bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal Homocysteine before Conception and throughout Pregnancy Predicts Fetal Homocysteine and Birth Weight
Authors: Murphy Michelle M , Scott John M , Arija Victoria , Molloy Anne M , Fernandez-Ballart Joan D 
Published: June 2004

Abstract
Background: Increased homocysteine has been associated with pregnancy complications.
Methods: We investigated prospectively the effect of maternal homocysteine on normal pregnancy outcome. The study included 93 women and their offspring; 39 of the women took folic acid during the second and/or third trimesters of pregnancy. We measured homocysteine at preconception; at weeks 8, 20, and 32 of pregnancy; during labor; and in the fetal cord; we also recorded birth weight.
Results: Geometric mean (SE) maternal total homocysteine (tHcy) increased between 32 weeks of pregnancy and labor [7.98 (1.05) μmol/L in unsupplemented women and 6.26 (1.07) μmol/L in supplemented women; P &lt;0.0001 for both]. Fetal tHcy was lower than maternal tHcy [6.39 (1.06) μmol/L in unsupplemented pregnancies (P &lt;0.0001), and 5.18 (1.06) μmol/L in supplemented pregnancies (P &lt;0.05)]. Maternal tHcy was correlated from preconception throughout pregnancy (8 weeks, r = 0.708; 20 weeks, r = 0.637; 32 weeks, r = 0.537; labor, r = 0.502; P &lt;0.0001 for all time points) and with fetal tHcy [preconception, r = 0.255 (P &lt;0.05); 8 weeks, r = 0.321 (P &lt;0.01); 20 weeks, r = 0.469; 32 weeks, r = 0.550; labor, r = 0.624 (P &lt;0.0001)]. Mothers in the highest tHcy tertile at 8 weeks of pregnancy were three times [odds ratio, 3.26 (95% confidence interval, 1.05–10.13); P &lt;0.05] and at labor were four times [3.65 (1.15–11.56); P &lt;0.05] more likely to give birth to a neonate in the lowest birth weight tertile. Neonates of mothers in the highest tHcy tertile at labor weighed, on average, 227.98 g less than those of mothers in the low and medium tertiles (P = 0.014).
Conclusions: Supplemented mothers had lower tHcy at labor than unsupplemented mothers, as did their neonates. Maternal and fetal tHcy was significantly correlated throughout the study. Neonates of mothers in the highest tertile of homocysteine weighed less.
Measurement of Urinary d- and l-2-Hydroxyglutarate Enantiomers by Stable-Isotope-Dilution Liquid Chromatography–Tandem Mass Spectrometry after Derivatization with Diacetyl-l-Tartaric Anhydride
Authors: Struys Eduard A , Jansen Erwin E W , Verhoeven Nanda M , Jakobs Cornelis 
Published: May 2004

Abstract
Background: The differential diagnosis of d-2-hydroxyglutaric aciduria (d-2-HGA), l-2-hydroxyglutaric aciduria (l-2-HGA), and the combined d/l-2-hydroxyglutaric aciduria (d/l-2-HGA) can be accomplished only by the measurement of the corresponding 2-hydroxyglutarate (2-HG). Available methods for the determination of d- and l-2-HG in urine are either time-consuming and expensive or have not been extensively validated. We aimed to develop a method for their rapid and sensitive measurement.
Methods: We used liquid chromatography–tandem mass spectrometry (LC-MS/MS) for the determination of d- and l-2-HG with stable-isotope-labeled internal standards. Urine samples of 20 μL were mixed with 250 μL of methanol containing the internal standards and subsequently dried under nitrogen. The analytes were derivatized by use of diacetyl-l-tartaric anhydride (DATAN) to obtain diastereomers, which were separated on an achiral C18 HPLC column and detected by MS/MS in multiple-reaction-monitoring mode.
Results: The use of DATAN as chiral derivatization reagent provided very well separated peaks of the formed diastereomers of d- and l-2-HG, with a total runtime of 5 min. The inter- and intraassay CVs for d- and l-2-HG ranged from 3.4% to 6.2%. Mean recoveries of d- and l-2-HG, evaluated on two concentrations, were 94%. Detection limit of the presented method was 20 pmol for a sample volume of 20 μL. Method comparison of the LC-MS/MS method with a gas chromatography–mass spectrometry method, in which d- and l-2-HG were derivatized with R-(−)-butanol, showed good agreement between the two methods.
Conclusions: Urinary d- and l-2-HG can be analyzed by MS/MS after derivatization with DATAN. The presented method may be suitable for the differential diagnosis of 2-HGA.
Closed-Tube Genotyping with Unlabeled Oligonucleotide Probes and a Saturating DNA Dye
Authors: Zhou Luming , Myers Alexander N , Vandersteen Joshua G , Wang Lesi , Wittwer Carl T 
Published: June 2004

