bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disposition of Two Oral Formulations of Cyclosporine in Pediatric Patients Receiving Hematopoietic Stem Cell Transplants
Authors: Dupuis L. Lee , Taylor Tracey , Saunders E. Fred 
Published: January 2006

Study Objectives. To compare the disposition of cyclosporine after the administration of two oral formulations to children undergoing hematopoietic stem cell transplantation, and to evaluate the relationship between whole blood cyclosporine concentrations during the dosing interval and the area under the whole blood concentration‐time curve.Design. Prospective, descriptive, crossover study.Setting. Hematopoietic stem cell transplantation unit in a tertiary‐quaternary university‐affiliated pediatric hospital.Patients. Twenty‐four pediatric patients aged 0.5–16.9 years undergoing allogeneic hematopoietic stem cell transplantation.Intervention. The modified oral formulation of cyclosporine was given on the first day (divided as two doses), and a single identical dose of the original oral formulation was given on the morning of the second day.Measurements and Main Results. Blood samples were obtained at 0, 0.5, 1.25, 2, 4, 6, 9, and 12 hours after the morning dose from the lumen of the central venous catheter not previously used for intravenous cyclosporine administration. Cyclosporine concentration‐time data were analyzed by using noncompartmental methods. Mean ± SD maximum concentrations were significantly higher after administration of the modified form than after administration of the original form (594.9 ± 349.7 vs 483.0 ± 363.0 μg/L, p=0.003), as was the area under the concentration‐time curve from 0–12 hours (AUC0–12; 3432 ± 1563 vs 3144 ± 1780 μg/L•hr, p=0.022). For both formulations, cyclosporine concentrations at 4 hours after administration were most strongly correlated with the AUC0–12. Unlike that of the original formulation, the trough cyclosporine concentration of the modified form had the weakest relationship with AUC (Spearman ρ coefficient 0.584, p=0.003).Conclusion. Cyclosporine absorption is lower in children undergoing hematopoietic stem cell transplantation than in children receiving solid organ transplants. Dosage adjustment for the modified formulation based on trough concentration may not be appropriate because its relationship with the AUC was weak. The link between pharmacokinetic parameters and clinical outcomes, such as graft‐versus‐host disease, must be further studied.
Osmol Gap as a Surrogate Marker for Serum Propylene Glycol Concentrations in Patients Receiving Lorazepam for Sedation
Authors: Barnes Brian J. , Gerst Christopher , Smith Jennifer R. , Terrell Andrea R. , Mullins Michael E. 
Published: January 2006

Study Objectives. To correlate serum propylene glycol concentration with osmol gap, serum lactate concentration, and amount of propylene glycol administered to mechanically ventilated patients receiving continuous infusions of lorazepam (80% propylene glycol by weight), and to characterize the prevalence of hyperosmolality and range of serum propylene glycol concentrations in this patient population.Design. Prospective, controlled, observational study.Setting. Adult surgical and cardiothoracic intensive care units (ICUs) of a 1200‐bed, urban, tertiary care, teaching hospital.Patients. Sixty‐four consecutively enrolled intensive care patients requiring mechanical ventilation and pharmacologic sedation.Intervention. Thirteen patients received continuous infusions of high‐dose lorazepam (≥ 6 mg/hr) for a minimum of 36 hours, and 26 received continuous infusions of low‐dose lorazepam (2–5.99 mg/hr) for 36 hours. Twenty‐five control patients received sedatives that did not contain propylene glycol.Measurements and Main Results. Serum propylene glycol and lactate concentrations, osmolality, and basic metabolic profiles were obtained 72–108 hours after ICU admission. Clinical data, drug administration, and severity of illness scores were recorded. Osmol gap and the amount of propylene glycol administered before serum sampling predicted propylene glycol concentrations (r2=0.692, p<0.05). Osmol gap alone also predicted serum propylene glycol concentrations (r2=0.532, p<0.05). Serum lactate concentrations did not correlate with serum propylene glycol concentrations. Unlike the low‐dose and control patients, eight (62%) of 13 high‐dose patients had osmol gaps above 10. All 13 high‐dose patients had serum propylene glycol concentrations previously associated with toxicity.Conclusion. Osmol gap can be used as a surrogate marker for serum propylene glycol concentration. In critically ill patients receiving lorazepam for sedation, an osmol gap above 10 was associated with concentrations previously reported to cause toxicity.
Pharmacoeconomic Modeling of Nesiritide versus Dobutamine for Decompensated Heart Failure
Authors: Gerhard Tobias , Zineh Issam , Winterstein Almut G. , Hartzema Abraham G. 
Published: January 2006

