bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelin signaling in osteoblasts: global genome view and implication of the calcineurin/NFAT pathway
Authors: Van Sant Charles , Wang Gang , Anderson Mark G. , Trask Oscar J. , Lesniewski Rick , Semizarov Dimitri 
Published: January 2007

Abstract
Patients with prostate cancer develop osteoblastic metastases when tumor cells arrive in the bone and stimulate osteoblasts by secreting growth-promoting factors. Endothelin 1 (ET-1) is believed to be a key factor in promoting osteoblastic metastasis. Selective blockade of the ETA receptor is an established strategy in the development of cancer therapeutics. However, the molecular mechanisms whereby prostate cancer promotes abnormal bone growth are not fully understood. In this study, we have applied genomic approaches to elucidate the molecular mechanism of stimulation of osteoblasts by ET-1. To examine the ET-1 axis, we generated genomic signatures for osteoblasts treated with ET-1, in the presence and absence of a selective ETA antagonist (ABT-627). The ET-1 signature was comprised of several motifs, such as osteoblastic differentiation, invasion, and suppression of apoptosis. The signature also pointed at possible activation of the calcineurin/NFAT pathway. We showed that ET-1 activates calcineurin and causes nuclear translocation of NFATc1, implicating the pathway in the ET-1–mediated stimulation of osteoblasts. We also showed that ET-1 inhibits apoptosis in osteoblasts, implying that the suppression of apoptosis may be an important factor in the promotion of osteoblastic growth by ET-1. [Mol Cancer Ther 2007;6(1):253–61]
Evolution of Dipole-Type Blocking Life Cycles: Analytical Diagnoses and Observations
Authors: Huang Fei , Tang Xiaoyan , Lou S. Y. , Lu Cuihua 
Published: January 2007

Abstract
A variable coefficient Korteweg–de Vries (VCKdV) system is derived by considering the time-dependent background flow and boundary conditions from a nonlinear, inviscid, nondissipative, and equivalent barotropic vorticity equation in a beta plane. One analytical solution obtained from the VCKdV equation can be successfully used to explain the evolution of atmospheric dipole-type blocking (DB) life cycles. Analytical diagnoses show that the background mean westerlies have great influence on evolution of DB during its life cycle. A weak westerly is necessary for blocking development and the blocking life period shortens, accompanied with the enhanced westerlies. The shear of the background westerlies also plays an important role in the evolution of blocking. The cyclonic shear is preferable for the development of blocking but when the cyclonic shear increases, the intensity of blocking decreases and the life period of DB becomes shorter. Weak anticyclonic shear below a critical threshold is also favorable for DB formation. Time-dependent background westerly (TDW) in the life cycle of DB has some modulations on the blocking life period and intensity due to the behavior of the mean westerlies. Statistical analysis regarding the climatological features of observed DB is also investigated. Observational results show that the Pacific is a preferred region for DB, especially at high latitudes. These features may associate with the weakest westerlies and the particular westerly shear structure over the northwestern Pacific.
On the Parameterization of Surface Roughness at Regional Scales
Authors: Bou-Zeid Elie , Parlange Marc B. , Meneveau Charles 
Published: January 2007

Abstract
A parameterization for surface roughness and blending height at regional scales, under neutral atmospheric stability, is studied and tested. The analysis is based on a suite of large-eddy simulations (LES) over surfaces with varying roughness height and multiple variability scales. The LES are based on the scale-dependent Lagrangian dynamic subgrid-scale model, and the surface roughnesses at the ground are imposed using the rough-wall logarithmic law. Several patterns of roughness distribution are considered, including random tiling of patches with a wide distribution of length scales. An integral length scale, based on the one-dimensional structure function of the spatially variable roughness height, is used to define the characteristic surface variability scale, which is a critical input in many regional parameterization schemes. Properties of the simulated flow are discussed with special emphasis on the turbulence properties over patches of unequal roughness. The simulations are then used to assess a generalized form of the parameterization for the blending height and the equivalent surface roughness at regional scales that has been developed earlier for regular patterns of surface roughness (regular stripes). The results are also compared with other parameterizations proposed in the literature. Good agreement is found between the simulations and the regional-scale parameterization for the surface roughness and the blending height when this parameterization is combined with the characteristic surface variability scale proposed in this paper.
The impact of introducing pre-printed chemotherapy medication charts to a day chemotherapy unit
Authors: Tran May 
Published: January 2007

