Oxycodone Plus Ultra-Low-Dose Naltrexone Attenuates Neuropathic Pain and Associated μ-Opioid Receptor–Gs Coupling

PubMed Central

Largent-Milnes, Tally M.; Guo, Wenhong; Wang, Hoau-Yan; Burns, Lindsay H.; Vanderah, Todd W.

2017-01-01

Both peripheral nerve injury and chronic opioid treatment can result in hyperalgesia associated with enhanced excitatory neurotransmission at the level of the spinal cord. Chronic opioid administration leads to a shift in μ-opioid receptor (MOR)–G protein coupling from Gi/o to Gs that can be prevented by cotreatment with an ultra-low-dose opioid antagonist. In this study, using lumbar spinal cord tissue from rats with L5/L6 spinal nerve ligation (SNL), we demonstrated that SNL injury induces MOR linkage to Gs in the damaged (ipsilateral) spinal dorsal horn. This MOR-Gs coupling occurred without changing Gi/o coupling levels and without changing the expression of MOR or Gα proteins. Repeated administration of oxycodone alone or in combination with ultra-low-dose naltrexone (NTX) was assessed on the SNL-induced MOR-Gs coupling as well as on neuropathic pain behavior. Repeated spinal oxycodone exacerbated the SNL-induced MOR-Gs coupling, whereas ultra-low-dose NTX cotreatment slightly but significantly attenuated this Gs coupling. Either spinal or oral administration of oxycodone plus ultra-low-dose NTX markedly enhanced the reductions in allodynia and thermal hyperalgesia produced by oxycodone alone and minimized tolerance to these effects. The MOR-Gs coupling observed in response to SNL may in part contribute to the excitatory neurotransmission in spinal dorsal horn in neuropathic pain states. The antihyperalgesic and antiallodynic effects of oxycodone plus ultra-low-dose NTX (Oxytrex, Pain Therapeutics, Inc., San Mateo, CA) suggest a promising new treatment for neuropathic pain. PMID:18468954

Oxycodone plus ultra-low-dose naltrexone attenuates neuropathic pain and associated mu-opioid receptor-Gs coupling.

PubMed

Largent-Milnes, Tally M; Guo, Wenhong; Wang, Hoau-Yan; Burns, Lindsay H; Vanderah, Todd W

2008-08-01

Both peripheral nerve injury and chronic opioid treatment can result in hyperalgesia associated with enhanced excitatory neurotransmission at the level of the spinal cord. Chronic opioid administration leads to a shift in mu-opioid receptor (MOR)-G protein coupling from G(i/o) to G(s) that can be prevented by cotreatment with an ultra-low-dose opioid antagonist. In this study, using lumbar spinal cord tissue from rats with L(5)/L(6) spinal nerve ligation (SNL), we demonstrated that SNL injury induces MOR linkage to G(s) in the damaged (ipsilateral) spinal dorsal horn. This MOR-G(s) coupling occurred without changing G(i/o) coupling levels and without changing the expression of MOR or Galpha proteins. Repeated administration of oxycodone alone or in combination with ultra-low-dose naltrexone (NTX) was assessed on the SNL-induced MOR-G(s) coupling as well as on neuropathic pain behavior. Repeated spinal oxycodone exacerbated the SNL-induced MOR-G(s) coupling, whereas ultra-low-dose NTX cotreatment slightly but significantly attenuated this G(s) coupling. Either spinal or oral administration of oxycodone plus ultra-low-dose NTX markedly enhanced the reductions in allodynia and thermal hyperalgesia produced by oxycodone alone and minimized tolerance to these effects. The MOR-G(s) coupling observed in response to SNL may in part contribute to the excitatory neurotransmission in spinal dorsal horn in neuropathic pain states. The antihyperalgesic and antiallodynic effects of oxycodone plus ultra-low-dose NTX (Oxytrex, Pain Therapeutics, Inc., San Mateo, CA) suggest a promising new treatment for neuropathic pain. The current study investigates whether Oxytrex (oxycodone with an ultra-low dose of naltrexone) alleviates mechanical and thermal hypersensitivities in an animal model of neuropathic pain over a period of 7 days, given locally or systemically. In this report, we first describe an injury-induced shift in mu-opioid receptor coupling from G(i/o) to G(s), suggesting

Virtual Colonoscopy Screening With Ultra Low-Dose CT and Less-Stressful Bowel Preparation: A Computer Simulation Study

NASA Astrophysics Data System (ADS)

Wang, Jing; Wang, Su; Li, Lihong; Fan, Yi; Lu, Hongbing; Liang, Zhengrong

2008-10-01

Computed tomography colonography (CTC) or CT-based virtual colonoscopy (VC) is an emerging tool for detection of colonic polyps. Compared to the conventional fiber-optic colonoscopy, VC has demonstrated the potential to become a mass screening modality in terms of safety, cost, and patient compliance. However, current CTC delivers excessive X-ray radiation to the patient during data acquisition. The radiation is a major concern for screening application of CTC. In this work, we performed a simulation study to demonstrate a possible ultra low-dose CT technique for VC. The ultra low-dose abdominal CT images were simulated by adding noise to the sinograms of the patient CTC images acquired with normal dose scans at 100 mA s levels. The simulated noisy sinogram or projection data were first processed by a Karhunen-Loeve domain penalized weighted least-squares (KL-PWLS) restoration method and then reconstructed by a filtered backprojection algorithm for the ultra low-dose CT images. The patient-specific virtual colon lumen was constructed and navigated by a VC system after electronic colon cleansing of the orally-tagged residue stool and fluid. By the KL-PWLS noise reduction, the colon lumen can successfully be constructed and the colonic polyp can be detected in an ultra low-dose level below 50 mA s. Polyp detection can be found more easily by the KL-PWLS noise reduction compared to the results using the conventional noise filters, such as Hanning filter. These promising results indicate the feasibility of an ultra low-dose CTC pipeline for colon screening with less-stressful bowel preparation by fecal tagging with oral contrast.

Tolerance to the anticonvulsant effect of morphine in mice: blockage by ultra-low dose naltrexone.

PubMed

Roshanpour, Maryam; Ghasemi, Mehdi; Riazi, Kiarash; Rafiei-Tabatabaei, Neda; Ghahremani, Mohammad Hossein; Dehpour, Ahmad Reza

2009-02-01

The present study evaluated the development of tolerance to the anticonvulsant effect of morphine in a mouse model of clonic seizures induced by pentylenetetrazole, and whether ultra-low doses of the opioid receptor antagonist naltrexone which selectively block G(s) opioid receptors were capable of preventing the observed tolerance. The results showed that the morphine anticonvulsant effect could be subject to tolerance after repeated administration. Both the development and expression of tolerance were inhibited by ultra-low doses of naltrexone, suggesting the possible involvement of G(s)-coupled opioid receptors in the development of tolerance to the anticonvulsant effect of morphine.

A photon recycling approach to the denoising of ultra-low dose X-ray sequences.

PubMed

Hariharan, Sai Gokul; Strobel, Norbert; Kaethner, Christian; Kowarschik, Markus; Demirci, Stefanie; Albarqouni, Shadi; Fahrig, Rebecca; Navab, Nassir

2018-06-01

Clinical procedures that make use of fluoroscopy may expose patients as well as the clinical staff (throughout their career) to non-negligible doses of radiation. The potential consequences of such exposures fall under two categories, namely stochastic (mostly cancer) and deterministic risks (skin injury). According to the "as low as reasonably achievable" principle, the radiation dose can be lowered only if the necessary image quality can be maintained. Our work improves upon the existing patch-based denoising algorithms by utilizing a more sophisticated noise model to exploit non-local self-similarity better and this in turn improves the performance of low-rank approximation. The novelty of the proposed approach lies in its properly designed and parameterized noise model and the elimination of initial estimates. This reduces the computational cost significantly. The algorithm has been evaluated on 500 clinical images (7 patients, 20 sequences, 3 clinical sites), taken at ultra-low dose levels, i.e. 50% of the standard low dose level, during electrophysiology procedures. An average improvement in the contrast-to-noise ratio (CNR) by a factor of around 3.5 has been found. This is associated with an image quality achieved at around 12 (square of 3.5) times the ultra-low dose level. Qualitative evaluation by X-ray image quality experts suggests that the method produces denoised images that comply with the required image quality criteria. The results are consistent with the number of patches used, and they demonstrate that it is possible to use motion estimation techniques and "recycle" photons from previous frames to improve the image quality of the current frame. Our results are comparable in terms of CNR to Video Block Matching 3D-a state-of-the-art denoising method. But qualitative analysis by experts confirms that the denoised ultra-low dose X-ray images obtained using our method are more realistic with respect to appearance.

Low-energy Bluetooth for detecting real-world penetrance of bystander naloxone kits: a pilot study.

PubMed

Lai, Jeffrey T; Chapman, Brittany P; Boyle, Katherine L; Boyer, Edward W; Chai, Peter R

2018-01-03

Opioid overdose is a growing public health emergency in the United States. The antidote naloxone must be administered rapidly after opioid overdose to prevent death. Bystander or "take-home" naloxone programs distribute naloxone to opioid users and other community members to increase naloxone availability at the time of overdose. However, data describing the natural history of take-home naloxone in the hands of at-risk individuals is lacking. To understand patterns of naloxone uptake in at-risk users, we developed a smart naloxone kit that uses low-energy Bluetooth (BLE) to unobtrusively detect the transit of naloxone through a hospital campus. In this paper, we describe development of the smart naloxone kit and results from the first 10 participants in our pilot study.

Low doses of cyclic AMP-phosphodiesterase inhibitors rapidly evoke opioid receptor-mediated thermal hyperalgesia in naïve mice which is converted to prominent analgesia by cotreatment with ultra-low-dose naltrexone.

PubMed

Crain, Stanley M; Shen, Ke-Fei

2008-09-22

Systemic (s.c.) injection in naïve mice of cyclic AMP-phosphodiesterase (cAMP-PDE) inhibitors, e.g. 3-isobutyl-1-methylxanthine [(IBMX) or caffeine, 10 mg/kg] or the more specific cAMP-PDE inhibitor, rolipram (1 mug/kg), rapidly evokes thermal hyperalgesia (lasting >5 h). These effects appear to be mediated by enhanced excitatory opioid receptor signaling, as occurs during withdrawal in opioid-dependent mice. Cotreatment of these mice with ultra-low-dose naltrexone (NTX, 0.1 ng/kg-1 pg/kg, s.c.) results in prominent opioid analgesia (lasting >4 h) even when the dose of rolipram is reduced to 1 pg/kg. Cotreatment of these cAMP-PDE inhibitors in naïve mice with an ultra-low-dose (0.1 ng/kg) of the kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI) or the mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA) also results in opioid analgesia. These excitatory effects of cAMP-PDE inhibitors in naïve mice may be mediated by enhanced release of small amounts of endogenous bimodally-acting (excitatory/inhibitory) opioid agonists by neurons in nociceptive networks. Ultra-low-dose NTX, nor-BNI or beta-FNA selectively antagonizes high-efficacy excitatory (hyperalgesic) Gs-coupled opioid receptor-mediated signaling in naïve mice and results in rapid conversion to inhibitory (analgesic) Gi/Go-coupled opioid receptor-mediated signaling which normally requires activation by much higher doses of opioid agonists. Cotreatment with a low subanalgesic dose of kelatorphan, an inhibitor of multiple endogenous opioid peptide-degrading enzymes, stabilizes endogenous opioid agonists released by cAMP-PDE inhibitors, resulting in conversion of the hyperalgesia to analgesia without requiring selective blockade of excitatory opioid receptor signaling. The present study provides a novel pharmacologic paradigm that may facilitate development of valuable non-narcotic clinical analgesics utilizing cotreatment with ultra-low-dose rolipram plus ultra-low-dose NTX or related

Interactions among aging, gender, and gonadectomy effects upon naloxone hypophagia in rats.

PubMed

Islam, A K; Beczkowska, I W; Bodnar, R J

1993-11-01

The present study examined the dose-dependent (0.25-5 mg/kg) effects of systemic naloxone upon deprivation-induced intake and high-fat intake as functions of age (4, 8, 14, and 20 months), gender, and gonadectomy in rats. Significant increases in body weight were observed as functions of age and gonadectomy. Whereas aging significantly reduced basal deprivation-induced intake, it generally failed to alter basal high-fat intake. Whereas age, gender, and gonadectomy failed to alter the decreases in deprivation-induced intake following low (0.25-2.5 mg/kg) naloxone doses, sham males displayed significantly greater age-related and gender-related inhibition following the 5 mg/kg dose of naloxone. Young gonadectomized rats displayed significant increases in naloxone's inhibition of deprivation-induced intake as well. More dramatic changes occurred in naloxone's inhibition of high-fat intake. Naloxone's potency increased in sham female rats as a function of age, and decreased in sham males and ovariectomized females as a function of age. Whereas sham males and ovariectomized females were most sensitive to naloxone's inhibition of high-fat intake at young ages, sham females were most sensitive at older ages. These data indicate that effects of age, gender, and gonadectomy upon naloxone-induced hypophagia dissociate as a function of the type of intake. Because selective opioid antagonist studies demonstrate that deprivation-induced intake is mediated by the mu1 receptor and high-fat intake is mediated by kappa and mu2 receptors, it is postulated that the differential effects of aging, gender, and gonadectomy variables upon opioid mediation of the two forms of intake may reflect their interaction with different opioid receptor subtypes.

Pharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers.

PubMed

Skulberg, Arne Kristian; Tylleskar, Ida; Nilsen, Turid; Skarra, Sissel; Salvesen, Øyvind; Sand, Trond; Loftsson, Thorsteinn; Dale, Ola

2018-03-22

This study aimed to develop a model for pharmacodynamic and pharmacokinetic studies of naloxone antagonism under steady-state opioid agonism and to compare a high-concentration/low-volume intranasal naloxone formulation 8 mg/ml to intramuscular 0.8 mg. Two-way crossover in 12 healthy volunteers receiving naloxone while receiving remifentanil by a target-controlled infusion for 102 min. The group were subdivided into three different doses of remifentanil. Blood samples for serum naloxone concentrations, pupillometry and heat pain threshold were measured. The relative bioavailability of intranasal to intramuscular naloxone was 0.75. Pupillometry showed difference in antagonism; the effect was significant in the data set as a whole (p < 0.001) and in all three subgroups (p < 0.02-p < 0.001). Heat pain threshold showed no statistical difference. A target-controlled infusion of remifentanil provides good conditions for studying the pharmacodynamics of naloxone, and pupillometry was a better modality than heat pain threshold. Intranasal naloxone 0.8 mg is inferior for a similar dose intramuscular. Our design may help to bridge the gap between studies in healthy volunteers and the patient population in need of naloxone for opioid overdose. clinicaltrials.gov : NCT02307721.

Effect of ultra-low doses, ASIR and MBIR on density and noise levels of MDCT images of dental implant sites.

PubMed

Widmann, Gerlig; Al-Shawaf, Reema; Schullian, Peter; Al-Sadhan, Ra'ed; Hörmann, Romed; Al-Ekrish, Asma'a A

2017-05-01

Differences in noise and density values in MDCT images obtained using ultra-low doses with FBP, ASIR, and MBIR may possibly affect implant site density analysis. The aim of this study was to compare density and noise measurements recorded from dental implant sites using ultra-low doses combined with FBP, ASIR, and MBIR. Cadavers were scanned using a standard protocol and four low-dose protocols. Scans were reconstructed using FBP, ASIR-50, ASIR-100, and MBIR, and either a bone or standard reconstruction kernel. Density (mean Hounsfield units [HUs]) of alveolar bone and noise levels (mean standard deviation of HUs) was recorded from all datasets and measurements were compared by paired t tests and two-way ANOVA with repeated measures. Significant differences in density and noise were found between the reference dose/FBP protocol and almost all test combinations. Maximum mean differences in HU were 178.35 (bone kernel) and 273.74 (standard kernel), and in noise, were 243.73 (bone kernel) and 153.88 (standard kernel). Decreasing radiation dose increased density and noise regardless of reconstruction technique and kernel. The effect of reconstruction technique on density and noise depends on the reconstruction kernel used. • Ultra-low-dose MDCT protocols allowed more than 90 % reductions in dose. • Decreasing the dose generally increased density and noise. • Effect of IRT on density and noise varies with reconstruction kernel. • Accuracy of low-dose protocols for interpretation of bony anatomy not known. • Effect of low doses on accuracy of computer-aided design models unknown.

Naloxone Antagonizes Soman-induced Central Respiratory Depression in Rats.

PubMed

Škrbić, Ranko; Stojiljković, Miloš P; Ćetković, Slavko S; Dobrić, Silva; Jeremić, Dejan; Vulović, Maja

2017-06-01

The influence of naloxone on respiration impaired by the highly toxic organophosphate nerve agent soman in anaesthetized rats was investigated. Soman, administered in a dose that was ineffective in blocking the electrically induced contractions of the phrenic nerve-diaphragm preparation in situ, induced a complete block of the spontaneous respiratory movements of the diaphragm, indicating the domination of central over the peripheral effects. Naloxone dose-dependently antagonized the soman-induced respiratory blockade. Atropine, at a dose that was per se ineffective in counteracting soman-induced respiratory depression, potentiated the protective effects of naloxone and completely restored respiration. Naloxone remained completely ineffective in antagonizing respiratory depression induced by the muscarinic receptor agonist the oxotremorine. It is assumed that naloxone antagonizes soman-induced respiratory inhibition by blocking endogenous opioidergic respiratory control pathways that are independent of the stimulation of muscarinic receptors. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Early detection of lung cancer using ultra-low-dose computed tomography in coronary CT angiography scans among patients with suspected coronary heart disease.

PubMed

Zanon, Matheus; Pacini, Gabriel Sartori; de Souza, Vinicius Valério Silveiro; Marchiori, Edson; Meirelles, Gustavo Souza Portes; Szarf, Gilberto; Torres, Felipe Soares; Hochhegger, Bruno

2017-12-01

To assess whether an additional chest ultra-low-dose CT scan to the coronary CT angiography protocol can be used for lung cancer screening among patients with suspected coronary artery disease. 175 patients underwent coronary CT angiography for assessment of coronary artery disease, additionally undergoing ultra-low-dose CT screening to early diagnosis of lung cancer in the same scanner (80kVp and 15mAs). Patients presenting pulmonary nodules were followed-up for two years, repeating low-dose CTs in intervals of 3, 6, or 12 months based on nodule size and growth rate in accordance with National Comprehensive Cancer Network guidelines. Ultra-low-dose CT identified 71 patients with solitary pulmonary nodules (41%), with a mean diameter of 5.50±4.00mm. Twenty-eight were >6mm, and in 79% (n=22) of these cases they were false positive findings, further confirmed by follow-up (n=20), resection (n=1), or biopsy (n=1). Lung cancer was detected in six patients due to CT screening (diagnostic yield: 3%). Among these, four cases could not be detected in the cardiac field of view. Most patients were in early stages of the disease. Two patients diagnosed at advanced stages died due to cancer complications. The addition of the ultra-low-dose CT scan represented a radiation dose increment of 1.22±0.53% (effective dose, 0.11±0.03mSv). Lung cancer might be detected using additional ultra-low-dose protocols in coronary CT angiography scans among patients with suspected coronary artery disease. Copyright © 2017 Elsevier B.V. All rights reserved.

The NAPRESSIM trial: the use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine in elective hepatobiliary surgery: a study protocol and statistical analysis plan for a randomised controlled trial.

PubMed

Cosgrave, David; Galligan, Marie; Soukhin, Era; McMullan, Victoria; McGuinness, Siobhan; Puttappa, Anand; Conlon, Niamh; Boylan, John; Hussain, Rabia; Doran, Peter; Nichol, Alistair

2017-12-29

Intrathecally administered morphine is effective as part of a postoperative analgesia regimen following major hepatopancreaticobiliary surgery. However, the potential for postoperative respiratory depression at the doses required for effective analgesia currently limits its clinical use. The use of a low-dose, prophylactic naloxone infusion following intrathecally administered morphine may significantly reduce postoperative respiratory depression. The NAPRESSIM trial aims to answer this question. 'The use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine' trial is an investigator-led, single-centre, randomised, double-blind, placebo-controlled, double-arm comparator study. The trial will recruit 96 patients aged > 18 years, undergoing major open hepatopancreaticobiliary resections, who are receiving intrathecally administered morphine as part of a standard anaesthetic regimen. It aims to investigate whether the prophylactic administration of naloxone via intravenous infusion compared to placebo will reduce the proportion of episodes of respiratory depression in this cohort of patients. Trial patients will receive an infusion of naloxone or placebo, commenced within 1 h of postoperative extubation continued until the first postoperative morning. The primary outcome is the rate of respiratory depression in the intervention group as compared to the placebo group. Secondary outcomes include pain scores, rates of nausea and vomiting, pruritus, sedation scores and adverse outcomes. We will also employ a novel, non-invasive, respiratory minute volume monitor (ExSpiron 1Xi, Respiratory Motion, Inc., 411 Waverley Oaks Road, Building 1, Suite 150, Waltham, MA, USA) to assess the monitor's accuracy for detecting respiratory depression. The trial aims to provide a clear management plan to prevent respiratory depression after the intrathecal administration of morphine, and thereby improve patient safety

Performance evaluation of multi-material electronic cleansing for ultra-low-dose dual-energy CT colonography

NASA Astrophysics Data System (ADS)

Tachibana, Rie; Kohlhase, Naja; Näppi, Janne J.; Hironaka, Toru; Ota, Junko; Ishida, Takayuki; Regge, Daniele; Yoshida, Hiroyuki

2016-03-01

Accurate electronic cleansing (EC) for CT colonography (CTC) enables the visualization of the entire colonic surface without residual materials. In this study, we evaluated the accuracy of a novel multi-material electronic cleansing (MUMA-EC) scheme for non-cathartic ultra-low-dose dual-energy CTC (DE-CTC). The MUMA-EC performs a wateriodine material decomposition of the DE-CTC images and calculates virtual monochromatic images at multiple energies, after which a random forest classifier is used to label the images into the regions of lumen air, soft tissue, fecal tagging, and two types of partial-volume boundaries based on image-based features. After the labeling, materials other than soft tissue are subtracted from the CTC images. For pilot evaluation, 384 volumes of interest (VOIs), which represented sources of subtraction artifacts observed in current EC schemes, were sampled from 32 ultra-low-dose DE-CTC scans. The voxels in the VOIs were labeled manually to serve as a reference standard. The metric for EC accuracy was the mean overlap ratio between the labels of the reference standard and the labels generated by the MUMA-EC, a dualenergy EC (DE-EC), and a single-energy EC (SE-EC) scheme. Statistically significant differences were observed between the performance of the MUMA/DE-EC and the SE-EC methods (p<0.001). Visual assessment confirmed that the MUMA-EC generated less subtraction artifacts than did DE-EC and SE-EC. Our MUMA-EC scheme yielded superior performance over conventional SE-EC scheme in identifying and minimizing subtraction artifacts on noncathartic ultra-low-dose DE-CTC images.

[Neuroprotective effect of naloxone in brain damage caused by repeated febrile seizure].

PubMed

Shan, Ying; Qin, Jiong; Chang, Xing-zhi; Yang, Zhi-xian

2004-04-01

The brain damage caused by repeated febrile seizure (FS) during developing age is harmful to the intellectual development of children. So how to decrease the related damage is a very important issue. The main purpose of the present study was to find out whether the non-specific opiate antagonist naloxone at low dose has the neuroprotective effect on seizure-induced brain damage. Warm water induced rat FS model was developed in this study. Forty-seven rats were randomly divided into two groups: normal control group (n = 10) and hyperthermic seizure groups (n = 37). The latter was further divided into FS control group (n = 13) and naloxone-treated group (n = 24). The dose of naloxone is different in two naloxone-treated groups (12/each group), in one group the dose was 1 mg/kg, in the other one 2 mg/kg. Seven febrile seizures were induced in each rat of hyperthermic seizure groups with the interval of 2 days. The rats were weighed and injected intraperitoneally with naloxone once the FS occurred in naloxone-treated group, while the rats of the other groups were injected with 0.9% sodium chloride. Latency, duration and grade of FS in different groups were observed and compared. HE-staining and the electron microscopy (EM) were used to detect the morphologic and ultrastructural changes of hippocampal neurons. In naloxone-treated group, the rats' FS duration and FS grade (5.02 +/- 0.63, 2.63 +/- 0.72) were significantly lower (t = 5.508, P < 0.01; t = 8.439, P < 0.01) than those in FS control group (7.70 +/- 2.25 min, 4.52 +/- 0.49), although no significant gap was observed on FS latency between them. In FS control group, HE-staining pattern of hippocampal CA(1) and CA(2) showed lots of disordered neurons with confused polarity and vacuoles formed. Nuclei were with various size, some rounded and some oblong. While in naloxone-treated groups, the arrangement of neurons was regular, only a small quantity of neurons had changed polarity and vacuoles formed. Most nuclei

Naloxone-induced electrographic seizures in the primate.

PubMed

Snyder, E W; Shearer, D E; Beck, E C; Dustmann, R E

1980-01-01

Electrographic seizure activity was recorded shortly following naxolone injections in artificially ventilated, methadone-treated stump-tailed macaques. Plasma-methadone concentrations prior to seizure activity were many times higher than those that have produced respiratory depression and death in nonventilated monkeys. The duration of seizure activity was clearly related to the dose of naloxone. Naloxone was without epileptogenic properties in animals that had not been pretreated with methadone. The results suggest that methadone and naloxone have additive epileptogenic properties when high blood levels of methadone are achieved in the artificially ventilated primate. Naloxone was devoid of antagonistic properties with respect to opiate-induced electroencephalographic spiking activity.

Ultra low-dose CT attenuation correction in PET SPM

NASA Astrophysics Data System (ADS)

Wang, Shyh-Jen; Yang, Bang-Hung; Tsai, Chia-Jung; Yang, Ching-Ching; Lee, Jason J. S.; Wu, Tung-Hsin

2010-07-01

The use of CT images for attenuation correction (CTAC) allows significantly shorter scanning time and a high quality noise-free attenuation map compared with conventional germanium-68 transmission scan because at least 10 4 times greater of photon flux would be generated from a CT scan under standard operating condition. However, this CTAC technique would potentially introduce more radiation risk to the patients owing to the higher radiation exposure from CT scan. Statistic parameters mapping (SPM) is a prominent technique in nuclear medicine community for the analysis of brain imaging data. The purpose of this study is to assess the feasibility of low-dose CT (LDCT) and ultra low-dose CT (UDCT) in PET SPM applications. The study was divided into two parts. The first part was to evaluate of tracer uptake distribution pattern and quantity analysis by using the striatal phantom to initially assess the feasibility of AC for clinical purpose. The second part was to examine the group SPM analysis using the Hoffman brain phantom. The phantom study is to simulate the human brain and to reduce the experimental uncertainty of real subjects. The initial studies show that the results of PET SPM analysis have no significant differences between LDCT and UDCT comparing to the current used default CTAC. Moreover, the dose of the LDCT is lower than that of the default CT by a factor of 9, and UDCT can even yield a 42 times dose reduction. We have demonstrated the SPM results while using LDCT and UDCT for PET AC is comparable to those using default CT setting, suggesting their feasibility in PET SPM applications. In addition, the necessity of UDCT in PET SPM studies to avoid excess radiation dose is also evident since most of the subjects involved are non-cancer patients or children and some normal subjects are even served as a comparison group in the experiment. It is our belief that additional attempts to decrease the radiation dose would be valuable, especially for children and

Combination of Continuous Dexmedetomidine Infusion with Titrated Ultra-Low-Dose Propofol-Fentanyl for an Awake Craniotomy

PubMed Central

Das, Samaresh; Al-Mashani, Ali; Suri, Neelam; Salhotra, Neeraj; Chatterjee, Nilay

2016-01-01

An awake craniotomy is a continuously evolving technique used for the resection of brain tumours from the eloquent cortex. We report a 29-year-old male patient who presented to the Khoula Hospital, Muscat, Oman, in 2016 with a two month history of headaches and convulsions due to a space-occupying brain lesion in close proximity with the left motor cortex. An awake craniotomy was conducted using a scalp block, continuous dexmedetomidine infusion and a titrated ultra-low-dose of propofolfentanyl. The patient remained comfortable throughout the procedure and the intraoperative neuropsychological tests, brain mapping and tumour resection were successful. This case report suggests that dexmedetomidine in combination with titrated ultra-low-dose propofolfentanyl are effective options during an awake craniotomy, ensuring optimum sedation, minimal disinhibition and a rapid recovery. To the best of the authors’ knowledge, this is the first awake craniotomy conducted successfully in Oman. PMID:27606116

Use of Intranasal Naloxone by Basic Life Support Providers.

