bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophage and Mast-Cell Invasion of Tumor Cell Islets Confers a Marked Survival Advantage in Non–Small-Cell Lung Cancer
Authors: Welsh Tomas J. , Green Ruth H. , Richardson Donna , Waller David A. , O'Byrne Kenneth J. , Bradding Peter 
Published: October 2005

Purpose The role played by the innate immune system in determining survival from non–small-cell lung cancer (NSCLC) is unclear. The aim of this study was to investigate the prognostic significance of macrophage and mast-cell infiltration in NSCLC. Methods We used immunohistochemistry to identify tryptase+ mast cells and CD68+ macrophages in the tumor stroma and tumor islets in 175 patients with surgically resected NSCLC. Results Macrophages were detected in both the tumor stroma and islets in all patients. Mast cells were detected in the stroma and islets in 99.4% and 68.5% of patients, respectively. Using multivariate Cox proportional hazards analysis, increasing tumor islet macrophage density (P < .001) and tumor islet/stromal macrophage ratio (P < .001) emerged as favorable independent prognostic indicators. In contrast, increasing stromal macrophage density was an independent predictor of reduced survival (P = .001). The presence of tumor islet mast cells (P = .018) and increasing islet/stromal mast-cell ratio (P = .032) were also favorable independent prognostic indicators. Macrophage islet density showed the strongest effect: 5-year survival was 52.9% in patients with an islet macrophage density greater than the median versus 7.7% when less than the median (P < .0001). In the same groups, respectively, median survival was 2,244 versus 334 days (P < .0001). Patients with a high islet macrophage density but incomplete resection survived markedly longer than patients with a low islet macrophage density but complete resection. Conclusion The tumor islet CD68+ macrophage density is a powerful independent predictor of survival from surgically resected NSCLC. The biologic explanation for this and its implications for the use of adjunctive treatment requires further study.
Not Working 3 Years After Breast Cancer: Predictors in a Population-Based Study
Authors: Drolet Mélanie , Maunsell Elizabeth , Brisson Jacques , Brisson Chantal , Mâsse Benoît , Deschênes Luc 
Published: October 2005

Purpose Little is known about factors increasing likelihood of not working among breast cancer survivors compared with women in the general population. Patients and Methods A population-based retrospective cohort study was conducted in Quebec, Canada, based on the consecutive series of working women aged younger than 60 years when first treated for breast cancer (identified through the Quebec Tumor Registry), and on a group of randomly selected similar women, living in Quebec, who were working at the time of survivors' diagnoses, but who were without cancer (identified through provincial health care files). Data came from a telephone interview, 3 years after diagnosis for 646 survivors (73% of those eligible) or during a similar period for 890 comparison women (51%). Results Slightly more survivors were not working 3 years after diagnosis compared with women never diagnosed with cancer (21% and 15%, respectively). Older age (for survivors and comparison women, relative risk [RR] = 4.62, P < .0001 and RR = 4.98, P < .0001, respectively) and union membership (RR = 1.88, P = .0003 and RR = 1.40, P = .06, respectively) increased the likelihood of not working at the end of follow-up. In addition, income less than $20,000 compared with ≥ $50,000 was associated with not working only among survivors (RR = 3.18; P = .0008). Adjuvant treatments did not predict work cessation, but any new cancer event during follow-up did (RR = 2.14; P < .0001). Conclusion Although reassuring that adjuvant treatments did not appear to play a role in survivors' not working, other aspects of the cancer experience might nonetheless have influenced the decision to reduce work effort after breast cancer.
Fatigue and Relating Factors in High-Risk Breast Cancer Patients Treated With Adjuvant Standard or High-Dose Chemotherapy: A Longitudinal Study
Authors: Nieboer Peter , Buijs Ciska , Rodenhuis Sjoerd , Seynaeve Caroline , Beex Louk V.A.M. , van der Wall Elsken , Richel Dick J. , Nooij Marianne A. , Voest Emile E. , Hupperets Pierre , Mulder Nanno H. , van der Graaf Winette T.A. , TenVergert Els M. , van Tinteren Harm , de Vries Elisabeth G.E. 
Published: October 2005