Context. The cytotoxic regimens used in the contemporary day chemotherapy unit are often complicated and present numerous opportunities for error, inadvertent misadventure in prescription orders and variations in drug administration. The introduction of pre-printed chemotherapy charts for each protocol was introduced to minimise incorrect or incomplete prescribing by medical staff. Objective. To assess the benefits of introducing pre-printed chemotherapy charts into a day chemotherapy unit. Method. Commonly used protocols in the unit were assessed and assembled into pre-printed chemotherapy charts. The doses and administration details of each protocol were reviewed by chemotherapy nursing staff, medical staff and the oncology pharmacist before the charts were finalised. Clinical interventions performed by the oncology pharmacist were recorded for 1 month prior and 1 month following the introduction of the pre-printed charts. Nursing and medical staff were surveyed on their level of satisfaction with the pre-printed chemotherapy charts. Results. Prior to the introduction of the pre-printed charts, 74% of chemotherapy charts were problematic requiring multiple pharmacy interventions per chart. After the introduction of the pre-printed charts, 43% of charts were problematic requiring an average of one pharmacy intervention per chart. Pharmacy interventions were significantly reduced, which has resulted in a significant reduction in workload for the oncology pharmacist. The medical and nursing staff strongly supported the introduction of the pre-printed charts. There has been a reduction in the variation of orders amongst medical officers, reduction in prescribing errors, decreased anxiety amongst staff and better work-flow in the Day Chemotherapy Unit. Conclusion. Pre-printed chemotherapy medication charts have promoted a more methodical approach to the prescribing and administration of chemotherapy, which has resulted in a more efficient day chemotherapy unit.
A review of dolasetron as management of nausea and vomiting in cancer patients
Authors: Valley Amy W. 
Published: January 2007

Objective. To systematically review the literature about the pharmacology, pharmacokinetics, efficacy, dosing, and adverse effects of dolasetron, and to define its role in the management of chemotherapy-and radiation-induced nausea and vomiting. Data Synthesis. A MedLine search was conducted using 5-HT3-receptor antagonists, antiemetics, chemotherapy toxicity, dolasetron, emesis, nausea, and vomiting as search terms. Reference lists and bibliographies of pertinent articles were also identified and reviewed. Both preclinical and clinical literature were reviewed and analyzed. Data Synthesis. Dolasetron is a serotonin type 3 (5-HT3)-receptor antagonist with potent antiemetic effects in the management of nausea and vomiting. Following administration, dolasetron is rapidly converted to hydrodolasetron, which is believed to be responsible for the drug's antiemetic activity. Results of multiple studies have demonstrated the efficacy of this agent in the prevention of chemotherapy-induced emesis, including that induced by cisplatin. As a single agent, dolasetron produces a complete response rate (RR) in 44% to 57% of patients treated with cisplatin (≥70 mg/m2) and in 59% to 80% of patients treated with moderately emetogenic chemotherapy, such as cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy. When combined with dexamethasone, the RRs are increased. Dolasetron is well tolerated, with headache (24%) and diarrhea (12%) the most commonly reported adverse effects. The efficacy and safety of dolasetron are comparable to those observed with other 5-HT3-receptor antagonists. According to four recently published clinical practice guidelines for use of antiemetics, dolasetron is an appropriate first-line option for the prevention of nausea and vomiting due to moderately to highly emetogenic chemotherapy. Further clinical trials will determine the optimal dose and the role of this highly effective antiemetic agent for other purposes, such as treatment of delayed emesis and emesis resulting from radiation therapy and high-dose chemotherapy followed by bone marrow transplantation.
Novel treatment for the management of ifosfamide neurotoxicity: Rationale for the use of methylene blue
Authors: Donegan Sarah 
Published: January 2007

