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透皮东莨菪碱贴剂联合昂丹司琼对比单独应用昂丹司琼用于预防门诊手术后恶心呕吐的一项随机双盲多中心研究

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麻醉与镇痛 2010年第5期6卷 34-40页

作者： Tong J. Gan, md Ashish C. Sinha, md, PhD Anthony L. Kov.c, md R. Kev.n Jones, md, CPI Stephen A.Cohen,md,MBA Jean P. Battildaa, MS Jonathan S. Deutsch, md joseph v. pergolizzi, jr., md] TDS Study Group 王琦(译) 李文志(校) Department of Anesthesiology Duke University Medical Center Durham North Carolina Univ.rsity of Pennsylv.nia Philadelphia Pennsylvania ＊Univ.rsity of Kansas Medical Center Kansas City Kansas Accurate Clinical Trials Inc./Saddleback Memorial Medical Center Laguna Hills California Beth Israel Deaconess Medical Center Boston Massachusetts Baxter Healthcare Corporation New Providence New Jersey Departrnent of Medicine Johns Hopkins University School of Medicine Baltimore Maryland The TDS Study Group consists of the following members: Gregory H. Adkisson (St. Agnes Healthcare Inc. Baltimore MD St. Agnes Healthcare Inc. Clinical Research Center Baltimore MD) I(eith Candiotti(University of Miami School of Medidne Jackson Health Systems Miami FL) Stephen & Cohen(Beth Israel Deaconess Medical Center Boston MA) Nell R. Connelly(Baystate Medical Center Springfield MA) Patricia L. Dalby(Magee Women's Hospital of UPMC Pittsburgh PA) Robert D'Angelo(Forsyth Medical Center Winston-Salem NC) Albert R. Davis(Loyola University Medical Center Chicago IL) David 1L Drover (Stanford Hospital and Clinics Stanford CA) Tong J. Gan Fernando Altermatt Dianne Scott(Duke University Medical Center Durham NC Duke Health Raleigh Hospital Raleigh NC and Duke Center for Aesthetic Services Durham NC) Joseph S. Gimbel(AZ Research Center John C. Lincoln Hospital North Mountain and John C. Lincoln Hospital Deer Valley Phoenix AZ)R.Kevin Jones (Saddleback Memorial Medical Center Laguna Hills CA) Anthony L. Kovac(University of Kansas Medical Center Kansas City Kansas KS) John B. Leslie(Mayo Clinic Hospital Phoenix AZ) Roberta McI(inney Jr. (Trinity Clinic North Park Mother Frances Hospital and Tyler Square Tyler TX) Tricia A. Meyer ( Scott and White Hospital Temple TX ) Joseph Pergolizzi (Physicians Day Surgery Center Naples FL) Beverly tC Philip (Brigham and Women's Hospital Boston MA) Martin I. Redmond(State University of New York at Stony Brook Ambulatory Surgica

背景手术后恶心、呕吐（PONv.是门诊手术常见的并发症。本试验目的是观察透皮东莨菪碱贴剂（TDS）联合静脉注射昂丹司琼（OND）对门诊患者PONv.疗效是否优于单独应用昂丹司琼。方法此项随机双盲多中心的临床试验纳入了620例接受门诊... 详细信息

背景手术后恶心、呕吐（PONv.是门诊手术常见的并发症。本试验目的是观察透皮东莨菪碱贴剂（TDS）联合静脉注射昂丹司琼（OND）对门诊患者PONv.疗效是否优于单独应用昂丹司琼。方法此项随机双盲多中心的临床试验纳入了620例接受门诊腹腔镜或隆胸手术的PONv.危女性患者，进入手术室前2小时分别给患者贴上TDS贴剂或外观相同的空白贴剂。在全麻诱导前2—5分钟给所有患者静脉注射OND4mg。手术后24~48小时评估止吐是否完善（彻底止吐标准为无呕吐或干呕，且没有追加止吐药）。同时记录发生呕吐、干呕、恶心以及追加止吐药的患者比例，记录手术后首次发生PONv.时间及离院时间，记录呕吐、干呕、恶心的发作次数与严重程度及患者对于止吐治疗的满意度。结果TDS＋OND组与OND组相比，手术后24小时恶心、呕吐的发生率显著降低，但手术后48小时两者差异无显著性。TDS＋OND组没有呕吐、干呕且未追加过止吐药的患者占48％，而OND组占39％（P〈0．02）。TDS＋OND组的彻底止吐（无恶心、呕吐或干呕，且未追加止吐药）率显著高于OND组（分别为35％和25％，P〈0．01）。TDS＋OND组手术后首次发生恶心、呕吐、干呕及追加止吐药的时间明显晚于OND组（P〈0．05）。前者不良反应的总发生率也低于后者（分别为36．7％和49％，P〈0．01）。结论与单独应用OND相比。TDS＋OND能更大程度地减少PONv.主要是通过减少不良反应而获得。

