bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of solar energy development on ants in the Mojave Desert
Authors: Grodsky Steven M. , Roeder Karl A. , Campbell Joshua W.
Published: October 2023

Land‐use change from solar energy development may affect desert ecosystems and the soils, plants, and animals therein, yet our understanding of these interactions is nascent. With their ubiquity, criticality as ecosystem constituents, and sensitivity to environmental variation, ants may be useful study organisms for elucidating ecological effects of solar energy development in deserts. Our objectives were to disentangle the response of a desert ant community to solar energy development decisions and test the efficacy of ants as bioindicators at a solar power facility (392 MW) in the Mojave Desert, USA. We used pitfall traps to collect ants in treatments representing different solar energy development decisions, including variably intense site preparation practices: blading (i.e., bulldozing) and mowing, and establishment of undeveloped patches in solar fields, replicated across three power blocks comprising the facility and in undeveloped control sites surrounding the facility. We determined that ant abundance, species richness, Shannon Diversity Index, and functional richness were lower in bladed treatments than in all other treatments and controls. For most taxonomic and functional ant responses, we detected no difference between nonbladed treatments and controls; these results suggest that less intensive site preparation and increased spatial heterogeneity (i.e., undeveloped patches in solar fields) can reduce the negative effects of solar energy development on desert ants. However, our results indicate that ants may serve as useful bioindicators of the severity of anthropogenic disturbance from solar energy development in deserts, and indicator analysis signifies that solar energy infrastructure may negatively affect some species with high ecological value (e.g., harvester ants). Negative effects of solar energy development on ants can have significant implications for desert ecosystem function and integrity, but conservation‐minded solar facility design and construction may lead to avoidance of “bottom‐up” ecological ramifications of increased solar production during the renewable energy transition.
Stereochemistry of aminoacylated cardiolipins and phosphatidylglycerols from bacteria
Authors: Kyselová Lucie , Řezanka Tomáš
Published: October 2023

Hydrophilic interaction liquid chromatography (HILIC) connected with electrospray high‐resolution tandem mass spectrometry (MS) was used for the analysis of unusual amino acid (AA) substituted phosphatidylglycerols (PG) and cardiolipins (CL) in mesophilic and thermophilic bacteria. Individual peaks from the lipid class separation by HILIC were isolated and hydrolyzed to determine the absolute configuration of the aminoacyl side chain. The configuration of the aminoacyl side chain was assigned by indirect liquid chromatography (LC) enantiomer separation after the hydrolysis of the aminoacylated (aminoacyl) lipids using N‐(4‐nitrophenoxycarbonyl)‐l‐phenylalanine 2‐methoxyethyl ester as chiral derivatizing agent and reversed phase LC–MS for analysis. When two chromatographic methods were combined, less common AAs, such as d‐allo‐Ile and d‐allo‐Thr, were identified. The taxonomic classification of bacteria showed that bacteria of the family Bacillaceae (Bacillus and Geobacillus) produce branched‐chain AAs, that is, d‐allo‐Ile, d‐Ile, and d‐Leu. These AAs were present only in the genera Bacillus and Geobacillus and not in Alicyclobacillus acidoterrestris (family Alicyclobacillaceae). On the contrary, hydroxy AAs, that is, l‐ and d‐Thr, and l‐ and d‐allo‐Thr, were identified as aminoacyl‐PG and aminoacyl‐CL in A. acidoterrestris and were not present in the genera Bacillus and Geobacillus. Therefore, the complete analysis made it possible to identify the stereochemistry of AAs in aminoacyl PGs and CLs and use this fact for chemotaxonomy.
T1 and FLAIR signal intensities are related to tau pathology in dominantly inherited Alzheimer disease
Authors: Rahmani Farzaneh , Brier Matthew R. , Gordon Brian A. , McKay Nicole , Flores Shaney , Keefe Sarah , Hornbeck Russ , Ances Beau , Joseph‐Mathurin Nelly , Xiong Chengjie , Wang Guoqiao , Raji Cyrus A. , Libre‐Guerra Jorge J. , Perrin Richard J. , McDade Eric , Daniels Alisha , Karch Celeste , Day Gregory S. , Brickman Adam M. , Fulham Michael , Jack Clifford R. , la La Fougère Christian , Reischl Gerald , Schofield Peter R. , Oh Hwamee , Levin Johannes , Vöglein Jonathan , Cash David M. , Yakushev Igor , Ikeuchi Takeshi , Klunk William E. , Morris John C. , Bateman Randall J. , Benzinger Tammie L. S. ,   For the Dominantly Inherited Alzheimer Network (DIAN)
Published: October 2023

