bluuebunny/crossref_metadata_2025 huggingface dataset:
Stabilization of Diborynes versus Destabilization of Diborenes by Coordination of Lewis Bases: Unravelling the Dichotomy
Authors: de Azevedo Santos Lucas , Trujillo‐González Daniel E. , Jiménez‐Halla J. Oscar C. , Bickelhaupt F. Matthias , Solà Miquel
Published: October 2023

We have quantum chemically investigated the boron‐boron bonds in B2, diborynes B2L2, and diborenes B2H2L2 (L=none, OH2, NH3) using dispersion‐corrected relativistic density functional theory at ZORA‐BLYP‐D3(BJ)/TZ2P. B2 has effectively a single B−B bond provided by two half π bonds, whereas B2H2 has effectively a double B=B bond provided by two half π bonds and one σ 2p–2p bond. This different electronic structure causes B2 and B2H2 to react differently to the addition of ligands. Thus, in B2L2, electron‐donating ligands shorten and strengthen the boron‐boron bond whereas, in B2H2L2, they lengthen and weaken the boron‐boron bond. The aforementioned variations in boron‐boron bond length and strength become more pronounced as the Lewis basicity of the ligands L increases.
Synergistic Effects of Tranylcypromine and NRF2 Inhibitor: A Repurposing Strategy for Effective Cancer Therapy
Authors: Chen Delos , Chen Skye , Zhou Fangheng , Bo Chen Lan , Chen Ming‐Wei
Published: October 2023

Drug repurposing has emerged as an attractive strategy for accelerating drug discovery for cancer treatment. In this study, we investigated combining Tranylcypromine (TCP) with a number of well‐characterized drugs. Among these combinations, NRF2 inhibitor (ML385) exhibited synergistic effects in combination with TCP. Specifically, our results showed that the combination of TCP and ML385 resulted in a significant reduction in tumor proliferation while neither drug affected cancer cell growth meaningfully on its own. While further studies are needed to understand fully the extent of the synergistic efficacy, the underlying respective mechanisms and the potential side effects of this approach, our study has yielded a promising start for the development of an effective combination cancer therapy.
A Mouse Model of MHV‐1 Virus Infection for Study of Acute and Long COVID Infection
Authors: Masciarella Andrew D. , Di Gregorio Dibe M. , Ramamoorthy Rajalakshmi , Hussain Hussain , Jayakumar Arumugam R. , Paidas Michael J.
Published: October 2023

COVID‐19, caused by SARS‐CoV‐2, has had a significant global impact. While vaccines and treatments have reduced severe cases and deaths, the long‐term effects are not yet well understood. Current models used for research, such as non‐human primates and transgenic mice, are expensive and require scarce Biosafety Level‐3 (BSL‐3) laboratories, thereby limiting their practicality. However, the mouse hepatitis virus 1 (MHV‐1) mouse model offers a promising alternative. This surrogate model can be investigated in more widely available Biosafety Level‐2 (BSL‐2) laboratories. Furthermore, mice are affordable and easy to handle, and utilizing MHV‐1 as a surrogate for SARS‐CoV‐2 eliminates the need for costly transgenic mice. Importantly, the MHV‐1 model successfully recapitulates COVID‐19‐related clinical symptoms, weight loss, multiorgan pathological changes and failure in acute stages, irreversible neurological complications, and other long‐term organ dysfunction post‐infection, which are similar to available human data post‐COVID‐19. To assist researchers in establishing and using the MHV‐1 mouse model, this protocol offers comprehensive guidance encompassing procedures for animal preparation, induction of viral infection, clinical observation, pathological changes, and tissue analysis for mechanistic studies, thereby yielding valuable insights into disease mechanisms and progression. By adopting the MHV‐1 model and the provided protocols, researchers can effectively circumvent financial constraints and the limited availability of BSL‐3 laboratories, thus facilitating a more accessible and cost‐effective approach to investigating the underlying mechanisms of SARS‐CoV‐2 pathophysiology and exploring potential therapeutic interventions. © 2023 Wiley Periodicals LLC.

Basic Protocol: Induction of mouse hepatitis virus 1 (MHV‐1) infection in A/J mice

Support Protocol 1: Histological evaluation

Support Protocol 2: Liver enzyme measurement

Support Protocol 3: Western blot analysis of aquaporin expression

Support Protocol 4: mRNA measurement

Support Protocol 5: Immunohistochemistry/immunofluorescence

Support Protocol 6: Tissue water measurement
Faculty job satisfaction increases, although support gaps remain
Authors: Sutton Halley
Published: October 2023

Despite challenges in higher education, most faculty members are reporting increased job satisfaction over last year, according to a study published by Cengage.
The importance of sustained professional development for diversifying leadership
Authors: Riskin Eve , Nur Aasli Abdi , Litzler Elizabeth , Yen Joyce
Published: October 2023

As longtime professional development providers and program evaluators, we share what we have learned about individual and institutional gender equity impacts of faculty development programs over 20 years, through the lens of current departmental leaders. We’ll describe our lessons learned from 18 interviews of 2020 science, technology, engineering, and mathematics chairs connected to the ADVANCE program at the University of Washington (UW), where we helped grow the number of women STEM department chairs from one to nine over the last 20 years.
wnt10a is required for zebrafish median fin fold maintenance and adult unpaired fin metamorphosis
Authors: Benard Erica L. , Küçükaylak Ismail , Hatzold Julia , Berendes Kilian U. W. , Carney Thomas J. , Beleggia Filippo , Hammerschmidt Matthias
Published: October 2023

Background

Mutations of human WNT10A are associated with odonto‐ectodermal dysplasia syndromes. Here, we present analyses of wnt10a loss‐of‐function mutants in the zebrafish.

