bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-Xa Stability of Diluted Enoxaparin for Use in Pediatrics
Authors: Dager William E , Gosselin Robert C , King Jeffery H , Christensen Cinda L , Owings John T , Larkin Edward C 
Published: March 2004

BACKGROUND The use of enoxaparin in low-weight pediatric patients is becoming common practice. Anti-Xa stability of unit-dose syringes prepared after dilution beyond one day is presently unknown. OBJECTIVE To evaluate the anti-Xa stability of diluted enoxaparin stored in glass vials and tuberculin syringes. METHODS Four separate batches of enoxaparin were diluted with sterile water to a final concentration of 20 mg/mL (2000 IU/mL) and aliquoted into plastic 1-mL syringes containing 6 mg (0.3 mL) or maintained in the glass vial. Syringes were stored at room temperature or under refrigeration. The glass vial used for diluting was stored at room temperature. The anti-Xa activity was measured on the date of preparation to 4 weeks. Statistical comparisons determined whether differences in anti-Xa activity in diluted enoxaparin are affected by the storage medium or temperature. A paired t-test was used to determine any significant differences between the anti-Xa activity on date of preparation (baseline) and subsequent time periods, with p < 0.05 considered statistically significant. RESULTS The mean baseline anti-Xa activity was 2607 IU/mL (95% CI 2300 to 2914). No measurable decrease occurred in diluted enoxaparin anti-Xa activity in the glass vial maintained over the 4-week period. Compared with the glass vial, room temperature and refrigerated syringe samples had trending decreases of anti-Xa activity at weeks 3 and 4, but did not reach statistical significance. CONCLUSIONS A nonsignificant decrease in anti-Xa activity occurred starting at day 22 for the diluted enoxaparin in tuberculin syringes, regardless of storage temperature. Storage up to 4 weeks of diluted enoxaparin in glass or prefilled syringes does not result in a statistically significant loss of anticoagulant potential, as measured by anti-Xa activity.
Variability of Plasma Anti-Xa Activities with Different Lots of Enoxaparin
Authors: Gosselin Robert C , King Jeffery H , Janatpour Kim A , Dager William E , Larkin Edward C , Owings John T 
Published: March 2004

BACKGROUND Previous studies have indicated the variability of anti-Xa activity in different sources of heparin and the variability of different methods used for measuring anti-Xa activity. Manufacturers of low-molecular-weight heparins (LMWHs) determine each lot's anti-Xa activity against the World Health Organization standard, but little information is known about anti-Xa activity variation between lots of LMWH and the impact on reported anti-Xa activity in patient samples. OBJECTIVE To determine the variation of plasma anti-Xa activity in patients receiving enoxaparin when different lots of enoxaparin are used for test calibration. METHODS We obtained 7 lots of enoxaparin containing approximately 10 000 IU/mL and one lot containing approximately 15 000 IU/mL of anti-Xa activity. For each lot, a 2.0 anti-Xa IU/mL dilution was prepared and a calibration curve performed using a chromogenic method. To test the variation in reported results between the different calibration lots, 20 patient samples were tested. Nineteen patients receiving enoxaparin and one patient not receiving enoxaparin (negative control) were tested in a blinded fashion, and the changes in light absorbance recorded. Anti-Xa activity results from tested plasmas were then extrapolated from each enoxaparin lot calibration curve. RESULTS Using Student's paired t-test, there were statistically significant differences between the plasma anti-Xa activities generated from the various enoxaparin lots. In the range of 0.5–1.0 IU/mL of anti-Xa activity, 3 (4.2%) samples had a >0.2 IU/mL difference (maximum difference 0.33 IU/mL) in anti-Xa activity between 2 lots of enoxaparin. For samples that had supratherapeutic anti-Xa activities (1.0–1.5 IU/mL anti-Xa activity), there was a wider variation (>0.2 IU/mL) in anti-Xa activity, which may have resulted in a dosing change. CONCLUSIONS The statistical differences in plasma anti-Xa activities noted between enoxaparin lots are not clinically significant. However, anti-Xa activities in the upper therapeutic and supratherapeutic ranges (>1.0 IU/mL of anti-Xa activity) resulted in a deviation of >0.3 IU/mL in reported anti-Xa activity, which may result in dosing changes.
Industry Sponsorship and Authorship of Clinical Trials Over 20 Years
Authors: Buchkowsky Susan S , Jewesson Peter J 
Published: March 2004