Carriers of mutations responsible for dominantly inherited Alzheimer disease provide a unique opportunity to study potential imaging biomarkers. Biomarkers based on routinely acquired clinical MR images, could supplement the extant invasive or logistically challenging) biomarker studies. We used 1104 longitudinal MR, 324 amyloid beta, and 87 tau positron emission tomography imaging sessions from 525 participants enrolled in the Dominantly Inherited Alzheimer Network Observational Study to extract novel imaging metrics representing the mean (μ) and standard deviation (σ) of standardized image intensities of T1‐weighted and Fluid attenuated inversion recovery (FLAIR) MR scans. There was an exponential decrease in FLAIR‐μ in mutation carriers and an increase in FLAIR and T1 signal heterogeneity (T1‐σ and FLAIR‐σ) as participants approached the symptom onset in both supramarginal, the right postcentral and right superior temporal gyri as well as both caudate nuclei, putamina, thalami, and amygdalae. After controlling for the effect of regional atrophy, FLAIR‐μ decreased and T1‐σ and FLAIR‐σ increased with increasing amyloid beta and tau deposition in numerous cortical regions. In symptomatic mutation carriers and independent of the effect of regional atrophy, tau pathology demonstrated a stronger relationship with image intensity metrics, compared with amyloid pathology. We propose novel MR imaging intensity‐based metrics using standard clinical T1 and FLAIR images which strongly associates with the progression of pathology in dominantly inherited Alzheimer disease. We suggest that tau pathology may be a key driver of the observed changes in this cohort of patients.
The effects of parental retirement on adult children's health: Evidence from China
Authors: Hao Zhuang , Cheng Huihui , Bärnighausen Till , Chen Simiao
Published: October 2023

Using representative data from China, we examine the causal effects of parental retirement on the health of adult children. To do so, we adopt a fuzzy regression discontinuity design and exploit the mandatory retirement ages in China as cut‐off points. We find no evidence that parental retirement has significant effects on the mental health, healthcare utilization, or risky health behaviors of adult children. However, paternal retirement and maternal retirement have different effects on adult children's Self‐reported health (SRH). Paternal retirement has a significantly negative effect only on the SRH of sons, while maternal retirement does not induce such effects. Potential mechanisms of intergenerational transfer through which parental retirement might affect adult children's health are also explored.
Conducting formative research during a pandemic threat to inform the development of an obesity prevention social and behaviour change communication strategy in Tonga
Authors: Turk Tahir , Hufanga Sione , Latailakepa Sela , Fifita Lydia , Tolu Ofa ki Haileni , Hola Hotaia , Khran Jutta , Osornprasop Sutayut
Published: October 2023

Issue Addressed

The global epidemic of obesity is overtaking many parts of the world with the Pacific Islands at particular risk. Tonga population surveys identify significant increases in overweight and obesity with Social and Behaviour Change Communication (SBCC) offering opportunities for curbing the rise in non‐communicable diseases. Formative research was conducted during the Covid‐19 pandemic to assess stakeholder and program beneficiary needs and wants toward an obesity prevention SBCC strategy in Tonga.

Methods

Semi‐structured interviews with 17 key informants and 18 focus group discussions (N = 168) were conducted in Tongatapu. Data analysis was conducted on Nvivo 2020 qualitative software with desk research of secondary data supporting in‐field findings.

Results

Potential barriers to behavioural compliance included social/cultural norms, poor attitudes; low motivation and capability; and vulnerabilities of gender and other social determinants. Opportunities included the Tongan collective mindset and the desire for greater social interaction and fun. Strong political will to affect change was apparent with the need to consider targeting to youth, social mobilisation of communities through empowering messaging, and an integrated range of activities.

Conclusions

Co‐design in the formative research process was able to be fostered via online communication processes to overcome the challenges of Covid‐19 travel restrictions. The innovative approach provided a number of learnings including identification of national and regional priorities and improved efficiencies in SBCC planning, implementation and evaluation.

So What?

Formative research adopting co‐design approaches with stakeholders and program beneficiaries can provide optimal engagement and ownership in the SBCC strategy including insights into messaging approaches.
Tele‐mental health during the COVID‐19 pandemic: A systematic review of the literature focused on technical aspects and challenges
Authors: Nazemi Maryam , Kiani Shamim , Zakerabasali Somayyeh
Published: October 2023

Introduction

Mental disorders are the leading cause of disability and the second leading cause of death worldwide, which leads to the death of more than 9 million people annually. The global impact of the Coronavirus epidemic on mental health includes insomnia, anxiety, and depression. Therefore, given the current situation, innovations such as telemedicine to provide prevention and treatment services for people with mental disorders seem necessary.

Methods

A literature review was performed according to the preferred items to report in systematic reviews and meta‐analyses (PRISMA). Covering a period from January 2020 to July 2023, we conducted a systematic literature search on five electronic databases (PubMed‐Mesh, Scopus, Web of Science, Science direct, and PsycInfo). The search strategy included three categories of keywords: Mental health, Tele, COVID‐19.

Results

A total of 112 articles were identified by searching the databases of published articles, 13 articles met our inclusion criteria. A total of 76.2% of them were related to patients with stress, anxiety, and depression issues. We found that the real‐time method has been the most common method used to communicate between the physician and the patient (92.3%). The communication technologies used also included telephone, video call, video conference, and E‐mail. During these communications, data was exchanged in text, voice, and video formats. In three studies (27%), interoperability with other systems was mentioned. In addition, 69.2% of the studies reported challenges, the most important of which were access to electronic and communication devices, network connection problems, audio and video problems, and privacy issues.

