bluuebunny/crossref_metadata_2025 huggingface dataset:
A Tunable Soft Silicone Bioadhesive for Secure Anchoring of Diverse Medical Devices to Wet Biological Tissue
Authors: Singh Manisha , Teodorescu Debbie L. , Rowlett Meagan , Wang Sophie X. , Balcells Mercedes , Park Clara , Bernardo Bruno , McGarel Sian , Reeves Charlotte , Mehra Mandeep R. , Zhao Xuanhe , Yuk Hyunwoo , Roche Ellen T.
Published: October 2023

Silicone is utilized widely in medical devices for its compatibility with tissues and bodily fluids, making it a versatile material for implants and wearables. To effectively bond silicone devices to biological tissues, a reliable adhesive is required to create a long‐lasting interface. BioAdheSil, a silicone‐based bioadhesive designed to provide robust adhesion on both sides of the interface is introduced here, facilitating bonding between dissimilar substrates, namely silicone devices and tissues. The adhesive's design focuses on two key aspects: wet tissue adhesion capability and tissue‐infiltration‐based long‐term integration. BioAdheSil is formulated by mixing soft silicone oligomers with siloxane coupling agents and absorbents for bonding the hydrophobic silicone device to hydrophilic tissues. Incorporation of biodegradable absorbents eliminates surface water and controls porosity, while silane crosslinkers provide interfacial strength. Over time, BioAdheSil transitions from nonpermeable to permeable through enzyme degradation, creating a porous structure that facilitates cell migration and tissue integration, potentially enabling long‐lasting adhesion. Experimental results demonstrate that BioAdheSil outperforms commercial adhesives and elicits no adverse response in rats. BioAdheSil offers practical utility for adhering silicone devices to wet tissues, including long‐term implants and transcutaneous devices. Here, its functionality is demonstrated through applications such as tracheal stents and left ventricular assist device lines.
Scalable Printing of Metal Nanostructures through Superluminescent Light Projection
Authors: Choi Jungho , Saha Sourabh K.
Published: October 2023

Direct printing of metallic nanostructures is highly desirable but current techniques cannot achieve nanoscale resolutions or are too expensive and slow. Photoreduction of solvated metal ions into metallic nanoparticles is an attractive strategy because it is faster than deposition‐based techniques. However, it is still limited by the resolution versus cost tradeoff because sub‐diffraction printing of nanostructures requires high‐intensity light from expensive femtosecond lasers. Here, this tradeoff is overcome by leveraging the spatial and temporal coherence properties of low‐intensity diode‐based superluminescent light. The superluminescent light projection (SLP) technique is presented to rapidly print sub‐diffraction nanostructures, as small as 210 nm and at periods as small as 300 nm, with light that is a billion times less intense than femtosecond lasers. Printing of arbitrarily complex 2D nanostructured silver patterns over 30 µm × 80 µm areas in 500 ms time scales is demonstrated. The post‐annealed nanostructures exhibit an electrical conductivity up to 1/12th that of bulk silver. SLP is up to 480 times faster and 35 times less expensive than printing with femtosecond lasers. Therefore, it transforms nanoscale metal printing into a scalable format, thereby significantly enhancing the transition of nano‐enabled devices from research laboratories into real‐world applications.
Critical levels and nitrogen fertilizer equivalencies for grain protein in winter wheat
Authors: Long Dan S. , Reardon Catherine L. , Adams Curtis B.
Published: October 2023

Precision nitrogen (N) application methods have been developed for dryland wheat that utilize site‐specific measurements of grain protein concentration (GPC) to determine N fertilizer recommendations for the next season. The objectives of this study were to determine the critical protein level and N equivalent to a unit change in GPC from relationships between GPC, and grain yield or plant‐available N in soft white winter wheat (SWW, Triticum aestivum L.), and assess the consistency of these relationships across SWW cultivars grown under a wide range of precipitation. A 3‐year study was undertaken near two sites: Lexington (225 mm of mean annual precipitation) and Adams (450 mm) in Oregon. Differences in precipitation and N fertilization rates between sites were used to induce variability in grain yield and GPC of four cultivars. A critical protein concentration of 117.5 g kg−1 was defined by Cate–Nelson analysis of scatter plots of relative yield versus GPC. Critical protein among cultivars ranged between 105 and 118 g kg−1 suggesting that 117.5 g kg−1 might be used as a general indicator of N sufficiency. Slopes of the regression of available N on GPC were consistent across cultivars and revealed that 4.2–8.4 kg N ha−1 is equivalent to a unit change protein (1 g kg−1) in lower precipitation areas of the region where SWW is under water stress during grain filling. This information is useful in calculating the N to apply from the GPC in the previous season to meet crop requirements in the next season.
The sulfur species in hot rocky exoplanet atmospheres
Authors: Janssen L. J. , Woitke P. , Herbort O. , Min M. , Chubb K. L. , Helling Ch. , Carone L.
Published: October 2023

