bluuebunny/crossref_metadata_2025_split huggingface dataset:
Foreign exchange hedging using regime‐switching models: The case of pound sterling
Authors: Lee Taehyun , Moutzouris Ioannis C. , Papapostolou Nikos C. , Fatouh Mahmoud 
Published: October 2023

AbstractWe develop a four‐state regime‐switching model for optimal foreign exchange (FX) hedging using forward contracts. The states correspond to four distinct market conditions, each defined by the direction and magnitude of deviation of the prevailing FX spot rate from its long‐term trends. The model's performance is evaluated for five currencies against the pound sterling for various horizons. Our examination compares the hedging outcomes of the proposed model to those of other commonly employed hedging methods. The empirical results suggest that our model demonstrates the highest level of risk reduction for the US dollar, euro, Japanese yen and Turkish lira and the second‐best performance for the Indian rupee. The risk reduction is significantly higher for lira compared with the other approaches, implying that the proposed model might be able to provide much more effective hedging for highly volatile currencies. The improved performance of the model can be attributed to the adjustability of the estimation horizon for the optimal hedge ratio based on the prevailing market conditions. This, in turn, allows it to better capture fat‐tail properties that are frequently observed in FX returns. Our findings suggest that FX investors tend to use short‐term memory during low market conditions (relative to trend) and long‐term memory in high ones. The results would be also useful to build a better understanding of how investor behaviour depends on market conditions and mitigate the adverse behavioural implications of short‐term memory, such as panic.
Hemodynamic Response to Intentionally Altered Flow Continuity of Dobutamine and Dopamine by an Infusion Pump in Infants
Authors: Stowe Cindy D. , Storgion Stephanie A. , Lee Kelley R. , Phelps Stephanie J. 
Published: October 2023

Study Objective. To evaluate the effect of an intentional alteration in infusion pump flow continuity on the hemodynamic stability of infants receiving either dobutamine or dopamine.Design. Prospective, open‐label study.Setting. A university‐affiliated children's hospital.Patients. Ten hemodynamically stable infants (age 2 wks–10 mo) in intensive care receiving dobutamine (5) or dopamine (5). Three patients received both agents and were studied at independent times.Interventions. Dobutamine and dopamine were administered using the Flo‐Gard VP pump that delivers an intentional alteration of flow continuity (rate pulse). Heart rate and mean arterial pressure (MAP) were recorded every second. Analysis was based on the measurements obtained from the first 5 minutes on the study pump and the 2 minutes before and after the rate pulse.Measurements and Main Results. Although hemodynamic changes in pre‐ and post‐rate pulses were statistically significant (p < 0.05) in some individuals, only one infant had a greater that 10% change in MAP 2 minutes after the rate pulse. Alterations in hemodynamics were not consistent among or within patients.Conclusion. In infants requiring dobutamine or dopamine, no clinically significant pharmacodynamic effects were associated with alteration in continuity of drug delivery caused by the single positive rate pulse. Therefore, we conclude there is no contraindication to the use of this infusion pump in hemodynamically stable infants receiving these drugs.
A Pilot Pharmacokinetic‐Pharmacodynamic Study of Benzodiazepine Antagonism by Flumazenil and Aminophylline
Authors: Bonfiglio Mark F , Fisher‐Katz Lynn E. , Saltis Lawrence M. , Traeger Sheldon M. , Martin Bradley R. , Nackes Nicholas A. , Perkins Thomas A. 
Published: October 2023

Study Objectives. To develop a pharmacokinetic‐pharmacodynamic model using quantitative electroencephalographic (EEG) analysis to compare two separate benzodiazepine antagonists and generate data concerning response variability.Design. A pilot study using a randomized, blinded, crossover design.Setting. The Neurology Laboratory at the Akron City Hospital campus of SUMMA Health System.Patients. Four healthy volunteers completed the protocol.Interventions. Subjects received midazolam 0.1–0.2 mg/kg by intravenous bolus on 3 study days, separated by a minimum washout period of 1 week. Subjects participated in an initial open‐label response phase followed by a randomized, crossover trial of each benzodiazepine antagonist.Measurements and Main Results. Venous blood samples were obtained to characterize the pharmacokinetics of all study compounds. The EEG parameter of total number of waves/second (recorded from FP1‐F3 and FP2‐F4 electrodes) in the frequency of 12–30 Hz was used to quantify effect. Flumazenil appeared to prolong the elimination half‐life of midazolam significantly (p < 0.05). Theophylline (aminophylline) also appeared to prolong the half‐life of flumazenil (p < 0.05). Despite considerable variability, flumazenil resulted in reversal of sedation at concentrations achieved by routine dosing. Resedation was apparent for all subjects following flumazenil reversal. Only partial reversal of sedation by theophylline was achieved by an aminophylline dose of 1–2 mg/kg.Conclusions. Flumazenil was consistently effective in reversing sedation by midazolam at routinely recommended dosing. Further investigation of aminophylline as a reversal agent should use an estimated dose of 6–8 mg/kg aminophylline. To achieve adequate reversal, some patients may require aminophylline dosages that exceed safe clinical administration.
Pharmacometric Analysis of the Effect of Furosemide on Suramin Pharmacokinetics
Authors: Piscitelli Stephen C. , Forrest Alan , Lush Richard M. , Ryan Nathan , Whitfield Lloyd R. , Figg William D. 
Published: October 2023