Study Objective. To model the cost‐effectiveness of nesiritide compared with dobutamine in patients with decompensated heart failure.Design. Cost‐effectiveness analysis.Measurements and Main Results. A decision tree model was derived from randomized clinical trial data and data from a previously published economic study. Four cost‐effectiveness analyses were performed: analysis 1—full probabilistic analysis, repeatedly sampled probabilities for 6‐month mortality and hospital readmission from distributions based on 95% confidence intervals (CIs); analysis 2—best‐case nesiritide analysis, used the limiting values of the 95% CI favorable to nesiritide; analysis 3—best‐case dobutamine analysis, used the limiting values of the 95% CI favorable to dobutamine; and analysis 4—replicated the previously published cost‐effectiveness study and served as a methodologic control. Fifty‐one consecutive Monte Carlo simulations for cohorts of 1000 hypothetical patients were performed for each analysis. Incremental cost, incremental effectiveness, and incremental cost‐effectiveness ratios (ICERs) were calculated for nesiritide versus dobutamine. Analysis 1 showed a mean ICER of $767/life‐year gained for nesiritide versus dobutamine (incremental cost $251 ± $290, incremental effectiveness 0.33 ± 0.22 yr). The 95% confidence region surrounding this point estimate spanned all four quadrants of the incremental cost‐effectiveness scatterplot, suggesting inconclusive results. Nesiritide was the dominant treatment strategy in analysis 2 (incremental cost −$734 ± $106, incremental effectiveness 1.19 ± 0.07 yrs), whereas dobutamine was dominant in analysis 3 (incremental cost $1242 ± $73, incremental effectiveness −0.57 ± 0.05 yr). Analysis 4 was comparable to the previously published cost‐effectiveness analysis (incremental cost −$77 ± $87, incremental effectiveness 0.48 ± 0.05 yr).Conclusions. Based on available randomized clinical trial data, nesiritide did not exhibit robust economic superiority over dobutamine. When incorporating the uncertainty (i.e., 95% CIs) in clinical effectiveness as reported in available clinical trial data into the economic analysis, either nesiritide or dobutamine may be the dominant treatment (i.e., more effective at lower cost) for the studied population. Economic analyses of nesiritide and any comparator must account for uncertainty in estimates of cost as well as in clinical effectiveness.
Evaluation of a Sex‐Based Difference in the Pharmacokinetics of Digoxin
Authors: Lee Lois S. , Chan Lingtak‐Neander 
Published: January 2006

Study Objective. To determine whether a sex‐based difference in digoxin pharmacokinetics exists in patients receiving long‐term digoxin therapy for chronic heart failure or atrial fibrillation.Design. Single‐center, retrospective review of medical records.Setting. University‐based teaching hospital and outpatient clinic.Patients. Sixty‐seven adults (32 men, 35 women) with chronic heart failure or atrial fibrillation who were receiving digoxin therapy.Measurements and Main Results. Serum digoxin concentrations and daily digoxin doses were obtained from patients' medical records. Daily doses were adjusted for patients' actual and ideal body weight and body mass index (BMI). The ratio between the serum digoxin concentration and each of the adjusted daily doses of digoxin was compared between men and women. The mean ± SD serum digoxin concentration was 0.85 ± 0.51 ng/ml for men compared with 1.02 ± 0.51 ng/ml for women. Mean ± SD unadjusted doses of digoxin were 0.180 ± 0.063 and 0.164 ± 0.059 mg/day for men and women, respectively; the difference was not statistically significant. Ratios of serum digoxin concentration to daily digoxin doses did not differ by sex when doses were estimated with actual or ideal weight. Only the ratio of the digoxin concentration to the BMI‐adjusted dose was significantly different between men and women (0.14 ± 0.09 and 0.19 ± 0.11, respectively, p<0.05).Conclusion. Sex‐based differences in digoxin pharmacokinetics were absent when actual or ideal body weight was used. However, the ratio of serum digoxin concentration to daily digoxin dose adjusted for BMI differed by sex. Because digoxin is distributed to lean body mass, use of the BMI could have overadjusted body weight, leading to inaccurate pharmacokinetic assumptions and calculations. The pharmacokinetics of digoxin do not appear to differ by sex.
Comparative Safety and Efficacy of Urokinase and Recombinant Tissue Plasminogen Activator for Peripheral Arterial Occlusion: A Meta‐Analysis
Authors: Sander Stephen , White C. Michael , Coleman Craig I. 
Published: January 2006