PubMed

Weiner, Scott G; Mitchell, Patricia M; Temin, Elizabeth S; Langlois, Breanne K; Dyer, K Sophia

2017-01-01

Intranasal delivery of naloxone to reverse the effects of opioid overdose by Advanced Life Support (ALS) providers has been studied in several prehospital settings. In 2006, in response to the increase in opioid-related overdoses, a special waiver from the state allowed administration of intranasal naloxone by Basic Life Support (BLS) providers in our city. This study aimed to determine: 1) if patients who received a 2-mg dose of nasal naloxone administered by BLS required repeat dosing while in the emergency department (ED), and 2) the disposition of these patients. This was a retrospective review of patients transported by an inner-city municipal ambulance service to one of three academic medical centers. We included patients aged 18 and older that were transported by ambulance between 1/1/2006 and 12/12/2012 and who received intranasal naloxone by BLS providers as per a state approved protocol. Site investigators matched EMS run data to patients from each hospital's EMR and performed a chart review to confirm that the patient was correctly identified and to record the outcomes of interest. Descriptive statistics were then generated. A total of 793 patients received nasal naloxone by BLS and were transported to three hospitals. ALS intervened and transported 116 (14.6%) patients, and 11 (1.4%) were intubated in the field. There were 724 (91.3%) patients successfully matched to an ED chart. Hospital A received 336 (46.4%) patients, Hospital B received 210 (29.0%) patients, and Hospital C received 178 (24.6%) patients. Mean age was 36.2 (SD 10.5) years and 522 (72.1%) were male; 702 (97.1%) were reported to have abused heroin while 21 (2.9%) used other opioids. Nasal naloxone had an effect per the prehospital record in 689 (95.2%) patients. An additional naloxone dose was given in the ED to 64 (8.8%) patients. ED dispositions were: 507 (70.0%) discharged, 105 (14.5%) admitted, and 112 (15.5%) other (e.g., left against medical advice, left without being seen, or

Ultra-low dose CT attenuation correction for PET/CT: analysis of sparse view data acquisition and reconstruction algorithms

NASA Astrophysics Data System (ADS)

Rui, Xue; Cheng, Lishui; Long, Yong; Fu, Lin; Alessio, Adam M.; Asma, Evren; Kinahan, Paul E.; De Man, Bruno

2015-09-01

For PET/CT systems, PET image reconstruction requires corresponding CT images for anatomical localization and attenuation correction. In the case of PET respiratory gating, multiple gated CT scans can offer phase-matched attenuation and motion correction, at the expense of increased radiation dose. We aim to minimize the dose of the CT scan, while preserving adequate image quality for the purpose of PET attenuation correction by introducing sparse view CT data acquisition. We investigated sparse view CT acquisition protocols resulting in ultra-low dose CT scans designed for PET attenuation correction. We analyzed the tradeoffs between the number of views and the integrated tube current per view for a given dose using CT and PET simulations of a 3D NCAT phantom with lesions inserted into liver and lung. We simulated seven CT acquisition protocols with {984, 328, 123, 41, 24, 12, 8} views per rotation at a gantry speed of 0.35 s. One standard dose and four ultra-low dose levels, namely, 0.35 mAs, 0.175 mAs, 0.0875 mAs, and 0.043 75 mAs, were investigated. Both the analytical Feldkamp, Davis and Kress (FDK) algorithm and the Model Based Iterative Reconstruction (MBIR) algorithm were used for CT image reconstruction. We also evaluated the impact of sinogram interpolation to estimate the missing projection measurements due to sparse view data acquisition. For MBIR, we used a penalized weighted least squares (PWLS) cost function with an approximate total-variation (TV) regularizing penalty function. We compared a tube pulsing mode and a continuous exposure mode for sparse view data acquisition. Global PET ensemble root-mean-squares-error (RMSE) and local ensemble lesion activity error were used as quantitative evaluation metrics for PET image quality. With sparse view sampling, it is possible to greatly reduce the CT scan dose when it is primarily used for PET attenuation correction with little or no measureable effect on the PET image. For the four ultra-low dose

Ultra-low dose CT attenuation correction for PET/CT: analysis of sparse view data acquisition and reconstruction algorithms

PubMed Central

Rui, Xue; Cheng, Lishui; Long, Yong; Fu, Lin; Alessio, Adam M.; Asma, Evren; Kinahan, Paul E.; De Man, Bruno

2015-01-01

For PET/CT systems, PET image reconstruction requires corresponding CT images for anatomical localization and attenuation correction. In the case of PET respiratory gating, multiple gated CT scans can offer phase-matched attenuation and motion correction, at the expense of increased radiation dose. We aim to minimize the dose of the CT scan, while preserving adequate image quality for the purpose of PET attenuation correction by introducing sparse view CT data acquisition. Methods We investigated sparse view CT acquisition protocols resulting in ultra-low dose CT scans designed for PET attenuation correction. We analyzed the tradeoffs between the number of views and the integrated tube current per view for a given dose using CT and PET simulations of a 3D NCAT phantom with lesions inserted into liver and lung. We simulated seven CT acquisition protocols with {984, 328, 123, 41, 24, 12, 8} views per rotation at a gantry speed of 0.35 seconds. One standard dose and four ultra-low dose levels, namely, 0.35 mAs, 0.175 mAs, 0.0875 mAs, and 0.04375 mAs, were investigated. Both the analytical FDK algorithm and the Model Based Iterative Reconstruction (MBIR) algorithm were used for CT image reconstruction. We also evaluated the impact of sinogram interpolation to estimate the missing projection measurements due to sparse view data acquisition. For MBIR, we used a penalized weighted least squares (PWLS) cost function with an approximate total-variation (TV) regularizing penalty function. We compared a tube pulsing mode and a continuous exposure mode for sparse view data acquisition. Global PET ensemble root-mean-squares-error (RMSE) and local ensemble lesion activity error were used as quantitative evaluation metrics for PET image quality. Results With sparse view sampling, it is possible to greatly reduce the CT scan dose when it is primarily used for PET attenuation correction with little or no measureable effect on the PET image. For the four ultra-low dose levels

Ultra-low dose of Mycobacterium tuberculosis aerosol creates partial infection in mice.

PubMed

Saini, Divey; Hopkins, Gregory W; Seay, Sarah A; Chen, Ching-Ju; Perley, Casey C; Click, Eva M; Frothingham, Richard

2012-03-01

A murine low dose (LD) aerosol model is commonly used to test tuberculosis vaccines. Doses of 50-400 CFU (24h lung CFU) infect 100% of exposed mice. The LD model measures progression from infection to disease based on organ CFU at defined time points. To mimic natural exposure, we exposed mice to an ultra-low dose (ULD) aerosol. We estimated the presented dose by sampling the aerosol. Female C57BL/6 mice were exposed to Mycobacterium tuberculosis H37Rv aerosol at 1.0, 1.1, 1.6, 5.4, and 11 CFU presented dose, infecting 27%, 36%, 36%, 100%, and 95% of mice, respectively. These data are compatible with a stochastic infection event (Poisson distribution, weighted R(2)=0.97) or with a dose-response relationship (sigmoid distribution, weighted R(2)=0.97). Based on the later assumption, the ID50 was 1.6CFU presented dose (95% confidence interval, 1.2-2.1). We compared organ CFU after ULD and LD aerosols (5.4 vs. 395CFU presented dose). Lung burden was 30-fold lower in the ULD model at 4 weeks (3.4 vs. 4.8 logs, p<0.001) and 18 weeks (≤3.6 vs. 5.0 logs, p=0.01). Mice exposed to ULD aerosols as compared to LD aerosols had greater within-group CFU variability. Exposure to ULD aerosols leads to infection in a subset of mice, and to persistently low organ CFU. The ULD aerosol model may resemble human pulmonary tuberculosis more closely than the standard LD model, and may be used to identify host or bacterial factors that modulate the initial infection event. Copyright © 2011 Elsevier Ltd. All rights reserved.

Naloxone fails to prolong seizure length in ECT.

PubMed

Rasmussen, K G; Pandurangi, A K

1999-12-01

Electroconvulsive shock (ECS) in animals has been shown to enhance endogenous opiate systems. The anticonvulsant effects of ECS are also partially blocked by the opiate receptor antagonist naloxone, leading some investigators to postulate that the anticonvulsant effects of ECS are mediated by activation of endogenous opiates. If such a phenomenon occurs in humans, then naloxone might prolong seizure length in electroconvulsive therapy (ECT). In the present study, nine patients were given 2.0 mg intravenous (i.v.) naloxone 2 minutes prior to one-half of their ECT treatments. Motor seizure length was measured via the cuff technique. EEG tracings were read by an investigator blind to naloxone status. There was no difference between the two groups in either EEG or nonblindly evaluated motor seizure length. It is concluded that a dose of 2 mg naloxone does not effectively increase seizure length in ECT.

Potential Treatment of Inflammatory and Proliferative Diseases by Ultra-Low Doses of Ionizing Radiations

PubMed Central

Sanders, Charles L.

2012-01-01

Ultra-low doses and dose- rates of ionizing radiation are effective in preventing disease which suggests that they also may be effective in treating disease. Limited experimental and anecdotal evidence indicates that low radiation doses from radon in mines and spas, thorium-bearing monazite sands and enhanced radioactive uranium ore obtained from a natural geological reactor may be useful in treating many inflammatory conditions and proliferative disorders, including cancer. Optimal therapeutic applications were identified via a literature survey as dose-rates ranging from 7 to 11μGy/hr or 28 to 44 times world average background rates. Rocks from an abandoned uranium mine in Utah were considered for therapeutic application and were examined by γ-ray and laser-induced breakdown fluorescence spectroscopy. The rocks showed the presence of transuranics and fission products with a γ-ray energy profile similar to aged spent uranium nuclear fuel (93% dose due to β particles and 7% due to γ rays). Mud packs of pulverized uranium ore rock dust in sealed plastic bags delivering bag surface β,γ dose-rates of 10–450 μGy/h were used with apparent success to treat several inflammatory and proliferative conditions in humans. PMID:23304108

CORK Study in Cystic Fibrosis: Sustained Improvements in Ultra-Low-Dose Chest CT Scores After CFTR Modulation With Ivacaftor.

PubMed

Ronan, Nicola J; Einarsson, Gisli G; Twomey, Maria; Mooney, Denver; Mullane, David; NiChroinin, Muireann; O'Callaghan, Grace; Shanahan, Fergus; Murphy, Desmond M; O'Connor, Owen J; Shortt, Cathy A; Tunney, Michael M; Eustace, Joseph A; Maher, Michael M; Elborn, J Stuart; Plant, Barry J

2018-02-01

Ivacaftor produces significant clinical benefit in patients with cystic fibrosis (CF) with the G551D mutation. Prevalence of this mutation at the Cork CF Centre is 23%. This study assessed the impact of cystic fibrosis transmembrane conductance regulator modulation on multiple modalities of patient assessment. Thirty-three patients with the G551D mutation were assessed at baseline and prospectively every 3 months for 1 year after initiation of ivacaftor. Change in ultra-low-dose chest CT scans, blood inflammatory mediators, and the sputum microbiome were assessed. Significant improvements in FEV 1 , BMI, and sweat chloride levels were observed post-ivacaftor treatment. Improvement in ultra-low-dose CT imaging scores were observed after treatment, with significant mean reductions in total Bhalla score (P < .01), peribronchial thickening (P = .035), and extent of mucous plugging (P < .001). Reductions in circulating inflammatory markers, including interleukin (IL)-1β, IL-6, and IL-8 were demonstrated. There was a 30% reduction in the relative abundance of Pseudomonas species and an increase in the relative abundance of bacteria associated with more stable community structures. Posttreatment community richness increased significantly (P = .03). Early and sustained improvements on ultra-low-dose CT scores suggest it may be a useful method of evaluating treatment response. It paralleled improvement in symptoms, circulating inflammatory markers, and changes in the lung microbiota. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

A BMI-adjusted ultra-low-dose CT angiography protocol for the peripheral arteries-Image quality, diagnostic accuracy and radiation exposure.

PubMed

Schreiner, Markus M; Platzgummer, Hannes; Unterhumer, Sylvia; Weber, Michael; Mistelbauer, Gabriel; Loewe, Christian; Schernthaner, Ruediger E

2017-08-01

To investigate radiation exposure, objective image quality, and the diagnostic accuracy of a BMI-adjusted ultra-low-dose CT angiography (CTA) protocol for the assessment of peripheral arterial disease (PAD), with digital subtraction angiography (DSA) as the standard of reference. In this prospective, IRB-approved study, 40 PAD patients (30 male, mean age 72 years) underwent CTA on a dual-source CT scanner at 80kV tube voltage. The reference amplitude for tube current modulation was personalized based on the body mass index (BMI) with 120 mAs for [BMI≤25] or 150 mAs for [2570%) was assessed by two readers independently and compared to subsequent DSA. Radiation exposure was assessed with the computed tomography dose index (CTDIvol) and the dosis-length product (DLP). Objective image quality was assessed via contrast- and signal-to-noise ratio (CNR and SNR) measurements. Radiation exposure and image quality were compared between the BMI groups and between the BMI-adjusted ultra-low-dose protocol and the low-dose institutional standard protocol (ISP). The BMI-adjusted ultra-low-dose protocol reached high diagnostic accuracy values of 94% for Reader 1 and 93% for Reader 2. Moreover, in comparison to the ISP, it showed significantly (p<0.001) lower CTDIvol (1.97±0.55mGy vs. 4.18±0.62 mGy) and DLP (256±81mGy x cm vs. 544±83mGy x cm) but similar image quality (p=0.37 for CNR). Furthermore, image quality was similar between BMI groups (p=0.86 for CNR). A CT protocol that incorporates low kV settings with a personalized (BMI-adjusted) reference amplitude for tube current modulation and iterative reconstruction enables very low radiation exposure CTA, while maintaining good image quality and high diagnostic accuracy in the assessment of PAD. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigation of ultra low-dose scans in the context of quantum-counting clinical CT

NASA Astrophysics Data System (ADS)

Weidinger, T.; Buzug, T. M.; Flohr, T.; Fung, G. S. K.; Kappler, S.; Stierstorfer, K.; Tsui, B. M. W.

2012-03-01

In clinical computed tomography (CT), images from patient examinations taken with conventional scanners exhibit noise characteristics governed by electronics noise, when scanning strongly attenuating obese patients or with an ultra-low X-ray dose. Unlike CT systems based on energy integrating detectors, a system with a quantum counting detector does not suffer from this drawback. Instead, the noise from the electronics mainly affects the spectral resolution of these detectors. Therefore, it does not contribute to the image noise in spectrally non-resolved CT images. This promises improved image quality due to image noise reduction in scans obtained from clinical CT examinations with lowest X-ray tube currents or obese patients. To quantify the benefits of quantum counting detectors in clinical CT we have carried out an extensive simulation study of the complete scanning and reconstruction process for both kinds of detectors. The simulation chain encompasses modeling of the X-ray source, beam attenuation in the patient, and calculation of the detector response. Moreover, in each case the subsequent image preprocessing and reconstruction is modeled as well. The simulation-based, theoretical evaluation is validated by experiments with a novel prototype quantum counting system and a Siemens Definition Flash scanner with a conventional energy integrating CT detector. We demonstrate and quantify the improvement from image noise reduction achievable with quantum counting techniques in CT examinations with ultra-low X-ray dose and strong attenuation.

Pharmacokinetics of concentrated naloxone nasal spray for opioid overdose reversal: Phase I healthy volunteer study.

PubMed

McDonald, Rebecca; Lorch, Ulrike; Woodward, Jo; Bosse, Björn; Dooner, Helen; Mundin, Gill; Smith, Kevin; Strang, John

2018-03-01

Take-home naloxone can prevent death from heroin/opioid overdose, but pre-provision is difficult because naloxone is usually given by injection. Non-injectable alternatives, including naloxone nasal sprays, are currently being developed. To be effective, the intranasal (i.n.) spray dose must be adequate but not excessive, and early absorption must be comparable to intramuscular (i.m.) injection. We report on the pharmacokinetics (PK) of a specially produced concentrated novel nasal spray. The specific aims were to: (1) estimate PK profiles of i.n. naloxone, (2) compare early systemic exposure with i.n. versus i.m. naloxone and (3) estimate i.n. bioavailability. Open-label, randomized, five-way cross-over PK study. Clinical trials facility (Croydon, UK). Thirty-eight healthy volunteers (age 20-54 years; 11 female). Three doses of i.n. (1 mg/0.1 ml, 2 mg/0.1 ml, 4 mg/0.2 ml) versus 0.4 mg i.m. (reference) and 0.4 mg intravenous (i.v.) naloxone. Regular blood samples were taken, with high-frequency sampling during the first 15 minutes to capture early systemic exposure. PK parameters were determined from plasma naloxone concentrations. Exploratory analyses involved simulation of repeat administration. Mean peak concentration (C max ) values for 1 mg (1.51 ng/ml), 2 mg (2.87 ng/ml) and 4 mg (6.02 ng/ml) i.n. exceeded 0.4 mg i.m. (1.27 ng/ml) naloxone. All three i.n. doses rapidly achieved plasma levels > 50% of peak concentrations (T50%) by 10 minutes, peaking at 15-30 minutes (T max ). For comparison, the i.m. reference reached T max at 10 minutes. Mean bioavailability was 47-51% for i.n. relative to i.m. naloxone. Simulation of repeat dosing (2 × 2 mg i.n. versus 5 × 0.4 mg i.m. doses) at 3-minute intervals showed that comparable plasma naloxone concentrations would be anticipated. Concentrated 2 mg intranasal naloxone is well-absorbed and provides early exposure comparable to 0.4 mg intramuscular naloxone, following the 0.4�

Usefulness of model-based iterative reconstruction in semi-automatic volumetry for ground-glass nodules at ultra-low-dose CT: a phantom study.

PubMed

Maruyama, Shuki; Fukushima, Yasuhiro; Miyamae, Yuta; Koizumi, Koji

2018-06-01

This study aimed to investigate the effects of parameter presets of the forward projected model-based iterative reconstruction solution (FIRST) on the accuracy of pulmonary nodule volume measurement. A torso phantom with simulated nodules [diameter: 5, 8, 10, and 12 mm; computed tomography (CT) density: - 630 HU] was scanned with a multi-detector CT at tube currents of 10 mA (ultra-low-dose: UL-dose) and 270 mA (standard-dose: Std-dose). Images were reconstructed with filtered back projection [FBP; standard (Std-FBP), ultra-low-dose (UL-FBP)], FIRST Lung (UL-Lung), and FIRST Body (UL-Body), and analyzed with a semi-automatic software. The error in the volume measurement was determined. The errors with UL-Lung and UL-Body were smaller than that with UL-FBP. The smallest error was 5.8% ± 0.3 for the 12-mm nodule with UL-Body (middle lung). Our results indicated that FIRST Body would be superior to FIRST Lung in terms of accuracy of nodule measurement with UL-dose CT.

High dose naloxone does not improve cerebral or myocardial blood flow during cardiopulmonary resuscitation in pigs.

PubMed

Gervais, H W; Eberle, B; Hennes, H J; Grimm, W; Kilian, A; Konietzke, D; Massing, C; Dick, W

1997-06-01

In a prospective, randomized, placebo-controlled, double-blind trial we tested the hypothesis that naloxone given during cardiopulmonary resuscitation (CPR) enhances cerebral and myocardial blood flow. Twenty-one anesthetized, normoventilated pigs were instrumented for measurements of right atrial and aortic pressures, and regional organ blood flow (radiolabeled microspheres). After 5 min of untreated fibrillatory arrest, CPR was commenced using a pneumatic chest compressor/ventilator. With onset of CPR, an i.v. bolus of 40 micrograms/kg b.w. of epinephrine was given, followed by an infusion of 0.4 micrograms/kg per min. After 5 min of CPR, either naloxone, 10 mg/kg b.w. (group N, n = 11) or normal saline (group S, n = 10) was given i.v. Prior to, and after 1, 15, and 30 min of CPR, hemodynamic and blood flow measurements were obtained. After 30 min of CPR, mean arterial pressure was significantly higher in group N (26 +/- 5 vs. 13 +/- 3 mmHg, P < 0.05). Groups did not differ with respect to myocardial perfusion pressure or arterial blood gases at any time during the observation period. Regional brain and heart blood flows were not different between N and S at any point of measurement. We conclude that high-dose naloxone does not augment cerebral or myocardial blood flow during prolonged closed-chest CPR.

Effects of morphine and naloxone on feline colonic transit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krevsky, B.; Libster, B.; Maurer, A.H.

1989-01-01

The effects of endogenous and exogenous opioid substances on feline colonic transit were evaluated using colonic transit scintigraphy. Naloxone accelerated emptying of the cecum and ascending colon, and filling of the transverse colon. Endogenous opioid peptides thus appear to play a significant role in the regulation of colonic transit. At a moderate dose of morphine cecum and ascending colon transit was accelerated, while at a larger dose morphine had no effect. Since naloxone, a relatively nonspecific opioid antagonist, and morphine, a principally mu opioid receptor agonist, both accelerate proximal colonic transit, a decelerating role for at least one of themore » other opioid receptors is inferred.« less

Naloxone effects on behavior of inbred mice with different response to emotional stress in open field test.

PubMed

Nadorova, A V; Kozlovskaja, M M; Seredenin, S B

2009-10-01

Effects of nonspecific opiate receptor antagonist naloxone in doses of 0.1, 0.5, 1.0, 5.0, 10.0 mg/kg on open field behavior and spontaneous motor activity were studied in male BALB/c and C57Bl/6 mice. Differently directed effects of naloxone on behavioral parameters of emotional-stress reaction in BALB/c and C57Bl/6 mice were observed. Naloxone increased motor activity in the open field test in BALB/c mice, but decreased it in C57Bl/6 mice. In the absence of stress, naloxone in the studied dose range did not affect spontaneous motor activity in C57Bl/6 mice, and significantly reduced activity in BALB/c mice in doses 0.5 and 1.0 mg/kg.

Statistical distributions of ultra-low dose CT sinograms and their fundamental limits

NASA Astrophysics Data System (ADS)

Lee, Tzu-Cheng; Zhang, Ruoqiao; Alessio, Adam M.; Fu, Lin; De Man, Bruno; Kinahan, Paul E.

2017-03-01

Low dose CT imaging is typically constrained to be diagnostic. However, there are applications for even lowerdose CT imaging, including image registration across multi-frame CT images and attenuation correction for PET/CT imaging. We define this as the ultra-low-dose (ULD) CT regime where the exposure level is a factor of 10 lower than current low-dose CT technique levels. In the ULD regime it is possible to use statistically-principled image reconstruction methods that make full use of the raw data information. Since most statistical based iterative reconstruction methods are based on the assumption of that post-log noise distribution is close to Poisson or Gaussian, our goal is to understand the statistical distribution of ULD CT data with different non-positivity correction methods, and to understand when iterative reconstruction methods may be effective in producing images that are useful for image registration or attenuation correction in PET/CT imaging. We first used phantom measurement and calibrated simulation to reveal how the noise distribution deviate from normal assumption under the ULD CT flux environment. In summary, our results indicate that there are three general regimes: (1) Diagnostic CT, where post-log data are well modeled by normal distribution. (2) Lowdose CT, where normal distribution remains a reasonable approximation and statistically-principled (post-log) methods that assume a normal distribution have an advantage. (3) An ULD regime that is photon-starved and the quadratic approximation is no longer effective. For instance, a total integral density of 4.8 (ideal pi for 24 cm of water) for 120kVp, 0.5mAs of radiation source is the maximum pi value where a definitive maximum likelihood value could be found. This leads to fundamental limits in the estimation of ULD CT data when using a standard data processing stream

Co-prescribing naloxone does not increase liability risk.

PubMed

Davis, Corey S; Burris, Scott; Beletsky, Leo; Binswanger, Ingrid

2016-01-01

The opioid overdose epidemic claims the lives of tens of thousands of Americans every year. Opioid overdose is reversible by the administration of naloxone, a pure antagonist now available in formulations specifically designed and labeled for layperson use. Despite broad support for layperson access to naloxone from professional organizations, health officials, and clinical experts, qualitative studies suggest that some providers have concerns about legal risks associated with naloxone prescribing, particularly co-prescribing naloxone to pain patients. Such concerns are unfounded. The legal risk associated with prescribing naloxone is no higher than that associated with any other medication and is lower than many. Additionally, laws in a majority of states provide explicit legal protections for providers who prescribe or dispense naloxone, in many cases extending this protection to prescriptions issued to friends, family members, and others. In this large and increasing number of states, the liability risk of prescribing or dispensing naloxone in good faith to a patient at risk of overdose (or, in states where such prescribing is permitted, to an associate of such a patient) is either extremely low or absent entirely. Where a prescriber determines, in his or her clinical judgment, that a patient is at risk of overdose, co-prescribing naloxone is a reasonable and prudent clinical and legal decision. No clinician should fail or refuse to issue such a prescription based on liability concerns.

Lack of effect of naloxone on prolactin and seizures in electroconvulsive therapy.

PubMed

Sperling, M R; Melmed, S; McAllister, T; Price, T R

1989-01-01

Both opiate agonist and antagonist injection have been reported to modulate prolactin secretion, alter brain excitability and produce seizures, and modify the postictal state. We studied the effects of administration of high-dose naloxone, an opiate antagonist, on postictal prolactin levels, seizure duration, and postictal behavior, using patients undergoing electroconvulsive therapy (ECT) as a seizure model. Seven patients had 8 mg naloxone injected prior to one ECT treatment and saline injected prior to another treatment, with the order of injection randomized. Before ECT and 15 min after ECT, prolactin levels were drawn, and no blunting of the expected postictal prolactin elevation by naloxone injection was observed. We found no evidence that endogenous opiates trigger prolactin secretion during seizures. Seizure duration was also similar in saline and naloxone groups, and naloxone did not reverse postictal depression, as has been reported in an animal model.

Non-randomized intervention study of naloxone co-prescription for primary care patients on long-term opioid therapy for pain

PubMed Central

Coffin, Phillip O.; Behar, Emily; Rowe, Christopher; Santos, Glenn-Milo; Coffa, Diana; Bald, Matthew; Vittinghoff, Eric

2018-01-01

Background Unintentional overdose involving opioid analgesics is a leading cause of injury-related death in the United States. Objectives To evaluate the feasibility and impact of implementing naloxone prescription to patients prescribed opioids for chronic pain. Design 2-year non-randomized intervention study. Setting 6 safety net primary care clinics in San Francisco. Participants 1985 adults receiving long-term opioids for pain. Intervention Providers and clinic staff were trained and supported in naloxone prescribing. Measurements Outcomes were proportion of patients prescribed naloxone, opioid-related emergency department (ED) visits, and prescribed opioid dose based on chart review. Results 38.2% of 1,985 patients on long-term opioids were prescribed naloxone. Patients on higher doses of opioids and with a past 12-month opioid-related emergency department (ED) visit were independently more likely to be prescribed naloxone. Patients who received a naloxone prescription had 47% fewer opioid-related ED visits per month six months after the receipt of the prescription (IRR=0.53, 95%CI=0.34–0.83, P=0.005) and 63% fewer visits after one year (IRR=0.37, 95%CI=0.22–0.64, P<0.001), compared to patients who did not receive naloxone. There was no net change over time in opioid dose among those who received naloxone compared to those who did not (IRR 1.03, 95% CI 0.91–1.27, P = 0.61). Limitations Results are observational and may not be generalizable beyond safety net settings. Conclusion Naloxone can be co-prescribed to primary care patients prescribed opioids for pain. When advised to offer naloxone to all patients on opioids, providers may prioritize those with established risk factors. Providing naloxone in primary care settings may have ancillary benefits such as reducing opioid-related adverse events. Funding Source National Institutes of Health grant R21DA036776 PMID:27366987

Evaluation of an iterative model-based CT reconstruction algorithm by intra-patient comparison of standard and ultra-low-dose examinations.

PubMed

Noël, Peter B; Engels, Stephan; Köhler, Thomas; Muenzel, Daniela; Franz, Daniela; Rasper, Michael; Rummeny, Ernst J; Dobritz, Martin; Fingerle, Alexander A

2018-01-01

Background The explosive growth of computer tomography (CT) has led to a growing public health concern about patient and population radiation dose. A recently introduced technique for dose reduction, which can be combined with tube-current modulation, over-beam reduction, and organ-specific dose reduction, is iterative reconstruction (IR). Purpose To evaluate the quality, at different radiation dose levels, of three reconstruction algorithms for diagnostics of patients with proven liver metastases under tumor follow-up. Material and Methods A total of 40 thorax-abdomen-pelvis CT examinations acquired from 20 patients in a tumor follow-up were included. All patients were imaged using the standard-dose and a specific low-dose CT protocol. Reconstructed slices were generated by using three different reconstruction algorithms: a classical filtered back projection (FBP); a first-generation iterative noise-reduction algorithm (iDose4); and a next generation model-based IR algorithm (IMR). Results The overall detection of liver lesions tended to be higher with the IMR algorithm than with FBP or iDose4. The IMR dataset at standard dose yielded the highest overall detectability, while the low-dose FBP dataset showed the lowest detectability. For the low-dose protocols, a significantly improved detectability of the liver lesion can be reported compared to FBP or iDose 4 ( P = 0.01). The radiation dose decreased by an approximate factor of 5 between the standard-dose and the low-dose protocol. Conclusion The latest generation of IR algorithms significantly improved the diagnostic image quality and provided virtually noise-free images for ultra-low-dose CT imaging.

One-on-one care management and procurement of Naloxone for ambulatory use.

PubMed

Whittington, Richard; Whittington, Kathleen; Whittington, John; Porter, Joel; Zimmermann, Karla; Case, Holly; Berg, Stacey

2018-02-16

Morbidity and mortality from prescription opioids has reached unprecedented levels. Opioids remain part of chronic pain treatment in primary care. This study was designed to determine whether one-on-one care management increases procurement of Naloxone, an opioid antagonist shown to reduce morbidity and mortality in opioid overdoses. Participants included all patients ≥18 years enrolled in a primary care-based chronic pain management program and who were prescribed a daily dose of opioids for treatment of chronic pain. In total, 153 patients chose to participate. Each had a 1 h one-on-one education meeting with a registered nurse. Among the enrolled, eight patients (5.2%) had procured Naloxone prior to intervention. Overall, 31 additional patients (20.2%) procured Naloxone after intervention, a 288% relative improvement in the attainment of Naloxone (P < 0.0001) (χ2 = 29.032 with 1 degree freedom). Of the 114 participants who never procured Naloxone, 69.3% believed it was unnecessary, 20% forgot about Naloxone, 8% said it was cost prohibitive, 3.5% had access concerns and 0.9% had concerns about side effects. Direct one-on-one nurse care management sessions were associated with an increased procurement of Naloxone in a primary care-based pain management program. A significant number of patients believed Naloxone was unnecessary after the intervention.

Effective Use of Naloxone by Law Enforcement in Response to Multiple Opioid Overdoses.

PubMed

Kitch, Bryan B; Portela, Roberto C

2016-01-01

Growing rates of opioid abuse and overdose throughout the nation have lead some community organizations to develop naloxone administration programs. In Pitt County North Carolina, two of our law enforcement agencies were trained in the identification of opioid overdose and use of naloxone therapy. Attributed partially to introduction of fentanyl into the illicit drug market, our community experienced a 48-hour period in which officers successfully deployed five doses of antagonist medication to four individuals. This article presents case descriptions demonstrating the feasibility and safety of law enforcement naloxone programs.

Pharmacy-based statewide naloxone distribution: A novel "top-down, bottom-up" approach.

