bluuebunny/crossref_metadata_2025 huggingface dataset:
What characteristics do we look for in our political leaders?
Authors: Hodges Dawn Z.
Published: October 2023

It's almost impossible to believe that this time next year, the citizens of the United States of America will be electing either our 46th or 47th president, depending on whether the incumbent wins. In some ways, it seems like the past three years have flown by, and in other ways, it seems the years have dragged on. The year 2024 could either go by really fast or really slow.
Long‐term efficacy and safety of adjunctive perampanel in patients from the Asia‐Pacific region with refractory focal‐onset seizures in Study 335 open‐label extension
Authors: Nishida Takuji , Lee Sang Kun , Inoue Yushi , Saeki Kazunori , Ishikawa Kohei , Malhotra Manoj , Patten Anna , Kaneko Sunao
Published: October 2023

Objective

To evaluate the long‐term efficacy, safety, and tolerability of adjunctive perampanel for the treatment of patients with refractory focal‐onset seizures (FOS), with or without focal to bilateral tonic–clonic seizures (FBTCS), from the Asia‐Pacific region.

Methods

Study 335 (NCT01618695) was a randomized, double‐blind, placebo‐controlled, Phase III study. Patients aged ≥12 years with refractory FOS who completed the Core Study could enter an open‐label extension (OLEx) Phase (6‐week Conversion and ≥46‐week Maintenance Period). Endpoints included median percent reduction in seizure frequency per 28 days, 50% responder and seizure‐freedom rates, and treatment‐emergent adverse events (TEAEs).

Results

The Intent‐to‐Treat Analysis Set included 704 patients (529 received perampanel and 175 received placebo during the Core Study; all patients received perampanel during OLEx). The median percent reduction in seizure frequency and 50% responder rates in patients who received perampanel during the Core Study were maintained throughout the OLEx Phase (Week 64–75: 55.9% and 54.3%, respectively). Seizure freedom for ≥12 consecutive months at any time during perampanel treatment was achieved by 4.1% of patients with FOS and 14.2% of patients with FBTCS. Among patients treated with perampanel 4 mg/day (n = 83), median reduction in seizure frequency was lower in those who received concomitant enzyme‐inducing anti‐seizure medications (EIASMs) than those who received non‐EIASMs. The most common TEAE was dizziness (n = 318; 46.8%); 141 (20.8%) patients had TEAEs that led to study/drug withdrawal.

Significance

Overall, long‐term seizure control was achieved with adjunctive perampanel in patients with refractory FOS, with or without FBTCS, in an Asia‐Pacific population.
Enhanced magnetic relaxation switching immunoassay for chlorpyrifos based on tyramine signal amplification
Authors: Zhan Chen , Wu Long , Dong Yongzhen
Published: October 2023

Chlorpyrifos, an organophosphorus pesticide, is widely used in agriculture to protect crops from insects. However, the presence of its residues in food has caused widespread concern due to the serious risks to human health. Traditional detection methods suffer from limitations, such as low sensitivity, long detection time, and complicated operations. Herein, based on the tyramine signal amplification (TSA) strategy, we developed a sensitive and rapid magnetic relaxation switching (MRS) immunosensor for the detection of chlorpyrifos. Wherein, magnetic Fe3O4 nanoparticles modified with tyramine (MNP150‐tyramine) acted as magnetic probes for magnetic relaxation signal output. In the presence of hydrogen peroxide (H2O2) and horseradish peroxidase (HRP), tyramine can be converted to the highly reactive intermediate that covalently binds with the nearby proteins, such as HRP and antibody, thus assembling MNPs to magnetic clusters and showing changes in transverse relaxation time (T2) signals. Based on the “antibody–antigen” immunoreaction, chlorpyrifos could make a connection of HRP/antibody‐modified MNPs and MNP150‐tyramine with a result of MNPs aggregation and strong T2 signals. In this study, the TSA‐MRS method showed sensitive detection of chlorpyrifos with a limit of detection of 0.54 ng/mL, a 4.5‐fold enhancement in the sensitivity compared with the ELISA method, providing an alternative method for the detection of harmful substances in food samples.
Crack detection in fuel cell electrodes using a spatial filtering technique for overcoming noisy backgrounds
Authors: Pfeilsticker Jason , Baez‐Cotto Carlos , Ulsh Michael , Mauger Scott
Published: October 2023

Image processing is a powerful tool that allows for rapid and automated data parsing in settings that occupy large variable spaces and require large data sets. Feature detection on difficultly discerned backgrounds is a subset of image processing that facilitates the extraction of quantitative metrics from otherwise subjective data. Crack detection and quantification is an important capability in polymer electrolyte membrane fuel cell quality control, failure analysis, and optimization. This work presents a technique to perform crack detection and quantification which overcomes challenges faced by commonly used image segmentation techniques. We demonstrate the use of a geometrically filtered noise‐level detection technique to select a binary threshold value from which we then quantify how cracked a sample is. We demonstrate the accuracy of our technique using programmatically generated test images of known crack amounts and their performance on real‐world fuel cell catalyst layer samples.
Extreme acute radiation‐induced toxicity in a patient with polymorphous low‐grade adenocarcinoma of the nasopharynx and rare variants in DNA repair genes
Authors: Nowicka Zuzanna , Kuna Kasper , Stawiski Konrad , Sołek Julia , Świderek Magdalena , Papis‐Ubych Anna , Fijuth Jacek , Fendler Wojciech , Tomasik Bartłomiej
Published: October 2023

Background

Polymorphous low‐grade adenocarcinoma (PLGA) is an extremely rare finding in the nasopharynx. There are no guidelines for the treatment of PLGA in this localization. Radiotherapy may be administered to treat this malignancy; however, in radiosensitive individuals, it is associated with a risk of severe radiotherapy‐induced toxicity.