The first JWST observations of hot Jupiters showed an unexpected detection of SO in their hydrogen‐rich atmospheres. We investigate how much sulfur can be expected in the atmospheres of rocky exoplanets and which sulfur molecules can be expected to be most abundant and detectable by transmission spectroscopy. We run thermochemical equilibrium models at the crust–atmosphere interface, considering surface temperatures 500–5000 K, surface pressures 1–100 bar, and various sets of element abundances based on common rock compositions. Between 1000 and 2000 K, we find gaseous sulfur concentrations of up to 25% above the rock in our models. SO, SO, HS, and S are by far the most abundant sulfur molecules. SO
shows potentially detectable features in transmission spectra at about 4 m, between 7 and 8 m, and beyond 15 m. In contrast, the sometimes abundant HS molecule is difficult to detect in these spectra, which are mostly dominated by HO and CO. Although the molecule PS only occurs with concentrations  ppm, it can cause a strong absorption feature between 0.3 and 0.65 m in some of our models for high surface pressures. The detection of sulfur molecules would enable a better characterization of the planetary surface.
The novel technique of drainage stenting using a tapered sheath dilator in endoscopic ultrasound‐guided biliary drainage
Authors: Kato Akihisa , Yoshida Michihiro , Hori Yasuki , Kachi Kenta , Sahashi Hidenori , Toyohara Tadashi , Adachi Akihisa , Kuno Kayoko , Kito Yusuke , Kataoka Hiromi
Published: October 2023

During endoscopic ultrasound‐guided biliary drainage (EUS‐BD), there is a risk for bile leakage until stent deployment, which can result in severe peritonitis, particularly when passing a drainage stent becomes challenging despite tract dilation. There is no established method or dedicated device to optimize EUS‐BD. Therefore, we have developed a novel stent deployment technique using the tapered sheath dilator. To address the safety and technical aspects of the EUS‐BD technique, we retrospectively analyzed 11 consecutive patients who underwent EUS‐BD using the tapered sheath dilator. The procedure involved the insertion of a guidewire, followed by mechanical dilation using the tapered sheath dilator. Subsequently, the inner catheter was removed and drainage stents (up to 6 Fr in diameter) were deployed through the outer sheath. We found a 100% technical success rate for tract dilation and stent deployment; moreover, all patients achieved clinical success. The median time for dilation was 40 s (range, 8–198), whereas the median time from dilation to stent deployment was 10 min (range, 6–19). Notably, no cases of bile leakage or peritonitis were observed. In conclusion, the use of the integrated device for tract dilation and stent delivery system might provide a safe and straightforward technique for drainage stenting during EUS‐BD.
New Insights into Radio Wave Energy Harvesting across Wide Geographical Ranges Harnessing Medium‐Wave Radio Broadcasting Infrastructure
Authors: Shoji Eiichi
Published: October 2023

This study conducts field experiments using the radio‐wave energy harvester of hoop‐shaped radio (HOOPRA) to elucidate the relationship between the distance from the medium‐wave (MW) radio broadcasting station and the resonance voltage as an index of harvested energy. Accordingly, a numerical equation that describes the relationship between the distance and voltage with a strong correlation coefficient of R2 > 0.996 is derived. HOOPRA can illuminate ultrabright white, green, and red light‐emitting diodes (LEDs) within a 5 km radius of the public Nihon Hoso Kyokai JOFG (927 kHz, 5 kW) in Fukui, thereby serving as a valuable energy source for the 150 000 residents (60 000 households) in this region. The public JOAK (594 kHz, 300 kW) and JOAB (693 kHz, 500 kW) are examined for similar field experiments in the Kanto region. The results reveal that HOOPRA can illuminate ultrabright white, green, and red LEDs within a radius of 30 km and ultrabright red LEDs within a radius of 50 km from JOAB, which will benefit the 23 million residents (1.1 million households) in this region. Overall, the results provide novel insights for developing ultrawide‐area wireless energy‐transfer technology by leveraging the global infrastructure of MW radio broadcasting.
Corn Husk‐Derived Activated Carbon as High‐Performance Anode Constituent for Rechargeable Aqueous Zn/α‐MnO2 Batteries
Authors: Anand Abhas , Ji Dixit Ram , Verma Anil , Basu Suddhasatwa
Published: October 2023

Zinc (Zn) aqueous batteries have gained significant research interest for large‐scale electrochemical energy storage applications due to their rich abundance of raw materials, high energy density, environmental friendliness, low capital, and maintenance expenditure. However, the progress of metallic Zn anode in the aqueous Zn battery chemistry is hindered by several critical challenges, including low Coulombic efficiency and the formation of Zn dendrites, irrespective of the pH of the electrolyte. Herein, the application of porous activated carbon (AC) derived from waste corn husk as Zn anode constituent to improve the cyclability of the aqueous Zn battery is reported. In the full cell study, it is observed that the battery containing 15 wt% of AC as anode coupled with α‐MnO2 nanorods cathode shows excellent capacity retention of 86.42% (initial discharge capacity = 211.67 mAh g−1) after 125 charge/discharge cycles at current rate of 100 mA g−1. Moreover, herein, insights into converting waste to energy by utilizing the biowaste precursor to develop stable and durable rechargeable aqueous Zn‐based batteries are provided.
Graphene‐Based Microfibers Electrode Materials for Wearable Fiber‐Shaped Supercapacitors
Authors: Wang Xiaomei
Published: October 2023