BACKGROUND The pharmaceutical industry has become a major source of funding for biomedical research. Our general observation is that pharmaceutical industry employees are appearing with increasing frequency as coauthors of clinical trial publications. OBJECTIVE To characterize clinical trial funding, reporting, and sources; investigate author—industry affiliation; and describe clinical outcome trends over time. METHODS We reviewed 500 randomly selected clinical trials published in 5 influential medical journals over a 20-year period (1981–2000). RESULTS Of the 500 clinical trials reviewed, 181 (36%) involved pharmaceutical industry as an independent (n = 104) or joint (n = 77) sponsor and 180 (36%) involved a peer-review funding source; the balance (139; 28%) lacked any declared sponsorship. The percentage of industry-sponsored clinical trials increased to 62% during 1997–2000. The percentage of nonprofit sponsored clinical trials remained constant over time, while the percentage of those without funding declaration declined. Reported author affiliation with industry increased to 66% of clinical trials sponsored only by industry. An increase in the percentage of clinical trials with reported author—industry affiliation was observed for all journals. Regardless of funding source, the majority of clinical trials reported clinical outcomes that favored the study drug. CONCLUSIONS Pharmaceutical industry—sponsored and mixed-funding clinical trials are common, and the relative incidence of published trials with these declared funding sources in the 5 journals reviewed has increased. Industry employees are appearing as coauthors of clinical trial publications with increasing frequency.
Pediatric Constipation Therapy Using Guidelines and Polyethylene Glycol 3350
Authors: Bell Edward A , Wall Geoffrey C 
Published: March 2004

OBJECTIVE To review current guidelines on the treatment of functional constipation in pediatric patients, with an emphasis on the role of polyethylene glycol 3350 (PEG 3350). DATA SOURCES Primary medical literature published in English was identified by MEDLINE search (1980—May 2003). STUDY SELECTION AND DATA EXTRACTION Recently published treatment guidelines relating to pediatric functional constipation and its pharmacotherapy are assessed and compared. Published trials evaluating PEG 3350 in pediatric subjects are discussed and their results applied to the clinical role and use of this new agent. DATA SYNTHESIS Constipation is a common disorder among children. A number of factors may play a role. A variety of medications are commonly used for this disorder, although few treatments have undergone evaluation by controlled clinical trials. Consensus guidelines recommend either osmotic laxatives, mineral oil, or their combination for maintenance treatment in concert with patient and parental education and behavioral training. PEG 3350 solution (MiraLax) has been shown in recent clinical studies to be an effective maintenance treatment for pediatric constipation. CONCLUSIONS PEG 3350 is an effective and well-tolerated treatment choice for pediatric constipation, especially as an adjunct to education and behavioral training. PEG 3350 is an option for children with constipation who have failed or are intolerant of other pharmacotherapies. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-04-016-H01
Reversible Coma Secondary to Cefepime Neurotoxicity
Authors: Abanades Sergio , Nolla Juan , Rodríguez-Campello Ana , Pedro Carme , Valls Antonio , Farré Magí 
Published: March 2004

OBJECTIVE To describe a case of cefepime neurotoxicity associated with acute renal failure that resulted in nonconvulsive status epilepticus. CASE SUMMARY A 66-year-old woman with acute myeloid leukemia had fever on the third day of the initial chemotherapy cycle. Empiric antibiotic treatment with cefepime 2 g every 8 hours was started; fluconazole and vancomycin were subsequently added due to the persistence of fever. Ten days after initiation of cefepime, the patient developed acute renal failure followed by altered consciousness (Glasgow coma scale 6) associated with nonconvulsive status epilepticus. Cefepime was discontinued. Epileptiform activity in the electroencephalogram disappeared with clonazepam, and the patient regained consciousness 48 hours after cefepime withdrawal. DISCUSSION Acute renal impairment combined with the use of cefepime may account for nonconvulsive status epilepticus. An objective causality assessment revealed that the adverse event was probably due to cefepime. Cefepime's neurotoxic effects derive from high serum concentrations resulting from decreased renal clearance, increased unbound antibiotic, and blood–brain barrier dysfunction during uremia. CONCLUSIONS The combination of cefepime treatment and acute renal failure may induce drug-related neurotoxicity. Nonconvulsive status epilepticus frequently passes unnoticed in severely ill patients without a history of epilepsy. This disorder should be included in the list of potential causes of coma. In this patient, early detection of nonconvulsive status epilepticus and withdrawal of the antibiotic resulted in full recovery.
Combining Quinupristin/Dalfopristin with Other Agents for Resistant Infections
Authors: Brown Jack , Freeman Burgess B 
Published: March 2004