Conclusions

Considering the many advantages of telemedicine technology in the field of mental health, the need to use this technology in developing countries, including our country, is obvious. But the application of these technologies requires the investigation of technical aspects and challenges related to them as much as possible, which have been seen in few studies.
Pharmacologic Treatment of Primary and Secondary Pulmonary Hypertension
Authors: Brown Glen
Published: October 2023

A variety of diseases are associated with elevation of pressure within the pulmonary circulation. Pulmonary hypertension is considered a contributor to the morbidity and mortality associated with these conditions. An understanding of the pathophysiology and consequences of pulmonary hypertension is required when considering pharmacologic treatment. Information regarding the potential benefits and toxicities of the drug therapy for primary and secondary hypertension is necessary when considering the use of specific agents for an individual patient.
Antimicrobial Prophylaxis for Arthroplasty and Total Joint Replacement: Discussion and Review of Published Clinical Trials
Authors: Heath Andrea Fus
Published: October 2023

Cephalosporins are often administered to prevent infections that can follow total joint replacements (TJR) and other arthroplastic procedures. However, recommendations contained within published guidelines and review articles vary greatly from those given by the manufacturer in product information circulars. Similarly, the results of published clinical trials vary substantially with regard to the choice of cephalosporin, the dose and dosing interval, and the duration of administration that should be used for antimicrobial prophylaxis in patients undergoing clean orthopedic procedures. Well‐designed clinical trials provide data concerning the appropriate use of cephalosporins for preventing infections that may follow TJR or joint arthroplasty.
Effects of Age on Reporting of Adverse Clinical Events: Results from Two Postmarketing Surveillance Methods
Authors: Bryant Stephen G. , Fisher Seymour , Prinsley Derek M. , Olins Nancy J. , Larson David B.
Published: October 2023

Two postmarketing surveillance methods were employed to determine the possible effects of age on reports by outpatients of adverse clinical events (ACEs) occurring shortly after treatment with targeted oral antibiotics or tricyclic antidepressants. One approach involved staff‐initiated interviews of patients by telephone and the other involved patient‐initiated telephone calls to report possible adverse drug reactions. Regardless of the method, the interviews obtained ACE reports both spontaneously and by review of organ systems. Both postmarketing methods confirmed monotonic relationships for age with treatment duration on the target drugs and with the number of concurrent medications. However, the expected positive correlation between age and spontaneously reported ACEs was evident only in the self‐monitoring patients who initiated reports. Negative correlations between age and the number of reported valid ACEs were seen in six independent samples, whereas only two demonstrated a positive relationship. This disparity may elucidate a critical methodologic problem: careful attention must be paid to the means of eliciting information about possible adverse clinical events before attempting to study adverse drug reactions, which are necessarily a subset of ACEs.
Ampicillin‐Sulbactam and Ticarcillin‐Clavulanic Acid: A Comparison of Their In Vitro Activity and Review of Their Clinical Efficacy
Authors: Itokazu Gail S. , Danziger Larry H.
Published: October 2023

Sulbactam (SB) and clavulanic acid (CA) are irreversible inhibitors of the β‐lactamases in the Richmond and Sykes classes II—VI. When combined with ampicillin and ticarcillin, SB and CA, respectively, extend the spectrum of activity of these penicillins to include some β‐lactamase‐producing aerobes (Enterobacteriaceae, Hemophilus influenzae, staphylococci) and anaerobes (Bacteroides fragilis group) which would otherwise be resistant. Neither effectively inhibits the class I β‐lactamases frequently produced by Pseudomonas aeruginosa, Enierobacter, and Serratia, in part explaining the resistance observed with these organisms. Clinically, both agents were as effective as the comparative therapies in all but two of the trials reviewed. Given the current data, the decision to add these agents to the formulary should be based on hospital resistance patterns and on the cost of these antimicrobials in comparison to conventional therapies.
Fatal Hepatotoxicity Induced by Hydralazine or Labetalol
Authors: Stumpf Janice L.
Published: October 2023

Antihypertensive agents have been associated with adverse reactions that, if unrecognized by health practitioners, may have devastating consequences. The pattern of hepatotoxicity observed during therapy with the vasodilator hydralazine is highly variable, often making its diagnosis difficult. Serious hepatic injury induced by the α‐ and β‐adrenergic receptor antagonist labetalol has only recently been reported and therefore, many clinicians may be unaware of this adverse effect. Familiarity with the clinical features and course of hydralazine‐ and labetalol‐induced hepatic injury is necessary to ensure prompt recognition and discontinuation of the agent.
The Efficacy of Nutrition Support in Infected Patients with Chronic Renal Failure
Authors: Vehe Kathryn L. , Brown Rex O. , Moore Linda W. , Acchiardo Sergio R. , Luther R. Wayne
Published: October 2023

Patients with chronic renal failure are at considerable nutritional risk due to restricted diets, poor intake, and dialysis‐related protein losses; therefore, they often require specialized nutrition support. It is difficult, however, to gauge the success of the intervention, since the gold standard nitrogen balance cannot be easily employed. We examined the usefulness of three visceral proteins, insulinlike growth factor 1 (IGF‐1), fibronectin (FBN), and prealbumin (PA), as markers of nutrition support efficacy in patients with chronic renal failure. Fourteen patients receiving enteral (1) or parenteral (13) nutrition were studied for 7–28 days. The six males and eight females attained intakes of protein and nonprotein energy of 1.3 ± 0.3 (mean ± SD) g/kg/day and 34 ± 6 kcal/kg/day, respectively. Blood samples taken on days 1, 4, 7, 14, 21, and 28 were assayed for IGF‐1, FBN, and PA concentrations. Protein levels were correlated with cumulative nonprotein energy and protein intake. Concentrations of IGF‐1 at baseline (0.90 ± 0.48 U/ml) rose significantly by day 4 (1.35 ± 0.78 U/ml) and remained significantly above baseline at days 7 (1.44 ± 0.68 U/ml), 14 (1.63 ± 1.05 U/ml), and 28 (1.59 ± 0.98 U/ml). Baseline FBN (113 ± 53 μg/ml) and PA (15.3 ± 7.8 mg/dl) concentrations rose significantly by day 28 (FBN, 163 ± 51 μg/ml; PA, 24.6 ± 19.0 mg/dl). The PA concentrations correlated significantly with cumulative nonprotein calories and cumulative protein intake (r = 0.37, p < 0.01; r = 0.43, p < 0.01, respectively). Both IGF‐1 and PA show promise as markers of nutrition support efficacy in this complex patient population.
Acute Hepatic Failure Associated with Oral Minocycline: A Case Report
Authors: Min David I. , Burke Peter A. , Lewis W. David , Jenkins Roger L.
Published: October 2023