Methods

We present a case of a 73‐year‐old woman with locally advanced polymorphous low‐grade adenocarcinoma of the nasopharynx who developed a severe adverse acute reaction to radiotherapy leading to treatment discontinuation. Despite intensive treatment, the patient died 40 days after RT initiation. Whole genome sequencing was performed using DNA from peripheral blood mononuclear cells in the search for variants that could explain such extreme toxicity.

Results

We identified a combination of pathogenic variants that may have contributed to the patient's reaction to radiation therapy, including predisposing variants in XRCC1, XRCC3, and LIG4. We also identified candidate variants, not previously described in this context, which could be associated with radiation toxicity based on plausible mechanisms. We discuss previous reports of this rare tumor from the literature and known contributors to radiation‐induced toxicity.

Conclusions

Genetic causes should be considered in cases of extreme radiosensitivity, especially when is not explained by clinical factors.
A Multiplex GPCR‐Mediated Peptide Tagging System for a Growing Yeast Synthetic Biology Toolbox
Authors: Matragrano Joseph , Cornish Virginia W. , Billerbeck Sonja
Published: October 2023

Straightforward methods for specifically detecting and quantifying proteins are essential for both basic and applied research and notably in synthetic biology. Previously we demonstrated that the yeast mating pathway could be hijacked to detect species‐specific fungal peptide pheromones using their corresponding mating GPCRs. Here we asked if our yeast biosensor could detect proteins in addition to peptides – a question not previously resolved in the literature. As such, we repurposed the Saccharomyces cerevisiae fungal mating pheromone α‐factor as a peptide tag and fused it terminally and internally to the protein Smt3. Our biosensor was able to detect the tagged protein in the nanomolar range using fluorescence as a read‐out. We extended the assay to four additional orthogonal peptide pheromone tags, demonstrating a cheap, non‐labor‐intensive, and high‐throughput assay compatible with multiplexing for protein detection. With its ability to detect proteins our living yeast biosensor could be useful for the optimization of protein producing cell‐factories, for building logic gates and myriad other applications in synthetic biology.
Clinical and genetic screening in a large Iranian family with Marfan syndrome: A case study
Authors: Vafaeie Farzane , Miri Karam Zahra , Yari Abolfazl , Safarpour Hossein , Kazemi Tooba , Etesam Shokoofeh , Mohammadpour Mojtaba , Miri‐Moghaddam Ebrahim
Published: October 2023

Background and Aims

Marfan syndrome (MFS) is an autosomal dominant genetic disorder caused by pathogenic variants of the fibrillin‐1‐encoding FBN1 gene that commonly affects the cardiovascular, skeletal, and ocular systems. This study aimed to evaluate the clinical features and genetic causes of the MFS phenotype in a large Iranian family.

Methods

Seventeen affected family members were examined clinically by cardiologists and ophthalmologists. The proband, a 48‐year‐old woman with obvious signs of MFS, her DNA sample subjected to whole‐exome sequencing (WES). The candidate variant was validated by bidirectional sequencing of proband and other available family members. In silico analysis and molecular modeling were conducted to determine the pathogenic effects of the candidate variants.

Results

The most frequent cardiac complications are mitral valve prolapse and regurgitation. Ophthalmic examination revealed iridodonesis and ectopic lentis. A heterozygous missense variant (c.2179T>C/p.C727R) in exon 19 of FBN1 gene was identified and found to cosegregate with affected family members. Its pathogenicity has been predicted using several in silico predictive algorithms. Molecular docking analysis indicated that the variant might affect the binding affinity between FBN1 and LTBP1 proteins by impairing disulfide bond formation.

Conclusion

Our report expands the spectrum of the Marfan phenotype by providing details of its clinical manifestations and disease‐associated molecular changes. It also highlights the value of WES in genetic diagnosis and contributes to genetic counseling in families with MFS.
Cluster‐associate viscosity model of tin chloride in comparison with the Frenkel model
Authors: Bekbayeva Lazzat , Makasheva Astra , Malyshev Vitaliy , Naboko Yelena , Sarkenov Berik
Published: October 2023

Determining the viscosity of inorganic molten compounds like tin chloride is critically important for material processing, chemical synthesis, and energy applications. However, experimental limitations have restricted the development of accurate viscosity models. This study tests a new cluster‐associate model for predicting the viscosity of molten tin chloride across a wide temperature range. The model links viscosity to the structure and dynamics of molecular clusters in the melt. The aim of this study is to establish a correlation between viscosity and cluster formation within a liquid, using tin chloride as an example. The data were calculated using a newly developed equation based on the concept of randomized particles. The temperature range studied was from the melting point to the boiling point. To verify the accuracy of the cluster‐associate model, it was compared with the Frenkel equation using logarithmic coordinates. Simulations were performed on tin chloride, which yielded results showing a linear relationship between the degree of cluster association and the activation energy of fluidity. The proportionality coefficient reflects the activation energy associated with a single cluster. The Frenkel equation in the logarithmic coordinate scale was compared with the cluster‐associate model. The functional dependence and correspondence of these models are indicated by their high coefficient mutual correlation. The proposed viscosity model underwent testing for the entire liquid state range of the substance, and calculations confirmed its validity. This enables reliable use of the suggested model for both high‐ and low‐temperature extrapolation, including the critical point region.
Body Composition Analysis by Bioelectrical Impedance: The Effects of Time of Day and Body Side on Estimated Gentamicin Pharmacokinetics
Authors: Robert Sylvie , Zarowitz Barbara J. , Pilla Alison M. , Peterson Edward L
Published: October 2023