Results

wnt10a mutant zebrafish embryos display impaired tooth development and a collapsing median fin fold (MFF). Rescue experiments show that wnt10a is essential for MFF maintenance both during embryogenesis and later metamorphosis. The MFF collapse could not be attributed to increased cell death or altered proliferation rates of MFF cell types. Rather, wnt10a mutants show reduced expression levels of dlx2a in distal‐most MFF cells, followed by compromised expression of col1a1a and other extracellular matrix proteins encoding genes. Transmission electron microscopy analysis shows that although dermal MFF compartments of wnt10a mutants initially are of normal morphology, with regular collagenous actinotrichia, positioning of actinotrichia within the cleft of distal MFF cells becomes compromised, coinciding with actinotrichia shrinkage and MFF collapse.

Conclusions

MFF collapse of wnt10a mutant zebrafish is likely caused by the loss of distal properties in the developing MFF, strikingly similar to the proposed molecular pathomechanisms underlying the teeth defects caused by the loss of Wnt10 in fish and mammals. In addition, it points to thus fur unknown mechanisms controlling the linear growth and stability of actinotrichia and their collagen fibrils.
Experimental study on failure precursors of coal and sandstone based on two‐step clustering of acoustic emission characteristics
Authors: Zheng Menghao , Liang Yunpei , Li Quangui , Mao Shuren , Li Shang , Li Jianbo , Qian Yanan , Zhou Junjiang
Published: October 2023

Accurately determining the precursors of coal and rock failures is crucial for preventing associated risks in coal mines. In this study, based on the values of the four parameters amplitude, duration, counts and energy of acoustic emission (AE) signals, the AE signals of coal and sandstone samples failure were clustered by the two‐step clustering method. And the precursory AE signals of sample failure under uniaxial compression were analyzed and identified. Results show that the peak of AE amplitude is before that of AE duration, counts, and energy. AE signals of both coal and sandstone samples can be classified into five types. Values of the parameters of Types I–IV AE signals of the sandstone sample are lower than that of the coal sample. The duration, counts, and energy of Type V AE signals of the sandstone sample are higher than that of the coal sample. Type V AE signals, which are middle amplitude (hundreds of mV), high duration (hundreds of thousands of μS), high counts (about 10,000), and high energy (tens of thousands of mV*mS), account for the lowest proportion of all AE signals, at approximately 0.1%. And they began to occur at 87% σcof the coal sample and at 97% σcof the sandstone sample, respectively. Type V AE signals can be used as precursors of coal and sandstone samples failure under uniaxial compression.
Airside friction and heat transfer performance of micro‐bare‐tube heat exchangers with bundle diameters varying gradually from 1.0 to 0.4 mm
Authors: Gong Zhenguo , Zhou Wenjie , Cai Bowen , Lu Junliang
Published: October 2023

In this paper, a micro‐bare‐tube heat exchanger structure with the tube bundle diameter varying gradually in the range of 1.0–0.4 mm is proposed. The airside friction and heat transfer performance correlations for this structure are given. This paper applies CFD simulation to develop and verify the correlation of the diameter gradually varied micro‐bare‐tube heat exchangers' performance. Compared with the traditional same diameter micro‐bare‐tube heat exchanger, the new structure not only reduces the pressure drop, but also improves the thermal hydraulic performance. The friction coefficient f is decreased by 8.59%, the pressure drop is reduced by 43.14%, the heat transfer coefficient j is increased by 12.07% compared to the constant diameter micro‐bare‐tube heat exchanger. At the same time, it reduces the void volume by 47.32% and the tube bundle manufacturing material by 28.57%. The proposed airside performance prediction equation can make the error of more than 70% source data within 10%, and the error of more than 90% source data within 20%. It is suggested to apply this empirical equation to 7–29 rows.
Promotion impact of different strontium doping on Ni‐9La+Zr catalyst for dry reforming of methane
Authors: Ibrahim Ahmed A. , Al‐Fatesh Ahmed S. , Alwadai Norah , Al‐Zahrani Salma A. , Abu‐Dahrieh Jehad K. , Abasaeed Ahmed E. , Fakeeha Anis H.
Published: October 2023

The potential dry reforming of methane technology allows for the synthesis of syngas from methane and carbon dioxide. Numerous investigations have been conducted on developing catalysts with exceptional activity and stability. Carbon deposition causes severe deactivation in typical nickel‐based catalysts, which is one of the most prevalent and important problems. In this study, methane was dry‐reformed over 5 wt.% Ni+xSr‐9La+Zr (x = 0–4 wt.%) catalysts for 7.5 h at 700°C and ambient pressure in a tubular fixed‐bed reactor. According to the weight percent of Sr loading, the features of the material's texture, morphology, and catalysis were investigated. N2‐physisorption, H2‐temperature programmed reduction, X‐ray diffraction, Raman, and TEM were used to evaluate the physicochemical characteristics of the catalysts. N2‐physisorption research revealed that changing the weight percentage loading of the Sr promoter had little effect on the textural qualities. The overall number of reducible NiO‐interacting species over the catalyst surface increased with increasing Sr loading. The 5Ni+2Sr‐9La+Zr catalyst exhibited the optimum CH4 and CO2 conversions of 62.9%–65.9% and 69.1%–70.3%, respectively, and the lowest deactivation factor of 4.7.
Myxoid epithelioid smooth muscle tumor of the vulva: A distinct entity with MEF2D::NCOA2 gene fusion
Authors: Warmke Laura M. , Mustafa Amin , Zou Ying S. , Davis Jessica L. , Ulbright Thomas M. , Segura Sheila E.
Published: October 2023