Objective. To provide an overview of the proposed pathophysiology of ifosfamide encephalopathy and the role of methylene blue for the treatment and prevention of this toxicity. Data Source. A Medline search using the terms ‘‘ifosfamide encephalopathy’’ and ‘‘methylene blue’’ was conducted for the period of 1990-2001. The reference lists from retrieved articles were reviewed Data Extraction. The author reviewed the retrieved material and included animal and pharmacokinetic data related to ifosfamide and the pathophysiology of ifosfamide neurotoxicity. Additionally, preclinical data and case reports describing the clinical use and rationale for methylene blue were included. Data Synthesis. Encephalopathy is a unique toxicity described with ifosfamide, but not with cyclophosphamide. Ifosfamide undergoes a secondary ‘‘deactivation’’ metabolic pathway to yield dechloroethylated metabolites and chloroacetalde-hyde. Chloroacetaldehyde is a metabolite that contributes to both the nephrotoxicity and neurotoxicity described with ifosfamide. Chloroacetaldehyde (or a dechloroethylated metabolite) may exert neurotoxic effects by one or more of the following mechanisms: (a) direct neurotoxic damage, (b) depletion of central nervous system (CNS) glutathione level, or (c) inhibition of mitochondrial oxidative phosphorylation resulting in impaired fatty acid metabolism. The biochemical derangements described with this acute toxicity appear to mimic a neonatal mitochondrial disorder, for which methylene blue has been used. Methylene blue has been shown to restore and maintain mitochondrial respiration and therefore can be used to correct or prevent acute neurotoxic effects. Methylene blue has been used to treat moderate to severe cases of ifosfamide neurotoxicity and has also been used prophylactically to prevent encephalopathy in high-risk conditions with the use of oral and bolus iv ifosfamide regimens. Methylene blue may be useful in the treatment of grade III or IV neurotoxicity or in those patients with recurrent neurological symptoms associated with ifosfamide administration. The use of prophylactic or concurrent administration of methylene blue with ifosfamide requires further clinical evaluation.
Viability of microorganisms in bags of cytotoxic drugs
Authors: Favier Bertrand , Latour Jean François , Fuhrmann Christine 
Published: January 2007

Objectives. The aim of this report was to study the viability of five microorganisms (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, S epidermidis and Candida albicans) in chemotherapeutic solutions made up 1-2 days before administration. Methods. The four preparations studied were 0.5 mg/mL cisplatin, 1.8 mg/mL doxorubicin, 5 mg/mL 5-fluorouracil, and 5 mg/mL cyclophosphamide. All four solutions were tested at a temperature of 258C, and doxorubicin and cyclophosphamide were also tested at 48C. The concentrations of the microorganisms in the preparations were determined 2, 24, 48, 72, and 96 hours after inoculation. Results. No microbial growth was found; on the contrary, bacterial and fungal growth decreased rapidly and substantially with cisplatin and doxorubicin (by 2log after 24 hours), moderately with 5-fluorouracil, and weakly or not at all with cyclophosphamide. Refrigeration at 48C appeared to slow the decreased growth of the microorganisms when compared with storage at 258C. Conclusion. As no bacterial or fungal growth was seen in the four solutions of cytotoxic agents tested, the practice of preparing such solutions under a hood with vertical laminar ventilation according to good practice in the preparation of sterile solutions 1 or 2 days before administration to patients is validated. J Oncol Pharm Practice (2001) 6, 167-171.
Pharmacologic study of Cremophor EL in cancer patients with impaired hepatic function receiving paclitaxel
Authors: Panday Vinodh R Nannan , Huizing Manon T , van Tellingen Olaf , Hakvoort Robert A , Willemse Pax H B , De Graeff Alexander , Vermorken Jan B , Beijnen Jos H 
Published: January 2007