Purpose Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients. Patients and Methods Eight hundred eighty-five patients were randomly assigned between two chemotherapy regimens both followed by radiotherapy and tamoxifen. Fatigue was assessed using vitality scale (score ≤ 46 defined as fatigue), poor mental health using mental health scale (score ≤ 56 defined as poor mental health) both of Short-Form 36, muscle and joint pain with Rotterdam Symptom Checklist, and Hb levels were assessed before and 1, 2, and 3 years after chemotherapy. Results Fatigue was reported in 20% of 430 assessable patients (202 standard-dose, 228 high-dose) with at least a 3-year follow-up, without change over time or difference between treatment arms. Mean Hb levels were lower following high-dose chemotherapy. Only 5% of patients experienced fatigue and anemia. Mental health score was the strongest fatigue predictor at all assessment moments. Menopausal status had no effect on fatigue. Linear mixed effect models showed that the higher the Hb level (P = .0006) and mental health score (P < .0001), the less fatigue was experienced. Joint (P < .0001) and muscle pain (P = .0283) were associated with more fatigue. Conclusion In 3 years after treatment, no significant differences in fatigue were found between standard and high-dose chemotherapy. Fatigue did not change over time. The strongest fatigue predictor was poor mental health.
Discriminant analysis as a tool to identify compounds with potential as transdermal enhancers
Authors: Pugh W J , Wong R , Falson F , Michniak B B , Moss G P 
Published: October 2005

Abstract
Structure-activity relationships were sought for 73 enhancers of hydrocortisone permeation from propylene glycol across hairless mouse skin. Enhancers had chain lengths (CC) from 0 to 16 carbon atoms, 1 to 8 H-bonding atoms (HB), molecular weight 60 to 450, log P (calculated) −1.7 to 9.7 and log S (calculated) −7.8 to 0.7. These predictive properties were chosen because of their ready availability. Enhancement ratio (ER) was defined as hydrocortisone transferred after 24 h relative to control. Values for the ER ranged from 0.2 to 25.3. Multiple regression analysis failed to predict activity; ER values for the ‘good’ enhancers (ER&gt;10) were underestimated. Simple guidelines suggested that high ER was associated with CC&gt;12 and HB 2–5. This was refined by multivariate analysis to identify significant predictors. Discriminant analysis using CC, HB, and molecular weight correctly assigned 11 of the 12 ‘good’ enhancers (92%). The incorrectly assigned compound was a known, idiosyncratic Br compound. Seventeen of the 61 ‘poor’ enhancers (28%) were incorrectly assigned but four could be considered marginal (ER&gt;8). The success of this simple approach in identifying potent enhancers suggested its potential in predicting novel enhancer activity.
Dexmedetomidine prolongs spinal anaesthesia induced by levobupivacaine 0.5% in guinea-pigs
Authors: Calasans-Maia Jorge A , Zapata-Sudo Gisele , Sudo Roberto T 
Published: October 2005

Abstract
Alpha-2 adrenoceptor agonists have been used in association with local anaesthetic to increase the duration of spinal anaesthesia. Intrathecal administration of clonidine prolonged motor blockade induced by local anaesthetic. Since the affinity of dexmedetomidine (DEX) to alpha-2 adrenoceptors is eight-times greater than clonidine, it is expected that DEX could be advantageous in clinical anaesthesia. We investigated the duration of motor nerve block induced by spinal injection of 0.5% levobupivacaine (LVB) associated with intrathecal or intraperitoneal administration of DEX. Seventy-two guinea-pigs were randomly divided in 12 groups, which were all treated with intrathecal injection of 50 μL of LVB. DEX was injected intrathecally with LVB in 6 groups or injected intraperitoneally after LVB in another 6 groups. Intrathecal DEX (0.1, 0.2 and 0.4 μg) increased the LVB-induced motor anaesthesia from 48 (41–66) min to 84.5 (52–91) min (P&lt;0.05), 101.5 (83–115) min (P&lt;0.05) and 105 (97–114) min (P&lt;0.05), respectively. Similarly, intraperitoneal DEX (20 and 40 μg kg−1) increased the motor blockade from 48.5 (33–59) min to 88 (71–114) min (P&lt;0.05) and 114.5 (103–156) min (P&lt;0.05), respectively. Pre-treatment with yohimbine reduced the duration of motor block from 101.5 (83–115) to 76.5 (68–86) min (P&lt;0.05) or from 114.5 (103–156) to 90 (83–93) min (P&lt;0.05) when DEX was administered by the intrathecal or intraperitoneal routes. Motor block induced by spinal injection of LVB was prolonged by intrathecal and systemic administration of DEX, which was partially dependent on activation of alpha-2 adrenoceptors.
Involvement of P-glycoprotein in the release of cytokines from peripheral blood mononuclear cells treated with methotrexate and dexamethasone
Authors: Pawlik A , Gawrońska-Szklarz B , Baśkiewicz-Masiuk M , Machaliński B , Safranow K 
Published: October 2005

