bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacoeconomics of Aztreonam‐Clindamycin versus Gentamicin‐Clindamycin in the Treatment of Penetrating Abdominal Injury
Authors: Fabian Timothy C. , Boucher Bradley A. , Croce Martin C. 
Published: October 2023

Study Objective. To evaluate the pharmacoeconomic implications of using aztreonam‐clindamycin (A‐C) versus gentamicin‐clindamycin (G‐C) from the perspective of the hospital and pharmacy directors.Design. Pharmacoeconomic analysis performed at one of the sites participating in the prospective, randomized, double‐blind, comparative, multicenter efficacy study.Setting. Referral hospital with level 1 trauma center.Patients. Eight‐five adults with a suspected penetrating intraabdominal injury requiring laparotomy.Interventions. Patients were randomized to receive aztreonam 2 g intravenously every 8 hours or gentamicin 2 mg/kg intravenous load followed by 5 mg/kg/day intravenously initially adjusted to peak concentrations of 6–8 μg/ml. All patients received clindamycin 900 mg intravenously every 8 hours.Measurements and Main Results. Charge data were gathered from the hospital billing system and converted to cost data using an institutional cost:charge ratio of 0.6. Study drug and aminoglycoside monitoring costs were also calculated. Overall, 43 (97%) of 44 patients receiving A‐C had a favorable clinical response compared with 35 (85.4%) of 41 receiving G‐C (p=0.052). The mean hospital cost of $66,336 for 7 infected patients was significantly higher than that of $8014 in 78 noninfected patients (p>0.0001). Mean hospital costs of $12,058 and $13,742 for A‐C and G‐C groups, respectively, were not significantly different (p<0.05) despite having only a single failure (total cost $162,666) in the A‐C group. Similarly, mean pharmacy costs of $1411 and $1604, respectively, were not significantly different (p>0.05).Conclusions. Hospital costs for infected patients with penetrating abdominal trauma exceed those of noninfected patients by 5‐fold. Despite a lower infection rate in the A‐C group, neither hospital nor pharmacy costs were significantly different compared with those in the G‐C group.
4‐Aminopyridine Improves Pulmonary Function in Quadriplegic Humans with Longstanding Spinal Cord Injury
Authors: Segal Jack L. , Brunnemann Sherry R. 
Published: October 2023

Study Objective. To test the hypothesis that 4‐aminopyridine (4‐AP) might cause clinically evident improvement in pulmonary function in humans with chronic spinal cord injury (chronic SCI).Design. Balanced, open‐label study with subjects consecutively enrolled.Setting. Spinal Cord Injury Service, university‐affiliated tertiary level care Department of Veterans Affairs Medical Center.Patients. Seventeen healthy men and women suffering from traumatic SCI (11 quadriplegic, 6 paraplegic patients) for more than 1 year.Interventions. Each subject was given a single dose of 4‐AP 10 mg orally in an immediate‐release formulation.Measurements and Main Results. Significant increases in mean values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) that persisted for at least 12 hours were demonstrated in quadriplegic patients beginning 6 hours after 4‐AP administration. Tests of pulmonary function that demonstrated statistically significant increases at any time were also numerically, if not statistically, increased at 24 hours compared with pretreatment values obtained in 4‐AP‐naive subjects.Conclusions. The administration of a single dose of an immediate‐release formulation of 4‐AP to humans with longstanding, traumatic quadriplegia is associated with sustained, clinically meaningful, and statistically significant improvements in pulmonary function. We suggest that the administration of 4‐AP may have a salutary effect in patients suffering from SCI and appears to be associated with potentially clinically significant reductions in the pathophysiologic pulmonary sequelae of SCI.
A Statistical and Clinical Evaluation of Fingerstick and Routine Laboratory Prothrombin Time Measurements
Authors: Bussey Henry I. , Chiquette Elaine , Bianco Theresa M. , Lowder‐Bender Kathryn , Kraynak Maura A. , Linn William D. , Farnett Lisa , Clark Gary M. 
Published: October 2023