Study Objective. To characterize the effects of furosemide on the pharmacokinetics of suramin, a renally eliminated investigational antineoplastic agent.Design. Retrospective population pharmacokinetic analysis.Setting. Government biomedical research facility.Patients. Twenty‐six men with hormone‐refractory prostate cancer and one with adrenocortical carcinoma.Interventions. Patients received suramin by continuous or intermittent infusion with and without concomitant furosemide.Measurements and Main Results. Optimum suramin regimens were achieved by adaptive feedback control, and pharmacokinetic data were collected both in the presence and absence of furosemide. Suramin concentrations were determined by high‐performance liquid chromatography (coefficient of variation < 8%). Suramin concentrations were fit to a three‐compartment linear model with six coefficients and two rate inputs, which allowed furosemide to affect suramin pharmacokinetics. Individual and population parameter estimates were determined using the iterative two‐stage approach. Concomitant furosemide was associated with a median decrease in total body clearance of suramin by 36% (range 0–63%, p<0.0001). No other parameter was significantly altered, and there was no trend for change in any pharmacokinetic value with time. Suramin plasma concentrations were simulated with and without prolonged furosemide therapy in 26 patients for 12 weeks. The average suramin concentration increased by greater than 33% in 12 patients; 2 patients had a greater than 67% increase in this extreme case model.Conclusion. Coadministration of furosemide with suramin can cause an increase in suramin concentrations; however, due to suramin's long half‐life, its rate of accumulation is very slow. Nonetheless, in individuals receiving suramin by nonadaptive control, appropriate precautions should be taken when prolonged furosemide therapy is begun.
Evidence for Negative Feedback of Extracellular Methotrexate on Blasts of Acute Lymphoblastic Leukemia in Vitro
Authors: Hum Martina C. , Smith Angela K. , Lark Richard H. , Winick Naomi J. , Kamen Barton A. 
Published: October 2023

Study Objective. To explore the value of high‐dose methotrexate (MTX).Subjects. Blast cells from 15 patients with acute lymphoblastic leukemia.Interventions. We compared uptake and polyglutamation of [3H]‐MTX by freshly isolated leukemic blasts in vitro after 24‐hour exposure to 1, 10, and 50 μM [3H]‐MTX.Measurements and Main Results. Mean MTX uptake (pmol/106 cells) was 0.78 ± 0.19, 2.3 ± 0.54, and 5.9 ± 1.9, respectively, and mean polyglutamation was 82%, 66%, and 46%. Consequently, mean MTX polyglutamates were 0.68 ± 0.18, 1.5 ± 0.47, and 2.2 ± 0.67 pmol/106 cells. Three of 15 patient samples had no detectable polyglutamation of MTX at 50 μM but MTX polyglutamates were detectable at 1 μM. Two of these three had a decrease in MTX polyglutamates at 10 versus 1 μM. In eight precursor B cell samples there was a significant difference in median MTX polyglutamates at 1 versus 10 μM but not 10 versus 50 μM.Conclusion. Increasing extracellular MTX concentrations may be counterproductive for some patients with acute lymphoblastic leukemia. If MTX polyglutamates are important for efficacy, optimal delivery of MTX may have to be determined by individual metabolism rather than by targeting a specific drug concentration.
The Interaction of Maintenance Interferon with Cytolytic Cells in Patients with Multiple Myeloma Who Responded to Cytotoxic Chemotherapy
Authors: Hall Philip D. , Self Sally E. , Hall Rayna Kneuper 
Published: October 2023