Abstract
P-glycoprotein (P-gp), a product of the MDR1 gene, is an important factor in the turnover of many drugs and xenobiotics. Recent reports have suggested that P-gp can also be involved in the transport of cytokines. The aim of this study was to examine the role of P-gp in cytokine release from phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (MNCs) as well as in the release of cytokines from MNCs treated with methotrexate (MTX) and dexamethasone (DEX). The study was carried out on PHA-stimulated MNC from 10 healthy subjects. Flow cytometry was applied to measure interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ and tumour necrosis factor (TNF)-α levels in the culture supernatants. In the experiments verapamil (VER) and P-gp specific monoclonal antibodies (mAb) (clone 17F9) were used to inhibit P-gp function. P-gp inhibitors suppressed the release of IL-2, IL-4, IFN-γ and TNF-α from PHA-stimulated MNC, whereas release of IL-6 and IL-10 remained unaffected. VER and mAb significantly decreased the release of IL-2, IL-4, TNF-α and INF-γ in MNC cultures treated with MTX or DEX. The results of this study suggest that P-gp may be involved in the transmembrane transport of some cytokines. Moreover, it seems that blocking of P-gp function may influence the release of some cytokines from MNCs, displaying an additive inhibitory effect to DEX and MTX.
Treatment with Y-40138, a multiple cytokine production modulator, inhibits lipopolysaccharide- or tumour necrosis factor-α-induced production of pro-inflammatory cytokines and augments interleukin-10
Authors: Fukuda Tetsuko , Hisadome Masao , Komatsu Hirotsugu 
Published: October 2005

Abstract
N-[1-(4-[4-(pyrimidin-2-yl)piperazin-1-yl]methyl phenyl)cyclopropyl] acetamide.HCl (Y-40138) suppresses liver injury in concanavalin A- and d-galactosamine/lipopolysaccharide (LPS)-induced mouse hepatitis models. However, the mechanism of action of Y-40138 has not been fully investigated. In this study, we examined the effect of Y-40138 on cytokine production in mice. Cytokine production was induced by intraperitoneal injection of LPS (0.5 mg kg−1) or intravenous injection of recombinant mouse tumour necrosis factor (TNF)-α (10μg mouse−1) in BALB/c mice. TNF-α and interleukin (IL)-10 reached maximum levels 1.5 h after the LPS injection. IL-12 and interferon-γ (IFN-γ) reached maximum levels 3 to 9 h after the injection. When Y-40138 was orally administered 30 min prior to the injection, it inhibited TNF-α, IL-12 and IFN-γ production and augmented IL-10 production. Y-40138 also inhibited IL-12 production and augmented IL-10 production in TNF-α-stimulated mice. In IL-10 knockout mice, Y-40138 inhibited TNF-α and IL-12 production 1.5h after the LPS injection but not after 3 h or later, unlike in wild mice. In addition, TNF-α production was inhibited by Y-40138 at concentrations that could not augment IL-10 production. These data suggest that Y-40138 modulates pro-inflammatory cytokine production by both IL-10-dependent and -independent mechanisms.
Attenuation of ciclosporin-induced nephrotoxicity by dietary supplementation of seal oil in Sprague-Dawley rats
Authors: Yang Wei , Kang Zhili , Wang Lili , Kara Mohamedtaki , Herzberg Gene R , Robb Desmond , Randell Edward , Smeda John , Xiong Jieying , Liu Hu 
Published: October 2005

