bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibiting scar formation via wearable multilayer stacked electret patch: Self‐creation of persistent and customizable DC electric field for fibrogenic activity restriction
Authors: Kim Sung‐Won , Cho Sumin , Lee Donghan , Hyun Jiyu , Jang Sunmin , Seo Inwoo , Park Hyun Su , Hwang Hee Jae , Han Hyung‐Seop , Yang Dae Hyeok , Chun Heung Jae , Bhang Suk Ho , Choi Dongwhi 
Published: October 2023

AbstractElectrical stimulation has recently received attention as noninvasive treatment in skin wound healing with its outstanding biological property for clinical setting. However, the complexity of equipment for applying appropriate electrical stimulation remains an ongoing challenge. Here, we proposed a strategy for skin scar inhibition by providing electrical stimulation via a multilayer stacked electret (MS‐electret), which can generate direct current (DC) electric field (EF) without any power supply equipment. In addition, the MS‐electret can easily control the intensity of EFs by simply stacking electret layers and maintain stable EF with the surface potential of 3400 V over 5 days owing to the injected charges on the electret surface. We confirmed inhibition of type 1 collagen and α‐SMA expression of human dermal fibroblasts (hDFs) by 90% and 44% in vitro, indicating that the transition of hDFs to myofibroblasts was restricted by applying stable electrical stimulation. We further revealed a 20% significant decrease in the ratio of myofibroblasts caused by the MS‐electret in vivo. These findings present that the MS‐electret is an outstanding candidate for effective skin scar inhibition with a battery‐free, physiological electrical microenvironment, and noninvasive treatment that allows it to prevent external infection.image
Single‐Dose, Placebo‐Controlled, Phase I Study of Oral Dolasetron
Authors: Dixon Russell M. , Cramer Michael , Shah Ajit K. , Whitmore James , Benedict Claude R. , Hahne William F. 
Published: October 2023

Study Objectives. To evaluate the safety, tolerability, and pharmacokinetics of single, escalating doses of oral dolasetron mesylate, a new 5‐HT3 receptor antagonist.Design. Double‐blind, placebo‐controlled, dose‐escalating phase I study.Setting. A clinical research center.Patients. One hundred twenty healthy male volunteers.Interventions. Subjects received either placebo or oral dolasetron mesylate 50, 100, 150, 200, 250, 300, or 400 mg.Measurements and Main Results. Compared with placebo, subjects receiving dolasetron mesylate reported a greater frequency of headache, lightheadedness, dizziness, increased appetite, and nausea. There were no clinically significant changes in mean laboratory values from before to after treatment. Adverse events were transient, mild or moderate, and similar to those after single intravenous doses of the drug. No clinically significant electrocardiographic changes occurred, but lengthening of the QRS complex duration and dose‐dependent lengthening of PR and QTc intervals were observed 1–2 hours after dosing. These effects were asymptomatic and were mainly associated with higher doses (≥ 300 mg).Conclusion. Dolasetron mesylate is well tolerated when administered in single oral doses up to 400 mg to healthy volunteers. Clinical trials are under way to evaluate the agent's efficacy in preventing chemotherapy‐induced and postoperative nausea and vomiting with doses up to 200 mg.
Pharmacokinetics and Pharmacodynamics of Subcutaneous Interleukin‐2 in HIV‐Infected Patients
Authors: Piscitelli Stephen C. , Wells Mary J. , Metcalf Julia A. , Baseler Michael , Stevens Randy , Davey Richard T. 
Published: October 2023

Study Objectives. To assess the pharmacokinetics and pharmacodynamics of subcutaneously administered interleukin‐2 (IL‐2) in patients infected with the human immunodeficiency virus (HIV).Design. Open, dose‐escalating phase I clinical trial.Setting. Government research hospital.Patients. Eighteen patients infected with HIV.Interventions. Recombinant IL‐2 at dosages of 12, 15, or 18 MIU/day was administered subcutaneously once or twice/day for 5 consecutive days every 2 months. A total of 28 cycles of therapy were included in the analysis.Measurements and Main Results. Concentrations of IL‐2 in serum were determined by a commercial enzyme‐linked immunosorbent assay. Interleukin‐2 was well absorbed, with peak concentrations from 21.9–112.9 IU/ml. Absorption was slow, with mean (± SD) time to maximum of 4.4 ± 1.8 hours and a lag time of 26.9 ± 13.7 minutes. Elimination half‐life was 3.3 ± 0.9 hours. The concentrations had wide variability both within and among patients. Levels of tumor necrosis factor‐α were increased. Maximum body temperature and systemic side effects were associated with peak serum levels.Conclusion. Interleukin‐2 is well absorbed after subcutaneous injection in HIV‐infected patients, and that route of administration is an alternative to intravenous infusions.
The Influence of Multiple Dosing and Age on the Pharmacokinetics and Pharmacodynamics of Glipizide in Patients with Type II Diabetes Mellitus
Authors: Jaber Linda A. , Ducharme Murray P. , Edwards David J. , Slaughter Richard L. , Grunberger George 
Published: October 2023