PubMed

Morton, Kate J; Harrand, Brianna; Floyd, Carly Cloud; Schaefer, Craig; Acosta, Julie; Logan, Bridget Claire; Clark, Karen

To highlight New Mexico's multifaceted approach to widespread pharmacy naloxone distribution and to share the interventions as a tool for improving pharmacy-based naloxone practices in other states. New Mexico had the second highest drug overdose death rate in 2014 of which 53% were related to prescription opioids. Opioid overdose death is preventable through the use of naloxone, a safe and effective medication that reverses the effects of prescription opioids and heroin. Pharmacists can play an important role in providing naloxone to individuals who use prescription opioids. Not applicable. Not applicable. A multifaceted approach was utilized in New Mexico from the top down with legislative passage of provisions for a statewide standing order and New Mexico Department of Health support for pharmacy-based naloxone delivery. A bottom up approach was also initiated with the development and implementation of a training program for pharmacists and pharmacy technicians. Naloxone Medicaid claims were used to illustrate statewide distribution and utilization of the pharmacist statewide standing order for naloxone. Percent of pharmacies dispensing naloxone in each county were calculated. Trained pharmacy staff completed a program evaluation form. Questions about quality of instruction and ability of trainer to meet stated objectives were rated on a Likert scale. There were 808 naloxone Medicaid claims from 100 outpatient pharmacies during the first half of 2016, a 9-fold increase over 2014. The "A Dose of R x eality" training program evaluation indicated that participants felt the training was free from bias and met all stated objectives (4 out of 4 on Likert scale). A multi-pronged approach coupling state and community collaboration was successful in overcoming barriers and challenges associated with pharmacy naloxone distribution and ensured its success as an effective avenue for naloxone acquisition in urban and rural communities. Copyright © 2017 American Pharmacists

The Effects of ELDRS at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Forney, James; Carts, Martin; Phan, Anthony; Pease, Ronald; Kruckmeyer, Kirby; Cox, Stephen; LaBel, Kenneth; Burns, Samuel; Albarian, Rafi;

Evaluation of an ultra-low-dose oral contraceptive for dysmenorrhea: a placebo-controlled, double-blind, randomized trial.

PubMed

Harada, Tasuku; Momoeda, Mikio

2016-12-01

To evaluate the efficacy and safety of an ultra-low-dose oral contraceptive (NPC-01; 0.02 mg ethinyl estradiol and 1 mg norethisterone) in subjects with dysmenorrhea. Placebo-controlled, double-blind, randomized trial. Clinical trial sites. Two hundred fifteen subjects with dysmenorrhea. Subjects were randomly assigned to receive NPC-01, placebo, or IKH-01 (0.035 mg ethinyl estradiol and 1 mg norethisterone) for four cycles. Total dysmenorrhea score (verbal rating scale) assessing pain on the basis of limited ability to work and need for analgesics. The reductions of total dysmenorrhea score and visual analog scale score after the treatment were significantly higher in the NPC-01 group than in the placebo group. Furthermore, the efficacy of NPC-01 was comparable to that of IKH-01. The overall incidence of side effects was significantly higher in the NPC-01 group than in the placebo group. All side effects that occurred in the NPC-01 group were previously reported in patients receiving IKH-01. No serious side effects occurred. The ultra-low-dose contraceptive NPC-01 relieved dysmenorrhea as effectively as IKH-01. Thus, NPC-01 could represent a new option for long-term treatment of dysmenorrhea. NCT01129102. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Naloxone and rimonabant reduce the reinforcing properties of exercise in rats.

PubMed

Rasmussen, Erin B; Hillman, Conrad

2011-12-01

Naloxone and rimonabant block neurotransmitter action of some drugs of abuse (such as ethanol, opiates, and nicotine), and thereby reduce drug seeking and self-administration by suppressing the drugs' reinforcing properties. The present study represents an attempt to elucidate whether these drugs may also reduce rewarding properties of other events, in this case, activity-based reinforcement. In Experiment 1, 10 obese and 10 lean Zucker rats pressed a locked door under a progressive ratio schedule of reinforcement that, when unlocked, provided access to a running wheel for 2-min intervals. After baseline breakpoints were established, doses of naloxone (0.3-10 mg/kg) were administered prior to experimental sessions. Obese rats exhibited lower baseline breakpoints for wheel activity, lower response rates, and fewer revolutions compared to lean rats. Naloxone decreased revolutions and response rates for lean and obese rats, but did not reduce breakpoints. In Experiment 2, five Long-Evans rats pressed a door to unlock a wheel for 20 s of wheel activity. Doses of rimonabant (1-10 mg/kg) were administered before some experimental sessions. The highest dose of rimonabant suppressed breakpoints and response rates, but did not affect revolutions. These data suggest that both drugs reduce the reinforcing properties of wheel running, but do so in different manners: naloxone may suppress wheel-based activity (consummatory behavior), but not seeking (appetitive behavior), and rimonabant does the converse. The data also support the role of endocannabinoids in the reinforcing properties of exercise, an implication that is important in terms of CB1 antagonists as a type of pharmacotherapy.

Community pharmacist knowledge, attitudes and confidence regarding naloxone for overdose reversal.

PubMed

Nielsen, Suzanne; Menon, Nadia; Larney, Sarah; Farrell, Michael; Degenhardt, Louisa

2016-12-01

Given the potential to expand naloxone supply through community pharmacy, the aim of this study was to estimate Australian pharmacists': (1) level of support for overdose prevention, (2) barriers and facilitators for naloxone supply and (3) knowledge about naloxone administration. Online survey from nationally representative sample of community pharmacies. Australia, September-November 2015. A total of 1317 community pharmacists were invited to participate with 595 responses (45.1%). We assessed attitudes towards harm reduction, support for overdose prevention, attitudes and knowledge about naloxone. We tested the association between attitudes towards harm reduction and different aspects of naloxone supply. Pharmacists were willing to receive training about naloxone (n = 479, 80.5%) and provide naloxone with a prescription (n = 537, 90.3%). Fewer (n = 234, 40.8%) were willing to supply naloxone over-the-counter. Positive attitudes towards harm reduction were associated with greater willingness to supply naloxone with a prescription [odds ratio (OR) = 1.15, 95% confidence interval (CI) = 1.11-1.19] and over-the-counter (OR = 1.13, 95% CI = 1.09-1.17). Few pharmacists were confident they could identify appropriate patients (n = 203, 34.1%) and educate them on overdose and naloxone use (n = 190, 31.9%). Mean naloxone knowledge scores were 1.8 (standard deviation 1.7) out of 5. More than half the sample identified lack of time, training, knowledge and reimbursement as potential barriers for naloxone provision. Community pharmacists in Australia appear to be willing to supply naloxone. Low levels of knowledge about naloxone pharmacology and administration highlight the importance of training pharmacists about overdose prevention. © 2016 Society for the Study of Addiction.

A Theoretical Approach to Selection of a Biologically Active Substance in Ultra-Low Doses for Effective Action on a Biological System.

PubMed

Boldyreva, Liudmila Borisovna

2018-05-01

 An approach is offered to selecting a biologically active substance (BAS) in ultra-low dose for effective action on a biological system (BS). The technique is based on the assumption that BAS in ultra-low doses exerts action on BS by means of spin supercurrent emerging between the spin structure created by BAS, on the one hand, and the spin structure created by BS, on the other hand. According to modern quantum-mechanical concepts, these spin structures may be virtual particles pairs having precessing spin (that is, be essentially spin vortices in the physical vacuum) and created by the quantum entities that BAS and BS consist of. The action is effective provided there is equality of precession frequencies of spins in these spin structures.  In this work, some methods are considered for determining the precession frequencies of spins in virtual particles pairs: (1) determination of energy levels of quantum entities that BS and BAS consist of; (2) the use of spin-flip effect of the virtual particles pair spin, the effect being initiated by action of magnetic vector potential (the spin-flip effect takes place when the varied frequency of the magnetic vector potential equals the precession frequency of the spin); (3) determining the frequencies of photons effectively acting on BS.  It is shown that the effect of BAS in ultra-low doses on BS can be replaced by the effect of a beam of low-intensity photons, if the frequency of photons equals the precession frequency of spin in spin structures created by BS. Consequently, the color of bodies placed near a biological system is able to exert an effective action on the biological system: that is "color therapy" is possible. It is also supposed that the spin-flip effect may be used not only for determining the precession frequency of spin in spin structures created by BS but also for therapeutic action on biological systems. The Faculty of Homeopathy.

Perpetuating stigma or reducing risk? Perspectives from naloxone consumers and pharmacists on pharmacy-based naloxone in 2 states.

PubMed

Green, Traci C; Case, Patricia; Fiske, Haley; Baird, Janette; Cabral, Shachan; Burstein, Dina; Schwartz, Victoriana; Potter, Nathan; Walley, Alexander Y; Bratberg, Jeffrey

Little is known about attitudes of pharmacists and consumers to pharmacy naloxone. We examined perceptions and experiences of pharmacy naloxone from people with opioid use disorder, patients taking chronic opioids for pain, caregivers of opioid users, and pharmacists from 2 early pharmacy naloxone adopter states: Massachusetts and Rhode Island. Eight focus groups (4 per state) were held in October to December 2015. Participants were recruited from pharmacies, health clinics, and community organizations; pharmacists were recruited from professional organizations and pharmacy colleges. Focus groups were led by trained qualitative researchers using a topic guide, and recorded and transcribed for analysis. Five analysts developed and applied a coding scheme to transcripts. Thematic analysis involved synthesis of coded data and connections between key themes, with comparisons across the groups. Sixty-one participants included patients with chronic pain (n = 15), people with opioid use disorders (n = 19), caregivers (n = 16), and pharmacists (n = 11). A majority of pharmacists had dispensed naloxone to patients; a minority of all consumer participants had obtained pharmacy naloxone. Four themes emerged: consumer fear of future consequences if requesting naloxone; pharmacists' concerns about practice logistics related to naloxone; differing perceptions of how opioid safety is addressed in the pharmacy; and solutions to addressing these barriers. Whereas consumer groups differed in awareness of naloxone and availability at pharmacies, all groups expressed support for the pharmacist's role and preferences for a universal offer of naloxone based on clear criteria. Pharmacies complement community naloxone provision to patients and caregivers. To overcome stigma of naloxone receipt, increased public awareness of naloxone and pharmacist training about naloxone and addiction are required. Pharmacists should offer naloxone via universal opt-out strategies-where all patients

Ultra-low dose of intravitreal bevacizumab in retinopathy of prematurity.

PubMed

Şahin, A; Gürsel-Özkurt, Z; Şahin, M; Türkcü, F M; Yıldırım, A; Yüksel, H

2018-05-01

We aimed to investigate the effectivity of the 0.0625 mg dose of bevacizumab in patients with retinopathy of prematurity (ROP) and compare the results with 0.625 mg dose of intravitreal bevacizumab (IVB) injection. The medical records of the patients with type 1 ROP who received IVB monotherapy were retrospectively reviewed. Demographic and clinical characteristics of the patients were recorded. The patients were classified into two groups with respect to received dose of bevacizumab as follows: group F (n = 46) (full dose of bevacizumab-0.625 mg/0.025 ml) and group L (n = 45) (low dose (one tenth) of bevacizumab-0.0625 mg/0.025 ml). Both treatment dose regimens have similar outcomes. Moreover, the mean retinal vascularization time seemed to be significantly higher in group F compared to group L, 168 ± 65 and 97 ± 29 days, respectively (p < 0.001). Disappearance of plus sign is observed earlier in group F (2.45 ± 1.7 vs 3.66 ± 2.46 days, respectively, p = 0.03). The low dose (0.0625 mg) of IVB treatment was effective as full (0.625 mg) dose in ROP treatment. Moreover, our results showed that low-dose treatment might provide faster retinal vascularization than the regular used dose. On the other hand, disappearance of the plus sign takes longer time in patients treated with low dose compared to eyes treated with full dose of IVB that should be taken into account.

An Innovative Model for Naloxone Use Within an OTP Setting: A Prospective Cohort Study

PubMed Central

Katzman, Joanna G.; Takeda, Mikiko Y.; Bhatt, Snehal R.; Moya Balasch, Monica; Greenberg, Nina; Yonas, Howard

2018-01-01

Objectives: Unintentional opioid overdose deaths are a public health crisis, and naloxone is the most effective harm reduction tool to curb many of these deaths. There is growing evidence that take-home naloxone can prevent opioid overdose in targeted populations. The goal of this study is to measure the opioid overdose reversal rate with take-home naloxone among participants with a diagnosis of opioid use disorder (OUD) in an opioid treatment program (OTP) setting. Methods: Patients enrolled in an outpatient OTP program were eligible for this prospective cohort study between April 4, 2016 and July 4, 2016. Two hundred forty-four study participants received overdose education, instruction on how to use naloxone, and were provided with 2 doses of a take-home naloxone auto-injector kit. They were subsequently followed for 3 months. Results: Thirty-one study participants reported overdose reversals using naloxone auto-injector kits on 38 community members. All overdose reversals were heroin-related. Eighty-seven per cent of the community members reversed with naloxone were friends or relatives of the study participants. Conclusions: This study validates that naloxone is not commonly used on the index study participant, but is often used on a secondary target among people who inject drugs. The large number of overdose reversals reported in this prospective study suggests that this novel model for naloxone use may be replicated at other OTP settings to reduce opioid overdose deaths. PMID:29227321

Pitfalls of Intranasal Naloxone

PubMed Central

Zuckerman, Matthew; Weisberg, Stacy N.; Boyer, Edward W.

2016-01-01

We present a case of failed prehospital treatment of fentanyl induced apnea with intranasal (IN) naloxone. While IN administration of naloxone is becoming more common in both lay and pre-hospital settings, older EMS protocols utilized intravenous (IV) administration. Longer-acting, higher potency opioids, such as fentanyl, may not be as easily reversed as heroin, and studies evaluating IN administration in this population are lacking. In order to contribute to our understanding of the strengths and limitations of IN administration of naloxone, we present a case where it failed to restore ventilation. We also describe peer reviewed literature that supports the use of IV naloxone following heroin overdose and explore possible limitations of generalizing this literature to opioids other than heroin and to IN routes of administration. PMID:24830404

Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect.

PubMed

Pioro, Erik P; Brooks, Benjamin Rix; Cummings, Jeffrey; Schiffer, Randolph; Thisted, Ronald A; Wynn, Daniel; Hepner, Adrian; Kaye, Randall

2010-11-01

To evaluate dextromethorphan combined with ultra low-dose quinidine (DMq) for treating pseudobulbar affect (PBA) in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). In a 12-week randomized, double-blind trial, ALS and MS patients with clinically significant PBA (a baseline score ≥13 on the Center for Neurologic Studies-Lability Scale [CNS-LS]) were maintained, twice daily, on placebo, DMq at 30/10mg (DMq-30), or DMq at 20/10mg (DMq-20). In 326 randomized patients (of whom 283, or 86.8%, completed the study), the PBA-episode daily rate was 46.9% (p < 0.0001) lower for DMq-30 than for placebo and 49.0% (p < 0.0001) lower for DMq-20 than for placebo by longitudinal negative binomial regression, the prespecified primary analysis. Mean CNS-LS scores decreased by 8.2 points for DMq-30 and 8.2 for DMq-20, vs 5.7 for placebo (p= 0.0002 and p= 0.0113, respectively). Other endpoints showing statistically significant DMq benefit included, for both dosage levels, the likelihood of PBA remission during the final 14 days and, for the higher dosage, improvement on measures of social functioning and mental health. Both dosages were safe and well tolerated. DMq markedly reduced PBA frequency and severity, decreasing the condition's detrimental impact on a patient's life, with satisfactory safety and high tolerability. The findings expand the clinical evidence that DMq may be an important treatment for patients suffering from the socially debilitating symptoms of PBA.

SU-C-206-07: A Practical Sparse View Ultra-Low Dose CT Acquisition Scheme for PET Attenuation Correction in the Extended Scan Field-Of-View

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miao, J; Fan, J; Gopinatha Pillai, A

Purpose: To further reduce CT dose, a practical sparse-view acquisition scheme is proposed to provide the same attenuation estimation as higher dose for PET imaging in the extended scan field-of-view. Methods: CT scans are often used for PET attenuation correction and can be acquired at very low CT radiation dose. Low dose techniques often employ low tube voltage/current accompanied with a smooth filter before backprojection to reduce CT image noise. These techniques can introduce bias in the conversion from HU to attenuation values, especially in the extended CT scan field-of-view (FOV). In this work, we propose an ultra-low dose CTmore » technique for PET attenuation correction based on sparse-view acquisition. That is, instead of an acquisition of full amount of views, only a fraction of views are acquired. We tested this technique on a 64-slice GE CT scanner using multiple phantoms. CT scan FOV truncation completion was performed based on the published water-cylinder extrapolation algorithm. A number of continuous views per rotation: 984 (full), 246, 123, 82 and 62 have been tested, corresponding to a CT dose reduction of none, 4x, 8x, 12x and 16x. We also simulated sparse-view acquisition by skipping views from the fully-acquired view data. Results: FBP reconstruction with Q. AC filter on reduced views in the full extended scan field-of-view possesses similar image quality to the reconstruction on acquired full view data. The results showed a further potential for dose reduction compared to the full acquisition, without sacrificing any significant attenuation support to the PET. Conclusion: With the proposed sparse-view method, one can potential achieve at least 2x more CT dose reduction compared to the current Ultra-Low Dose (ULD) PET/CT protocol. A pre-scan based dose modulation scheme can be combined with the above sparse-view approaches, which can even further reduce the CT scan dose during a PET/CT exam.« less

No Clinically Relevant Drug-Drug Interactions between Methadone or Buprenorphine-Naloxone and Antiviral Combination Glecaprevir and Pibrentasvir

PubMed Central

Kosloski, Matthew P.; Zhao, Weihan; Asatryan, Armen; Kort, Jens; Geoffroy, Pierre

2017-01-01

ABSTRACT The combination of glecaprevir (formerly ABT-493), a nonstructural protein 3/4A (NS3/4A) protease inhibitor, and pibrentasvir (formerly ABT-530), an NS5A protein inhibitor, is being developed as treatment for HCV genotype 1 to 6 infection. The pharmacokinetics, pharmacodynamics, safety, and tolerability of methadone or buprenorphine-naloxone when coadministered with the glecaprevir-pibrentasvir combination in HCV-negative subjects on stable opioid maintenance therapy were investigated in a phase 1, single-center, two-arm, multiple-dose, open-label sequential study. Subjects received methadone (arm 1) or buprenorphine-naloxone (arm 2) once daily (QD) per their existing individual prescriptions alone (days 1 to 9) and then in combination with glecaprevir at 300 mg QD and pibrentasvir at 120 mg QD (days 10 to 16) each morning. Dose-normalized exposures were similar with and without glecaprevir and pibrentasvir for (R)- and (S)-methadone (≤5% difference) and for buprenorphine and naloxone (≤24% difference); the norbuprenorphine area under the curve was 30% higher with glecaprevir and pibrentasvir, consistent with maximum and trough plasma concentrations that increased by 21% to 25%. No changes in pupil response, short opiate withdrawal scale score, or desire for drugs questionnaire were observed when glecaprevir and pibrentasvir were added to methadone or buprenorphine-naloxone therapy. No dose adjustment is required when glecaprevir and pibrentasvir are coadministered with methadone or buprenorphine-naloxone. PMID:28807904

Predictors of Delayed Postoperative Respiratory Depression Assessed From Naloxone Administration

PubMed Central

Weingarten, Toby N.; Herasevich, Vitaly; McGlinch, Maria C.; Beatty, Nicole C.; Christensen, Erin D.; Hannifan, Susan K.; Koenig, Amy E.; Klanke, Justin; Zhu, Xun; Gali, Bhargavi; Schroeder, Darrell R.; Sprung, Juraj

2015-01-01

Background To identify patient and procedural characteristics associated with postoperative respiratory depression or sedation that required naloxone intervention. Methods We identified patients who received naloxone to reverse opioid-induced respiratory depression or sedation within 48 hours after discharge from anesthetic care (transfer from the post anesthesia care unit, or transfer from the operating room to postoperative areas) between July 1, 2008 and June 30, 2010. Patients were matched to two controls based on age, sex, and exact type of procedure performed during the same year. A chart review was performed to identify patient, anesthetic and surgical factors that may be associated with risk for intervention requiring naloxone. In addition, we identified all patients who developed adverse respiratory events [hypoventilation, apnea, oxyhemoglobin desaturation, pain/sedation mismatch] during Phase I anesthesia recovery. We performed conditional logistic regression taking into account the 1:2 matched set case-control study design to assess patient and procedural characteristics associated with naloxone use. Results We identified 134 naloxone administrations, 58% within 12 hours of discharge from anesthesia care, with incidence of 1.6 per 1,000 (95% CI 1.3 – 1.9) anesthetics. Presence of obstructive sleep apnea (odds ratio = 2.45, 95%CI 1.27-4.66, P = 0.008), and diagnosis of adverse respiratory event in postanesthesia recovery room (odds ratio = 5.11, 95%CI 2.32-11.27, P < 0.001) were associated with increased risk for requiring naloxone to treat respiratory depression or sedation following discharge from anesthesia care. Following discharge from anesthesia care, patients administered naloxone used a greater median dose of opioids (10 [interquartile range 0, 47.1] vs. 5 [0, 24.8] intravenous morphine equivalents, P = 0.020) and more medications with sedating side effects (N = 41 [31%] vs. 24 [9%], P<0.001). Conclusion Obstructive sleep apnea and adverse

Ultra-Low-Dropout Linear Regulator

NASA Technical Reports Server (NTRS)

Thornton, Trevor; Lepkowski, William; Wilk, Seth

2011-01-01

A radiation-tolerant, ultra-low-dropout linear regulator can operate between -150 and 150 C. Prototype components were demonstrated to be performing well after a total ionizing dose of 1 Mrad (Si). Unlike existing components, the linear regulator developed during this activity is unconditionally stable over all operating regimes without the need for an external compensation capacitor. The absence of an external capacitor reduces overall system mass/volume, increases reliability, and lowers cost. Linear regulators generate a precisely controlled voltage for electronic circuits regardless of fluctuations in the load current that the circuit draws from the regulator.

Predictors of participant engagement and naloxone utilization in a community-based naloxone distribution program.

PubMed

Rowe, Christopher; Santos, Glenn-Milo; Vittinghoff, Eric; Wheeler, Eliza; Davidson, Peter; Coffin, Philip O

2015-08-01

To describe characteristics of participants and overdose reversals associated with a community-based naloxone distribution program and identify predictors of obtaining naloxone refills and using naloxone for overdose reversal. Bivariate statistical tests were used to compare characteristics of participants who obtained refills and reported overdose reversals versus those who did not. We fitted multiple logistic regression models to identify predictors of refills and reversals; zero-inflated multiple Poisson regression models were used to identify predictors of number of refills and reversals. San Francisco, California, USA. Naloxone program participants registered and reversals reported from 2010 to 2013. Baseline characteristics of participants and reported characteristics of reversals. A total of 2500 participants were registered and 702 reversals were reported from 2010 to 2013. Participants who had witnessed an overdose [adjusted odds ratio (AOR)=2.02, 95% confidence interval (CI)= 1.53-2.66; AOR = 2.73, 95% CI = 1.73-4.30] or used heroin (AOR = 1.85, 95% CI =  1.44-2.37; AOR = 2.19, 95% CI = 1.54-3.13) or methamphetamine (AOR=1.71, 95% CI=1.37-2.15; AOR=1.61, 95% CI=1.18-2.19) had higher odds of obtaining a refill and reporting a reversal, respectively. African American (AOR = 0.63, 95% CI = 0.45-0.88) and Latino (AOR = 0.65, 95% CI =  0.43-1.00) participants had lower odds of obtaining a naloxone refill, whereas Latino participants who obtained at least one refill reported a higher number of refills [incidence rate ratio (IRR) = 1.33 (1.05-1.69)]. Community naloxone distribution programs are capable of reaching sizeable populations of high-risk individuals and facilitating large numbers of overdose reversals. Community members most likely to engage with a naloxone program and use naloxone to reverse an overdose are active drug users. © 2015 Society for the Study of Addiction.

Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure.

PubMed

Mesnage, Robin; Arno, Matthew; Costanzo, Manuela; Malatesta, Manuela; Séralini, Gilles-Eric; Antoniou, Michael N

2015-08-25

Glyphosate-based herbicides (GBH) are the major pesticides used worldwide. Converging evidence suggests that GBH, such as Roundup, pose a particular health risk to liver and kidneys although low environmentally relevant doses have not been examined. To address this issue, a 2-year study in rats administering 0.1 ppb Roundup (50 ng/L glyphosate equivalent) via drinking water (giving a daily intake of 4 ng/kg bw/day of glyphosate) was conducted. A marked increased incidence of anatomorphological and blood/urine biochemical changes was indicative of liver and kidney structure and functional pathology. In order to confirm these findings we have conducted a transcriptome microarray analysis of the liver and kidneys from these same animals. The expression of 4224 and 4447 transcript clusters (a group of probes corresponding to a known or putative gene) were found to be altered respectively in liver and kidney (p < 0.01, q < 0.08). Changes in gene expression varied from -3.5 to 3.7 fold in liver and from -4.3 to 5.3 in kidneys. Among the 1319 transcript clusters whose expression was altered in both tissues, ontological enrichment in 3 functional categories among 868 genes were found. First, genes involved in mRNA splicing and small nucleolar RNA were mostly upregulated, suggesting disruption of normal spliceosome activity. Electron microscopic analysis of hepatocytes confirmed nucleolar structural disruption. Second, genes controlling chromatin structure (especially histone-lysine N-methyltransferases) were mostly upregulated. Third, genes related to respiratory chain complex I and the tricarboxylic acid cycle were mostly downregulated. Pathway analysis suggests a modulation of the mTOR and phosphatidylinositol signalling pathways. Gene disturbances associated with the chronic administration of ultra-low dose Roundup reflect a liver and kidney lipotoxic condition and increased cellular growth that may be linked with regeneration in response to toxic effects causing damage

Biphasic and triphasic dose responses in zebrafish embryos to low-dose 150 kV X-rays with different levels of hardness.

PubMed

Kong, Eva Yi; Cheng, Shuk Han; Yu, Kwan Ngok

2016-07-01

The in vivo low-dose responses of zebrafish (Danio rerio) embryos to 150 kV X-rays with different levels of hardness were examined through the number of apoptotic events revealed at 24 h post fertilization by vital dye acridine orange staining. Our results suggested that a triphasic dose response was likely a common phenomenon in living organisms irradiated by X-rays, which comprised an ultra-low-dose inhibition, low-dose stimulation and high-dose inhibition. Our results also suggested that the hormetic zone (or the stimulation zone) was shifted towards lower doses with application of filters. The non-detection of a triphasic dose response in previous experiments could likely be attributed to the use of hard X-rays, which shifted the hormetic zone into an unmonitored ultra-low-dose region. In such cases where the subhormetic zone was missed, a biphasic dose response would be reported instead. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Effect of Steady-State Faldaprevir on the Pharmacokinetics of Steady-State Methadone and Buprenorphine-Naloxone in Subjects Receiving Stable Addiction Management Therapy

PubMed Central

Joseph, David; Schobelock, Michael J.; Riesenberg, Robert R.; Vince, Bradley D.; Webster, Lynn R.; Adeniji, Abidemi; Elgadi, Mabrouk

2014-01-01

The effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC0–24,ss), the steady-state maximum concentration of the drug in plasma (Cmax,ss), and the steady-state concentration of the drug in plasma at 24 h (C24,ss) of 0.92 to 1.18 for (R)-methadone, (S)-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This study

SU-F-J-45: Sparing Normal Tissue with Ultra-High Dose Rate in Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Y

Purpose: To spare normal tissue by reducing the location uncertainty of a moving target, we proposed an ultra-high dose rate system and evaluated. Methods: High energy electrons generated with a linear accelerator were injected into a storage ring to be accumulated. The number of the electrons in the ring was determined based on the prescribed radiation dose. The dose was delivered within a millisecond, when an online imaging system found that the target was in the position that was consistent with that in a treatment plan. In such a short time period, the displacement of the target was negligible. Themore » margin added to the clinical target volume (CTV) could be reduced that was evaluated by comparing of volumes between CTV and ITV in 14 cases of lung stereotactic body radiation therapy (SBRT) treatments. A design of the ultra-high dose rate system was evaluated based clinical needs and the recent developments of low energy (a few MeV) electron storage ring. Results: This design of ultra-high dose rate system was feasible based on the techniques currently available. The reduction of a target volume was significant by reducing the margin that accounted the motion of the target. ∼50% volume reduction of the internal target volume (ITV) could be achieved in lung SBRT treatments. Conclusion: With this innovation of ultra-high dose rate system, the margin of target is able to be significantly reduced. It will reduce treatment time of gating and allow precisely specified gating window to improve the accuracy of dose delivering.« less

Effect of naloxone treatment on luteinizing hormone and testosterone concentrations in boars with high and low libido

USDA-ARS?s Scientific Manuscript database

The objective was to determine the effects of naloxone, an opioid peptide receptor antagonist on circulating concentrations of luteinizing hormone (LH) and testosterone in boars characterized as having high (n = 8) or low libido (n = 8) based on the willingness to mount an artificial sow and allow s...

Naloxone inhibits and morphine potentiates. The adrenal steroidogenic response to ACTH

NASA Technical Reports Server (NTRS)

Heybach, J. P.; Vernikos, J.

1980-01-01

The adrenal actions were stereospecific since neither the positve stereoisomer of morphine, nor that of naloxone, had any effect on the adrenal response to exogenous adrenocorticotrophic hormone (ACTH). The administration of human beta endorphin to phyophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone secreting cells of the adrenal cortex.

Opiate users' knowledge about overdose prevention and naloxone in New York City: a focus group study

PubMed Central

Worthington, Nancy; Markham Piper, Tinka; Galea, Sandro; Rosenthal, David

2006-01-01

Background Drug-induced and drug-related deaths have been increasing for the past decade throughout the US. In NYC, drug overdose accounts for nearly 900 deaths per year, a figure that exceeds the number of deaths each year from homicide. Naloxone, a highly effective opiate antagonist, has for decades been used by doctors and paramedics during emergency resuscitation after an opiate overdose. Following the lead of programs in Europe and the US who have successfully distributed take-home naloxone, the Overdose Prevention and Reversal Program at the Lower East Side Harm Reduction Center (LESHRC) has started providing a similar resource for opiate users in NYC. Participants in the program receive a prescription for two doses of naloxone, with refills as needed, and comprehensive training to reduce overdose risk, administer naloxone, perform rescue breathing, and call 911. As of September 2005, 204 participants have received naloxone and been trained, and 40 have revived an overdosing friend or family member. While naloxone accessibility stands as a proven life-saving measure, some opiates users at LESHRC have expressed only minimal interest in naloxone use, due to past experiences and common misconceptions. Methods In order to improve the naloxone distribution program two focus groups were conducted in December 2004 with 13 opiate users at LESHRC to examine knowledge about overdose and overdose prevention. The focus groups assessed participants' (i) experiences with overdose response, specifically naloxone (ii) understanding and perceptions of naloxone, (iii) comfort level with naloxone administration and (iv) feedback about increasing the visibility and desirability of the naloxone distribution program. Results Analyses suggest that there is both support for and resistance to take-home naloxone, marked by enthusiasm for its potential role in reviving an overdosing individual, numerous misconceptions and negative views of its impact and use. Conclusion Focus group

Analysis of buprenorphine/naloxone dosing impact on treatment duration, resource use and costs in the treatment of opioid-dependent adults: a retrospective study of US public and private health care claims.

