bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug‐Induced Pure Red Cell Aplasia
Authors: Thompson Dennis F. , Gales Mark A.
Published: October 2023

Pure red cell aplasia (PRCA) is an uncommon hematologic disorder characterized by the absence of erythroblasts in otherwise normal bone marrow. It is commonly an autoimmune disorder sometimes associated with a congenital error. It may also be acquired in association with thymomas, hematologic malignancies, human parvovirus B19 infection, drugs, and other disease states. Thirty drugs have been implicated as causative in PRCA, but most literature reports describe only one or two patients. Data evaluating possible mechanisms of drug‐induced PRCA are extremely limited, with conflicting results from different investigators. The criteria we used were at least five patients reported, reports from at least three separate investigators, and a minimum of one case of probable causality or better using a published assessment scale. With these criteria, phenytoin, azathioprine, and isoniazid had sufficient evidence of causality. All three are documented causes of PRCA and should be considered in any case of selective erythrocyte aplasia.
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.
Correlates of Oral Contraceptive Use in Two New England Communities: 1981–1993
Authors: Hume Anne L. , Barbour Marilyn M. , Lapane Kate L. , Flint Patricia M. , Carleton Richard A.
Published: October 2023

This study compared the sociodemographic and cardiovascular correlates of oral contraceptive users and nonusers between 1981 and 1993. We also sought to determine changes in the prevalence of oral contraceptive use among older premenopausal women. Using data from six biennial cross‐sectional household surveys in a population‐based sample of two New England communities, 5239 women between ages 18 and 45 years were identified. Women using oral contraceptives were 5 years younger and better educated than nonusers, and users more frequently reported a per capita income above the median for the survey population than nonusers. Users were more likely to report smoking and have a lower body mass index than nonusers. Little use of oral contraceptives was detected among women ages 40–45 years despite changes in FDA recommendations about their use and increasing evidence of their noncontraceptive benefits in healthy older nonsmoking women.
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.
The Use of Microdialysis in Pharmacokinetics and Pharmacodynamics
Authors: Johansen Mary J. , Newman Robert A. , Madden Timothy
Published: October 2023

Microdialysis is a new in vivo sampling technology applied to the study of pharmacokinetics and drug metabolism in the blood and soft tissues of living systems. A small‐diameter probe containing a dialysis membrane is implanted into tissue and perfused with a suitable fluid. Low‐molecular‐weight substances passively diffuse through the semipermeable membrane along a concentration gradient, resulting in the collection of purified dialysate samples. The advantage of this approach over blood sampling and dissection of tissues is the ability to sample blood and extracellular fluid with minimal tissue damage or alteration of fluid balance. Sampling several tissues simultaneously and continuously in animal models allows data to be obtained that more directly reflect interactions of drugs at their sites of activity and detoxification. Techniques such as this will have a tremendous impact on preclinical and clinical pharmacologic research.
Clinical Issues Associated with Urine Testing of Substances of Abuse
Authors: Eskridge Kimberly D. , Guthrie Sally K.
Published: October 2023

Several factors may affect the validity and outcome of urine testing for abused drugs such as amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, ethanol, opiates, and phencyclidine. Urine is used for large‐scale testing because acquisition of the sample is noninvasive and because most abused drugs can be detected in urine for a reasonable duration after ingestion. Urine testing for drugs of abuse is a two‐step process. In the first step, screening assays are used to identify presumably positive specimens. Common screening tests are radioimmunoassays, enzyme immunoassays, fluorescence polarization immunoassay, and thin layer chromatography. Since they may be subject to cross‐reactivity, once a possible positive sample has been identified by a preliminary test, a second more specific methodology, gas chromatography with mass spectrometry, is done to confirm the results. Knowledge of the pharmacology and pharmacokinetics of abused drugs affects selection and interpretation of test results.
Early Switch from Intravenous to Oral Antibiotics in Hospitalized Patients with Infections: A 6‐Month Prospective Study
Authors: Ahkee Sunket , Smith Scott , Newman David , Ritter William , Burke John , Ramirez Julio A.
Published: October 2023