Smooth muscle tumors are the most common mesenchymal tumors of the female genital tract, including the vulva. Since vulvar smooth muscle tumors are rare, our understanding of them compared to their uterine counterparts continues to evolve. Herein, we present two cases of morphologically distinct myxoid epithelioid smooth muscle tumors of the vulva with novel MEF2D::NCOA2 gene fusion. The tumors involved 24 and 37‐year‐old women. Both tumors presented as palpable vulvar masses that were circumscribed, measuring 2.8 and 5.1 cm in greatest dimension. Histologically, they were composed of epithelioid to spindle‐shaped cells with minimal cytologic atypia and prominent myxoid matrix. Rare mitotic figures were present (1–3 mitotic figures per 10 high‐power field (HPF)), and no areas of tumor necrosis were identified. By immunohistochemistry, the neoplastic cells strongly expressed smooth muscle actin, calponin, and desmin, confirming smooth muscle origin. Next‐generation sequencing identified identical MEF2D::NCOA2 gene fusions. These two cases demonstrate that at least a subset of myxoid epithelioid smooth muscle tumors of the vulva represent a distinct entity characterized by a novel MEF2D::NCOA2 gene fusion. Importantly, recognition of the distinct morphologic and genetic features of these tumors is key to understanding the biological potential of these rare tumors.
Colchicine: A State‐of‐the‐Art Review
Authors: Levy Maurice , Spino Michael , Read Stanley E.
Published: October 2023

Colchicine is an ancient drug that is attracting renewed interest because of its actions at a subcellular level. Specifically, it interferes with microtubule growth and therefore affects mitosis and other microtubule‐dependent functions. Various mechanisms have been proposed to account for the action of colchicine in acute gouty arthritis, its interaction with cellular membrane and cyclic 3′,5′‐adenosine monophosphate, and its action in amyloidosis. Pharmacokinetic studies have been relatively limited and their results somewhat contradictory, with mean terminal elimination half‐lives of 19 minutes to 9 hours being reported. Some of these differences may be attributed to assay difficulties. Colchicine can cause gastrointestinal side effects and should be used with care to protect patients from toxic doses. Colchicine‐induced myopathy and neuropathy may be more frequent than previously recognized, and therefore patients receiving long‐term therapy should be monitored carefully. Bone marrow depression has been reported, primarily in cases of acute colchicine intoxication, and intravenous administration of the drug has been associated with severe pancytopenia and death. Colchicine intoxication causes multiple organ failure. Because of its cytogenic effects and reported association with Down's syndrome, the agent should not be used by pregnant women.
Pharmacotherapy of Otitis Media
Authors: Thoene Daniel E. , Johnson Cary E.
Published: October 2023

The clinical manifestations of acute otitis media and otitis media with effusion are the result of abnormal eustachian tube function most often caused by inflammation from infection or allergy. The majority of cases involve bacterial infection of the middle ear caused by Streptococcus pneumoniae, Haemophilus influenzae, or Branhamella catarrhalis. Nearly half of all children will have had at least one episode of acute otitis media by 1 year of age, and over 70% by 3 years of age. The signs and symptoms include pain with rubbing or tugging at the ear, fever, irritability, lethargy, and hearing loss. The primary therapy for acute otitis media and otitis media with effusion is antibiotics with the goal of preventing possible complications and providing symptomatic relief. Amoxicillin remains the initial drug of choice in communities where β‐lactamase‐producing strains of the common middle ear pathogens are infrequently isolated. If resistant organisms are prevalent, cefaclor, amoxicillin‐clavulanate, or cotrimoxazole should be selected. Adjuvant agents such as decongestants have not been shown to provide additional therapeutic benefit. Children who develop chronic otitis media may require prophylactic antibiotic therapy and insertion of typanostomy tubes.
Management of Patients with Alzheimer's Disease
Authors: Odenheimer Germaine L
Published: October 2023

Alzheimer's disease represents the most common cause of dementia in the elderly. Current estimates suggest that nearly 50% of those over age 85 years have the disorder. Many gaps still exist in our understanding of its etiology and management. Scientific discoveries that once seemed to promise effective treatments have not lived up to our expectations. There are, however, many therapeutic interventions (environmental and pharmacologic) that can greatly enhance the quality of the lives of patients with Alzheimer's disease and that of their families.
Current Topics in Immunotherapy and the Role of the Pharmacist on a Solid Organ Transplant Service
Authors: Shaefer Mark S.
Published: October 2023

