bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of environmental, social, and governance disclosure: A systematic literature review
Authors: Seow Richard Yeaw Chong
Published: October 2023

The popularity of environmental, social, and governance (ESG) investing or socially responsible investing is pushing private sectors to improve their ESG performance. Stakeholders, namely, investors, are relying on firms' environmental, social, and governance disclosures (ESGD) to evaluate their ESG performance and strategize their investment decision‐making. Since firms have substantial discretionary power in deciding the quantity and quality of ESGD, understanding the drivers and motivations of ESGD is paramount. This study examines the literature on the determinants of ESGD, and 36 articles published in a period spanning from 2006 to 2022 were analyzed and synthesized via a systematic literature review approach. Ninety‐one researchers from 30 countries contributed to these studies. Of these studies, 28% perform cross‐country investigations. This study found that although there is no single underpinning theory for ESGD, ESGD determinant studies are well supported by multiple theoretical frameworks, such as stakeholder theory, legitimacy theory, and institutional theory. This study reveals many factors that have an impact on ESGD, such as natural disasters, political and legal systems, ownership structure, board characteristics, and the CEO's characteristics. This study contributed to the burgeon of literature on ESG by offering valuable insights into the antecedents to ESG performance and facilitating future enhancements of a better ESGD framework. Lastly, this study also reveals future research directions for scholars to enrich the burgeoning literature in ESG.
Panax quinquefolium saponins attenuates microglia activation following acute cerebral ischemia‐reperfusion injury via Nrf2/miR‐103‐3p/TANK pathway
Authors: Bai Xuesong , Qiu Yan , Wang Jian , Dong Yafen , Zhang Tao , Jin Hui
Published: October 2023

Ischemic stroke is one of the leading causes of death and disability among adults worldwide. Intravenous thrombolysis is the only approved pharmacological treatment for acute ischemic stroke. However, reperfusion by thrombolysis will lead to the rapid activation of microglia cells which induces interferon‐inflammatory response in the ischemic brain tissues. Panax quinquefolium saponins (PQS) has been proven to be effective in acute ischemic stroke, but there is no unified understanding about its specific mechanism. Here, we will report for the first time that PQS can significantly inhibit the activation of microglia cells in cerebral of MCAO rats via activation of Nrf2/miR‐103‐3p/TANK axis. Our results showed that PQS can directly bind to Nrf2 protein and inhibit its ubiquitination, which result in the indirectly enhancing the expression of TANK protein via transcriptional regulation on miR‐103‐3p, and finally to suppress the nuclear factor kappa‐B dominated rapid activation of microglial cells induced by oxygen–glucose deprivation/reoxygenation  vitro and cerebral ischemia‐reperfusion injury in vivo. In conclusion, our study not only revealed the new mechanism of PQS in protecting against the inflammatory activation of microglia cells caused by cerebral ischemia‐reperfusion injury, but also suggested that Nrf2 is a potential target for development of new drugs of ischemic stroke. More importantly, our study also reminded that miR‐103‐3p might be used as a prognostic biomarker for patients with ischemic stroke.
Routine postaccess‐closure angiography to detect vascular complications following transfemoral TAVR
Authors: Savvoulidis Panagiotis , Nadir Adnan M. , Mechery Anthony , Lawton Ewa , Khan Kumail , Maqableh Ghaith M. , Raja Waseem , Wong Chun Wai , Radhakrishnan Ashwin , Doshi Sagar N.
Published: October 2023

Background

Vascular complications following transfemoral TAVR are associated with increased morbidity and mortality. Measures that may mitigate this risk are important.

Aim

To evaluate the utility of routine, access‐vessel angiography post sheath‐removal in the detection and management of complications in patients undergoing transcatheter aortic valve replacement (TAVR).

Methods

This was a retrospective study of 512 consecutive patients who underwent transfemoral TAVR with routine post access‐closure angiography from the radial artery. Rates of mild angiographically evident bleeding, bleeding requiring surgery/interventional‐radiology, ischemia, 90‐day access‐site‐related events, and major and minor vascular complications using Valve Academic Research Consortium 3 definitions were recorded.

Results

Of 512 patients, digital subtraction angiography (DSA) was undertaken via the radial artery in 467 patients (91%). In the remaining patients (9%) DSA was either not attempted, due to concerns regarding kidney disease and contrast volume, or failed due to anatomical factors (aortic tortuosity/calcification). Significant chronic kidney disease was present at baseline in 72.4% of this cohort (stages III–IV or dialysis). Ninety‐four percent of cases underwent TAVR using a balloon‐expandable platform. Mild iliofemoral extravasation was observed in 7.7% of the DSA cases. These cases were managed by manual compression with none requiring any vascular intervention subsequently. Valve Academic Research Consortium 3 major and minor access‐site‐related complications were observed in 0.4% and 12.2%, respectively. Access‐site‐related bleeding and ischemic events requiring interventional‐radiology or vascular‐surgery were observed in 0.9% and 1.7% of the DSA cases, respectively. No new renal replacement therapy was needed in any of the DSA cases. Discharge to 90‐day access‐related complications was 0.8%.