In recent times, fiber‐shaped supercapacitors (FSCs) have emerged as a highly promising class of energy storage devices owing to their superb flexibility, elevated energy density, and lengthy cycle life. Herein, the recent advancements in the application of graphene‐based microfibers electrode materials in FSCs are comprehensively reviewed. The synthesis methodologies of graphene‐based materials and their subsequent integration into FSCs are thoroughly discussed. Additionally, the performance characteristics of FSCs based on graphene, including their elevated specific capacitance, exceptional cycling stability, and superior flexibility, are highlighted. Finally, the challenges and future prospects of graphene‐based FSCs are discussed. On the whole, this article provides a detailed insight into the expansive potential of graphene‐based FSCs, along with current challenges and future opportunities.
Investigation on Nonisothermal Dehydrogenation Behavior of Mg–Ni–La–H Materials Prepared by Mechanochemical Reaction
Authors: Cao Qianhong , Hou Xiaojiang , Xu Guangsheng , Li Danting , Hu Ping , Shu Qiang , Wang Chenlu , Zhao Duode , Bai Jing
Published: October 2023

Mg10NixLa–H alloys are synthesized by mechanochemical reaction starting with Mg–Ni–La multiphase polycrystalline alloys prepared by resistance melting furnace. The nonisothermal hydrogen desorption behaviors are investigated herein. All prepared samples are characterized by scanning electron microscopy, X‐ray diffraction, fully automatic fast surface and porosity analysis meter Brunauer–Emmett–Teller (BET), differential scanning calorimetry, and thermogravimetric analyzer to get information of phase compositions, microstructure, BET surface area, and dehydrogenation properties. The results demonstrate that Mg10NixLa–H exhibits enhanced nonisothermal hydrogen desorption behavior owing to the synergistic effects among hydrides. The main peak dehydrogenation temperatures for Mg10Ni5La–H, Mg10Ni10La–H, and Mg10Ni15La–H alloys are 375.3, 374.4, and 359.7 °C at 5 °C min−1, respectively. And the apparent activation energy for Mg10Ni5La–H, Mg10Ni10La–H, and Mg10Ni15La–H is 111.7, 275.5, and 184.7 kJ mol−1, respectively. However, the actual hydrogen release capacities of Mg10Ni5La–H, Mg10Ni10La–H, and Mg10Ni15La–H are about 5.09, 3.98, and 4.49 wt%, respectively. Mg10Ni15La–H exhibits the lowest onset dehydrogenation temperature due to its reduced particle size and uniformly distributed hydride phase. The modification of Mg‐based hydrogen storage materials by combining mechanochemical reaction and multiple microalloying is essential for further improvement of thermal properties.
Evaluation of collaborative mental health services in Latin America: Theoretical and methodological basis
Authors: Sapag Jaime C. , Rush Brian
Published: October 2023

Objectives

Approaches to collaborative mental health care (CMHC) have been implemented in many countries to strengthen the accessibility and delivery of mental health services in primary care. However, there are not well‐defined frameworks to evaluate CMHC models. The purpose of this article is to identify, contextualize and discuss relevant health services research approaches, theory, and evaluation models for the development of an appropriate evaluation framework in order to foster effective CMHC in Latin America.

Methods

A comprehensive literature review informed a critical analysis of relevant theories and alternative methods to be considered in the development of the framework.

Results

Specific health services research frameworks are discussed in the context of evaluating CMHC. Two theoretical perspectives ‐ collaboration theory and systems theory – and three evaluation models‐ realistic, developmental and collaborative ‐ are analyzed in terms of their relevance. Methodological implications are identified.

Conclusion

An appropriate evaluation framework for CMHC in Latin America needs to reflect theoretical and contextual considerations and relevant evaluation approaches and methods, including key dimensions and attributes/variables, core indicators, and recommendations for implementation.
Dilevalol: An Overview of Its Clinical Pharmacology and Therapeutic Use in Hypertension
Authors: Lalonde Richard L. , Tenero David M. , Kazierad David J.
Published: October 2023

Dilevalol is a novel antihypertensive drug that combines nonselective ß blockade with selective ß2‐receptor agonist activity. Its antihypertensive effect is mediated through arterial vasodilation and a decrease in systemic vascular resistance. At rest, dilevalol has little effect on heart rate or cardiac output. The drug is rapidly and completely absorbed but undergoes significant first‐pass hepatic extraction. Its elimination half‐life of approximately 12 hours allows for once‐daily administration. In controlled clinical trials, dilevalol was at least as effective as angiotensin‐converting enzyme inhibitors and comparable to ß blockers in antihypertensive efficacy. Preliminary data indicate that dilevalol reverses left ventricular hypertrophy in some patients. It does not adversely affect renal function and may have a favorable effect on plasma lipids, especially high‐density lipoprotein cholesterol. The agent is usually well tolerated and may prove to be a useful addition to our antihypertensive drugs.
Pharmacokinetics of Methylprednisolone Sodium Succinate and Methylprednisolone in Patients Undergoing Cardiopulmonary Bypass
Authors: Kong Ah‐Ng , Jungbluth Gail L. , Pasko Mary T. , Beam Thomas R. , Jusko William J.
Published: October 2023