Study Objective. To determine the long‐term effects of maintenance interferon on CD56+ and CD3+ cell activity.Design. Prospective phase II trial.Setting. Tertiary medical center and level 2 Veterans Administration hospital.Patients. Seven patients (age 45–74 yrs) with multiple myeloma who had reached the plateau phase from cytotoxic chemotherapy, and seven age‐ and sex‐matched controls.Interventions. All patients were given interferon‐α2b 3 × 106 U/m2 3 times/week.Measurements and Main Results. The CD56+, CD3+, and CD16+ counts were determined by flow cytometry in both peripheral blood and bone marrow. Natural killer (NK) cell functional activity was determined by a 51chromium release assay. Monocyte cell numbers were determined from the white blood cell count with differential. Interleukin‐6 (IL‐6) concentrations were determined by a commercially available enzyme‐linked immunosorbent assay. During the 24‐week study, the peripheral blood CD3+ and monocyte counts in patients with myeloma remained constant (p>0.39) but their absolute CD56+ counts decreased significantly (p=0.05). In peripheral blood, CD56+, CD16‐, CD3‐ was the predominant phenotype in patients. The predominant phenotype in bone marrow was CD56+, CD16‐, CD3+ at baseline but changed to CD56+, CD16‐, CD3‐ by week 24. The cytolytic activity of NK cells significantly increased in bone marrow (p=0.05) whereas it remained stable in the peripheral blood (p=0.55), but only half that of the controls. Concentrations of IL‐6 did not increase significantly during the study.Conclusion. In peripheral blood, NK cell activity remained stable in patients but was significantly lower than that in controls, probably secondary to the predominance of the CD56+, CD16‐, CD3‐ phenotype in the patients. In contrast, NK cell activity increased significantly in bone marrow despite the predominance of the CD56+, CD16‐, CD3‐ phenotype by week 24.
Effects of Dialysis Membrane on Intradialytic Vancomycin Administration
Authors: Scott Meri K. , Macias William L. , Kraus Michael A. , Clark William R. , Carfagna Mark A. , Mueller Bruce A. 
Published: October 2023

Study Objective. To quantify the influence of hemodialyzers on vancomycin removal when the drug was infused during hemodialysis.Design. Prospective, controlled, crossover study with three arms.Setting. A university‐affiliated medical center.Patients. Eight subjects receiving outpatient hemodialysis.Interventions. The three treatment arms were vancomycin 1000 mg infused after dialysis was completed (control), and the same dosages infused during the last hour of hemodialysis with a cellulose triacetate (CT) and a cellulose acetate (CA) hemodialyzer.Measurements and Main Results. The areas under the curve from time zero to 44 hours (AUC0‐44 hrs) for the three study arms were significantly different (p<0.05), with the mean vancomycin AUC0–44 hrs being significantly lower when administered during CT and CA dialysis (73.7% and 87.2% of control; p<0.05 vs control). The mean vancomycin peak concentration achieved during CT dialysis was significantly lower than for the CA and control arms (20.5, 23.9, 27.0 mg/L, respectively). Forty‐four‐hour postinfusion concentrations were similarly lower.Conclusion. Clinicians should recognize that the composition of the hemodialyzer significantly influences vancomycin serum concentrations when the drug is administered during hemodialysis.
Antianginal Response to Once‐Daily Diltiazem CD in Patients Receiving Concomitant β‐Blockers, Long‐Acting Nitrates, or Both
Authors: Heller Gary V , Sridharan Marandapalli , Morse John , Glasser Stephen , Beach C. L. ,   Diltiazem CD Study Group
Published: October 2023

Study Objective. To determine the safety and efficacy of diltiazem CD 180 mg administered once/day in patients with chronic stable angina inadequately controlled with β‐blockers, long‐acting nitrates, or both.Design. Multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group trial.Setting. Medical clinics in the private and academic sectors.Patients. Of 172 patients, 170 completed the 2‐week double‐blind treatment period.Interventions. Patients received either diltiazem CD 180 mg or placebo once/day in combination with existing antianginal therapy.Measurements and Main Results. The time to termination of exercise tolerance testing, 24 hours after the dose increased significantly in the diltiazem CD group (37.2 sec) compared with the placebo group (21.3 sec, p=0.0438). Time to onset of angina during exercise testing also increased (57.6 vs 35.0 sec, respectively, p=0.0324), as did time to moderate angina (37.5 vs 20.6 sec, respectively, p=0.0354). The rates of total angina attacks and of angina attacks on exertion were significantly reduced in the diltiazem CD group versus placebo (p<0.05). Significant reductions in systolic and diastolic blood pressures and heart rate‐blood pressure product measured at rest, submaximum exercise, and exercise termination were observed in diltiazem CD‐treated patients compared with placebo (p<0.05). The frequency of treatment‐related adverse events was identical in the two groups, 15.1%.Conclusion. Diltiazem CD 180 mg once/day is an effective, safe, and beneficial initial dosage when added to existing antianginal therapy.
Evaluation of Effects of Terbinafine on Single Oral Dose Pharmacokinetics and Anticoagulant Actions of Warfarin in Healthy Volunteers
Authors: Guerret Madeleine , Francheteau Patrice , Hubert Martine 
Published: October 2023

