bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical evaluation of transcriptional targeting strategies for carcinoma of the breast in a tissue slice model system
Authors: Stoff-Khalili Mariam A , Stoff Alexander , Rivera Angel A , Banerjee Nilam S , Everts Maaike , Young Scott , Siegal Gene P , Richter Dirk F , Wang Minghui , Dall Peter , Mathis J Michael , Zhu Zeng B , Curiel David T 
Published: November 2005

Abstract
Introduction
In view of the limited success of available treatment modalities for metastatic breast cancer, alternative and complementary strategies need to be developed. Adenoviral vector mediated strategies for breast cancer gene therapy and virotherapy are a promising novel therapeutic platform for the treatment of breast cancer. However, the promiscuous tropism of adenoviruses (Ads) is a major concern. Employing tissue specific promoters (TSPs) to restrict transgene expression or viral replication is an effective way to increase specificity towards tumor tissues and to reduce adverse effects in non-target tissues such as the liver. In this regard, candidate breast cancer TSPs include promoters of the genes for the epithelial glycoprotein 2 (EGP-2), cyclooxygenase-2 (Cox-2), α-chemokine SDF-1 receptor (stromal-cell-derived factor, CXCR4), secretory leukoprotease inhibitor (SLPI) and survivin.

Methods
We employed E1-deleted Ads that express the reporter gene luciferase under the control of the promoters of interest. We evaluated this class of vectors in various established breast cancer cell lines, primary breast cancer cells and finally in the most stringent preclinical available substrate system, constituted by precision cut tissue slices of human breast cancer and liver.

Results
Overall, the CXCR4 promoter exhibited the highest luciferase activity in breast cancer cell lines, primary breast cancer cells and breast cancer tissue slices. Importantly, the CXCR4 promoter displayed a very low activity in human primary fibroblasts and human liver tissue slices. Interestingly, gene expression profiles correlated with the promoter activities both in breast cancer cell lines and primary breast cancer cells.

Conclusion
These data suggest that the CXCR4 promoter has an ideal 'breast cancer-on/liver-off' profile, and could, therefore, be a powerful tool in Ad vector based gene therapy or virotherapy of the carcinoma of the breast.
Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study
Authors: Christ-Crain Mirjam , Morgenthaler Nils G , Struck Joachim , Harbarth Stephan , Bergmann Andreas , Müller Beat 
Published: November 2005

Abstract
Introduction
Measurement of biomarkers is a potential approach to early assessment and prediction of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of mid-regional pro-adrenomedullin (MR-proADM) levels in a cohort of medical intensive care patients and to compare it with other biomarkers and physiological scores.

Method
We evaluated blood samples from 101 consecutive critically ill patients admitted to the intensive care unit and from 160 age-matched healthy control individuals. The patients had initially been enrolled in a prospective observational study investigating the prognostic value of endocrine dysfunction in critically ill patients ("PEDCRIP" Study). The prognostic value of MR-proADM levels was compared with those of two physiological scores and of various biomarkers (for example C-reactive Protein, IL-6, procalcitonin). MR-proADM was measured in EDTA plasma from all patients using a new sandwich immunoassay.

Results
On admission, 53 patients had sepsis, severe sepsis, or septic shock, and 48 had systemic inflammatory response syndrome. Median MR-proADM levels on admission (nmol/l [range]) were 1.1 (0.3–3.7) in patients with systemic inflammatory response syndrome, 1.8 (0.4–5.8) in those with sepsis, 2.3 (1.0–17.6) in those with severe sepsis and 4.5 (0.9–21) in patients with septic shock. In healthy control individuals the median MR-proADM was 0.4 (0.21–0.97). On admission, circulating MR-proADM levels in patients with sepsis, severe sepsis, or septic shock were significantly higher in nonsurvivors (8.5 [0.8–21.0]; P < 0.001) than in survivors (1.7 [0.4–17.6]). In a receiver operating curve analysis of survival of patients with sepsis, the area under the curve (AUC) for MR-proADM was 0.81, which was similar to the AUCs for IL-6, Acute Physiology and Chronic Health Evaluation II score and Simplified Acute Physiology Score II. The prognostic value of MR-proADM was independent of the sepsis classification system used.