Study Objectives. To determine the pharmacokinetics and pharmacodynamics of glipizide after a single dose and 12 weeks of dosing in patients with type II diabetes mellitus, and evaluate the influence of aging.Design. Comparison of single and multiple doses of glipizide.Setting. University‐affiliated outpatient internal medicine clinic and diabetes care unit.Patients. Twenty patients (11 men, 9 women, mean age 55.2 ± 9.9 yrs) with type II diabetes mellitus who were currently receiving oral hypoglycemic agents or were hyperglycemic with diet.Interventions. A 24‐hour pharmacokinetic evaluation of glipizide was assessed after a 5‐mg dose at the start of therapy and after 12 weeks of therapy. Pharmacokinetic parameters were assessed using compartmental population analysis techniques. Glipizide pharmacodynamic evaluation was assessed by serum glucose, insulin, and C‐peptide responses during a 4‐hour Sustacal tolerance test performed at baseline before instituting glipizide therapy, with the first 5‐mg dose, and at week 12 of therapy. Glipizide dosages were titrated to a targeted goal of fasting plasma glucose of 7.8 mmol/L or less or to reach maximum daily doses of 40 mg.Measurements and Main Results. No significant differences in time to peak concentration, apparent volumes of distribution for the central and peripheral compartments, apparent oral clearance from the central compartment, distributional clearance between the central and peripheral compartments, or terminal elimination half‐life were observed with a single dose and long‐term dosing. The mean ± SD terminal elimination half‐lives were 9.67 ± 5.6 and 9.35 ± 4.6 hours after a single dose and 12 weeks, respectively. Fasting plasma glucose concentrations decreased from 12.3 ± 3.6 mmol/L before the first dose of glipizide to 9.2 ± 1.7 mmol/L after 12 weeks of treatment. The values for area under the serum concentration‐time curve from zero to 4 hours for glucose (AUC0–4.glucose) were significantly reduced at week 12 (baseline 49.8 ± 15.6, week 12 37.8 ± 9.8 mmol/L/hr). Glipizide provoked an increase in serum insulin and C‐peptide concentrations (AUC0–4.insulin: baseline 698 ± 327, single dose 954 ± 461, long‐term dosing 945 ± 600 pmol/L/hr). No significant change in insulin response was observed between single and multiple doses. No age‐related differences in the pharmacokinetic parameters or the pharmacodynamic responses of glipizide were observed.Conclusions. Long‐term dosing and aging have little effect on the pharmacokinetic profile of glipizide. In addition, glipizide stimulates insulin secretion to a similar extent following glucose challenge after a single dose and long‐term administration.
Pharmacokinetics of Aztreonam and Imipenem in Critically Ill Patients with Pneumonia
Authors: McKindley David S. , Boucher Bradley A. , Hess Mary M. , Croce Martin A. , Fabian Timothy C. 
Published: October 2023

Study Objective. To evaluate the pharmacokinetic profiles of aztreonam and imipenem in critically ill trauma patients with pneumonia.Methods. Trauma patients in intensive care units who were intubated within 3 days of hospital admission were eligible for the study. Patients with the clinical diagnosis of pneumonia were consecutively randomized to receive either aztreonam plus vancomycin or imipenem‐cilastatin. Serial blood samples were taken and sputum was collected to determine aztreonam and imipenem concentrations after 2–3 days and 7–8 days of therapy. Pharmacokinetics of both agents were estimated and compared with estimates from healthy volunteers.Results. Twenty patients were enrolled in the study, 10 patients received imipenem‐cilastatin, and 10 received aztreonam plus vancomycin. Steady‐state volume of distribution (Vss) for aztreonam at 2–3 days and 7–8 days was significantly greater in patients than in historical controls, whereas the Vss for imipenem was greater at 2–3 days. The β‐half‐life for aztreonam at both sampling periods was significantly greater in patients than in controls. No significant changes in pharmacokinetics occurred over time for either antibiotic. Sputum concentrations of aztreonam and imipenem were highly variable when sampled 2 hours after the infusion.Conclusion. Larger volumes of distribution were observed for both aztreonam and imipenem in trauma patients than in volunteers, suggesting that standard initial dosages of the antibiotics may result in lower concentrations in these critically ill patients. Both antibiotics penetrated into the sputum of most patients; however, the degree of penetration was highly variable in relation to serum concentrations.
Comparison of Trimethoprim‐Sulfamethoxazole, Dapsone, and Pentamidine in the Prophylaxis of Pneumocystis carinii Pneumonia
Authors: Warnock Allison C. , Rimland David 
Published: October 2023