The pharmacokinetics of methylprednisolone sodium succinate (MPHS) and methylprednisolone (MP) were determined in six patients undergoing open heart surgery with cardiopulmonary bypass. Plasma concentrations of both compounds were measured by high‐performance liquid chromatography after doses of MPHS of 1.7‐2.4 g. The prodrug ester MPHS yields MP with an average formation rate constant of 0.70 + 0.29 hr−1. Peak concentrations of MP occur around 1–2 hours after loading and additional administration of MPHS. The pharmacokinetic values of the two drugs in patients having cardiopulmonary bypass were compared to those in younger, healthy subjects. The volume of distribution of MPHS was lower in the patients, and that of MP was similar to the value in controls. Total clearances of both agents were reduced by about 5 and 2 times. The elimination half‐life of MPHS was increased slightly, whereas that of MP increased more than twice in the patients. Significant alterations in clearances occurred in patients, but concentrations of MP were appreciable and prolonged MP due to the extensive formation of MP from MPHS and reduced clearance of MP.
Relationship Between Values of Bioelectrical Impedance and Creatinine Clearance
Authors: Smythe Maureen A. , Baumann Terry J. , Zarowitz Barbara J. , Peterson Edward , Dumler Francis
Published: October 2023

This investigation was conducted to determine if measurements of bioelectrical impedance in conjunction with serum creatinine concentrations are useful in predicting creatinine clearance. Twenty‐eight healthy volunteers between 23 and 50 years of age followed an individualized protein diet to provide 1.2 g protein/kg/day for 3 consecutive days. At the beginning of day 3, a 24‐hour urine collection was initiated. At the midpoint of urine collection, bioelectrical impedance measurements of resistance and reactance were taken, together with a single blood sample for assessment of serum creatinine concentration. Multiple linear regression techniques were used to identify significant values for predicting creatinine clearance. Resistance and serum creatinine concentration were identified as significant predictors. The measured creatinine clearance was compared to that predicted by the impedance‐derived model that we developed, as well as other established estimation methods. Mean absolute prediction errors in creatinine clearance using this model were significantly lower than those obtained using four empiric methods. Bioelectrical impedance may provide a noninvasive, quick, and accurate method for predicting creatinine clearance from serum creatinine concentration values.
Cocaine Abuse and Its Treatment
Authors: Hall W. Carey , Talbert Robert L. , Ereshefsky Larry
Published: October 2023

Widespread use and abuse of cocaine have increased the frequency with which health professionals must manage acute and chronic intoxication and the complications stemming from drug ingestion. Acute intoxication from catecholamine excess progresses through three stages, affecting the cardiovascular, respiratory, and central nervous systems. Management is to support or return these systems to normal with sedation, ß blockade, and antiarrhythmics. Casual cocaine use is no longer considered benign, and numerous related medical complications are now recognized. Dopaminergic systems are the principal sites of reward and participate in abstinence symptomatology, putatively through depletion of dopamine and changes in receptor sensitivity and responsiveness. Long‐term treatment approaches have focused on psychologic strategies of behavior modification and supportive psychotherapy. Pharmacotherapy with desipramine, amantadine, and bromocriptine was shown in preliminary studies to minimize the symptoms of cocaine withdrawal when used adjunctively with psychotherapy. The response to treatment may depend on the patient's premorbid psychiatric status.
The Cloning and Production of Recombinant Human Erythropoietin
Authors: Egrie Joan
Published: October 2023

The production of recombinant human erythropoietin (r‐HuEPO) began with a search for the gene coding for human erythropoietin (EPO). Two radiolabeled pools of oligonucleotide probes were designed, based on amino acid sequence information obtained from human urinary EPO. Each probe, consisting of complex mixtures of 128 short synthetic sequences of DNA, was used to search a human genomic library for clones containing the human EPO gene sequence. To verify that the isolated clones contained the complete functional gene encoding human EPO, these sequences were expressed in Chinese hamster ovary cells, and the secreted r‐HuEPO was purified, characterized, and compared with the human urinary hormone using a variety of different techniques. Results of these studies indicate that r‐HuEPO is virtually indistinguishable from human urinary EPO in its biochemical and immunological properties. It is a 165‐amino acid protein whose primary sequence is identical to that of urine‐derived EPO. The subsequent development of large‐scale cell culture and production techniques has made available sufficient amounts of r‐HuEPO for clinical use in the treatment of the debilitating anemia that almost invariably accompanies chronic renal failure.
The Effect of Theophylline on Respiratory Muscle Contractility and Fatigue
Authors: Landsberg Karen F. , Vaughan Leigh M. , Heffner John E.
Published: October 2023

The traditional role of theophylline as a bronchodilator has been expanded by recent findings that suggest this drug has more than smooth muscle relaxant properties. Several investigators indicate that theophylline has an inotropic effect on respiratory muscle, causing enhanced muscular contraction and prevention of muscle fatigue. In animal studies, the drug enhanced respiratory muscle contraction by 15–20%, with levels in the upper end of the therapeutic range (15–20 mg/L). Results of studies in healthy volunteers and patients with lung disease, however, are conflicting. Five clinical trials demonstrated increased diaphragmatic contractility, whereas seven trials showed no effect, with five referring to the diaphragm and the remaining two to the sternomastoid muscle. Disparity in outcomes may be attributed to differences in patient populations, study designs, and techniques used to determine diaphragmatic contractility. Few long‐term trials exist that document significant clinical benefit. Theophylline may prove to be of value in selected populations, such as adults with hypercapnic obstructive lung disease.
Liver Function Assessment by Drug Metabolism
Authors: Barstow Lynda , Small Ralph E.
Published: October 2023