Abstract
Fish oil, rich in omega-3 (n-3) polyunsaturated fatty acids (PUFAs), has been reported to attenuate nephrotoxicity induced by ciclosporin (cyclosporine A). Harp seal oil is a rich source of n-3 PUFAs. This study investigated the ability of dietary seal oil to reduce nephrotoxicity caused by ciclosporin. Sprague-Dawley rats were maintained on a standard diet (with sunflower oil as lipid, SFO) or a diet enriched with seal oil (with 85% seal oil and 15% sunflower oil as lipid, SO) for four weeks before and four weeks after intravenous administration of ciclosporin (15 mg kg−1 daily). Kidney function was assessed by measuring blood urea nitrogen, creatinine clearance, urinary N-acetyl-1-β-d-glucosaminidase, 6-keto-prostaglandin F1α, thromboxane B2 and malondialdehyde. Systolic blood pressure (SBP) was monitored. Ciclosporin concentrations in blood were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The fatty acid compositions of the diets and erythrocyte membranes were analysed by gas chromatography (GC). The results showed that nephrotoxicity was induced by ciclosporin in rats maintained on both SO and SFO diets. However, rats fed on SO diet endured less toxicity than those on SFO diet. The n-3 and n-6 PUFAs in the erythrocyte membrane of rats maintained on SO diet were found to be 10.79% and 11.93%, while those in rats maintained on SFO diet were found to be 1.67% and 22.71%, respectively. In conclusion, dietary supplementation of seal oil was found to reduce ciclosporin-induced nephrotoxicity in rats.
Protective effects of Polygala paniculata extract against methylmercury-induced neurotoxicity in mice
Authors: Farina Marcelo , Franco Jeferson Luis , Ribas Camila Mafalda , Meotti Flávia Carla , Dafré Alcir Luiz , Santos Adair R S , Missau Fabiana , Pizzolatti Moacir G 
Published: October 2005

Abstract
We have examined the possible protective effects of Polygala paniculata extract against methylmercury (MeHg)-induced neurotoxicity in adult mice. MeHg was diluted in drinking water (40 mg L−1, freely available) and the hydroalcoholic Polygala extract was diluted in a 150 mm NaCl solution and administered by gavage (100 mg kg−1 b.w., twice a day). After a two-week treatment, MeHg exposure significantly inhibited glutathione peroxidase and increased glutathione reductase activity, while the levels of thiobarbituric acid reactive substances were increased in the cerebral cortex and cerebellum. These alterations were prevented by administration of Polygala extract, except for glutathione reductase activity, which remained elevated in the cerebral cortex. Behavioural interference in the MeHg-exposed animals was evident through a marked deficit in the motor performance in the rotarod task, which was completely recovered to control levels by Polygala extract co-administration. This study has shown, for the first time, the in-vivo protective effects of Polygala extract against MeHg-induced neurotoxicity. In addition, our findings encourage studies concerning the beneficial effects of P. paniculata on neurological conditions related to excitotoxicity and oxidative stress.
Aralast: A New α1-Protease Inhibitor for Treatment of α-Antitrypsin Deficiency
Authors: Louie Stan Gee , Sclar David Alexander , Gill Mark Anthony 
Published: October 2005

OBJECTIVE To review the epidemiology, pathogenesis, and management of patients with α-antitrypsin (AAT) deficiency syndrome and compare Aralast with Prolastin, 2 of the 3 available human plasma–derived AAT agents. DATA SOURCES Articles were identified using a MEDLINE (1966–September 2005) search with MESH headings that included α-antitrypsin and emphysema. STUDY SELECTION AND DATA EXTRACTION All papers from peer-reviewed journals on the laboratory or clinical efficacy of plasma-derived AAT (eg, Prolastin, Aralast) for patients with this autosomal recessive disorder were reviewed. DATA SYNTHESIS Clinical trials found that AAT augmentation prevents progression of AAT-deficient emphysema and thus its associated morbidity and mortality. Treatment with Aralast has been shown to be safe and well tolerated, with a low incidence of mild to moderate adverse events. Pharmacoeconomics studies of AAT augmentation demonstrated that the use of Aralast was cost-effective as lifelong augmentation therapy for AAT-deficient emphysema. CONCLUSIONS Because of its effectiveness and extra safety measure compared with Prolastin, Aralast should be recommended for formulary inclusion.
Identification of Inappropriate Drug Prescribing by Computerized, Retrospective DUR Screening in Korea
Authors: Yeom Jong Hum , Park Ji Sun , Oh Ock-Hee , Shin Hyun Taek , Oh Jung Mi 
Published: October 2005