To assess if repetitive measures are useful in a clinical setting, the effects of time of day and body side on bioelectrical impedance (BI) measurements were evaluated. Fifteen healthy, male volunteers underwent serial BI measurements at 0, 3, 6, 9, 24, and 48 hours on both sides of the body using a four‐electrode plethysmograph. Analysis of variance for repeated measures indicated that the mean resistance (R) value of the right side was statistically lower from that of the left side (447 ± 27.9 vs 457 ± 29.1 ohms; p = 0.006). Both R and reactance (Xc) varied significantly over time. For R, the mean response at 0, 6, 9, and 48 hours was different from the overall mean of the remaining time points (p < 0.007). Only times 6 and 24 hours were significantly different for Xc (p < 0.006). No relevant time and side effects were noted in calculated gentamicin pharmacokinetic parameters on incorporation of BI measurements into impedance‐derived predictive equations for clearance, volume of distribution, and elimination constant. Correlation coefficients of reliability were high within 1 day and across days (R ≥ 0.8407). These data suggest that under normal conditions, BI analysis provides reliable results, and that time and side standardizations in its measurements are not necessary.
Opiate Receptors: Opioid Agonist‐Antagonist Effects
Authors: Goldstein David J. , Meador‐Woodruff James H.
Published: October 2023

Two concepts are especially important in understanding the action of agonist‐antagonist opioid analgesics. First, knowing to which receptor classes an agonist‐antagonist binds permits prediction of its pharmacodynamics. For instance, psychotomimetic effects occur with binding to specific opiate (k) and nonopiate (Σ) receptors. Second, to have limited agonist activity despite increasing dose ceiling effect, the antagonist effect usually is of the same receptor class as the agonist effect.
Perspectives on Geriatric Pharmacotherapy
Authors: Delafuente Jeffrey C.
Published: October 2023

In the United States the population over 85 years of age use a disproportionately large percentage of health care resources, including drugs. The elderly take approximately one‐third of all medications. Among other factors, the need for several agents predisposes them to adverse drug reactions and drug interactions. Sequelae from drug usage in the elderly are more common than in younger patient populations, and often result in hospitalization. Careful patient monitoring is imperative for optimum pharmacotherapy in elderly patients.
Hypertension in the Elderly: Conventional Wisdom Revisited
Authors: Lopez Larry M.
Published: October 2023

Elevated systolic and/or diastolic blood pressure in the elderly is a problem the extent of which may be somewhat overstated. In those elderly with definite hypertension, pathophysiology may differ from that of younger counterparts. The contribution of elevated plasma renin activity to hypertension and to the choice of therapy also appears to be exaggerated. The risks of ignoring hypertension in the elderly are similar to those in younger patients, and therefore excessively elevated blood pressure should no longer be considered a normal consequence of aging. Notably, elevated systolic pressure is a better predictor of future adverse occurrences than is elevated diastolic pressure. Unfortunately, there is no well defined therapeutic regimen to manage isolated systolic hypertension. Conservative reduction of elevated systolic and diastolic pressures may nevertheless be accomplished safely and effectively. Individualization of therapy is recommended based primarily on concomitant disease(s). Thus no single agent or combination of agents is preferable in all elderly hypertensive patients. Aggressive use of non‐pharmacologic therapy preferably precedes judicious of antihypertensive medication. Aggressive blood pressure reduction with potent drugs is not recommended.
The Effect of Multiple Doses of Phenylpropanolamine on the Blood Pressure of Patients Whose Hypertension Was Controlled With β Blockers
Authors: O'Connell Mary Beth , Gross Cynthia R.
Published: October 2023

Single‐dose phenylpropanolamine (PPA) can cause blood pressure elevation in healthy volunteers and in patients whose hypertension is controlled with β blockers. Few data exist on the effect of long‐term PPA dosing on blood pressure in normotensive or hypertensive patients. Therefore, we studied the effect of multiple PPA doses in seven hypertensive men whose blood pressure was controlled with β blockers. These patients had previously demonstrated a mean increase in blood pressure after 25 mg PPA compared to placebo. Each patient received 25 mg PPA 3 times a day for 6.3 days. Five patients completed the study. After drug therapy on days 1 and 7, statistically significant increases in the peak measured systolic and diastolic blood pressures from baseline were found, with ranges of maximum increase 3–22 mm Hg and 0–16 mm Hg, respectively. The peak measured blood pressures on days 1 and 7 were significantly different from placebo values for both systolic and diastolic pressures. The area under the blood pressure‐time curve and the change between baseline and peak for systolic and diastolic blood pressures on days 1 and 7 were not significantly different. Tolerance and hypersensitivity were not detected. Several doses of PPA did not alter the blood pressure effect from the first‐dose response, however, caution and close monitoring are still necessary for these patients.
Noncompliance in Organ Transplant Recipients
Authors: Swanson Mary A. , Palmeri Debera , Vossler Elizabeth D. , Bartus Stanley A. , Hull David , Schweizer Robert T.
Published: October 2023