AbstractBackground: Homogeneous PCR methods for genotyping usually require fluorescently labeled oligonucleotide probes. Amplicon melting with the DNA dye LCGreen™ I was recently introduced as a closed-tube method of genotyping that does not require probes or real-time PCR. However, some single-nucleotide polymorphisms (SNPs) could not be completely genotyped without addition of a known genotype, and high-resolution melting techniques were necessary.Methods: A 3′-blocked, unlabeled oligonucleotide probe and the saturating dye, LCGreen I, were added to standard PCR reagents before amplification. After PCR, the samples were melted at 0.1–0.3 °C/s in high-resolution (HR-1™), high-throughput (LightTyper™), and rapid-cycle, real-time (LightCycler®) instruments, and fluorescence melting curves were recorded.Results: Derivative melting curves of the probe–target duplexes were characteristic of the genotype under the probe. With synthetic plasmid templates, all SNP base combinations could be genotyped. For human genomic DNA, the technique was demonstrated with mutations associated with cystic fibrosis, including SNPs (G542X, I506V, and F508C) and 3-bp deletions (F508del and I507del).Conclusions: Genotyping of SNPs and small deletions by melting analysis of an unlabeled probe in the presence of LCGreen I is simple and rapid. Only three unlabeled oligonucleotides (two primers and one probe), a saturating DNA dye, PCR, and a melting instrument are required. The method is closed-tube, does not require fluorescently labeled probes or real-time PCR, and can be completed in &lt;10 min on any instrument capable of monitoring melting curves by fluorescence.
Risk Markers for Thrombocytopenia in Critically Ill Patients: A Prospective Analysis
Authors: Shalansky Stephen J. , Verma Arun K. , Levine Marc , Spinelli John J. , Dodek Peter M. 
Published: June 2004

Study Objective. To identify independent risk markers for thrombocytopenia in critically ill patients.Design. Prospective, observational study.Setting. Eleven‐bed intensive care unit‐coronary care unit (ICU‐CCU) in a community hospital.Patients. Three hundred sixty‐two consecutive patients meeting inclusion criteria during 1 year.Intervention. Potential risk marker data were collected on admission to the ICU‐CCU and for the period before development of thrombocytopenia (defined as two or more consecutive platelet counts < 150 × 103/mm3 obtained at least 12 hours apart), or for the duration of ICU‐CCU stay if thrombocytopenia did not develop.Measurements and Main Results. Thrombocytopenia developed in 68 patients (18.8%). Multivariate logistic regression analyses identified patients at risk on admission, but the predictive potential of the regression model improved when all risk marker exposures during the ICU‐CCU stay were considered. Independent risk markers included fresh frozen plasma administration, sepsis, musculoskeletal diagnosis, pulmonary artery catheter insertion, gastrointestinal diagnosis, packed red blood cell administration, and nonsurgical respiratory diagnosis. Higher admission platelet count and aspirin administration were associated with a lower risk of thrombocytopenia. Heparin administration was not identified as a risk marker, and no patient developed heparin‐induced thrombocytopenia with thrombosis. Patients with thrombocytopenia had longer ICU‐CCU and hospital stays, and higher ICU‐CCU and hospital mortality than those without thrombocytopenia.Conclusions. Development of thrombocytopenia in critically ill patients is associated with specific diagnoses, packed red cell and fresh frozen plasma transfusions, pulmonary artery catheter insertion, and admission platelet count.
Effects of Orlistat on Fat‐Soluble Vitamins in Obese Adolescents
Authors: McDuffie Jennifer R. , Calis Karim A. , Booth Sarah L. , Uwaifo Gabriel I. , Yanovski Jack A. 
Published: June 2004