We assessed what percentage of hospitalized patients treated with intravenous antibiotics would be candidates for early switch to oral therapy, and evaluated the clinical outcomes of patients after the switch. All hospitalized patients in whom an intravenous antibiotic was prescribed for treatment of an infection were prospectively screened to identify candidates for switch in therapy. Of the 655 patients treated with intravenous antibiotics, 300 (46%) were candidates for a switch, and the change was implemented in 262 (40%). Of the 171 evaluable patients, the switch was associated with clinical cure in 167 (98%) and failure in 4 (2%). In hospitalized patients with infections, the duration of intravenous antibiotic therapy can be minimized with early switch to oral therapy. This practice is associated with good patient outcome.
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.
Neuroleptic Malignant Syndrome with Risperidone
Authors: Gleason Patrick P. , Conigliaro Rosemarie L.
Published: October 2023

Neuroleptic malignant syndrome is thought to be a result of dopamine D2 receptor blockade in the striatum of the basal ganglia. Risperidone, a benzisoxazole derivative antipsychotic, has high serotonin 5‐HT2 receptor blockade and dose‐related D2 receptor blockade. The high ratio is believed to impart the low frequency of extrapyramidal symptoms with risperidone at low dosages. With this low frequency of extrapyramidal symptoms, it was thought the frequency of neuroleptic malignant syndrome might also be lowered. A 73‐year‐old woman developed neuroleptic malignant syndrome after monotherapy with risperidone. The syndrome reversed after discontinuing risperidone and starting treatment with dantrolene and bromocriptine. It appears that the protection from extrapyramidal side effects observed with risperidone does not ensure protection from neuroleptic malignant syndrome.
Multisite Mucous Membrane Bleeding Due to a Possible Interaction Between Warfarin and 5‐Fluorouracil
Authors: Brown Michael C.
Published: October 2023

A 59‐year‐old man being treated for colon cancer experienced epistaxis, hematemesis, hematuria, and hematochezia. Laboratory evaluation revealed a greatly prolonged prothrombin time. It is possible that the bleeding was due to an interaction between 5‐fluorouracil and warfarin. The former may inhibit the synthesis of cytochrome P‐4502C9, leading to impaired metabolism of the latter.
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.
Cytokine Networks with Infection: Mycobacterial Infections, Leishmaniasis, Human Immunodeficiency Virus Infection, and Sepsis
Authors: DiPiro Joseph T.
Published: October 2023

Distinct cytokine profiles are clearly associated with and relate to the severity of several types of infections. Cytokine networks are apparent with selected human infectious diseases, such as mycobacterial infections (leprosy, tuberculosis), the parasitic infection leishmaniasis, human immunodeficiency virus (HIV) infection, and gram‐negative sepsis. Cytokine profiles are determined to some extent by two functional subsets of T lymphocytes, Th1 and Th2. The Th1 cytokines (interferon γ, interleukin‐2 [IL‐2], IL‐12) enhance cell‐mediated immunity, inhibit humoral immunity, and result in protective effect for pathogens that are removed primarily through cell‐mediated immunity (Mycobacterium tuberculosis, Mycobacterium leprae, Leishmania). The Th2 cytokines (IL‐4, IL‐5, IL‐10, IL‐13) enhance humoral immunity and inhibit cell‐mediated immunity, and result in protective effect for pathogens removed primarily through humoral mechanisms. Progression of HIV infection is associated with a switch from a Th1 to a Th2 profile. For sepsis, uncontrolled activation of proinflammatory cytokines (IL‐1, tumor necrosis factor‐α, interferon‐γ) may be a fundamental defect that promotes the detrimental aspects of inflammation, whereas Th2 cytokines may be beneficial in controlling inflammation. Knowledge of basic cytokine immunopharmacology, networks, and relationships with infectious processes will aid clinicians in determining treatment approaches that are likely to be effective.
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.
Pharmacodynamic Activity of Five Oral Cephalosporins Against Haemophilus influenzae
Authors: Stein Gary E. , Schooley Sharon , Walker Robert D. , Strenkoski‐Nix Laura
Published: October 2023

Study Objectives. To determine the time above minimum inhibitory concentration (T > MIC) and serum bactericidal activity of five oral cephalosporins against two strains of Haemophilus influenzae.

