bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemotherapy-induced moderate tolife-threatening anemia in early-stage breast cancer
Authors: Caggiano Vincent , Gupta Sanjay , Tannous Rima E , Fridman Moshe , Carter William B 
Published: October 2002

Purpose. We evaluated the incidence and severity of anemia experienced by women treated with doxorubicin and cyclophosphamide (AC) therapy for early-stage breast cancer are described. We also explored the possibility of identifying clinical characteristics that will allow early identification of women more likely to develop anemia and may require anemia treatment. Methods. This study used a historic case series from 13 oncology practices that participated in the Oncology Practice Pattern Study. The analysis focused on 411 patients who received AC chemotherapy from 1993 through 1999. Seventeen percent of the study population was excluded from the analysis due to missing data. Anemia was defined as a hemoglobin (Hb) value of < 12 g/dL. Hb ≤10 g/dL was considered the threshold value for treatment. Results. Among patients receiving AC, 18.0% was anemic prior to chemotherapy. Overall, 14.9 -16.9% of women with early-stage breast cancer who started AC chemotherapy with a normal Hb (≥12 g/dL) developed anemia. Nearly 11% developed severe to life-threatening anemia (Hb < 8 g/dL). Data on blood transfusions and erythropoietic therapy were unavailable. Multivariate logistic regression analysis showed that patients who started with a normal prechemotherapy Hb and dropped to ≤10 g/dL at some point during chemotherapy were more likely to be ≥65 years of age, have a low body surface area (< 1.78), and have four or more positive nodes. Conclusion. The incidence of anemia increased substantially from baseline to post-chemotherapy. The data suggested the importance of monitoring and managing Hb levels of patients at increased risk for developing chemotherapy-induced anemia.
Influence of International Emergency Medicine Opportunities on Residency Program Selection
Authors: Dey Chayan C. , Grabowski Jurek G. , Gebreyes Kulleni , Hsu Edbert , VanRooyen Michael J. 
Published: October 2002

Abstract Objectives: In the last several years, there has been increasing interest in international emergency medicine (IEM) programs. A number of residency programs offer or encourage international opportunities during residency. The purpose of this study was twofold: 1) to determine whether the availability of international opportunities during residency affected the ranking of emergency medicine (EM) residency programs by graduating medical students and 2) to determine whether prior international health experience among medical students influences interviewing and ranking of residency programs with international opportunities. Methods: An eight‐question survey measuring interest in IEM and its effect on ranking of programs was mailed to all 1,205 first‐year EM residents from 122 accredited allopathic EM residency programs in the United States. International opportunities were defined as any program that offered an international elective during residency or had an IEM fellowship. Data were analyzed using descriptive statistics and chi‐square tests. Results: Of the 1,205 mailed surveys, 34% were returned by the first‐year residents. Of all respondents, 281/408 (69%) interviewed at programs with international opportunities. Study findings revealed 62% (164/264) of the students who interviewed at programs with international opportunities considered the availability of international opportunities a positive factor in ranking residency programs. Analysis revealed that applicants with previous international health experience, 68% (104/152), were more likely to rank EM residency programs with international opportunities higher than those that did not. Conclusions: This study suggests that the availability of international opportunities during residency positively affected residency ranking. This relationship was stronger in medical students with prior international health experience.
Preventive Care in the Emergency Department: Diagnosis and Management of Smoking and Smoking‐related Illness in the Emergency Department: A Systematic Review
Authors: Bernstein Steven L. , Becker Bruce M. 
Published: October 2002

AbstractSmoking remains the leading preventable cause of morbidity and mortality in the United States. The efficacy of emergency department (ED)‐based patient screening and counseling for smoking cessation is not currently known. Objectives: To perform a structured, systematic review of the medical literature to assess the efficacy of limited screening and counseling for tobacco use cessation among adults in the primary care and ED settings, and develop recommendations for emergency physicians based on these data. Methods: A two‐person template‐driven review of all English‐language articles from Medline, the Cochrane Database, and two recent smoking cessation guidelines, with evidence graded according to the scheme of the U.S. Preventive Services Task Force (USPSTF), was performed. Recommendations were developed, and strength graded, based on this evidence. Results: Of 2,078 citations reviewed, 16 were selected for inclusion, based on their methodologic strength and relevance to emergency medicine. Routine physician screening and counseling may increase quit rates at 6‐12 months from 3% (usual care) to 8‐11%. Interventions include brief counseling (<3 minutes), possibly supplemented with self‐help literature, nicotine replacement therapy (NRT), and follow‐up telephone calls. Conclusions: Strong evidence exists, in the primary care setting, that smoking cessation screening and counseling are effective. Limited data exist for ED‐based practice, but, based on the burden of disease, relative ease of intervention, and likely efficacy, routine screening of all patients for tobacco use and referral of smokers to primary care and cessation programs are recommended.
Adjuvant Immunotherapy of Patients With High-Risk Melanoma Using Vaccinia Viral Lysates of Melanoma: Results of a Randomized Trial
Authors: Hersey Peter , Coates Alan S. , McCarthy William H. , Thompson John F. , Sillar Robert W. , McLeod Roderick , Gill P. Grantley , Coventry Brendon J. , McMullen Amanda , Dillon Haryana , Simes R. John 
Published: October 2002