The frequency of noncompliance with postoperative medical therapy ranges from 2% to 43% in organ transplant recipients and causes more graft loss than uncontrolled rejection in compliant patients. Retrospective and prospective studies undertaken at our center showed no difference in the rate of noncompliance between males and females or between recipients of cadaveric kidneys and those from living, related donors. Patients less than 20 years of age were statistically the most noncompliant (p=0.0001) compared with those over 40 years. A significant difference in compliance was seen among blacks, Hispanics, and non‐Hispanic whites, with the greatest frequency in blacks. This was not due to race, but to socioeconomic status, with those in the low socioeconomic group the most noncompliant. Problems of noncompliance may be reduced if they are identified early in the treatment course.
Antidepressant Effects of Flupenthixol
Authors: Gruber Amanda J. , Cole Jonathan O.
Published: October 2023

Strong evidence exists that flupenthixol, not presently distributed in the United States, is an effective antidepressant. Its advantages over available antidepressants include its safety with respect to overdose and in combination with other medications, low dependency risk, rapid onset of action, and availability in depot preparation. Flupenthixol also may be useful as a mood elevator for schizophrenics, an alternative mood stabilizer for patients with bipolar disease, and a facilitator for cocaine withdrawal.
Antimicrobial Cost and Quality Control: Challenges in the 1990s
Authors: Barriere Steven L.
Published: October 2023

Increasing constraints on health care reimbursement, competition among hospitals, and new high‐cost technologies all contribute to escalation of costs in hospitals. The goal in the 1990s is to provide optimum, cost‐effective care for patients without compromising quality. Among many proved methods is an effective formulary system with explicit criteria for use of medications, guidelines for use in specialized circumstances, and suggestions for therapeutic alternatives. This last method of cost control received endorsement from several organizations and offers an important function for hospital pharmacists. Hospital pharmacies can play a major role in minimizing antimicrobial costs and promoting optimum patient care. (Pharmacotherapy 1991;11(1 Pt 2):4S‐5S)
Antimicrobial Formulary Management: A Consultant's Perspective
Authors: Holzman Martin S.
Published: October 2023

Health care administrators are concerned with the need for cost containment, including how pharmacies may contribute to cost savings. They also must be aware of how quality assurance activities and cost containment are related. Various techniques are available for reducing antibiotic costs, such as formulary alternatives, improved pricing, use of guidelines, controlling dosage frequency and strength, and converting from intravenous to oral route of administration. Two kinds of savings are involved: soft and hard. Soft savings are usually not real in the sense that overall hospital expenses will probably not be reduced as a result of implementing change. Hard savings will increase a hospital's profits and reduce expenses as a result of the intended change. (Pharmacotherapy 1991;11(1 Pt 2):14S‐18S)
Absorption of Oral Ciprofloxacin in a Patient with Cardiogenic Shock
Authors: Ujhelyi Michael R. , Sullivan Maureen , Nightingale Charles
Published: October 2023

Congestive heart failure and cardiogenic shock can alter the absorption process of some drugs. The absorption of ciprofloxacin has been studied in several disease states, but the effect of cardiogenic shock on its absorption is unknown. A 63‐year‐old man had a large myocardial infarction complicated by cardiogenic shock. When he began taking ciprofloxacin for pneumonia, he had renal and cardiac failure. Ciprofloxacin 500 mg was administered every 24 hours by nasogastric tube. Blood samples were collected 5 minutes prior to the second dose (20 hrs after the initial dose) and then regularly until 11 hours after the dose. Samples were analyzed using high‐performance liquid chromatography. The trough concentration 20 hours after the initial dose was 3.7 μg/ml, and the serum concentrations after the second dose went from 5.6 to 4.94 μg/ml over the 11‐hour sampling period. The peak concentration of 5.6 μg/ml occurred within 30 minutes after ciprofloxacin administration. It can be concluded from this case study that ciprofloxacin was adequately absorbed in this patient with multiple organ failure.
Gentamicin Pharmacokinetics in Term Neonates Receiving Extracorporeal Membrane Oxygenation
Authors: Bhatt‐Mehta Varsha , Johnson Cary E. , Schumacher Robert E.
Published: October 2023

Extracorporeal membrane oxygenation (ECMO) may affect the pharmacokinetics of certain drugs. The objectives of this study were to determine (1) the pharmacokinetics of gentamicin in neonates on ECMO and compare them to reported values for a similar patient population not on ECMO, (2) if the pharmacokinetics of gentamicin differ between venous‐venous and venous‐arterial bypass, and (3) if the pharmacokinetics of gentamicin are affected by oxygenator surface area (0.6 m2 vs 0.8 m2 oxygenators). The medical records of 29 term neonates who received gentamicin while on ECMO were reviewed. Data collected included gentamicin dosage, peak and trough serum concentrations determined at steady state, duration of treatment, time on ECMO, daily weights, and pertinent laboratory values. An initial dosage of gentamicin 2.5 mg/kg every 18 hours is suggested for term neonates on ECMO. Dosage adjustments should be based on gentamicin serum concentrations, and modifications may also be required after ECMO.
Ex Vivo Protein Binding of Clindamycin in Sera With Normal and Elevated α1‐Acid Glycoprotein Concentrations
Authors: Kays Michael B. , White Roger L. , Gatti Giorgio , Gambertoglio John G.
Published: October 2023