Study Objectives.To determine whether orlistat causes fat‐soluble vitamin deficiencies in African‐American and Caucasian adolescents.Design.Prospective, open‐label pilot study.Setting.Warren Grant Magnuson Clinical Center of the National Institutes of Health.Patients.Seventeen adolescents with body mass indexes above the 95th percentile for age, race, and gender who also had at least one obesity‐related comorbid condition.Intervention.Subjects received orlistat 120 mg 3 times/day and a daily multivitamin supplement containing vitamin A 5000 IU, vitamin D 400 IU, vitamin E 300 IU, and vitamin K 25 μg.Measurements and Main Results.During 3–6 months of orlistat treatment, acute absorption of retinol (vitamin A) was not significantly altered, but absorption of α‐tocopherol (vitamin E) was significantly reduced compared with baseline levels (p<0.001). Serum levels of vitamins A and E did not change significantly; however, there was a nonsignificant decrease in vitamin K. Mean vitamin D levels were significantly reduced compared with baseline (p<0.02) after 1 month of orlistat, despite multivitamin supplementation.Conclusion.It may be prudent to monitor vitamin D concentrations in adolescents who take orlistat, even when a multivitamin is prescribed.
Tachyphylaxis Associated with Continuous Cisatracurium versus Pancuronium Therapy
Authors: Kanji Salmaan , Barletta Jeffrey F. , Janisse James J. , Kruse James A. , Devlin John W. 
Published: June 2004

Study Objectives. To compare dosing requirements over time among patients receiving continuous cisatracurium versus pancuronium therapy, and to identify factors that may account for changes in pancuronium versus cisatracurium infusion requirements over time.Design. Retrospective, comparative cohort analysis.Setting. A tertiary level 1 trauma center.Patients. Forty‐five consecutive adult patients who were admitted to intensive care units at our institution from January 1998–August 2000 and received continuous cisatracurium or pancuronium therapy for at least 48 hours.Measurements and Main Results. Dosing requirements of patients treated with pancuronium or cisatracurium were recorded over time throughout the treatment period. Factors that could affect dosing requirements of a neuromuscular blocking agent (NMBA) were stratified as time invariant (admitting service, acute physiology and chronic health evaluation II score, duration of mechanical ventilation, pressure control ventilation, baseline hepatic or renal insufficiency, thermal injury, train‐of‐four assessment, and concurrent drug administration or disorders affecting neuromuscular transmission) or time variant (concurrent sedation and narcotic analgesia therapy; serum magnesium, potassium, and creatinine concentrations; arterial pH level; temperature; peak airway pressure; and partial pressure of oxygen:fraction of inspired oxygen ratio). Hierarchical linear modeling was used to compare the dosing requirements and to identify confounders affecting the relationship. The infusion rate escalation for the cisatracurium group was greater (0.39 μg/kg/min; 95% confidence interval [CI] 0.22–0.56; 23 patients) than for the pancuronium group (−0.06 μg/kg/min; 95% CI −0.24‐0.12; 22 patients; p<0.001) and was associated with an average daily cost/patient significantly higher (p<0.001) with cisatracurium ($258 ± $114) than pancuronium ($11 ± $5). Confounder analysis revealed that only the admitting service and the number of times the NMBA infusion was suspended because no twitch was detected differed between groups. Neither of these confounders significantly affected the temporal relationship between cisatracurium and pancuronium infusion rates.Conclusion. Dosing requirements increase over time at a significantly greater rate for cisatracurium than pancuronium infusions. Tachyphylaxis with cisatracurium is associated with substantial drug‐related costs and is not accounted for by various disease‐, patient‐, and therapy‐related factors. Further investigation is required to elucidate the mechanisms and risk factors underlying this phenomenon.
Topiramate and Weight Loss in Patients with Neurodevelopmental Disabilities
Authors: Brown Rex O. , Orr Carla D. , Hanna Debra L. , Williams John E. , Dickerson Roland N. 
Published: June 2004

Study Objective. To characterize weight changes in patients with neurodevelopmental disabilities who received topiramate.Design. Retrospective, observational study.Setting. State‐supported developmental center.Patients. Fifteen patients with neurodevelopmental disabilities who received topiramate therapy.Measurements and Main Results. Monthly weights for 1 year after the start of topiramate therapy were recorded. Mean body weight at drug initiation differed significantly compared with the nadir weight during the next 12 months (52.2 ± 7.5 vs 49.9 ± 7.2 kg, p<0.02). Twelve patients who were receiving ad libitum oral diets demonstrated a significant decrease in body weight (52.1 ± 7.5 vs 49.0 ± 7.3 kg, p<0.01), whereas the three patients who received enteral nutrition through enterostomy did not experience significant weight loss.Conclusion. Weight loss is common in patients with neurodevelopmental disabilities who receive topiramate. Since patients who received oral diets lost weight whereas those receiving enteral nutrition did not, decreased nutrient intake is the likely cause of weight loss.
Nonsteroidal Antiinflammatory Drug Starter Packs for Chronic Musculoskeletal Pain
Authors: Voris John C. , Phillips Cynthia M. , Voris Cynthia T. 
Published: June 2004