PURPOSE: Patients with high-risk melanoma treated by immunotherapy with vaccinia viral lysates were found in phase II studies to have improved survival compared with historical controls. We therefore elected to test this therapy in a phase III study. PATIENTS AND METHODS: A prospective, randomized, multicenter trial to determine whether immunotherapy with a vaccine prepared from vaccinia melanoma cell lysates (VMCL) over a 2-year period after definitive surgery would improve relapse-free survival (RFS) and overall survival (OS) in patients with American Joint Committee on Cancer stage IIB and III melanoma compared with a control group treated only with surgery. RESULTS: A total of 700 patients were randomized: 353 to VMCL and 347 to no immunotherapy. Seventy-seven percent had lymph node (LN) metastases and 66% had clinically detected LN metastases. Analysis on the basis of all eligible, randomized patients (n = 675) found, after a median follow-up period of 8 years, a median OS of 88 months in the control versus 151 months in the treated group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.64 to 1.02; P = .068 by stratified univariate Cox analysis). At 5 and 10 years, survival rates for control and treated patients were 54.8% v 60.6% and 41% v 53.4%, respectively. Median RFS was 43 months in the control group compared with 83 months in the treated group (HR, 0.86; 95% CI, 0.7 to 1.07; P = .17). RFS at 5 years was 50.9% for the treated group and 46.8% for the control group. There were no selective benefits from the vaccine for particular subsets of patients. CONCLUSION: Immunotherapy with VMCL was not associated with a statistically significant improvement in OS or RFS, with CIs not ruling out important gains from such treatment.
Uptake of lamivudine by rat renal brush border membrane vesicles
Authors: Takubo Takatoshi , Kato Toshihiro , Kinami Junji , Hanada Kazuhiko , Ogata Hiroyasu 
Published: October 2002

Abstract
Uptake of lamivudine, a nucleoside analogue antiviral agent, by brush border membrane vesicles (BBMV) prepared from rat renal cortex was investigated. Initial uptake of lamivudine by BBMV was stimulated in the presence of an outward pH gradient. Determination of the kinetic parameters of the initial uptake yielded apparent Km and Vmax values of 2.28 mM and 1.56 nmol (mg protein)−1 (20 s)−1, respectively. The pH-driven uptake of lamivudine was inhibited by organic cations such as trimethoprim and cimetidine. The inhibitory effect of trimethoprim on lamivudine uptake was competitive, with an apparent Ki of 27.6 μM. The uptake of lamivudine was also inhibited by nitrobenzylthioinosine, a representative inhibitor of nucleoside transport, and by other nucleoside analogues, such as azidothymidine and dideoxycytidine, that are excreted by renal tubular secretion. These findings suggest that efflux of lamivudine at the brush border membrane of renal tubular epithelium is mediated by an H+/lamivudine antiport system, which may correspond to the H+/organic cation antiport system, and that this system is also involved in the renal secretion of other nucleoside analogues.
Microemulsion formulation of clonixic acid: solubility enhancement and pain reduction
Authors: Lee Jung-Mi , Park Kyung-Mi , Lim Soo-Jeong , Lee Mi-Kyung , Kim Chong-Kook 
Published: October 2002