Conclusions

Routine post access‐closure angiography is feasible via the radial artery in patients undergoing transfemoral TAVR and appears safe. It facilitates early identification of complications and mitigates risk by enabling prompt action to be taken. Larger studies are needed to confirm these findings.
Safety and efficacy of catheter ablation of para‐Hisian accessory pathway via a direct superior vena cava approach: A multicenter study
Authors: Chai Chanjuan , Sun Qi , Guo Xiao‐Gang , Yang Jian‐Du , Xie Hai‐Yang , Ma Jian , Wei Hui‐Qiang , Yu Jie
Published: October 2023

Background

Radiofrequency (RF) catheter ablation of para‐Hisian accessory pathways (APs) can be challenging due to proximity to the conduction system.

Methods

A total of 30 consecutive patients with para‐Hisian AP were enrolled for ablation in three centers, 12 (40%) of whom had previously failed attempted ablation from the inferior vena cava (IVC) approach. Ablation was preferentially performed using a superior approach from the superior vena cava (SVC) in all patients.

Results

The para‐Hisian AP was eliminated from the SVC approach in 28 of 30 (93.3%) patients. In the remaining two patients, additional ablation from IVC was required to successfully eliminate the AP. There were two patients experienced reversible complete atrial‐ventricular block and PR prolongation during the first RF application. Long‐term freedom from recurrent arrhythmia was achieved in 29 (96.7%) patients over a mean follow‐up duration of 15.6 ± 4.6 months.

Conclusion

Catheter ablation of para‐Hisian AP from above using a direct SVC approach is both safe and effective, and should be considered especially in patients who have failed conventional ablation attempts from IVC approach.
A machine learning model to predict the need for conversion of operative approach in patients undergoing colectomy for neoplasm
Authors: Guidolin Keegan , Ng Deanna , Zorigtbaatar Anudari , Chadi Sami , Quereshy Fayez
Published: October 2023

Background

Studies comparing conversion from laparoscopic to open approaches to colectomy have found an association between conversion and morbidity, mortality, and length of stay, suggesting that certain patients may benefit from an open approach “up‐front.”

Aim

The objective of this study was to use machine learning algorithms to develop a model enabling the prediction of which patients are likely to require conversion.

Methods and Results

We used ACS NSQIP data to identify patients undergoing colectomy (2014‐2019). We included patients undergoing elective colectomy for colorectal neoplasm via a minimally invasive approach or a converted approach. The outcome of interest was conversion. Variables were included in the model based on their correlation with conversion by logistic regression (p < .05). Two models were used: weighted logistic regression with regularization, and Random Forest classifier. The data was randomly split into training (70%) and test (30%) cohorts, and prediction performance was calculated. 24 327 cases were included (17 028 training, 7299 test). When applied to the test cohort, the models had an accuracy of 0.675 (range 0.65–0.70) in predicting conversion; c‐index ranged from 0.62–0.63. This machine learning model achieved a moderate area under the curve and a high negative predictive value, but a low positive predictive value; therefore, this model can predict (with 95% accuracy) whether a colectomy for neoplasm can be successfully completed using a minimally invasive approach.

Conclusion

This model can be used to reassure surgeons of the appropriateness of a minimally invasive approach when planning for an elective colectomy.
Downregulation of Rab23 inhibits hepatocellular carcinoma by repressing SHH signaling pathway
Authors: Liu Si‐Jia , Zang Yu‐Wei , Huang Cui‐Jun , Liu Yun‐Jian
Published: October 2023

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumors and the third leading cause of cancer‐related death worldwide. As an oncogene, Rab23 has been shown to be significantly related to the growth and migration of hepatocellular carcinoma in both in vitro and in vivo studies, but its underlying mechanism remains obscure. In the present study, we examined the effect of inhibiting Rab23 expression on the pathological progression of HCC. The correlation between liver Rab23 gene expression and survival probability in human HCC patients was analyzed using the TCGA database and CPTAC database. Rab23 knockdown hepatocellular carcinoma cell line was generated through lentiviral transduction, then we established a nude HCC xenograft model by subcutaneously implanting the transfected cells. The analysis of gene and protein expression was carried out using Western blot or RT‐qPCR, respectively. Flow cytometry analysis was used to detect the level of apoptosis. The expression levels of key proteins involved in the Sonic Hedgehog (SHH) signaling pathway were assessed. The results showed that HCC patients with low levels of hepatic Rab23 mRNA and protein had a better survival tendency than those with higher levels of Rab23. Cell proliferations were reduced and apoptosis levels were increased after Knocking down Rab23 in HCC cell lines. Furthermore, in vivo studies have demonstrated that suppression of the Rab23 gene results in decreased tumor size, proliferation rate, and reduced levels of SHH‐related proteins Smoothened and GLI‐1. The above results suggest that Rab23 is involved in the pathological progression of HCC as an important regulator of the SHH signaling pathway, which also provides an important research basis for new therapeutic strategies for HCC.
Supreme Court decision will impact religious accommodations requests
Authors: Porter Michael
Published: October 2023

The last few days of the U.S. Supreme Court term usually include headliner cases, and this year was no different with the affirmative action admissions cases and the Court's decision permitting a web‐designer to limit wedding services based on religious beliefs. Relatively speaking, the Court's decision on a different religious accommodations case, Groff v. DeJoy, Postmaster General, S. Ct. Case 22‐174, June 29, 2023, flew under the radar. But the Court's ruling on this case will have a significant impact on the way institutions respond to requests for religious accommodations from employees and may also bring students’ religious accommodations issues to light.
A multisource data‐driven approach for carbon footprint analysis of remanufacturing systems
Authors: Yan Wei , He Xue , Zhang Hua
Published: October 2023