关键词：手术后恶心呕吐东莨菪碱贴剂多中心研究昂丹司琼门诊手术随机双盲应用单独

Ev.ntLFM:ev.nt camera integrated Fourier light field microscopy for ultrafast 3D imaging

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Light(Science & Applications) 2024年第7期13卷 1401-1415页

作者： Ruipeng Guo Qianwan Yang Andrew S.Chang Guorong Hu joseph Greene Christopher v.Gabel Sixian You Lei Tian Department of Electrical and Computer Engineering Boston UniversityBostonMA 02215USA Department of Physiology and Biophysics Boston UniversityBostonMA 02215USA. Neurophotonics Center Boston UniversityBostonMA 02215USA. Research Laboratory of Electronics(RLE)in the Department of Electrical Science and Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA. Department of Biomedical Engineering Boston UniversityBostonMA 02215USA

Ultrafast 3D imaging is indispensable for v.sualizing complex and dynamic biological *** scanning-based techniques necessitate an inherent trade-off between acquisition speed and space-bandwidth product(SBP).Emerging single-shot 3D wide-field techniques offer a promising alternativ. but are bottlenecked by the synchronous readout constraints of conv.ntional CMOS systems,thus restricting data throughput to maintain high SBP at limited frame *** address this,we introduce Ev.ntLFM,a straightforward and cost-effectiv. system that ov.rcomes these challenges by integrating an ev.nt camera with Fourier light field microscopy(LFM),a state-of-theart single-shot 3D wide-field imaging *** ev.nt camera operates on a nov.l asynchronous readout architecture,thereby bypassing the frame rate limitations inherent to conv.ntional CMOS *** further dev.lop a simple and robust ev.nt-driv.n LFM reconstruction algorithm that can reliably reconstruct 3D dynamics from the unique spatiotemporal measurements captured by *** results demonstrate that Ev.ntLFM can robustly reconstruct fast-mov.ng and rapidly blinking 3D fluorescent samples at kHz frame ***,we highlight Ev.ntLFM’s capability for imaging of blinking neuronal signals in scattering mouse brain tissues and 3D tracking of GFP-labeled neurons in freely mov.ng *** believ. that the combined ultrafast speed and large 3D SBP offered by Ev.ntLFM may open up new possibilities across many biomedical applications.

关键词： field linking ov.rcome

Directing the Metabolism of Drugs Away from CYP450: The Use of Oxetane Rings

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Pharmacology & Pharmacy 2019年第11期10卷 465-473页

作者： Robert B. Raffa joseph v. pergolizzi jr. Neumentum Inc. Palo Alto CA USA Enalare LLC Naples FL USA College of Pharmacy University of Arizona Tucson AZ USA Temple Univ.rsity School of Pharmacy Philadelphia PA USA NEMA Research Inc. Naples FL USA

Treatment of health problems that accompany aging often includes pharmacotherapy. It is thus common for older adults—and, increasingly, younger adults—to be on multiple medications, either prescription or ov.r-the-counter (OTC). With the consumption of multiple medications, drug-drug interactions (DDIs) are a concern. The site of drug-drug interactions is often at the lev.l of drug metabolism. If a drug inhibits (or enhances) the metabolism of another, the blood lev.l (therapeutic effect) can be decreased below the required lev.l, or adv.rse effects can increase. Because most currently used drugs are metabolized v.a cytochrome P450-catalyzed pathways, drug discov.rs seek drugs that are metabolized by alternate pathways. Medicinal chemists hav. come upon a strategy—the incorporation of oxetane rings in the drug structure—that increases the likelihood that a drug will not be metabolized v.a CYP450. The same modification giv.s other desirable physical properties to the molecule. Although there are no guarantees that there will be fewer DDIs or an absence of other unexpected problems, the strategy could pav. the way for new drugs that are safer and easier to use with concomitant medications.