Conclusion
MR-proADM may be helpful in individual risk assessment in septic patients.
Does taking endurance into account improve the prediction of weaning outcome in mechanically ventilated children?
Authors: Noizet Odile , Leclerc Francis , Sadik Ahmed , Grandbastien Bruno , Riou Yvon , Dorkenoo Aimée , Fourier Catherine , Cremer Robin , Leteurtre Stephane 
Published: November 2005

Abstract
Introduction
We conducted the present study to determine whether a combination of the mechanical ventilation weaning predictors proposed by the collective Task Force of the American College of Chest Physicians (TF) and weaning endurance indices enhance prediction of weaning success.

Method
Conducted in a tertiary paediatric intensive care unit at a university hospital, this prospective study included 54 children receiving mechanical ventilation (≥6 hours) who underwent 57 episodes of weaning. We calculated the indices proposed by the TF (spontaneous respiratory rate, paediatric rapid shallow breathing, rapid shallow breathing occlusion pressure [ROP] and maximal inspiratory pressure during an occlusion test [Pimax]) and weaning endurance indices (pressure-time index, tension-time index obtained from P0.1 [TTI1] and from airway pressure [TTI2]) during spontaneous breathing. Performances of each TF index and combinations of them were calculated, and the best single index and combination were identified. Weaning endurance parameters (TTI1 and TTI2) were calculated and the best index was determined using a logistic regression model. Regression coefficients were estimated using the maximum likelihood ratio (LR) method. Hosmer–Lemeshow test was used to estimate goodness-of-fit of the model. An equation was constructed to predict weaning success. Finally, we calculated the performances of combinations of best TF indices and best endurance index.

Results
The best single TF index was ROP, the best TF combination was represented by the expression (0.66 × ROP) + (0.34 × Pimax), and the best endurance index was the TTI2, although their performance was poor. The best model resulting from the combination of these indices was defined by the following expression: (0.6 × ROP) – (0.1 × Pimax) + (0.5 × TTI2). This integrated index was a good weaning predictor (P < 0.01), with a LR+ of 6.4 and LR+/LR- ratio of 12.5. However, at a threshold value <1.3 it was only predictive of weaning success (LR- = 0.5).

Conclusion
The proposed combined index, incorporating endurance, was of modest value in predicting weaning outcome. This is the first report of the value of endurance parameters in predicting weaning success in children. Currently, clinical judgement associated with spontaneous breathing trials apparently remain superior.
Intensive insulin therapy does not alter the inflammatory response in patients undergoing coronary artery bypass grafting: a randomized controlled trial [ISRCTN95608630]
Authors: Hoedemaekers Cornelia W , Pickkers Peter , Netea Mihai G , van Deuren Marcel , Van der Hoeven Johannes G 
Published: November 2005

Abstract
Introduction
Strict control of plasma glucose in diabetic and non-diabetic patients has been shown to improve outcome in several clinical settings. There is extensive evidence that glucose can stimulate the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α and IL-6, with no effect on the anti-inflammatory cytokine IL-10. We hypothesized that strict glucose regulation results in a change in cytokine balance from a pro-inflammatory state to a more balanced anti-inflammatory condition. In a randomized controlled trial we studied the effect of strict glycemic control on the local and systemic pro-inflammatory and anti-inflammatory balance in non-diabetic patients undergoing elective coronary artery bypass grafting with cardiopulmonary bypass.

Methods
After surgery patients were randomly assigned to intensive insulin therapy (blood glucose between 80 and 110 mg/dl) or conventional insulin therapy (blood glucose less than 200 mg/dl). At 0, 1, 2, 4, 8, 12, 16 and 24 hours after admission to the intensive care unit, plasma samples and samples from the mediastinal drains were obtained. We measured the concentrations of the pro-inflammatory cytokines TNF-α and IL-6 and the anti-inflammatory cytokine IL-10 by enzyme-linked immunosorbent assay.