Design. Randomized, crossover study.

Setting. University‐associated research center.

Subjects. Ten healthy volunteers.

Interventions. Each subject received a single dose of cefpodoxime 200 mg, cefuroxime 500 mg, cefaclor 500 mg, cefprozil 500 mg, or loracarbef 400 mg each week for 5 weeks. Blood for serum levels was obtained at time zero and 1, 2, 3, 4, 6, 8, and 12 hours after each dose.

Measurements and Main Results. Cefopodoxime produced serum concentrations above the MIC for more than 90% of the time for both β‐lactamase‐negative and ‐positive strains of H. influenzae. Moreover, it had serum bactericidal activity for 12 hours against both isolates. Cefuroxime was the second most active cephalosporin, with serum concentrations above the MIC of both isolates for 60% of the time. Cefuroxime provided serum bactericidal activity for 12 hours against the β‐lactamase‐negative strain and 6 hours against the β‐lactamase‐positive strain of H. influenzae. Even though the T > MIC was less than 50% of the study period for the other cephalosporins, all but cefaclor provided serum bactericidal activity for 12 hours against the β‐lactamase‐negative isolate. Cefaclor provided measurable serum bactericidal activity for only 3 hours. The duration of serum bactericidal activity of cefprozil, loracarbef, and cefaclor against the β‐lactamase‐positive isolate was 4, 2, and 0 hours, respectively.

Conclusion. Cefpodoxime was the most active cephalosporin studied based on T > MIC and serum bactericidal activity against isolates of H. influenzae.
High‐Dose versus Standard‐Dose Epinephrine Treatment of Cardiac Arrest after Failure of Standard Therapy
Authors: Sherman Bruce W. , Munger Mark A. , Foulke Garrett E. , Rutherford William F. , Panacek Edward A.
Published: October 2023

Study Objective. To assess the efficacy of high‐dose epinephrine (HDE) compared with standard‐dose epinephrine (SDE) in emergency department patients in cardiac arrest after SDE failed to improve asystole or ventricular fibrillation.

Design. Prospective, multicenter, blinded, controlled trial.

Setting. Eight academic center emergency departments.

Patients. One hundred forty patients treated for cardiac arrest.

Measurements and Main Results. Primary outcomes were either improvement in cardiac rhythm or return of spontaneous circulation (ROSC). Of the 140 patients enrolled, 78 received HDE and 62 received SDE. Of the 34 patients with ventricular fibrillation, 3 were resuscitated with HDE and 2 with SDE (p=0.60). Of those with asystole, ROSC occurred in 12 of HDE and 5 of SDE recipients (p=0.11). No patient had return of significant neurologic function and none survived to hospital discharge. Overall, there was no advantage to HDE after failure of SDE.

Conclusion. Our results are similar to those of controlled clinical trials comparing HDE with SDE in cardiac arrest.
Fentanyl Pharmacokinetics in Patients Undergoing Renal Transplantation
Authors: Koehntop Douglas E. , Rodman John H.
Published: October 2023

Study Objective. To describe the pharmacokinetics of fentanyl in patients undergoing renal transplantation.

Design. Prospective.

Setting. A large university teaching hospital.

Patients. Eight patients (mean ± SD age 35.5 ± 11.5 yrs, weight 73.4 ± 24.8 kg) with end‐stage renal failure receiving kidneys from a living relative; three patients were never dialyzed, three were receiving peritoneal dialysis, and two were receiving hemodialysis.

Interventions. Plasma was sampled before and at intervals up to 8 hours after intravenous injection of fentanyl 25 pg/kg before skin incision.