Study Objective. To determine whether prescribing a nonsteroidal antiinflammatory drug (NSAID) starter pack for chronic musculoskeletal pain expedites the process of finding an appropriate drug for a given patient.Design. Prospective patient interviews.Setting. Veterans Affairs Medical Center.Patients. Sixty‐four patients with chronic musculoskeletal pain were prescribed NSAID starter packs. Of those, 42% were interviewed and their data evaluated.Intervention. Between March and June 2001, patients received starter packs containing 1‐week supplies of the following NSAIDs: ibuprofen, salsalate, etodolac, naproxen, sulindac, and piroxicam. The patients took one drug each week, then returned to their providers to receive a prescription for the agent that was considered most effective and tolerable.Measurements and Main Results. Patients assessed pain each day based on a numeric pain‐rating scale. During telephone interviews, seven patients reported better pain control when they were able to select a drug from the starter pack than when they were prescribed a specific drug by their providers. Providers rated the starter pack as easy to use by patients and generally effective for finding the best NSAID for a particular patient. Drugs prescribed after completing the starter pack were salsalate 25.9%, piroxicam 22.2%, etodolac 14.8%, ibuprofen 14.8%, naproxen 11.1%, celecoxib 7.4%, and an opiate 3.7%.Conclusion. The NSAID starter pack appears to be a successful method for quickly and easily finding an NSAID that is effective and tolerated.
Olanzapine‐Associated Diabetes Mellitus
Authors: Koller Elizabeth A. , Doraiswamy P. Murali 
Published: June 2004

Study Objective. To explore the clinical characteristics of hyperglycemia in patients treated with olanzapine.Design. Retrospective, epidemiologic survey of spontaneously reported adverse events related to olanzapine therapy.Setting. Government‐affiliated drug evaluation center.Patients. Two hundred thirty‐seven patients with olanzapine‐associated diabetes or hyperglycemia.Intervention. One hundred ninety‐six cases from January 1994‐May 15, 2001, were identified with the United States Food and Drug Administration's MedWatch Drug Surveillance System, and 41 cases published through May 15, 2001, were identified with MEDLINE or through meeting abstracts.Measurements and Main Results. Of the 237 cases, 188 were new‐onset diabetes, 44 were exacerbations of preexistent disease, and 5 could not be classified. Mean patient age for newly diagnosed cases was 40.7 ± 12.9 years and male:female ratio was 1.8. Seventy‐three percent of all cases of hyperglycemia appeared within 6 months of start of olanzapine therapy. Eighty patients had metabolic acidosis or ketosis, 41 had glucose levels of 1000 mg/dl or greater, and 15 patients died. When olanzapine was discontinued or the dosage decreased, 78% of patients had improved glycemic control. Hyperglycemia recurred in 8 of 10 cases with rechallenge.Conclusions. Number of reports, temporal relationship to start of olanzapine therapy, relatively young age, and improvement on drug withdrawal suggest that olanzapine may precipitate or unmask diabetes in susceptible patients.
Drug‐Related Visits to the Emergency Department: How Big Is the Problem?
Authors: Patel Payal , Zed Peter J. 
Published: June 2004

Objectives. To review the literature concerning drug‐related problems that result in emergency department visits, estimate the frequency of these problems and the rates of hospital admissions, and identify patient risk factors and drugs that are associated with the greatest risk.Methods. A systematic search of MEDLINE (January 1966–December 2001), EMBASE (January 1980–December 2001), and PubMed (January 1966–December 2001) databases for full reports published in English was performed. The Ottawa Valley Regional Drug Information Service database of nonindexed pharmacy journals also was searched.Results. Data from eight retrospective and four prospective trials retrieved indicated that as many as 28% of all emergency department visits were drug related. Of these, 70% were preventable, and as many as 24% resulted in hospital admission. Drug classes often implicated in drug‐related visits to an emergency department were nonsteroidal antiinflammatory drugs, anticonvulsants, antidiabetic drugs, antibiotics, respiratory drugs, hormones, central nervous system drugs, and cardiovascular drugs. Common drug‐related problems resulting in emergency department visits were adverse drug reactions, noncompliance, and inappropriate prescribing.Conclusion. Drug‐related problems are a significant cause of emergency department visits and subsequent resource use. Primary caregivers, such as family physicians and pharmacists, should collaborate more closely to provide and reinforce care plans and monitor patients to prevent drug‐related visits to the emergency department and subsequent morbidity and mortality.
CYP2D6 Inhibition by Selective Serotonin Reuptake Inhibitors: Analysis of Achievable Steady‐State Plasma Concentrations and the Effect of Ultrarapid Metabolism at CYP2D6
Authors: Lam Y. W. Francis , Gaedigk Andrea , Ereshefsky Larry , Alfaro Cara L. , Simpson Joe 
Published: June 2004