Study Objective. To compare the incidence of Pneumocystis carinii pneumonia (PCP) in patients infected with the human immunodeficiency virus (HIV) receiving one of three prophylactic agents.Design. Retrospective chart review.Setting. A university‐affiliated Department of Veterans' Affairs medical center HIV clinic.Patients. All 200 HIV‐infected patients enrolled in the clinic who were prescribed a PCP prophylactic drug during 18 months.Interventions. Patients were administered oral trimethoprim‐sulfamethoxazole (TMP‐SMX) DS, oral dapsone, or aerosolized pentamidine in a heirarchic fashion. A subset of 110 patients received only one of the prophylaxis regimens for at least 6 months; they were examined separately for the purpose of statistical analysis.Measurements and Main Results. One case of PCP was diagnosed in 1110 patient‐months of oral TMP‐SMX DS therapy, 6 in 418 patient‐months of oral dapsone therapy, and 3 in 164 patient‐months of aerosolized pentamidine therapy. In the subset population, the documented incidence of PCP was 0% among 71 TMP‐SMX DS‐treated patients, 16% among 25 dapsone‐treated patients (p < 0.004), and 14% among 14 aerosolized pentamidine‐treated patients (p < 0.03). For patients receiving primary prophylaxis, the incidence of PCP was 0% for 58 receiving TMP‐SMX, 15% for 20 receiving dapsone (p = 0.015), and 17% for 6 receiving pentamidine (p = 0.094).Conclusion. We believe TMP‐SMX DS was more effective than oral dapsone or aerosolized pentamidine in preventing PCP in these HIV‐infected patients.
Effect of Vehicle on the Nasal Absorption of Epinephrine During Cardiopulmonary Resuscitation
Authors: Bleske Barry E. , Rice Ted L. , Warren Eric W. , Giacherio Donald A. , Gilligan Lori J. , Massey Kenneth D. , Chrisp Clarence E. , Tait Alan R. 
Published: October 2023

Study Objectives. We have shown in previous studies that epinephrine administered intranasally is a feasible route of administration during cardiopulmonary resuscitation (CPR). To promote the absorption of epinephrine we administered phentolamine prior to epinephrine and used a bile salt as a vehicle to dissolve the epinephrine. The purpose of this study was to compare the effect of two different vehicles (bile salt vs surfactant) in promoting the absorption of nasally administered epinephrine during CPR and to determine their effects on the nasal mucosa.Study Design. A randomized, blinded study.Setting. A controlled laboratory environment.Subjects. Eleven mongrel dogs.Interventions. Each dog underwent 3 minutes of unassisted ventricular fibrillation (VF) followed by 7 minutes of VF with CPR. Five minutes after the start of VF, 10 dogs received intranasal phentolamine 0.25 mg/kg/nostril followed 1 minute later by intranasal epinephrine 7.5 mg/kg/nostril. The epinephrine was dissolved in a randomly assigned vehicle consisting of either taurodeoxycholic acid (group A, bile salt) or polyoxyethylene‐9‐lauryl ether (group B, surfactant). One animal acted as a control and received 0.9% sodium chloride nasally.Measurements and Main Results. Data from eight dogs (one control) were included for analysis. Histology of the nasal cavity demonstrated severe multifocal erosion and ulceration of the respiratory epithelium for groups A and B compared with the control. The severity was similar between the two groups. In addition, no significant differences in plasma epinephrine concentrations or blood pressure responses were seen between the groups.Conclusion. Based on histology, polyoxyethylene‐9‐lauryl ether offered no advantage over taurodeoxycholic acid in its effect on the nasal mucosa. The data available for changes in epinephrine concentration and pressure also suggest no difference between the two vehicles in promoting the absorption of epinephrine during CPR in an animal model.
Effects of Spontaneous Gastric Hypoacidity on the Pharmacokinetics of Zidovudine and Didanosine
Authors: Shelton Mark J. , Adams John M. , Hewitt Ross G. , Steinwandel Cindy , DeRemer Mary , Cousins Steve , Morse Gene D. 
Published: October 2023