A 39‐year‐old woman was evaluated for possible liver transplantation due to rapidly developing hepatic failure 4 weeks after initiation of oral minocycline 100 mg twice a day for the treatment of acne. The patient developed a maculopapular rash, malaise, fever, nausea, and vomiting 2 weeks prior to admission to the hospital. On admission, her symptoms rapidly progressed to liver failure characterized by rapidly rising liver enzyme levels, worsening encephalopathy, and coagulopathy. Viral hepatitis serologies and blood cultures were all negative. After intensive supportive care for 2 weeks, the patient's condition gradually improved and she was discharged with mildly elevated liver enzyme levels and pruritus, without need of liver transplantation. Minocycline‐induced hepatic injury is an idiosyncratic reaction with a sensitization period that appears to be 3–4 weeks in duration. The characteristic features include rash, fever, lymphadenopathy, and eosinophilia, as well as severe alterations in liver function. The high liver enzyme levels and the significant prolongation of the prothrombin time suggest massive hepatocellular damage. In light of the profound liver damage that occurs with this adverse reaction, care should be taken in administering minocycline to patients who have concomitant liver disease. It is recommended that patients should be instructed as to the possible signs and symptoms of toxicity and be monitored for evidence of idiosyncratic reaction or liver failure.
Disposition of Oral Dipyridamole in Patients Undergoing Thallium 201 Myocardial Imaging
Authors: Stringer Kathleen A. , Branconi Joseph M. , Abadier Ralph , Wilton John H. , Royal Stephen H.
Published: October 2023

Oral dipyridamole has been used in conjunction with thallium 201 imaging to diagnose coronary artery disease in patients unable to exercise. However, the pharmacokinetic disposition of high‐dose dipyridamole, particularly the time to maximum drug concentration, has not been described in patients undergoing oral dipyridamole‐thallium 201 scanning. Therefore, we measured serial concentrations in 20 outpatients undergoing thallium 201 testing after a single 400‐mg oral dose of dipyridamole. In patients with positive thallium scans (group A), concentrations were slightly higher than in those with negative scans (group B). The variability in concentrations for both groups ranged from 3–118%. The area under the dipyridamole concentration‐time curve from 0–4 hours ranged from 2.9–2.3 μg·hr/ml. The time to peak plasma level for dipyridamole ranged from 0.5–2.5 hours, with two patients having undetectable levels at the time of thallium 201 injection. Dipyridamole concentrations did not correlate with changes in diastolic or systolic blood pressure, or heart rate. Although it is unknown what concentration is required to produce changes in coronary flow velocity, use of oral dipyridamole in this setting resulted in highly variable concentrations. In addition, these data suggest that a small percentage of patients will not have detectable concentrations at the time of the first thallium 201 scan, possibly limiting the usefulness of this agent in conjunction with thallium scintigraphy in some patients.
The Bioavailability of Morphine in Controlled‐Release 30‐mg Tablets per Rectum Compared With Immediate‐Release 30‐mg Rectal Suppositories and Controlled‐Release 30‐mg Oral Tablets
Authors: Kaiko Robert F. , Fitzmartin Ronald D. , Thomas Gordon B. , Goldenheim Paul D.
Published: October 2023

The bioavailability of controlled‐release morphine 30‐mg tablets (MSC) administered orally or rectally and immediate‐release morphine (RMS) 30‐mg suppositories per rectum, was compared in this 14‐subject, randomized, single‐dose, analytically blinded, crossover study. Rectal MSC plasma morphine area under the curve from 0–24 hours (AUC0–24) was 50.8% of RMS and was similar for MSC administered by either route (rectal MSC = 90% oral MSC). Rectal MSC had a significantly delayed time to peak plasma level (5.4 vs 1.07 and 2.5 hrs for rectal MSC vs RMS and oral MSC, respectively) and a significantly attenuated time to maximum concentration (6.1 vs 25.4 and 9.7 ng/ml, respectively). Proctoscopy 24 hours after insertion revealed seven instances of mild, transient mucosal erythema or edema with rectal MSC and 12 with RMS. The number of nonlocal adverse effects was 14 with rectal MSC, 19 with RMS, and 18 with oral MSC. Further studies must determine the therapeutic consequences of pharmacokinetic differences and establish guidelines for rectal MSC use. The product is currently not recommended by the manufacturer for rectal administration.
Parenteral Ondansetron for the Treatment of Chemotherapy‐ and Radiation‐Induced Nausea and Vomiting
Authors: Burnette P.K. , Perkins Janelle
Published: October 2023