Abstract
Clonixic acid is currently marketed as a salt form because of its poor water-solubility. However, the commercial dosage form causes severe pain after intramuscular or intravenous injection. To improve the solubility of clonixic acid and to reduce pain on injection, clonixic acid was incorporated into oil-in-water microemulsions prepared from pre-microemulsion concentrate composed of varying ratios of oil and surfactant mixture. As an oil phase for drug incorporation, up to 14% castor oil could be included in the pre-microemulsion concentrate without a significant increase in droplet size. Both drug contents and droplet size increased as the weight ratio of Tween 20 to Tween 85 decreased. Taken together, when microemulsions were prepared from pre-microemulsion concentrate composed of 5:12:18 weight ratio of castor oil:Tween 20:Tween 85, clonixic acid could be incorporated at 3.2 mg mL−1 in the micro-emulsion with a droplet size of less than 120 nm. The osmotic pressure of this microemulsion was remarkably lower than the commercial formulation, irrespective of the dilution ratios. The rat paw-lick test was used to compare pain responses among formulations. The microemulsion formulation significantly reduced the number of rats licking their paws as well as the total licking time, suggesting less pain induction by the microemulsion formulation. The pharmacokinetic parameters of clonixic acid after intravenous administration of the clonixic acid microemulsion to rats were not significantly different from those of the commercial formulation, lysine clonixinate. The present study suggests that microemulsion is an alternative formulation for clonixic acid with improved characteristics.
Evaluation of increased bioavailability of tacrolimus in rats with experimental renal dysfunction
Authors: Okabe Hiromi , Yano Ikuko , Hashimoto Yukiya , Saito Hideyuki , Inui Ken-ichi 
Published: October 2002

Abstract
The effects of renal failure on the hepatic and intestinal extraction of tacrolimus were evaluated to examine the mechanisms for the increased bioavailability of this drug in cisplatin-induced renal failure model rats. Tacrolimus extractions in the liver and intestine were evaluated by intravenous, intraportal and intraintestinal infusion. The intestinal metabolism and absorption rate were estimated by incubating the isolated intestine with drug solution and by an in situ loop method, respectively. Blood concentrations of tacrolimus following the intraintestinal infusion were significantly increased in rats with renal failure compared with those in normal rats. The blood concentration of tacrolimus during intraportal infusion in rats with renal failure showed non-linearity against dose, and was increased as compared with that in normal rats. The intestinal metabolism was not altered, but the absorption rate was significantly increased in the intestine from rats with renal dysfunction. These results suggest that the hepatic metabolism of tacrolimus is impaired in rats with renal failure, and that the accelerated absorption rate in the intestine in renal dysfunction is followed by partial saturation of hepatic extraction, which may be one of the mechanisms of increased bioavailability of tacrolimus.
Pharmacokinetics of ABT-773, a new semi-synthetic ketolide in neutropenic lung-infected mice: a population approach
Authors: Xuan Dawei , Ye Min , Kim Myo , Nightingale Charles H , Nicolau David P 
Published: October 2002

Abstract
ABT-773 is an investigational ketolide antimicrobial agent with an in-vitro bactericidal activity against macrolide-susceptible and -resistant Streptococcus pneumoniae. The pharmacokinetics of this drug candidate were evaluated in lung-infected (108 CFU mL−1 starting inoculum) mice following a single dose (25, 50, 100 or 200 mg kg−1) oral administration as a solution in 10 % of 95% ethanol and 90% of 0.1 M pH 6.5 phosphate buffer solution. Serum ABT-773 concentrations were measured using a validated HPLC assay with fluorescence detection (excitation at 324 nm and emission at 364 nm). Population pharmacokinetic analysis was performed using the NONMEM computer program. Results from data analysis showed non-linear pharmacokinetics of ABT-773, noted by the increases in half-life (3.1 to 27.2 h) and AUC/dose (23.7 to 149 mg h−1 L−1 mg−1), with doses from 25 to 200 mg kg−1. A non-linear one-compartment model with parallel capacity-limited and linear first-order elimination best described the pharmacokinetics of ABT-773 in the mouse. The total volume of distribution was 0.316 L. The clearance for the linear first-order elimination was 0.0027 L h−1. The Vm and Km were 0.0385 L h−1 and 0.141 mg L−1, respectively, for the capacity-limited elimination.
Potent apoptotic effects of saponins from Liliaceae plants in L1210 cells
Authors: Candra E , Matsunaga K , Fujiwara H , Mimaki Y , Kuroda M , Sashida Y , Ohizumi Y 
Published: October 2002

