bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement of Nε-(Carboxymethyl)lysine and Nε-(Carboxyethyl)lysine in Human Plasma Protein by Stable-Isotope-Dilution Tandem Mass Spectrometry
Authors: Teerlink Tom , Barto Rob , ten Brink Herman J , Schalkwijk Casper G 
Published: May 2004

Abstract
Background: N ε-(Carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) are two stable, nonenzymatic chemical modifications of protein lysine residues resulting from glycation and oxidation reactions. We developed a tandem mass spectrometric method for their simultaneous measurement in hydrolysates of plasma proteins.
Methods: CML and CEL were liberated from plasma proteins by acid hydrolysis after addition of deuterated CML and CEL as internal standards. Chromatographic separation was performed by gradient-elution reversed-phase chromatography with a mobile phase containing 5 mmol/L nonafluoropentanoic acid as ion-pairing agent. Mass transitions of 205.1→84.1 and 219.1→84.1 for CML and CEL, respectively, and 209.1→88.1 and 223.1→88.1 for their respective internal standards were monitored in positive-ion mode.
Results: CML and CEL were separated with baseline resolution with a total analysis time of 21 min. The lower limit of quantification was 0.02 μmol/L for both compounds. Mean recoveries from plasma samples to which CML and CEL had been added were 92% for CML and 98% for CEL. Within-day CVs were &lt;7.2% for CML and &lt;8.2% for CEL, and between-day CVs were &lt;8.5% for CML and &lt;9.0% for CEL. In healthy individuals (n = 10), mean (SD) plasma concentrations of CML and CEL were 2.80 (0.40) μmol/L (range, 2.1–3.4 μmol/L) and 0.82 (0.21) μmol/L (range, 0.5–1.2 μmol/L), respectively. In hemodialysis (n = 17) and peritoneal dialysis (n = 9) patients, plasma concentrations of CML and CEL were increased two- to threefold compared with controls, without significant differences between dialysis modes [7.26 (1.36) vs 8.01 (3.80) μmol/L (P = 0.89) for CML, and 1.84 (0.39) vs 1.71 (0.42) μmol/L (P = 0.53) for CEL].
Conclusions: This stable-isotope-dilution tandem mass spectrometry method is suitable for simultaneous analysis of CML and CEL in hydrolysates of plasma proteins. Its robustness makes it suitable for assessing the value of these compounds as biomarkers of oxidative stress resulting from sugar and lipid oxidation.
Warfarin Therapy and Risk of Hip Fracture Among Elderly Patients
Authors: Mamdani Muhammad , Upshur Ross E. G. , Anderson Geoff , Bartle Bill R. , Laupacis Andreas 
Published: May 2004

Study Objective. To ascertain the relationship between warfarin therapy and subsequent hip fracture in a large elderly population.Design. Retrospective, population‐based cohort study.Setting. Population‐based health care administrative databases for Ontario, Canada.Patients. Elderly patients receiving warfarin (52,701 patients), thyroid replacement therapy (40,555), an oral corticosteroid (43,915), or a proton pump inhibitor (60,383). The proton pump inhibitor group served as controls.Measurements and Main Results. The association between warfarin therapy and subsequent hospitalization for hip fracture in elderly patients was examined by researching administrative data from January 1, 1994‐March 31, 1999, for the elderly population of Ontario. Relative to patients receiving proton pump inhibitors, patients receiving warfarin (adjusted risk ratio [aRR] 0.94, 95% confidence interval [CI] 0.81–1.09) or thyroid replacement therapy (aRR 1.02, 95% CI 0.89–1.18) incurred similar risks of hip fracture. As expected, patients receiving oral corticosteroids incurred an increased risk (aRR 1.44, 95% CI 1.21–1.70) relative to patients receiving proton pump inhibitors.Conclusion. Warfarin was not associated with increased risk of hip fracture.
Erythromycin Accelerates Gastric Emptying in a Dose‐Response Manner in Healthy Subjects
Authors: Boivin Michel A. , Carey Michael C. , Levy Howard 
Published: May 2004