Clindamycin is a lincosamide antibiotic that binds primarily to α1‐acid glycoprotein (AAG), an acute‐phase serum protein. Many studies have shown that AAG concentrations increase in response to stress, including infection, myocardial infarction, and trauma. The objectives of this study were to determine the serum protein binding of various clindamycin concentrations in sera with normal and elevated AAG concentrations. Serum was obtained from 4 healthy volunteers and 12 patients with pathophysiologic conditions known to elevate serum AAG concentrations. Timing for collection was determined from the literature, corresponding with the expected peak concentration for each disease state. Samples were assayed for AAG by radial immunodiffusion and were spiked with clindamycin to achieve total concentrations of 10 μg/ml (n = 18), 4 μg/ml (n = 10), and 2 μg/ml (n = 7). Protein binding was determined by ultrafiltration and subsequent high‐performance liquid or gas chromatography. Protein binding was dependent on the serum concentrations of both AAG and clindamycin. When AAG concentrations increased from 101–150 mg/dl to 201 mg/dl or greater, mean protein binding increased from 81.2% to 92.4% (p = 0.1265) and from 61.3% to 88.6% (p < 0.05) at clindamycin concentrations of 2 and 4 μg/ml, respectively. With AAG concentrations between 101 and 150 mg/dl, mean protein binding increased from 62.4% at 10 μg/ml to 81.2% at 2 μg/ml (p = 0.1514). Since AAG concentrations may increase in certain patients, the concentration of free (pharmacologically active) drug may fall below the minimum inhibitory concentration for several pathogens earlier in a dosing interval.
Naloxone and Restraint Stress: Effects on Gastric Mucosal Injury and Gastric Function
Authors: Kleiman‐Wexler Rachel L. , Ephgrave Kimberly S. , Adair Colin G.
Published: October 2023

Contradictory findings have been reported from previous investigations of the effects of opiate receptor blockade on stress‐related gastric injury. We performed two studies of the effects of naloxone on gastric mucosal injury and gastric function in cold restraint stress. In the first, naloxone had a linear, dose‐dependent effect, reducing mucosal injury both parenterally and enterally. Gastric acidity was not related to the dose of naloxone, or to the amount or extent of mucosal injury. Gastric residual volume, by contrast, was related to both naloxone dose and gastric mucosal injury. In the second study we investigated the effect of gastric distention by enteral vehicle in the restraint model, and the interaction of the vehicle with the effects of naloxone. Periodic distention of the stomach with enteral vehicle did not alter the drug's effects on mucosal injury or on gastric residual volume. Because cold restraint stress produces harmful gastric contractions, naloxone is likely to be protective by altering gastric motility.
Introduction to Immunology
Authors: McIntyre William J. , Tami Joseph A.
Published: October 2023

The immune system is a complex network of components functioning to provide host defense. This network consists of immunologic cells and their products (e.g., interleukins and colony‐stimulating factors), organs, tissues, complement, and major histocompatibility complex antigens. These components are organized into specific and nonspecific immune systems, the major functional activities of which include antigen presentation and cell‐mediated cytotoxicity.
A Pharmacokinetic and Endoscopic Comparison of an Oral and an Experimental Buccal Piroxicam Formulation
Authors: Mueller Bruce A. , Rex Douglas K. , Figueroa Neysa , Greene Paula , Brater D. Craig
Published: October 2023

We compared the endoscopic effects and pharmacokinetic profiles of an experimental buccal formulation of piroxicam to oral capsules in an attempt to determine whether nonsteroidal antiinflammatory drug‐induced gastropathy is due to a local or systemic effect. Ten healthy subjects received 20 mg piroxicam daily in a double‐blind, randomized, crossover, placebo‐controlled study. Upper endoscopies were performed at the baseline and at the end of each 2‐week dosing arm of the study. Pharmacokinetic data obtained included serum and gastric piroxicam concentrations and serum 5′‐hydroxypiroxicam metabolite concentrations after the first dose and 2 weeks of dosing. No differences in endoscopy scores or patient symptom scores were noted between the two dosage forms after 2 weeks of dosing. Pharmacokinetic data of piroxicam and the metabolite revealed that the buccal formulation may not have been absorbed exclusively from the buccal mucosa.
A Longitudinal Analysis of Factors Associated With Morbidity in Cocaine Abusers With Psychiatric Illness
Authors: Stanislav Steven W. , Sommi Roger W. , Watson William A.
Published: October 2023

We conducted a study to characterize a population of cocaine users who were referred to a state psychiatric institution, identify treatment problems including reasons for relapse, and develop strategies to improve treatment outcome. Using a data base system from a tertiary‐care hospital emergency department, we identified a sample of 80 patients with a cocaine‐related presentation who came to the emergency department and were referred to the psychiatric facility. Forty‐six percent had consumed crack cocaine, and 65% reported ingesting cocaine with other drugs, half of them with alcohol. Suicidal ideation or attempt was the most common reason for referral. A retrospective review of 58 of the 80 referrals to the psychiatric facility showed that over half of the patients were given a concurrent psychiatric diagnosis and required hospitalization on an acute‐care psychiatric unit. Sixty‐two percent of those admitted had prior hospitalizations at the psychiatric facility, yet only five patients had received treatment for substance abuse. Seventy‐four percent were readmitted to the psychiatric facility within 1 year of their index episode, with a higher rate of relapse among persons with dual diagnoses compared to cocaine users without dual diagnoses (p<0.05). Possible reasons for relapse included lack of referral for substance abuse treatment, nonintegrated treatment of psychiatric illness and substance abuse, lack of psychosocial support, and unresolved financial or job‐related stressors. The data support increased funding to facilities that treat persons with dual diagnoses, and suggest the need to develop comprehensive treatment approaches involving a multidisciplinary team to address issues of mental illness and substance abuse concomitantly, and to identify and resolve stressors leading to relapse.
Captopril Ameliorates the Posturally Induced Fall in Creatinine Clearance in Patients With Chronic Glomerulonephritis
Authors: Kuriyama Satoru , Shimada Toshiki , Hashimoto Takao , Sakai Osamu
Published: October 2023