Results
Both patient groups were comparable in demographics, clinical characteristics and peri-operative data. In the intensive treatment group, glucose levels were significantly lower than in the conventionally treated group. No differences were found between both groups in the concentrations of TNF-α, IL-6 and IL-10 in plasma samples or in fluid draining the mediastinal cavity. Levels of IL-6 and IL-10 were significantly higher in mediastinal fluid samples than in plasma samples, suggesting a compartmentalized production of cytokines.

Conclusion
The protective effect of intensive insulin therapy in patients after cardiac surgery with cardiopulmonary bypass is not related to a change in cytokine balance from a pro-inflammatory to an anti-inflammatory pattern. Systemic cytokine levels are not representative of the local inflammatory response.
Drug-Related Emergency Department Visits in an Elderly Veteran Population
Authors: Yee Jennie L , Hasson Noelle K , Schreiber Donald H 
Published: November 2005

BACKGROUND Given that adverse drug events result in extensive costs and healthcare resource utilization, the goal is to better understand drug-related emergency department (ED) visits so that programs can be implemented to improve the quality of health care. OBJECTIVE To (1) determine the incidence of drug-related ED visits at a large, tertiary care, Veterans Affairs hospital; (2) identify causes of these drug-related ED visits; (3) determine patient outcomes, healthcare resource utilization, and costs associated with these visits; and (4) determine the proportion of adverse drug reaction (ADR)–related ED visits that were spontaneously reported to the hospital's ADR reporting program. METHODS We conducted a retrospective electronic chart review of all patients who visited the ED during the second week of each month in 2003. Causes for drug-related visits were identified. ADRs in this study included side effects, drug allergies, and drug–drug interactions (DDIs) and were assessed using the Naranjo probability scale. RESULTS A total of 2169 patients were included in the study. Drug-related visits accounted for 12.6% of all ED visits. The main causes of drug-related visits were ADRs and nonadherence, which accounted for 33% and 19% of drug-related visits, respectively. Only 11% of these ADRs were spontaneously reported to the hospital's ADR reporting program. Thirty-five percent of drug-related visits led to hospitalizations, which resulted in an average length of stay of 9.3 days. The institution's total cost of drug-related visits was approximately $1.5 million over 12 weeks. CONCLUSIONS Many ED visits are drug related and often result in hospitalization and increased healthcare resource utilization. Only a minimal number of the ADRs resulting in ED visits are spontaneously reported to hospital ADR reporting programs.
Myocardial Infarction Associated with Intravenous Immune Globulin
Authors: Stenton Sunita Bond , Dalen Dawn , Wilbur Kerry 
Published: November 2005

OBJECTIVE To report a case of acute myocardial infarction (MI) experienced by a patient receiving intravenous immune globulin (IVIG) and review other published cases of MI associated with IVIG. CASE SUMMARY An 81-year-old Vietnamese man was prescribed IVIG for treatment of toxic epidermal necrolysis secondary to allopurinol. Thirty minutes following the start of the IVIG infusion, the patient developed crushing retrosternal chest pain and shortness of breath. The pain improved upon discontinuation of IVIG infusion but recurred when IVIG was restarted. The troponin level reached 140 μg/L, and a persantine sestamibi stress test (MIBI) indicated anterolateral ischemia. The patient was diagnosed with non–ST-elevation MI. An objective causality assessment using the Naranjo probability scale revealed a probable association between this adverse reaction and IVIG treatment. DISCUSSION Although an association between IVIG administration and MI has not been demonstrated in clinical trials, accumulating clinical experience suggests that a relationship between IVIG and myocardial ischemia exists. Twenty published case reports were identified. Risk of acute MI seems to be increased with use of high-dose IVIG and in older individuals, especially those with at least one cardiovascular risk factor, such as ischemic heart disease or hypertension. CONCLUSIONS Case reports suggest a causal relationship between the use of IVIG and MI and other thrombotic events. While cardiovascular disease is not considered an absolute contraindication to therapy, expanding indications and subsequent use of IVIG merit that clinicians be aware of patient characteristics that may increase the risk for adverse reactions and recognize early signs of infarction.
Providing Patient Care in Community Pharmacies in Spain
Authors: Gastelurrutia Miguel Angel , Faus Maria José , Fernández-Llimós Fernando 
Published: November 2005