Aims. Cremophor EL (CrEL) (polyoxyethylene glycerol triricinoleate 35) is used as a pharmaceutical vehicle for the formulation of several drugs, including the anticancer agent paclitaxel (Taxolt). This excipient has been associated with hypersensitivity reactions and affects the pharmacokinetic properties of paclitaxel, especially in patients with hepatic dysfunction. In this study, we investigated the pharmacokinetics of CrEL in a specific population of patients. Methods. Patients were stratified in five cohorts based on hepatic function, received paclitaxel for metastatic disease, and were monitored pharmacokinetically during course 1 and course 2. CrEL levels were measured and related to the extent of hepatic dysfunction. Results. A total of 46 courses were measured from 27 patients. CrEL pharmacokinetic parameters in patients with mild hepatic dysfunction (cohorts I-III) were not significantly different from patients with normal hepatic function, whereas the patients with moderate to severe hepatic dysfunction (cohorts IV and V) displayed a different pharmacokinetic profile. Conclusions. The results indicate a nonlinear pharmacokinetic behavior of CrEL. No differences were found for CrEL pharmacokinetics when course 1 was compared with course 2 per cohort. A possible influence of the specific characteristics of patients with severe hepatic dysfunction, such as altered physiologic and metabolic states, could play a role in the deposition of CrEL.
Risk of breast cancer associated with hormone replacement therapy
Authors: Dopp John M , Kolesar Jill M 
Published: January 2007

Purpose. The primary objective of this paper is to provide a brief overview of the risk of breast cancer associated with hormone replacement therapy (HRT) in healthy postmenopausal women, in breast cancer survivors, and in women at increased risk for breast cancer. Data Sources. The literature was reviewed through a MEDLINE search covering the years 1988 to 1999. Relevant articles cited in the literature obtained by MEDLINE searching were also considered. The following terms were searched: estrogen, progesterone, breast cancer, and HRT. The search was restricted to the English language. Data Extraction. The current literature is reviewed with regard to the risk of breast cancer associated with HRT in healthy postmenopausal women, in breast cancer survivors, and in women at increased risk for breast cancer. Data Synthesis. HRT is used commonly in post-menopausal women to alleviate both climacteric menopausal symptoms such as hot flashes and urogenital atrophy and to reduce the degree and frequency of osteoporosis. However, exposure to estrogen is one of the most important risk factors for breast cancer, and HRT is a relative contraindication in women with a personal history of breast cancer. The majority of epidemiological literature indicates that healthy women taking short-term HRT are not at increased risk of developing breast cancer. In breast cancer survivors, HRT does not appear to increase the risk of relapse. Some epidemiological studies show that women with a family history of breast cancer are at a substantially increased risk of developing breast cancer when receiving HRT. The decision to use HRT should be made individually by each woman and her health care provider by weighing the expected benefits and potential risks of therapy.
Oprelvekin (Neumega®)
Authors: Adams Val R , Brenner Timothy L 
Published: January 2007