Ondansetron hydrochloride dihydrate is a 5‐hydroxytryptamine (5‐HT3) antagonist that was recently approved by the Food and Drug Administration for the treatment of chemotherapy‐induced emesis. The mechanism of action is thought to be due to competitive inhibition of specific serotonin receptors in the central nervous system and gastrointestinal tract. In clinical trials with cisplatin‐induced emesis, ondansetron resulted in complete control of vomiting (0–2 episodes) in 55–87% of patients during the first 24 hours of chemotherapy administration. It was significantly more effective than metoclopramide in comparative trials. Ondansetron is also being investigated for the treatment of radiation‐ and anesthesia‐associated nausea and vomiting. Studies in animals demonstrate potential efficacy in the treatment of anxiety, drug withdrawal, and schizophrenia. The drug is generally well tolerated, with no reported extrapyramidal reactions.
Patient‐Controlled Analgesia: A Review
Authors: Smythe Maureen
Published: October 2023

The patient‐activated analgesic system was introduced in 1968. Early trials, although uncontrolled, supported the safety and efficacy of patient‐controlled analgesia (PCA) in several kinds of pain, such as that relating to surgery, cancer, trauma, and obstetric procedures. In the past decade, prospective, randomized trials have reported several advantages of PCA over conventional analgesia in the early postoperative period. Although not supported by all controlled trials, they include improved pain relief, less sedation, lower level of narcotic consumption, fewer postoperative complications, greater patient satisfaction, and improved pulmonary function. Preliminary results in the management of chronic pain indicate that PCA can lead to significant lifestyle improvements in ambulatory patients with cancer. The most significant, although infrequent, adverse effect is respiratory depression, the majority of cases occurring in patients predisposed secondary to concomitant illness or as a result of human error. The clinical use of PCA will likely see a significant increase among persons with cancer, and an increase in epidural administration. The cost benefit of PCA has yet to be assessed in inpatient and outpatient settings.
Theophylline — An Alternative Therapy for Bradyarrhythmia in the Elderly
Authors: Kragie Laura , Sekovski Blaze
Published: October 2023

Treating elderly debilitated patients with symptomatic bradyarrhythmia may be difficult. Traditional therapy includes use of limited resources (intensive care unit monitoring) and expensive interventions (permanent pacemaker insertion). When a pacemaker is not ideal or appropriate, yet intervention is desired to improve quality of life, theophylline may be a safe and effective alternative therapy. We expanded this use of theophylline in a series of 11 patients admitted 14 consecutive times with hemodynamically compromising bradyarrhythmias, including atropine‐resistant complete heart block with idioventricular rhythm. Three patients experienced deterioration of status and recurrence of bradycardia with the withdrawal or reduction of theophylline, and subsequent recovery of heart rate and conduction with its resumption.
Emesis as a Complication of Cancer Chemotherapy: Pathophysiology, Importance, and Treatment
Authors: Graves Terri
Published: October 2023

Up to 30% of patients receiving chemotherapy experience uncontrolled nausea and vomiting despite pharmacotherapeutic advances. Currently marketed agents used to treat these symptoms are compared. Dose escalation of these agents may improve response rates. Recent focus has been on a new class of antiemetics, the serotonin antagonists. Ondansetron, currently the only serotonin antagonist with Food and Drug Administration approval for treatment of chemotherapy‐induced emesis, demonstrates the efficacy and potential advantages of this class of antiemetics.
Potential Warfarin‐Ciprofloxacin Interaction in Patients Receiving Long‐Term Anticoagulation
Authors: Bianco Theresa M. , Bussey Henry I. , Farnett Lisa E. , Linn William D. , Roush Maura K. , Wong Y.W. James
Published: October 2023

This study prospectively evaluated the potential interaction between the oral anticoagulant warfarin and the quinolone antimicrobial agent ciprofloxacin. After a 10‐day placebo lead‐in phase, 16 patients stabilized with long‐term warfarin therapy were randomized to receive ciprofloxacin 500 mg or a matching placebo twice/day for 10 days. International normalized ratios (INRs) measured by both standard laboratory analysis and by Coumatrak (finger‐stick) methods were evaluated at 3‐ to 5‐day intervals. No patient experienced a significant increase in INR. No patient experienced a bleeding event. These data support the fact that a warfarin‐ciprofloxacin interaction does not routinely occur at this dosage and duration of ciprofloxacin therapy.
Review of Drug‐Induced Acute Interstitial Nephritis
Authors: Murray Kim M. , Keane William R.
Published: October 2023

Drug‐induced acute interstitial nephritis (AIN) is a rare, potentially correctable cause of acute renal failure. Early recognition and appropriate therapy are essential to its management. Several drugs have been associated with the development of AIN, including antibiotics and nonsteroidal antiinflammatory agents, all with characteristic mechanisms of toxicity.
Mathematic Modeling of Drug Disposition and Postdialysis Rebound in Patients Requiring Hemodialysis
Authors: Spivey J. Michael , Blum Robert A. , Nix David E.
Published: October 2023

We developed a model to describe intradialysis and postdialysis serum concentration changes and, in concert with nonlinear regression, to estimate drug removal during hemodialysis. A Lotus‐based computer simulation program was developed that describes drug disposition in this therapy. The hemodialysis removal rate constant and β were two important factors identified that influence postdialysis rebound. Also, a nonlinear regression routine using PCNONLIN was developed that enables simultaneous fitting of predialysis, intradialysis, and postdialysis drug concentration data. Data from four patients who received intravenous sulbactam were analyzed using this model. The mean measured amount of sulbactam removed by hemodialysis was 446 ± 32 mg versus predicted amounts of 456 ± 92 mg from model estimates, and 449 ± 33 mg when dialysate recovery of drug was included in the input. This program will be useful in characterizing pharmacokinetic constants and predicting hemodialysis drug removal.
Liver Disease Associated With Diclofenac, Naproxen, and Piroxicam
Authors: Jick Hershel , Derby Laura E. , Rodríguez Luis A. García , Jick Susan S. , Dean Alan D.
Published: October 2023