Study Objective. To compare prothrombin time measurements by fingerstick and routine laboratory methods.Design. Prospective cohort study.Setting. University‐affiliated anticoagulation clinic.Patients. Thirty‐three patients receiving warfarin with stable anticoagulation for 3 months preceding the two studies.Interventions. Groups 1 (17 patients) and 2 (16 patients) provided 150 and 125 paired samples, respectively, for fingerstick and routine laboratory analysis. The fact that no patient required a dosage change allowed for a clinical assessment.Measurements and Main Results. Correlation and agreement between methods were good in group 1 but poor in group 2. Fingerstick results were less variable (smaller standard deviation and smaller coefficient of repeatability) in both groups. By analysis of discrepant pairs (25 in group 1, 63 in group 2), the routine laboratory results indicated dosage changes erroneously more often than did the fingerstick method.Conclusions. In these two trials, the fingerstick system was superior to the routine laboratory method in that it was more reliable (less variability and more repeatable) and less likely to indicate dosage changes erroneously. (Pharmacotherapy 1997;17(5):861–866)Conclusions: Although it is entirely feasible that RL and FS comparisons in other locations might differ from those presented here, it is important that any such comparison go beyond calculating a correlation coefficient. Additionally, any such evaluation should take into account that the “gold standard” (the RL) may be the inferior method. While there are a number of potential explanations as to why data from groups 1 and 2 were not more similar, the fact remains that under the conditions of the two trials, the FS method demonstrated less variability, was more repeatable, and was less likely to indicate dosage changes erroneously than was the RL method in either the hospital or clinic laboratory of a large university health science center. The FS system was superior to either RL.
Comparison of 5‐Fluorouracil Pharmacokinetics in Whole Blood, Plasma, and Red Blood Cells in Patients with Colorectal Cancer
Authors: Wattanatorn Wiboon , McLeod Howard L. , Macklon Fiona , Reid Muriel , Kendle Keith E. , Cassidy James 
Published: October 2023

Study Objective. To compare 5‐fluorouracil (5‐FU) pharmacokinetics in whole blood, plasma, and red blood cells in patients with colorectal cancer.Design. Prospective, unblinded observational study in consecutive patients.Setting. Large regional teaching hospital.Patients. Five patients with colorectal cancer.Interventions. Patients received folinic acid 200 mg/m2 intravenously over 2 hours, followed by 5‐FU 600 mg/m2 intravenous bolus over 30 minutes, then 5‐FU 600 mg/m2 intravenous infusion over 22 hours, administered on days 1 and 2. This 48‐hour cycle was repeated every 14 days.Measurements and Main Results. Concentrations of 5‐FU in whole blood, plasma, and red blood cells were determined by high‐performance liquid chromatography. ADAPT II was used for pharmacokinetic computations. The optimum model was determined for each matrix by calculating Akaike's information criteria values. Concentrations of 5‐FU in whole blood were 106–115% of simultaneous plasma concentrations (median 112%), and packed red blood cell levels were 5–17% of plasma concentrations (median 11%). The drug's concentration‐time profile was similar in the three matrices. The drug is reported to be unstable in whole blood, and red blood cell 5‐FU concentrations were near the limit of detection (10 ng/ml), supporting plasma as the preferred matrix for therapeutic drug monitoring studies. Six pharmacokinetic models were fitted to the 5‐FU individual data sets to determine the best curve fit. The optimal model for whole blood and plasma data sets was one compartment with both linear and nonlinear elimination models; a one‐compartment model with nonlinear elimination provided the best curve fit for 5‐FU in red blood cells. A two‐compartment model with nonlinear elimination gave a similar degree of curve fit for plasma 5‐FU as the one‐compartment model with both linear and nonlinear elimination.Conclusions. These pharmacokinetic results provide the basis for further investigation into the ability to correlate 5‐FU systemic exposure with clinical drug activity. (Pharmacotherapy 1997;17(5):881–886)
Methylprednisolone Disposition Kinetics in Patients with Acute Spinal Cord Injury
Authors: Segal Jack L. , Maltby Brian F. , Langdorf Mark I. , Jacobson Ray , Brunnemann Sherry R. , Jusko William J. 
Published: October 2023