Study Objective. To determine the effect of spontaneous gastric hypoacidity on the pharmacokinetics of zidovudine and didanosine in subjects infected with the human immunodeficiency virus (HIV).Design. Controlled, open‐label, single‐dose, pharmacokinetic study.Subjects. Thirty‐two asymptomatic HIV‐infected subjects.Interventions. Gastric pH studies were conducted in all 32 subjects, and 20 of these subjects (8 women, 12 men) were enrolled into the pharmacokinetic study. They were stratified into two groups according to fasting gastric pH: those without and with gastric hypoacidity (minimum gastric pH < 3 and ≥ 3, respectively). Gastric pH was measured using the Heidelberg pH monitoring system in all subjects before and during pharmacokinetic analysis of zidovudine 100 mg or didanosine 200 mg (given as two 100‐mg tablets dissolved in 6 oz water). Plasma samples were collected over 8 hours after dosing.Measurements and Main Results. Six (20%) of 30 subjects had a minimum gastric pH of 3 or above on at least two occasions, and the remaining 2 had variable gastric pH. Although gastric pH was unchanged during the administration of zidovudine, it increased to greater than 9 in 11 of 12 subjects with didanosine, regardless of baseline value. For both drugs, there were no statistically significant differences in peak plasma concentration (Cmax), time to reach peak plasma concentration (Tmax), elimination rate constant (ke), and area under the plasma concentration‐time curve from time zero to infinity (AUC0–∞) between subjects with and without gastric hypoacidity despite sufficient statistical power to detect a 56% difference in clearance for either drug (α 0.05, β 0.1).Conclusion. Gastric hypoacidity occurs in approximately 20% of HIV‐infected patients and does not appear to influence zidovudine or didanosine pharmacokinetics.
Is the Volume of Distribution of Digoxin Reduced in Patients with Renal Dysfunction? Determining Digoxin Pharmacokinetics by Fluorescence Polarization Immunoassay
Authors: Cheng Judy W.M. , Charland Scott L. , Shaw Leslie M. , Kobrin Sidney , Goldfarb Stanley , Stanek Eric J. , Spinier Sarah A. 
Published: October 2023

Study Objective. To determine digoxin pharmacokinetics in subjects with different degrees of renal function using fluorescence polarization immunoassay (FPIA), which is associated with less interference from digoxin‐like immunoreactive substances (DLIS) than radioimmunoassay.Setting. University hospital clinical research center.Participants. Eighteen subjects (mean age 44 yrs) with different degrees of renal function: group 1, creatinine clearance (Clcr) below 10 ml/minute; group 2, Clcr 10–50 ml/minute; and group 3, Clcr greater than 50 ml/minute (6 patients in each group).Intervention. Over 5–7 days, 15 serum samples were collected after a single intravenous dose of digoxin 7 or 10 μg/kg actual body weight (WT) for serum concentration measurements by FPIA. Two‐compartment pharmacokinetic parameters (zero‐time intercept of the concentration‐time curve of the initial distribution phase [A], zero‐time intercept of the concentration‐time curve of the terminal elimination phase [B], initial distribution phase constant [α], terminal elimination rate constant [β], volume of distribution in the central compartment [Vc] and at steady state [Vss], total body clearance [Cl], mean residence time [MRT], area under the concentration‐time curve [AUC]) were determined using a nonlinear least squares regression program.Measurements and Main Results. No significant differences were found among groups for A, B, α, β, β‐half‐life, Vc/WT, MRT, AUC, and Cl/WT. Significant differences were observed in VssAVT (4.8 ± 1.0, 6.6 ± 0.5, 6.4 ± 0.7 L/kg) between group 1 versus group 2 and group 1 versus group 3 (p<0.01). Measured Clcr was correlated with Cl (r2=0.40, p<0.01), Cl/WT (r2 = 0.29, p<0.05), Vss (r2=0.35, p=0.01), and Vss/WT (r2=0.24, p<0.05).Conclusion. This study confirmed that Vss is smaller in patients with chronic renal failure (Clcr < 10 ml/min) than those without chronic renal failure. Therefore, previous recommendations that lower digoxin loading doses should be administered in patients with renal failure are applicable to digoxin serum concentration monitoring using FPIA.
Cisplatin Nephrotoxicity: A Multivariate Analysis of Potential Predisposing Factors
Authors: Lagrange Jean Leon , Médecin Blandine , Etienne Marie Christine , Pivot Xavier , Cassuto‐Viguier Elisabeth , Renée Nicole , Thyss Antoine , Ferrero Jean Marc , Otto Josiane , François Eric , Milano Gérard 
Published: October 2023