PubMed

Khemiri, Amine; Kharitonova, Elizaveta; Zah, Vladimir; Ruby, Jane; Toumi, Mondher

2014-09-01

The buprenorphine/naloxone combination is used to treat the chronic relapsing disorder of opioid dependence. Adequate dosing levels are important to control cravings, prevent withdrawal syndrome, and maintain patients in treatment. The objective of this study was to estimate the impact of dosing on treatment persistence, resource utilization, and total direct health care costs. A retrospective cohort analysis was performed using administrative claims extracted from the MarketScan and Clinformatics databases from January 2007 to June and November 2012. Patients initiating treatment with buprenorphine/naloxone were classified into 2 groups based on the prescribed average dose over the entire treatment period and matched by multiple criteria. The threshold for differentiating the dosing groups was set at 15 and 15.7 mg/day for publicly and privately insured patients, respectively. Resource utilization and related costs were calculated over the 12-month period after the treatment initiation. Patient characteristics at baseline were considerably different between the privately and publicly insured patients. Publicly insured patients were slightly younger (33.1 vs 34.3 years old for privately insured) and had a higher prevalence of mental disorders (70.9% vs 64.9%). In both groups, patients treated with higher doses (> 15 mg and > 15.7 mg per day for publicly and privately insured patients, respectively) had lower risk of discontinuation (public: 11% lower; private: 9% lower) and lower probability of a psychiatric hospitalization than patients treated with lower doses (public: 17% lower; private: 41% lower). Total costs were comparable between the 2 groups (public: $14 600; private: $21 000) despite the expected higher cost of pharmacy in the higher-dose group. Treatment with higher doses of buprenorphine/naloxone was associated with a longer time to treatment discontinuation, less resource use, and lower total medical costs despite higher pharmacy acquisition cost.

Effects of aqueous, methanolic and chloroform extracts of rhizome and aerial parts of Valeriana officinalis L. on naloxone-induced jumping in morphine-dependent mice.

PubMed

Sharifzadeh, Mohammad; Hadjiakhoondi, Abbas; Khanavi, Mahnaz; Susanabadi, Maryam

2006-06-01

In the present study, the effects of rhizomes and aerial parts extracts of Valeriana officinalis L. on morphine dependence in mice have been investigated. Animals were treated subcutaneously with morphine (50, 50 and 75 mg/kg) three times daily (10 am, 1 pm and 4 pm) for 3 days, and a last dose of morphine (50 mg/kg) was administered on the fourth day. Withdrawal syndrome (jumping) was precipitated by naloxone (5 mg/kg) which was administered intraperitoneally 2 hours after the last dose of morphine. To study the effects of the aqueous, methanolic and chloroform extracts of both aerial parts and rhizome of the V. officinalis L. on naloxone-induced jumping in morphine-dependent animals, 10 injections of morphine (three administrations each day) for dependence and a dose of 5 mg/kg of naloxone for withdrawal induction were employed. Intraperitoneal injection of different doses (1, 5, 25 and 50 mg/kg) of aqueous, methanolic and chloroform extracts of the rhizome of V. officinalis L. 60 minutes before naloxone injection decreased the jumping response dose-dependently. Pre-treatment of animals with different doses (1, 5, 25, 50 and 100 mg/kg) of aqueous and methanolic extracts of aerial parts of V. officinalis L. 60 minutes before naloxone injection caused a significant decrease on naloxone-induced jumping. The chloroform extract of the aerial parts of V. officinalis L. did not show any significant changes on jumping response in morphine-dependent animals. It is concluded that the extracts of V. officinalis L. could affect morphine withdrawal syndrome via possible interactions with inhibitory neurotransmitters in nervous system.

Comparison of (+)- and (−)-Naloxone on the Acute Psychomotor-Stimulating Effects of Heroin, 6-Acetylmorphine, and Morphine in Mice

PubMed Central

Andersen, Jannike Mørch; Boix, Fernando; Bergh, Marianne Skov-Skov; Vindenes, Vigdis; Rice, Kenner C.; Huestis, Marilyn A.; Mørland, Jørg

2016-01-01

Toll-like receptor 4 (TLR4) signaling is implied in opioid reinforcement, reward, and withdrawal. Here, we explored whether TLR4 signaling is involved in the acute psychomotor-stimulating effects of heroin, 6-acetylmorphine (6-AM), and morphine as well as whether there are differences between the three opioids regarding TLR4 signaling. To address this, we examined how pretreatment with (+)-naloxone, a TLR4 active but opioid receptor (OR) inactive antagonist, affected the acute increase in locomotor activity induced by heroin, 6-AM, or morphine in mice. We also assessed the effect of pretreatment with (−)-naloxone, a TLR4 and OR active antagonist, as well as the pharmacokinetic profiles of (+) and (−)-naloxone in the blood and brain. We found that (−)-naloxone reduced acute opioid-induced locomotor activity in a dose-dependent manner. By contrast, (+)-naloxone, administered in doses assumed to antagonize TLR4 but not ORs, did not affect acute locomotor activity induced by heroin, 6-AM, or morphine. Both naloxone isomers exhibited similar concentration versus time profiles in the blood and brain, but the brain concentrations of (−)-naloxone reached higher levels than those of (+)-naloxone. However, the discrepancies in their pharmacokinetic properties did not explain the marked difference between the two isomers’ ability to affect opioid-induced locomotor activity. Our results underpin the importance of OR activation and do not indicate an apparent role of TLR4 signaling in acute opioid-induced psychomotor stimulation in mice. Furthermore, there were no marked differences between heroin, 6-AM, and morphine regarding involvement of OR or TLR4 signaling. PMID:27278234

Submillisievert standard-pitch CT pulmonary angiography with ultra-low dose contrast media administration: A comparison to standard CT imaging.

PubMed

Suntharalingam, Saravanabavaan; Mikat, Christian; Stenzel, Elena; Erfanian, Youssef; Wetter, Axel; Schlosser, Thomas; Forsting, Michael; Nassenstein, Kai

2017-01-01

To evaluate the image quality and radiation dose of submillisievert standard-pitch CT pulmonary angiography (CTPA) with ultra-low dose contrast media administration in comparison to standard CTPA. Hundred patients (56 females, 44 males, mean age 69.6±15.4 years; median BMI: 26.6, IQR: 5.9) with suspected pulmonary embolism were examined with two different protocols (n = 50 each, group A: 80 kVp, ref. mAs 115, 25 ml of contrast medium; group B: 100 kVp, ref. mAs 150, 60 ml of contrast medium) using a dual-source CT equipped with automated exposure control. Objective and subjective image qualities, radiation exposure as well as the frequency of pulmonary embolism were evaluated. There was no significant difference in subjective image quality scores between two groups regarding pulmonary arteries (p = 0.776), whereby the interobserver agreement was excellent (group A: k = 0.9; group B k = 1.0). Objective image analysis revealed that signal intensities (SI), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the pulmonary arteries were equal or significantly higher in group B. There was no significant difference in the frequency of pulmonary embolism (p = 0.65). Using the low dose and low contrast media protocol resulted in a radiation dose reduction by 71.8% (2.4 vs. 0.7 mSv; p<0.001). This 80 kVp standard pitch CTPA protocol with 25 ml contrast agent volume can obtain sufficient image quality to exclude or diagnose pulmonary emboli while reducing radiation dose by approximately 71%.

Ultra-low-dose lung screening CT with model-based iterative reconstruction: an assessment of image quality and lesion conspicuity.

PubMed

Ju, Yun Hye; Lee, Geewon; Lee, Ji Won; Hong, Seung Baek; Suh, Young Ju; Jeong, Yeon Joo

2018-05-01

Background Reducing radiation dose inevitably increases image noise, and thus, it is important in low-dose computed tomography (CT) to maintain image quality and lesion detection performance. Purpose To assess image quality and lesion conspicuity of ultra-low-dose CT with model-based iterative reconstruction (MBIR) and to determine a suitable protocol for lung screening CT. Material and Methods A total of 120 heavy smokers underwent lung screening CT and were randomly and equally assigned to one of five groups: group 1 = 120 kVp, 25 mAs, with FBP reconstruction; group 2 = 120 kVp, 10 mAs, with MBIR; group 3 = 100 kVp, 15 mAs, with MBIR; group 4 = 100 kVp, 10 mAs, with MBIR; and group 5 = 100 kVp, 5 mAs, with MBIR. Two radiologists evaluated intergroup differences with respect to radiation dose, image noise, image quality, and lesion conspicuity using the Kruskal-Wallis test and the Chi-square test. Results Effective doses were 61-87% lower in groups 2-5 than in group 1. Image noises in groups 1 and 5 were significantly higher than in the other groups ( P < 0.001). Overall image quality was best in group 1, but diagnostic acceptability of overall image qualities in groups 1-3 was not significantly different (all P values > 0.05). Lesion conspicuities were similar in groups 1-4, but were significantly poorer in group 5. Conclusion Lung screening CT with MBIR obtained at 100 kVp and 15 mAs enables a ∼60% reduction in radiation dose versus low-dose CT, while maintaining image quality and lesion conspicuity.

Naloxone reversal of an overdose of a novel, long-acting transdermal fentanyl solution in laboratory Beagles.

PubMed

Freise, K J; Newbound, G C; Tudan, C; Clark, T P

2012-08-01

Opioid overdose in dogs is manifested by clinical signs such as excessive sedation, bradycardia, and hypothermia. The ability of two different intramuscular (i.m.) naloxone reversal regimens to reverse the opioid-induced effects of a fivefold overdose of long-acting transdermal fentanyl solution was evaluated in dogs. Twenty-four healthy Beagles were administered a single 13 mg/kg dose (fivefold overdose) of transdermal fentanyl solution and randomized to two naloxone reversal regimen treatment groups, hourly administration for 8 h of 40 (n = 8) or 160 μg/kg i.m. (n = 16). All dogs were sedated and had reduced body temperatures and heart rates (HRs) prior to naloxone administration. Both dosage regimens significantly reduced sedation (P < 0.001), and the 160 μg/kg naloxone regimen resulted in a nearly threefold lower odds of sedation than that of the 40 μg/kg i.m. naloxone regimen (P < 0.05). Additionally, naloxone significantly increased the mean body temperatures and HR (P < 0.001), although the 160 μg/kg regimen increased body temperature and HR more (P < 0.05). However, the narcotic side effects of fentanyl returned within 1-3 h following termination of the naloxone dosage regimens. The opioid-induced effects of an overdose of transdermal fentanyl solution can be safely and effectively reversed by either 40 or 160 μg/kg i.m. naloxone administered at hourly intervals. © 2012 Blackwell Publishing Ltd.

Clinical experience with fortnightly buprenorphine/naloxone versus buprenorphine in Italy: preliminary observational data in an office-based setting.

PubMed

Amato, Patrizia

2010-01-01

Buprenorphine/naloxone is a new option for the management of opioid dependence. It has a reduced potential for abuse or misuse compared with methadone and buprenorphine alone, and has a long half-life allowing less frequent dosing. Buprenorphine/naloxone appears to be well suited for the management of opioid dependence in an office-based setting. The aim of this study was to evaluate the efficacy and safety of a buprenorphine/naloxone combination treatment in an office-based setting. Therefore, we evaluated the effect on misuse/diversion, quality of care, quality of life and service delivery. Seventy-eight patients were switched to buprenorphine/naloxone from either methadone or buprenorphine alone; the median duration of previous buprenorphine or methadone treatment was 10 years. Patients received buprenorphine/naloxone and were evaluated throughout a 1-year follow-up period. Treatment was self-administered by the patients every 2 weeks and the mean buprenorphine dosage at 1 year was 8 mg/day. Comparisons were made before and after the switch for patients who switched from buprenorphine alone to buprenorphine/naloxone. Switching to buprenorphine/naloxone was not associated with clinically relevant problems in 50% of patients studied. Buprenorphine/naloxone provided satisfactory coverage of withdrawal symptoms in 78.1% of patients, and 50% of patients were satisfied with buprenorphine/naloxone therapy. Seventy-eight per cent of patients reported improved psychosocial functioning. The majority of patients (approximately 85%) were negative for opioids during toxicological testing. A significantly higher proportion of treatment recipients were highly satisfied during buprenorphine/naloxone administration (p < 0.001 compared with buprenorphine given before the switch). Other outcomes were similar during buprenorphine and buprenorphine/naloxone administration. Fortnightly self-administration of buprenorphine/naloxone appeared to be cost saving for the clinic

Ultra-Low Doses of Naltrexone Enhance the Antiallodynic Effect of Pregabalin or Gabapentin in Neuropathic Rats.

PubMed

Pineda-Farias, Jorge B; Caram-Salas, Nadia L; Salinas-Abarca, Ana B; Ocampo, Jorge; Granados-Soto, Vinicio

2017-12-01

Preclinical Research Treatment of neuropathic pain is an area of largely unmet medical need. Pregabalin and gabapentin are anticonvulsants widely used for the treatment of neuropathic pain. Unfortunately, these drugs are only effective in 50-60% of the treated patients. In addition, both drugs have substantial side effects. Several studies have reported that ultralow doses of opioid receptor antagonists can induce analgesia and enhance the analgesic effect of opioids in rodents and humans. The objective of the present study was to assess the antiallodynic synergistic interaction between gabapentinoids and naltrexone in rats. Oral administration of pregabalin (ED 50  = 2.79 ± 0.16 mg/kg) or gabapentin (ED 50  = 21.04 ± 2.87 mg/kg) as well as intrathecal naltrexone (ED 50  = 0.11 ± 0.02 ng) reduced in a dose-dependent manner tactile allodynia in rats. Maximal antiallodynic effects (∼100%) were reached with 30 mg/kg of pregabalin, 300 mg/kg of gabapentin or 0.5 ng of naltrexone. Co-administration of pregabalin or gabapentin and naltrexone in a fixed-dose ratio (1:1) remarkably reduced spinal nerve ligation-induced tactile allodynia showing a synergistic interaction. The data indicate that combinations of pregabalin or gabapentin and ultra-low doses of naltrexone are able to reduce tactile allodynia in neuropathic rats with lower doses that those used when drugs are given individually and with an improved side effects profile. Drug Dev Res 78 : 371-380, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Adaptive Statistical Iterative Reconstruction-Applied Ultra-Low-Dose CT with Radiography-Comparable Radiation Dose: Usefulness for Lung Nodule Detection.

PubMed

Yoon, Hyun Jung; Chung, Myung Jin; Hwang, Hye Sun; Moon, Jung Won; Lee, Kyung Soo

2015-01-01

To assess the performance of adaptive statistical iterative reconstruction (ASIR)-applied ultra-low-dose CT (ULDCT) in detecting small lung nodules. Thirty patients underwent both ULDCT and standard dose CT (SCT). After determining the reference standard nodules, five observers, blinded to the reference standard reading results, independently evaluated SCT and both subsets of ASIR- and filtered back projection (FBP)-driven ULDCT images. Data assessed by observers were compared statistically. Converted effective doses in SCT and ULDCT were 2.81 ± 0.92 and 0.17 ± 0.02 mSv, respectively. A total of 114 lung nodules were detected on SCT as a standard reference. There was no statistically significant difference in sensitivity between ASIR-driven ULDCT and SCT for three out of the five observers (p = 0.678, 0.735, < 0.01, 0.038, and < 0.868 for observers 1, 2, 3, 4, and 5, respectively). The sensitivity of FBP-driven ULDCT was significantly lower than that of ASIR-driven ULDCT in three out of the five observers (p < 0.01 for three observers, and p = 0.064 and 0.146 for two observers). In jackknife alternative free-response receiver operating characteristic analysis, the mean values of figure-of-merit (FOM) for FBP, ASIR-driven ULDCT, and SCT were 0.682, 0.772, and 0.821, respectively, and there were no significant differences in FOM values between ASIR-driven ULDCT and SCT (p = 0.11), but the FOM value of FBP-driven ULDCT was significantly lower than that of ASIR-driven ULDCT and SCT (p = 0.01 and 0.00). Adaptive statistical iterative reconstruction-driven ULDCT delivering a radiation dose of only 0.17 mSv offers acceptable sensitivity in nodule detection compared with SCT and has better performance than FBP-driven ULDCT.

Adaptive Statistical Iterative Reconstruction-Applied Ultra-Low-Dose CT with Radiography-Comparable Radiation Dose: Usefulness for Lung Nodule Detection

PubMed Central

Yoon, Hyun Jung; Hwang, Hye Sun; Moon, Jung Won; Lee, Kyung Soo

2015-01-01

Objective To assess the performance of adaptive statistical iterative reconstruction (ASIR)-applied ultra-low-dose CT (ULDCT) in detecting small lung nodules. Materials and Methods Thirty patients underwent both ULDCT and standard dose CT (SCT). After determining the reference standard nodules, five observers, blinded to the reference standard reading results, independently evaluated SCT and both subsets of ASIR- and filtered back projection (FBP)-driven ULDCT images. Data assessed by observers were compared statistically. Results Converted effective doses in SCT and ULDCT were 2.81 ± 0.92 and 0.17 ± 0.02 mSv, respectively. A total of 114 lung nodules were detected on SCT as a standard reference. There was no statistically significant difference in sensitivity between ASIR-driven ULDCT and SCT for three out of the five observers (p = 0.678, 0.735, < 0.01, 0.038, and < 0.868 for observers 1, 2, 3, 4, and 5, respectively). The sensitivity of FBP-driven ULDCT was significantly lower than that of ASIR-driven ULDCT in three out of the five observers (p < 0.01 for three observers, and p = 0.064 and 0.146 for two observers). In jackknife alternative free-response receiver operating characteristic analysis, the mean values of figure-of-merit (FOM) for FBP, ASIR-driven ULDCT, and SCT were 0.682, 0.772, and 0.821, respectively, and there were no significant differences in FOM values between ASIR-driven ULDCT and SCT (p = 0.11), but the FOM value of FBP-driven ULDCT was significantly lower than that of ASIR-driven ULDCT and SCT (p = 0.01 and 0.00). Conclusion Adaptive statistical iterative reconstruction-driven ULDCT delivering a radiation dose of only 0.17 mSv offers acceptable sensitivity in nodule detection compared with SCT and has better performance than FBP-driven ULDCT. PMID:26357505

Submillisievert standard-pitch CT pulmonary angiography with ultra-low dose contrast media administration: A comparison to standard CT imaging

PubMed Central

Mikat, Christian; Stenzel, Elena; Erfanian, Youssef; Wetter, Axel; Schlosser, Thomas; Forsting, Michael

2017-01-01

Objectives To evaluate the image quality and radiation dose of submillisievert standard-pitch CT pulmonary angiography (CTPA) with ultra-low dose contrast media administration in comparison to standard CTPA. Materials and methods Hundred patients (56 females, 44 males, mean age 69.6±15.4 years; median BMI: 26.6, IQR: 5.9) with suspected pulmonary embolism were examined with two different protocols (n = 50 each, group A: 80 kVp, ref. mAs 115, 25 ml of contrast medium; group B: 100 kVp, ref. mAs 150, 60 ml of contrast medium) using a dual-source CT equipped with automated exposure control. Objective and subjective image qualities, radiation exposure as well as the frequency of pulmonary embolism were evaluated. Results There was no significant difference in subjective image quality scores between two groups regarding pulmonary arteries (p = 0.776), whereby the interobserver agreement was excellent (group A: k = 0.9; group B k = 1.0). Objective image analysis revealed that signal intensities (SI), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the pulmonary arteries were equal or significantly higher in group B. There was no significant difference in the frequency of pulmonary embolism (p = 0.65). Using the low dose and low contrast media protocol resulted in a radiation dose reduction by 71.8% (2.4 vs. 0.7 mSv; p<0.001). Conclusions This 80 kVp standard pitch CTPA protocol with 25 ml contrast agent volume can obtain sufficient image quality to exclude or diagnose pulmonary emboli while reducing radiation dose by approximately 71%. PMID:29045463

A low-cost, ultra-fast and ultra-low noise preamplifier for silicon avalanche photodiodes

NASA Astrophysics Data System (ADS)

Gasmi, Khaled

2018-02-01

An ultra-fast and ultra-low noise preamplifier for amplifying the fast and weak electrical signals generated by silicon avalanche photodiodes has been designed and developed. It is characterized by its simplicity, compactness, reliability and low cost of construction. A very wide bandwidth of 300 MHz, a very good linearity from 1 kHz to 280 MHz, an ultra-low noise level at the input of only 1.7 nV Hz-1/2 and a very good stability are its key features. The compact size (70 mm  ×  90 mm) and light weight (45 g), as well as its excellent characteristics, make this preamplifier very competitive compared to any commercial preamplifier. The preamplifier, which is a main part of the detection system of a homemade laser remote sensing system, has been successfully tested. In addition, it is versatile and can be used in any optical detection system requiring high speed and very low noise electronics.

Effects of opiate-like peptides, morphine, and naloxone in the photosensitive baboon, Papio papio.

PubMed

Meldrum, B S; Menini, C; Stutzmann, J M; Naquet, R

1979-07-13

The effects of intracerebroventricular (i.c.v.) or systemic injections of Met- or Leu-enkephalin, beta-endorphin, FK 33.824 (D-Ala2, MePhe4, Met(O5)-ol-enkephalin) and of morphine and naloxone have been studied in baboons, Papio papio, which spontaneously show photically induced epileptic responses. Animals were chronically implanted with epidural or deep recording electrodes and a cannula in one lateral ventricle, and tested whilst seated in a primate chair. In some animals the natural syndrome was enhanced by the prior administration of DL-allylglycine, 100--200 mg/kg, i.v. Met- or Leu-enkephalin, 1--10 mg, i.c.v., did not lead to any manifest focal or generalized seizure discharges. Nor did it lead to any consistent enhancement or reduction of photically induced myoclonic responses (as tested 5--10 min after injection). beta-Endorphin, 0.1--0.5 mg, i.c.v., did not enhance or impair photically induced myoclonic responses. FK 33.824, 0.1--0.5 mg, i.c.v., depressed respiration and slowed EEG background rhythms for 9--15 h. This was associated with a loss of myoclonic responses to photic stimulation. These effects were reversed for 20--40 min following the injection of naloxone, 1 mg/kg i.m. A depression of respiration and a slowing of EEG rhythms was seen beginning 5--20 min after FK 33.824, 2 or 4 mg/kg, i.v. The higher dose also abolished photically induced myoclonic responses. Naloxone, 1 mg/kg, definitively reversed these effects. Morphine, 5--10 mg i.c.v., tended to increase the latency to onset of generalized myoclonus during photic stimulation. Myoclonic responses were delayed or diminished after morphine, 5 mg/kg, i.m. Naloxone, 1--2 mg/kg i.m., reversed this effect. Naloxone, 0.2--5.0 mg/kg i.m., alone, did not significantly modify photically induced myoclonus, either in animals of low or high initial responsiveness, or in those pretreated with allylglycine.

Propranolol blocks the stimulatory effects of naloxone on ventilation and oxygen consumption in hamsters.

PubMed

Schlenker, E H; Eikanger, J

1997-06-01

The purposes of these studies were: 1) to determine the effects of various doses of propranolol, a nonspecific beta-adrenergic antagonist, on ventilation, oxygen consumption, and body temperature in hamsters, and 2) to test the hypothesis that in hamsters the stimulatory effects of naloxone, an opioid receptor antagonist, on ventilation and oxygen consumption occur, at least in part, through the release of catecholamines that act via beta-adrenergic receptors. Propranolol, a non-specific beta adrenergic receptor antagonist, at a 20 mg/kg depressed body temperature, oxygen consumption, tidal volume, and ventilation relative to saline. The lower dose of 10 mg/kg had only transitory effects on tidal volume at 60 min and ventilation at 30 min post-injection-Naloxone (1 mg/kg) relative to saline stimulated ventilation and oxygen consumption. These effects were blocked by propranolol pretreatment. The results of these experiments demonstrate that in the hamster, 1) body temperature, oxygen consumption, and ventilation appear to be modulated by beta-adrenergic receptors, and 2) the stimulatory effects of naloxone on oxygen consumption and ventilation may occur through the interaction of endogenous opioids and beta-adrenergic receptor systems.

Is multidetector CT-based bone mineral density and quantitative bone microstructure assessment at the spine still feasible using ultra-low tube current and sparse sampling?

PubMed

Mei, Kai; Kopp, Felix K; Bippus, Rolf; Köhler, Thomas; Schwaiger, Benedikt J; Gersing, Alexandra S; Fehringer, Andreas; Sauter, Andreas; Münzel, Daniela; Pfeiffer, Franz; Rummeny, Ernst J; Kirschke, Jan S; Noël, Peter B; Baum, Thomas

2017-12-01

Osteoporosis diagnosis using multidetector CT (MDCT) is limited to relatively high radiation exposure. We investigated the effect of simulated ultra-low-dose protocols on in-vivo bone mineral density (BMD) and quantitative trabecular bone assessment. Institutional review board approval was obtained. Twelve subjects with osteoporotic vertebral fractures and 12 age- and gender-matched controls undergoing routine thoracic and abdominal MDCT were included (average effective dose: 10 mSv). Ultra-low radiation examinations were achieved by simulating lower tube currents and sparse samplings at 50%, 25% and 10% of the original dose. BMD and trabecular bone parameters were extracted in T10-L5. Except for BMD measurements in sparse sampling data, absolute values of all parameters derived from ultra-low-dose data were significantly different from those derived from original dose images (p<0.05). BMD, apparent bone fraction and trabecular thickness were still consistently lower in subjects with than in those without fractures (p<0.05). In ultra-low-dose scans, BMD and microstructure parameters were able to differentiate subjects with and without vertebral fractures, suggesting osteoporosis diagnosis is feasible. However, absolute values differed from original values. BMD from sparse sampling appeared to be more robust. This dose-dependency of parameters should be considered for future clinical use. • BMD and quantitative bone parameters are assessable in ultra-low-dose in vivo MDCT scans. • Bone mineral density does not change significantly when sparse sampling is applied. • Quantitative trabecular bone microstructure measurements are sensitive to dose reduction. • Osteoporosis subjects could be differentiated even at 10% of original dose. • Radiation exposure should be considered when comparing quantitative bone parameters.

Naloxone Injection

MedlinePlus

... emergency medical treatment to reverse the life-threatening effects of a known or suspected opiate (narcotic) overdose. ... is also used after surgery to reverse the effects of opiates given during surgery. Naloxone injection is ...

Police officer attitudes towards intranasal naloxone training.

PubMed

Ray, Bradley; O'Donnell, Daniel; Kahre, Kailyn

2015-01-01

One approach to reduce fatal opioid overdose is by distributing naloxone to law enforcement officers. While several cities have implemented these naloxone programs, little research has investigated officer attitudes about their training. The present research attempts to fill this gap by analyzing survey data from police officers following intranasal naloxone training. All of the police officers within the same district in Indianapolis, Indiana, underwent training to recognize opioid overdose and to administer intranasal naloxone (N=117). Following training, officers completed a survey that measured prior experience with opioid overdose, perceived importance of training, and items from the Opioid Overdose Attitudes Scale (OOAS) to measure attitudes following training. The officers had overwhelmingly positive feelings about the training, that it was not difficult, and that other officers should be trained to use naloxone. The OOAS items suggest that officers know the appropriate actions to take in the event of an overdose and feel that administering intranasal naloxone will not be difficult. Finally, we found that officers who had more experience with opioid overdose had more positive attitudes about the training. Distributing naloxone to police officers is likely a trend that will continue so it is important to understand how police officers respond to training to assure that future trainings are as effective as possible. Further research is needed to investigate the impact that these programs have on the community. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Ultra-low Doses of Follicle Stimulating Hormone and Progesterone Attenuate the Severity of Polycystic Ovary Syndrome Features in a Hyperandrogenized Mouse Model

PubMed Central

Tessaro, Irene; Modina, Silvia; Lodde, Valentina; Sivelli, Giulia; Franciosi, Federica; Terzaghi, Laura; Luchini, Patrizia; Rumio, Cristiano; Luciano, Alberto Maria

2017-01-01

Background: Polycystic-ovary syndrome (PCOS) is a reproductive illness characterized by hyperandrogenism and anovulation. Using hyperandrogenized mice, it was demonstrated that the oral administration of incremental dose of follicle stimulating hormone (FSH) attenuated some of PCOS characteristics. This work aimed to study the effect of ultra-low doses of combined FSH and progesterone orally administered on PCOS murine model. Moreover, the effect of sequential kinetic activation of administered hormones was tested. Methods: Thirty-two female mice were used as animal model (four groups of eight animals each). Mice were hyperandrogenized by injection of dehyidroepiandrosterone diluted in sesame oil. Control group received only oil. Simultaneously, each animal daily received per os an activated or a not-activated combination of FSH (0.44 pg) plus progesterone (0.44 pg) or saline solution as control. Serum testosterone, estradiol, progesterone and luteinizing hormone were analyzed as endocrine markers and a morphological study of antral follicle was conducted. Data were analyzed by one-way ANOVA, followed by multiple comparison test. The p<0.05 was considered significant. Results: Dehyidroepiandrosterone treatment increased both estradiol and progesterone serum levels, besides testosterone, while reduced luteinizing hormone (p<0.05); histological examination revealed an increase of cystic follicles (p<0.05). Irrespective of activation, the combined FSH and progesterone treatments restored estradiol level (p>0.05 vs. control group) and reduced cystic signs in the follicles (p<0.05 vs. dehyidroepiandrosterone treatment). Conclusion: This study indicate that ultra-low doses of FSH and progesterone orally administrated can reduce the sternness of PCOS in the mouse model and open a route for the study of innovative approaches for PCOS treatment. PMID:29062793

Caged Naloxone: Synthesis, Characterization, and Stability of 3- O-(4,5-Dimethoxy-2-nitrophenyl)carboxymethyl Naloxone (CNV-NLX).

PubMed

Lewin, Anita H; Fix, Scott E; Zhong, Desong; Mayer, Louise D; Burgess, Jason P; Mascarella, S Wayne; Reddy, P Anantha; Seltzman, Herbert H; Carroll, F Ivy

2018-03-21

The photolabile analogue of the broad-spectrum opioid antagonist naloxone, 3- O-(4,5-dimethoxy-2-nitrophenyl)carboxymethyl naloxone (also referred to as "caged naloxone", 3- O-(α-carboxy-6-nitroveratryl)naloxone, CNV-NLX), has been found to be a valuable biochemical probe. While the synthesis of CNV-NLX is simple, its characterization is complicated by the fact that it is produced as a mixture of α R,5 R,9 R,13 S,14 S and α S,5 R,9 R,13 S,14 S diastereomers. Using long-range and heteronuclear NMR correlations, the 1 H NMR and 13 C NMR resonances of both diastereomers have been fully assigned, confirming the structures. Monitoring of solutions of CNV-NLX in saline buffer, in methanol, and in DMSO has shown CNV-NLX to be stable for over a week under fluorescent laboratory lights at room temperature. Exposure of such solutions to λ 365 nm from a hand-held UV lamp led to the formation of naloxone and CNV-related breakdown products.