Measurements and Main Results. Mean ± SD (range) preoperative values were blood urea nitrogen (BUN) 66 ± 30 (35–111) mg/dl; albumin 3.6 ± 0.7 (2.6‐4.5) g/dl; and triglycerides 414 ± 352 (156–1270) mg/dl. Elimination half‐life was 382 ± 205 minutes; volume of distribution for the central compartment 0.74 ± 0.48 L/kg; volume of distribution at steady state (Vdss) 3.1 ± 2.0 L/kg; total body clearance 7.5 ±5.1 ml • kg−1 • min−1 • A significant inverse relationship between degree of azotemia and fentanyl clearance was found. The two patients with the highest preoperative BUNs had the lowest multiple of clearance and Vdss, and were also the only ones to require postoperative mechanical ventilation.

Conclusion. Although all patients received a kidney that functioned well after revascularization, the large intersubject variability in fentanyl kinetics may, in part, reflect their heterogeneity in dialysis status and renal failure‐induced abnormalities. Marked decreases in fentanyl clearance do occur in these patients, appear to be related to very high BUN concentrations, and can lead to prolonged postoperative ventilatory depression.
Recovery Parameters after Sevoflurane and Isoflurane Anesthesia
Authors: Cantillo Joaquin , Goldberg Michael E. , Larijani Ghassem E. , Vekeman Denis
Published: October 2023

We compared recovery times in patients with American Society of Anesthesiologists physical status 1—III receiving sevoflurane or isoflurane during surgical procedures longer than 1 hour in duration. Of the 50 patients enrolled, 23 received sevoflurane and 27 received isoflurane. Anesthetic gases were discontinued abruptly at the end of the surgical procedure. The following parameters were recorded: time to emergence (opens eyes), time to extubation, response to verbal command (squeezes hand of observer), and orientation (time and place). Exposure times to the agents were similar. The time to emergence was significantly less with sevoflurane than with isoflurane (5.6 vs 11.2 min, respectively). There were no significant differences in time to extubation, response to verbal command, or orientation between the groups. Our data support more rapid emergence with sevoflurane than with isoflurane in surgical procedures longer than 1 hour in duration.
Pharmacist's Management of Drug‐Related Problems: A Tool for Teaching and Providing Pharmaceutical Care
Authors: Winslade Nancy E. , Bajcar Jana M. , Bombassaro Anne‐Marie , Caravaggio Ciro D. , Strong Dawn K. , Yamashita Sharon K.
Published: October 2023

During the development of education and practice models based on the philosophy of pharmaceutical care (PC), six pharmacists worked with the University of Toronto Faculty of Pharmacy to implement the PC model in their practice sites. These pharmacists found it necessary to modify existing tools to create one that explicitly guided them through the PC process, including the phase of monitoring patients for desired outcomes. This resulted in the development of the Pharmacist's Management of Drug Related Problems. This tool requires pharmacists to collect patient drug and medical data and write responses to specific questions about the data to interpret their significance. As proficiency in providing PC is attained, the questions and space for written responses can be eliminated, leaving a comprehensive documentation system of patient outcomes and the data collected, recommendations made, and monitoring completed by the pharmacist. This tool has been adopted by the University of Toronto Faculty of Pharmacy and is being used in various continuing education programs and by practicing pharmacists across Canada.
Pharmacoeconomic Impact of Once‐Daily Aminoglycoside Administration
Authors: Hitt Catherine M. , Klepser Michael E. , Nightingale Charles H. , Quintiliani Richard , Nicolau David P.
Published: October 2023