The remanufacturing industry is experiencing significant growth, resulting in a substantial increase in its carbon footprint. Unfortunately, this issue is not receiving adequate attention at present. Moreover, existing methods for analyzing carbon footprints in remanufacturing systems are inefficient and inaccurate due to the complex relationship between carbon emissions and the dynamic nature of the systems. In this paper, we propose a multisource data‐driven approach for carbon footprint analysis of remanufacturing systems. First, we examine the relationship between carbon emissions and the uncertainty surrounding end‐of‐life (EOL) product components, as well as the corresponding resource recovery strategies, such as reuse, recycle, and remanufacture. This analysis allows us to define the carbon footprint boundary of remanufacturing systems. Next, we establish a carbon footprint model for recycling strategies using recycling data. Additionally, we propose a carbon footprint model for remanufacture strategies by utilizing the back propagation neural network based on particle swarm optimization algorithm and data from the materials flow, energy flow, and waste flow of these strategies. By combining these models, we can accurately calculate the carbon footprint of remanufacturing systems. To demonstrate the effectiveness of our approach, we present a case study on the remanufacturing of an EOL automobile engine. This case study showcases how our methodology can be utilized as a valuable tool for analyzing carbon footprints and identifying strategies to reduce carbon emissions in remanufacturing systems.
Securing AI‐based healthcare systems using blockchain technology: A state‐of‐the‐art systematic literature review and future research directions
Authors: Shinde Rucha , Patil Shruti , Kotecha Ketan , Potdar Vidyasagar , Selvachandran Ganeshsree , Abraham Ajith
Published: October 2023

Healthcare institutions are progressively integrating artificial intelligence (AI) into their operations. The extraordinary potential of AI is restricted by insufficient medical data for AI model training and adversarial attacks wherein attackers perturb the dataset by adding some noise to it, which leads to the malfunctioning of the AI models, and a lack of trust caused by the opaque operational approach it employs. This Systematic Literature Review (SLR) is a state‐of‐the‐art survey of the research on blockchain technology for securing AI‐integrated healthcare applications. The most relevant articles from the Scopus and Web of Science (WoS) databases were identified using the PRISMA model. Most of the existing literature is about protecting the healthcare data used by AI‐based healthcare systems using blockchain technology, but the modality of data (text, images, audio, and sound) was not specifically mentioned. Information on protecting the training phase and model deployment for AI‐based healthcare systems considering the variations in feature extraction based on the modality of data was also not clearly specified. Hence, the three subfields of AI, namely, natural language processing (NLP), computer vision, and acoustic AI are further studied to identify security loopholes in its implementation pipeline. The three phases, namely the dataset, the training phase, and the trained models need to be protected from adversaries to avoid malfunctioning of the deployed AI models. The nature of the data processed by NLP, computer vision, and acoustic AI, underlying deep neural network (DNN) architectures, the complexity of attacks, and the perceivability of attacks by humans are analyzed to identify the need for security. A blockchain solution for AI‐based healthcare systems is synthesized based on the findings that have demonstrated the distinctive technological features of blockchains. It offers a solution for the privacy and security issues encountered by NLP, computer vision, and acoustic AI to boost the widespread adoption of AI applications in healthcare.
Flame‐retardant composite derived from polyurethane/wood‐fiber
Authors: Wang Xuanye , Wang Beibei , Sun Jingmeng , Yu Lei , Yang Guochao , Guo Hongwu
Published: October 2023

Wood–plastic composites (WPCs) are facing fire hazard when they are used in construction and furniture and need to be treated with fire protection. In this work, polyurethane (PU) was applied to derive simultaneously flame‐retardancy‐improved and mechanically strengthened wood‐polyurethane composites (WPUCs). It was constructed with ammonium polyphosphate (APP) and PU by a simple way. The results showed that a decrease in smoke production in the Cone Calorimeter Test was measured. When the mass of APP is 18% of PU, limiting oxygen index can reach 31.2%. In the combustion test, the peak of heat release rate and total smoke production for WPUCs were, respectively, decreased by 42.1% and 89.7% in the presence of the above ratio of APP and PU. In addition, the results of the functional group test show that PU contains highly reactive ‐NCO which is bonded to the ‐OH and moisture in the wood fiber, resulting in improvement of physical and mechanical properties. The mechanism for the flame retardancy of WPUCs revealed that polyphosphoric acid produced by APP pyrolysis catalyzed PU into the char, and PU was arched by the resulting gases such as NH3 to form the tiny spherical structure, which worked in blocking heat and the exchange of substances. WPUCs with APP prepared by this method are shown to have improved results, and, therefore, it is expected to provide a new strategy for the preparation of flame‐retardant WPCs.
Cost‐Consequence Models for Varicella‐Zoster Virus Infections
Authors: Paul John E. , Mauskopf Josephine A. , Bell Larry
Published: October 2023

Three cost‐consequence models were developed for treatment of infections due to varicella‐zoster virus (VZV) with acyclovir in immunocompetent patients—adult‐ and childhood‐onset chickenpox, and herpes zoster (shingles) in adults. For chickenpox, separate models allow examination of differences in severity and impact of the disease for children and adults, as well as in the management of civilians and adults in military service. Each model includes direct medical costs, indirect costs and health‐related productivity loss, symptom and quality of life impact, and model assumptions and conclusions. Alternatives of treatment and no treatment are addressed. Quality of life impact is conceptualized in terms of a quality‐adjusted life‐days decrement due to VZV symptoms of importance to the patient, such as pain, rash, and itching. As experience and data become available, alternative agents such as valacyclovir and famciclovir for the treatment of patients with herpes zoster should be included in the modeling process.
Pharmacokinetic Evaluation of Thiacetazone
Authors: Peloquin Charles A. , Nitta Annette T. , Berning Shaun E. , Iseman Michael D. , James Gordon T.
Published: October 2023

Study Objective. To investigate the steady‐state pharmacokinetics of thiacetazone (TB‐1), which is active in vitro against Mycobacterium avium complex (MAC).