Study Objective. To evaluate the potential effects of oral terbinafine, a new synthetic antifungal agent of the allylamine class, on the pharmacokinetics and pharmacodynamics of racemic warfarin.Design. Randomized, double‐blind, placebo‐controlled, crossover study.Subjects. Sixteen healthy men.Interventions. Placebo or terbinafine 250 mg was administered once/day for 14 consecutive days, separated by a washout period lasting at least 2 weeks. A single oral dose of racemic warfarin 30 mg was coadministered with placebo or terbinafine on day 8 of each treatment period. Blood samples were collected for 168 hours after administration of warfarin to determine the drug's pharmacokinetics and anticoagulant effects.Measurements and Main Results. No major differences were seen in the plasma concentration‐time profiles of a single dose of warfarin administered with terbinafine or with placebo.Conclusions. Because of the lack of clinically significant interactions between terbinafine and warfarin during multiple‐dose administration of terbinafine, no adjustment of warfarin dosage during concomitant therapy appears to be necessary.
The Influence of Bromfenac on the Pharmacokinetics and Pharmacodynamic Responses to Glyburide in Diabetic Subjects
Authors: Boni Joseph P , Cevallos William H. , DeCleene Sheryl , Korth‐Bradley Joan M. 
Published: October 2023

Study Objective. To assess the effect of bromfenac sodium, a nonnarcotic analgesic drug under development, on the pharmacokinetics and pharmacodynamics of glyburide in patients with type II diabetes.Design. Randomized, double‐blind, placebo‐controlled, multiple‐dose study with a two‐period crossover design.Patients. Eleven men and one woman (age 36–64 yrs) whose diabetes was responsive to oral sulfonylurea therapy.Interventions. Placebo or bromfenac 50 mg was given as a single oral dose 3 times/day for the first 3 days of the study. On days 4–6, patients received the alternative treatment. For at least 3 months before and during the study, patients took their usual single daily dose of glyburide 10 mg.Measurements and Main Results. Bromfenac concentrations were measured by high‐performance liquid chromatography with ultraviolet detection. Glyburide concentrations were measured by gas chromatography with nitrogen‐phosphorus detection. Glycemia was measured repeatedly on day 3 of each treatment. Pharmacokinetic analysis was performed with noncompartmental techniques. No significant differences in the pharmacokinetics of glyburide or in the pharmacodynamic response of serum glucose levels were observed between placebo and bromfenac. Intersubject variability of concentrations was modest for glyburide and glucose, with a CV of 43% or less.Conclusion. Glyburide levels are not changed during concomitant administration of bromfenac.
Penetration of Levofloxacin into Lung Tissue after Oral Administration to Subjects Undergoing Lung Biopsy or Lobectomy
Authors: Lee Ling‐Jar , Sha Xue , Gotfried Mark H. , Howard Joan R. , Dix Robert K. , Fish Douglas N. 
Published: October 2023

Study Objective. To evaluate the pulmonary tissue distribution of levofloxacin, the new once‐daily fluoroquinolone, after a single 500‐mg oral dose.Design. Open‐label study.Setting. One pulmonary clinic and two university‐affiliated teaching hospitals.Patients. Eighteen adults undergoing lung biopsy or lobectomy.Interventions. Levofloxacin plasma and lung tissue concentrations were determined by high‐performance liquid chromatography with fluorescence detection. Lung tissue levofloxacin concentrations were corrected for blood contamination by measuring hemoglobin.Measurements and Main Results. After a single 500‐mg oral dose, concentrations of levofloxacin in lung tissue consistently exceeded those in plasma at every time point over the 24‐hour sampling period, with tissue:plasma penetration ratios of 2.02 (2–3 hrs), 5.02 (4–6 hrs), 5.13 (11–17 hrs), and 4.13 (22–25 hrs). The mean penetration ratio over the 24‐hour sampling period was 3.95 (range 1.06–9.98). Lung tissue concentrations of levofloxacin also exceeded minimum inhibitory concentration values for most community‐acquired respiratory tract pathogens over the 24 hours.Conclusion. This study supports clinical evaluation of levofloxacin as once‐daily oral therapy for community‐acquired lower respiratory tract infections.
Intratesticular Testosterone Concentration Following Intratunical Administration in the Hypogonadal Animal
Authors: SHAFIK AHMED 
Published: October 2023