A retrospective cost analysis compared hospital costs of standard gentamicin dosing and once‐daily regimens in 1127 patients. Hospital costs compared were drug/supply/preparation/administration (DSPA; $4.56/500 mg once‐daily dose and $3.32/100 mg every 8 hrs standard dose); therapeutic drug monitoring (TDM) ($25/gentamicin level); and nephrotoxicity management. The mean length of therapy was 4.5 days with both regimens. The mean number of blood samples drawn to measure drug levels was 0.65 for once‐daily dosing and 1.7 for standard dosing. Mean DSPA and TDM costs/patient for a 4.5‐day course of once‐daily therapy were $20.52 and $16.25, respectively ($36.77/course of therapy). In comparison, estimated mean DSPA and TDM costs for 4.5 days standard therapy were $44.82 and $42.50, respectively ($87.32/course of therapy). We observed an overall reduction in nephrotoxicity from approximately 4% to 1.2% with the once‐daily program, resulting in a nephrotoxicity management cost reduction from $182 to $55/patient exposed to aminoglycosides. The once‐daily program resulted in a 58% reduction in aminoglycoside‐associated hospital cost and a nephrotoxicity management savings of 70%/patient.
Differences Among Raters Evaluating the Success of EMLA Cream in Alleviating Procedure‐Related Pain in Children with Cancer
Authors: Holdsworth Mark T. , Raisch Dennis W. , Winter Stuart S. , Chavez Cathy M. , Leasure Mary M. , Duncan Marilyn H.
Published: October 2023

We evaluated the analgesic efficacy of EMLA cream after repeated bone marrow aspirations or lumbar punctures (LPs) in children with cancer, and compared the ratings among patients, their parents, physicians, and nurses. Data from LPs were analyzed at the last procedure without EMLA (T1) and the first and last procedures with EMLA (T2 and T3). Friedman's nonparametric analysis of variance was used for statistical analysis. A total of 272 procedures in 29 children were analyzed. For 179 procedures without EMLA, physicians rated pain lower than other raters, and for the 93 with EMLA physicians rated pain less than the children. Children rated pain at T2 lower than at T1 or T3. Physicians rated pain at T2 less than at T3. Both children and physicians rated pain at T3 as not different from that at T1. No differences were noted at these time points for other raters in LP distress ratings, or in bone marrow aspiration pain or distress ratings. Thus EMLA was associated with decreased pain ratings for LPs, but this effect was not sustainable with repeated procedures. The cream alone should not be relied on to control pain of bone marrow aspiration or repeated LPs in children. Physicians underestimated pain, which may have implications for undertreatment in this patient population.
Two Cases of Clarithromycin‐Induced Digoxin Toxicity
Authors: Guerriero Stephanie E. , Ehrenpreis Eli , Gallagher Kathryn L.
Published: October 2023

Two patients experienced clarithromycin‐induced digoxin toxicity. Both had stable renal function within normal limits and had been maintained on a consistent dosage of digoxin. No changes in drug therapy had been made except for the addition of clarithromycin. Administration of clarithromycin to patients receiving long‐term digoxin therapy may induce digoxin toxicity. When concomitant therapy is employed, patients should be closely monitored for clinical signs and symptoms of digoxin toxicity, and digoxin concentrations should be measured to avoid it.
Biological and Clinical Correlates after Chemotherapy and Granulocyte Colony‐Stimulating Factor Administration
Authors: Higa Gerald M. , DeVore Russell F. , Auber Miklos L. , Lynch Joseph P. , Landreth Kenneth S.
Published: October 2023

Study Objective. To evaluate specific biological markers to improve understanding and use of granulocyte colony‐stimulating factor (G‐CSF) in patients receiving chemotherapy.

Design. Prospective, randomized study.

Setting. University‐affiliated hospital and cancer center.

Patients. Twenty‐five patients randomized to begin G‐CSF either 24 hours after chemotherapy (standard arm), or on the day the absolute neutrophil count (ANC) was below 1000/mm3 after chemotherapy (delayed arm).

Interventions. To determine the effect of G‐CSF on granulopoiesis, peripheral blood mononuclear cells were assayed by semisolid culture medium and flow cytometry for granulocyte progenitors and clonogenic CD34 antigen‐positive cells. These biological markers were correlated with G‐CSF administration schedules and the ANC.