Abstract
We isolated eight saponins, a hexacyclic lanosterol tetraglycoside (1), a 27-norlanosterol tetraglycoside (2) and six spirostanol oligoglycosides (3–8), from the plants of the family Liliaceae. In murine leukaemic L1210 cells, saponins 5 and 7 at a concentration of 1 μM showed potent cytotoxic activity and the activities were in the following decreasing order: 5, 7, 1, 3, 2, 8,4, 6. At a concentration of 10 μM, not only 5 and 7 but also 3 and 8 markedly caused cell death. The flow cytometric analysis indicated that 7 and 8 caused a concentration- and time- dependent apoptosis of L1210 cells (EC50 value = ∼5 μM). The morphological observation using a light microscope revealed that both 7 and 8 induced shrinkage in cell soma and chromatin condensation, suggesting apoptotic cell death. Moreover, in agarose gel electrophoretic analysis, a typical apoptotic DNA ladder pattern was observed after treatment with both 7 and 8. These results suggest that 7 and 8 caused the death of L1210 cells through the apoptotic process. These compounds may become powerful pharmacological tools for studying the molecular mechanism of apoptosis.
Effects of adenosine agonists on consumptive behaviour and body temperature
Authors: Coupar Ian M , Tran Binh L T 
Published: October 2002

Abstract
This study was designed to determine the effects of the A1-receptor selective agonist N6- cyclopentyladenosine (CPA), and the A2-selective agonist, 2-p-(2-carboxyethyl)-phenethyl-amino-5′-N-ethylcarboxamidoadenosine-hydrochloride (CGS-21680) on consumptive behaviour and body temperature in rats in relation to the non-selective A1/A2 adenosine agonist, N-ethylcarboxamidoadenosine (NECA), and to morphine. It was shown that two subcutaneous injections of 0.1 and 0.3 mg kg−1 CPA caused a similar decrease in food consumption to NECA (2 × 0.03 mg kg−1) and morphine (2 × 10 mg kg−1). However, two doses of 0.03 mg kg−1 CPA and 0.1 and 0.3 mg kg−1 CGS-21680 enhanced feeding. These effects were not directly correlated to faecal output at all doses of the selective agonists, as NECA and morphine induced constipation. The doses of CPA and 0.1 and 0.3 mg kg−1 of CGS-21680 enhanced water consumption, as did NECA, but not morphine. The stimulation of drinking by CPA was not absolutely associated with diuresis. Instead, urine output was reduced by 0.03 and 0.1 mg kg−1 and increased by 0.3 mg kg−1. CGS-21680 at 0.1 and 0.3 mg kg−1 and NECA also induced diuresis, which was opposite to the effect of morphine. CPA and CGS-21680 both caused significant dose-dependent decreases in body temperature after the two-injection treatment, but their effects were significantly less after 36 h when four doses had been administered. The study indicates that highly selective A1 and A2A adenosine agonists might have the ability to interfere with consumptive behaviour, induce constipation, affect renal function and to lower body temperature.
Aminated gelatin as a nasal absorption enhancer for peptide drugs: evaluation of absorption enhancing effect and nasal mucosa perturbation in rats
Authors: Wang Jian , Sakai Shigeko , Deguchi Yoshiharu , Bi Dianzhou , Tabata Yasuhiko , Morimoto Kazuhiro 
Published: October 2002

Abstract
This study was carried out to evaluate the potential of aminated gelatin as a nasal absorption enhancer for peptide drugs. The absorption-enhancing effect was investigated in rats using insulin and fluorescein isothiocyanate-dextran with a molecular weight of 4.4 kDa (FD-4) as model drugs. The absorption of insulin was estimated by measuring the changes in plasma glucose levels following intranasal administration, and that of FD-4 was determined by measuring its plasma concentration after dosing. The hypoglycaemic effect after intranasal administration of insulin with aminated gelatin significantly increased compared with that after intranasal administration of insulin in phosphate buffered saline, indicating that aminated gelatin effectively enhanced the nasal absorption of insulin. In contrast, neither kind of native gelatin (isoelectric point = 5.0 and 9.0) showed any absorption-enhancing effect. The pH of the formulations and the concentration of aminated gelatin were found to affect the hypoglycaemic effect. In addition, aminated gelatin at a concentration of 0.2 % significantly enhanced the absorption and the efflux of FD-4 through the rat nasal mucosa. The possible perturbation of aminated gelatin to nasal mucosa was evaluated by measuring the leaching of lactate dehydrogenase (LDH) using an in-situ perfusion rat model. Aminated gelatin presented a concentration-dependent (0.1-0.4 %) but relatively small effect on the LDH leaching from the rat nasal epithelial membrane. These results suggest that positively charged aminated gelatin could be a new absorption enhancer for nasal delivery of peptide drugs.
Recent trends in stabilizing protein structure upon encapsulation and release from bioerodible polymers
Authors: Pérez Caroline , Castellanos Ingrid J , Costantino Henry R , Al-Azzam Wasfi , Griebenow Kai 
Published: October 2002