Design. Open‐label phase I study.

Setting. Specialized referral hospital.

Patients. Twelve healthy men and women.

Interventions. Oral TB‐1 150 mg/day was administered for 7 days, followed by blood and urine collection over 48 hours.

Measurements and Main Results. The serum concentration versus time curves of TB‐1 showed sustained concentrations, with maximum values of 1.59 ± 0.47 μg/ml, time to maximum 3.30 ± 1.18 hours, and serum half‐life of 15–16 hours. Less than 25% of TB‐1 was recovered unchanged in the urine over 48 hours. Rashes occurred in two subjects at the end of the 7‐day dosing period and resolved without progression or sequelae.

Conclusions. Based on these data, we initiated a phase II study of TB‐1 in patients with pulmonary MAC infection who do not have the acquired immunodeficiency syndrome.
Vancomycin‐Binding Characteristics in Patients with Serious Infections
Authors: Li Li , Miles Michael V. , Lakkis Hassan , Zaritsky Arno L.
Published: October 2023

Study Objective. To examine the extent, variability, and factors affecting vancomycin protein binding.

Design. Prospective, open‐label, cohort study.

Setting. A general hospital.

Patients. Forty‐four adults [mean (± SD) age 50.9 ± 17.1 yrs, range 16.8–92.0 yrs] with serious infections.

Interventions. Unbound (Vu) and total (Vtot) vancomycin concentrations were determined by fluorescence polarization immunoassay. A statistical analysis model used the maximum likelihood method to evaluate the association between several important variables and log Vu while controlling for log Vtot effects.

Measurements and Main Results. The mean fraction percentage of unbound vancomycin was 79.5 ± 6.0% (range 53.0–96.3%). While controlling for Vtot the total variability of Vu was 8.3%, suggesting that vancomycin binding is relatively constant in sick adults. We were able to demonstrate a significant statistical interaction effect between gender and globulin protein concentration on Vu (p = 0.022). Globulin protein concentration in men was negatively associated with Vu (p = 0.0009), but there was no association in women (p = 0.645). Age, race, peak‐trough association, serum creatinine, serum albumin, serum prealbumin, and hemodialysis were not significantly associated with log Vu in the statistical model.

Conclusion. Compared with earlier studies in healthy adults, vancomycin binding appears to be decreased during acute illness, and intrapatient and interpatient variability are relatively small. Unbound vancomycin concentration appears to be gender dependent.
Comparison of Publication Rates for Basic Sciences versus Practice from Pharmacy‐Based Grant Programs
Authors: Ateshkadi Arasb , Munger Mark A.
Published: October 2023

The future of a profession in an era of scarce resources depends on maintaining a focus on science. The times demand that pharmacy practice examine its commitment to science. To address this concern, pharmacy practice‐based research awards from the American College of Clinical Pharmacy Research Institute Award Program, American Society of Health‐System Pharmacists Research and Education Foundation Grant Program, and American Association of Colleges of Pharmacy New Investigator Program were compared with basic sciences awards from the American Association Colleges of Pharmacy New Investigator Program from their inception to 1991 to determine the percentage of awarded grants successfully published (publication rate). Pharmacy practice published awarded grants' at 46% (70/154) versus 62% (26/42) for basic sciences (p = 0.09). A significant decline of 37% in pharmacy practice publication rate was observed over the study period. Economically, an average of $11,393 was spent to publish one manuscript in pharmacy practice versus $8077 in basic sciences. The results suggest that pharmacy practice should redefine a paradigm of commitment to scholarship to provide firm evidence for supporting science and sustaining professional growth.
Anticonvulsants and Congenital Malformations
Authors: Jick Susan S. , Terris Barbara Z.
Published: October 2023

Earlier studies indicated that the prevalence of congenital anomalies is greater in infants of epileptic mothers treated with anticonvulsants than in infants of mothers without epilepsy. We carried out a study of women in the General Practice Research Database who delivered liveborn infants between January 1988 and March 1993 and who were exposed to an anticonvulsant drug during the first trimester of pregnancy, and women with epilepsy not treated with anticonvulsants during pregnancy. We matched two nonexposed women without epilepsy to each exposed woman for age at delivery, date of baby's birth, and general practice. Two hundred ninety‐seven women treated for epilepsy had 10 liveborn infants with major anomalies (3.4%) compared with 6 of the 594 nonexposed women (1.0%, RR = 3.3, 95% CI 1.2–9.2). We conclude that the infants of women with epilepsy who are treated with an anticonvulsant during the first trimester of pregnancy have an increased risk of major congenital anomalies.
Pharmacokinetics of Mycophenolate Mofetil and Intravenous Ganciclovir Alone and in Combination in Renal Transplant Recipients
Authors: Wolfe Erika J. , Mathur Vandana , Tomlanovich Stephen , Jung Don , Wong Rodney , Griffy Kay , Aweeka Francesca T.
Published: October 2023

Study Objectives. To evaluate the pharmacokinetics of mycophenolic acid and its glucuronide metabolite alone and in the presence of ganciclovir, and to determine the pharmacokinetics of ganciclovir alone and in combination with mycophenolate mofetil.