Study Objective. To evaluate differences in the efficacy and safety of recombinant tissue plasminogen activator (rt‐PA) and urokinase in the treatment of peripheral arterial occlusion.Design. Systematic review and meta‐analysis of prospective comparative trials.Data Source. PubMed/MEDLINE database from 1966‐October 2004.Conclusion. Urokinase was less effective than rt‐PA in successfully lysing acute peripheral arterial occlusion, but it was associated with lower rates of total and minor bleeding. Overall, rt‐PA was a reasonable substitute for urokinase, now that urokinase has been removed from the market in the United States. However, judicious monitoring for minor bleeding is necessary
Impact of a Piperacillin‐Tazobactam Shortage on Antimicrobial Prescribing and the Rate of Vancomycin‐Resistant Enterococci and Clostridium difficile Infections
Authors: Mendez Marisa N. , Gibbs Laurel , Jacobs Richard A. , McCulloch Charles E. , Winston Lisa , Guglielmo B. Joseph 
Published: January 2006

Study Objective. To evaluate the impact of a shortage of piperacillintazobactam in the United States in 2002 on antimicrobial prescribing and associated rates of vancomycin‐resistant enterococci (VRE) and Clostridium difficile infections.Design. Retrospective chart review.Setting. University‐affiliated medical center.Measurements and Main Results. Microbiologic reports, patient demographics, and antimicrobial utilization were evaluated for patients admitted 6 months before the shortage (March 1‐August 31, 2001) and for 6 months during the shortage (March 1‐August 31, 2002). Significant increases in usage of alternative β‐lactamase inhibitor combinations, cefepime, levofloxacin, vancomycin, clindamycin, and metronidazole were observed during the shortage; in contrast, a significant decrease in the use of ceftriaxone took place. No change in the rate of VRE infection was observed from before to during the piperacillin‐tazobactam shortage. However, a paradoxical 47% decrease in the rate of C. difficile colitis was documented during the shortage. Subsequent multivariate analyses suggested the reduced use of ceftriaxone and increased use of levofloxacin, but not the reduced use of piperacillin‐tazobactam, correlated with the decreased rate of C. difficile infections.Conclusion. The piperacillin‐tazobactam shortage was associated with significant changes in antimicrobial prescribing, which resulted in a significant reduction in the rate of C. difficile but not VRE infections.
Pharmacotherapy for Idiopathic Pulmonary Arterial Hypertension During the Past 25 Years
Authors: Hackman Anna M. , Lackner Thomas E. 
Published: January 2006