Study Objective. To evaluate the usefulness of biologic and pharmacologic parameters for early identification of cisplatin‐induced renal dysfunction.Design. Prospective evaluation of 62 consecutively admitted patients with cancer.Setting. Cancer center.Patients. Sixty‐two consecutive patients with cancer (52 men, 10 women; mean age 61.9 yrs).Interventions. Patients received cisplatin as a single short intravenous infusion every 3 weeks. One hundred twenty‐one cycles were analyzed. The dosage in the first cycle ranged between 61 and 105 mg/m2 (mean 84 mg/m2). All patients received a standard hydration protocol.Measurements and Main Results. Renal function was evaluated for each cycle before treatment (day 0) and before next cycle (day 21) based on the estimated creatinine clearance (Clcr). For each cycle, the weighted relative decrease (WD) of Clcr was calculated (WDClcr = 100 × [Clcr (day 0) — Clcr (day 21)]/[Clcr (day 0)]2. Total and ultrafilterable (UF) platinum were measured as a single‐sample assay taken 16 hours after the end of cisplatin administration. The mean WDClcr was 0.07 mm/100 ml (range −1.0 to +1.7 min/100 ml). The intensity of renal dysfunction evaluated by WDClcr was independent of cisplatin dosage, age, sex, body surface area, initial Clcr, and cycle number. Of interest, total and UF platinum concentrations were significantly correlated to WDClcr: the higher the platinum concentration, the greater the intensity of renal dysfunction. In stepwise regression analysis, UF platinum concentration was the only selected factor. The best prediction of UF platinum was obtained by stepwise regression including cisplatin dosage, initial Clcr, and cycle number (r=0.58, p<0.0001).Conclusion. We consider our results to be a first step toward a clinical strategy to identify patients at risk for renal dysfunction after cisplatin treatment.
Premenstrual Asthma: The Effect of Estrogen on Symptoms, Pulmonary Function, and β2‐Receptors
Authors: Chandler Mary H.H. , Schuldheisz Sandra , Phillips Barbara A. , Muse Ken N. 
Published: October 2023

Study Objectives. To characterize asthma symptoms, pulmonary function, and responsiveness to β2‐agonist stimulation, and in vitro β2‐receptor density and cyclic adenosine 3′,5′‐monophosphate (cAMP) response throughout the menstrual cycle in women with premenstrual asthma (PMA); and to examine the effect of exogenous estradiol administration on asthma symptoms, pulmonary function and responsiveness, and β2‐receptor density and function in these women.Design. Open‐label, longitudinal, 9‐week study.Setting. A university clinical research center.Patients. Seventeen women with mild to moderate asthma, of whom 14 completed the study.Interventions. Every morning on awakening during the entire 9‐week study, each subject completed visual analog scales for asthma symptomatology (cough, wheezing, breathlessness, chest tightness) and measured and recorded her peak expiratory flow rate (PEFR) with a peak flow meter. Also measured at various times throughout the menstrual cycle were dyspnea index scores, pulmonary function (PEFR, forced expiratory volume in 1 sec [FEV1]), pulmonary response to subcutaneous terbutaline, T lymphocyte β2‐receptor density (Bmax) and function (cAMP), and estradiol, progesterone, and catecholamine concentrations, both with and without exogenous estradiol administration.Measurements and Main Results. At the time of enrollment, only 5 subjects reported premenstrual worsening of asthma symptoms, but all 14 had greater than 20% decrease in PEFR and/or increase in symptoms premenstrually during the study. Significant differences (p<0.05) existed in asthma symptoms and PEFR between day 13 (highest estradiol concentrations) and day 26 (lowest estradiol concentrations) of the menstrual cycle. Asthma symptoms and dyspnea index scores were significantly improved (p<0.05) after estradiol administration compared with baseline (premenstrual period without exogenous estrogen). Pulmonary response to terbutaline, β2‐receptor density and function, and catecholamine concentrations were not significantly altered after estradiol administration, but the trend was toward significant differences (0.05 < p < 0.2) in pulmonary function tests (PEFR, FEV1).Conclusions. Even asthmatics not previously aware of PMA may experience premenstrual worsening of asthma symptoms and/or PEFR. Estradiol is associated with a significant improvement in asthma symptoms and dyspnea index scores. This ameliorating effect does not appear to be related to β2‐receptors.