Study Objectives. To evaluate whether a dose‐response curve exists for erythromycin, determine the lowest effective dose of erythromycin needed to improve gastric motility, and compare erythromycin's effectiveness with that of metoclopramide in improving gastric emptying.Design. Randomized, crossover, multiintervention trial.Setting. Inpatient clinical research center.Subjects. Ten healthy volunteers (four men, six women) from the general population.Intervention. On each study day, the subjects were infused with erythromycin 0.75 mg/kg, 1.5 mg/kg, or 3.0 mg/kg; metoclopramide 10 mg; or placebo, in random order. Subjects then drank Ensure 200 ml mixed with acetaminophen 1.5 g. Gastric emptying was estimated by comparing the area under the curve after 60 minutes for acetaminophen absorption using four timed blood draws.Measurements and Main Results. Erythromycin increased gastric emptying in a dose‐response manner. Erythromycin 3.0 mg/kg and metoclopramide 10 mg were associated with statistically significant increases in liquid gastric emptying compared with placebo. During infusion, nausea and stomach cramping were associated with the 3.0‐mg/kg dose of erythromycin; drowsiness was associated with metoclopramide.Conclusion. In patients requiring intravenous erythromycin for gastric motility, the 3.0‐mg/kg dose seems the most effective, with a reasonable side effect profile.
Clinic at the Health Food Store? Employee Recommendations and Product Analysis
Authors: Glisson James K. , Rogers Holly E. , Abourashed Ehab A. , Ogletree Richard , Hufford Charles D. , Khan Ikhlas 
Published: May 2004

Study Objectives. To determine what products health food store employees recommend for depression, to analyze the content of these products based on label claims, and to evaluate employee statements or recommendations for accuracy and safety.Methods. Twelve health food stores were selected for the study. One investigator approached an employee in each store and asked what they recommended for depression plus five additional questions regarding product use. Thirteen products containing St. John's wort were purchased and analyzed for hypericin and pseudohypericin content using high‐performance liquid chromatography (HPLC). Total hypericin content was calculated by adding the values for hypericin and pseudohypericin.Results. All 12 health food store employees recommended a St. John's wort supplement for treatment of depression. Furthermore, numerous comments made by employees regarding St. John's wort and the treatment of depression were unsafe and inaccurate. The HPLC analysis revealed that no product contained ± 10% of the stated label claim for hypericin content, and two products contained 0% hypericin. The total hypericin content (hypericin plus pseudohypericin) of only two products was within ± 10% of the label claim for hypericin.Conclusions. Health food store employees offer health care advice regarding treatment of depression with dietary supplements without proper scientific and medical training. Their comments could cause significant harm to customers. In addition, the inconsistencies of dietary supplement content continue to raise concern for individuals who use these agents as medical treatment.
Improving Aspirin Prophylaxis in a Primary Care Diabetic Population
Authors: Faragon John J. , Waite Nancy M. , Hobson Eric H. , Seoldo Nathalie , VanAmburgh Jenny A. , Migden Hedy 
Published: May 2004

Study Objective. To evaluate and improve adherence to American Diabetes Association guidelines for prophylactic aspirin therapy in ambulatory patients with diabetes using a pharmacy‐directed intervention.Design. Unblinded, single intervention.Setting. Rural, primary care clinic.Subjects. Eighty‐five patients with a diagnosis of diabetes mellitus.Intervention. Patients with diabetes were identified from database searches and routine clinic visits. Medical records were screened for aspirin use, allergies, adverse events, and contraindications. During routine clinic visits or structured telephone interviews, patients with indications for aspirin therapy were advised to begin enteric‐coated aspirin 81 mg/day. A follow‐up survey assessed adherence.Measurements and Main Results. At baseline, 28 (33%) of 85 patients were receiving aspirin therapy. An additional 8 patients had contraindications to aspirin, and 2 patients had no indications for aspirin therapy. Aspirin was recommended to 27 patients during clinic interventions and to 15 patients during telephone interventions. Two patients declined the recommendation. At the completion of this intervention, 70 (82%) of 85 patients were receiving daily aspirin or had accepted the recommendation to begin therapy.Conclusions. A pharmacy‐directed intervention increased prophylactic aspirin therapy in patients with diabetes from 33% of patients at baseline to 82% at the end of the study. The intervention, which has a simple, patient‐focused design, serves as a template for improving aspirin prophylaxis among patients with diabetes in other ambulatory settings.
Meta‐Analysis of Interventions To Improve Drug Adherence in Patients with Hyperlipidemia
Authors: Peterson Andrew M. , Takiya Liza , Finley Rebecca 
Published: May 2004