OBJECTIVE To review the current status of Spanish community pharmacy, both in practice and research terms, and analyze its future trends. FINDINGS Spain has a social security system where all citizens receive health care, social services, and pensions. All medical care and surgery are free for citizens; however, community pharmacies in Spain are privately owned. There are geographic and population standards for the establishment of new pharmacies, resulting in an average of 1 pharmacy per 2000 residents. Almost all pharmacies offer the same services: compounding, weight and blood pressure measurement, and cholesterol and glucose testing. There are also other, less-implemented services, such as methadone supply or directed observed treatments. Most of these services are freely provided, except compounding (fee for service), methadone, and directed observed treatments. University pharmacy practice departments do not exist in Spain, which leads to scarce research in this area. DISCUSSION Efforts have been made to describe and measure the prevalence of negative clinical outcomes produced by pharmacotherapy and create an operational procedure to provide pharmacotherapy follow-up. CONCLUSIONS Spain has many community pharmacies, but there is little pharmacy practice research. Some advanced cognitive services exist, but few are being remunerated.
Dose Intensification with Infliximab in Patients with Rheumatoid Arthritis
Authors: Berger Ariel , Edelsberg John , Li Tracy T , Maclean John R , Oster Gerry 
Published: November 2005

BACKGROUND Infliximab, in combination with methotrexate, is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA). While there is anecdotal evidence that many patients beginning infliximab therapy have their dose and/or frequency of infusions increased over time (“dose intensification”), relatively little is known about actual patterns of use in clinical practice. OBJECTIVE To examine patterns of infliximab use in patients with RA. METHODS Using a large US healthcare claims database, all patients with RA who initiated infliximab therapy between January 1, 2000, and September 30, 2001, were identified. The date of each patient's first claim for infliximab was identified and designated as the index date; attention was limited to patients who received infliximab for at least one year. Patterns of infliximab use were then examined over the 12-month period following the index date, based on information on paid claims. RESULTS Fifty-three patients met all entry criteria; the mean age was 61 years, and 81% were women. Twenty-eight percent of patients received >8 infusions over 12 months. The mean dose of infliximab at initial infusion was 296.2 mg; at final infusion, it was 401.9 mg (36% increase). One-half of study subjects had their dose of infliximab increased by ≥30% between the initial and final infusions; one-third had their dose increased by ≥50%. CONCLUSIONS Many patients with RA beginning treatment with infliximab have their frequency of infusions and/or medication dose increased within the first 12 months.
Effect of Bupropion on Sexual Dysfunction
Authors: Ginzburg Regina , Wong Yvonne , Fader Jonathan S 
Published: November 2005

OBJECTIVE To determine the role of bupropion in treatment of sexual dysfunction. DATA SOURCES Studies and case reports were identified through MEDLINE (1970–July 2005) using search terms bupropion, antidepressants, sexual function, and sexual dysfunction. DATA SYNTHESIS Bupropion has been shown to have a favorable effect on sexual dysfunction. Several reports and small, short-term trials have examined bupropion as an adjunct or substitute for other antidepressants in sexually dysfunctional patients. Use of bupropion has also been studied in nondepressed patients. Bupropion may be a promising medication for treating sexual dysfunction. However, specific dosing is unclear. CONCLUSIONS While the studies reviewed here demonstrated some benefit in using bupropion to treat sexual dysfunction, limitations exist. Future studies should be conducted using larger sample sizes.
Acute Hypersensitivity Reaction to Ferric Gluconate in a Premedicated Patient
Authors: Saadeh Claire E , Srkalovic Gordan 
Published: November 2005