The clinical usefulness of an angiotensin‐converting enzyme inhibitor on the posturally induced fall in creatinine clearance (Clcr) was studied in patients with biopsy‐proved chronic glomerulonephritis (CGN). After a change from supine to upright position, Clcr fell significantly in all patients. This fall was significantly ameliorated by the pretreatment with captopril (fall in Clcr 28.8 ± 14.3% for nontreated vs 16.5 ± 11.5% for treated patients; n = 12; p<0.05). The ameliorating effect was more marked in patients with mesangial cell proliferation (MP) than those without it (fall in Clcr 7.2 ± 6.3% for MP vs 17.1 ± 12.3% for no MP; n=6; p<0.05). The results suggest that captopril apparently had a renoprotective effect on the orthostatic acute fall in Clcr in patients with CGN, especially those with MP.
Comparative Assessment of the Effect of Lomefloxacin, Ciprofloxacin, and Placebo on Cerebral Blood Flow, and Glucose and Oxygen Metabolism in Healthy Subjects by Positron Emission Tomography
Authors: Bednarczyk Edward M. , Green Jeffrey A. , Nelson A. Dennis , Leisure Gregory P. , Little Dana , Adler Lee P. , Berridge Marc S. , Panacek Edward A. , Miraldi Floro D.
Published: October 2023

The mechanism by which the fluorinated quinolones produce central nervous system (CNS) effects is currently unknown. We measured the effect of lomefloxacin on cerebral blood flow and metabolism using positron emission tomography. Eighteen healthy, nonsmoking volunteers were randomized to receive lomefloxacin 400 mg, ciprofloxacin 750 mg, or placebo given in a single‐blind fashion every 12 hours for 72 hours, the time window for maximum lomefloxacin CNS effects. Subjects receiving lomefloxacin had a mean (± SEM) cerebral blood flow (CBF) of 46 (2.9) ml/min/100 g, glucose metabolism (FDG) 4.7 (0.4) mg/min/100 g, oxygen metabolism (OM) 3.3 (0.3) ml/min/100 g, and oxygen extraction (%OM) 0.4 (0.04). Posttreatment values were 43 (3.6) ml/min/100 g, 4.2 (0.4) mg/min/100 g, 2.6 (0.3) ml/min/100 g, and 0.4 (0.03), respectively. Values for subjects receiving ciprofloxacin were CBF 44.8 (1.6) ml/min/100 g, FDG 4.9 (0.7) mg/min/100 g, OM 4.1 (0.4) ml/min/100 g, and %OM 0.6 (0.03) at baseline, and 40.3 (3.5), 4.5 (0.6), 3.4 (0.4), and 0.5 (0.09), respectively, after treatment. For placebo‐treated subjects, baseline values were CBF 41.4 (1.9) ml/min/100 g, FDG 4.9 (0.5) mg/min/100 g, OM 3.3 (0.4) ml/min/100 g, and %OM 0.5 (0.07), and respective posttreatment values were 42.1 (2.3), 5.0 (0.6), 3.5 (0.3), and 0.5 (0.02). No effect was observed on visual (qualitative), blinded reading of the scans. No significant effect on cerebral blood flow or metabolism was detected. We conclude that short‐term administration of lomefloxacin or ciprofloxacin to healthy volunteers does not have a significant effect on cerebral blood flow, or on oxygen or glucose metabolism. Trends toward decreased metabolism in the quinolone‐treated subjects are consistent with findings from other published trials, although their significance is unclear.
In Vivo and In Vitro β2‐Adrenergic Receptor Responsiveness in Young and Elderly Asthmatics
Authors: Hamelin Bettina A. , Blouin Robert A. , Wolf Karen M. , Clifton G. Dennis , Chandler Mary H. H.
Published: October 2023

This pilot study was undertaken to characterize age‐related alterations in airway and metabolic β2‐adrenergic receptor response using terbutaline as a probe. A single dose of terbutaline 0.007 mg/kg was administered subcutaneously to 10 young (range 20–35 yrs) and 10 elderly (range 60–73 yrs) men and women with asthma. β‐Receptor function was assessed by serial pulmonary function tests, heart rate, blood pressure, plasma potassium, glucose, insulin, and catecholamine levels, and in vitro 3′, 5′‐cyclic adenosine monophosphate (cAMP) production of pure T lymphocytes. The trend was for lung β2‐receptor response (bronchodilation) and T lymphocyte cAMP production to be lower in elderly than in young asthmatics, but differences did not reach statistical significance. Elderly subjects' β1‐adrenergic receptor responsiveness (systolic blood pressure) was also dampened. These data suggest that T lymphocyte stimulation does reflect pulmonary β2‐receptor response. Whether elderly asthmatics require and tolerate higher dosages of parenteral terbutaline than younger asthmatics deserves further study.
Clinical Implications of Antibiotic Resistance
Authors: Quinn John P.
Published: October 2023

Great advances have been made in the last two decades in understanding mechanisms of antibiotic resistance among pathogenic bacteria.1 From the clinician's perspective, the value of this scientific information at the bedside is not always obvious. Its importance can be emphasized by exploring two separate avenues: anecdotal reports illustrating the clinical cases in which one often sees resistance, and reports to the Centers for Disease Control (CDC) and some relevant findings from the results of a recent multicenter study of Enterobacter bacteremia.
Comparative Pharmacokinetics of Zidovudine in Healthy Volunteers and in Patients With AIDS With and Without Hepatic Disease
Authors: Fletcher Courtney V. , Rhame Frank S. , Beatty Carolyn C. , Simpson Margaret , Balfour Henry H.
Published: October 2023