Liver function can be assessed by administering an exogenous substance to quantify changes in hepatic blood flow, uptake, biotransformation, and excretion. Characterization of drug half‐life, clearance, and product formation rates are possible methods for measuring hepatic efficiency. Allopurinol and caffeine have been used to measure metabolite formation followed by renal elimination of both parent substance and metabolite. Sorbitol, a substance with high intrinsic clearance, can reflect liver blood flow, while trimethadione, a low‐extraction drug, has been used to measure liver enzyme capacity. Metabolites from lidocaine, methacetin, and aminopyrine have been measured in serum, urine, and breath tests. Salivary clearance measurements of caffeine and antipyrine are reported as suitable for routine use. Genetic diversity of isoenzymes and the many metabolic processes used by hepatocytes make it extremely difficult to quantify functional changes with one substance. Combinations of model substrates have been suggested to assess the many hepatic processes.
Pharmacokinetics and Pharmacodynamics of Anticancer Agents: Contributions to the Therapy of Childhood Cancer
Authors: Petros William P. , Evans William E.
Published: October 2023

Strategies for treating pediatric malignancies have not only been successful (i.e., curative) for several disseminated childhood cancers, they have also served as paradigms for the therapy of many adult cancers. Initial strategies included combined treatment modalities (chemotherapy, surgery, radiotherapy) and combinations of different pharmacologic classes of anticancer drugs given in the appropriate schedules. Despite the currently successful therapy for some malignancies (e.g., 70% 4‐year disease‐free survival in acute lymphocytic leukemia), many children die without known reason. Recent advances in the clinical pharmacology of anticancer drugs have identified relationships between dose intensity and response (efficacy, toxicity). Traditional methods of measuring dose intensity (prescribed dose) have evolved to more sophisticated approaches in maximizing the intensity of treatment, with good response rates. Other methods of optimizing chemotherapy for individual patients include bone marrow support procedures and therapy with biologic response modifiers. Relatively few clinically useful new anticancer drugs have been discovered in the past several years. Fortunately, the potential to improve therapy with currently available agents has come about through enhanced knowledge of the biochemical and clinical pharmacology of anticancer drugs and biologic response modifiers, as well as improved understanding drug resistance biology.
Pharmacokinetics and Pharmacodynamics of Heparin During Hemodialysis: Interpatient and Intrapatient Variability
Authors: Kandrotas Robert J. , Gal Peter , Douglas Jean B. , Deterding James
Published: October 2023

Heparin pharmacokinetics and pharmacodynamics were studied in 17 patients undergoing hemodialysis, once a week for 4 weeks in order to evaluate intrapatient variability over time. A single bolus injection of heparin was administered directly into the circulation immediately prior to the start of hemodialysis in doses ranging from 3000 to 12,000 U. Blood samples were obtained to determine activated coagulation times (ACT) and heparin concentrations (HC). Combined zero‐ and first‐order elimination was seen in each of the 4 weeks. The half‐life of heparin decreased from beginning to end of hemodialysis during each week, with the percentage of decrease from the start of dialysis ranging from 70–74%, indicating concentration‐dependent elimination. Since the zero‐order component did not appear to be clinically significant, first‐order elimination was assumed. A linear decline in ACT over the time of the dialysis period was also seen during each week. A profile of ACT versus HC was generated for each patient as well as for the mean data to assess the relationship of HC to response. An excellent correlation was found for both individual patient data and mean data. In the third week the patients were randomized to receive standard treatment or an individualized dose. They were then crossed over to the opposite group in the fourth week to see if this relationship between ACT and HC would be useful in predicting heparin dose. These profiles were used to individualize the dose during either the third or fourth week of the study. No significant differences were noted between actual and predicted ACT. A significant degree of interpatient variability was demonstrated. Since no such variability was found when elimination rate constant, half‐life, clearance, distribution volume, and ACT were compared over the 4‐week study period, however, pharmacokinetic and pharmacodynamic profiling of patients when hemodialysis is first initiated may be useful for dosing heparin during subsequent hemodialysis periods.
Evaluation of Aspirin, Caffeine, and Their Combination in Postoperative Oral Surgery Pain
Authors: Forbes James A. , Jones Katherine F. , Kehm Carolyn J. , Smith W. King , Gongloff Charles M. , Zeleznock John R. , Smith John W. , Beaver William T. , Kroesen Manfred
Published: October 2023

Three hundred fifty outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double‐blind basis, to receive a single oral dose of aspirin 650 or 1000 mg, caffeine 65 mg, a combination of aspirin 650 mg with caffeine 65 mg, or placebo. Using a self‐rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. Estimates of summed pain intensity difference, peak pain intensity difference, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active treatments except caffeine were significantly superior to placebo. Pairwise comparisons indicated the aspirin‐caffeine combination was statistically superior to aspirin 650 mg alone for hours of 50% relief among patients who had severe baseline pain. Adverse effects were transitory and none were serious.
A Comparison of the Risk of Hypoglycemia Between Users of Human and Animal Insulins. 1. Experience in the United Kingdom
Authors: Jick Hershel , Hall Gillian C. , Dean Alan D. , Jick Susan S. , Derby Laura E.
Published: October 2023