Objective. To examine the results of meta‐analyses addressing the net effect of tools and methods to enhance drug adherence in patients with hyperlipidemia.Methods. We searched MEDLINE, International Pharmaceutical Abstracts (IPA), PsychLit, Educational Resource Information Clearinghouse (ERIC), and Excerpta Medica Database (EMBASE) databases (1996–2000) for randomized controlled trials of interventions to improve patients' adherence to drug regimens for hyperlipidemia. All trials selected had at least 10 subjects/group. Effect sizes, represented as the correlation coefficient, were calculated from Cohen's d and d'. Analysis of variance and the Q test were performed to evaluate statistical significance and heterogeneity.Results. Of the 484 articles evaluated, only four met the criteria for inclusion. Multiple interventions or study samples were identified in two articles. Each intervention was counted as a separate study, yielding seven cohorts with a total of 3077 subjects. Behavioral interventions accounted for five cohorts (2915 subjects). No cohorts received solely educational interventions. Two cohorts, with a total of 162 subjects, received a combination of behavioral and educational interventions. Homogeneity of groupings and effect sizes were calculated for the overall grouping as well as for each type of intervention. Overall, the effect size for the data was 0.14 (95% confidence interval [CI] 0.10–0.17) and the data were homogenous (Q = 7.36, df = 4, p=0.29). The effect size for the behavioral interventions was 0.14 (95% CI 0.11–0.18, Q = 5.25, df = 4, p=0.26). For interventions that combined behavioral and educational components, the effect size was 0.03 (CI −0.13–0.18, Q = 0.204, df = 1, p=0.65).Conclusions. The interventions evaluated had little impact on drug adherence. More studies are needed to assess how to improve drug adherence in patients with hyperlipidemia.
Wood Creosote, the Principal Active Ingredient of Seirogan, an Herbal Antidiarrheal Medicine: A Single‐Dose, Dose‐Escalation Safety and Pharmacokinetic Study
Authors: Kuge Tomoo , Shibata Takashi , Willett Michael S. 
Published: May 2004

Study Objective. To assess the safety, tolerability, and pharmacokinetics of escalating single doses of wood creosote, an herbal antidiarrheal and antispasmodic agent.Design. Randomized, double‐blind, placebo‐controlled study.Setting. Clinical research center.Subjects. Forty (32 men, 8 women) healthy volunteers aged 19–42 years.Intervention. By random assignment, 22 men and 8 women received escalating single doses of wood creosote (45, 90, 135, 180, and 225 mg) and 10 men received placebo (for each of the five dose levels, 6 subjects received active substance and 2 subjects received placebo).Measurements and Main Results. Vital signs, laboratory tests, and electrocardiograms were assessed; no dose‐related or clinically significant changes were noted. Serial blood samples were obtained to determine the pharmacokinetics of four major active components of wood creosote: total (conjugated plus free) guaiacol, creosol, o‐cresol, and 4‐ethylguaiacol. The most common adverse events were mild headache and dizziness, with no dose‐related trends being apparent. Area under the concentration‐time curve from time zero to infinity increased in a dose‐proportional manner for total guaiacol, creosol, and o‐cresol and was not assessed for total 4‐ethylguaiacol owing to lack of data at the low dose level. No apparent differences by sex were noted for any of the four active components. All four components were rapidly eliminated.Conclusion. Single oral doses of wood creosote up to 225 mg were safe and well tolerated in healthy men and women. Also, the doses of wood creosote were rapidly absorbed, conjugated, and eliminated. Such a rapid onset and short duration of action would appear desirable in the treatment of acute nonspecific diarrhea.
Effects of the Angiotensin II Subtype 1 Receptor Antagonist Losartan on Functional Recovery of Isolated Rat Hearts Undergoing Global Myocardial Ischemia‐Reperfusion
Authors: Flynn Jeremy D. , Akers Wendell S. 
Published: May 2004

Study Objective. To investigate the effects of the angiotensin II subtype 1 receptor (AT1R) antagonist losartan on functional recovery of isolated rat hearts undergoing global myocardial ischemia‐reperfusion compared with myocardial protective effects of ischemic preconditioning.Design. Ex vivo experiment using isolated perfused rat heart.Setting. Academic laboratory.Intervention. Hearts from Sprague‐Dawley rats were perfused with oxygenated Krebs‐Henseleit buffer and randomized to one of four groups: time control, vehicle, ischemic preconditioning, or losartan.Measurements and Main Results. After randomization, hearts underwent 30 minutes of global ischemia followed by 30 minutes of reperfusion. Changes in end‐diastolic pressure (EDP), left ventricular developed pressure (LVDP), and infarct size were examined between treatment groups by two‐way analysis of variance with repeated measures. Cardiac angiotensin II receptor (ATR) density and infarct size were measured in control hearts and in a subgroup of hearts exposed to ischemia‐reperfusion injury. Total ATR density and percentage of myocardial AT1R were increased in hearts exposed to ischemia‐reperfusion. Myocardial ischemia‐reperfusion injury resulted in a 56% reduction in LVDP from baseline in hearts randomized to vehicle. However, it declined by only 22% and 28% in hearts randomized to ischemic preconditioning and losartan, respectively. Compared with vehicle, both ischemic preconditioning and losartan decreased EDP (ischemic preconditioning 39 ± 3 mm Hg, losartan 54 ± 5 mm Hg, vs vehicle 78 ± 8 mm Hg), and reduced infarct size (ischemic preconditioning 9%, losartan 12%, vs vehicle 36%).Conclusion. Treatment of isolated rat hearts with losartan before ischemia‐reperfusion injury resulted in significant cardioprotection similar to that observed with ischemic preconditioning.
Exploring the Association Between Atypical Neuroleptic Agents and Diabetes Mellitus in Older Adults
Authors: Etminan Mahyar , Streiner David L. , Rochon Paula A. 
Published: May 2004