Abstract
Sustained release of pharmaceutical proteins from biocompatible polymers offers new opportunities in the treatment and prevention of disease. The manufacturing of such sustained-release dosage forms, and also the release from them, can impose substantial stresses on the chemical integrity and native, three-dimensional structure of proteins. Recently, novel strategies have been developed towards elucidation and amelioration of these stresses. Non-invasive technologies have been implemented to investigate the complex destabilization pathways that can occur. Such insights allow for rational approaches to protect proteins upon encapsulation and release from bioerodible systems. Stabilization of proteins when utilizing the most commonly employed procedure, the water-in-oil-in-water (w/o/w) double emulsion technique, requires approaches that are based mainly on either increasing the thermodynamic stability of the protein or preventing contact of the protein with the destabilizing agent (e.g. the water/oil interface) by use of various additives. However, protein stability is still often problematic when using the w/o/w technique, and thus alternative methods have become increasingly popular. These methods, such as the solid-in-oil-in-oil (s/o/o) and solid-in-oil-in-water (s/o/w) techniques, are based on the suspension of dry protein powders in an anhydrous organic solvent. It has become apparent that protein structure in the organic phase is stabilized because the protein is “rigidified” and therefore unfolding and large protein structural perturbations are kinetically prohibited. This review focuses on strategies leading to the stabilization of protein structure when employing these different encapsulation procedures.
The long-lasting anti-anginal effects of CP-0605 in a rat model of arginine vasopressin-induced myocardial ischaemia
Authors: Adachi Yuichiro , Suzuki Yoshiyuki , Hatanaka Takahiro , Fukazawa Masanori , Tamura Kazuhiko 
Published: October 2002

Abstract
The anti-anginal effect of CP-060S, a new cardioprotective agent that prevents myocardial Na+-, Ca2+-overload and has Ca2+-channel blocking activity, was evaluated in a rat model of arginine8-vasopressin (AVP)-induced cardiac ischaemia. Infusion of AVP (0.2 IU kg−1) depressed the electrocardiogram (ECG) ST segment, an index of myocardial ischaemia. Vehicle, CP-060S and diltiazem were given orally 1, 2, 4, 8, 12 and 24 h before the administration of AVP. CP-060S, at 3 mg kg−1 and 10 mg kg−1, suppressed AVP-induced ST-segment depression for 2 h and 12 h, respectively. In contrast, diltiazem, at 10 and 30 mg kg−1, suppressed AVP-induced ST-segment depression for only 1 h. The persistent suppression of the AVP-induced ST-segment depression by CP-060S correlated with the time course of changes in its plasma concentration. The minimum effective concentration of CP-060S was estimated to be 30 ng mL−1 (≅ 50 nwi), consistent with its vasorelaxant potency in rat isolated aortic strips (concentration producing 50% relaxation of KCl contraction, IC50 = 32.6 ± 8.3 nM). Intravenously administered CP-060S, at 300 μg kg−1 and diltiazem at 500 μg kg−1 showed similar haemodynamic changes, whereas CP-060S, at 300 μg kg−1, significantly suppressed AVP-induced ST-segment depression and diltiazem, at 500 μg kg−1, had no effect on AVP-induced ST-segment depression. In summary, orally administered CP-060S exerted a long-lasting anti-anginal effect proportionate to the time course of changes in its plasma concentration in a rat model of AVP-induced ischaemia.
A validated high performance liquid chromatographic method for the analysis of Goldenseal
Authors: Li Wenkui , Fitzloff John F 
Published: October 2002

Abstract
Goldenseal (Hydrastis canadensis L.) has emerged as one of the top ten herbal supplements on the worldwide market. A rapid, simple and validated high performance liquid chromatographic method, with photodiode array detection, has been developed for the analysis of commercial Goldenseal products. Samples were treated by sonication with acidified methanol/water. The method was validated for LOD, LOQ, linearity, reproducibility and recovery with good results.