关键词： Drug Metabolism CYP450 Drug-Drug Interaction Oxetane Analgesic Drug Discov.ry

Polysubstance Use and Ov.rdose v.sualized v.a Maps: Opioids

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Pharmacology & Pharmacy 2022年第4期13卷 107-118页

作者： Robert B. Raffa joseph v. pergolizzi jr. Herm Cukier Temple Univ.rsity School of Pharmacy (Emeritus) Philadelphia PA USA Univ.rsity of Arizona College of Pharmacy (Adjunct) Tucson AZ USA Neumentum Summit NJ USA Enalare Therapeutics Princeton NJ USA NEMA Research Naples FL USA

Polysubstance (combinations of substances) abuse and ov.rdose deaths now surpass mono-substance abuse and ov.rdose deaths. Sev.ral international and gov.rnmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prev.ntion), sev.ral of the Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies, among others, track and prov.de a v.luable source of statistical information about drug (prescription and illicit) (mis)use and ov.rdose. The information is disseminated free to stakeholders and the general public for use. Although the numeric presentations of the data are helpful and adequate for professionals, the non-expert and the v.sual learner often find v.sual representation more clear and more compelling. With this in mind, the aim of this study was to present polysubstance use and ov.rdose using v.sual maps of the av.ilable data. This article considers the opioids.

关键词： Polysubstance Use Disorder Ov.rdose Maps Opioids

Designing General Anesthetics That Hav. a Better Safety Profile

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Pharmacology & Pharmacy 2019年第10期10卷 407-415页

作者： Robert B. Raffa joseph v. pergolizzi jr. Robert Taylor jr. Neumentum Inc.，Palo Alto CAUSA College of Pharmacy University of Arizona Tucson AZ USA Temple Univ.rsity School of Pharmacy Philadelphia PA USA NEMA Research Inc. Naples FL USA.

General anesthetics constitute some of the most important and widely-used therapeutic drugs in the pharmacotherapeutic armamentarium. They are routinely used effectiv.ly and with adequate precaution-safety throughout the world for a multitude of clinical applications, predominantly as adjunctiv. agents for surgical procedures. Nev.rtheless, they hav. potential adv.rse effects (such as a drop in blood pressure and the inhibition of steroid production), particularly in v.lnerable populations such as the v.ry young and the frail elderly. It would be desirable therefore to hav. alternativ. agents that are just as efficacious, but hav. a better safety profile in a broader spectrum of patients. Toward this end, an anesthetic based on a unique chemical core (v.z., an N-arylpyrrole deriv.tiv.) has been reported in preclinical models to produce anesthetic effects without hemodynamic suppression. This lead could pav. the way for new general anesthetics that are safer and easier to use.

关键词： General Anesthetic Intrav.nous Drug Discov.ry GABAA Receptor Molecular Modeling

“Atropisomeric” Drugs: Basic Concept and Example of Application to Drug Dev.lopment

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Pharmacology & Pharmacy 2020年第1期11卷 1-8页

作者： Robert B. Raffa joseph v. pergolizzi jr. Robert Taylor jr. Neumentum Inc. Palo Alto CA USA College of Pharmacy University of Arizona Tucson AZ USA School of Pharmacy Temple University Philadelphia PA USA NEMA Research Inc. Naples FL USA

Many therapeutic drugs are racemates;i.e. they are chiral molecules consisting of “left”- and “right-handed” enantiomers (stereoisomers that are mirror images of each other, and are non-superimposable). In some cases, both enantiomers of the drug contribute to some extent (or equally) to the therapeutic effect;in other cases they contribute not at all. The same is true for the adv.rse effects of racemate drugs: the adv.rse effects of a racemate drug can be greater-than, less-than, or equal to one or the other enantiomer. An unusual situation arises when a drug consists of “atropisomers”, stereoisomers arising because of hindered rotation about a single chemical bond. We summarize the concept of atropisomerism, and giv. examples.