Solid organ transplantation has become a well‐accepted therapy for the treatment of end‐stage disease of the liver, heart, kidney, and pancreas. The development of highly effective immunosuppressant drugs has led to major improvements in graft and patient survival over the last decade. In spite of this success the perfect immunosuppressive drug has yet to be discovered. Currently available agents have numerous short‐term and, more disturbingly, long‐term toxicities. This has led to the use of triple‐ and quadruple‐drug regimens in an attempt to maintain good graft and patient survival rates with less toxicity. Multiple‐drug combinations have questionable benefits compared to double‐drug regimens containing cyclosporine and prednisone. With the advent of new immunosuppressant drugs, it will be important to perform randomized, controlled trials to assess their efficacy and toxicities in comparison with current regimens. Pharmacists who work with solid organ transplant teams can function as pharmacotherapists and provide skills such as pharmacokinetic and pharmacodynamic drug monitoring. In addition, they can become involved with clinical and laboratory‐based research to assess the properties of conventional and newly developed immunosuppressive agents.
Zidovudine and Other Reverse Transcriptase Inhibitors in the Management of Human Immunodeficiency Virus‐Related Disease
Authors: Matthews S. James , Cersosimo Robert J. , Spivack Martin L.
Published: October 2023

Licensed in 1987, zidovudine remains the only medication with proved efficacy for the treatment of disease caused by the human immunodeficiency virus (HIV). New information on the pharmacology (adults and children), effects of kidney and liver dysfunction on the disposition of the drug, and drug‐drug interactions have improved the way we use and monitor this agent. The serious toxicity associated with zidovudine has led researchers to develop safer dosage regimens. Also, recognition that zidovudine slows but does not halt progression of disease has increased the search for effective alternatives. The best‐studied agents are didanosine (2′, 3′‐dideoxyinosine, ddI), zalcitabine (2′,3′‐dideoxycytidine, ddC), and foscarnet.
Urinary Tract Infections in Childhood: Definition, Pathogenesis, Diagnosis, and Management
Authors: Feld Leonard G.
Published: October 2023

Urinary tract infections in childhood are defined as significant bacterial growth in urine obtained by bladder catheterization, suprapubic aspiration, or several clean‐voided specimens. In infants and young children they may be easily overlooked because of nonspecific symptoms. This leads to an underestimation of their true prevalence. The severity of these infections is a function of the balance between the various host defense mechanisms and the virulence of the microorganism. The assessment of symptomatic infants and children requires a complete radiographic evaluation (renal ultrasound and voiding cystourethrogram), because of the high frequency of anatomic abnormalities, particularly vesicoureteral reflux. The major issues in the management of children with uncomplicated lower urinary tract infections are whether a single dose or short course of therapy is as efficacious as the conventional 7–10 days, and whether asymptomatic bacteriuria requires treatment.
Buspirone in the Treatment of Posttraumatic Stress Disorder
Authors: Wells Barbara G. , Chu Chung‐Chou , Johnson Richard , Nasdahl Clifford , Ayubi Mohammed A. , Sewell Edith , Statham Paul
Published: October 2023

Three patients with a DSM‐III‐R diagnosis of posttraumatic stress disorder were successfully treated with buspirone in final maximum dosages ranging from 35–60 mg daily. The onset of clinical efficacy ranged from 5–29 days. Symptoms that improved included anxiety, insomnia, flashbacks, and depressed mood. Patients experienced no side effects. Serotonin partial agonist effects are a possible mechanism underlying buspirone's efficacy.
Antidepressants and the Risk of Seizures
Authors: Skowron Diane M. , Stimmel Glen L.
Published: October 2023

As new antidepressants have been marketed, the issue of drug‐induced seizures has assumed new relevance. The risk of such seizures depends on at least three critical factors. Of most importance are an individual's predisposing factors that may increase the risk, followed by the amount and rate of dosage titration, and the relative epileptogenic potential of the particular drug.
Zidovudine Phamacokinetics in Five HIV Seronegative Patients Undergoing Continuous Ambulatory Peritoneal Dialysis
Authors: Kremer Dag , Munar Myrna Y. , Kohlhepp Sue J. , Swan Suzanne K. , Stinnett Eric A. , Gilbert David N. , Young Eric W. , Bennett William M.
Published: October 2023

A few reports in the literature describe zidovudine (AZT) pharmacokinetics in patients undergoing hemodialysis; however, the effect of continuous ambulatory peritoneal dialysis (CAPD) on the drug's disposition has not been studied. The pharmacokinetics of AZT were evaluated in five patients, age 37–62 years, who were seronegative for the human immunodeficiency virus and were undergoing CAPD. Serial plasma, urine, and dialysate samples were collected after oral administration of AZT 200 mg. Samples were assayed using radioimmunoassay (RIA). Model‐independent analysis was used to determine total plasma clearance, apparent volume of distribution, mean residence time, and half‐life. Net peritoneal dialysis clearance was calculated to measure the effect of CAPD on AZT disposition. We found wide interpatient variability in AZT pharmacokinetics. Peak serum concentrations ranged from 0.3–47.8 μm and area under the curve from 0.5–26.1 mg × hour/L. These differences resulted in corresponding differences in clearance (range 66–3176 ml/min/1.73 m2) and volume of distribution (range 16–825 L). Interpatient variability in glucuronidation may partially account for this variability. Net peritoneal dialysis clearance of AZT was 5 ml/minute. Although the effect of peritoneal dialysis on AZT disposition was negligible, clinicians should be aware of the large differences in the way in which individual patients with renal dysfunction handle this drug.
Strategic Planning for the Colony‐Stimulating Factors
Authors: Huber Stephen L.
Published: October 2023