Measurements and Main Results. The effect of timing of G‐CSF administration on rate of neutrophil recovery, duration of neutropenia, length of G‐CSF therapy, delays of chemotherapy cycles, and neutropenic fever events was evaluated. Regardless of G‐CSF schedule or chemotherapy regimen, the appearance of mobilized hematopoietic progenitors begins at the neutrophil nadir and parallels granulocyte recovery. Our data also demonstrate that proper timing of G‐CSF administration produces similar rates of neutrophil recovery and comparable clinical outcomes.

Conclusion. Based on the correlation between biological markers and ANC, we propose that the postchemotherapy ANC is a surrogate marker of renewed granulopoietic activity. The relevance of this finding in relationship to the clinical application of G‐CSF remains to be further defined.
Preservatives in Nebulizer Solutions: Risks without Benefit
Authors: Beasley Richard , Fishwick David , Miles Jon F , Hendeles Leslie
Published: October 2023

Edetate disodium (EDTA) and benzalkonium chloride (BAC) are often present as preservative or stabilizing agents in nebulizer solutions used to treat asthma and chronic obstructive pulmonary disease. Benzalkonium chloride is a potent bronchoconstrictor when inhaled in concentrations similar to those in which it is present in these solutions. Inclusion of BAC (together with EDTA) in the ipratropium bromide (Atrovent) nebulizer solution resulted in paradoxic bronchoconstriction in some asthmatic patients and an overall reduction in bronchodilator efficacy. The presence of BAC in albuterol nebulizer solutions does not affect the short‐term bronchodilator response to a single dose, although case reports suggest that its repeated use in patients with severe asthma may result in paradoxic bronchoconstriction. When inhaled by asthmatic subjects, EDTA also causes dose‐dependent bronchoconstriction, although it is less potent than BAC. The Use of preservative‐free bronchodilator nebulizer solutions does not result in clinically significant bacterial contamination if they are dispensed in sterile unit‐dose vials, in volumes and concentrations that do not require modification by the user. Despite this evidence, in the United States a number of solutions, including some preparations of albuterol, contain either BAC or EDTA. Current regulations do not require that the concentration of preservatives be documented on the product; however, considerably different doses of BAC are delivered with different products. For example, a standard 2.5‐mg dose of albuterol nebulizer solution contains 50 μg of BAC when administered from the multidose dropper bottle and 300 μg from the unit‐dose screw‐cap product. Furthermore, it is legal for pharmacists to substitute or compound solutions containing high concentrations of BAC when the physician has prescribed a preservative‐free product. We recommend that the United States follow the practice of most Western countries and withdraw bronchodilator nebulizer solutions that contain preservatives such as BAC. We further recommend that the solutions should be prepared under sterile conditions, formulated preservative free, and made available in unit‐dose vials.
Molecular Characterizations of an Intraacrosomal Antigen Defined by HS‐33 Monoclonal Antibody
Authors: YOSHIKI TATSUHIRO , LAI BENJAMIN C. L. , DORJEE SONAM , LEE CHI‐YU GREGORY
Published: October 2023

ABSTRACT: Among the numerous anti‐sperm monoclonal antibodies generated in our laboratory, HS‐33 was shown to react with a conserved antigen on the acrosome of spermatozoa from human and mouse. By using indirect immunofluorescent assay, it was demonstrated that HS‐33 did not bind to live human sperm. However, this antibody was found to react with the methanol‐fixed acrosomeintact, but not with acrosome‐reacted sperm. The human sperm antigen recognized by this antibody was purified from human sperm extract by immunoaffinity chromatography. The purified cognate human sperm antigen designated as HSAg‐33 was found to be a protein with a molecular weight of approximately 72 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions. The tissue‐specificity and the developmental expression of this sperm antigen were examined using frozen sections of various human and mouse tissues. The antigen was shown to be expressed specifically in the testicular sperm at the postmeiotic stages of spermatogenesis but not in any other somatic tissues. “Spontaneous” acrosome reaction was determined following 18 hours of incubation in Biggers, Whitten, and Whittingham (BWW) medium by using HS‐33 monoclonal antibody and Pisum sativum agglutinin (PSA) as probes. The number of sperm stained positively with this antibody decreased significantly following overnight incubation, indicating the occurrence of an acrosome reaction. The results of this study suggest that HSAg‐33 is a potentially useful sperm‐specific acrosome marker for studies of sperm capacitation and acrosome reaction.
HCG Binding to the Testicular LH Receptor Is Similar in Fertile, Subfertile, and Infertile Stallions
Authors: MOTTON DEBORAH D. , ROSER JANET F.
Published: October 2023