Opioid overdose and naloxone education in a substance use disorder treatment program.

PubMed

Lott, David C; Rhodes, Jonathan

2016-04-01

Opioid users in treatment are at high risk of relapse and overdose, making them an important target for efforts to reduce opioid overdose mortality. Overdose Education (OE) is one such intervention, and this study tests the effectiveness of OE in a community substance use disorder treatment program. Opioid users were recruited from a community treatment center for the study. The Opioid Overdose Knowledge Scale (OOKS) was administered before and after an educational intervention (small group lecture, slideshow, and handout based on previously published content) to assess knowledge of the risks, signs, and actions associated with opioid overdose, including use of naloxone. Additional survey questions assessed naloxone access, naloxone education, and overdose experiences at treatment and 3-month follow-up. Subjects (n = 43) were 28% female and had a mean age of 31 years. OOKS scores were compared at pre-intervention, post-intervention, and follow-up, and results were also compared with a historical non-intervention control group (n = 14). Total score on the OOKS increased significantly from pre- to post-education, and improvement was maintained at follow-up (p < .0001). OOKS subdomains of actions and naloxone use also had significant increases (p < .0001). Four subjects reported possessing naloxone in the past, and only one subject who did not already have naloxone at the time of treatment had obtained it at follow-up. Education about opioid overdose and naloxone use in a community treatment program increases overdose knowledge, providing support for the idea of making OE a routine part of substance use disorder treatment. However, the rate of follow through on accessing naloxone was low with this education-only intervention. © 2016 The Authors. The American Journal on Addictions Published by American Academy of Addiction Psychiatry.

Does Naloxone Prevent Seizure in Tramadol Intoxicated Patients?

PubMed Central

Eizadi-Mood, Nastaran; Ozcan, Dilek; Sabzghabaee, Ali Mohammad; Mirmoghtadaee, Parisa; Hedaiaty, Mahrang

2014-01-01

Background: Tramadol poisoning has increased in recent years. Seizure is one of the side-effects of tramadol toxicity. There is a controversy about possible preventive effect of naloxone in tramadol poisoning induced seizure. Therefore, this study was performed to compare seizure incidence in tramadol poisoning patients who received and did not receive naloxone, as an opioid antagonist. Methods: This study involved prospective data collection followed by retrospective analysis on 104 tramadol poisoning patients who were admitted in a referral poisoning center. The incidences of seizure were compared between patients received naloxone and those did not. Outcome was considered as survived without or with complications and death. Logistic Regression analysis was used to determine the effects of different variables on seizure incidence. Results: 70 (67.3%) of the patients were men. The mean age of the patients was 26.3 ± 9 years old. 18.3% of the patients received naloxone in their treatment period. Seizure incidence was significantly higher among tramadol poisoning patients who did not receive naloxone compare with those received naloxone (14.1% vs. 5.1%). Among different variable studied, age had a significant effect on predicting of seizure (odds ratio = 2.09; 95% of confidence interval: 1.82-2.26; P value, 0.004). Conclusions: Although the seizure incidence was lower in patients with tramadol poisoning who received naloxone, the logistic regression did not support the preventive effect of naloxone on seizure in tramadol poisoning cases. PMID:24829714

Assessment of provider attitudes toward #naloxone on Twitter.

PubMed

Haug, Nancy A; Bielenberg, Jennifer; Linder, Steven H; Lembke, Anna

2016-01-01

As opioid overdose rates continue to pose a major public health crisis, the need for naloxone treatment by emergency first responders is critical. Little is known about the views of those who administer naloxone. The current study examines attitudes of health professionals on the social media platform Twitter to better understand their perceptions of opioid users, the role of naloxone, and potential training needs. Public comments on Twitter regarding naloxone were collected for a period of 3 consecutive months. The occupations of individuals who posted tweets were identified through Twitter profiles or hashtags. Categories of emergency service first responders and medical personnel were created. Qualitative analysis using a grounded theory approach was used to produce thematic content. The relationships between occupation and each theme were analyzed using Pearson chi-square statistics and post hoc analyses. A total of 368 individuals posted 467 naloxone-related tweets. Occupations consisted of professional first responders such as emergency medical technicians (EMTs), firefighters, and paramedics (n = 122); law enforcement officers (n = 70); nurses (n = 62); physicians (n = 48); other health professionals including pharmacists, pharmacy technicians, counselors, and social workers (n = 31); naloxone-trained individuals (n = 12); and students (n = 23). Primary themes included burnout, education and training, information seeking, news updates, optimism, policy and economics, stigma, and treatment. The highest levels of burnout, fatigue, and stigma regarding naloxone and opioid overdose were among nurses, EMTs, other health care providers, and physicians. In contrast, individuals who self-identified as "naloxone-trained" had the highest optimism and the lowest amount of burnout and stigma. Provider training and refinement of naloxone administration procedures are needed to improve treatment outcomes and reduce provider stigma. Social networking sites such as Twitter

Do heroin overdose patients require observation after receiving naloxone?

PubMed

Willman, Michael W; Liss, David B; Schwarz, Evan S; Mullins, Michael E

2017-02-01

included non-heroin opioid overdoses, there were 5443 patients treated without transport and four deaths from rebound opioid toxicity. The number needed to transport to save one life (NNT) is 1361. Adverse effects were mostly related to opioid withdrawal. If a heroin user is treated in the ED, how long must the patient stay under observation before being safe for discharge? Five articles addressing the duration of ED observation required for patients treated with naloxone for opioid overdoses. Although a wide range of observation durations were reported, one study supported observing patients for one hour. If after this period the patient mobilizes as usual, has normal vital signs, and a Glasgow Coma Scale of 15, they can be discharged safely. What are the likely risks in heroin users following naloxone use by lay bystanders or first responders? Of the 15 relevant papers, a systematic review reported a 100% survival rate in eleven studies and a range of 96-99% survival in the remaining four. Two other studies suffered from poor follow-up and had lower success rates of 83% and 89%. Few if any risks were associated with opioid overdose prevention programs in which lay people were trained to administer naloxone. Patients revived with naloxone after heroin overdose may be safely released without transport to the hospital if they have normal mentation and vital signs. In the absence of co-intoxicants and further opioid use there is very low risk of death from rebound opioid toxicity. For those patients treated in the ED for opioid overdose, an observation period of one hour is sufficient if they ambulate as usual, have normal vital signs and a Glasgow Coma Scale of 15. Patients suffering opioid toxicity can be administered naloxone safely by first responders and trained lay people. Programs that train these individuals are likely safe and beneficial, however further research is necessary.

International patent applications for non-injectable naloxone for opioid overdose reversal: Exploratory search and retrieve analysis of the PatentScope database.

PubMed

McDonald, Rebecca; Danielsson Glende, Øyvind; Dale, Ola; Strang, John

2018-02-01

Non-injectable naloxone formulations are being developed for opioid overdose reversal, but only limited data have been published in the peer-reviewed domain. Through examination of a hitherto-unsearched database, we expand public knowledge of non-injectable formulations, tracing their development and novelty, with the aim to describe and compare their pharmacokinetic properties. (i) The PatentScope database of the World Intellectual Property Organization was searched for relevant English-language patent applications; (ii) Pharmacokinetic data were extracted, collated and analysed; (iii) PubMed was searched using Boolean search query '(nasal OR intranasal OR nose OR buccal OR sublingual) AND naloxone AND pharmacokinetics'. Five hundred and twenty-two PatentScope and 56 PubMed records were identified: three published international patent applications and five peer-reviewed papers were eligible. Pharmacokinetic data were available for intranasal, sublingual, and reference routes. Highly concentrated formulations (10-40 mg mL -1 ) had been developed and tested. Sublingual bioavailability was very low (1%; relative to intravenous). Non-concentrated intranasal spray (1 mg mL -1 ; 1 mL per nostril) had low bioavailability (11%). Concentrated intranasal formulations (≥10 mg mL -1 ) had bioavailability of 21-42% (relative to intravenous) and 26-57% (relative to intramuscular), with peak concentrations (dose-adjusted C max  = 0.8-1.7 ng mL -1 ) reached in 19-30 min (t max ). Exploratory analysis identified intranasal bioavailability as associated positively with dose and negatively with volume. We find consistent direction of development of intranasal sprays to high-concentration, low-volume formulations with bioavailability in the 20-60% range. These have potential to deliver a therapeutic dose in 0.1 mL volume. [McDonald R, Danielsson Glende Ø, Dale O, Strang J. International patent applications for non-injectable naloxone for opioid overdose reversal

Gold nanoshells-mediated bimodal photodynamic and photothermal cancer treatment using ultra-low doses of near infra-red light.

PubMed

Vankayala, Raviraj; Lin, Chun-Chih; Kalluru, Poliraju; Chiang, Chi-Shiun; Hwang, Kuo Chu

2014-07-01

Previously, gold nanoshells were shown to be able to effectively convert photon energy to heat, leading to hyperthermia and suppression of tumor growths in mice. Herein, we show that in addition to the nanomaterial-mediated photothermal effects (NmPTT), gold nanoshells (including, nanocages, nanorod-in-shell and nanoparticle-in-shell) not only are able to absorb NIR light, but can also emit fluorescence, sensitize formation of singlet oxygen and exert nanomaterial-mediated photodynamic therapeutic (NmPDT) complete destruction of solid tumors in mice. The modes of NmPDT and NmPTT can be controlled and switched from one to the other by changing the excitation wavelength. In the in vitro experiments, gold nanocages and nanorod-in-shell show larger percentage of cellular deaths originating from NmPDT along with the minor fraction of NmPTT effects. In contrast, nanoparticle-in-shell exhibits larger fraction of NmPTT-induced cellular deaths together with minor fraction of NmPDT-induced apoptosis. Fluorescence emission spectra and DPBF quenching studies confirm the generation of singlet O2 upon NIR photoirradiation. Both NmPDT and NmPTT effects were confirmed by measurements of reactive oxygen species (ROS) and subsequent sodium azide quenching, heat shock protein expression (HSP 70), singlet oxygen sensor green (SOSG) sensing, changes in mitochondria membrane potential and apoptosis in the cellular experiments. In vivo experiments further demonstrate that upon irradiation at 980 nm under ultra-low doses (∼150 mW/cm(2)), gold nanocages mostly exert NmPDT effect to effectively suppress the B16F0 melanoma tumor growth. The combination of NmPDT and NmPTT effects on destruction of solid tumors is far better than pure NmPTT effect by 808 nm irradiation and also doxorubicin. Overall, our study demonstrates that gold nanoshells can serve as excellent multi-functional theranostic agents (fluorescence imaging + NmPDT + NmPTT) upon single photon NIR light excitation under

Police Officers Can Safely and Effectively Administer Intranasal Naloxone.

PubMed

Fisher, Rian; O'Donnell, Daniel; Ray, Bradley; Rusyniak, Daniel

2016-01-01

Opioid overdose rates continue to rise at an alarming rate. One method used to combat this epidemic is the administration of naloxone by law enforcement. Many cities have implemented police naloxone administration programs, but there is a minimal amount of research examining this policy. The following study examines data over 18 months, after implementation of a police naloxone program in an urban setting. We describe the most common indications and outcomes of naloxone administration as well as examine the incidence of arrest, immediate detention, or voluntary transport to the hospital. In doing so, this study seeks to describe the clinical factors surrounding police use of naloxone, and the effects of police administration. All police officer administrations were queried from April 2014 through September 2015 (n = 126). For each incident we collected the indication, response, and disposition of the patient that was recorded on a "sick-injured civilian" report that officers were required to complete after administration of naloxone. All of the relevant information was abstracted from this report into an electronic data collection form that was then input into SPSS for analysis. The most common indication for administration was unconscious/unresponsive (n = 117; 92.9%) followed by slowed breathing (n = 72; 57.1%), appeared blue (n = 63; 50.0%) and not breathing (n = 41; 32.5%). After administration of naloxone the majority of patients regained consciousness (n = 82; 65.1%) followed by began to breath (n = 71; 56.3%). However, in 17.5% (n = 22) of the cases "Nothing" happened when naloxone was administered. The majority of patients were transported voluntarily to the hospital (n = 122; 96.8%). Lastly, there was only one report where the patient became combative. Our study shows that police officers trained in naloxone administration can correctly recognize symptoms of opioid overdose, and can appropriately administer naloxone without significant adverse effects or

Increase in Naloxone Prescriptions Dispensed in US Retail Pharmacies Since 2013.

PubMed

Jones, Christopher M; Lurie, Peter G; Compton, Wilson M

2016-04-01

Distribution of naloxone, traditionally through community-based naloxone programs, is a component of a comprehensive strategy to address the epidemic of prescription opioid and heroin overdose deaths in the United States. Recently, there has been increased focus on naloxone prescription in the outpatient setting, particularly through retail pharmacies, yet data on this practice are sparse. We found an 1170% increase in naloxone dispensing from US retail pharmacies between the fourth quarter of 2013 and the second quarter of 2015. These findings suggest that prescribing naloxone in the outpatient setting complements traditional community-based naloxone programs.

Correlation of ultra-low dose chest CT findings with physiologic measures of asbestosis.

PubMed

Manners, David; Wong, Patrick; Murray, Conor; Teh, Joelin; Kwok, Yi Jin; de Klerk, Nick; Alfonso, Helman; Franklin, Peter; Reid, Alison; Musk, A W Bill; Brims, Fraser J H

2017-08-01

The correlation between ultra low dose computed tomography (ULDCT)-detected parenchymal lung changes and pulmonary function abnormalities is not well described. This study aimed to determine the relationship between ULDCT-detected interstitial lung disease (ILD) and measures of pulmonary function in an asbestos-exposed population. Two thoracic radiologists independently categorised prone ULDCT scans from 143 participants for ILD appearances as absent (score 0), probable (1) or definite (2) without knowledge of asbestos exposure or lung function. Pulmonary function measures included spirometry and diffusing capacity to carbon monoxide (DLCO). Participants were 92% male with a median age of 73.0 years. CT dose index volume was between 0.6 and 1.8 mGy. Probable or definite ILD was reported in 63 (44.1%) participants. Inter-observer agreement was good (k = 0.613, p < 0.001). There was a statistically significant correlation between the ILD score and both forced expiratory volume in 1 second (FEV 1 ) and forced vital capacity (FVC) (r = -0.17, p = 0.04 and r = -0.20, p = 0.02). There was a strong correlation between ILD score and DLCO (r = -0.34, p < 0.0001). Changes consistent with ILD on ULDCT correlate well with corresponding reductions in gas transfer, similar to standard CT. In asbestos-exposed populations, ULDCT may be adequate to detect radiological changes consistent with asbestosis. • Interobserver agreement for the ILD score using prone ULDCT is good. • Prone ULDCT appearances of ILD correlate with changes in spirometric observations. • Prone ULDCT appearances of ILD correlate strongly with changes in gas transfer. • Prone ULDCT may provide sufficient radiological evidence to inform the diagnosis of asbestosis.

Therapeutic switch to buprenorphine/naloxone from buprenorphine alone: clinical experience in an Italian addiction centre.

PubMed

Montesano, Franco; Zaccone, Domenico; Battaglia, Egidio; Genco, Felice; Mellace, Vincenzo

2010-01-01

Pharmacological therapy has an important place in the management of opioid dependence. Methadone has been the mainstay of therapy but has a number of limitations. Buprenorphine monotherapy is another option, but misuse and diversion can have negative consequences. The opioid receptor antagonist, naloxone, has been added to buprenorphine to create a combination product with a reduced potential for misuse and diversion. This study evaluated the use of buprenorphine/naloxone for 24 weeks as a pharmacological management of opioid-dependent patients after therapeutic switch from buprenorphine alone. Patients (n = 43) received sublingual tablets of buprenorphine/naloxone. The buprenorphine dose was 2-24 mg (mean 16). Patients saw a physician, including an interview using a structured data sheet, and had counselling each week. Assessments were performed at week 2 (period 1), week 6 (period 2), week 16 (period 3) and week 24 (period 4). Laboratory immunoenzymatic testing was performed weekly to detect drugs in the urine. The management of withdrawal symptoms was rated as 'satisfactory' by 67% of patients during period 1 and 91% during period 4. The majority of patients was highly satisfied with therapy and considered that buprenorphine/naloxone provided good control of cravings. Two patients dropped out of therapy, but all others continued to receive buprenorphine throughout the study. Approximately 50% of patients stated that they disliked the sensory properties (taste, colour, odour and feel) of buprenorphine/naloxone. Adverse effects were as would be expected on the basis of the mechanism of action of buprenorphine (i.e. opioid-induced constipation) and for patients undergoing drug withdrawal. Only 2% of patients attempted the intravenous misuse of buprenorphine/naloxone, none of whom experienced any gratifying effects. Opioid-dependent patients maintained on buprenorphine monotherapy can be safely switched to a sublingual buprenorphine/naloxone tablet without any loss

A Subanalgesic Dose of Morphine Eliminates Nalbuphine Anti-analgesia in Postoperative Pain

PubMed Central

Gear, Robert W.; Gordon, Newton C.; Hossaini-Zadeh, Mehran; Lee, Janice S.; Miaskowski, Christine; Paul, Steven M.; Levine, Jon D.

2008-01-01

The agonist-antagonist kappa-opioid nalbuphine administered for postoperative pain produces greater analgesia in females than in males. In fact, males administered nalbuphine (5 mg) experience pain greater than those receiving placebo, suggesting the existence of an anti-analgesic effect. These sexually dimorphic effects on postoperative pain can be eliminated by co-administration of a fixed ratio of the prototypical opioid receptor antagonist naloxone with nalbuphine, implying a role for opioid receptors in the anti-analgesic as well as analgesic effects of nalbuphine. In the present study, we further evaluated the role of opioid receptors in the sex-specific effects on pain produced by nalbuphine by co-administering a dose of morphine low enough that it does not produce analgesia. Following extraction of bony impacted third molar teeth, nalbuphine (5 mg) was administered alone or in combination with either of two low doses of morphine (2 mg or 4 mg). Both doses of morphine reversed nalbuphine-induced anti-analgesia in males, but only the lower dose (2 mg) reached statistical significance. Neither dose affected nalbuphine-induced analgesia in females, and when administered alone in either males or females, morphine (2 mg) had no analgesic effect. Though not observed in females, the effect of morphine in males argues that, like naloxone, low dose morphine may act as an anti-analgesia opioid receptor antagonist. Perspective Previously we reported that the nalbuphine produces both analgesic and anti-analgesic effects, and that the opioid antagonist naloxone can enhance nalbuphine analgesia by selectively antagonizing the anti-analgesic effect. Here we show that morphine, given in a subanalgesic dose, reverses nalbuphine-induced anti-analgesia in males, perhaps by a similar mechanism. PMID:18201935

Safety and tolerability of the switch from buprenorphine to buprenorphine/naloxone in an Italian addiction treatment centre.

PubMed

Stimolo, Clementina; Favero, Valentina Del; Zecchinato, Giancarlo; Buson, Roberto; Cusin, Davide; Pellachin, Patrizia; Simonetto, Pamela

2010-01-01

Abuse and misuse of pharmacological therapies represent major challenges in the healthcare system, particularly in patients receiving long-acting opioid drugs for the treatment of heroin or opioid addiction. The partial mu-opioid receptor agonist buprenorphine is used to treat opioid dependence, but diversion and misuse may occur. The sublingual combination formulation of buprenorphine and the opioid receptor antagonist naloxone (buprenorphine/naxolone) is associated with a reduced abuse potential, and has been shown to have promising efficacy for the treatment of opioid dependence. This observational study assessed the safety and efficacy of sublingual buprenorphine/naloxone combination therapy in patients with opioid dependence after therapeutic switch from buprenorphine monotherapy. A total of 94 patients being treated with buprenorphine monotherapy (average dose 8 mg/day; mean duration of therapy 840 days) were switched to buprenorphine/naloxone combination therapy. Patients were asked to rate their level of satisfaction with buprenorphine/naloxone combination treatment with respect to the management of withdrawal symptoms, and urinary toxicology tests were carried out before and 14 days after switching to combination therapy. Within 3 months, 75/94 patients (80%) previously treated with buprenorphine monotherapy had switched to sublingual buprenorphine/naloxone combination treatment (average dose buprenorphine 8 mg). Among patients receiving combination treatment for >3 months, 83% were receiving medication either weekly or fortnightly, based on the results of toxicological testing. A reduction in positive urinary toxicology tests was observed in patients within two weeks after being switched to combination treatment (before switch: 28, 9 and 2 positive tests for heroin, cocaine and heroin + cocaine, respectively vs 11, 3 and 1 after switch) and a total of 64 patients of the 75 who switched to combination therapy (85%) were satisfied with the management of

Magnetic Resonance Relaxometry at Low and Ultra low Fields.

PubMed

Volegov, P; Flynn, M; Kraus, R; Magnelind, P; Matlashov, A; Nath, P; Owens, T; Sandin, H; Savukov, I; Schultz, L; Urbaitis, A; Zotev, V; Espy, M

2010-01-01

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are ubiquitous tools in science and medicine. NMR provides powerful probes of local and macromolecular chemical structure and dynamics. Recently it has become possible and practical to perform MR at very low fields (from 1 μT to 1 mT), the so-called ultra-low field (ULF) regime. Pulsed pre-polarizing fields greatly enhance the signal strength and allow flexibility in signal acquisition sequences. Improvements in SQUID sensor technology allow ultra-sensitive detection in a pulsed field environment.In this regime the proton Larmor frequencies (1 Hz - 100 kHz) of ULF MR overlap (on a time scale of 10 μs to 100 ms) with "slow" molecular dynamic processes such as diffusion, intra-molecular motion, chemical reactions, and biological processes such as protein folding, catalysis and ligand binding. The frequency dependence of relaxation at ultra-low fields may provide a probe for biomolecular dynamics on the millisecond timescale (protein folding and aggregation, conformational motions of enzymes, binding and structural fluctuations of coupled domains in allosteric mechanisms) relevant to host-pathogen interactions, biofuels, and biomediation. Also this resonance-enhanced coupling at ULF can greatly enhance contrast in medical applications of ULF-MRI resulting in better diagnostic techniques.We have developed a number of instruments and techniques to study relaxation vs. frequency at the ULF regime. Details of the techniques and results are presented.Ultra-low field methods are already being applied at LANL in brain imaging, and detection of liquid explosives at airports. However, the potential power of ultra-low field MR remains to be fully exploited.

Law enforcement attitudes towards naloxone following opioid overdose training.

PubMed

Purviance, Donna; Ray, Bradley; Tracy, Abigail; Southard, Erik

2017-01-01

Opioid intoxication and overdoses are life-threatening emergencies requiring rapid treatment. One response to this has been to train law enforcement to detect the signs of an opioid overdose and train them to administer naloxone to reverse the effects. Although not a new concept, few studies have attempted to examine this policy. At 4 different locations in Indiana, law enforcement personnel were trained to detect the signs of an opioid-related overdose and how to administer naloxone to reverse the effects of the overdose. Pre and post surveys were administered at each location (N = 97). To examine changes in attitudes following training, the authors included items from the Opioid Overdose Attitudes Scale (OOAS), which measures respondents' competency, concerns, and readiness to administer naloxone. Among the full sample, naloxone training resulted in significant increases in competency, concerns, and readiness. Examining changes in attitudes by each location revealed that the training had the greatest effect on competency to administer naloxone and in easing concerns that law enforcement personal might have in administering naloxone. This study adds to others in showing that law enforcement personnel are receptive to naloxone training and that the OOAS is able to capture these attitudes. This study advances this literature by examining pre-post changes across multiple locations. As the distribution of naloxone continues to proliferate, this study and the OOAS may be valuable towards the development of an evidence-based training model for law enforcement.

[Regulation of the neuronal functional state by ultra low doses of different biologically active substances. Nonspecific effect ].

PubMed

Terekhova, S F; Grechenko, T N

2003-01-01

The role of biologically active substances in ultra-low doses (10(-15)-10(-27) mol/l) is discussed from the different points of view. The most detailed analysis of neurobiological effects produced by these doses can be studied on the preparate of completely isolated molluscan neurones. In this case the possibility arises to control the first modifications of action at the electrophysiological characteristics of neuronal activity. These changes of electrical activity can be regarded as a reaction to biologically active substance. The following characteristics were controlled: the level of membrane resting potential (MP), the electroexcitable membrane and pacemaker mechanism, chemical sensitivity of somatic membrane loci to neurotransmitter acetylcholine (Ach). Several substances were used in these experiments: two kinds of synthetic antioxidant, GABA, ethanol, serotonine, DSIP (delta-sleep inducing peptide), antibiotic ruboxil, nootrop GVS-111. The isolated neurones were placed into the special chamber. All these substances (0.35 ml) were added single dosing into this chamber with living physiological solution in concentration 10(-15)-10(-27) mol/l. The results demonstrated that all substances had initiated the development of prolonged neurophysiological responses. The intensities of neuronal reactions didn't depend in contact period on the concentration and on the type of substance. It is suggested that these data reveal the existence of unknown modes of regulation of neuronal functional states and presence of hidden channel for information transfer and receiving. This different way of regulation is extremely important influence living organisms.

Evaluation of buprenorphine dosage adequacy in opioid receptor agonist substitution therapy for heroin dependence: first use of the BUprenorphine-naloxone Dosage Adequacy eVAluation (BUDAVA) questionnaire.

PubMed

D'Amore, Antonio; Romano, Filomena; Biancolillo, Vincenzo; Lauro, Guglielmo; Armenante, Ciro; Pizzirusso, Anna; Del Tufo, Salvatore; Ruoppolo, Ciro; Auriemma, Francesco; Cassese, Francesco; Oliva, Patrizia; Amato, Patrizia

2012-07-01

The dosing of opioid receptor agonist medications adequately and on an individual basis is crucial in the pharmacotherapy of opioid dependence. Clinical tools that are able to measure dose appropriateness are sorely needed. The recently developed and validated Opiate Dosage Adequacy Scale (ODAS) comprehensively evaluates the main outcomes relevant for methadone dose optimization, namely relapse, cross-tolerance, objective and subjective withdrawal symptoms, craving and overdose. Based on the ODAS, we developed a new assessment tool (BUprenorphine-naloxone Dosage Adequacy eVAluation [BUDAVA]) for evaluating dosage adequacy in patients in treatment with buprenorphine-naloxone. The main goal of this observational study was to explore whether the BUDAVA questionnaire could be used to assess buprenorphine-based, long-term substitution therapy for heroin addiction. The study included heroin-dependent patients who had been in treatment with buprenorphine-naloxone for at least 3 months. Patients (n = 196) were recruited from 11 drug abuse treatment centres in Italy. Dosage adequacy was assessed with the BUDAVA questionnaire. Patients classified as inadequately treated had their dosage modified. After 1 week, they were again administered the questionnaire to assess the adequacy of the new dosage. The buprenorphine-naloxone dosage was found to be inadequate in 61 of the 196 patients. In 13 patients, the treatment scored as inadequate only in the subjective withdrawal symptoms item of the questionnaire and therefore no dosage adjustment was made in the 2 weeks that have characterized this work. The remaining 48 inadequately treated patients had their dosage modified (42 dose increases and six dose decreases). After 1 week on the modified dosage, in 24 of these patients the new regimen was found by the assessment with the questionnaire to be adequate. These preliminary results suggest that the BUDAVA questionnaire may be useful for guiding buprenorphine-naloxone maintenance

A cluster-analytic profiling of heroin-dependent patients based on level, clinical adequacy, and patient-desired adjustment of buprenorphine dosage during buprenorphine-naloxone maintenance treatment in sixteen Spanish centers.

PubMed

Alcaraz, Saul; González-Saiz, Francisco; Trujols, Joan; Vergara-Moragues, Esperanza; Siñol, Núria; Pérez de Los Cobos, José

2018-06-01

Buprenorphine dosage is a crucial factor influencing outcomes of buprenorphine treatment for heroin use disorders. Therefore, the aim of the present study is to identify naturally occurring profiles of heroin-dependent patients regarding individualized management of buprenorphine dosage in clinical practice of buprenorphine-naloxone maintenance treatment. 316 patients receiving buprenorphine-naloxone maintenance treatment were surveyed at 16 Spanish centers during the stabilization phase of this treatment. Patients were grouped using cluster analysis based on three key indicators of buprenorphine dosage management: dose, adequacy according to physician, and adjustment according to patient. The clusters obtained were compared regarding different facets of patient clinical condition. Four clusters were identified and labeled as follows (buprenorphine average dose and percentage of participants in each cluster are given in brackets): "Clinically Adequate and Adjusted to Patient Desired Low Dosage" (2.60 mg/d, 37.05%); "Clinically Adequate and Adjusted to Patient Desired High Dosage" (10.71 mg/d, 29.18%); "Clinically Adequate and Patient Desired Reduction of Low Dosage" (3.38 mg/d, 20.0%); and "Clinically Inadequate and Adjusted to Patient Desired Moderate Dosage" (7.55 mg/d, 13.77%). Compared to patients from the other three clusters, participants in the latter cluster reported more frequent use of heroin and cocaine during last week, lower satisfaction with buprenorphine-naloxone as a medication, higher prevalence of buprenorphine-naloxone adverse effects and poorer psychological adjustment. Our results show notable differences between clusters of heroin-dependent patients regarding buprenorphine dosage management. We also identified a group of patients receiving clinically inadequate buprenorphine dosage, which was related to poorer clinical condition. Copyright © 2018 Elsevier B.V. All rights reserved.

Surveying the opinions of Pennsylvania Chiefs of Police toward officers carrying and administering naloxone.

PubMed

Smyser, Paul A; Lubin, Jeffrey S

2018-01-01

Recent legislation in Pennsylvania allows police officers to administer naloxone to individuals in an opioid overdose. Pressure has subsequently been placed on police departments to adopt naloxone programs. To survey Pennsylvania Chiefs of Police regarding potential obstacles to officer-administered naloxone, and their overall opinion toward such programs. A confidential survey was administered at the Annual Conference for the Pennsylvania Chiefs of Police Association and online over the organization's listserv. Respondents rated their level of concern toward four potential obstacles on a Likert scale from 1 to 5. A fifth question asked the degree to which they agree that the benefits of naloxone programs outweigh the risks. Of 180 attendees, 36 Chiefs of Police responded at the conference and 48 to the online survey. The potential agitation of revived victims was their largest reported concern, with 60% responding either a 4 or 5; this was followed by officers correctly identifying situations to use naloxone (42%), the cost of the medication (38%), and the additional administrative duties of the department (32%). Overall 60% responded they "Strongly Agree" or "Agree" the benefits of naloxone programs outweigh the risks, while 23% responded "Strongly Disagree" or "Disagree." No significant differences were seen when separating participants from rural and urban counties or from counties with high, medium, and low rates of overdose fatalities. The results suggest that although a significant subset shows concern for the above obstacles, the majority of Chiefs of Police believe that the benefits of equipping officers with naloxone outweigh the risks.

Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone

PubMed Central

Hutchinson, Mark R.; Zhang, Yingning; Brown, Kimberley; Coats, Benjamen D.; Shridhar, Mitesh; Sholar, Paige W.; Patel, Sonica J.; Crysdale, Nicole Y.; Harrison, Jacqueline A.; Maier, Steven F.; Rice, Kenner C.; Watkins, Linda R.

2008-01-01

Although activated spinal cord glia contribute importantly to neuropathic pain, how nerve injury activates glia remains controversial. It has recently been proposed, on the basis of genetic approaches, that toll-like receptor 4 (TLR4) may be a key receptor for initiating microglial activation following L5 spinal nerve injury. The present studies extend this idea pharmacologically by showing that TLR4 is key for maintaining neuropathic pain following sciatic nerve chronic constriction injury (CCI). Established neuropathic pain was reversed by intrathecally delivered TLR4 receptor antagonists derived from lipopolysaccharide. Additionally, (+)-naltrexone, (+)-naloxone, and (-))-naloxone, which we show here to be TLR4 antagonists in vitro on both stably transfected HEK293-TLR4 and microglial cell lines, suppressed neuropathic pain with complete reversal upon chronic infusion. Immunohistochemical analyses of spinal cords following chronic infusion revealed suppression of CCI-induced microglial activation by (+)-naloxone and (-))-naloxone, paralleling reversal of neuropathic pain. Together, these CCI data support the conclusion that neuron-to-glia signaling through TLR4 is important not only for initiating neuropathic pain, as suggested previously, but also for maintaining established neuropathic pain. Furthermore, these studies suggest that the novel TLR4 antagonists (+)-naloxone and (-))-naloxone can each fully reverse established neuropathic pain upon multi-day administration. This finding with (+)-naloxone is of potential clinical relevance. This is because (+)-naloxone is an antagonist that is inactive at the (-))-opioid selective receptors on neurons that produce analgesia. Thus, these data suggest that (+)-opioid antagonists such as (+)-naloxone may be useful clinically to suppress glial activation, yet (-))-opioid agonists suppress pain. PMID:18662331

Reversal effect of intra-central amygdala microinjection of L-arginine on place aversion induced by naloxone in morphine conditioned rats.

PubMed

Karimi, Sara; Karami, Manizheh; Sahraei, Hedayat; Rahimpour, Mahnaz

2011-01-01

Role of nitric oxide (NO) on expression of morphine conditioning using a solely classic task has been proposed previously. In this work, the involvement of NO on the expression of opioid-induced conditioning in the task paired with an injection of naloxone was investigated. Conditioning was established in adult male Wistar rats (weighing 200-250 g) using an unbiased procedure. Naloxone (0.05-0.4 mg/kg, i.p.), a selective antagonist of mu-opioid receptor, was administered once prior to morphine response testing. NO agents were administered directly into the central amygdala (CeA) prior to naloxone injection pre-testing. Morphine (2.5-10 mg/kg, s.c.) produced a significant dose-dependent place preference in experimental animals. When naloxone (0.05-0.4 mg/kg, i.p.) was injected before testing of morphine (5 mg/kg, s.c.) response, the antagonist induced a significant aversion. This response was reversed due to injection of L-arginine (0.3-3 microg/rat), intra-CeA prior to naloxone administration. However, pre-injection of L-NAME (intra-CeA), an inhibitor of NO production, blocked this effect. The finding may reflect that NO in the nucleus participates in morphine plus naloxone interaction.

Naloxone for Opioid Overdose and the Role of the Pharmacist.

PubMed

Toderika, Yuliana; Williams, Shalonda

2018-02-01

With the rise of the opioid epidemic in the United States and increased mortality as a result of opioid overdoses, there have been many national and statewide initiatives to combat this health crisis. Many states have expanded accessibility to naloxone, an opioid-reversal agent. Naloxone is safe, cost-effective, and nonaddictive. In addition, simple administration allows naloxone to be used by patients, family members, caregivers, and bystanders in the event of an opioid overdose. While a great emphasis has been placed on the prescribing practices of health care providers as it pertains to opioid therapy for chronic pain, a new focus has been placed on coprescribing naloxone with opioids for high-risk patients. Naloxone standing orders have allowed health care providers, including pharmacists, to prescribe, dispense, and/ or administer the medication in an attempt to save lives. In addition, pharmacists play a role in counseling and educating patients, family members, caregivers, and bystanders on the safe administration of naloxone in the event of an emergency.

Nebulized naloxone gently and effectively reverses methadone intoxication.

PubMed

Mycyk, Mark B; Szyszko, Amy L; Aks, Steven E

2003-02-01

A 46-year-old woman presented to the Emergency Department with lethargy and respiratory depression after ingesting methadone. Initial oxygen saturation of 61% on room air did not improve with supplemental oxygenation. As venous access was initially unobtainable, naloxone was administered by nebulizer. Within 5 min oxygen saturation was 100% and mental status was normal. The patient did not develop severe withdrawal symptoms. Naloxone hydrochloride has been administered by various routes to treat opioid toxicity. Our report describes the successful use of nebulized naloxone for methadone toxicity.

Rapid biosynthesis of silver nanoparticles using Crotalaria verrucosa leaves against the dengue vector Aedes aegypti: what happens around? An analysis of dragonfly predatory behaviour after exposure at ultra-low doses.

PubMed

Murugan, Kadarkarai; Sanoopa, C P; Madhiyazhagan, Pari; Dinesh, Devakumar; Subramaniam, Jayapal; Panneerselvam, Chellasamy; Roni, Mathath; Suresh, Udaiyan; Nicoletti, Marcello; Alarfaj, Abdullah A; Munusamy, Murugan A; Higuchi, Akon; Kumar, Suresh; Perumalsamy, Haribalan; Ahn, Young-Joon; Benelli, Giovanni

2016-01-01

Aedes aegypti is a primary vector of dengue, a mosquito-borne viral disease infecting 50-100 million people every year. Here, we biosynthesised mosquitocidal silver nanoparticles (AgNP) using the aqueous leaf extract of Crotalaria verrucosa. The green synthesis of AgNP was studied by UV-vis spectroscopy, SEM, EDX and FTIR. C. verrucosa-synthesised AgNPs were toxic against A. aegypti larvae and pupae. LC50 of AgNP ranged from 3.496 ppm (I instar larvae) to 17.700 ppm (pupae). Furthermore, we evaluated the predatory efficiency of dragonfly nymphs, Brachydiplax sobrina, against II and III instar larvae of A. aegypti in an aquatic environment contaminated with ultra-low doses of AgNP. Under standard laboratory conditions, predation after 24 h was 87.5% (II) and 54.7% (III). In an AgNP-contaminated environment, predation was 91 and 75.5%, respectively. Overall, C. verrucosa-synthesised AgNP could be employed at ultra-low doses to reduce larval population of dengue vectors enhancing predation rates of dragonfly nymphs.

Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide

PubMed Central

Mesnage, Robin; Renney, George; Séralini, Gilles-Eric; Ward, Malcolm; Antoniou, Michael N.

2017-01-01

The impairment of liver function by low environmentally relevant doses of glyphosate-based herbicides (GBH) is still a debatable and unresolved matter. Previously we have shown that rats administered for 2 years with 0.1 ppb (50 ng/L glyphosate equivalent dilution; 4 ng/kg body weight/day daily intake) of a Roundup GBH formulation showed signs of enhanced liver injury as indicated by anatomorphological, blood/urine biochemical changes and transcriptome profiling. Here we present a multiomic study combining metabolome and proteome liver analyses to obtain further insight into the Roundup-induced pathology. Proteins significantly disturbed (214 out of 1906 detected, q < 0.05) were involved in organonitrogen metabolism and fatty acid β-oxidation. Proteome disturbances reflected peroxisomal proliferation, steatosis and necrosis. The metabolome analysis (55 metabolites altered out of 673 detected, p < 0.05) confirmed lipotoxic conditions and oxidative stress by showing an activation of glutathione and ascorbate free radical scavenger systems. Additionally, we found metabolite alterations associated with hallmarks of hepatotoxicity such as γ-glutamyl dipeptides, acylcarnitines, and proline derivatives. Overall, metabolome and proteome disturbances showed a substantial overlap with biomarkers of non-alcoholic fatty liver disease and its progression to steatohepatosis and thus confirm liver functional dysfunction resulting from chronic ultra-low dose GBH exposure. PMID:28067231

Naloxone inhibits nod-like receptor protein 3 inflammasome.

PubMed

Lin, Han-Yu; Chang, Ya-Ying; Kao, Ming-Chang; Huang, Chun-Jen

2017-11-01

Naloxone, an opioid receptor antagonist, possesses potent anti-inflammation effects. We previously confirmed the effects of naloxone on inhibiting upregulation of inflammatory cytokine interleukin-1β (IL-1β). Production of mature form IL-1β is mediated by the nod-like receptor protein 3 (NLRP3) inflammasome, a multiprotein complex composed of NLRP3, and the adaptor protein apoptosis-associated speck-like protein contains a caspase recruitment domain (ASC). We elucidated whether naloxone could inhibit the activation of NLRP3 inflammasome. To induce IL-1β production and NLRP3 inflammasome activation, the human monocytic leukemia cell line THP-1 cells were first primed with lipopolysaccharide (LPS, 1 μg/mL) and then activated with adenosine triphosphate (ATP, 1 mM). For NLRP3 transcription, THP-1 cells were only treated with LPS priming. Enzyme-link immunosorbent assay data revealed that the concentration of IL-1β in THP-1 cells treated with LPS plus ATP was significantly higher than that in THP-1 cells treated with LPS plus ATP plus naloxone (0.1 μM) (P < 0.001). Real-time quantitative reverse transcription and polymerase chain reaction data also revealed that NLRP3 mRNA concentration in THP-1 cells treated with LPS was significantly higher than that in THP-1 cells treated with LPS plus naloxone (P = 0.001). ASC speck formation, that is, ASC assembles into a large protein complex, is an indicator for NLRP3 inflammasome activation. Our data revealed that the percentage of cells containing ASC specks in THP-1 cells treated with LPS plus ATP was also significantly higher than that in THP-1 cells treated with LPS plus ATP plus naloxone (P < 0.001). Naloxone inhibits NLRP3 inflammasome activation. Copyright © 2017 Elsevier Inc. All rights reserved.

Does adding low doses of oral naltrexone to morphine alter the subsequent opioid requirements and side effects in trauma patients?

PubMed

Farahmand, Shervin; Ahmadi, Omid; Dehpour, Ahmadreza; Khashayar, Patricia

2012-01-01

The present study aims to assess the influence of ultra-low doses of opioid antagonists on the analgesic properties of opioids and their side effects. In the present randomized, double-blind controlled trial, the influence of the combination of ultra-low-dose naltrexone and morphine on the total opioid requirement and the frequency of the subsequent side effects was compared with that of morphine alone (added with placebo) in patients with trauma in the upper or lower extremities. Although the morphine and naltrexone group required 0.04 mg more opioids during the study period, there was no significant difference between the opioid requirements of the 2 groups. Nausea was less frequently reported in patients receiving morphine and naltrexone. The combination of ultra-low-dose naltrexone and morphine in extremity trauma does not affect the opioid requirements; it, however, lowers the risk of nausea. Copyright © 2012 Elsevier Inc. All rights reserved.

Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria.

PubMed

McDonald, Rebecca; Strang, John

2016-07-01

Fatal outcome of opioid overdose, once detected, is preventable through timely administration of the antidote naloxone. Take-home naloxone provision directly to opioid users for emergency use has been implemented recently in more than 15 countries worldwide, albeit mainly as pilot schemes and without formal evaluation. This systematic review assesses the effectiveness of take-home naloxone, with two specific aims: (1) to study the impact of take-home naloxone distribution on overdose-related mortality; and (2) to assess the safety of take-home naloxone in terms of adverse events. PubMed, MEDLINE and PsychINFO were searched for English-language peer-reviewed publications (randomized or observational trials) using the Boolean search query: (opioid OR opiate) AND overdose AND prevention. Evidence was evaluated using the nine Bradford Hill criteria for causation, devised to assess a potential causal relationship between public health interventions and clinical outcomes when only observational data are available. A total of 1397 records (1164 after removal of duplicates) were retrieved, with 22 observational studies meeting eligibility criteria. Due to variability in size and quality of the included studies, meta-analysis was dismissed in favour of narrative synthesis. From eligible studies, we found take-home naloxone met all nine Bradford Hill criteria. The additional five World Health Organization criteria were all either met partially (two) or fully (three). Even with take-home naloxone administration, fatal outcome was reported in one in 123 overdose cases (0.8%; 95% confidence interval = 0.4, 1.2). Take-home naloxone programmes are found to reduce overdose mortality among programme participants and in the community and have a low rate of adverse events. © 2016 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

MK-801, but not naloxone, attenuates high-dose dextromethorphan-induced convulsive behavior: Possible involvement of the GluN2B receptor.

PubMed

Tran, Hai-Quyen; Chung, Yoon Hee; Shin, Eun-Joo; Tran, The-Vinh; Jeong, Ji Hoon; Jang, Choon-Gon; Nah, Seung-Yeol; Yamada, Kiyofumi; Nabeshima, Toshitaka; Kim, Hyoung-Chun

2017-11-01

Dextromethorphan (DM) is a dextrorotatory isomer of levorphanol, a typical morphine-like opioid. When administered at supra-antitussive doses, DM produces psychotoxic and neurotoxic effects in humans. Although DM abuse has been well-documented, few studies have examined the effects of high-dose DM. The present study aimed to explore the effects of a single high dose of DM on mortality and seizure occurrence. After intraperitoneal administration with a high dose of DM (80mg/kg), Sprague-Dawley rats showed increased seizure occurrence and intensity. Hippocampal expression levels of N-methyl-d-aspartate (NMDA) receptor subunits (GluN1dose DM, whereas an opioid antagonist, naloxone, did not affect DM-induced neurotoxicity. Moreover, pretreatment with a highly specific GluN2B subunit inhibitor, traxoprodil, was selectively effective in preventing DM-induced c-Fos expression and apoptotic changes. These results suggest that high-dose DM produces convulsive behaviors by activating GluN2B/NMDA signaling that leads to pro-apoptotic changes. Copyright © 2017. Published by Elsevier Inc.

Accuracy of computer-aided design models of the jaws produced using ultra-low MDCT doses and ASIR and MBIR.

PubMed

Al-Ekrish, Asma'a A; Alfadda, Sara A; Ameen, Wadea; Hörmann, Romed; Puelacher, Wolfgang; Widmann, Gerlig

2018-06-16

To compare the surface of computer-aided design (CAD) models of the maxilla produced using ultra-low MDCT doses combined with filtered backprojection (FBP), adaptive statistical iterative reconstruction (ASIR) and model-based iterative reconstruction (MBIR) reconstruction techniques with that produced from a standard dose/FBP protocol. A cadaveric completely edentulous maxilla was imaged using a standard dose protocol (CTDIvol: 29.4 mGy) and FBP, in addition to 5 low dose test protocols (LD1-5) (CTDIvol: 4.19, 2.64, 0.99, 0.53, and 0.29 mGy) reconstructed with FBP, ASIR 50, ASIR 100, and MBIR. A CAD model from each test protocol was superimposed onto the reference model using the 'Best Fit Alignment' function. Differences between the test and reference models were analyzed as maximum and mean deviations, and root-mean-square of the deviations, and color-coded models were obtained which demonstrated the location, magnitude and direction of the deviations. Based upon the magnitude, size, and distribution of areas of deviations, CAD models from the following protocols were comparable to the reference model: FBP/LD1; ASIR 50/LD1 and LD2; ASIR 100/LD1, LD2, and LD3; MBIR/LD1. The following protocols demonstrated deviations mostly between 1-2 mm or under 1 mm but over large areas, and so their effect on surgical guide accuracy is questionable: FBP/LD2; MBIR/LD2, LD3, LD4, and LD5. The following protocols demonstrated large deviations over large areas and therefore were not comparable to the reference model: FBP/LD3, LD4, and LD5; ASIR 50/LD3, LD4, and LD5; ASIR 100/LD4, and LD5. When MDCT is used for CAD models of the jaws, dose reductions of 86% may be possible with FBP, 91% with ASIR 50, and 97% with ASIR 100. Analysis of the stability and accuracy of CAD/CAM surgical guides as directly related to the jaws is needed to confirm the results.

Implementing an overdose education and naloxone distribution program in a health system.

PubMed

Devries, Jennifer; Rafie, Sally; Polston, Gregory

To design and implement a health system-wide program increasing provision of take-home naloxone in patients at risk for opioid overdose, with the downstream aim of reducing fatalities. The program includes health care professional education and guidelines, development, and dissemination of patient education materials, electronic health record changes to promote naloxone prescriptions, and availability of naloxone in pharmacies. Academic health system, San Diego, California. University of California, San Diego Health (UCSDH), offers both inpatient and outpatient primary care and specialty services with 563 beds spanning 2 hospitals and 6 pharmacies. UCSDH is part of the University of California health system, and it serves as the county's safety net hospital. In January 2016, a multisite academic health system initiated a system-wide overdose education and naloxone distribution program to prevent opioid overdose and opioid overdose-related deaths. An interdisciplinary, interdepartmental team came together to develop and implement the program. To strengthen institutional support, naloxone prescribing guidelines were developed and approved for the health system. Education on naloxone for physicians, pharmacists, and nurses was provided through departmental trainings, bulletins, and e-mail notifications. Alerts in the electronic health record and preset naloxone orders facilitated co-prescribing of naloxone with opioid prescriptions. Electronic health record reports captured naloxone prescriptions ordered. Summary reports on the electronic health record measured naloxone reminder alerts and response rates. Since the start of the program, the health system has trained 252 physicians, pharmacists, and nurses in overdose education and take-home naloxone. There has been an increase in the number of prescriptions for naloxone from a baseline of 4.5 per month to an average of 46 per month during the 3 months following full implementation of the program including

Application of human factors engineering (HFE) to the design of a naloxone auto-injector for the treatment of opioid emergencies.

PubMed

Raffa, Robert B; Taylor, Robert; Pergolizzi, Joseph V; Nalamachu, Srinivas; Edwards, Eric S; Edwards, Evan T

2017-02-01

The increased use of opioids for chronic treatment of pain and the resulting epidemic of opioid overdoses have created a major public health challenge. Parenteral naloxone has been used since the 1970's to treat opioid overdose. Recently, a novel naloxone auto-injector device (EVZIO, kaleo, Inc., Richmond, VA) was approved by the Food and Drug Administration. In this article, we review the Human Factors Engineering (HFE) process used in the development and testing of this novel naloxone auto-injector currently used in nonmedical settings for the emergency treatment of known or suspected opioid overdose. HFE methods were employed throughout the product development process for the naloxone auto-injector including formative and summative studies in order to optimize the auto-injector's user interface, mitigate use-related hazards and increase reliability during an opioid emergency use scenario. HFE was also used to optimize the product's design and user interface in order to reduce or prevent user confusion and misuse. The naloxone auto-injector went through a rigorous HFE process that included perceptual, cognitive, and physical action analysis; formative usability evaluations; use error analysis and summative design validation studies. Applying HFE resulted in the development of a product that is safe, fast, easy and predictably reliable to deliver a potentially life-saving dose of naloxone during an opioid overdose emergency. The naloxone auto-injector may be considered as a universal precaution option for at-risk patients prescribed opioids or those who are at increased risk for an opioid overdose emergency.

Overdose Education and Naloxone Rescue Kits for Family Members of Opioid Users: Characteristics, Motivations and Naloxone Use

PubMed Central

Bagley, Sarah M; Peterson, Joanne; Cheng, Debbie M.; Jose, Charles; Quinn, Emily; O’Connor, Patrick G.; Walley, Alexander Y.

2016-01-01

Background In response to the overdose epidemic, a network of support groups for family members in Massachusetts has been providing overdose education and naloxone rescue kits (OEN). The aims of this study were to describe the characteristics, motivations and benefits of family members who receive OEN and to describe the frequency of naloxone used during an overdose rescue. Methods This cross-sectional, multisite study surveyed attendees of community support groups for family members of opioid users where OEN training was offered using a 42 item self-administered survey that included demographics, relationship to opioid user, experience with overdose, motivations to receive OEN, and naloxone rescue kit use. Results Of 126 attendees who completed surveys at 8 sites, most attendees were white (95%), female (78%), married or partnered (74%), parents of an opioid user (85%), and provide financial support for opioid user (52%). The OEN trainees (79%) were more likely than attendees not trained (21%) to be parents of an opioid user (91% v 65%, p <0.05), provide financial support to an opioid user (58% v 30%, p <0.05), and to have witnessed an overdose (35% v 12%, p=0.07). The major motivations to receive training were: wanting a kit in their home (72%), education provided at the meeting (60%) and hearing about benefits from others (57%). Sixteen parents reported witnessing their child overdose and five attendees had used naloxone successfully during an overdose rescue. Conclusions Support groups for families of people who use opioids are promising venues to conduct overdose prevention trainings, because attendees are motivated to receive training and will use naloxone to rescue people when witnessing an overdose. Further study is warranted to understand how to optimize this approach to overdose prevention in the community setting. PMID:25564892

What is known about community pharmacy supply of naloxone? A scoping review.

PubMed

Nielsen, Suzanne; Van Hout, Marie Claire

2016-06-01

There is growing evidence that expanded supply of take-home naloxone to prevent opioid overdose deaths is needed. Potential routes for expansion of naloxone provision include through community pharmacies. The aim of this scoping review is to establish what is known about community pharmacy supply of naloxone, in light of unique challenges and opportunities present in pharmacy settings. A scoping review methodology was employed using the six stage iterative process advocated by Arksey and O'Malley (2005) and Levac et al. (2010). Searches used key words and terms such as 'naloxone'; 'overdose prevention/drug overdose/opiate overdose'; 'community/retail pharmacy'; 'pharmacist/pharmacy/community pharmacy/pharmaceutical services'; 'professional practice/role'; 'community care'; attitude of health personnel'; 'training/supply/cost'. Appropriate search terms were selected for each database. After initial exploratory searches, comprehensive searches were conducted with Cochrane Database of Systematic Reviews, Medline, Medline in Process, Embase, PsycINFO and CINAHL. Eligibility criteria centered on whether studies broadly described supply of naloxone in community pharmacy or had content relating to community pharmacy supply. The search identified 95 articles, of which 16 were related to pharmacy supply of naloxone. Five themes were presented after initial review of the data and consultation with the project Expert Group, and are; 'Pharmacists Perceptions of Naloxone: Facilitators and Barriers', 'Patient Populations: Identification and Recruitment', 'Supply Systems and Cost', 'Legal Issues', and 'Training of Pharmacists and Community Pharmacy Naloxone Recipients'. Findings from this scoping review suggest that community pharmacy based supply of take-home naloxone warrants the community pharmacy based route for distribution of take home naloxone provision warrants further consideration and development. Existing strengths include a range of established supply models, and

Brain MR imaging at ultra-low radiofrequency power.

PubMed

Sarkar, Subhendra N; Alsop, David C; Madhuranthakam, Ananth J; Busse, Reed F; Robson, Philip M; Rofsky, Neil M; Hackney, David B

2011-05-01

To explore the lower limits for radiofrequency (RF) power-induced specific absorption rate (SAR) achievable at 1.5 T for brain magnetic resonance (MR) imaging without loss of tissue signal or contrast present in high-SAR clinical imaging in order to create a potentially viable MR method at ultra-low RF power to image tissues containing implanted devices. An institutional review board-approved HIPAA-compliant prospective MR study design was used, with written informed consent from all subjects prior to MR sessions. Seven healthy subjects were imaged prospectively at 1.5 T with ultra-low-SAR optimized three-dimensional (3D) fast spin-echo (FSE) and fluid-attenuated inversion-recovery (FLAIR) T2-weighted sequences and an ultra-low-SAR 3D spoiled gradient-recalled acquisition in the steady state T1-weighted sequence. Corresponding high-SAR two-dimensional (2D) clinical sequences were also performed. In addition to qualitative comparisons, absolute signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) for multicoil, parallel imaging acquisitions were generated by using a Monte Carlo method for quantitative comparison between ultra-low-SAR and high-SAR results. There were minor to moderate differences in the absolute tissue SNR and CNR values and in qualitative appearance of brain images obtained by using ultra-low-SAR and high-SAR techniques. High-SAR 2D T2-weighted imaging produced slightly higher SNR, while ultra-low-SAR 3D technique not only produced higher SNR for T1-weighted and FLAIR images but also higher CNRs for all three sequences for most of the brain tissues. The 3D techniques adopted here led to a decrease in the absorbed RF power by two orders of magnitude at 1.5 T, and still the image quality was preserved within clinically acceptable imaging times. RSNA, 2011

Low-cost ultra-thin broadband terahertz beam-splitter.

PubMed

Ung, Benjamin S-Y; Fumeaux, Christophe; Lin, Hungyen; Fischer, Bernd M; Ng, Brian W-H; Abbott, Derek

2012-02-27

A low-cost terahertz beam-splitter is fabricated using ultra-thin LDPE plastic sheeting coated with a conducting silver layer. The beam splitting ratio is determined as a function of the thickness of the silver layer--thus any required splitting ratio can be printed on demand with a suitable rapid prototyping technology. The low-cost aspect is a consequence of the fact that ultra-thin LDPE sheeting is readily obtainable, known more commonly as domestic plastic wrap or cling wrap. The proposed beam-splitter has numerous advantages over float zone silicon wafers commonly used within the terahertz frequency range. These advantages include low-cost, ease of handling, ultra-thin thickness, and any required beam splitting ratio can be readily fabricated. Furthermore, as the beam-splitter is ultra-thin, it presents low loss and does not suffer from Fabry-Pérot effects. Measurements performed on manufactured prototypes with different splitting ratios demonstrate a good agreement with our theoretical model in both P and S polarizations, exhibiting nearly frequency-independent splitting ratios in the terahertz frequency range.

Extreme sensitivity of gene expression in human SH-SY5Y neurocytes to ultra-low doses of Gelsemium sempervirens

PubMed Central

2014-01-01

Background Gelsemium sempervirens L. (Gelsemium s.) is a traditional medicinal plant, employed as an anxiolytic at ultra-low doses and animal models recently confirmed this activity. However the mechanisms by which it might operate on the nervous system are largely unknown. This work investigates the gene expression of a human neurocyte cell line treated with increasing dilutions of Gelsemium s. extract. Methods Starting from the crude extract, six 100 × (centesimal, c) dilutions of Gelsemium s. (2c, 3c, 4c, 5c, 9c and 30c) were prepared according to the French homeopathic pharmacopoeia. Human SH-SY5Y neuroblastoma cells were exposed for 24 h to test dilutions, and their transcriptome compared by microarray to that of cells treated with control vehicle solutions. Results Exposure to the Gelsemium s. 2c dilution (the highest dose employed, corresponding to a gelsemine concentration of 6.5 × 10-9 M) significantly changed the expression of 56 genes, of which 49 were down-regulated and 7 were overexpressed. Several of the down-regulated genes belonged to G-protein coupled receptor signaling pathways, calcium homeostasis, inflammatory response and neuropeptide receptors. Fisher exact test, applied to the group of 49 genes down-regulated by Gelsemium s. 2c, showed that the direction of effects was significantly maintained across the treatment with high homeopathic dilutions, even though the size of the differences was distributed in a small range. Conclusions The study shows that Gelsemium s., a medicinal plant used in traditional remedies and homeopathy, modulates a series of genes involved in neuronal function. A small, but statistically significant, response was detected even to very low doses/high dilutions (up to 30c), indicating that the human neurocyte genome is extremely sensitive to this regulation. PMID:24642002

Low Doses of Allyphenyline and Cyclomethyline, Effective against Morphine Dependence, Elicit an Antidepressant-like Effect

PubMed Central

2012-01-01

This study demonstrated that cyclomethyline (2) and the corresponding enantiomers (R)-(−)-2 and (S)-(+)-2, displaying α2C-adrenoreceptor (AR) agonism/α2A-AR antagonism, similarly to allyphenyline (1) and its enantiomers, significantly decreased the naloxone-precipitated withdrawal symptoms in mice at very low doses. It also highlighted that such positive effects on morphine dependence can even be improved by additional serotoninergic 5-HT1A receptor (5-HT1A-R) activation. Indeed, 1 or the single (S)-(+)-1, 2, or both its enantiomers, all behaving as α2C-AR agonists/α2A-AR antagonists/5-HT1A-R agonists, alone and at the same low dose, improved morphine withdrawal syndrome and exerted a potent antidepressant-like effect. Therefore, considering the elevated comorbidity between opiate abuse and depressed mood and the benefit of these multifunctional compounds to both disorders, it is possible that they prove more efficacious and less toxic than a cocktail of drugs in managing opioid addiction. PMID:24900506

Opioid Overdose Prevention Programs Providing Naloxone to Laypersons - United States, 2014.

PubMed

Wheeler, Eliza; Jones, T Stephen; Gilbert, Michael K; Davidson, Peter J

2015-06-19

Drug overdose deaths in the United States have more than doubled since 1999. During 2013, 43,982 drug overdose deaths (unintentional, intentional [suicide or homicide], or undetermined intent) were reported. Among these, 16,235 (37%) were associated with prescription opioid analgesics (e.g., oxycodone and hydrocodone) and 8,257 (19%) with heroin. For many years, community-based programs have offered opioid overdose prevention services to laypersons who might witness an overdose, including persons who use drugs, their families and friends, and service providers. Since 1996, an increasing number of programs provide laypersons with training and kits containing the opioid antagonist naloxone hydrochloride (naloxone) to reverse the potentially fatal respiratory depression caused by heroin and other opioids. In July 2014, the Harm Reduction Coalition (HRC), a national advocacy and capacity-building organization, surveyed 140 managers of organizations in the United States known to provide naloxone kits to laypersons. Managers at 136 organizations completed the survey, reporting on the amount of naloxone distributed, overdose reversals by bystanders, and other program data for 644 sites that were providing naloxone kits to laypersons as of June 2014. From 1996 through June 2014, surveyed organizations provided naloxone kits to 152,283 laypersons and received reports of 26,463 overdose reversals. Providing opioid overdose training and naloxone kits to laypersons who might witness an opioid overdose can help reduce opioid overdose mortality.