Study Objective. To evaluate the pharmacokinetics of high‐dose methylprednisolone in patients with acute spinal cord injury (ASCI).Design. Open‐label study of consecutive patients with ASCI, and retrospective review of able‐bodied controls.Setting. Emergency Medicine Department of a large, urban, university‐affiliated, tertiary care trauma center.Patients. Eleven men with ASCI.Interventions. Methylprednisolone sodium succinate 30 mg/kg intravenous bolus, followed by 5.4 mg/kg/hour for 23 hours, administered according to the second National Acute Spinal Cord Injury Study (NASCIS 2) protocol.Measurements and Main Results. The total systemic clearance of methylprednisolone was significantly less in acutely injured patients (mean ± SD 30.04 ± 12.03 L/hr) than in historically reported able‐bodied controls (44.70 ± 4.90 L/hr). An inverse correlation between the neurologic level of injury and systemic clearance was seen. No differences in volume of distribution were discernible between patients (126.90 L) and controls (135.45 L).Conclusion. Patients with acute spinal cord injury administered methylprednisolone according to the NASCIS 2 protocol had an apparent decrease in total systemic clearance of the drug without a commensurate change in volume of distribution. Additional studies are warranted to confirm these findings and assess the potential impact of diminished clearance on the efficacy of the agent in ASCI.
Interaction Between Cyclosporine and Grapefruit Juice Requires Long‐Term Ingestion in Stable Renal Transplant Recipients
Authors: Brunner Lane J. , Munar Myrna Y. , Vallian John , Wolfson Marsha , Stennett Douglass J. , Meyer Mary M. , Bennett William M. 
Published: October 2023

Study Objective. To examine the effect of the concurrent administration of increasing amounts of grapefruit juice, an inhibitor of drug metabolism, on the steady‐state pharmacokinetics of cyclosporine.Design. Open‐label, three‐period crossover, food‐drug interaction study in stable renal transplant patients.Setting. A university‐affiliated clinical research center.Patients. Sixteen stable renal transplant recipients.Intervention. Cyclosporine was administered with 240 ml of water, 240 ml of grapefruit juice, or several 240‐ml glasses of grapefruit juice, and serial blood samples were taken to estimate the effect of grapefruit juice on cyclosporine pharmacokinetics.Measurements and Main Results. Grapefruit juice caused a significant increase in cyclosporine area under the curve, however, no significant effect was seen in other pharmacokinetic parameters. Grapefruit juice caused an increase in the 24‐hour trough cyclosporine concentration, which may be of clinical significance if long‐term ingestion of grapefruit juice is recommended.Conclusion. A drug interaction exists between cyclosporine and grapefruit juice, and it is likely at the level of intestinal drug absorption.
Morphometric Study of the Gubernaculum in Male Estrogen Receptor Mutant Mice
Authors: DONALDSON KAREN M. , TONG STEVEN Y. C. , WASHBURN TODD , LUBAHN DENNIS B. , EDDY EDWARD M. , HUTSON JOHN M. , KORACH KENNETH S. 
Published: October 2023

ABSTRACT: To determine role of estrogen receptors in testicular descent, a morphometric study of the testis and structures derived from the gubernaculum was made in sexually mature male mice having an estrogen receptor disrupted gene mutation (ERKO). Macroscopic dissections and sagittal serial sections were made of the pelvis of four wild‐type mice, four mice heterozygous for the ERKO mutation, and four homozygous ERKO males. By external morphological examination the testes appeared to be descended in all three genotypes. All mice had development of a cremaster sac, which is derived from the gubernaculum, but this was twice as large in wild‐type mice than in both the heterozygote or homozygote ERKO groups.The cause for the smaller cremaster sac appeared to be excessive development of the cremaster muscle in ERKO mice. The thickened muscle was associated with postmortem retraction of the testes into the inguinal canal or abdomen. Spermatogenesis and testicular volume were deficient in homozygous ERKO mice at this age. This study demonstrates that estrogen has a previously unknown role in masculine sexual development of the gubernaculum and the structures derived from it, such as the cremaster muscle.
Comparison Between Testosterone Enanthate‐Induced Azoospermia and Oligozoospermia in a Male Contraceptive Study. V. Localization of Higher 5α‐Reductase Activity to the Reproductive Tract in Oligozoospermie Men Administered Supraphysiological Doses of Testosterone
Authors: ANDERSON R. A. , KELLY R. W. , WU F. C. W. 
Published: October 2023