ABSTRACT: Recent evidence in our laboratory suggests that the cause of idiopathic subferttlity/infertility in breeding stallions may originate in the testes at the luteinizing hormone (LH) receptor or postreceptor level. The objective of this research was to determine if LH receptor binding activity is altered in subfertile and infertile stallions. Six fertile, three subfertile, and three infertile stallions, ages 11–23 years, were classified according to normal semen parameters and pregnancy rates and then castrated in the breeding season. Blood was collected prior to castration, and plasma was stored until analyzed for LH, follicle stimulating hormone (FSH), estrogen conjugates (EC), estradiol (E2), testosterone (T), and inhibin (I) by radioimmunoassay (RIA). Testicular cell membranes were prepared and snap‐frozen until analyzed for LH binding activity by radioreceptorassay (RRA) using increasing amounts of I125 human chorionic gonadotropin (hCG). Luteinizing hormone receptor numbers and affinity constants were determined by Scatchard analysis. Plasma LH, FSH, EC, E2, and T levels did not differ between fertile and subfertile stallions, but LH and FSH were significantly higher (P < 0.05) and EC, E2, T, and I levels were significantly lower (P < 0.05) in infertile stallions as compared to fertile and subfertile stallions. Receptor number (Rt) and affinity constants Ka were similar (P > 0.05) between fertile (Rt = 9.44 × 10−11 M, Ka = 0.300 × 1010 M−1), subfertile (Rt = 13.02 × 10−11 M, Ka = 0.194 × 1010 M−1), and infertile (Rt = 7.65 × 10−11 M, Ka = 0.380 × 1010 M−1) stallions. In conclusion, these data suggest that an endocrine dysfunction in the testes of stallions with poor fertility may not be due to a LH receptor disorder but may be due to a postreceptor malfunction.
Can an apophatic meditation promote long‐term adjustment in hope? A time‐series model of centering meditation
Authors: Dorais Stephanie , Gutierrez Daniel , Fox Jesse , Niles Spencer G.
Published: October 2023

The authors investigate the effects of centering meditation on state hope among college and graduate students through a randomized controlled trial. Participants (n = 150; 65% white, 84% female) were randomized to either a centering meditation group or a waitlist control group. Time‐series analyses indicated that centering meditation significantly improved hope, suggesting long‐term dynamic adjustment, compared to a control group. Specifically, the autoregressive integrated moving average (ARIMA) procedures indicated that the treatment group exhibited a statistically significant upward trend in hope, ARIMA (1, 1, 0). As expected, the control group's levels of hope were stationary, ARIMA (1, 0, 1). The study highlights the potential benefits of centering meditation as an evidence‐based counseling intervention for improving hope in the college population.
Indirect Z‐scheme TiO2/BC/g‐C3N4 for efficient photocatalytic reduction of Cr(VI) in aqueous solution
Authors: Chen Mingliang , Wang Guanghui , Dai Jialing , Li Haifeng , Deng Nansheng
Published: October 2023

BACKGROUND

There is increasing concern regarding the rising issue of Cr(VI) pollution in aqueous solutions. It is crucial to find an effective technology for the removal of Cr(VI) in aqueous solutions. In this work, a novel TiO2/BC/g‐C3N4 heterostructure photocatalyst was successfully prepared by a simple hydrothermal method and characterized by scanning electron microscopy, transmission electron microscopy, X‐ray diffraction, Brunauer–Emmett–Teller analysis, Fourier transform infrared spectroscopy, photoluminescence, ultraviolet–visible diffuse reflectance spectroscopy and X‐ray photoelectron spectroscopy. The photocatalytic reduction behavior of Cr(VI) on the TiO2/BC/g‐C3N4 heterostructure was investigated under visible light irradiation, and the possible mechanism of photocatalytic reduction of Cr(VI) was elucidated.