Based on information derived from computers used by general practitioners in the United Kingdom, we identified all patients with any recorded diagnosis of a liver disorder within 90 days of a prior prescription for diclofenac, naproxen, or piroxicam, three nonsteroidal antiinflammatory drugs (NSAIDs). The follow‐up cohort consisted of 102,644 persons who used one or more of these drugs. A case history was requested from the physician to provide a description of the liver disorder and its relation to NSAID exposure. One case of clinically important liver disease was likely to have been caused by a study drug and another appeared to be caused by use of numerous NSAIDs. In 10 additional patients a causal connection between a study NSAID and the liver disorder seemed unlikely but could not be fully ruled out. We conclude that serious liver disease caused by diclofenac, naproxen, or piroxicam appears to be uncommon.
Chemistry, Pharmacology, Pharmacokinetics, and Clinical Applications of Mesalamine for the Treatment of Inflammatory Bowel Disease
Authors: Small Ralph E. , Schraa Charles C.
Published: October 2023

Mesalamine is the therapeutically active moiety of sulfasalazine used to treat inflammatory bowel disease. A controlled‐release mesalamine capsule (Pentasa) is designed to release the agent continuously, and largely unaffected by intestinal pH, throughout the small and large bowel due to a diffusion‐dependent, semipermeable ethylcellulose coating. It is a safe and efficacious single agent for inducing remission and producing therapeutic benefit in patients with mild to moderately active ulcerative colitis (UC) (2 or 4 g/day) or Crohn's disease (4 g/day), as well as for significantly enhancing quality of life for patients with mild to moderately active UC (2 or 4 g/day). It is also effective for maintaining remission in patients with quiescent UC and Crohn's disease (4 g/day). Disease location (left‐sided UC or pancolitis) did not affect the agent's effect in active disease or maintaining remission. Fewer treatment‐related adverse events were reported with mesalamine than with placebo in treating UC. In the treatment of active Crohn's disease, data showed no statistically significant differences in response for patients with ileitis, ileocolitis, or Crohn's colitis. This formulation of mesalamine may also be a possible steroid‐sparing agent for patients with either active or quiescent Crohn's disease.
A Pharmacoeconomic Model to Evaluate Antibiotic Costs
Authors: Garrelts James C. , Horst W. Dale , Silkey Beryl , Gagnon Suzanne
Published: October 2023

Study Objectives. To characterize patient sociodemographics and health, describe vancomycin treatment parameters and clinician‐rated outcomes, and determine costs associated with treatment including preparation and administration, adverse events, and toxicity.

Design. A prospective study to develop a model for costs associated with antibiotic treatment (vancomycin).

Setting. A community hospital.

Patients. One hundred adults with active infections.

Interventions. Mean duration of therapy was 10 days, and most patients received 2000 mg/day. Serum concentrations were monitored in two of three patients. Detailed cost analyses were completed on a subset of 26 patients selected at random from the overall sample.

Measurements and Main Results. Sepsis and skin and skin structure infections were the most common indications for vancomycin therapy. Treatment was effective in 81 patients, failed in 9, and was not evaluable in 10. Thirty‐eight percent of patients experienced adverse events attributable to the drug. Phlebitis was common, and red man syndrome, nephrotoxicity, and ototoxicity were infrequent.

Conclusions. Total cost of vancomycin treatment for 100 patients was $30,251: $23,855 for preparation and administration, $1710 for monitoring serum concentrations, and $4686 for treating adverse reactions. Drug costs accounted for only 55% of the total cost. Vancomycin is safe and effective, but phlebitis is underreported and significantly affects cost.
Albumin and Prealbumin Concentrations in Patients Receiving Postoperative Parenteral Nutrition
Authors: Erstad Brian L. , Campbell David J. , Rollins Carol J. , Rappaport William D.
Published: October 2023

This prospective, nonrandomized study was conducted to compare the increases in albumin and prealbumin concentrations in postoperative patients given adequate nutrition support. All surgery patients at least 18 years of age and who required parenteral nutrition were included. Of 86 patients evaluated, 16 met all criteria for study entry. Blood for albumin concentrations was drawn within 48 hours of beginning parenteral nutrition and then weekly. Blood for prealbumin concentrations was drawn within 48 hours of beginning parenteral nutrition and then twice weekly. Albumin concentrations increased from 2.00 ± 0.35 to 2.21 ± 0.42 g/dl (NS). Prealbumin concentrations increased from 11.97 ± 6.31 to 17.29 ± 8.93 mg/dl (p=0.017). All but one prealbumin concentration was in the normal range for our laboratory when parenteral nutrition was discontinued. None of the albumin concentrations were ever in the normal range. The prealbumin concentration is a better indicator than albumin of nutrition status in the postoperative patient. Since prealbumin concentrations typically rise into the normal range within a week after adequate caloric supplementation, clinicians may avoid unnecessary increases in protein‐calorie intake and laboratory testing of nutrition status by using this measurement.
Issues in the Statistical Analysis of Sperm Motion Data Derived from Computer‐assisted Systems
Authors: GLADEN BETH C. , WILLIAMS JACQUELINE , CHAPIN ROBERT E.
Published: October 2023