Design. Randomized, open‐label, three‐way crossover study.

Patients. Twelve kidney transplant recipients.

Interventions. Mycophenolate mofetil 1500 mg orally and ganciclovir 5 mg/kg intravenously were each given alone and in combination with at least a 1‐week washout period between treatment arms.

Measurements and Main Results. Blood samples were obtained to measure mycophenolic acid and ganciclovir by high‐performance liquid chromatography. Mean (± SD) oral plasma clearance for mycophenolic acid alone and with ganciclovir was 3.11 ± 0.72 and 3.19 ± 0.72 ml/min/kg (p=0.64). The overall disposition of the major metabolite, MPA‐glucuronide, was unchanged, with approximately 70% of the administered dose eliminated as the glucuronide conjugate for both arms of the study. Mean ganciclovir serum clearance was 1.80 ± 0.58 ml/min/kg for ganciclovir and 1.70 ± 0.55 ml/min/kg for ganciclovir plus mycophenolate mofetil (p=0.11; 10 patients). Renal clearance of ganciclovir was decreased when the drugs were administered in combination, 1.43 ± 0.54 (ganciclovir) and 1.26 ± 0.44 (both drugs) ml/min/kg (p=0.02; 10 patients).

Conclusion. The single‐dose pharmacokinetics of mycophenolic acid and its glucuronide metabolite were unchanged by the addition of ganciclovir. Total serum clearance of ganciclovir was unchanged by the addition of mycophenolate mofetil, however, renal clearance was slightly decreased.
QT Prolongation and Development of Torsades de Pointes with the Concomitant Administration of Oral Erythromycin Base and Quinidine
Authors: Lin Jennifer C. , Quasny Holly A.
Published: October 2023

Torsades de pointes is a polymorphic ventricular tachycardia characterized by marked QT prolongation on the electrocardiogram. It can be induced by both antiarrhythmic and nonantiarrhythmic drugs, such as quinidine and erythromycin. No extensive literature documents an interaction between quinidine and erythromycin when the agents are administered orally. A 95‐year‐old man received oral quinidine and erythromycin for the treatment of atrial fibrillation and community‐acquired pneumonia. He developed torsades de pointes and subsequently cardiac arrest. Since erythromycin and quinidine are known to cause arrhythmias individually, caution and close monitoring are necessary when the drugs are administered concomitantly.
A Pharmacist‐Initiated Program of Intravenous to Oral Antibiotic Conversion
Authors: Przybylski Kevin G. , Rybak Michael J. , Martin Patricia R. , Weingarten Cindy M. , Zaran Frank K. , Stevenson James G. , Levine Donald P
Published: October 2023

A prospective program to convert patients from parenteral to oral antibiotics was evaluated over 12 months to determine its pharmacoeconomic impact on antibiotic acquisition and length of hospital stay. Physicians of patients meeting predetermined clinical criteria for mild and moderate infections were contacted to discuss potential oral alternative therapy. Clinical end points and economic data were followed in 242 patients (200 converted and 42 not converted but meeting criteria). No significant differences were noted between the groups with regard to demographic data, infection diagnosis, clinical outcome, or adverse effects. The average number of days of therapy for patients converted was 1.53 days shorter than that of patients who were not converted to oral therapy (p<0.003). Cost savings for drug acquisition and length of stay were $15,149.24 and $161,071.88, respectively. The intervention program appeared to provide a cost‐effective conversion from parenteral to oral antimicrobial administration without compromising patient care. It is anticipated that expansion of the program to include additional antibiotics will result in even greater cost savings for the institution.
Methazolamide‐Induced Delirium
Authors: Cyr Monica , Laizure S. Casey , daCunha Carl M.
Published: October 2023

A 74‐year‐old man became delirious 2 days after beginning oral therapy with methazolamide. The delirium was manifested by intermittent psychosis, incontinence of bowel and bladder, lethargy, and disorientation. These symptoms continued for 25 days despite many changes in his drug regimen, and complete laboratory, urologic, and neurologic work‐ups. The symptoms resolved completely within 1 week of discontinuing methazolamide. This is the first case reported of delirium associated with methazolamide not accompanied by a metabolic imbalance.
Meropenem, a New Carbapenem Antibiotic
Authors: Fish Douglas N. , Singletary Tony J.
Published: October 2023

Meropenem is the second carbapenem antibiotic available in the United States. It has a broad spectrum of activity that includes moderate activity against gram‐positive bacteria and excellent gram‐negative aerobic and anaerobic activity. Meropenem has enhanced gram‐negative activity relative to imipenem‐cilastatin and often retains activity against strains resistant to third‐generation cephalosporins and imipenem‐cilastatin. The drug penetrates well into most body fluids and tissues, including cerebrospinal fluid. It is also stable against renal dehydropeptidase hydrolysis and does not require coadministration of a dehydropeptidase inhibitor. Meropenem showed excellent efficacy in clinical studies involving seriously ill patients with intraabdominal, central nervous system, lower respiratory tract, skin and soft tissue, urinary tract, and febrile neutropenic infections. It appears well tolerated and, relative to imipenem‐cilastatin, may have reduced potential for causing seizures and other central nervous system toxicities. Although it has many favorable qualities and some potential advantages relative to other broad‐spectrum agents, additional trials and clinical experience are necessary to define its optimal place in clinical practice.
Advances in the Treatment and Prophylaxis ofPneumocystis cariniiPneumonia
Authors: Warren Eric , George Sarah , You Joyce , Kazanjian Powel
Published: October 2023