RESULTS

The TiO2/BC/g‐C3N4 heterostructure photocatalyst exhibited better photoreduction activity for Cr(VI) under visible light irradiation. After 100 min irradiation with visible light, the TiO2/BC/g‐C3N4 photocatalyst achieved a removal efficiency of 89% for Cr(VI). Compared with TiO2, TiO2/BC and TiO2/g‐C3N4, the photocatalytic removal efficiency of Cr(VI) on the TiO2/BC/g‐C3N4 increased by 40%, 20% and 10% respectively. The photocatalytic reduction of Cr(VI) was dependent on the initial concentration of Cr(VI), catalyst dosage, pH value and atmosphere. Moreover, TiO2/BC/g‐C3N4 presented excellent stability and reusability after five cycles.

CONCLUSION

The TiO2/BC/g‐C3N4 heterojunction enables highly efficient photocatalytic reduction of Cr(VI) under visible light irradiation. This enhancement is primarily attributed to the construction of an indirect Z‐scheme TiO2/BC/g‐C3N4 heterojunction, which significantly improves the separation efficiency of photo‐ generated charge carriers during the photochemical process. Furthermore, the presence of BC enhances the adsorption performance of Cr(VI) on TiO2/BC/g‐C3N4, thereby facilitating its photocatalytic reduction. © 2023 Society of Chemical Industry.
Achieving diagnostic excellence through prevention and teamwork (ADEPT) study protocol: A multicenter, prospective quality and safety program to improve diagnostic processes in medical inpatients
Authors: Schnipper Jeffrey L. , Raffel Katie E. , Keniston Angela , Burden Marisha , Glasheen Jeffrey , Ranji Sumant , Hubbard Colin , Barish Peter , Kantor Molly , Adler‐Milstein Julia , John Boscardin W. , Harrison James D. , Dalal Anuj K. , Lee Tiffany , Auerbach Andrew
Published: October 2023

Background

Few hospitals have built surveillance for diagnostic errors into usual care or used comparative quantitative and qualitative data to understand their diagnostic processes and implement interventions designed to reduce these errors.

Objectives

To build surveillance for diagnostic errors into usual care, benchmark diagnostic performance across sites, pilot test interventions, and evaluate the program's impact on diagnostic error rates.

Methods and Analysis

Achieving diagnostic excellence through prevention and teamwork (ADEPT) is a multicenter, real‐world quality and safety program utilizing interrupted time‐series techniques to evaluate outcomes. Study subjects will be a randomly sampled population of medical patients hospitalized at 16 US hospitals who died, were transferred to intensive care, or had a rapid response during the hospitalization. Surveillance for diagnostic errors will occur on 10 events per month per site using a previously established two‐person adjudication process. Concurrent reviews of patients who had a qualifying event in the previous week will allow for surveys of clinicians to better understand contributors to diagnostic error, or conversely, examples of diagnostic excellence, which cannot be gleaned from medical record review alone. With guidance from national experts in quality and safety, sites will report and benchmark diagnostic error rates, share lessons regarding underlying causes, and design, implement, and pilot test interventions using both Safety I and Safety II approaches aimed at patients, providers, and health systems. Safety II approaches will focus on cases where diagnostic error did not occur, applying theories of how people and systems are able to succeed under varying conditions. The primary outcome will be the number of diagnostic errors per patient, using segmented multivariable regression to evaluate change iny‐intercept and change in slope after initiation of the program.

Ethics and Dissemination

The study has been approved by the University of California, San Francisco Institutional Review Board (IRB), which is serving as the single IRB. Intervention toolkits and study findings will be disseminated through partners including Vizient, The Joint Commission, and Press‐Ganey, and through national meetings, scientific journals, and publications aimed at the general public.