To understand whether disease caused by the human immunodeficiency virus (HIV) affects zidovudine disposition, we compared the drug's pharmacokinetics in six healthy volunteers; six persons with the acquired immunodeficiency syndrome (AIDS) and no evidence of gastrointestinal (nausea, vomiting, diarrhea), renal (elevated blood urea nitrogen, serum creatinine), or hepatic (elevated liver function tests) disease; and three patients with AIDS and hepatic disease. After a single oral dose of zidovudine, serial blood samples were analyzed for drug concentration by radioimmunoassay. A one‐compartment oral absorption model was fit to the concentration‐time data. The absorption rate constant (4.05 vs 2.11 hr−1) and time to maximum concentration (0.61 vs 1.03 hr) were significantly different in healthy volunteers versus patients with AIDS without hepatic disease. Differences in half‐life, oral clearance, and area under the curve were not statistically significant. In the three patients with AIDS plus hepatic disease, clearance was reduced an average of 63%, and area under the curve was increased by a factor of 2.3. These comparative pharmacokinetic data do not support profound differences between zidovudine's disposition in healthy volunteers and individuals with AIDS; however, the differences and trends that were observed may represent an effect of HIV disease. Although the presence of hepatic disease clearly indicates a need to modify individual dosages, these pharmacokinetic data may have more generalized implications for zidovudine dosing as the relationships between drug concentration and therapeutic or toxic effects are clarified.
Comparison of Frequencies of Suicidal Tendencies Among Patients Receiving Fluoxetine, Lofepramine, Mianserin, or Trazodone
Authors: Jick Hershel , Ulcickas Marianne , Dean Alan
Published: October 2023

To evaluate whether fluoxetine causes an important increased risk of suicidal behavior, we compared the frequency of attempted suicide, suicidal ideation, and aggressive behavior in persons who received fluoxetine, lofepramine, mianserin, and trazodone, based on information available on general practitioners' computers provided by Value Added Medical Products, Ltd. The frequency of these events was higher in fluoxetine users in the year prior to first treatment than in users of the other three antidepressants. The frequency of these events in the 90 days after the study drug was started was similar for the users of all four drugs. These data indicate that fluoxetine does not directly cause suicidal behavior at a substantially higher frequency than do lofepramine, mianserin, and trazodone.
Single‐Agent versus Combination Antibiotic Therapy in the Management of Intraabdominal Infections
Authors: DiPiro Joseph T. , Cué Jorge I.
Published: October 2023

For the treatment of intraabdominal infection, single‐agent antimicrobial regimens such as β‐lactams with good antianaerobic activity are frequent alternatives to combination regimens such as aminoglycosides or aztreonam plus an antianaerobic agent such as clindamycin or metronidazole. The major issues in selecting a regimen are relative efficacy, potential for adverse drug effects, and cost. Single agents are clearly equivalent to combinations in preventing infectious complications after penetrating abdominal trauma and in treating established intraabdominal infections of mild to moderate severity or in relatively low‐risk patients. A few trials demonstrated their equivalency in patients at high risk of mortality, although experience is limited. Single‐agent regimens may reduce the risks of adverse drug effects compared with combination regimens, but they are not always less expensive.
Comparison of Specialized and Standard Enteral Formulas in Trauma Patients
Authors: Brown Rex O. , Hunt Heather , Mowatt‐Larssen Christine A. , Wojtysiak Stacey L. , Henningfield Mary F. , Kudsk Kenneth A.
Published: October 2023

Study Objective. To compare selected nutrition and immunologic markers and infection in trauma patients receiving a specialized enteral formula with those receiving standard enteral therapy.

Design. Prospective, randomized clinical trial.

Setting. Level 1 trauma center at a county government hospital.

Patients. Forty‐one consecutive patients with major trauma who required enteral nutrition support. Thirty‐seven patients completed the study. Four patients (two in each group) were excluded, as additional operative procedures prevented initiation of enteral feedings within 7 days of injury.

Interventions. Nineteen patients fed the specialized enteral formula received supplemental arginine, linolenic acid, β‐carotene, and hydrolyzed protein for up to 10 days. Eighteen control patients received standard enteral nutrition.

Measurements and Main Results. After study entry, patients who received the specialized enteral formula had fewer infections than those receiving standard enteral nutrition (3/19 vs 10/18; p<0.05). The change in nitrogen balance was significantly better (p<0.05) from day 1 (−11.8 ± 1.8 g/day) to day 5 (−5.9 ± 2.0 g/day) for the group who received the specialized formula compared with the group who received standard enteral nutrition (‐7.3 ± 1.7 g/day to −7.4 ± 2.8 g/day). Similarly, the change in C‐reactive protein serum concentration was significantly better (p<0.05) from day 1 (18.0 ± 2.1 mg/dl) to day 5 (11.8 ± 1.5 mg/dl) in the group who received the specialized formula compared with the group who received standard enteral nutrition (17.6 ± 1.2 mg/dl to 14.4 ± 1.7 mg/dl). The CD4:CD8 ratio increased more in the group who received the specialized formula, although this difference did not reach statistical significance.

Conclusion. Trauma patients who received the specialized enteral formula demonstrated a decreased incidence of infection and increased improvements in nitrogen balance and other indexes of stress. Additional clinical trials demonstrating positive patient outcomes are necessary before these specialized enteral formulas are used as the standard of practice in critically ill patients.
A Pilot Project to Assess the Association of Anticholinergic Symptoms With Anticholinergic Serum Levels in the Elderly
Authors: Remillard Alfred J.
Published: October 2023

Study Objective. To evaluate whether serum anticholinergic drug activity would be a useful clinical tool in helping to predict anticholinergic toxicity.