Pneumocystis cariniipneumonia (PCP) is the most common illness associated with the acquired immunodeficiency syndrome (AIDS) in the United States and also occurs in immunocompromised persons not infected with the human immunodeficiency virus. Several advances have taken place in the treatment and prophylaxis of PCP, with most clinical trials conducted in patients with AIDS. Treatment of choice is trimethoprim‐sulfamethoxazole (TMP‐SMX). Desensitization regimens are available for those who have a fever or rash associated with the agent. Patients with severe PCP who cannot tolerate TMP‐SMX may be treated successfully with pentamidine or trimetrexate. Those with mild to moderate disease may receive dapsone‐trimethoprim, clindamycin‐primaquine, or atovaquone if they cannot take TMP‐SMX. Adjunctive therapy with corticosteroids improves the outcome in patients with AIDS and severe PCP. (Pharmacotherapy 1997;17(5):900–916)
Identification, Diagnosis, and Treatment of Acid‐Related Diseases in the Elderly: Implications for Long‐Term Care
Authors: Garnett William R. , Garabedian‐Ruffalo Susan M.
Published: October 2023

Acid‐related disorders such as peptic ulcer disease and gastroesophageal reflux disease occur frequently in the elderly and are associated with a high frequency of morbidity and mortality. The proton pump inhibitors lansoprazole and omeprazole produce faster rates of healing and greater symptomatic relief in patients with acid‐related disorders than histamine2‐receptor antagonists, are well tolerated, and are associated with few adverse events. Compared with omeprazole, which interacts with diazepam, warfarin, and phenytoin, lansoprazole produces only a minor increase in theophylline clearance. Proton pump inhibitors in combination with antibiotic therapy can eradicate Helicobacter pylori, the main risk factor in the recurrence of peptic ulcer disease, obviating the need for maintenance therapy. Long‐term acid suppression with proton pump inhibitors may be necessary to prevent the recurrence of gastroesophageal reflux disease. The safety and efficacy profile of these agents makes them ideal for the treatment of acid‐related diseases in elderly patients. (Pharmacotherapy 1997;17(5);938–958)
The Effect of Timing of a Standard Meal on the Pharmacokinetics and Pharmacodynamics of the Novel Atypical Antipsychotic Agent Ziprasidone
Authors: Hamelin Bettina A. , Allard Sylvie , Laplante Louis , Miceli Jeffrey , Wilner Keith D. , Tremblay J. , LeBel Marc
Published: October 2023

Study Objective. To evaluate the influence of a high‐fat meal on the pharmacokinetics and pharmacodynamics of the novel atypical antipsychotic drug ziprasidone.

Design. Open, randomized, three‐way crossover study.

Setting. University‐based research facility.

Subjects. Eight healthy male volunteers.

Interventions. Ziprasidone 20 mg was administered under fasting conditions (treatment A), and directly after (treatment B) and 2 hours after (treatment C) a standard high‐fat breakfast.

Measurements and Main Results. Serial blood samples were obtained over 36 hours. Three objective psychometric tests were employed to evaluate daytime vigilance at baseline and 2 hours after each dose. Ziprasidone had a significant effect on area under the curve (AUC0‐∞), maximum serum concentration, and half‐life (analysis of variance all p<0.05), with the mean AUC0‐∞ being significantly greater (627.2 ± 206.4 vs 371.0 ± 126.5 ng • hr/ml, ANOVA with Bonferroni's criteria p<0.016) and half‐life significantly shorter (4.7 ± 0.8 vs 6.6 ± 1.3 hrs, ANOVA with Bonferroni's criteria p<0.016) after treatment B compared with treatment A. Although similar trends were observed after treatment C compared with treatment A, the differences did not reach statistical significance when Bonferroni's correction criteria were applied (p>0.016).

Conclusion. These data suggest an increase in systemic exposure to the highly lipophilic compound ziprasidone when taken after fatty foods, possibly due to improved drug dissolution and solubilization. The drug's longer half‐life under fasting conditions may reflect dissolution‐limited absorption, although this could not be directly assessed. Despite postprandial increases in ziprasidone AUC0‐∞ and maximum concentration, daytime vigilance was not affected.
Intravenous Nitroglycerin Tolerance in Patients with Ischemic Cardiomyopathy and Congestive Heart Failure
Authors: Earl Grace L. , Stanek Eric J. , Spinier Sarah A.
Published: October 2023

A daily nitrate‐free interval (NFI) lasting 4–7 hours was instituted in four patients with severe congestive heart failure secondary to myocardial ischemia who were awaiting orthotopic heart transplantation. The duration of intravenous nitroglycerin therapy ranged from 14–55 days, and the maximum dosage was 50–400 μg/minute. Anginal events occurred more frequently during the NFI than during intravenous therapy. An NFI of 8–12 hours reduces tolerance in patients with congestive heart failure and stable angina. However, the experience in these patients with recurrent ischemia does not support its use to prevent ischemic events during hospitalization.
Conjugated Estrogens for the Management of Gastrointestinal Bleeding Secondary to Uremia of Acute Renal Failure
Authors: Heunisch Carol , Resnick Daniel J. , Vitello Joseph M. , Martin Steven J.
Published: October 2023