Objective. To review the current pharmacotherapy for idiopathic pulmonary arterial hypertension (IPAH).Methods. A search of the primary literature was conducted by using MEDLINE, the National Institutes of Health medical research Web site (www.clinicaltrials.gov), and the United States Food and Drug Administration's Center for Drug Evaluation and Research Web site (www.fda.govcder).Results. Until the early 1980s, conventional therapy for IPAH consisted of anticoagulation, diuretics, digitalis extracts, and supplemental oxygen, yet the 5‐year mortality rate remained at 66%. Calcium channel blocker therapy was introduced with the hope that it would improve survival in patients with IPAH, but it was found to be effective in only approximately 25% of patients. In 1996, intravenous epoprostenol was the first drug to show long‐term benefit on hemodynamics, exercise capacity, and survival. However, administration of epoprostenol requires a permanently indwelling central venous catheter, and tachyphylaxis is common, necessitating continuous dosage escalations. Subsequently, treprostinil, a prostacyclin analog of epoprostenol that can be administered by continuous subcutaneous infusion, was introduced, followed by aerosolized iloprost, a prostacyclin analog for inhalation. An increasing understanding of the multiple pathogeneses of IPAH led to the discovery of another target for drug therapy, and bosentan, an orally administered agent, became the first endothelin‐receptor antagonist approved for treatment of IPAH. Most recently, the phosphodiesterase inhibitor, sildenafil, has received approval from the United States Food and Drug Administration for the treatment of IPAH.Conclusion. Recently developed pharmacotherapies offer greater effectiveness and safety than traditional agents for the treatment of IPAH.
Asian Oral-Facial Cleft Birth Prevalence
Authors: Cooper Margaret E. , Ratay Jessica S. , Marazita Mary L. 
Published: January 2006

Objective: To determine the clefting birth prevalence among Asian populations, specifically Chinese and Japanese, using raw counts from nonoverlapping published studies of Asian populations, and to investigate whether Asian clefting rates have been interpreted accurately as being up to twice the Caucasian rate. Design: A literature review of articles giving raw counts of clefting in Asian populations, primarily Japanese and Chinese. Main Outcome Measures: Where possible, clefts were identified by the patients’ ethnicity, country of origin, cleft type, syndromic status, and birth status. Results: Prevalence rates of cleft lip with or without cleft palate per 1000 live births are reported. Syndromic plus nonsyndromic cleft lip with or without cleft palate: Chinese, 1.30; Japanese, 1.34; Other Asian, 1.47; and total, 1.33. Nonsyndromic cleft lip with or without cleft palate: Chinese, 1.20; Japanese, 1.18; Other Asian, 1.22; and total, 1.19. Conclusions: Overall, Chinese and Japanese live birth prevalence rates for nonsyndromic cleft lip with or without cleft palate, based on the published reports of birth prevalence, are significantly lower than the oft-quoted rate of 2 per 1000 for Asians. The apparent reason for the discrepancy is that many published prevalence rates included all pregnancies (live births plus pregnancy losses) and do not distinguish between syndromic and nonsyndromic clefts or between cleft palate alone and cleft lip with or without cleft palate. These results demonstrate that it is extremely important for current population-based studies of clefts to include careful delineation of population groups, syndromes, cleft type, and birth status.
Fluctuating asymmetry and condition in golden shiner (Notemigonus crysoleucas) and channel catfish (Ictalurus punctatus) reared in sublethal concentrations of isopropyl methylphosphonic acid
Authors: Green Chris C. , Lochmann Steve E. 
Published: January 2006

Abstract
Fluctuating asymmetry (FA; small, random differences between the left and right sides of a bilateral character) has been related to embryological stress during development. Some populations exhibit positive relations between FA and exposure to toxicants during development. The United States has agreed to demilitarize chemical warfare agents in accordance with the Chemical Weapons Convention Treaty. Isopropyl methylphosphonic acid (IMPA), the main hydrolysis product of sarin, could be introduced accidentally into the environment during demilitarization. The present study examined the use of FA as a biomarker of developmental stress caused by sublethal exposures to IMPA. A suite of morphometric and meristic traits were measured in two fish species exposed to IMPA. Significant differences were found in composite FA among groups of channel catfish (Ictalurus punctatus) exposed to sublethal concentrations of IMPA during development. No differences were found in composite FA among groups of golden shiner (Notemigonus crysoleucas) exposed to IMPA. No relation was found between individual relative condition and FA in channel catfish or golden shiner.
Metal blood levels and hematological characteristics in wood mice (Apodemus sylvaticus L.) along a metal pollution gradient
Authors: Rogival Damien , Scheirs Jan , De Coen Wim , Verhagen Ron , Blust Ronny 
Published: January 2006