The rapid development and emergence into the marketplace of therapeutic and diagnostic biotechnology products pose a considerable challenge to pharmacists, particularly in light of economic strictures wrought by changes in the health care field. At the same time, the pharmacy profession is moving to a position of greater involvement and responsibility in the clinical management of drug therapy. These changes mandate that pharmacists become strategic thinkers, capable of designing and implementing plans that can integrate biotechnology products into their institutions' practices in a way that both enhances patient care and maintains or promotes financial stability. A strategic plan model incorporating the components of environmental scanning and strategy formulation, implementation, and analysis can be applied to the recombinant colony‐stimulating factors.
Use of Nonlinear, Mixed‐Effects Modeling for Population Analysis of Ofloxacin: Effects of Age on Oral Drug Pharmacokinetics
Authors: Yuen Geoffrey J. , Drusano George L. , Brooks Janet , Flor Soledad
Published: October 2023

To compare the effect of age on pharmacokinetics of orally administered ofloxacin, two separate studies were reanalyzed using mixed‐effect modeling with the program NONMEM. Subjects were male volunteers, 36 age 65 years or greater and 24 age 18–40 years. The younger group received three 100‐mg tablets and the older group received two 200‐mg tablets of ofloxacin. Serial blood samples obtained throughout dosing were assayed for drug concentrations using high‐performance liquid chromatography. A pharmacostatistical model was developed for the data using mixed‐effect modeling with NONMEM. A one‐compartment open model with first‐order absorption, which included the covariables weight and age, best fit the data. Mean (SE) population values were clearance/F 0.219 (0.009) L/hr/kg, volume of distribution/F 1.50 (0.071) L/kg, and absorption rate constant 2.26 (0.048) hr−1. Older subjects had a 29% lower clearance and 13% lower volume of distribution then the younger subjects.
Cerebral Blood Flow Changes With Enalapril
Authors: Fagan Susan C. , Robert Sylvie , Ewing James R. , Levine Steven R. , Ramadan Nabih M. , Welch K. M. A.
Published: October 2023

Patients with carotid artery occlusive disease (CAOD) may be at increased risk of iatrogenic cerebral hypoperfusion. Using the 133xenon‐inhalation technique, we evaluated the effects of enalapril on regional cerebral blood flow (CBF) in 14 patients with chronic hypertension, 7 with CAOD and 7 without CAOD (no CAOD). Regional CBF and blood pressure were measured before and 60 minutes after a single dose of enalapril. Changes in mean arterial pressure after enalapril were not significantly different between the two groups: CAOD −4.67 ± 8.7 mm Hg, no CAOD −6.18 ± 8.2 mm Hg. Changes in mean CBF after enalapril were also not statistically different: CAOD −1.0 ± 3.9, no CAOD 1.0 ± 2.8. In the CAOD group only, however, changes in CBF were significantly related to increasing age (r= −0.9253, p>0.01), such that in patients 65 years or older CBF tended to decrease, whereas in younger patients it increased. Elderly patients with CAOD may be at increased risk of iatrogenic cerebral hypoperfusion, and it may be appropriate to evaluate prospectively the effects of antihypertensive medications on CBF.
Increase in Serum Digoxin Concentrations After Indomethacin Therapy in a Full‐Term Neonate
Authors: Haig George M. , Brookfield Ernest G.
Published: October 2023

Digoxin was administered to an 18‐day‐old infant who showed evidence of cardiac failure. When a Doppler echogram revealed a patent ductus, indomethacin was administered for medical management. Therapeutic digoxin doses then resulted in toxic serum concentrations of 8.2 ng/ml. Serum creatinine rose accordingly. Although this patient did not manifest signs of digoxin toxicity, practitioners should be alerted to the potential complications of these commonly used agents.
Quality of Life Measurements in Oncology
Authors: Lindley Celeste
Published: October 2023

Quality of life (QOL) has transcended from an implicit concern to an explicit measurement in oncology. In contemporary clinical research, QOL can now often be identified and objectively measured in health as well as in illness. The major domains which comprise QOL in patients with cancer include symptoms and side effects, social function, physical function, and psychological status. One of the preferred methods for measuring QOL consists of self‐administered questionnaires. A number of instruments have been developed which vary in features such as type of domains included, number of items, response options, specificity for disease type, and psychometric assessments. The role of QOL assessment is becoming increasingly important in clinical oncology.
Parenteral Nutrition Support in Patients With Cancer
Authors: Ignoffo Robert J.
Published: October 2023

In the patient with cancer, malnutrition may result from the disease itself or from its treatment. Total parenteral nutrition (TPN) has been used for many years to treat or prevent malnutrition in the patient with cancer. There have been few studies, however, that demonstrate significant benefit from TPN therapy in these patients. Patients receiving high‐dose chemotherapy (as in bone marrow transplantation), and patients with solid tumors who have documented malnutrition (cachexia, weight loss) prior to cancer surgery, may benefit from TPN. No other groups of patients with cancer appear to derive significant benefit from TPN, and some groups may actually be harmed by its use. Practical considerations in the use of TPN include periodic calorie‐protein assessment, electrolyte management, and monitoring for drug‐TPN interactions.
Bacterial Resistance to β‐Lactams, and Its Prevention With Combination Antimicrobial Therapy
Authors: Barriere Steven L.
Published: October 2023