Engaging Law Enforcement in Overdose Reversal Initiatives: Authorization and Liability for Naloxone Administration

PubMed Central

Carr, Derek; Southwell, Jessica K.; Beletsky, Leo

2015-01-01

Opioid overdose is reversible through the timely administration of naloxone, which has been used by emergency medical services for decades. Law enforcement officers (LEOs) are often the first emergency responders to arrive at an overdose, but they are not typically equipped with naloxone. This is rapidly changing; more than 220 law enforcement agencies in 24 states now carry naloxone. However, rollout in some departments has been hampered by concerns regarding officer and agency liability. We systematically examined the legal risk associated with LEO naloxone administration. LEOs can be authorized to administer naloxone through a variety of mechanisms, and liability risks related to naloxone administration are similar to or lower than those of other activities in which LEOs commonly engage. PMID:26066921

Combination Treatment of Glioblastoma by Low-Dose Radiation and Genistein.

PubMed

Atefeh, Zamanian; Vahid, Changizi; Hasan, Nedaie; Saeed, Amanpour; Mahnaz, Haddadi

2016-01-01

Gioblastoma multiforme as a chemoresistant and radioresistant malignant cell line needs to novel strategies to treatment. Low-dose hyper-radiosensitivity (LDHRS) seems to be an effective phenomenon to irradiation that can save normal brain fibroblasts. Genistein which is a soy isoflavone can be cytotoxic in some tumor cell lines. So we determined to study the effect of combining these two treatment modalities. After 30 hours incubation with Genistein in different concentrations on U87MG cell line, proliferation and clonogenicity were conducted by both clonogenic and MTT assays. A conventional 2Gy radiation dose was compared with 10 doses of 0.2Gy gamma irradiation with 3 minutes and 1 hour intervals. Finally, concurrent effect of these modalities was assessed. Based on acquired cell doubling time (30 hours), one doubling time treatment by Genistein could decrease clonogenicity. U87MG cell line exhibited HRS at low dose irradiations. 2Gy irradiation was more effective than ultra-fractionation methods in comparison with control group. All groups with 50uM concentration of Genistein showed decrease in the survival. This decrease compared with control group, in 10x0.2Gy with 3 minutes intervals plus 50uM Genistein was significant and for groups with the same dose of Genistein but along with continuous 2Gy was more significant. In one day treatment regimen, 10x0.2Gy ultra-fractionation with 3 minutes and 1 hour intervals seems to be less effective than conventional 2Gy irradiation, however adding 50uM Genistein can decrease survival more. Although 2Gy conventional dose plus 50uM Genistein was the most effective regimen. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Low dose transdermal oestradiol suppresses gonadotrophin secretion in breast-feeding women.

PubMed

Illingworth, P J; Seaton, J E; McKinlay, C; Reid-Thomas, V; McNeilly, A S

1995-07-01

The object of the study was to investigate the effect on gonadotrophin secretion of a small increase in oestradiol concentration. A total of 13 fully breast-feeding women (12 weeks post-partum) underwent serial blood sampling at 10 min intervals for 12 h on 2 different days; day 1 untreated and day 5 after 3 days of treatment with transcutaneous oestradiol (100 micrograms/day). On both days bolus gonadotrophin-releasing hormone (GnRH; 10 micrograms i.v.) was given after a 10 h baseline period. In six of the subjects, a naloxone infusion was administered during the second study day. Application of transdermal oestradiol raised the oestradiol concentration within the normal follicular phase range. The mean luteinizing hormone (LH) concentration on day 5 was found to be significantly lower than that on day 1 (P < 0.05). The LH response to GnRH was, however, significantly higher on day 5 than day 1 (P < 0.001). The mean follicle stimulating hormone (FSH) concentration on day 5 was also significantly lower than that on day 1 (P < 0.01), while the peak concentration after GnRH was unchanged. When the opioid antagonist naloxone was infused after oestradiol treatment, the subjects with low pre-study oestradiol concentrations exhibited no effect on LH concentration, while in the subjects with higher oestradiol concentrations the LH concentration was increased. It was concluded that the administration of small doses of oestradiol caused a significant fall in gonadotrophin concentration in breast-feeding women.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of Naloxone by Emergency Medical Services During Opioid Drug Overdose Resuscitation Efforts

PubMed Central

Sumner, Steven Allan; Mercado-Crespo, Melissa C.; Spelke, M. Bridget; Paulozzi, Leonard; Sugerman, David E.; Hillis, Susan D.; Stanley, Christina

2015-01-01

Naloxone administration is an important component of resuscitation attempts by emergency medical services (EMS) for opioid drug overdoses. However, EMS providers must first recognize the possibility of opioid overdose in clinical encounters. As part of a public health response to an outbreak of opioid overdoses in Rhode Island, we examined missed opportunities for naloxone administration and factors potentially influencing EMS providers’ decision to administer naloxone. We reviewed medical examiner files on all individuals who died of an opioid-related drug overdose in Rhode Island from January 1, 2012 through March 31, 2014, underwent attempted resuscitation by EMS providers, and had records available to assess for naloxone administration. We evaluated whether these individuals received naloxone as part of their resuscitation efforts and compared patient and scene characteristics of those who received naloxone to those who did not receive naloxone via chi-square, t-test, and logistic regression analyses. One hundred and twenty-four individuals who underwent attempted EMS resuscitation died due to opioid overdose. Naloxone was administered during EMS resuscitation attempts in 82 (66.1%) of cases. Females were nearly three-fold as likely not to receive naloxone as males (OR 2.9; 95% CI 1.2–7.0; p-value 0.02). Additionally, patients without signs of potential drug abuse also had a greater than three-fold odds of not receiving nalox-one (OR 3.3; 95% CI 1.2–9.2; p-value 0.02). Older individuals, particularly those over age 50, were more likely not to receive naloxone than victims younger than age 30 (OR 4.8; 95% CI 1.3–17.4; p-value 0.02). Women, older individuals, and those patients without clear signs of illicit drug abuse, were less likely to receive naloxone in EMS resuscitation attempts. Heightened clinical suspicion for opioid overdose is important given the recent increase in overdoses among patients due to prescription opioids. PMID:26383533

Naloxone attenuates the conditioned place preference induced by wheel running in rats.

PubMed

Lett, B T; Grant, V L; Koh, M T

2001-02-01

Pairings, during which an episode of wheel running is followed by confinement in a distinctive place, produce conditioned place preference (CPP) in rats. This finding indicates that wheel running has a rewarding effect that outlasts the activity itself. In two similar experiments, we tested the hypothesis that this rewarding effect of wheel running is mediated by endogenous opioids. During a paired trial, the rats in the naloxone group were first allowed to wheel run for 2 h, then injected with naloxone (0.5 or 0.1 mg/kg in Experiments 1 and 2, respectively), and 10 min later placed in a distinctive chamber. During an unpaired trial, these rats were confined in an adjoining chamber without wheel running. Naloxone was injected before placement in both chambers, so that if naloxone-induced conditioned place aversion occurred, it would have counteracting effects on performance during the preference test. The rats in the saline group were similarly treated, except that saline was injected instead of naloxone. CPP occurred in the saline group, but not in the naloxone group. Thus, naloxone attenuated the CPP induced by wheel running. This finding supports the hypothesis that the rewarding effect of wheel running is mediated by endogenous opioids.

Effects of Iterative Reconstruction Algorithms on Computer-assisted Detection (CAD) Software for Lung Nodules in Ultra-low-dose CT for Lung Cancer Screening.

PubMed

Nomura, Yukihiro; Higaki, Toru; Fujita, Masayo; Miki, Soichiro; Awaya, Yoshikazu; Nakanishi, Toshio; Yoshikawa, Takeharu; Hayashi, Naoto; Awai, Kazuo

2017-02-01

This study aimed to evaluate the effects of iterative reconstruction (IR) algorithms on computer-assisted detection (CAD) software for lung nodules in ultra-low-dose computed tomography (ULD-CT) for lung cancer screening. We selected 85 subjects who underwent both a low-dose CT (LD-CT) scan and an additional ULD-CT scan in our lung cancer screening program for high-risk populations. The LD-CT scans were reconstructed with filtered back projection (FBP; LD-FBP). The ULD-CT scans were reconstructed with FBP (ULD-FBP), adaptive iterative dose reduction 3D (AIDR 3D; ULD-AIDR 3D), and forward projected model-based IR solution (FIRST; ULD-FIRST). CAD software for lung nodules was applied to each image dataset, and the performance of the CAD software was compared among the different IR algorithms. The mean volume CT dose indexes were 3.02 mGy (LD-CT) and 0.30 mGy (ULD-CT). For overall nodules, the sensitivities of CAD software at 3.0 false positives per case were 78.7% (LD-FBP), 9.3% (ULD-FBP), 69.4% (ULD-AIDR 3D), and 77.8% (ULD-FIRST). Statistical analysis showed that the sensitivities of ULD-AIDR 3D and ULD-FIRST were significantly higher than that of ULD-FBP (P < .001). The performance of CAD software in ULD-CT was improved by using IR algorithms. In particular, the performance of CAD in ULD-FIRST was almost equivalent to that in LD-FBP. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Expanding access to naloxone for family members: The Massachusetts experience.

PubMed

Bagley, Sarah M; Forman, Leah S; Ruiz, Sarah; Cranston, Kevin; Walley, Alexander Y

2018-05-01

The Massachusetts Department of Public Health Overdose Education and Naloxone Distribution Program provides overdose education and naloxone rescue kits to people at risk for overdose and bystanders, including family members. Using Massachusetts Department of Public Health data, the aims are to: (i) describe characteristics of family members who receive naloxone; (ii) identify where family members obtain naloxone; and (iii) describe characteristics of rescues by family members. We conducted a retrospective review using program enrollee information collected on a standardised form between 2008 and 2015. We calculated descriptive statistics, including demographics, current substance use, enrolment location, history of witnessed overdoses and rescue attempt characteristics. We conducted a stratified analysis comparing family members who used drugs with those who did not. Family members were 27% of total program enrollees (n = 10 883/40 801). Family members who reported substance use (n = 4679) were 35.6 years (mean), 50.6% female, 76.3% non-Hispanic white, 75.6% had witnessed an overdose, and they obtained naloxone most frequently at HIV prevention programs. Family members who did not report substance use (n = 6148) were 49.2 years (mean), 73.8% female, 87.9% non-Hispanic white, 35.3% had witnessed an overdose, and they obtained naloxone most frequently at community meetings. Family members were responsible for 20% (n = 860/4373) of the total rescue attempts. The Massachusetts experience demonstrates that family members can be active participants in responding to the overdose epidemic by rescuing family members and others. Targeted intervention strategies for families should be included in efforts to expand overdose education and naloxone in Massachusetts. © 2017 Australasian Professional Society on Alcohol and other Drugs.

An ultra-low-power filtering technique for biomedical applications.

PubMed

Zhang, Tan-Tan; Mak, Pui-In; Vai, Mang-I; Mak, Peng-Un; Wan, Feng; Martins, R P

2011-01-01

This paper describes an ultra-low-power filtering technique for biomedical applications designated as T-wave sensing in heart-activities detection systems. The topology is based on a source-follower-based Biquad operating in the sub-threshold region. With the intrinsic advantages of simplicity and high linearity of the source-follower, ultra-low-cutoff filtering can be achieved, simultaneously with ultra low power and good linearity. An 8(th)-order 2.4-Hz lowpass filter design example optimized in a 0.35-μm CMOS process was designed achieving over 85-dB dynamic range, 74-dB stopband attenuation and consuming only 0.36 nW at a 3-V supply.

Pharmacists' role in opioid overdose: Kentucky pharmacists' willingness to participate in naloxone dispensing.

PubMed

Freeman, Patricia R; Goodin, Amie; Troske, SuZanne; Strahl, Audra; Fallin, Amanda; Green, Traci C

To assess pharmacists' willingness to initiate the dispensing of naloxone. As of 2015, Kentucky law permits certified pharmacists to dispense naloxone under a physician-approved protocol. Electronic survey (e-mail) gauging perception of pharmacists' role in opioid overdose and attitudes toward, and barriers to, naloxone dispensing. All Kentucky pharmacists with active licenses in 2015. Ordinal logistic regression was used to estimate the impact of pharmacist characteristics and attitudes on willingness to initiate naloxone dispensing, where the dependent variable was operationalized as a Likert-type question on a scale of 1 (not at all willing) to 6 (very willing). Of 4699 practicing Kentucky pharmacists, 1282 responded, of which 834 were community practitioners (response rate 27.3%). Pharmacists reported varying willingness to initiate naloxone dispensing, with 37.3% very willing (score 5 or 6) and 27.9% not willing (score 1 or 2). However, a majority of pharmacists reported willingness to dispense naloxone with a valid prescription (54.0%, score 5 or 6). Women pharmacists were 1.3 times more likely than men to be willing to initiate naloxone dispensing (95% confidence interval [CI] 1.0-1.6). Those who reported confidence in identifying individuals at risk for overdose were 1.2 times more likely to initiate dispensing, and those who reported confidence in ability to educate patients about overdose were 1.6 times more likely to express willingness to initiate naloxone dispensing (95% CIs, respectively, 1.0-1.3 and 1.4-1.8). Community pharmacists reported barriers to naloxone access at higher rates than pharmacists from other practice settings. Kentucky pharmacists are divided in their willingness to initiate naloxone dispensing; however, those who are confident in their ability to identify overdose risks are more willing. Increasing pharmacist confidence through appropriately designed education programs could facilitate pharmacist participation in naloxone

Community-based opioid overdose prevention programs providing naloxone - United States, 2010.

PubMed

2012-02-17

Drug overdose death rates have increased steadily in the United States since 1979. In 2008, a total of 36,450 drug overdose deaths (i.e., unintentional, intentional [suicide or homicide], or undetermined intent) were reported, with prescription opioid analgesics (e.g., oxycodone, hydrocodone, and methadone), cocaine, and heroin the drugs most commonly involved . Since the mid-1990s, community-based programs have offered opioid overdose prevention services to persons who use drugs, their families and friends, and service providers. Since 1996, an increasing number of these programs have provided the opioid antagonist naloxone hydrochloride, the treatment of choice to reverse the potentially fatal respiratory depression caused by overdose of heroin and other opioids. Naloxone has no effect on non-opioid overdoses (e.g., cocaine, benzodiazepines, or alcohol) . In October 2010, the Harm Reduction Coalition, a national advocacy and capacity-building organization, surveyed 50 programs known to distribute naloxone in the United States, to collect data on local program locations, naloxone distribution, and overdose reversals. This report summarizes the findings for the 48 programs that completed the survey and the 188 local programs represented by the responses. Since the first opioid overdose prevention program began distributing naloxone in 1996, the respondent programs reported training and distributing naloxone to 53,032 persons and receiving reports of 10,171 overdose reversals. Providing opioid overdose education and naloxone to persons who use drugs and to persons who might be present at an opioid overdose can help reduce opioid overdose mortality, a rapidly growing public health concern.

Management of opioid painkiller dependence in primary care: ongoing recovery with buprenorphine/naloxone

PubMed Central

Hard, Bernadette

2014-01-01

Opioid painkiller dependence is a growing problem and best-practice management is not well defined. We report a case of a young woman exhibiting dependence on codeine, originally prescribed for myalgic encephalopathy, after escalating use over a 10-year period. In 2012, a consultation with a new general practitioner, who had extensive experience of patients with substance abuse, revealed the underlying dependence. After building trust for 6 months, she was able to admit to medication abuse, and was referred to the community drug and alcohol team. On presentation to the team, the patient had no pain issues and the dihydrocodeine use—600 tablets/week—solely reflected her dependence. The patient successfully underwent rapid induction with buprenorphine/naloxone as opioid substitution treatment over 2 days. She is currently stable, engaged with recovery support services and psychosocial counselling, and has just returned to work. She is maintained on a therapeutic dose of buprenorphine 10 mg/naloxone 2.5 mg. PMID:25432908

Feasibility of ultra low-dose thallium stress-redistribution protocol including prone imaging in obese patients using CZT camera.

PubMed

Kincl, Vladimír; Kamínek, Milan; Vašina, Jiří; Panovský, Roman; Havel, Martin

2016-09-01

High efficiency cadmium-zinc-telluride (CZT) cameras provide an opportunity to lower the injected activities of radiopharmaceuticals for single photon emission tomography (SPECT) myocardial perfusion imaging (MPI). The limits for reducing activities of thallium have not been determined, particularly in obese patients. After an injection of 0.7 megabecquerel (MBq) of thallium/kg, we collected an average 1.5 million counts for the 10-min acquisition in a pilot cohort of ten patients. After extrapolation, we reduced the administered activity to 0.5 MBq/kg to obtain the expected 1 million counts. We studied the image quality in 124 patients (86 men, 43 obese with body mass index over 30 kg/m 2 ) referred for MPI. The quality of images was assessed by a number of recorded counts and visually by a four-grade scale (one-poor quality, four-excellent quality). In non-obese and obese patients, the average number of recorded counts was 1.1 vs. 1.07 million counts for the 10-min stress acquisition, 1.04 vs. 1.06 million counts for the 13-min rest acquisition, and the average quality score was 3.97 vs. 3.90, respectively (p = NS).The mean administered activity was 39.2 ± 7 MBq for non-obese and 48.7 ± 6 for obese patients (p < 0.0001), and the calculated effective dose was 4.0 ± 0.7 and 4.9 ± 0.6 mSv respectively (p < 0.0001). The ultra-low-dose thallium stress-redistribution protocol, including post-stress prone imaging, provides good quality of images with a low radiation burden, even in obese patients.

A content review of online naloxone Continuing Education courses for pharmacists in states with standing orders.

PubMed

Carpenter, Delesha M; Roberts, Courtney A; Westrick, Salisa C; Ferreri, Stefanie P; Kennelty, Korey A; Look, Kevin A; Abraham, Olufunmilola; Wilson, Courtenay

2017-11-21

Many community pharmacists are uncomfortable educating patients about naloxone, an opioid reversal agent. To examine whether training materials prepare pharmacists to counsel patients and caregivers about naloxone, online naloxone education materials for pharmacists in the 13 states with standing orders were analyzed. Two coders reviewed 12 naloxone training programs and extracted data for 15 topics that were clustered in four categories: background/importance, naloxone products, business/operations, and communication. Programs that included communication content were coded for whether they: 1) suggested specific verbiage for naloxone counseling; 2) recommended evidence-based communication practices; and 3) included example naloxone conversations. Most programs covered the majority of topics, with the exception of extended treatment for individuals who overdose and naloxone storage/expiration information. Eleven programs addressed pharmacist-patient communication, although information on communication was often limited. Only one program included an example pharmacist-patient naloxone conversation, but the conversation was 10 min long and occurred in a private room, limiting its applicability to most community pharmacies. Online naloxone training materials for pharmacists include limited content on how to communicate with patients and caregivers. Training materials that include more in-depth content on communication may increase pharmacists' confidence to discuss the topics of overdose and naloxone. Copyright © 2017 Elsevier Inc. All rights reserved.

Morbidity after Ultra Low Anterior Resection of the Rectum.

PubMed

Straja, N D; Ionescu, S; Brătucu, E; Alecu, M; Simion, L

2015-01-01

Anterior resections of the rectum, used as an alternative to amputation of the rectum, are performed more and more frequently, being presently indicated for neoplasms located ata distance of 7 to 4 cm from the anus. Complications of low and ultra low anterior resections are not at all negligible, and local neoplastic recurrence rate is significantly higher than after amputation of the rectum. However, literature data recommends low and ultra low anterior rectal resections, even if sometimes the method indications are pushed to the limit or the interventions are performed at the patient's request, in order to avoid permanent colostomy. The authors of this article aim to outline a true picture of the changes caused by anterior resections of the rectum, low and ultra low, so that, without denying the merits of these resections, the entire postoperative pathology that occurs in these patients is depicted and understood. Ultra low rectal resections, up to 3-4 cm from the anus, bring important morphological and functional changes to the act of defecation and to anal continence. These changes in colo-anal bowel movement have a much higher incidence than postoperative genitourinary disorders. Another important aspect emerging from the present study is related to the increased incidence of anastomotic disunity, stenosis and various degrees of incontinence, complications that often can only be solved by completion of rectum amputation and permanent colostomy. In addition, the functional outcomes of these ultra low resections are not always at the level expected by the patient. Also, in terms of surgical performance, the higher share of specific complications of the procedure raises questions with regard to the technique. For all these reasons the authors consider it necessary to review the lower limit to which an anterior rectal resection can descend. Celsius.

Naloxone-induced seizures in rats infected with Borna disease virus.

PubMed

Solbrig, M V; Koob, G F; Lipkin, W I

1996-04-01

The opioid antagonist naloxone is widely used in the emergency treatment of nontraumatic coma. Although it is uncommon for serious side effects to result from administration of opiate antagonists, we report that naloxone can have epileptogenic effects in the context of encephalitis. In an experimental model of viral encephalitis, rats infected with Borna disease virus developed myoclonic, generalized clonic, or atonic seizures; behavior arrest; and staring spells when treated with naloxone. These findings suggest a novel neuropharmacologic link, through opioid peptide systems, between epilepsy and encephalitis and disclose a potential contraindication to use of opioid antagonists in nontraumatic coma.

Cancer radiotherapy based on femtosecond IR laser-beam filamentation yielding ultra-high dose rates and zero entrance dose.

PubMed

Meesat, Ridthee; Belmouaddine, Hakim; Allard, Jean-François; Tanguay-Renaud, Catherine; Lemay, Rosalie; Brastaviceanu, Tiberius; Tremblay, Luc; Paquette, Benoit; Wagner, J Richard; Jay-Gerin, Jean-Paul; Lepage, Martin; Huels, Michael A; Houde, Daniel

2012-09-18

Since the invention of cancer radiotherapy, its primary goal has been to maximize lethal radiation doses to the tumor volume while keeping the dose to surrounding healthy tissues at zero. Sadly, conventional radiation sources (γ or X rays, electrons) used for decades, including multiple or modulated beams, inevitably deposit the majority of their dose in front or behind the tumor, thus damaging healthy tissue and causing secondary cancers years after treatment. Even the most recent pioneering advances in costly proton or carbon ion therapies can not completely avoid dose buildup in front of the tumor volume. Here we show that this ultimate goal of radiotherapy is yet within our reach: Using intense ultra-short infrared laser pulses we can now deposit a very large energy dose at unprecedented microscopic dose rates (up to 10(11) Gy/s) deep inside an adjustable, well-controlled macroscopic volume, without any dose deposit in front or behind the target volume. Our infrared laser pulses produce high density avalanches of low energy electrons via laser filamentation, a phenomenon that results in a spatial energy density and temporal dose rate that both exceed by orders of magnitude any values previously reported even for the most intense clinical radiotherapy systems. Moreover, we show that (i) the type of final damage and its mechanisms in aqueous media, at the molecular and biomolecular level, is comparable to that of conventional ionizing radiation, and (ii) at the tumor tissue level in an animal cancer model, the laser irradiation method shows clear therapeutic benefits.

Prevention of hyperthermia-induced seizures in immature rats by a hydantoin derivative of naloxone.

PubMed

Chatterjie, N; Laorden, M L; Puig, M M; Alexander, G J

1989-01-01

The non-specific opiate antagonist naloxone protects immature rats from hyperthermic seizures which occur when the animals are exposed to an environment of 40 degrees C and 55% humidity. Most of the currently used antiepileptic therapeutic agents can be said to contain either a hydantoin or a moiety stereochemically closely related to one. We have added a hydantoin group to naloxone and created a new combined chemical, naloxyl-6-alpha spirohydantoin. The new compound was ten times as effective as naloxone against hyperthermic seizures in 15-day old rat pups. Unlike naloxone, the new naloxone-hydantoin derivative retained a protective effect 24 hrs after injection.

Expanded access to naloxone among firefighters, police officers, and emergency medical technicians in Massachusetts.

PubMed

Davis, Corey S; Ruiz, Sarah; Glynn, Patrick; Picariello, Gerald; Walley, Alexander Y

2014-08-01

Naloxone is a medication that reverses respiratory depression from opioid overdose if given in time. Paramedics routinely administer naloxone to opioid overdose victims in the prehospital setting, and many states are moving to increase access to the medication. Several jurisdictions have expanded naloxone administration authority to nonparamedic first responders, and others are considering that step. We report here on policy change in Massachusetts, where several communities have equipped emergency medical technicians, law enforcement officers, and firefighters with naloxone.

Opioid systems in the response to inflammatory pain: sustained blockade suggests role of kappa- but not mu-opioid receptors in the modulation of nociception, behaviour and pathology.

PubMed

Millan, M J; Colpaert, F C

1991-01-01

One day after intraplantar inoculation of Mycobacterium butyricum into the right hind-paw, unilaterally inflamed and control rats were implanted subcutaneously with osmotic mini-pumps delivering naloxone at 0.16 or 3.0 mg/kg/h or vehicle. As determined three days after implantation, 0.16 mg/kg/h of naloxone completely antagonized the antinociceptive action of the mu-agonist, morphine, but did not affect antinociception evoked by the kappa-agonist, U69,593. In contrast, at 3.0 mg/kg/h, naloxone blocked both morphine- and U69,593-induced antinociception. Thus, 0.16 mg/kg ("low dose") and 3.0 mg/kg ("high dose") of naloxone block mu, or mu- plus kappa-opioid receptors, respectively. Pumps were removed one week following their implantation. Inoculation was associated with a sustained hyperalgesia of the inflamed paw to noxious pressure, and elevation in resting core temperature, a loss of body weight, hypophagia, hypodipsia and a reduction in mobility. These parameters were differentially modified by the high as compared to the low dose of naloxone. Two days following implantation of pumps delivering the high dose of naloxone, the hyperalgesia of the inflamed paw was potentiated: by six days, this effect was lost. Further, one day after removal of pumps yielding the high dose, the inflamed paw showed a normalization of thresholds, that is a "rebound antinociception". One day later, this effect had subsided. In distinction, at no time did the low dose of naloxone modify nociceptive thresholds. The high dose of naloxone enhanced the reduction in body weight and food intake shown by unilaterally inflamed rats whereas the low dose was ineffective. Neither dose affected the reduction in water intake or hypothermia of unilaterally inflamed animals. The high dose of naloxone reduced the mobility of unilaterally inflamed rats whereas the low dose was ineffective. Finally, by 10 days following pump removal, pathology had transferred to the contralateral paw. In rats which had

Ultra-Low-Cost Room Temperature SiC Thin Films

NASA Technical Reports Server (NTRS)

Faur, Maria

1997-01-01

The research group at CSU has conducted theoretical and experimental research on 'Ultra-Low-Cost Room Temperature SiC Thin Films. The effectiveness of a ultra-low-cost room temperature thin film SiC growth technique on Silicon and Germanium substrates and structures with applications to space solar sells, ThermoPhotoVoltaic (TPV) cells and microelectronic and optoelectronic devices was investigated and the main result of this effort are summarized.

Note: Ultra-low birefringence dodecagonal vacuum glass cell.

PubMed

Brakhane, Stefan; Alt, Wolfgang; Meschede, Dieter; Robens, Carsten; Moon, Geol; Alberti, Andrea

2015-12-01

We report on an ultra-low birefringence dodecagonal glass cell for ultra-high vacuum applications. The epoxy-bonded trapezoidal windows of the cell are made of SF57 glass, which exhibits a very low stress-induced birefringence. We characterize the birefringence Δn of each window with the cell under vacuum conditions, obtaining values around 10(-8). After baking the cell at 150 °C, we reach a pressure below 10(-10) mbar. In addition, each window is antireflection coated on both sides, which is highly desirable for quantum optics experiments and precision measurements.

Ultra-Low Loss Waveguides with Application to Photonic Integrated Circuits

NASA Astrophysics Data System (ADS)

Bauters, Jared F.

The integration of photonic components using a planar platform promises advantages in cost, size, weight, and power consumption for optoelectronic systems. Yet, the typical propagation loss of 5-10 dB/m in a planar silica waveguide is nearly five orders-of-magnitude larger than that in low loss optical fibers. For some applications, the miniaturization of the photonic system and resulting smaller propagation lengths from integration are enough to overcome the increase in propagation loss. For other more demanding systems or applications, such as those requiring long optical time delays or high-quality-factor (Q factor) resonators, the high propagation loss can degrade system performance to a degree that trumps the potential advantages offered by integration. Thus, the reduction of planar waveguide propagation loss in a Si3-N4 based waveguide platform is a primary focus of this dissertation. The ultra-low loss stoichiometric Si3-N4 waveguide platform offers the additional advantages of fabrication process stability and repeatability. Yet, active devices such as lasers, amplifiers, and photodetectors have not been monolithically integrated with ultra-low loss waveguides due to the incompatibility of the active and ultra-low loss processing thermal budgets (ultra-low loss waveguides are annealed at temperatures exceeding 1000 °C in order to drive out impurities). So a platform that enables the integration of active devices with the ultra-low losses of the Si3- N4 waveguide platform is this dissertation's second focus. The work enables the future fabrication of sensor, gyroscope, true time delay, and low phase noise oscillator photonic integrated circuits.

Ultra Low Outgassing silicone performance in a simulated space ionizing radiation environment

NASA Astrophysics Data System (ADS)

Velderrain, M.; Malave, V.; Taylor, E. W.

2010-09-01

The improvement of silicone-based materials used in space and aerospace environments has garnered much attention for several decades. Most recently, an Ultra Low Outgassing™ silicone incorporating innovative reinforcing and functional fillers has shown that silicone elastomers with unique and specific properties can be developed to meet applications requiring stringent outgassing requirements. This paper will report on the next crucial step in qualifying these materials for spacecraft applications requiring chemical and physical stability in the presence of ionizing radiation. As a first step in this process, selected materials were irradiated with Co-60 gamma-rays to simulate the total dose received in near- Earth orbits. The paper will present pre-and post-irradiation response data of Ultra Low Outgassing silicone samples exposed under ambient air environment coupled with measurements of collected volatile condensable material (CVCM) and total mass loss (TML) per the standard conditions in ASTM E 595. The data will show an insignificant effect on the CVCMs and TMLs after exposure to various dosages of gamma radiation. This data may favorably impact new applications for these silicone materials for use as an improved sealant for space solar cell systems, space structures, satellite systems and aerospace systems.

Stereoselective action of (+)-morphine over (-)-morphine in attenuating the (-)-morphine-produced antinociception via the naloxone-sensitive sigma receptor in the mouse.