OBJECTIVE To review the resistance mechanisms of Enterococcus and Staphylococcus spp. and summarize quinupristin/dalfopristin's (QD's) effects on these resistant organisms when combined with other antibiotics via review of the literature and unpublished data. DATA SOURCES Data were identified by a PubMed search (1996—May 2003) using the search terms quinupristin/dalfopristin, synergy, in vitro, in vivo, vancomycin-resistant Enterococcus faecium (VREF), methicillin-resistant Staphylococcus aureus (MRSA), and individual antibiotic names. Bibliographies of the resultant PubMed searches were reviewed and included if applicable. STUDY SELECTION AND DATA EXTRACTION All studies reviewed were analyzed; specific drug data were included only if clinically pertinent. In vitro data from studies with adequate design were discussed, whereas all case reports and clinical trials were utilized. DATA SYNTHESIS In the treatment of VREF, available information seems conflicting, although some clear differences have become apparent. QD—ampicillin and QD—doxycycline combinations have demonstrated beneficial activity, usually displaying synergistic or additive effects even in macrolide-, lincosamine-, and streptogramin-resistant (MLSB) isolates. Vancomycin and chloramphenicol have shown some efficacy, but antagonistic or null results also have been observed. Regarding MRSA, results from many studies of QD combinations have been ambiguous. More common combinations displayed synergy or additive effects against MRSA, but only QD—rifampin showed consistent beneficial activity against MRSA and MLSB isolates. Most other combinations displayed antagonism when tested in vitro. CONCLUSIONS Data supporting the use of various QD—antibiotic combinations against VREF and MRSA are increasing, but further in vitro and in vivo data are needed to confirm the findings.
Low-Dose Granisetron for Postoperative Nausea and Vomiting Prophylaxis
Authors: Corman Shelby L , Skledar Susan J , Ansani Nicole T 
Published: March 2004

OBJECTIVE To evaluate the use of low-dose granisetron in postoperative nausea and vomiting prophylaxis. DATA SOURCES Clinical trials available through PubMed and OVID (1966—July 2003), as well as information supplied by the drug manufacturer, were accessed. DATA SYNTHESIS Safety concerns associated with droperidol and limited availability of other agents have created a need to restructure prophylaxis guidelines for postoperative nausea and vomiting. It has recently been proposed that granisetron may be effective at a dose that is one-tenth of the Food and Drug Administration—approved dose. Conflicting evidence for this regimen is evaluated. CONCLUSIONS Based on the scarcity of supporting data, this regimen is not recommended for prophylaxis in patients at risk for postoperative nausea and vomiting.
Diuretic Effects of Subcutaneous Furosemide in Human Volunteers: A Randomized Pilot Study
Authors: Verma Arun K , da Silva Jack H , Kuhl David R 
Published: March 2004

BACKGROUND Furosemide is usually administered by the oral or intravenous route to cardiac patients with hypertension and heart failure, as well as edema. Occasionally, furosemide cannot be administered by these routes. OBJECTIVE To evaluate the diuretic/natriuretic efficacy of subcutaneously administered furosemide in healthy volunteers. METHODS This single-center, double-blind, placebo-controlled, randomized, crossover pilot study compared the diuretic effect of subcutaneously administered furosemide and NaCl 0.9% (placebo) in 12 healthy volunteers. The study was conducted over 5 days. Baseline values were determined on day 1. On days 3 and 5, each volunteer was injected with either furosemide 20 mg (2 mL) or 2 mL of placebo subcutaneously. A washout period occurred on day 4. Fluid and dietary intake were controlled on all 3 data collection days. Primary outcome measures consisted of urine volume voided, urine sodium concentration, onset time and volume of initial urine output, and number of voids during 8 hours of urine collection. RESULTS All outcomes demonstrated statistically significant differences when treatment and placebo groups were compared (p < 0.05). Adverse effects most commonly reported by the participants were minor and included transient burning and stinging at the injection site. CONCLUSIONS This study demonstrates that subcutaneously administered furosemide is a viable alternative when the oral or intravenous route of administration is not desirable or possible in humans. However, the results of this study need to be corroborated in various patient populations.
Interpretation of Drug Risk and Benefit: Individual and Population Perspectives
Authors: Bjornson Darrel C 
Published: March 2004