In a case‐control study of 121 young insulin‐dependent diabetics diagnosed as having an episode of hypoglycemia, the relative risk estimate comparing human with animal insulins was 0.8 (95% confidence interval 0.4, 1.6) controlling for age, general practice, and calendar time. We conclude that in this study population derived from general practices in the United Kingdom, the risk of hypoglycemia was no higher in users of human insulin than it was in users of animal insulins.
The Time to Reach Steady State After the Administration of Intravenous Bolus, Constant Infusion, and Oral Immediate‐Release and Sustained‐Release Preparations
Authors: Chow Moses S. S. , Sun He
Published: October 2023

Based on one‐compartment pharmacokinetic model, the equations to calculate the specific fractional steady‐state of drug level achieved at any time (FSS) after administration of intravenous bolus, constant infusion, and oral immediate‐release preparations are reviewed. Also the equation to calculate FSS after administering an oral sustained‐release dosage form is derived. From these equations, it can be shown that the drug FSS after these routes of administration is dependent primarily on the elimination rate constant (K). However, for a sustained‐release preparation, the FSS is dependent on K, drug release rate constant (K1), as well as the fraction of sustained release (Fs) of the dosage form. Using the new derived equation for FSS, several simulations were performed to evaluate the effects of K1 K, and Fs. These indicate that the time to achieve a given FSS is prolonged as K1 or K becomes smaller and as Fs becomes large.
The Effect of Theophylline on Estimated Hepatic Blood Flow
Authors: Kisor David F. , Wooding‐Scott Ronald A.
Published: October 2023

We observed the effect of aminophylline administration on estimated hepatic blood flow. Indocyanine green (ICG) 0.5 mg/kg was administered as an intravenous bolus dose before and after intravenous infusion of 7 mg/kg aminophylline. Venous blood was collected at timed intervals over 15 minutes to construct ICG concentration‐time graphs. Pharmacokinetic values were calculated using non‐compartmental methods. Estimated hepatic blood flow decreased from 790 ± 190 to 665 ± 100 ml/minute (p < 0.05) after administration of aminophylline.
The Pharmacologic Activity of Ketorolac Tromethamine
Authors: Rooks Wendell H.
Published: October 2023

Ketorolac tromethamine is a highly potent member of a class of compounds having both analgesic and antiinflammatory activity. In animal pain models using underlying inflammation, ketorolac markedly inhibited the pain response and increased the pain threshold; it did not exhibit any narcotic or central nervous system depressant effects. It was also active in rat models of acute and chronic inflammation and pyresis. These activities are mediated primarily by potent prostaglandin cyclooxygenase inhibitory activity. Mild central nervous system and cardiovascular effects occurred only at doses far greater than those required for analgesic and antiinflammatory activity. Solutions of ketorolac tromethamine are not irritating. When given intramuscularly to rabbits (0.31‐5% solutions), no drug‐related irritation or changes in serum creatine phosphokinase were seen. The agent was not irritating when applied to the skin or eyes (≤0.5% solutions) of animals.
Ketorolac Tromethamine Pharmacokinetics and Metabolism After Intravenous, Intramuscular, and Oral Administration in Humans and Animals
Authors: Mroszczak Edward J. , Jung Donald , Yee James , Bynum Lincoln , Sevelius Hilli , Massey Ian
Published: October 2023

In humans, ketorolac is completely bioavailable and its kinetics are linear. It is absorbed rapidly (half‐life for absorption 3.8 min) after oral (fasting) and intramuscular administration; food delays but does not reduce its absorption. The drug is highly protein bound in humans (>99%). The mean plasma elimination half‐life is 5–6 hours, and ketorolac is not extensively distributed outside the vascular compartment (Vd815 L). Virtually all of the drug‐related material circulating in plasma is in the form of ketorolac (>96%), with the only metabolite the pharmacologically inactive p‐hydroxyketorolac (PHK). Humans excrete about 90% of the administered dose in urine. About 60% of drug‐related material recovered from urine is ketorolac, about 12% is PHK, and 28% represents polar, glucuronide conjugates of ketorolac. The animal models in which ketorolac's metabolism and kinetics are most similar to those in humans are the mouse and monkey, respectively.
Efficacy and Safety of Single Doses of Intramuscular Ketorolac Tromethamine Compared with Meperidine for Postoperative Pain
Authors: Stanski Donald R. , Cherry Carter , Bradley Rita , Sarnquist Frank H. , Yee James P.
Published: October 2023

Ketorolac tromethamine, a potent nonnarcotic prostaglandin synthetase‐inhibiting analgesic, was compared with meperidine for relief of moderate to severe postoperative pain. In a double‐blind, randomized study, 125 patients received single intramuscular doses of ketorolac 30 or 90 mg or meperidine 50 or 100 mg. The degree of pain and pain relief were quantified verbally and with visual analog scales at baseline and 30 minutes, then hourly for 6 hours. Ketorolac 30 and 90 mg were significantly superior to meperidine 50 mg in six of nine efficacy measures.