The clinical and economic impacts of bacterial resistance are substantial. The development of bacterial resistance during a course of therapy often leads to clinical failure, prolonged hospitalization, increased morbidity, mortality, and increased health care costs. Resistance has been reported to occur most frequently with aminoglycosides, quinolones, and β‐lactam antimicrobials, and often occurs during the course of treatment of gram‐negative bacillary infection. Resistance is most commonly due to enzymatic inactivation, permeability changes, or receptor mutation. Strategies for the prevention of resistance include appropriate infection‐control practices, judicious use of antimicrobials, enhancement of host defenses, and the use of antimicrobial combinations. Despite success in vitro and in experimental animal models of infection, clinical trials in humans of antimicrobial combinations for the prevention of resistance have yielded mixed results. Use of the most potent agents available, preferably in bactericidal synergistic combinations, may be effective in preventing in vivo emergence of bacterial resistance.
Exacerbation of Congestive Heart Failure Secondary to Moricizine
Authors: O'Rangers Eleanor A. , Kluger Jeffrey
Published: October 2023

Moricizine, a recently approved phenothiazine antiarrhythmic agent, is reported to be associated with a low frequency of congestive heart failure. A 61‐year‐old man with a history of congestive heart failure and ischemic heart disease began taking moricizine 250 mg every 8 hours to suppress his monomorphic sustained ventricular tachycardia. After five doses he became progressively short of breath and was in pulmonary edema. Moricizine was discontinued, intravenous diuretics were administered, and the patient's clinical status stabilized. Twelve hours later, however, he developed polymorphic ventricular tachycardia and was not successfully resuscitated. Despite claims as to its safety, limited data strongly suggest that moricizine, like other antiarrhythmics, may be detrimental in patients with preexisting ventricular dysfunction, and should be prescribed with caution.
Oral Nifedipine Pharmacokinetics in Pregnancy‐Induced Hypertension
Authors: Prevost Rebecca R. , Aki Sherif A. , Whybrew W. David , Sibai Baha M.
Published: October 2023

The pharmacokinetics of oral nifedipine were studied in 15 women with pregnancy‐induced hypertension in the third trimester of pregnancy to determine if the drug's disposition was different from that in nonpregnant patients. Peak serum concentrations of 38.6 ± 18 ng/ml occurred at approximately 40 minutes after ingestion of nifedipine 10 mg. The terminal elimination half‐life (mean 1.3 ± 0.5 hrs) was shorter than that reported for normotensive volunteers and nonpregnant hypertensives after oral dosing. Mean ± SD apparent elimination clearance of 2.0 ± 0.8 L/hr/kg was more rapid than that in healthy volunteers (mean 0.49 ± 0.09 L/hr/kg). Random serum concentrations were progressively higher in patients receiving larger daily doses. Nifedipine was detected in samples of fetal cord blood and amniotic fluid at concentrations approximately 93% and 53% those of simultaneous maternal vein samples, respectively. The findings indicate that nifedipine may achieve greater antihypertensive efficacy in pregnant women if administered at shorter intervals.
Relationship Between Serum Quinidine Concentration and Quinidine Dosage
Authors: Allen Nancy M.
Published: October 2023

This retrospective study was designed to identify and assess which patient‐specific factors affect the relationship between the steady‐state trough serum quinidine concentration (SQC) measured by fluorescence polarization immunoassay and quinidine dosage. Data were obtained from 100 hospitalized patients (72 males, 28 females) receiving quinidine for atrial or ventricular arrhythmias, or both, between ages 24 and 85 years (mean age 63 yrs). Age, lean body weight, creatinine clearance (Clcr), and sex were statistically significant factors affecting this relationship; ejection fraction, total body weight, smoking history, alcohol history, recent myocardial infarction, recent surgery, elevated liver function tests, and sampling time were not statistically significant. The Clcr alone provided the most additional information in predicting SQC, and Clcr and weight provided the most additional information in predicting dosage. Currently in clinical practice, quinidine dosage adjustments are not routinely recommended for patients with renal insufficiency. These data suggest that the calculated Clcr is important in predicting both SQC and dosage when a nonspecific quinidine assay is used. This dosing model must be evaluated prospectively.
A Simple Method to Estimate the Initial Dose of Gentamicin
Authors: Lackner Thomas E. , Lyss Alan P.
Published: October 2023

A simple equation to estimate the initial dosing interval of gentamicin was compared with the “rule of eights” equation in 81 adult patients with stable renal function. The Sawchuk‐Zaske method was employed as the standard with which dosing intervals estimated by the simple equation and the rule of eights method were compared. The actual mean peak gentamicin concentration was not significantly different from that predicted by the Sawchuk‐Zaske method. The actual mean trough concentration was significantly higher than the predicted concentration, but trough concentrations within the usual therapeutic range of 0.5–2 μg/ml were achieved in more than 90% of patients. The mean dosing interval calculated by Sawchuk‐Zaske was not significantly different from that calculated by the equation, but was longer than the one calculated by the rule of eights. A peak gentamicin concentration within the usual therapeutic range was generally achieved with a total daily dose of 3–5 mg/kg of actual body weight. Until gentamicin concentrations are known, an easily remembered equation can be used to estimate the initial dosing interval for gentamicin. When used together with a standard total daily dose of 3–5 mg/kg total body weight, usual therapeutic concentrations are achieved in the majority of patients.
Teicoplanin Nephrotoxicity: First Case Report
Authors: Frye Reginald F. , Job Martin L. , Rosenbaum Barry J.
Published: October 2023