OBJECTIVE To provide pharmacists with the necessary nomenclature and tools to interpret the medical literature on drug risks and benefits. DATA SOURCES Primary articles were identified by MEDLINE search (1990—December 2003) and through secondary sources. STUDY SELECTION AND DATA EXTRACTION All of the articles identified from the data sources were evaluated, and all information from secondary sources deemed relevant was included. DATA SYNTHESIS Articles in the primary and secondary literature were reviewed. The articles show that measurement of drug risks and benefits is consistently reported with similar terminology. However, the interpretation and subsequent balancing of risks and benefits can be difficult. CONCLUSIONS All drugs have concomitant risks and benefits. The medical literature documents those risks and benefits and it is this medical evidence that is typically used to make drug therapy decisions. Pharmacists who either manage individual patients or populations of patients (pharmacy benefit managers) may interpret this medical evidence more clearly by understanding the implications of various statistical methods used in studies.
Guidelines for Acute Decompensated Heart Failure Treatment
Authors: DiDomenico Robert J , Park Hayley Y , Southworth Mary Ross , Eyrich Heather M , Lewis Richard K , Finley Jamie M , Schumock Glen T 
Published: March 2004

OBJECTIVE To describe the development of guidelines for the treatment of acute decompensated heart failure (ADHF) in the emergency department/observation unit (ED-OU) setting for hospitals that are part of a group purchasing organization (GPO). DATA SOURCES A MEDLINE search (1966-March 2003) using the following search terms: cardiotonic agents; diuretic; dobutamine; heart failure, congestive; milrinone; natriuretic peptide, brain; nesiritide; nitroglycerin; vasodilator agents, was conducted. STUDY SELECTION AND DATA EXTRACTION Relevant articles in the English language were identified. All randomized studies and meta-analyses for each category of drugs were included. DATA SYNTHESIS A group consensus method was used to develop guidelines. An expert panel reviewed and revised the guidelines. The final guidelines were approved June 1, 2003, and are described here. They are organized based upon a patient's symptomatology at the time the diagnosis of ADHF is made. Patients with evidence of volume overload require intravenous diuretics and/or intravenous vasodilators to alleviate the symptoms of ADHF. Patients with signs and symptoms of low cardiac output require inotropic support to manage their ADHF. A timeline for diagnosis, treatment, reassessment, and disposition is provided and encourages an early, aggressive approach to treating patients with ADHF. CONCLUSIONS Hospitalization for ADHF is common and costly. Consensus guidelines for the treatment of ADHF did not previously exist, resulting in inconsistent and inefficient treatment. Consequently, hospitals struggling with the treatment of ADHF may find these guidelines and the process by which they were developed useful. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-04-015-H01
Multigene Reverse Transcription-PCR Profiling of Circulating Tumor Cells in Hormone-Refractory Prostate Cancer
Authors: O’Hara S Mark , Moreno Jose G , Zweitzig Daniel R , Gross Steve , Gomella Leonard G , Terstappen Leon W M M 
Published: March 2004