The onset of and peak analgesic effect of both doses of ketorolac and of meperidine were equivalent. Compared with both doses of meperidine, the two doses of ketorolac exhibited significantly longer duration of analgesic effect, as measured by the percentage of patients who terminated the study because of inadequate pain relief. The frequency of side effects was not significantly different between the drugs. The prolonged efficacy of intramuscular ketorolac combined with the reduced risk of respiratory depression suggest an important use of this drug for the relief of postoperative pain.
Intramuscular Ketorolac and Morphine in the Treatment of Moderate to Severe Pain After Major Surgery
Authors: Spindler Joseph S. , Mehlisch Donald , Brown Colin R.
Published: October 2023

A multicenter, randomized, open, parallel study in 227 patients with moderate or severe postoperative pain compared the analgesic efficacy and safety of multiple intramuscular injections of ketorolac 30 mg (184 patients) and morphine 10 mg (43 patients) administered as needed as often as every 2 hours for a maximum of 40 doses or 10 days. Supplemental standard analgesics, usually opiates, were permitted if additional pain medication was required. When used with supplemental analgesics (averaging less than 1 dose/day), ketorolac afforded equal or superior efficacy to morphine used with other supplemental analgesics. Given alone or with supplemental analgesics, ketorolac was better tolerated than morphine, as reflected by rate of terminations due to adverse events and frequency of common complaints. Intramuscular ketorolac thus provides an important additional approach to management of pain.
Evaluation of Ketorolac, Ibuprofen, Acetaminophen, and an Acetaminophen‐Codeine Combination in Postoperative Oral Surgery Pain
Authors: Forbes James A. , Kehm Carolyn J. , Grodin Mss. Charlene D. , Beaver William T.
Published: October 2023

Two‐hundred six outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned on a double‐blind basis to receive oral doses of ketorolac tromethamine 10 and 20 mg, ibuprofen 400 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self‐rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. Analgesia was similar for ketorolac 10 and 20 mg and ibuprofen 400 mg; however, these treatments were superior to acetaminophen alone and the acetaminophen‐codeine combination. The analgesic effect of each active medication was significant by hour 1 and persisted for 5–6 hours. The data suggest a plateau in ketorolac's analgesic efficacy at the 10‐mg level. Repeat‐dose data indicated that on the day of surgery ketorolac 10 and 20 mg and ibuprofen 400 mg were superior to acetaminophen 600 mg; ketorolac 20 mg was also superior to acetaminophen‐codeine. Differences among active medications were not significant when data for the entire postoperative period (days 0–6) were evaluated. The frequency of adverse effects was similar for the active medications.
Comparison of Long‐Term Safety of Ketorolac Tromethamine and Aspirin in the Treatment of Chronic Pain
Authors: Rubin Paul , Yee James P. , Ruoff Gary
Published: October 2023

A double‐blind, randomized trail was conducted in 823 patients who required longterm analgesic therapy for chronic pain such as that caused by osteoarthritis, fibromyopathies or fibromyalgias, other nonarticular chronic soft tissue pain syndromes, or headaches. The safety and analgesic efficacy of ketorolac tromethamine 10 mg 4 times a day as needed was compared with that of aspirin 650 mg 4 times a day as needed. The primary emphasis of this 52‐week study was on evaluating the safety of the drugs. Patients returned to the clinics at 2, 5, 10, 15, 20, 28, 36, 44, and 52 weeks for assessments of safety and efficacy. Both patients' and investigators' evaluations of overall efficacy and safety favored ketorolac over aspirin. The probability of early withdrawal from the study was significantly higher with aspirin than with ketorolac, primarily because of lack of efficacy. Early withdrawal for safety‐related reasons alone was similar for those taking aspirin and ketorolac.
Intravenous Ketorolac Tromethamine versus Morphine Sulfate in the Treatment of Immediate Postoperative Pain
Authors: Peirce Richard J. , Fragen Robert J. , Pemberton Donna M.
Published: October 2023

Intravenous ketorolac tromethamine was compared with morphine sulfate for the relief of moderate to severe postoperative pain and for side effects in 125 women undergoing major abdominal gynecologic surgery. Patients were randomly assigned to receive an initial intravenous dose of ketorolac 10 mg, ketorolac 30 mg, morphine 2 mg, or morphine 4 mg, administered in a double‐blind fashion. No other narcotics were administered in the 3 hours preceding the first dose of study drug. A second dose was administered on request, but no sooner than 15 minutes after the initial dose. Patients who required additional analgesia within the 6‐hour observation period were remedicated with a backup analgesic and withdrawn from the study. Pain scores and side effect evaluations were performed at baseline, 30 minutes, 1 hour, and then hourly for up to 6 hours or until the subject terminated the study. No significant differences among the treatments were noted in terms of area under the time‐effect curves for pain intensity differences or pain relief. In each treatment group, 70–80% of patients withdrew within 1 hour and approximately 90% within 3 hours of the initial drug dose because of inadequate analgesia. With the dosage regimens used, neither drug adequately controlled moderate to severe pain in the immediate postoperative period. Patients receiving ketorolac experienced significantly less drowsiness than those given morphine, and some subjects in each experienced nausea. No serious adverse effects were reported.
Hemodynamic Effects of Two Intravenous Doses of Ketorolac Tromethamine Compared with Morphine
Authors: Camu Frederic , Van Overberge Luc , Bullingham Roy , Lloyd Julia
Published: October 2023

The cardiovascular effects of intravenous administration of ketorolac tromethamine 10 and 90 mg were measured and compared with those of morphine sulfate 10 mg in 18 anesthetized patients after major vascular surgery. Morphine caused a significant reduction in mean arterial pressure, left cardiac work index, and left ventricular stroke work index. Stroke volume index, cardiac output, and pulmonary artery pressures decreased to a lesser extent. Ketorolac at either dose was not associated with any significant change in cardiac and hemodynamic parameters.