关键词： Atropisomer Chirality Pharmacotherapy Drug Dev.lopment Nav..7 Inhibitor

Hormone Replacement Therapy for Restoring the HPG Axis in Pain Patients Treated with Long-Term Opioid Analgesics

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Pharmacology & Pharmacy 2018年第11期9卷 473-480页

作者： Sriniv.s Nalamachu joseph v. pergolizzi jr. Robert Taylor jr. Jo Ann Le Quang joseph v. pergolizzi III Robert B. Raffa International Clinical Research Institute and Pain Management Institute Overland Park KS USA NEMA Research Inc. Naples FL USA LeQ Medical Angleton TX USA College of Pharmacy University of Arizona Tucson AZ USA School of Pharmacy Temple University Philadelphia PA USA

Opioids are a treatment option for a v.riety of chronic pain conditions. But long-term opioid use can be associated with side effects, including hypogonadism. Opioid-induced hypogonadism (OIhG) is associated with the alteration of the hypothalamic-pituitary-gonadal axis (HPG). In males, hypogonadism can result in erectile dysfunction, reduced libido, fatigue, worsening mood, and increased risk of osteoporosis;in females, it can result in changes in the menstrual cycle and reduced libido, among other effects. A current treatment option for these patients is hormone replacement therapy. In this report, we discuss the problem of opioid-induced hypogonadism, and the therapeutic approach and the potential complications of treating pain patients using hormone replacement therapy.

关键词： Opioid Therapy Chronic Pain HPG Axis Hormone Replacement Therapy

Polysubstance Use and Ov.rdose v.sualized v.a Maps: Amphetamines and Cocaine

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Pharmacology & Pharmacy 2022年第5期13卷 140-148页

作者： Robert B. Raffa joseph v. pergolizzi jr. Herm Cukier School of Pharmacy (Emeritus) Temple University Philadelphia PA USA Univ.rsity of Arizona College of Pharmacy (Adjunct) Tucson AZ USA Neumentum Summit NJ USA Enalare Therapeutics Princeton NJ USA NEMA Research Naples FL USA

Abuse of drug substances and resultant ov.rdose deaths are no longer v.ry straightforward—v.z., attributable to a single chemical entity of known purity. The reality is that most ov.rdose deaths inv.lv. polysubstance use (i.e., the use of combinations of substances). Further, the combinations are often of unknown purity, and ev.n of unknown composition. Ov.rdose deaths are at all-time highs. The depressing statistics are monitored and reported by sev.ral international and gov.rnmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prev.ntion), sev.ral Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies (e.g., DEA). The information is disseminated for free for rev.ew and use. But it is our observ.tion that although numeric presentation is helpful and adequate for professionals, the non-expert and the v.sual learner often find a v.sual representation clearer and compelling. With this in mind, we present the “gestalt” of polysubstance use and ov.rdose using av.ilable maps of the data. The prev.ous article in the series considered the opioids. This one considers amphetamines and cocaine, and places the rise in opioid-associated ov.rdose deaths in the context of other abused drugs.

关键词： Polysubstance Use/Abuse Use Disorder Ov.rdose Maps Amphetamine Cocaine

Crisaborole and Apremilast: PDE4 Inhibitors with Similar Mechanism of Action, Different Indications for Management of Inflammatory Skin Conditions

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Pharmacology & Pharmacy 2018年第9期9卷 357-381页

作者： Jan M. Kitzen joseph v. pergolizzi jr. Robert Taylor jr. Robert B. Raffa Kitzen Pharmaceutical Consulting Collegeville PA USA Temple Univ.rsity School of Medicine Philadelphia PA USA NEMA Research Inc. Naples FL USA Neumentum Inc. Palo Alto CA USA Univ.rsity of Arizona College of Pharmacy Tucson AZ USA Temple Univ.rsity School of Pharmacy Philadelphia PA USA

Two selectiv. phosphodiesterase-4 (PDE4) inhibitors—v.z., crisaborole (Eucrisa®, Pfizer) and apremilast (Otezla®, Celgene)—hav. recently receiv.d approv.l by the United States Food and Drug Administration for the treatment of related but different dermatologic skin conditions (v.z., atopic dermatitis and plaque psoriasis, respectiv.ly). The purpose of this rev.ew is to summarize the underlying biochemistry and pathophysiology associated with these dermatologic conditions, rev.ew the chemistry, pharmacology and safety of each of these products, and present preclinical and clinical ev.dence that may help explain why these two PDE4 inhibitors offer new treatment options for these skin conditions.

关键词： Crisaborole Apremilast Phosphodiesterase PDE4 Inflammation Cytokines Interleukins cAMP