MCDM) problem. This provides important and timely feedback to the DMs. Its core consists of four indices and their relationships. The solution framework consists of three stages. In the first, each DM provides the limits of variation for each problem parameter. These are subsequently combined into a unique interval of variation. Then, the stochastic multiobjective problem is transformed into a deterministic one. In the second stage, DMs use the four MCDM characteristics to familiarize themselves with the problem before expressing their preferences for nondominated solutions. The DMs are then guided through an interactive procedure to find their best nondominated solutions. In the last stage, all best nondominated solutions provided by the DMs are combined using a twofold approach to find the best-compromise nondominated solution. This final choice represents the opinion of the group of DMs. Our results show that the learning phase is beneficial to DMs in judging the quality of solutions, leading to better informed decisions.