ABSTRACT: Sex steroid contraceptive regimens result in incomplete suppression of spermatogenesis in 30–45% of Caucasian men. The basis for this is unclear, but differences in the activity of 5α‐reductase (5αR) have been demonstrated. Two isoforms of 5αR have been described: 5αR1 is found in skin, whereas the predominant form in reproductive tissues is 5αR2. To investigate possible contributions of these isoenzymes, we have investigated androgen‐dependent changes in seminal plasma androgens (5αR2) and sebum production (5αR1) during administration of a supraphysiological dose (200 mg IM weekly) of testosterone enanthate (TE) to 33 normal men.Eighteen men rapidly (<20 weeks treatment) became azoospermia, the remainder having a mean sperm density of 2.0 ± 0.6 × 106 at that time. The concentrations of testosterone and 3α, 17β‐andros‐tanediol glucuronide (AdiolG) were lower in seminal plasma than in blood but rose by a similar degree (100%) after 16 weeks TE treatment in both groups. There were no differences in seminal‐plasma concentration of testosterone or AdiolG between azoospermic and Oligozoospermie responders, either pretreatment or after 16 weeks TE treatment. Although the concentrations of dihydrotestosterone (DHT) were similar in seminal plasma and blood pre‐ and posttreatment, there was a selective increase in seminal plasma DHT concentration in the Oligozoospermie responders from 2.12 ± 0.29 to 2.94 ± 0.33 nmol/L (P < 0.05), while there was no significant change in the azoospermic responders (2.18 ± 0.31–2.54 ± 0.27 nmol/L) after 16 weeks of TE treatment. Dihydrotestosterone in seminal plasma is primarily derived from 5αR activity in the epididymis. The concentration of prostaglandin E2 (PGE2) in seminal plasma was unchanged during TE treatment. Sebum excretion was increased during TE treatment, but there were no differences between azoospermic and Oligozoospermie responders pretreatment or after 16 weeks TE treatment. These results are consistent with the hypothesis that incomplete suppression of spermatogenesis during TE treatment is associated with a relatively higher 5αR activity in the reproductive tract (epididymis and/or testis) during TE treatment. As the predominant form of 5αR in the reproductive tract is 5αR2 (type 2), we conclude that the increase in activity derives from this form of the enzyme, rather than the type 1 form (5αR1) predominantly found in nongenital skin.
Brown adipose tissue evaluation using water and triglyceride as indices by diffuse reflectance spectroscopy
Authors: Iida Tomomi , Ueda Yukio , Tsukada Hideo , Fukumoto Dai , Hamaoka Takafumi 
Published: October 2023

AbstractBrown adipose tissue (BAT) is related to lipid and glucose metabolism, and BAT evaluation is expected to contribute to disease prevention and treatment. We aimed to establish a BAT evaluation method using simple and non‐invasive diffuse reflectance spectroscopy (DRS). We acquired diffuse reflectance spectra of BAT using DRS from rats with cold stimulation and analyzed the second‐derivative spectra. To predict the amount of triglyceride in BAT from the second‐derivative spectra, partial least‐squares regression analysis was performed, and we examined whether BAT weight can be predicted from the amount of triglyceride by single regression analysis. By focusing on changes in the amount of triglyceride in BAT with cold stimulation, it was suggested that this amount could be predicted spectroscopically, and the predicted amount of triglyceride could be used to estimate the BAT weight with cold stimulation. If these results can be translated into humans, they may contribute to preventing metabolic disorders.
A multilayered, dynamic model of refugee resilience: A grounded theory
Authors: Kondili Elvita , Interiano‐Shiverdecker Claudia G. , Sabah May 
Published: October 2023

AbstractThe goal of this study was to explore the individual, cultural–relational–communal, and systemic factors associated with refugee resilience. Using constructivist grounded theory, we explored the concept of resilience through individual and focus group interviews with 21 refugees and 25 staff members working with this population in the United States. Our findings illustrate a multilayered and dynamic model that presents resilience in refugees as a fluid and complex phenomenon involving (a) individual, (b) community, and (c) societal conditions that either facilitate or hinder refugees’ ability to bounce back from the trauma(s) they have experienced. The authors discuss the implications of this model for developing a range of intervention strategies that aid in fostering refugee resilience at individual, community, and societal levels.
Water‐free two‐phase systems: phase equilibria and partitioning of vitamins from tomatoes (Solanum lycopersicum)
Authors: Lima Thailan Souza Pereira , Buarque Filipe Smith , Pinto Ronnie Emanuel Pereira , Vasconcelos Ana Luiza dos Santos , Soares Cleide Mara Faria , de Souza Ranyere Lucena , Lima Álvaro Silva 
Published: October 2023