A 71‐year‐old man with type I diabetes mellitus was admitted to the hospital for the treatment of osteomyelitis of the left great toe secondary to methicillin‐resistant Staphylococcus aureus. The patient was enrolled in an investigational protocol and was treated with teicoplanin 1200 mg/day. Following 40 days of treatment, the patient developed both markedly elevated serum creatinine and blood urea nitrogen. Urine analysis also showed the presence of protein. The eosinophils were markedly elevated in the blood. The patient was subsequently diagnosed with a probable drug‐induced acute interstitial nephritis. Treatment with furosemide and hemodialysis over the next two weeks failed to produce improvement in renal function. The patient was referred for long‐term dialysis. The data presented in this report suggest the possible relationship of teicoplanin and the development of renal failure in this patient. Periodic monitoring of renal function and follow‐up are probably warranted in patients receiving long‐term teicoplanin therapy.
Effect of Long‐Term Angiotensin‐Converting Enzyme Inhibitor Therapy on Arterial Oxygen Saturation in Patients With Mild to Moderate Heart Failure
Authors: Stanek Eric J. , Nara Andrew R. , Strohl Kingman P. , Nair Ravi N. , Decker Michael J. , Munger Mark A.
Published: October 2023

Study Objective. To evaluate the effects of angiotensin‐converting enzyme (ACE) inhibition on continuous pulse oximetry recordings of arterial oxygen saturation (SpO2).

Design. Open‐label study.

Setting. Cardiology clinics at two large teaching hospitals.

Patients. Eight patients with New York Heart Association Functional Class (NYHA FC) II‐III heart failure.

Interventions. Patients were studied after an ACE inhibitor washout (baseline, B), and after 3 months following resumption of therapy (ACEI).

Measurements and Main Results. Monitoring times for B and ACEI were approximately 22 hours. Reduction trends were observed for number (190 ± 170 vs 125 ± 67 B vs ACEI), magnitude (8.2 ± 1.4% vs 7.5 ± 1.8%), and duration (2.45 ± 2.8 vs 1.35 ± 0.8 min) of desaturations/monitoring period, and for nadir SpO2/desaturation (88.1 ± 1.5% vs 89.9 ± 3.3%). The B desaturation index [(cumulative desaturation time/monitoring period time) × 100, a measure of hypoxic stress or burden] decreased from 19.4 ± 8.1% to 11.9 ± 8.1% at ACEI (p=0.024).

Conclusion. Long‐term ACE inhibitor therapy improves the profile of SpO2 values over time in patients with NYHA FC II‐III heart failure.
Clinical Decision Analysis Modeling: Short‐Term Control of Ventricular Response Rate in Atrial Fibrillation or Atrial Flutter—Digoxin versus Diltiazem
Authors: Gonzalez Edgar R. , Ornato Joseph P. , Lawson Cathy L.
Published: October 2023

Objective. To develop a clinical decision model to compare the outcome of therapy with digoxin versus diltiazem for short‐term control of ventricular response rate (VRR) in patients with atrial fibrillation or atrial flutter.

Design. Review of data from two studies that examined the percentages of response and frequency of adverse reactions in patients treated with intravenous digoxin or diltiazem to control VRR in atrial fibrillation or flutter. We constructed a clinical decision model and performed sensitivity analysis to determine if the model's predictions could be altered.

Setting. Large teaching, university hospitals.

Participants. Adults age 18 years or older treated with intravenous digoxin or intravenous diltiazem for atrial fibrillation or flutter (VRR > 120 beats/min). Patients with severe heart failure New York Heart Association class III or IV, a surgical procedure prior to the exacerbation, or an acute myocardial infarction were excluded.

Measurements and Main Results. We measured VRR control after 1 and 24 hours of therapy (VRR < 100 beats/min or decrease of ≥ 20%) and assessed the likelihood that a patient would suffer an adverse drug reaction. Initial assumptions were that the probability digoxin would achieve VRR control was 0.10 (95% confidence interval 0.04–0.20) at 1 hour and 0.70 (95% CI 0.56–0.80) at 24 hours; the probability that diltiazem would achieve VRR control was 0.94 (95% CI 0.82–0.99) at 1 hour and 0.83 (95% CI 0.68–0.94) at 24 hours; and the probability of no serious adverse drug reaction would be 0.90 (95% CI 0.80–0.96) for digoxin and 0.96 (95% CI 0.86–0.98) for diltiazem.

Results. Diltiazem was superior to digoxin with respect to the composite end point score at 1 hour (91.20 vs 17.29) and 24 hours (81.65 vs 66.43). Digoxin was superior to diltiazem at 24 hours only if the VRR was assumed to be at the highest 95% CI limit for digoxin and simultaneously at the lowest 95% CI for diltiazem (74.62 vs 68.63).

Conclusions. Clinical decision analysis suggests that intravenous diltiazem is superior to intravenous digoxin in controlling VRR in patients with atrial fibrillation or flutter.
Family Leave Policies, Job Share, and Child Care at U.S. Schools and Colleges of Pharmacy
Authors: Marinac Jacqueline S. , Oki Julie C.
Published: October 2023

A 10‐question survey was mailed to the deans of 74 schools and colleges of pharmacy to characterize family leave policies, child care, and job share opportunities. Data were tabulated as percentage response received, and analyzed by geographic region and by public compared with private institutions. Sixty‐four surveys were completed (response rate 86%). Forty‐eight (75%) schools reported having a formal written family leave policy: 47 offered maternity leave, 31 parental leave, 27 caregiver leave, 24 paternal leave, and 24 adoptive or foster parent leave. The duration and compensation for family leave varied among schools. A statistical difference was found between the Northeast (100%) and South (55%) in having such a policy. On‐site child care was available at 26 (41%) schools, including both infant and child care in 12 and additional sick child care in 2. Three (5%) schools reported faculty job share positions.
Clinical and Medicoeconomic Impact of the Cyclosporine‐Diltiazem Interaction in Renal Transplant Recipients
Authors: Smith Curtis L. , Hampton Edward M. , Pederson James A. , Pennington Larry R. , Bourne David WA.
Published: October 2023