Objective. Our objective was to review oprelvekin, which is a new thrombopoietic cytokine approved in the United States to prevent severe thrombocytopenia and reduce the number of platelet transfusions after myelosuppressive chemotherapy. This article focuses on oprelvekin’s pharmacology, pharmacokinetics, and place in therapy. Data Sources. A search of the National Cancer Institute-sponsored Cancerlit database from 1963 to 1999 was completed. Subject mesh headings that were searched included interleukin-11, oprelvekin, breast cancer, chemotherapy dose intensity, and cancer pharmacoeconomics. Data were also collected from the package insert and from Genetics Institute (Cambridge, MA) publications. Study Selection. Searches were limited to studies with humans, which included clinical trials, news articles, and review articles. After reading all of the human clinical trials, additional pertinent citations were obtained and read. Data Synthesis. Oprelvekin has been studied in both adults and children, with the bulk of the data coming from the treatment of women with breast cancer. A phase I study in adults evaluated doses of 10, 25, 50, 75, and 100 mg/kg/day and determined the maximum tolerated dose to be 50 mg/kg/day. The toxicity seen with the 75 and 100 mg/kg/day doses includes constitutional symptoms (arthralgias, myalgias, fatigue, nausea, and headache) and a cerebral vascular accident. Phase II and III trials showed that 25-50 mg/kg/day effectively reduced the number of patients requiring platelet transfusions and decreased the number of platelet transfusions after chemotherapy. Pharmacokinetics performed with the 50 mg/kg/day subcutaneous (s.c.) dose resulted in a maximum sera concentration of 17.4 6 5.4 ng/mL, which occurred at 3.2 6 2.4 hours. The terminal half-life was 6.9 6 1.7 hours. Clearance decreases with increasing age, and pediatric patients have a 1.2- to 1.6-fold higher clearance than adults. These pharmacokinetic parameters led to a dosing recommendation of 75- 100 mg/kg/day in pediatric patients. Due to the high cost of oprelvekin and the lack of data demonstrating that it affects mortality, its role in current therapies is unclear. It is currently being promoted to maintain dose intensity in patients with breast cancer, testicular cancer, and lymphoma. Depending upon institutional platelet and oprelvekin costs, it may also be useful in patients receiving a large number of platelet transfusions. Thus far, it has not demonstrated efficacy in bone marrow transplant patients. Conclusion. Oprelvekin can effectively prevent the need for platelet transfusion in nontransplant patients receiving myelosuppressive chemotherapy. Due to its high cost, it will most likely be used to maintain chemotherapy dose intensity, which may translate into a survival advantage.
Beneficial clinical outcomes resulting from pharmacist interventions
Authors: McLennan Danielle N , Dooley Michael J , Brien Jo-anne E 
Published: January 2007

Objective. To assess the contribution pharmacists make to patient care by determining the clinical outcomes associated with pharmacist interventions. Methods. A 2-month prospective intervention study was conducted at Peter MacCallum Cancer Institute, a tertiary referral center. During the study, clinical pharmacists documented intervention episodes, patient demographical details, and the drug(s) involved. Clinical outcomes resulting from pharmacist-initiated changes to drug therapy and patient management were assessed by an independent pharmacist according to defined criteria. Outcomes were determined through review of patient medical progress notes and discussion with members of the health care team. Results. A total of 674 interventions were documented during the data collection period. Outcomes could be assessed for 10% of the interventions reported, and 90% of these interventions resulted in documented clinical benefit. The drug classes most frequently associated with pharmacist interventions were antiemetics, antimicrobials, and analgesics. Conclusion. This prospective study demonstrated a high rate of beneficial outcomes achieved by pharmacist interventions.
Audit of efficacy of 3 mg versus 1 mg of intravenous granisetron as antiemetic prophylaxis against acute emesis caused by cisplatin or melphalan
Authors: Hole Alison , Conway Alison , Quadir Suraya 
Published: January 2007

Objective. In the United Kingdom, granisetron is licensed at an adult dose of 3 mg for prophylaxis of emesis due to cytotoxic chemotherapy. In the United States, however, the licensed dose is 10 mg/kg, which, for most adults, equates to 1 mg. In view of the cost implications of this difference in dosage recommendations, the local drug and therapeutics advisory committee supported a proposal to evaluate the use of the 1-mg dose for our own patients. We report the results of this evaluation in patients receiving the highly emetic drugs cisplatin and melphalan, given alone or in combination with other cytotoxics. Design. Prospective, open, non-randomised study of patients receiving 3 mg and 1 mg of granisetron as part of their antiemetic regimen. Data collection was carried out before and after a change in hospital antiemetic policy. Setting. A specialist oncology hospital in England. Patients. A total of 57 patients received 3 mg of granisetron, and 70 patients received 1 mg of granisetron. Results. There was a small increase in the incidence of nausea and vomiting following the change in the granisetron dose from 3 mg to 1 mg, but this increase was not big enough to be significant. Conclusion. Guidelines recommending the use of granisetron at a dose of 1 mg were successfully implemented at the Royal Marsden Hospital with the potential to save the Trust over £50,000 per year without detriment to patient care.