Bleeding commonly occurs secondary to the uremia of acute and chronic renal failure. Hemodialysis is indicated for the management of uremic bleeding, and administration of red blood cells and cryoprecipitate is also helpful. Desmopressin successfully reduces the bleeding tendency in patients with chronic renal failure for short‐term operations or procedures, but the frequency of tachyphylaxis is high and limits the drug's usefulness for major bleeds. Conjugated estrogens shorten bleeding times in uremia and may provide a more sustained hemostatic effect over desmopressin. A patient with acute renal failure and uncontrolled gastrointestinal bleeding was successfully treated with conjugated estrogens after failing desmopressin and octreotide therapy.
Localization of Androgen Receptor and Cell‐Specific Cytokeratins in Basal Cells of Rat Ventral Prostate
Authors: SOEFFING WILLIAM J. , TIMMS BARRY G.
Published: October 2023

ABSTRACT: Immunocytochemical techniques labeled androgen receptor and cell‐specific cytokeratins in the basal cells of rat ventral prostate. In addition, nonradioactive in situ hybridization verified the production of androgen receptor transcripts in the basal cells. Androgen receptors and transcripts were localized in the nuclei and cytoplasm of the adult basal cells using these two techniques. Monoclonal anti‐cytokeratin antibodies identified temporal changes in the expression of basal cell‐specific intermediate filaments of fetal, neonatal, normal adult, orchidectomized adult, and testosterone‐treated orchidectomized adult prostates. Labeling intensity of the basal cells was elevated during development when compared to the staining in normal adult tissue. Orchidectomized adults exhibited the greatest intensity of labeling, which decreased after testosterone treatment. The detection of androgen receptor and its transcripts in the basal cells supports the hypothesis that these cells are androgen responsive. The observed change in the anti‐cytokeratin staining patterns of these cells during development, growth, and regression is an indirect measure of androgenic influence. The androgen‐repressed cytokeratin expression in basal cells is similar to that found in prostatic luminal cells.
Hypertensive Changes in Intratesticular Arteries Impair Spermatogenesis of the Stroke‐Prone Spontaneously Hypertensive Rat
Authors: AKAGASHI KEIGO , ITOH NAOKI , KUMAMOTO YOSHIAKI , TSUKAMOTO TAUI , SUZUKI TSUNEYUKI , OHTA YOSHIO
Published: October 2023

ABSTRACT: It is reported that some elderly males exhibit both hyospermatogenesis and intratesticular arterial changes. These arterial changes are thought to contribute to spermatogenic damage. In this study the process of the damage to spermatogenesis induced by such changes was evaluated using stroke‐prone spontaneously hypertensive rats (SHRSP). SHRSP showed a rapid increase of blood pressure, followed by hypertensive vascular changes. At 23 weeks of age, 61.8% of seminiferous tubules were atrophic in SHRSP, simultaneously with the development of hypertensive vascular changes. In addition, the transferrin concentration in the cytosolic fraction of the testicular homogenate was decreased at 23 weeks of age exactly when the severe damage to the spermatogenesis was seen, suggesting that Sertoli cell function in SHRSP regressed at 23 weeks of age. Based on these findings, it was suggested that the decline in the Sertoli cell function caused by the hypertensive vascular changes is part of the mechanism whereby spermatogenic damage occurs in SHRSP.
Use of Peanut Agglutinin to Assess the Acrosomal Status and the Zona Pellucida‐Induced Acrosome Reaction in Stallion Spermatozoa
Authors: CHENG FENG‐PANG , FAZELI ALIREZA , VOORHOUT WIM F. , MARKS ABRAHAM , BEVERS MART M. , COLENBRANDER BEN
Published: October 2023

ABSTRACT:Peanut agglutinin (PNA) was used to assess the sperm acrosomal status and the acrosome reaction during gamete interaction in the equine species. PNA exclusively binds to the outer acrosomal membrane of stallion spermatozoa, as was established by transmission electron microscopy. Fluorescein isothiocyanate‐PNA (FITC‐PNA) labeling was used to monitor sperm acrosomal changes during a prolonged incubation period of 24 hours and during a 2‐hours incubation in the presence of 5 μM calcium ionophore A23187. In addition, after a 4‐hours preincubation in SP‐TALP medium, sperm samples were incubated with matching hemizonae for 1 minute (onset binding), followed by a 60‐minute incubation (1‐hour binding) of the sperm‐hemizona complexes in sperm‐free medium to assess the acrosomal status of the bound spermatozoa. For acrosome assessment, spermatozoa and washed sperm‐hemizona complexes were air dried onto microscope slides, fixed, permeabilized in ethanol, stained with FITC‐PNA, and counterstained with the DNA dye ethidium homodimer. Both zona‐bound and non‐bound spermatozoa showed similar staining patterns. Acrosome‐intact spermatozoa displayed intensively green fluorescence over the acrosomal cap, whereas reacting spermatozoa showed a patchy disrupted image of fluorescence. Sperm cells that completed the acrosome reaction were principally stained on the equatorial segment or not stained at all. During prolonged incubation and during the calcium ionophore treatment, the proportion of spermatozoa with an acrosomal modification (reacting) and a complete breakdown of the acrosome (reacted) increased noticeably. Significant induction of the acrosome reaction was observed within 60 minutes of sperm‐zona contact (P< 0.001). In conclusion, a rapid and reliable assessment of the acrosomal status and the incidence of the acrosome reaction of stallion spermatozoa at the zona surface were demonstrated in this study.
Analysis of the Effect of Nitric Oxide Synthase Inhibition on Mouse Sperm Employing a Modified Staining Method for Assessment of the Acrosome Reaction
Authors: Viggiano J. Marcelo , Herrero M. Belén , Martínez Silvina P. , de Gimeno Martha F.
Published: October 2023

ABSTRACT: A commercially available staining kit (Spermac) was combined with swelling in a hypoosmotic medium (HOS) for simultaneous assessment of viability and acrosome reaction in mouse spermatozoa. We compared the results obtained with the combined technique (HOS‐Spermac) with those obtained with currently used techniques: the chlortetracycline fluorescence assay and eosin exclusion. The results obtained with HOS‐Spermac were the same as those obtained with the chlortetracycline fluorescence assay. Viability assessment with HOS‐Spermac showed a good correlation with the percentage of spermatozoa showing eosin dye exclusion.