OBJECTIVE To report a case of an acute hypersensitivity reaction to ferric gluconate in a patient premedicated with dexamethasone, diphenhydramine, and prochlorperazine. CASE SUMMARY A 38-year-old female with persistent iron deficiency anemia was initiated on parenteral iron therapy with ferric gluconate 125 mg intravenously over 10 minutes. The patient initially tolerated this first dose well; however, she later experienced nausea, dizziness, and minor tongue swelling. On her second course of therapy, the woman was premedicated with dexamethasone, diphenhydramine, and prochlorperazine prior to the same dose of ferric gluconate infused over 30 minutes. Subsequently, the patient developed epigastric pain, nausea, swelling of her lips and tongue, and hypotension. The symptoms abated after administration of diphenhydramine, dexamethasone, morphine, cimetidine, intravenous fluids, and oxygen. She was discharged after a short stay in the emergency department observation unit. DISCUSSION Data are limited on the relative safety of ferric gluconate compared with iron dextran. Ferric gluconate does not appear to be associated with severe life-threatening events; however, the possibility of an acute hypersensitivity reaction with this product does exist. In this case, use of the Naranjo probability scale indicated a probable relationship between the hypersensitivity reaction and ferric gluconate. CONCLUSIONS Healthcare professionals should be aware of this serious but rare event and encouraged to further document and report these events.
Update in Handheld Electronic Resources for Evidence-Based Practice in the Community Setting
Authors: Burkiewicz Jill S , Vesta Kimi S , Hume Anne L 
Published: November 2005

OBJECTIVE To provide an update on the handheld electronic resources for evidence-based practice (EBP) in the community setting. DATA SOURCES Electronic resources for EBP in the community setting were identified by compiling the commonly used, well-established resources and by searching MEDLINE and other Internet sites. Search terms included evidence-based medicine, evidence-based practice, resources, and abstraction. Only sources available for personal digital assistants were included. DATA EXTRACTION Three databases were identified that provided abstraction and evaluation of the medical literature for the handheld platform. Content, features, ease of use, system requirements, and costs of each resource were evaluated. DATA SYNTHESIS FIRSTConsult, InfoRetriever, and UpToDate were evaluated, and the utility of each in the community pharmacy setting was evaluated by tracking a clinically relevant example through each system. FIRSTConsult provides evidence-based information organized by diagnosis but is not searchable on the handheld platform. InfoRetriever focuses on searchable evidence-based summaries, while UpToDate includes comprehensive topic reviews. The latter 2 platforms have large system memory requirements. All 3 sources provide evidence-based abstraction of the medical literature for the PDA platform, convenient for use at the point of care in community pharmacy. CONCLUSIONS While users may select a particular resource based on unique features, each provides evidence-based abstraction of the medical literature that is a practical approach to EBP in the community pharmacy setting.
Stress and coping strategies among Zimbabwean adolescents
Authors: Magaya Lindiwe , Asner‐Self Kimberly K. , Schreiber James B. 
Published: November 2005

Background. Stress and social support influence adolescents' coping strategies. Adolescents need to acquire a large repertoire of coping strategies in light of a rapidly changing socio‐economic and political situation.Aim. This study reports on the coping strategies of Zimbabwean adolescents and highlights some major stressors they face. The interplay among stress, social support and the coping strategies of Zimbabwean adolescents are also reported.Sample. A sample of 101 Zimbabwean students (ages 17–19) participated in this study.Method. Participants completed three instruments: the Perceived Stress Scale, the Social Provision Scale and the Ways of Coping Scale.Results. Zimbabwean adolescents experienced slight stress as measured by the Perceived Stress Scale. Major stressors included schoolwork, relationships, social life and financial hardship. Females reported a higher level of perceived stress than males. Zimbabwean adolescents reported having fewer social provisions than the norm group. Results from the Ways of Coping Scale indicated that Zimbabwean adolescents use emotion‐focused strategies more frequently than problem‐solving strategies.Conclusion. The implications of the study are that Zimbabwean adolescents may need to acquire a larger repertoire of coping skills adding to what they may already have. Problem‐solving skills need to be employed in face of today's challenging situations.