ABSTRACT: Computer‐assisted sperm motion measurements present certain features that must be accounted for in statistical analyses. Some are specific to this type of data, whereas others are standard considerations. For example, the measurement of multiple sperm from individuals creates correlations that must be accounted for if each sperm's measurement is used, and unequal variances may arise that need to be addressed if an average measurement from the individual is used. Also, the limitations on the ranges of some measurements create discrepancies between observed and actual means and may make treatment‐related effects more difficult to detect — a circumstance that has an impact on study design. When variables that are truly continuous are measured in a discrete fashion, odd effects may arise and care is needed. Other considerations, such as the shapes of distributions and correlations among various measurements, should also be examined. Attention to these details of statistical analysis are vital to proper interpretation of data.
Effects of Follicular Fluid Administration on Serum Bioactive and Immunoreactive FSH Concentrations and Compensatory Testosterone Secretion in Hemicastrated Adult Rats
Authors: BROWN JANINE L. , DAHL KRISTINE D. , CHAKRABORTY PRABIR K.
Published: October 2023

ABSTRACT: In adult rats, removal of one testis (hemicastration) results in an elevation of serum follicle‐stimulating hormone (FSH) concentrations and a compensation in testosterone secretion by the remaining testis without a corresponding increase in testis size. To determine whether changes in FSH secretion and compensatory androgen production are related, serum testosterone concentrations were measured after inhibin‐rich porcine follicular fluid was administered twice daily for 4 days to block the hemicastration‐induced rise in FSH. Both serum immunoreactive FSH (immuno‐FSH) and bioactive FSH (bio‐FSH) concentrations were increased 4 days after hemicastration. The significant increase in serum immuno‐FSH in hemicastrated animals was prevented by follicular fluid administration, whereas the serum bio‐FSH activity and biologic to immunologic (B/l) ratios were increased in follicular fluid‐treated animals. The follicular fluid‐induced reduction in serum immuno‐FSH had no effect on serum testosterone secretion in hemicastrated rats. Serum inhibin concentrations were reduced 27% in hemicastrated rats compared with intact controls, while administration of exogenous follicular fluid increased serum inhibin concentrations. An elevation in serum immuno‐FSH secretion after hemicastration apparently is not required for the compensatory testosterone response. However, the observation of increased bio‐FSH in hemicastrated and follicular fluid‐treated animals raises questions about the importance of FSH quality (bioactivity), rather than quantity, for controlling testicular steroidogenic activity.
Hypergonadotropic Hypogonadism and Sperm Abnormalities in Men Born with Benign Sacrococcygeal Teratoma
Authors: LAHDENNE PEKKA , DUNKEL LEO , HEIKINHEIMO MARKKU , KOSKIMIES AARNE I. , SIIMES MARTTI A.
Published: October 2023

ABSTRACT:To elucidate the hypothetical role of a primary germ cell defect in the development of a germ cell tumor, with subsequent testicular dysfunction, the authors studied a series of men who had surgery performed for a benign sacrococcygeal teratoma when newborns. The mean levels of serum testosterone and gonadotropins did not differ from the control patients. However, gonadotropin‐releasing hormone stimulation caused exaggerated responses of serum luteinizing hormone and follicle‐stimulating hormone. Testicular size was small in three of eight patients. Semen analysis showed abnormal semen quality in five of eight patients. Only one patient had no evidence of testicular dysfunction. The results indicate that men born with benign sacrococcygeal teratoma may have Leydig cell dysfunction, abnormal spermatogenesis, or both. It was speculated that the associated abnormalities may have a common etiology: for instance, they might be due to a congenital germ cell defect.
Mitosis in Normal Adult Guinea Pig Leydig Cells
Authors: MENDIS‐HANDAGAMA S. M. L. CHAMINDRANI
Published: October 2023

ABSTRACT: In this study, Leydig cells in mitosis in adult guinea pigs were quantified. Testes of adult control guinea pigs (n = 10) were fixed by whole body perfusion with 2.5% glutaraldehyde in cacodylate buffer, postfixed in a mixture of osmium tetroxide‐potassium ferrocyanide, and embedded in Epon Araldite for qualitative and quantitative microscopy. Using stereologic techniques, the total number of Leydig cells per testis and the number of dividing Leydig cells per testis were quantified. Light microscopic studies revealed the presence of dividing Leydig cells. Ultrastructural studies on a few of these Leydig cells showed that they contained abundant smooth endoplasmic reticulum and mitochondria, which further supported this identity. The total number of Leydig cells per testis and the number of dividing Leydig cells per testis were determined as 14.1 × 106 (standard error [SE] = 0.33) and 8 × 103 (SE = 5), respectively. These results indicate that Leydig cells undergo mitosis at a rate of 1 per 1.75 × 104 in adult guinea pigs.
Influence of Bovine Follicular and Oviduct Fluids on Sperm Capacitation In Vitro
Authors: McNUTT TAMARA L. , KILLIAN GARY J.
Published: October 2023