AbstractBACKGROUNDThe present work provides diagrams for water‐free two‐phase systems based on polypropylene glycol 2000 (PPG 2000) + [C2mim][OAc] + alcohols (primary: methanol, ethanol, 1‐propanol and 1‐butanol; secondary: 2‐propanol and 2‐butanol; and tertiary: 2‐methyl‐2‐propanol) at 298.15 ± 1.00 K and 0.10 ± 0.01 MPa. As a proof of concept, the systems were applied to study the selective partitioning of vitamins, namely β‐carotene and α‐tocopherol.RESULTSThe hydrophilic/hydrophobic balance is the driving force for phase separation. The more hydrophilic alcohols are responsible for the wider biphasic area, and branching increases hydrophilicity and the biphasic area compared to linear alcohols. Additionally, it was verified that the mathematical determination of the tie‐lines satisfactorily describes the positioning in the phase diagram when compared with the analytical determination. In the proposed systems, pure biomolecules partitioned selectively: α‐tocopherol migrated to the PPG 2000 phase (top phase) while β‐carotene to the [C2mim][OAc] phase (bottom phase). For the study with real biomolecules, solid–liquid extraction was performed using 1‐butanol (more selective alcohol) in a solid–liquid ratio of 1:10 at 200 rpm for 60 min. The partitioning trend followed the behavior of systems using pure biomolecules. The highest selectivity (5.3) was observed for the system composed of PPG 2000 + [C2mim][OAc] + 1‐butanol or 2‐butanol. The partition system did not impair the antioxidant potential expressed as DPPH inhibition.CONCLUSIONSWater‐free two‐phase systems can be formed and applied to partitioning vitamins from tomatoes. © 2023 Society of Chemical Industry (SCI).
Population‐level analysis of natural control of HIV infection in Zambia and South Africa: HPTN 071 (PopART)
Authors: Grant‐McAuley Wendy , Piwowar‐Manning Estelle , Clarke William , Breaud Autumn , Zewdie Kidist Belay , Moore Ayana , Ayles Helen Mary , Kosloff Barry , Shanaube Kwame , Bock Peter , Meehan Sue‐Ann , Maarman Gerald , Fidler Sarah , Hayes Richard , Donnell Deborah , Eshleman Susan H. ,   for the HPTN 071 (PopART) Study Team
Published: October 2023

AbstractIntroductionHIV controllers have low viral loads (VL) without antiretroviral treatment (ART). We evaluated viraemic control in a community‐randomized trial conducted in Zambia and South Africa that evaluated the impact of a combination prevention intervention on HIV incidence (HPTN 071 [PopART]; 2013–2018).MethodsVL and antiretroviral (ARV) drug testing were performed using plasma samples collected 2 years after enrolment for 4072 participants who were HIV positive at the start of the study intervention. ARV drug use was assessed using a qualitative laboratory assay that detects 22 ARV drugs in five drug classes. Participants were classified as non‐controllers if they had a VL ≥2000 copies/ml with no ARV drugs detected at this visit. Additional VL and ARV drug testing was performed at a second annual study visit to confirm controller status. Participants were classified as controllers if they had VLs <2000 with no ARV drugs detected at both visits. Non‐controllers who had ARV drugs detected at either visit were excluded from the analysis to minimize potential confounders associated with ARV drug access and uptake.ResultsThe final cohort included 126 viraemic controllers and 766 non‐controllers who had no ARV drugs detected. The prevalence of controllers among the 4072 persons assessed was 3.1% (95% confidence interval [CI]: 2.6%, 3.6%). This should be considered a minimum estimate, since high rates of ARV drug use in the parent study limited the ability to identify controllers. Among the 892 participants in the final cohort, controller status was associated with biological sex (female > male, p = 0.027). There was no significant association between controller status and age, study country or herpes simplex virus type 2 (HSV‐2) status at study enrolment.ConclusionsTo our knowledge, this report presents the first large‐scale, population‐level study evaluating the prevalence of viraemic control and associated factors in Africa. A key advantage of this study was that a biomedical assessment was used to assess ARV drug use (vs. self‐reported data). This study identified a large cohort of HIV controllers and non‐controllers not taking ARV drugs, providing a unique repository of longitudinal samples for additional research. This cohort may be useful for further studies investigating the mechanisms of virologic control.