Abstract
Background: Circulating tumor cells (CTCs) represent a surrogate source of tissue and conceptually represent a “real-time” biopsy. We previously reported that the number of CTCs mirrors disease progression in hormone-refractory prostate cancer (HRPC). To improve characterization of CTCs we further investigated whether in vitro transcription-based multigene reverse transcription-PCR expression profiles could be obtained from CTCs in HRPC.
Methods: We evaluated the expression of 37 genes with potential utility for epithelial cell characterization from antisense RNA libraries constructed from immunomagnetically enriched CTCs from 7.5-mL blood samples from healthy donors and patients with HRPC.
Results: In the control group 13 of 37 genes were not expressed. The most notable of the genes expressed in CTCs of 23 blood specimens drawn from 9 patients with metastatic prostate cancer were prostate-specific antigen (20 of 23; 87%), prostate-specific membrane antigen (17 of 23; 74%), androgen receptor (16 of 23; 70%), human glandular kallikrein 2 (7 of 23; 30%), epidermal growth factor receptor (4 of 23; 17%), and prostate-specific gene with homology to G protein receptor (2 of 23; 9%). The number of CTCs in these samples ranged from 4 to 283 in 7.5 mL of blood (mean, 87; median, 89). Expression of some of the genes was low in the control samples and higher in the patient samples. In all 23 samples, cytokeratin 19, epithelial cell adhesion molecule, or mucin 1 was expressed. Because of background expression in the controls, expression of 13 of the 37 genes, including HER-2, p53, and BCL-2, could not be measured in CTCs.
Conclusion: Antisense RNA libraries can be constructed from CTCs and gene expression profiles of CTCs obtained from patients with HRPC. This could enhance the characterization of HRPC and facilitate the development of more effective therapies.
Determination of Absolute Configuration of Acyclic 1,2‐Diols with [Mo2(OAc)4], Part 2: New Structural Evidence toward a Rationale of the Method: What Remains of [Mo2(OAc)4] in DMSO Solution?
Authors: Bari Lorenzo Di , Pescitelli Gennaro , Salvadori Piero 
Published: March 2004

AbstractThe nature of the CD‐active species obtained by mixing dimolybdenum tetraacetate and a chiral 1,2‐diol in DMSO has been studied by different techniques (1D and 2D 1H NMR, CD, UV/Vis) with two substrates, (R)‐phenyl‐1,2‐ethanediol (1) and (R,R)‐butane‐2,3‐diol (2). The diol/dimolybdenum adducts have diagnostic CD spectra whose sign correlates with the absolute configuration of the organic substrate. It is demonstrated that, in DMSO solution, the acetate ligands of [Mo2(OAc)4] dissociate to a large extent under the action of the dissolved water, yielding acetic acid and a polyhydrated dimolybdenum species. Addition of a 1,2‐diol leads to chelation with formation of one main active species for 2 and two for 1, all with 1:1 stoichiometries at diol/dimolybdenum molar ratios less than 1.5. Only a small fraction (less than 20 %) of the 1,2‐diol is bound. The structures of the active complexes are estimated on the basis of NMR spectra, by correlating the observed chemical shifts with the quadruple bond diamagnetic anisotropy. In the predominating complexes for 1 and 2, the 1,2‐diol moiety bridges the Mo2 core forming a six‐membered ring.
Photocycloaddition of Some Difluoro(aminoenonato)boron Complexes with Arylalkenes
Authors: Itoh Kuniaki , Okazaki Kazuhiko , Chow Yuan L. 
Published: February 2004

AbstractThe photocycloaddition of some difluoro[(methylamino‐κN)alkenonato‐κO]boron complexes 1 with arylalkenes 2 is discussed. The resulting [2+2] photoaddition gave the cyclobutane and azetidine derivatives (Schemes 1, 3, and 5). Rearrangements of the cyclobutane gave 1,5‐diketones derivatives (Schemes 2, 4, and 5). The yields of the photoadducts were governed by the reduction and oxidation potentials. Furthermore, the configurations of the products established high regio‐ and stereoselectivity, suggesting the presence of a singlet exciplex. The reactivity and the stereochemistry were rationalized by means of FMO (frontier molecular orbital) calculations.
Synthesis and Triple‐Helix‐Stabilization Properties of Branched Oligonucleotides Carrying 8‐Aminoadenine Moieties
Authors: Aviño Anna , Grimau Marta G. , Frieden Miriam , Eritja Ramon 
Published: February 2004

AbstractThe synthesis of several branched oligonucleotides, i.e., of the parallel hairpins 5–8 and the Y‐shaped 9 is described, together with their use in the formation of pyrimidine⋅pyrimidine⋅purine triple helices. Special attention was paid to the optimization of the assembly of the second strand from asymmetric branching molecules. The presence of 8‐aminoadenine moieties in the WatsonCrick purine strand and 2′‐O‐methyl‐RNA in the Hoogsteen pyrimidine strand produced strong stabilization of the triplex.