Study Objective. To assess the correlation between plasma concentrations of four commonly administered selective serotonin reuptake inhibitors (SSRIs) and the magnitude of cytochrome P450 (CYP) 2D6 inhibition.Design. Prospective analysis.Setting. University‐affiliated research laboratory.Patients. Thirty‐two healthy, drug‐free volunteers.Intervention. Subjects were randomized to four groups and received daily administration of either fluoxetine 60 mg (as a loading dose), fluvoxamine 100 mg, paroxetine 20 mg, or sertraline 100 mg for 8 days.Measurements and Main Results. The urinary concentration ratio of dextromethorphan:dextrorphan (interpreted as an in vivo index of CYP2D6 activity) was determined for each subject before and after the 8 days of receiving SSRIs. Plasma SSRI trough concentrations were measured on days 6–9. The CYP2D6 genotype was determined in a subject with an undetectable paroxetine concentration. Inhibition of CYP2D6 correlated significantly with plasma concentrations of paroxetine and fluoxetine. In contrast, no significant correlations emerged between CYP2D6 inhibition and plasma concentrations of sertraline or fluvoxamine. The subject with an undetectable paroxetine concentration was found to carry at least three functional CYP2D6 genes.Conclusions. For paroxetine and fluoxetine, plasma concentrations and dosage strongly influence the magnitude of enzyme inhibition. The potential of paroxetine (a CYP2D6 substrate) as an inhibitor may be affected by the genotypes and metabolic capacities of individual subjects.
Do Butalbital‐Containing Products Have a Role in the Management of Migraine?
Authors: Wenzel Richard G. , Sarvis Carrie A. 
Published: June 2004

Study Objective. To evaluate the role of butalbital‐containing products in the management of migraine.Methods. Qualitative systematic search using MEDLINE (January 1966–November 2001), review of the United States Headache Consortium's evidence‐based guidelines for migraine treatment, and review of other pertinent literature.Results. Over 28 million people suffer with migraine, yet this illness is less than optimally diagnosed and managed. Between 14% and 36% of diagnosed migraineurs are prescribed butalbital‐containing products, often as initial therapy. However, the only identified controlled trial of these drugs for migraine treatment showed that butalbital‐containing products were inferior to butorphanol. The consortium's guidelines specifically discourage administration of butalbital‐containing products for migraine. In addition, other published literature highlights the frequent adverse consequences of butalbital‐containing products for migraineurs, such as poor migraine control, disability, drug‐induced headaches, and withdrawal symptoms.Conclusion. Although butalbital‐containing products commonly are prescribed for migraine, no evidence in the literature demonstrates their benefit over other agents or placebo. Drugs with proven migraine efficacy, as listed in the consortium's evidence‐based guidelines, should be prescribed instead.
Drug‐Information Software for Palm Operating System Personal Digital Assistants: Breadth, Clinical Dependability, and Ease of Use
Authors: Enders Shelly J. , Enders Jason M. , Holstad Sheldon G. 
Published: June 2004

Study Objective. To examine the breadth, clinical dependability, and ease of use of drug‐information software programs for personal digital assistants that incorporate the Palm operating system.Design. Prospective evaluation with descriptive analysis.Methods. Nine drug‐information software programs were evaluated for breadth, clinical dependability, and ease of use, based on responses to 56 questions.Results. Breadth of information (percentage of questions that could be answered) was 32–75%; LexiComp Platinum was the leader in this category. Clinical dependability (factual completeness) of information was 66.7–100%; LexiComp Platinum led this category as well. MobileMicromedex provided the narrowest breadth of information and the least clinically dependable information. Time to locate an answer to posed questions averaged 17.5 ± 4.98 seconds. The fastest retrieval time was achieved by Davis's Drug Guide for Physicians (12.1 sec). Tarascon's Pharmacopoeia required the fewest viewed PDA screens to locate the requested information (3.3 screens). Cost of programs ranged from free to $129.95. Cost was not related to breadth or clinical dependability.Conclusions. LexiComp Platinum offered the greatest breadth of information and the most clinically dependable content. MobileMicromedex was the least helpful of these products for answering straightforward drug‐information questions.