ABSTRACT: The ability of bovine follicular fluid (FF) and oviduct fluid (ODF) to capacitate sperm was determined. At concentrations of greater than 20%, both FF and ODF capacitated sperm within 4 hours, but at concentrations greater than 40%, FF also initiated the acrosome reaction. Non‐luteal ODF at a concentration greater than 60% capacitated sperm within 2 hours. Non‐luteal ODF maintained sperm motility better than either luteal ODF or FF. Sperm previously capacitated in ODF underwent the acrosome reaction when exposed to solubilized zonae pellucidae (25 ng/μL) or FF (20%, V/V). Sperm treated with 60% non‐luteal ODF or 60% FF fertilized more oocytes at 2 hours than did sperm in treatments with less concentrated fluid. After 4 hours, all fluid treatments and modified Tyrode's medium supplemented with heparin exhibited a higher percentage of fertilized oocytes than the modified Tyrode's medium alone. Concentrations of both protein and glycosaminoglycans were significantly lower in ODF than in either blood serum or FF. These studies demonstrated that ODF capacitated sperm and sustained motility, but sperm were capacitated more rapidly in non‐luteal than in luteal ODF. In contrast, FF was able to both capacitate sperm and induce the acrosome reaction. These effects of ODF and FF on aspects of sperm function were uniquely concentration‐dependent, suggesting that different mechanisms may operate in ODF and FF to regulate these events.
Evaluation of Human Sperm Hyperactivated Motility and Its Relationship with the Zona‐Free Hamster Oocyte Sperm Penetration Assay
Authors: WANG CHRISTINA , LEUNG ANDREW , TSOI WAI‐LOONG , LEUNG JOANNE , NG VICTOR , LEE KAM‐FAI , CHAN STEVEN Y.W.
Published: October 2023

ABSTRACT: The authors studied hyperactivated motility of human spermatozoa as a method of evaluating capacitation by examining its relationship to results of zona‐free hamster oocyte sperm penetration assays (SPA) of semen samples from 50 men attending the infertility clinic. Hyperactivated motility was assessed in the seminal plasma and after swim‐up preparation of spermatozoa at 1, 3, and 24 hours of incubation in capacitation media using a computer‐assisted semen analysis system equipped with a hyperactivation module. Hyperactivated motility reached a peak at 1 hour and plateaued at 3 hours. The percentage of spermatozoa in seminal plasma with star‐spin hyperactivated motility was significantly lower in the group showing no penetration in the SPA. The hyperactivated motility characteristics did not differ in the groups with positive or negative penetration. Correlation analysis failed to show any significant relationship between the hyperactivated motility parameters and SPA score. When the hyperactivated motility characteristics were compared in samples with normal and abnormal semen analyses, the total percentage of spermatozoa with hyperactivated motility and the percentage with star‐spin at 3 hours were significantly lower in the group with abnormal semen analysis. The data indicate that lower hyperactivated motility of spermatozoa was found in patients with a score of zero for SPA and in patients with abnormal semen analysis. It was concluded that although no direct correlations were found between the results of SPA and hyperactivated motility, evaluating hyperactivated motility may still be useful as an early indicator of capacitation abnormalities of human spermatozoa not measured by SPA.
Pituitary Regulation of the Expression of the Farnesyl Pyrophosphate Synthetase Gene in the Testes of the Sexually Maturing Rat
Authors: NAZIAN S.J. , BREWER L.D. , NESS G.C.
Published: October 2023

ABSTRACT: While investigating the coordinate regulation of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase and farnesyl pyrophosphate synthetase, the authors observed that rat testes contained high levels of a farnesyl pyrophosphate synthetase mRNA that was larger than that found in most other tissues. This mRNA contains upstream AUG codons that may alter its rate of translation. The developmental and hormonal regulation of this testicular mRNA were investigated. Testicular levels of farnesyl pyrophosphate synthetase mRNA increased in rats between 30 and 40 days of age and remained elevated. Significant increases in serum testosterone concentrations and secondary sexual organ weights first occurred at 50 days of age. Hypophysectomy resulted in nearly undetectable levels of testicular farnesyl pyrophosphate synthetase mRNA. Treatment of hypophysectomized rats with gonadotropins increased the levels of this mRNA toward normal. These data indicate that an increase in farnesyl pyrophosphate synthetase mRNA takes place in testes just before the onset of puberty. This may be induced by the peripubertal rise in follicle‐stimulating hormone.
One‐Year Experience in the Treatment of Benign Prostatic Hyperplasia with Finasteride
Authors: Gormley Glenn
Published: October 2023

Finasteride (MK‐906) is a 5α‐reductase inhibitor that reduces circulating dihydrotestosterone (DHT) levels without lowering testosterone levels. The goal of this study was to evaluate the effects of long‐term (12 months) treatment with finasteride in 67 men with benign prostatic hyperplasia to determine if previously reported short‐term efficacy was maintained with chronic therapy. Treatment with 10 mg of finasteride resulted in a 78% to 80% reduction in DHT levels (P < 0.001) levels, and a small but significant increase in testosterone levels (P < 0.05) that were maintained over the 12‐month period. Significant reduction in prostate volume was observed after 6 months of treatment and maintained at month 12 (P < 0.05). In patients with baseline maximum flow rates ≤15 ml/second, maximum urinary flow significantly increased by a mean of 4 ml/second (P < 0.01), with at least a 3 ml/second improvement observed in up to 70% of the patients at month 12. These results indicate that finasteride can reduce prostate size and improve maximum urinary flow with no loss of efficacy after 1 year of treatment. It is concluded that finasteride has the potential to be an effective chronic therapy for benign prostatic hyperplasia.