BACKGROUND In Korea, the drug use process has changed significantly since the new pharmacy law was implemented in 2000, separating the prescribing and dispensing functions between physicians and pharmacists and mandating prospective drug use review (DUR) practice by pharmacists immediately before dispensing medications. However, a high prevalence of inappropriate prescribing has been suspected by the public, pharmacists, and health insurance managers, possibly due to suboptimal DUR practice by pharmacists. OBJECTIVE To assess overall patterns of drug usage and potential problems of inappropriate use in outpatient settings by analyzing prescription data that were electronically submitted to the national health insurance manager with a computerized DUR system and develop a computerized adjudication system model for drug claims. METHODS The national prescription drug claims data that were submitted electronically by pharmacies located in the northern part of Korea during 15 days in 2002 were retrospectively screened against the predetermined DUR standards of the selected criteria on drug dosage, duration of therapy, and drug interaction using the DUR screening system. The results of all the DUR conflicts were further validated manually by an expert panel and statistically analyzed to determine drug use patterns. RESULTS Of 31 994 260 drugs prescribed, 3 325 760 (10.4%) items showed a conflict with at least one of the DUR standards. The average number of drugs prescribed on each prescription was 4.07, and even more troubling was the high incidence of under-dosing, over-dosing, and contraindicated drug prescribing. CONCLUSIONS It is evident that inappropriate drug prescribing is very common in Korea; thus, a great deal of attention is urgently needed in the country with respect to proper prescribing and supportive interventions.
Levosimendan: A Novel Inotropic Agent for Treatment of Acute, Decompensated Heart Failure
Authors: Earl Grace L , Fitzpatrick James T 
Published: October 2005

OBJECTIVE To review the literature on a novel calcium sensitizer, levosimendan. DATA SOURCES Articles were identified through searches of MEDLINE (1966–June 2005), International Pharmaceutical Abstracts (1970–June 2005), and EMBASE (1992–June 2005) using the key words levosimendan, simendan, calcium sensitizer, calcium sensitiser, and congestive heart failure. STUDY SELECTION AND DATA EXTRACTION Clinical trials and pharmacokinetic studies evaluating the safety and efficacy of levosimendan were selected. DATA SYNTHESIS Levosimendan 6–24 μg/kg intravenous bolus followed by a 24-hour continuous infusion of 0.05—0.2 μg/kg/min improved cardiac output and reduced pulmonary capillary wedge pressure in a dose-dependent manner. Dose-ranging and randomized clinical trials have demonstrated improvement in symptoms and hemodynamics and short-term survival outcomes in the treatment of acute, decompensated heart failure. Clinical trials evaluating retrospective mortality data and combined endpoints (mortality, rehospitalization) have demonstrated better outcomes with levosimendan compared with dobutamine. The incidence of hypotension with levosimendan is not significantly different than with dobutamine, but there is a dose-related increase in heart rate. CONCLUSIONS Levosimendan is useful in moderate to severe low-output heart failure in patients who have failed to respond to diuretics and vasodilators. Based on current studies, levosimendan appears to be a safe alternative to dobutamine for treatment of acute, decompensated heart failure. Prospective clinical trials are needed to confirm the effect of levosimendan on long-term survival and its role in heart failure in the setting of myocardial infarction.
Providing Patient Care in Community Pharmacies in Australia
Authors: Benrimoj Shalom I , Roberts Alison S 
Published: October 2005

OBJECTIVE To describe Australia's community pharmacy network in the context of the health system and outline the provision of services. DATA SYNTHESIS The 5000 community pharmacies form a key component of the healthcare system for Australians, for whom health expenditures represent 9% of the Gross Domestic Product. A typical community pharmacy dispenses 880 prescriptions per week. Pharmacists are key partners in the Government's National Medicines Policy and contribute to its objectives through the provision of cognitive pharmaceutical services (CPS). The Third Community Pharmacy Agreement included funding for CPS including medication review and the provision of written drug information. Funding is also provided for a quality assurance platform with which the majority of pharmacies are accredited. Fifteen million dollars (Australian) have been allocated to research in community pharmacy, which has focused on achieving quality use of medicines (QUM), as well as developing new CPS and facilitating change. Elements of the Agreements have taken into account QUM principles and are now significant drivers of practice change. Although accounting for 10% of remuneration for community pharmacy, the provision of CPS represents a significant shift in focus to view pharmacy as a service provider. Delivery of CPS through the community pharmacy network provides sustainability for primary health care due to improvement in quality presumably associated with a reduction in healthcare costs. CONCLUSIONS Australian pharmacy practice is moving strongly in the direction of CPS provision; however, change does not occur easily. The development of a change management strategy is underway to improve the uptake of professional and business opportunities in community pharmacy.