ABSTRACT: The serum and intratesticular testosterone concentration (ITC) after testosterone administration in the tunica vaginalis (TV) sac compared to parenteral administration was studied in 20 dogs that were rendered hypogonadal by gonadotropin‐releasing hormone antagonist (‘Nal‐Glu’ GnRH antagonist) in a daily dose of 80 μg for 15 days. The 20 dogs were divided into two equal groups. Twenty milligrams of testosterone propionate were administered In the TV cavity in the TV group and intramuscularly (IM) In the IM group. In add‐on four dogs acted as controls and another four as sham controls.Serum and ITC were determined In all the dogs 1,2, and 15 days after testosterone administration. Biopsies from TV were taken 3 weeks after testosterone injection for histologic examination. Serum and ITC were significantly reduced (P < 0.01) 15 days after GnRH antagonist. They increased after intratunical testosterone administration to reach the pre‐GnRH antagonist level (P > 0.05). After IM testosterone injection, the serum testosterone increased to the pre‐ GnRH antagonist level (P > 0.05), while the ITC did not. The TV did not show histopathologic abnormalities apart from submesothelial infiltration with Inflammatory cells in one dog.In conclusion, TV testosterone administration delivers a major dose of testosterone to the testicle without exposing other tissues to high testosterone levels. The method is safe and may be used as an office treatment. It may be tried in the treatment of patients who are Infertile due to a low ITC.
Effect of Sperm Lipid Peroxidation on Fertilization
Authors: KODAMA HIDEYA , KURIBAYASHI YASUSHI , GAGNON CLAUDE 
Published: October 2023

ABSTRACT: This study was aimed at determining, with homologous mouse gametes, whether a level of membrane lipid peroxidation insufficient to affect sperm motility parameters can alter sperm fertilizing potential. The addition of ferrous ions and ascorbic acid (Fe2+/ Asc) to mouse sperm suspensions increases the formation of thiobarbituric acid‐reactive substances (TBARS), an indicator of lipid peroxide breakdown products, without significantly affecting the level of sulfhydryl groups. In the presence of Fe2+/Asc concentrations above >0.4/2.0 mM, spermatozoa become immotile. However, at concentrations ≥0.4/2.0 mM of Fe2+/Asc, i.e., conditions in which the TBARS formation is increased by ≥4.6‐fold over that of controls, motility remains unaffected for up to 3 hours. In the presence of 0.4/2.0 mM Fe2+/Asc, treated spermatozoa increase their fertilizing potential by 50%, as measured by the formation of two‐cell embryos.This increase is not caused by improvements in sperm motility parameters (percentage, linearity, velocity, hyperactivation) or sperm capacitation. On the other hand, there is a significant increase in the capacity of mouse spermatozoa to bind to homologous zona pellucida. In conclusion, mild peroxidative conditions, that increase lipid peroxide formation 4.6‐fold without significantly modifying free sulfhydryl groups and sperm motility parameters, improve the fertilizing potential of spermatozoa by increasing their binding capacity to zona pellucida.
Direct visualization of immune status for tumor‐infiltrating lymphocytes by rolling circle amplification
Authors: Sun Yupeng , Liu Yan , Li Rui , Zhang Cuilin , Wu Ming , Zhang Xiaolong , Xu Haipo , Zeng Rui , Zeng Yongyi , Liu Xiaolong 
Published: October 2023

AbstractThe immune status of tumor‐infiltrating lymphocytes (TILs) is essential for the effectiveness of cancer immunotherapies. However, due to the diversity of immune status in TILs, cellular heterogeneity, and the applicability to the clinic, it is still lacking effective strategies to meet clinical needs. We developed a novel immuno‐recognition‐induced method based on rolling circle amplification (RCA), namely immunoRCA, to in situ visualize the immune status of TILs in actual clinical samples. This developed immunoRCA method, in which, feature mRNAs were used as the biomarkers for the immune status of TILs, has a low fluorescence background, high sensitivity, and specificity. The immunoRCA was able to efficiently evaluate the immune status of CD8+ T cells regulated by activating or inhibiting factors, track the T cell type and immune status during in vitro expansion, and in situ visualize the number, location, and immune status of TILs in clinical specimens.