Design. A prospective study that included a retrospective chart review.

Setting. Two nursing home facilities.

Subjects. Thirty‐one elderly volunteers between ages 69 and 98 years.

Intervention. Each subject completed a two‐part interview. First, anticholinergic symptoms were evaluated and then cognitive function was assessed by three neuropsychiatric tests. Blood (10 ml) was collected to measure anticholinergic activity.

Measurements and Main Results. Eight subjects had detectable serum anticholinergic activity and scored higher on the Symbol Digit Modalities test than those with no detectable activity. No statistical difference was seen between the groups with respect to symptoms or results of the Mini‐Mental and Auditory‐Verbal Learning tests.

Conclusion. The clinical usefulness of serum anticholinergic activity as a predictor for anticholinergic toxicity was not established under the experimental design of this study.
A “Miniacrosome” Sperm Defect Causing Infertility in Two Brothers
Authors: BACCETTI BACCIO , BURRINI ANNA G. , COLLODEL GIULIA , PIOMBONI PAOLA , RENIERI TOMMASO
Published: October 2023

ABSTRACT: A sperm defect causing infertility in two brothers is described. The malformation, named the “miniacrosome sperm defect,” occurs in the total sperm population. It involves both the nuclei, which have a roundish apex, and the acrosomes, which are small, located in an apical position on the top of the nucleus, and sometimes ring‐shaped. The midpiece and tail segments are normal, and the sperm are perfectly motile but fail to fertilize zona‐free hamster ova in vitro. In spermatids, the absence of a microtubular manchette and reduction of the Golgi complex are evident.
Relationship Between Sperm Motility Assessed with the Hamilton‐Thorn Motility Analyzer and Fertilization Rates In Vitro
Authors: LIU DE YI , CLARKE GARY N. , BAKER H. W. GORDON
Published: October 2023

ABSTRACT: To determine which sperm movement characteristics are related to in vitro fertilization rates, semen and swim‐up preparations used for in vitro fertilization in 108 patients were assessed using the Hamilton‐Thorn HTM‐2030 Motility Analyzer (HTMA) and other sperm tests. There were highly significant correlations between manual and HTMA results for sperm concentration (Spearman r = 0.881; P < 0.001) and the percentage of motile spermatozoa (Spearman r = 0.580; P < 0.001). The percentage of motile spermatozoa with average path velocities greater than 10 μ/s and greater than 20 μ/s, straight line and curvilinear velocity, linearity (straight line velocity vs curvilinear velocity), amplitude of lateral head displacement, and beat‐cross frequency were significantly higher in the insemination medium after selection of motile spermatozoa by the swim‐up technique than in the semen. Linearity (P < 0.01), the percentage of morphologically normal spermatozoa (P < 0.05) and straight line velocity (P < 0.05) in semen, and the percentage of motile spermatozoa with average path velocities greater than 10 μ/s in both semen (P < 0.05) and insemination medium (P < 0.05) were significantly correlated with in vitro fertilization rate when examined by a nonparametric (Spearman) test. With logistic regression analysis of all data, only the diagnoses of male infertility and tubal disease, linearity in semen, and the percentage of motile spermatozoa with average path velocities between 10 and 20 μ/s in insemination medium were significantly related to in vitro fertilization rates. All other variables were not significant. In patients with poor sperm morphology (normal < 30%), only linearity in semen and the proportion of spermatozoa with normal intact acrosomes in the insemination medium were significantly related to in vitro fertilization rates. In conclusion, objective measurement of the motility characteristics by HTMA may provide useful information for predicting in vitro fertilization rates that can be used in addition to that derived from assessment of sperm morphology and acrosomes.
4‐MAPC, a 5α‐Reductase Inhibitor, Reduces Rat Ventral Prostate Weight, DNA, and Prostatein Concentrations
Authors: GHUSN HUSAM F. , SHAO TSANG C. , KLIMA MARCELLA , CUNNINGHAM GLENN R.
Published: October 2023

ABSTRACT: Several compounds, such as 4‐MAPC (4‐methyl‐3‐oxo‐4‐aza‐5α‐pregnane‐20‐carboxylate), that inhibit conversion of testosterone (T) to dihydrotestosterone (DHT) by 5α‐reductase have been demonstrated to reduce prostate size in rats and dogs. The current studies were undertaken to determine if this effect is due to a reduction in cell number, in epithelial cell synthetic activity, or both. Eight‐week‐old intact rats were treated daily for 14 days with sesame seed oil, 4‐MAPC (10 mg/kg), 4‐MAPC + testosterone propionate (TP, 1 mg/kg), or 4‐MAPC + TP (3 mg/kg). Rats were killed 24 hours after the last injection. In the animals treated only with 4‐MAPC, ventral prostate weight was reduced 37%, but the 14% reduction in total DNA was not significant. The mean intraprostatic concentration of prostatein, a major secretory protein, was reduced 45% (P < 0.05). The 3 mg/kg dose of TP increased ventral prostate weight, prostatein concentrations, and acid phosphatase activity, even though DNA/ventral prostate was similar to that in control animals. These observations indicate that the reduction in ventral prostate weight in adult rats is due in part to a reduction in cell number, but the primary effect was due to a reduction in synthetic activity, and possibly atrophy of the epithelial cells. Furthermore, TP in pharmacologic doses increased ventral prostate weight and synthetic activity without increasing DNA.