Study Objective. To explore the suggested association between atypical neuroleptic use and the development of diabetes mellitus, with a focus on older adults.Design. Retrospective cohort study.Subjects. Eleven thousand one hundred four older (> 65 yrs) residents of long‐term care institutions in Ontario, Canada, who received either atypical neuroleptic agents, typical neuroleptic agents, benzodiazepines, or corticosteroids.Measurements and Main Results. Each subject was followed for the development of a diabetic event, defined as newly prescribed antidiabetic drug therapy. Our Cox regression model was adjusted for age, sex, socioeconomic status, comorbidity, and concomitant use of β‐blockers, thiazide diuretics, and antiepileptic agents. The adjusted hazard ratio for the development of diabetes in patients receiving atypical neuroleptics compared with those receiving benzodiazepines (control group) was 0.89 (95% confidence interval [CI] 0.66–1.21). The adjusted hazard ratio for typical neuroleptic users compared with the benzodiazepine group was 1.27 (95% CI 0.91–1.77). As expected, patients receiving corticosteroid therapy were almost twice as likely to develop diabetes as those receiving benzodiazepines (adjusted hazard ratio 2.2, 95% CI 1.41–3.12). For patients receiving atypical neuroleptic agents, no statistically significant difference in the percentage of diabetic events was found among individual agents (2.1% olanzapine, 1% quetiapine, 2.1% risperidone).Conclusion. Drug therapy with atypical neuroleptic agents in older adults did not increase their risk of developing diabetes mellitus.
Comparison of Changes in Blood Pressure Measurements and Antihypertensive Therapy in Older, Hypertensive, Ambulatory Care Patients Prescribed Celecoxib or Rofecoxib
Authors: Nietert Paul J. , Ornstein Steven M. , Dickerson Lori M. , Rothenberg Ralph J. 
Published: May 2004

Study Objective. To determine if changes in blood pressure and changes in class or dosing of antihypertensive drugs were significantly different in patients treated with celecoxib versus rofecoxib, two cyclooxygenase (COX)‐2 inhibitors.Design. Retrospective cohort study.Setting. Thirty‐one ambulatory care practices that shared an electronic medical record.Patients. Nine hundred sixty men and women over age 55 years with stable hypertension.Intervention. Patients had to have at least a 30‐day supply of celecoxib or rofecoxib (any dose) prescribed between July 1, 1999, and June 30, 2000.Measurements and Main Results. Patients were followed for 6 months, and logistic regression and survival models were used to compare outcomes between groups while adjusting for confounders. Baseline characteristics of 517 patients receiving celecoxib and 443 receiving rofecoxib were similar. No significant differences were observed, regardless of the COX‐2 inhibitor prescribed, in the proportion of patients whose systolic blood pressure increased by 20 mm Hg, whose diastolic blood pressure increased by 15 mm Hg, or who were prescribed a new class of antihypertensive drug. Compared with patients taking celecoxib, those taking rofecoxib were significantly more likely (odds ratio 1.68, 95% confidence interval 1.09–2.60) to have had the dosage of their antihypertensive drug increased and also the dosage increased sooner (p<0.05). New‐onset cardiac and renal comorbidity, number of physician visits, and changes in body weight and laboratory values were not significantly different between the groups.Conclusion. No significant differences in blood pressure changes or in the proportion of patients who were prescribed a new class of antihypertensive drug were found between rofecoxib‐ and celecoxib‐treated patients. However, significantly more rofecoxib‐treated patients had the dosage of their existing antihypertensive drug increased compared with those receiving celecoxib.
Filgrastim‐Mediated Neutrophil Recovery in Patients with Breast Cancer Treated with Docetaxel and Doxorubicin
Authors: Meza Luis A. , Green Michael D. , Hackett James R. , Neumann Theresa A. , Holmes Frankie A. 
Published: May 2004