The effect of the diltiazem‐cyclosporine interaction on cyclosporine pharmacokinetics, pharmacodynamics, and pharmacoeconomics was studied in 10 recipients of renal allografts. Each subject was studied while receiving diltiazem 60 mg twice/day and while not taking the drug. After achieving steady‐state conditions, cyclosporine and metabolite concentrations were determined in whole blood from samples drawn after the morning cyclosporine dose. After pharmacokinetic analysis, all patients were followed for 6 months during treatment with cyclosporine plus diltiazem or cyclosporine alone. Cyclosporine blood clearance decreased significantly after treatment with diltiazem (18.0–11.0 ml/minkg; p=0.008). The apparent volume of cyclosporine distribution also decreased significantly (4.26–2.62 L/kg; p<0.05). After 6 months, diltiazem had no effect on renal function indexes, and no apparent effect on immunosuppression. Alterations in cyclosporine clearance and apparent volume of distribution secondary to diltiazem result in dosage reduction and potential cost savings in transplant pharmacotherapy. The mean decrease in cyclosporine dosage requirements would produce a cost saving of $1520 or 28% per patient per year.
Diphenhydramine‐Induced Acute Dystonia
Authors: Etzel Joseph V.
Published: October 2023

A 45‐year‐old woman was administered oral and intravenous diphenhydramine 25 mg for the treatment of an allergic reaction. Within 2 minutes she rapidly developed trismus, dysarthria, tremors of the upper extremities, left‐sided weakness, and diminished consciousness. She was treated with intravenous diazepam and benztropine with good response. After approximately 12 hours the patient's condition was completely resolved except for minor subjective weakness of her left extremities. Her hospital stay was uneventful, and she was discharged after 4 days after refusing rechallenge with the drug. Several cases of acute dystonic reactions secondary to antihistamines have been reported in the literature, four of which involved diphenhydramine. Such reactions may occur after short‐ or long‐term therapy. Most patients experienced rapidly developing trismus, facial dystonia, dysarthria, and occasionally, decreases in consciousness, motor incoordination, and weakness. Because of the widespread availability of diphenhydramine and other antihistamines to the general public, awareness of this effect is of great importance.
The Fix Vital Stain Method
Authors: de LEEUW A.M. , den DAAS J.H.G. , WOELDERS H.
Published: October 2023

ABSTRACT: A rapid, accurate and precise method for simultaneous determination of acrosomal status and viability of bull spermatozoa is introduced and evaluated. The method involves fixation of semen with glutaraldehyde and subsequent addition of the fluorescent dye Hoechst bisbenzimide 33258 (H33258). Wet mounts were examined using a combination of phase‐contrast and fluorescence microscopy (×500) for simultaneous visualization of the acrosomal apical ridge, which is indicative of the presence of an intact acrosome, and H33258‐labeled nuclei, which is indicative of membrane‐damaged cells. This fix‐vital stain method allows differentiation between true acrosome reactions and degenerative postmortem loss of acrosomal membranes. Incubation of frozen‐thawed spermatozoa for 60 minutes at 37°C in the presence of calcium ionophore A23187 resulted in an increase in the percentage of true acrosome‐reacted spermatozoa. The fix‐vital stain method does not contain any processing steps that result in loss, selection, or damage of spermatozoa and therefore allows evaluation of representative semen samples.
The Origin and Development of Benign Prostatic Hyperplasia An Age‐Dependent Process
Authors: OESTERLING JOSEPH E.
Published: October 2023

Although the exact cause of benign prostatic hyperplasia (BPH) is not well defined, it is thought to occur as the result of epithelial‐stromal interactions in the appropriate hormonal milieu. Benign prostatic hyperplasia originates in the periurethral and transition zones of the prostate in a microscopic (histologically identifiable) state as early as the third decade of life. With advancing age and the presence of androgens, approximately 50% of microscopic BPH will develop into macroscopic (palpably enlarged prostate) BPH. However, clinically significant BPH necessitating treatment will develop in only 50% of men with an enlarged prostate gland. In the United States, the estimated risk of a 50‐year‐old man undergoing a prostatectomy in his lifetime is approximately 25% to 40%. If left untreated, a significant number of symptomatic patients will remain stable or improve without adverse sequelae.
Transurethral Incision of the Prostate and Bladder Neck
Authors: RIEHMANN MORTEN , BRUSKEWITZ REGINALD
Published: October 2023

Transurethral incision of the prostate (TUIP) is compared to transurethral resection of the prostate (TURP) by reviewing nonrandomized, matched, and randomized studies. These studies indicate that incision of the prostate and bladder neck relieves outflow urinary obstruction, as does TURP. The incision is relatively easier to learn and perform, and requires shorter operative time compared to TURP. The incidence of retrograde ejaculation is lower after incision than after TURP—16% versus 63%, on average. Transurethral incision of the prostate has a potential for reduced costs due to reduced operative time, shortened hospital stay, and the potential for local anesthesia.