Abstract
The present study evaluated whether blood could be used as a nondestructive tool for monitoring metal exposure and related hematological effects in wood mice (Apodemus sylvaticus L.) living along a metal pollution gradient. Soil concentrations of arsenic, cadmium, copper, lead, silver, and zinc decreased with distance from the emission source. Blood levels of cadmium and lead differed significantly among sites, whereas those of the other metals did not. Blood levels of cadmium and lead correlated with soil concentrations of cadmium and lead, respectively. No such significant relationships were found for the other measured metals. Hematocrit levels decreased in wood mice from the most polluted site (45.96% ± 0.53% [mean ± standard error]) compared to the reference site (48.04% ± 0.47%). A negative correlation between hematocrit and blood levels of cadmium and lead was found. Erythrocyte count, leukocyte count, hemoglobin concentration, mean corpuscular hemoglobin (average wt of hemoglobin in a red blood cell in pg), and lysozyme activity did not differ among study sites. Mean corpuscular volume (average volume of a red blood cell in μm3) and mean corpuscular hemoglobin concentration (average proportion of hemoglobin in a red blood cell as a %) differed among study sites but showed no relationship with metal exposure. We conclude that whole blood from mice can be used for nondestructive monitoring of the exposure to nonessential metals under natural conditions. The present results indicate that decreased hematocrit levels may be an early warning signal for a negative impact of metal exposure on the oxygen-transport capacity of blood in wood mice in their natural environment.
Flows of dioxins and furans in coastal food webs: Inverse modeling, sensitivity analysis, and applications of linear system theory
Authors: Saloranta Tuomo M. , Andersen Tom , Næs Kristoffer 
Published: January 2006

Abstract
Rate constant bioaccumulation models are applied to simulate the flow of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in the coastal marine food web of Frierfjorden, a contaminated fjord in southern Norway. We apply two different ways to parameterize the rate constants in the model, global sensitivity analysis of the models using Extended Fourier Amplitude Sensitivity Test (Extended FAST) method, as well as results from general linear system theory, in order to obtain a more thorough insight to the system's behavior and to the flow pathways of the PCDD/Fs. We calibrate our models against observed body concentrations of PCDD/Fs in the food web of Frierfjorden. Differences between the predictions from the two models (using the same forcing and parameter values) are of the same magnitude as their individual deviations from observations, and the models can be said to perform about equally well in our case. Sensitivity analysis indicates that the success or failure of the models in predicting the PCDD/F concentrations in the food web organisms highly depends on the adequate estimation of the truly dissolved concentrations in water and sediment pore water. We discuss the pros and cons of such models in understanding and estimating the present and future concentrations and bioaccumulation of persistent organic pollutants in aquatic food webs.
A pollution-monitoring pilot study involving contaminant and biomarker measurements in the Seine Estuary, France, using zebra mussels (Dreissena polymorpha)
Authors: Minier Christophe , Abarnou Alain , Jaouen-Madoulet Agnès , Le Guellec Anne-Marie , Tutundjian Renaud , Bocquené Gilles , Leboulenger François 
Published: January 2006

Abstract
Zebra mussel (Dreissena polymorpha) is an invasive species that has proliferated in European and North American rivers and lakes during the last century. In this study, D. polymorpha has been used to provide information on contamination levels and biological effects in the Seine Estuary (France). The bivalves accumulated polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) to a high degree with values reaching 800 ng/g dry weight for PCBs (sum of 20 congeners), and 1,000 ng/g dry weight of PAHs (sum of 14 compounds) in the whole body. These values are among the highest reported of PCBs and, to a lesser extent, of PAHs in other contaminated areas in the world. Toxic equivalent quantities of PCBs and PAHs detected in zebra mussels varied from 20 to 40 pg dioxin equivalents/g dry weight for PCBs and up to 120 ng benzo[a]pyrene equivalents/g dry weight for PAHs, indicating a high potential risk for animals feeding on them. Biological impacts, such as altered condition index, decreased lysosomal stability, and high levels of multixenobiotic resistance (MXR) proteins also were detected in mussels living downstream of Rouen, the main city of the Seine Estuary. Taken together, these results indicate that the Seine Estuary is a heavily polluted area with the potential to cause deleterious health effects in some endogenous living organisms. This study also shows that chemical and biological measurements bring different but complementary results that can help diagnose environmental health.