Study Objectives. To study the impact of filgrastim 5 μg/kg given once/day through absolute neutrophil count (ANC) recovery on the duration of grade 4 neutropenia (ANC < 0.5 × 103/mm3) and time to ANC recovery. Additional objectives were to study the average number of filgrastim injections/cycle required to achieve ANC recovery and differences in outcome by cycle.Design. Combined analysis of two double‐blind, randomized, multicenter trials.Patients. Two hundred twenty‐two patients treated for breast cancer.Measurements and Main Results. All patients but one were evaluable for efficacy end points. Mean ± SD duration of grade 4 neutropenia was 1.7 ± 1.3 days in cycle 1; the duration decreased in cycles 2–4 to between 1.0 and 1.2 days. Fifty percent of patients had ANC recovery to 10 times 103/mm3 or greater by day 11 of the cycle, and 90% by day 13, corresponding to 10 and 12 days of filgrastim administration, respectively. Across all cycles, the mean ± SD number of filgrastim injections/cycle was 10.51 ± 1.70, with little variation among cycles.Conclusion. When filgrastim is administered as recommended, starting 24 hours after chemotherapy and continuing through an ANC of 10 times 103/mm3 or greater, neutrophil recovery is rapid and predictable. Because the first cycle of chemotherapy has the highest rates of neutropenia and febrile neutropenia, it seems prudent to administer growth factor support preemptively.
Twice‐Daily Trizivir versus Combivir‐Abacavir in Antiretroviral‐Experienced Adults with Human Immunodeficiency Virus‐1 Infection: A Formulation‐Switch Trial
Authors:   For the ESS40005 Study Team, Fischl Margaret A. , Burnside Alfred F. , Farthing Charles F. , Thompson Melanie A. , Bellos Nicholaos C. , Williams Vanessa C. , Kauf Teresa L. , Wannamaker Paul G. , Shaefer Mark S. 
Published: May 2004

Study Objective. To establish the clinical equivalence (noninferiority) of one tablet containing abacavir 300 mg‐lamivudine 150 mg‐zidovudine 300 mg (Trizivir) versus a tablet containing lamivudine 150 mg‐zidovudine 300 mg (Combivir) given with one abacavir (ABC) 300‐mg tablet, administered twice/day, in antiretroviral‐experienced, human immunodeficiency virus (HIV)‐1‐infected patients.Design. Randomized, open‐label, parallel‐group, multicenter, formulation‐switch study.Setting. Twenty seven outpatient treatment sites.Patients. Adults with HIV‐1 RNA levels of 400 copies/ml or less and CD4+ cell counts above 200 cells/mm3 who had been treated for 16 weeks or more with highly active antiretroviral therapy containing Combivir‐ABC.Intervention. Patients were randomized 1:1 to Trizivir (97 patients) or Combivir‐ABC (98) for 24 weeks.Measurements and Main Results. The primary study end point was the proportion of patients who maintained less than a 0.5‐log10 increase from baseline in HIV‐1 RNA (virologic success) through week 24. Clinical equivalence of the treatments was established if the 95.1% lower confidence limit (LCL) for the difference in proportion of virologic success with Trizivir minus Combivir‐ABC was −0.12 or greater. Trizivir was clinically equivalent to Combivir‐ABC. The intent‐to‐treat observed analysis at week 24 with Trizivir and Combivir‐ABC showed a similar rate of virologic success (83% [80/97] and 77% [75/98], respectively, 95.1% LCL −0.026), of patients with HIV‐1 RNA levels of 400 or fewer copies/ml (99% [82/83] and 93% [77/83], respectively, 95.1% LCL 0.021), and of patients with HIV‐1 RNA levels of fewer than 50 copies/ml (89% [74/83] and 77% [64/83], respectively, 95.1% LCL 0.038). The intent‐to‐treat missing = failure analysis showed comparable results. Changes in CD4+ cell count from baseline, overall mean self‐reported adherence (Trizivir 97%, Combivir‐ABC 92%), and adverse events did not differ significantly between treatments. No ABC‐related hypersensitivity reactions occurred.Conclusion. Trizivir was clinically equivalent to Combivir‐ABC and may be substituted for the latter to simplify treatment and reduce pill burden.