Using this novel technique, we studied the effect of a nitric oxide synthase inhibitor (NG‐nitro‐L‐arginine methyl ester, L‐NAME) on the acrosome reaction. L‐NAME produced a dose‐dependent inhibition of spontaneous acrosome reaction and its inhibitory effect was specifically counteracted by L‐arginine. We conclude that HOS‐Spermac provides a simple and reliable tool for assessment of the acrosome reaction and that nitric oxide synthase participates in this important function of the spermatozoon.
Continuous Assessment of Human Spermatozoa Viability During Cryopreservation
Authors: MOHAMMAD S. N. , BARRATT C. L. , COOKE I. D. , MOORE H. D.
Published: October 2023

ABSTRACT:Cryomicroscopy has enabled direct observation of freezing and thawing of human spermatozoa. When used with a fluorescent viability kit, sperm membrane damage was not apparent down to temperatures of −5°C, but significant damage occurred after thawing (55% of spermatozoa had damaged membranes). Semen samples were cooled or frozen to temperatures (at decrements of 10°C) from 0°C to — 110°C. At all these temperatures the proportion of live to membrane‐damaged cells remained constant. Samples held at temperatures above −30°C were not adversely affected. Below −30°C there was a gradual increase in the proportion of membrane‐damaged cells on thaw and a decrease in the number of live cells recovering motility. At temperatures between −50°C and −60°C there was an equal proportion of live motile, immotile, and membrane‐damaged cells. It is concluded that some irreversible damage to spermatozoa was a result of freezing processes in cells frozen to −30°C or less, but most of the cryodamage was incurred during thawing, possibly due to recrystallization.
Alternative Splicing of CREB and CREM mRNAs in an Immortalized Germ Cell Line
Authors: SANBORN BARBARA M. , MILLAN JOSE L. , MEISTRICH MARVIN L. , MOORE LISA C.
Published: October 2023

ABSTRACT: Alternative splicing of CREB (cAMP response element binding protein) and CREM (cAMP response element modulator) mRNAs in separated pachytene spermatocyte, round spermatid, and elongated spermatid fractions and the germ cell‐derived immortalized cell line GC‐2spd(ts) was studied by reverse transcription polymerase chain reaction (RT‐PCR). Both primary germ cells and the GC‐2spd(ts) cell line expressed the testis‐specific CREB splice variant containing exon W. In the CREB C‐E exon region, both primary germ cells and GC‐2spd(ts) cells produced RT‐PCR products that included exon Y. RT‐PCR using CREM primers produced multiple bands in primary germ cells. The truncated CREAMδC‐G form was found in all the germ cell fractions. The smaller splice forms of CREM were more prominent in the GC‐2spd(ts) cells. GC‐2spd(ts) cells resembled F9 teratocarcinoma cells more closely than primary germ cells with respect to the relative expression of both CREB and CREM alternative splice products. In Sertoli cells, RT‐PCR products of CREB exon lacking W and the product corresponding to CREMδC‐G were most prominent. These data show that the GC‐2spd(ts) cell line retains some qualitative characteristics of primary germ cells with respect to alternative splicing of CREB and CREM mRNA.
Antifertility Potential of Ornidazole Analogues in Rats
Authors: COOPER TREVOR G. , YEUNG CHING‐HEI , SKUPIN ROLF , HAUFE GÜNTER
Published: October 2023

ABSTRACT: In order to determine which part of the ornidazole molecule [1‐(3‐chloro‐2‐hydroxy)propyhl‐2‐methyl‐5‐nitroimidazole] is responsible for its antifertility action, structural analogues were fed to male rats of proven fertility at doses equivalent to the antifertility dose of ornidazole (1.82 mmol/kg/day). The fertility of the males was tested, before oral gavage (control mating) and after 10 and 14 days of feeding, by counting the number of fetuses and corpora lutea present in females 12 days after mating. The day after the last mating, the kinematic parameters of sperm from the cauda epididymldis were assessed objectively with a Hamilton‐Thome motility analyzer. Analogues bearing the 2‐nitro and 5‐methyl groups on the imidazole ring were inactive if the (chlorohydroxy)propyl group were substituted by proton or methyl, hydroxyethyl, chloroethyl, or (sulfonylethyl)ethyl groups, indicating that the three‐carbon side chain of ornidazole was necessary for the antifertility action. Only ornidazole and its acetate were effective antifertility agents, but a compound bearing the (chlorohydroxy)propyi side chain attached to a nitrogen atom of a heterocyclic phthalimide produced a partial but temporary reduction in fertility. Similarities of the action of ornidazole with the male antifertility agent, α‐chbrohydrin [3‐chloro‐1,2‐propanediol], are discussed.