The data suggest that even high doses of the drug may be safely administered in clinical situations where hypotension is disadvantageous or where reduction in afterload is not a specific therapeutic aim.
Parenteral Ketorolac: Opiate‐Sparing Effect and Lack of Cardiorespiratory Depression in the Perioperative Patient
Authors: Kenny Gavin N. C. , McArdle Colin S. , Aitken Hilary H.
Published: October 2023

Two studies evaluated the intraoperative and postoperative use of ketorolac, a nonopioid analgesic. Compared with the opioid analgesic alfentanil, ketorolac administered intraoperatively exerted no adverse effects on cardiorespiratory functions (i.e., no changes in heart rate, arterial partial pressure of carbon dioxide, or mean arterial pressure, and no associated apnea). Analgesic efficacy of both agents was judged to be equal. The study of postoperative infusion of ketorolac in combination with patient‐controlled administration of morphine confirmed the analgesic efficacy of ketorolac when used after upper abdominal surgery. The narcotic‐sparing effect was demonstrated by the finding that patients who received placebo self‐administered over 40% more morphine in the first 24 hours after surgery than those in the ketorolac group. The better pain scores with ketorolac may be associated with the reduction in unpleasant morphine‐related side effects or with the provision of continuous background analgesia. The lack of respiratory depression with ketorolac, which would be anticipated from its inability to bind to central opioid receptors, was also demonstrated. In the placebo group, arterial partial pressure of carbon dioxide was significantly increased postoperatively, whereas a similar increase was not found in the ketorolac group. Results of the two investigations demonstrate the absence of opioid effects with ketorolac, and support its use for intraoperative and postoperative analgesia in patients undergoing major surgery.
Evolution of ß‐Lactamase Inhibitors
Authors: Jackson Derrick
Published: October 2023

After the introduction of penicillin G into therapeutics, bacteria became increasingly resistant to this penicillin and subsequent ß‐lactam antibiotics. The major cause of this resistance is ß‐lactamase, an enzyme produced by the bacterium, that destroys the antibiotic before it reaches its target within the bacterial cell. One of the ways to combat this resistance has been the use of ß‐lactamase inhibitors, which protect the antibiotic by inactivating the destructive enzyme before the antibiotic reaches the infection site. At present, at least two ß‐lactamase inhibitors are in clinical use, clavulanic acid and sulbactam, that are effective against most ß‐lactamases, although relatively inactive against class I ß‐lactamases, the cephalosporinases. Newly developed ß‐lactamase inhibitors, however, especially BRL‐42715, show some promise against these enzymes.
Newer ß‐Lactam Agents and the Bacteroides fragilis Group
Authors: Cuchural George J.
Published: October 2023

A continuing nationwide susceptibility survey of the Bacteroides fragilis group, begun in 1981, is being conducted at the New England Medical Center. Review of susceptibility testing in years 1986 through 1988 is reported here. Totals of 557 strains in 1986, 506 in 1987, and 534 in 1988 were obtained from seven centers in the United States. The most active ß‐lactam drugs were ß‐lactamase‐inhibitor combinations ticarcillin‐clavulanic acid, ampicillin‐sulbactam, cefoperazone‐sulbactam and the carbapenem imipenem. These drugs had virtually no resistance detected. Their rank order of activity was imipenem, ampicillin‐sulbactam, ticarcillin‐clavulanic acid, and cefoperazone‐sulbactam, all with activity levels greater than cefoxitin or piperacillin, which, in turn, had activity levels greater than moxalactam, ceftizoxime, cefotetan, cefotaxime, cefoperazone, and ceftazidime. No metronidazole‐ or chloramphenicol‐resistant isolates were found. Clindamycin resistance averaged 6% over the 3 years of testing. Ticarcillin‐clavulanic acid, ampicillin‐sulbactam, imipenem, and the non‐ß‐lactam drugs displayed uniform excellent activity against the five species of the B. fragilis group tested. The other ß‐lactams displayed significant variability of activity among the various species.
The Effect of Timentin in the Treatment of Female Pelvic Soft Tissue Infections
Authors: Faro Sebastian
Published: October 2023

Ticarcillin plus clavulanic acid (Timentin) has a broad‐spectrum activity that includes gram‐positive aerobes, and facultative and obligate anaerobes. Numerous studies have demonstrated that single agents, including this combination, are as efficacious as clindamycin plus an aminoglycoside in treating gynecologic soft tissue infections. Its spectrum of activity, together with its potential for treating Chlamydia trachomatis, makes it suitable for the treatment of pelvic inflammatory disease.
Diagnosis and Management of Pneumonia
Authors: Kemper Carol A. , Deresinski Stanley C.
Published: October 2023

The management of patients with pneumonia, the fifth leading cause of death in the United States, remains frequently problematical. Because a precise etiologic diagnosis is often not possible when the patient is first examined, initial antibiotic therapy is often empiric. Problems in early diagnosis include the frequent lack of access to true respiratory secretions, necessary delays in identification of organisms in culture, and contamination of expectorated sputum with oropharyngeal bacteria. Early management must therefore depend on epidemiologic and clinical clues as well as examination of available respiratory secretions. It is generally helpful in the selection of initial antibiotic therapy to consider the disease in two broad epidemiologic categories, community‐ and nosocomially acquired. As new laboratory and clinical information become available, the appropriateness of the antibiotic therapy must be continually reevaluated.