PubMed

Wu, Hsiang-en; Hong, Jau-Shyong; Tseng, Leon F

2007-10-01

We have previously demonstrated that (+)-morphine and (-)-morphine given spinally stereoselectively attenuate the spinally-administered (-)-morphine-produced tail-flick inhibition in the mouse. The phenomenon has been defined as antianalgesia. Present studies were then undertaken to determine if the systemic administration of (+)-morphine and (-)-morphine also stereoselectively attenuates the systemic (-)-morphine-produced tail-flick inhibition and the effects of (+)-morphine and (-)-morphine are mediated by the naloxone-sensitive sigma receptor activation in male CD-1 mice. Pretreatment with (+)-morphine at a dose of 0.01-10 ng/kg given subcutaneously dose-dependently attenuated the tail-flick inhibition produced by subcutaneously-administered (-)-morphine (5 mg/kg). Pretreatment with (-)-morphine (0.01-1.0 mg/kg) given subcutaneously also attenuates the (-)-morphine-produced tail-flick inhibition. The ED50 values for (+)-morphine and (-)-morphine for inhibiting the (-)-morphine-produced tail-flick inhibition were estimated to be 30.6 pg/kg and 97.5 microg/kg, respectively. The attenuation of the (-)-morphine-produced tail-flick inhibition induced by (+)-morphine or (-)-morphine pretreatment was reversed by the pretreatment with (+)-naloxone or by the sigma receptor antagonist BD1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide) given subcutaneously. Pretreatment with (+)-pentazocine, a selective sigma receptor agonist, (1-10 mg/kg) given subcutaneously also attenuates (-)-morphine-produced tail-flick inhibition, which was restored by (+)-naloxone (4 mg/kg) or BD1047 (10 mg/kg) pretreated subcutaneously. It is concluded that (+)-morphine exhibits extremely high stereoselective action over (-)-morphine given systemically in attenuating the systemic (-)-morphine-produced antinociception and the antianalgesic effect of (+)-morphine and (-)-morphine is mediated by activation of the naloxone-sensitive sigma receptor.

Prehospital Naloxone Administration as a Public Health Surveillance Tool: A Retrospective Validation Study.

PubMed

Lindstrom, Heather A; Clemency, Brian M; Snyder, Ryan; Consiglio, Joseph D; May, Paul R; Moscati, Ronald M

2015-08-01

Abuse or unintended overdose (OD) of opiates and heroin may result in prehospital and emergency department (ED) care. Prehospital naloxone use has been suggested as a surrogate marker of community opiate ODs. The study objective was to verify externally whether prehospital naloxone use is a surrogate marker of community opiate ODs by comparing Emergency Medical Services (EMS) naloxone administration records to an independent database of ED visits for opiate and heroin ODs in the same community. A retrospective chart review of prehospital and ED data from July 2009 through June 2013 was conducted. Prehospital naloxone administration data obtained from the electronic medical records (EMRs) of a large private EMS provider serving a metropolitan area were considered a surrogate marker for suspected opiate OD. Comparison data were obtained from the regional trauma/psychiatric ED that receives the majority of the OD patients. The ED maintains a de-identified database of narcotic-related visits for surveillance of narcotic use in the metropolitan area. The ED database was queried for ODs associated with opiates or heroin. Cross-correlation analysis was used to test if prehospital naloxone administration was independent of ED visits for opiate/heroin ODs. Naloxone was administered during 1,812 prehospital patient encounters, and 1,294 ED visits for opiate/heroin ODs were identified. The distribution of patients in the prehospital and ED datasets did not differ by gender, but it did differ by race and age. The frequency of naloxone administration by prehospital providers varied directly with the frequency of ED visits for opiate/heroin ODs. A monthly increase of two ED visits for opiate-related ODs was associated with an increase in one prehospital naloxone administration (cross-correlation coefficient [CCF]=0.44; P=.0021). A monthly increase of 100 ED visits for heroin-related ODs was associated with an increase in 94 prehospital naloxone administrations (CCF=0.46; P=.0012

Adjunctive Counseling During Brief and Extended Buprenorphine-Naloxone Treatment for Prescription Opioid Dependence

PubMed Central

Weiss, Roger D.; Potter, Jennifer Sharpe; Fiellin, David A.; Byrne, Marilyn; Connery, Hilary S.; Dickinson, William; Gardin, John; Griffin, Margaret L.; Gourevitch, Marc N.; Haller, Deborah L.; Hasson, Albert L.; Huang, Zhen; Jacobs, Petra; Kosinski, Andrzej S.; Lindblad, Robert; McCance-Katz, Elinore F.; Provost, Scott E.; Selzer, Jeffrey; Somoza, Eugene C.; Sonne, Susan C.; Ling, Walter

2012-01-01

Context No randomized trials have examined treatments for prescription opioid dependence, despite its increasing prevalence. Objective To evaluate the efficacy of brief and extended buprenorphine-naloxone treatment, with different counseling intensities, for patients dependent upon prescription opioids. Setting, Participants 653 treatment-seeking outpatients dependent on prescription opioids, at 10 U.S. sites from June 2006-July 2009. Design Multi-site, randomized clinical trial, using a two-phase adaptive treatment research design. Brief treatment (Phase 1) included 2-week buprenorphine-naloxone stabilization, 2-week taper, and 8-week post-medication follow-up. Patients with successful opioid use outcomes exited the study; unsuccessful patients entered Phase 2: extended (12-week) buprenorphine-naloxone treatment, 4-week taper, and 8-week post-medication follow-up. Main outcome measures Pre-defined “successful outcome” in each phase: composite measures indicating minimal or no opioid use, based on urine-confirmed self-reports. Interventions In both phases, patients were randomized to Standard Medical Management (SMM) or SMM+Opioid Drug Counseling (ODC); all received buprenorphine-naloxone. Results During Phase 1, only 6.6% (43/653) of patients had successful outcomes, with no difference between the SMM and SMM+ODC. In contrast, 49.2% (177/360) attained successful outcomes in Phase 2 during extended buprenorphine-naloxone treatment (week 12), with no difference between counseling conditions. Success rates 8 weeks after completing the buprenorphine-naloxone taper (Phase 2, week 24) dropped sharply to 8.6% (31/360), again with no counseling difference. In secondary analyses, successful Phase 2 outcomes were far more common while taking buprenorphine-naloxone than 8 weeks post-taper (49.2% (177/360) vs. 8.6% (31/360), p<0.001). Chronic pain did not affect opioid use outcomes; a history of ever using heroin was associated with lower Phase 2 success rates while

Reliability testing of ultra-low noise InGaAs quad photoreceivers

NASA Astrophysics Data System (ADS)

Joshi, Abhay M.; Datta, Shubhashish; Prasad, Narasimha; Sivertz, Michael

2018-02-01

We have developed ultra-low noise quadrant InGaAs photoreceivers for multiple applications ranging from Laser Interferometric Gravitional Wave Detection, to 3D Wind Profiling. Devices with diameters of 0.5 mm, 1mm, and 2 mm were processed, with the nominal capacitance of a single quadrant of a 1 mm quad photodiode being 2.5 pF. The 1 mm diameter InGaAs quad photoreceivers, using a low-noise, bipolar-input OpAmp circuitry exhibit an equivalent input noise per quadrant of <1.7 pA/√Hz in 2 to 20 MHz frequency range. The InGaAs Quad Photoreceivers have undergone the following reliability tests: 30 MeV Proton Radiation up to a Total Ionizing Dose (TID) of 50 krad, Mechanical Shock, and Sinusoidal Vibration.

Naloxone and epinephrine are equally effective for cardiopulmonary resuscitation in a rat asphyxia model.

PubMed

Chen, M-H; Xie, L; Liu, T-W; Song, F-Q; He, T

2006-10-01

It is not known whether naloxone is as efficacious as epinephrine during cardiopulmonary resuscitation (CPR). The aim of the study was to compare the effects of naloxone and epinephrine on the outcomes of CPR following asphyxial cardiac arrest in rats. Cardiac arrest was induced with asphyxia by clamping the tracheal tubes. Twenty-four Sprague-Dawley rats were randomized prospectively into a saline group (treated with normal saline, 1 ml intravenously, n = 8), an epinephrine group (treated with epinephrine, 0.04 mg/kg intravenously, n = 8) or a naloxone group (treated with naloxone, 1 mg/kg intravenously, n = 8) in a blind fashion during resuscitation after asphyxial cardiac arrest. After 5 min of untreated cardiac arrest, conventional manual CPR was started and each drug was administered at the same time. The rates of restoration of spontaneous circulation (ROSC) were one of eight (12.5%), seven of eight (87.5%) and seven of eight (87.5%) in the saline, epinephrine and naloxone groups, respectively. The rates of ROSC in the epinephrine and naloxone groups were equal and significantly greater than that in the saline group (P = 0.01 and P = 0.01, respectively). The administration of naloxone or epinephrine alone may increase the resuscitation rate, and both drugs are equally effective for CPR in a rat asphyxia model. However, the mechanism by which naloxone produces its efficacy during CPR remains unclear and further experimentation will be necessary.

Effects of a sustained-release naloxone pellet on luteinizing hormone secretion in female rats.

PubMed

Gabriel, S M; Simpkins, J W

1983-11-01

Studies were undertaken to develop a naloxone implant capable of chronically blocking opioid receptors for several weeks in an effort to evaluate the effect of this prolonged narcotic antagonism on luteinizing hormone (LH) secretion in female rats. Antagonism of opiate receptors was achieved with a tablet formulation which contained 75 mg naloxone free base and a high content of the insoluble binding material, Mg stearate. Subcutaneous placement of this implant prevented morphine-induced analgesia for 2 weeks and antagonized the LH suppressory effects of morphine (15 or 30 mg/kg) administration. Thus, this naloxone delivery system is capable of chronically occupying the opioid receptors which mediate morphine's effects on analgesia and LH secretion. Despite this, the naloxone pellet only moderately enhanced the initial rate of increase in LH secretion following ovariectomy (day 1) and was ineffective in further augmenting LH secretion at 3 and 7 days after implantation. In rats which were ovariectomized and implanted immediately with estradiol-containing Silastic capsules, the naloxone pellet was ineffective in altering LH secretion 1, 3 or 7 days later. Thus, while chronic exposure to naloxone persistently antagonizes the pharmacologic actions of morphine, the naloxone pellet only transiently blocked the tonic inhibitory effect of endogenous opioid peptides. The mechanism by which the LH secretory effects of naloxone are lost following chronic exposure to the antagonist are at present unknown, but may involve the activation of compensatory mechanisms which are inhibitory to LH secretion.

Note: Ultra-low birefringence dodecagonal vacuum glass cell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brakhane, Stefan, E-mail: brakhane@iap.uni-bonn.de; Alt, Wolfgang; Meschede, Dieter

We report on an ultra-low birefringence dodecagonal glass cell for ultra-high vacuum applications. The epoxy-bonded trapezoidal windows of the cell are made of SF57 glass, which exhibits a very low stress-induced birefringence. We characterize the birefringence Δn of each window with the cell under vacuum conditions, obtaining values around 10{sup −8}. After baking the cell at 150 °C, we reach a pressure below 10{sup −10} mbar. In addition, each window is antireflection coated on both sides, which is highly desirable for quantum optics experiments and precision measurements.

Typical doses and dose rates in studies pertinent to radiation risk inference at low doses and low dose rates

PubMed Central

Rühm, Werner; Azizova, Tamara; Bouffler, Simon; Cullings, Harry M; Grosche, Bernd; Little, Mark P; Shore, Roy S; Walsh, Linda; Woloschak, Gayle E

2018-01-01

Abstract In order to quantify radiation risks at exposure scenarios relevant for radiation protection, often extrapolation of data obtained at high doses and high dose rates down to low doses and low dose rates is needed. Task Group TG91 on ‘Radiation Risk Inference at Low-dose and Low-dose Rate Exposure for Radiological Protection Purposes’ of the International Commission on Radiological Protection is currently reviewing the relevant cellular, animal and human studies that could be used for that purpose. This paper provides an overview of dose rates and doses typically used or present in those studies, and compares them with doses and dose rates typical of those received by the A-bomb survivors in Japan. PMID:29432579

Beneficial effects of naloxone in a patient with intestinal pseudoobstruction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schang, J.C.; Devroede, G.

1985-06-01

A 15-day course of Naloxone treatment was given to a patient with intestinal pseudoobstruction who had previously undergone subtotal colectomy with terminal ileostomy for invalidating constipation. The effects of the drug were assessed according to symptoms, by recording the myoelectric activity of the stomach, and by measuring gastric emptying of a radiolabeled solid-liquid meal and the intestinal transit time of radiopaque markers. All tests were performed 1) at baseline; 2) after 2 wk with Naloxone 1.6 mg subcutaneous per day; and 3) after 8 days of placebo. Results showed that before treatment gastric emptying of solids was delayed, emptying ofmore » liquids was normal, myoelectric activity of the stomach was normal, small intestinal transit time of radiopaque markers was considerably increased while ileal output was markedly decreased. After Naloxone, gastric emptying of solids was markedly accelerated, emptying of liquids remained normal, gastric electrical spiking activity increased, small intestinal transit time strikingly decreased, and ileal output increased. After placebo, a tendency to return to pretreatment values was observed. This observation suggests that Naloxone may be helpful in the treatment of some patients with intestinal pseudoobstruction.« less

Priori mask guided image reconstruction (p-MGIR) for ultra-low dose cone-beam computed tomography

NASA Astrophysics Data System (ADS)

Park, Justin C.; Zhang, Hao; Chen, Yunmei; Fan, Qiyong; Kahler, Darren L.; Liu, Chihray; Lu, Bo

2015-11-01

Recently, the compressed sensing (CS) based iterative reconstruction method has received attention because of its ability to reconstruct cone beam computed tomography (CBCT) images with good quality using sparsely sampled or noisy projections, thus enabling dose reduction. However, some challenges remain. In particular, there is always a tradeoff between image resolution and noise/streak artifact reduction based on the amount of regularization weighting that is applied uniformly across the CBCT volume. The purpose of this study is to develop a novel low-dose CBCT reconstruction algorithm framework called priori mask guided image reconstruction (p-MGIR) that allows reconstruction of high-quality low-dose CBCT images while preserving the image resolution. In p-MGIR, the unknown CBCT volume was mathematically modeled as a combination of two regions: (1) where anatomical structures are complex, and (2) where intensities are relatively uniform. The priori mask, which is the key concept of the p-MGIR algorithm, was defined as the matrix that distinguishes between the two separate CBCT regions where the resolution needs to be preserved and where streak or noise needs to be suppressed. We then alternately updated each part of image by solving two sub-minimization problems iteratively, where one minimization was focused on preserving the edge information of the first part while the other concentrated on the removal of noise/artifacts from the latter part. To evaluate the performance of the p-MGIR algorithm, a numerical head-and-neck phantom, a Catphan 600 physical phantom, and a clinical head-and-neck cancer case were used for analysis. The results were compared with the standard Feldkamp-Davis-Kress as well as conventional CS-based algorithms. Examination of the p-MGIR algorithm showed that high-quality low-dose CBCT images can be reconstructed without compromising the image resolution. For both phantom and the patient cases, the p-MGIR is able to achieve a clinically

Self-management of buprenorphine/naloxone among online discussion board users.

PubMed

Brown, Shan-Estelle; Altice, Frederick L

2014-06-01

Buprenorphine/naloxone is an effective medication used to treat opioid dependence. Patients in treatment and those using it illegally without prescriptions have discussed using buprenorphine/naloxone anonymously on Internet discussion boards. Their beliefs about self-treatment and efforts to self-treat are not well known. To identify facilitators of self-treatment by online buprenorphine/naloxone users. A qualitative, retrospective study of discussion board postings from September 2010 to November 2012 analyzed 121 threads from 13 discussion boards using grounded theory. Facilitators of self-management themes that emerged included: (1) a ready supply of buprenorphine/naloxone from a variety of sources; (2) distrust of buprenorphine prescribers and pharmaceutical companies; (3) the declaration that buprenorphine/naloxone is a "bad-tasting" medicine; (4) the desire to adopt a different delivery method other than sublingually; and (5) a desire to become completely "substance-free." The sublingual film formulation appears to be an important facilitator in self-treatment because it can more easily be apportioned to extend the medication because of limited supply, cost, or to taper. CONCLUSIONS/IMPORTANCE: The findings indicate a range of self-management activities ranging from altering the amount taken to modifying the physical medication composition or changing the administration route; some of these behaviors constitute problematic extra-medical use. Contributors to discussion boards seem to trust each other more than they trust pharmacists and prescribing physicians. The shared knowledge and behaviors of this understudied online community are important to healthcare providers because of the previously unknown precautions and risks taken to self-treat.

Self-Management of Buprenorphine/Naloxone Among Online Discussion Board Users

PubMed Central

Brown, Shan-Estelle; Altice, Frederick L.

2017-01-01

Background Buprenorphine/naloxone is an effective medication used to treat opioid dependence. Patients in treatment and those using it illegally without prescriptions have discussed using buprenorphine/naloxone anonymously on Internet discussion boards. Their beliefs about self-treatment and efforts to self-treat are not well known. Objectives To identify facilitators of self-treatment by online buprenorphine/naloxone users. Methods A qualitative, retrospective study of discussion board postings from September 2010 to November 2012 analyzed 121 threads from 13 discussion boards using grounded theory. Results Facilitators of self-management themes that emerged included: (1) a ready supply of buprenorphine/naloxone from a variety of sources; (2) distrust of buprenorphine prescribers and pharmaceutical companies; (3) the declaration that buprenorphine/naloxone is a “bad-tasting” medicine; (4) the desire to adopt a different delivery method other than sublingually; and (5) a desire to become completely “substance-free.” The sublingual film formulation appears to be an important facilitator in self-treatment because it can more easily be apportioned to extend the medication because of limited supply, cost, or to taper. Conclusions/Importance The findings indicate a range of self-management activities ranging from altering the amount taken to modifying the physical medication composition or changing the administration route; some of these behaviors constitute problematic extra-medical use. Contributors to discussion boards seem to trust each other more than they trust pharmacists and prescribing physicians. The shared knowledge and behaviors of this understudied online community are important to healthcare providers because of the previously unknown precautions and risks taken to self-treat. PMID:24779501

Skin dose measurement by using ultra-thin TLDs.

PubMed

Lin, J P; Chu, T C; Lin, S Y; Liu, M T

2001-09-01

The treatment schedule for radiation therapy is often interrupted because of complicated skin reactions. Quantitative information relating beam parameters and skin reactions will be helpful. Measurements were performed for 6-15 MV photons and 6-21 MeV electrons with ultra thin TLD films (GR-200F, surface area 0.5 x 0.5cm2, nominal thickness 5 mg cm(-2)). The skin doses for various field sizes, ranging from 10 x 10 to 40 x 40 cm2, and various incident angles of beam from 0 degrees to 80 degrees were measured. The ratios of skin dose to maximum dose in phantom for 10 x 10 cm2 are 16.10+/-0.68%, 14.03+/-1.04% and 10.59+/-0.64% for 6, 10 and 15 MV, respectively. Such ratios increase with a larger field size. For electrons the ratios are 72.59+/-1.72%, 78.52+/-2.99%, 78.89+/-2.86%, 86.08+/-2.62%. 87.75+/-1.94% and 86.33+/-3.09% for 6, 9, 12, 15, 18 and 21 MeV, respectively. They also increase with a larger size. The oblique factors also increase with larger incident angle.

Prolonged-Release Oxycodone/Naloxone Improves Anal Sphincter Relaxation Compared to Oxycodone Plus Macrogol 3350.

PubMed

Poulsen, Jakob Lykke; Brock, Christina; Grønlund, Debbie; Liao, Donghua; Gregersen, Hans; Krogh, Klaus; Drewes, Asbjørn Mohr

2017-11-01

Opioid analgesics inhibit anal sphincter function and contribute to opioid-induced bowel dysfunction (OIBD). However, it is unknown whether the inhibition can be reduced by opioid antagonism with prolonged-release (PR) naloxone and how this compares to laxative treatment. To compare the effects of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350 on anal sphincter function and gastrointestinal symptoms. A randomized, double-blind, crossover trial was conducted in 20 healthy men. Participants were treated for 5 days with combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Resting anal pressure, anal canal distensibility, and relaxation of the internal sphincter to rectal distension were evaluated before treatment (baseline) and on day 5. The Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire, stool frequency, and stool consistency were assessed daily. Both PR oxycodone/naloxone and PR oxycodone plus macrogol treatment decreased sphincter relaxation compared to baseline (- 27.5%; P < 0.001 and - 14.7%; P = 0.01). However, sphincter relaxation was increased after PR naloxone/oxycodone treatment compared to macrogol (difference = + 17.6%; P < 0.001). Resting anal pressure and anal canal distensibility did not differ between treatments. PAC-SYM abdominal symptoms score was lower during PR naloxone compared to macrogol (0.2 vs. 3.2; P = 0.002). The number of bowel movements was lower during PR naloxone versus macrogol (4.2 vs. 5.4; P = 0.035). Relaxation of the internal anal sphincter was significantly better after PR oxycodone/naloxone treatment compared to PR oxycodone plus macrogol 3350. These findings highlight that OIBD may require specific therapy against the complex, pan-intestinal effects of opioids.

Ultra-low temperature curable nano-silver conductive adhesive for piezoelectric composite material

NASA Astrophysics Data System (ADS)

Yan, Chao; Liao, Qingwei; Zhou, Xingli; Wang, Likun; Zhong, Chao; Zhang, Di

2018-01-01

Limited by the low thermal resistance of composite material, ultra-low temperature curable conductive silver adhesive with curing temperature less than 100 °C needed urgently for the surface conduction treatment of piezoelectric composite material. An ultra-low temperature curable nano-silver conductive adhesive with high adhesion strength for the applications of piezoelectric composite material was investigated. The crystal structure of cured adhesive, SEM/EDS analysis, thermal analysis, adhesive properties and conductive properties of different content of nano-silver filler or micron-silver doping samples were studied. The results show that with 60 wt.% nano-silver filler the ultra-low temperature curable conductive silver adhesive had the relatively good conductivity as volume resistivity of 2.37 × 10-4 Ω cm, and good adhesion strength of 5.13 MPa. Minor micron-doping (below 15 wt.%) could improve conductivity, but would decrease other properties. The ultra-low temperature curable nano-silver conductive adhesive could successfully applied to piezoelectric composite material.

Traceable low and ultra-low temperatures in The Netherlands

NASA Astrophysics Data System (ADS)

Peruzzi, A.; Bosch, W. A.

2009-02-01

The basis for worldwide uniformity of low and ultra-low temperature measurements is provided by two international temperature scales, the International Temperature Scale of 1990 (ITS-90) for temperatures above 0.65 K and the Provisional Low Temperature Scale of 2000 (PLTS-2000) for temperatures in the range 0.9 mK to 1 K. Over the past 10 years, the thermometry research in the Netherlands provided substantial contributions to the definition, realization and dissemination of these scales. We first give an overview of the Dutch contributions to the ITS-90 realization: a) 3He and 4He vapour pressure thermometer range of the ITS-90, 0.65 K to 4 K (1997), b) 4He interpolating constant volume gas thermometry for the ITS-90 range 3 K to 24.5 K (2007) and c) cryogenic fixed points for the ITS-90 range 13.8 K to 273.16 K (2005). Then we highlight our work on 3He melting pressure thermometry from 10 mK to 1 K (2003) to support the dissemination of the PLTS-2000. Finally we present the current status of the Dutch calibration facilities and dissemination devices providing for traceable low and ultra-low temperatures for use in science and industry: a) the NMi-VSL cryogenic calibration facility for the range 0.65 K to 273.16 K and b) the SRD1000 superconductive reference devices for the range 10 mK to 1 K.

Differential renal effects of candesartan at high and ultra-high doses in diabetic mice–potential role of the ACE2/AT2R/Mas axis

PubMed Central

Callera, Glaucia E.; Antunes, Tayze T.; Correa, Jose W.; Moorman, Danielle; Gutsol, Alexey; He, Ying; Cat, Aurelie Nguyen Dinh; Briones, Ana M.; Montezano, Augusto C.; Burns, Kevin D.; Touyz, Rhian M.

2016-01-01

High doses of Ang II receptor (AT1R) blockers (ARBs) are renoprotective in diabetes. Underlying mechanisms remain unclear. We evaluated whether high/ultra-high doses of candesartan (ARB) up-regulate angiotensin-converting enzyme 2 (ACE2)/Ang II type 2 receptor (AT2R)/Mas receptor [protective axis of the of the renin–angiotensin system (RAS)] in diabetic mice. Systolic blood pressure (SBP), albuminuria and expression/activity of RAS components were assessed in diabetic db/db and control db/+ mice treated with increasing candesartan doses (intermediate, 1 mg/kg/d; high, 5 mg/kg/d; ultra-high, 25 and 75 mg/kg/d; 4 weeks). Lower doses candesartan did not influence SBP, but ultra-high doses reduced SBP in both groups. Plasma glucose and albuminuria were increased in db/db compared with db/+ mice. In diabetic mice treated with intermediate dose candesartan, renal tubular damage and albuminuria were ameliorated and expression of ACE2, AT2R and Mas and activity of ACE2 were increased, effects associated with reduced ERK1/2 phosphorylation, decreased fibrosis and renal protection. Ultra-high doses did not influence the ACE2/AT2R/Mas axis and promoted renal injury with increased renal ERK1/2 activation and exaggerated fibronectin expression in db/db mice. Our study demonstrates dose-related effects of candesartan in diabetic nephropathy: intermediate–high dose candesartan is renoprotective, whereas ultra-high dose candesartan induces renal damage. Molecular processes associated with these effects involve differential modulation of the ACE2/AT2R/Mas axis: intermediate–high dose candesartan up-regulating RAS protective components and attenuating pro-fibrotic processes, and ultra-high doses having opposite effects. These findings suggest novel mechanisms through the protective RAS axis, whereby candesartan may ameliorate diabetic nephropathy. Our findings also highlight potential injurious renal effects of ultra-high dose candesartan in diabetes. PMID:27612496

Low-Dose Carcinogenicity Studies

EPA Science Inventory

One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...

Extended vs Short-term Buprenorphine-Naloxone for Treatment of Opioid-Addicted Youth

PubMed Central

Woody, George E.; Poole, Sabrina A.; Subramaniam, Geetha; Dugosh, Karen; Bogenschutz, Michael; Abbott, Patrick; Patkar, Ashwin; Publicker, Mark; McCain, Karen; Potter, Jennifer Sharpe; Forman, Robert; Vetter, Victoria; McNicholas, Laura; Blaine, Jack; Lynch, Kevin G.; Fudala, Paul

2008-01-01

Context The usual treatment for opioid-addicted youth is detoxification and counseling. Extended medication-assisted therapy may be more helpful. Objective To evaluate the efficacy of continuing buprenorphine-naloxone for 12 weeks vs detoxification for opioid-addicted youth. Design, Setting, and Patients Clinical trial at 6 community programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were randomized to 12 weeks of buprenorphine-naloxone or a 14-day taper (detox). Interventions Patients in the 12-week buprenorphine-naloxone group were prescribed up to 24 mg per day for 9 weeks and then tapered to week 12; patients in the detox group were prescribed up to 14 mg per day and then tapered to day 14. All were offered weekly individual and group counseling. Main Outcome Measure Opioid-positive urine test result at weeks 4, 8, and 12. Results The number of patients younger than 18 years was too small to analyze separately, but overall, patients in the detox group had higher proportions of opioid-positive urine test results at weeks 4 and 8 but not at week 12 ( χ22 = 4.93, P = .09). At week 4, 59 detox patients had positive results (61%; 95% confidence interval [CI] = 47%-75%) vs 58 12-week buprenorphine-naloxone patients (26%; 95% CI = 14%-38%). At week 8, 53 detox patients had positive results (54%; 95% CI = 38%-70%) vs 52 12-week buprenorphine-naloxone patients (23%; 95% CI = 11%-35%). At week 12, 53 detox patients had positive results (51%; 95% CI = 35%-67%) vs 49 12-week buprenorphine-naloxone patients (43%; 95% CI = 29%-57%). By week 12, 16 of 78 detox patients (20.5%) remained in treatment vs 52 of 74 12-week buprenorphine-naloxone patients (70%; χ12 = 32.90, P < .001). During weeks 1 through 12, patients in the 12-week buprenorphine-naloxone group reported less opioid use ( χ12 = 18.45, P < .001), less injecting ( χ12 = 6.00, P = .01), and less nonstudy addiction treatment ( χ12 = 25.82, P < .001). High levels of opioid use

Prescribe to Prevent: Overdose Prevention and Naloxone Rescue Kits for Prescribers and Pharmacists

PubMed Central

Lim, Jamie K.; Bratberg, Jeffrey P.; Davis, Corey S.; Green, Traci C.; Walley, Alexander Y.

2016-01-01

In March of 2015, the United States Department of Health and Human Services identified 3 priority areas to reduce opioid use disorders and overdose, which are as follows: opioid-prescribing practices; expanded use and distribution of naloxone; and expansion of medication-assisted treatment. In this narrative review of overdose prevention and the role of prescribers and pharmacists in distributing naloxone, we address these priority areas and present a clinical scenario within the review involving a pharmacist, a patient with chronic pain and anxiety, and a primary care physician. We also discuss current laws related to naloxone prescribing and dispensing. This review was adapted from the Prescribe to Prevent online continuing medical education module created for prescribers and pharmacists (http://www.opioidprescribing.com/naloxone_module_1-landing). PMID:27261669

Effects of naloxone distribution to likely bystanders: Results of an agent-based model.

PubMed

Keane, Christopher; Egan, James E; Hawk, Mary

2018-05-01

Opioid overdose deaths in the US rose dramatically in the past 16 years, creating an urgent national health crisis with no signs of immediate relief. In 2017, the President of the US officially declared the opioid epidemic to be a national emergency and called for additional resources to respond to the crisis. Distributing naloxone to community laypersons and people at high risk for opioid overdose can prevent overdose death, but optimal distribution methods have not yet been pinpointed. We conducted a sequential exploratory mixed methods design using qualitative data to inform an agent-based model to improve understanding of effective community-based naloxone distribution to laypersons to reverse opioid overdose. The individuals in the model were endowed with cognitive and behavioral variables and accessed naloxone via community sites such as pharmacies, hospitals, and urgent-care centers. We compared overdose deaths over a simulated 6-month period while varying the number of distribution sites (0, 1, and 10) and number of kits given to individuals per visit (1 versus 10). Specifically, we ran thirty simulations for each of thirteen distribution models and report average overdose deaths for each. The baseline comparator was no naloxone distribution. Our simulations explored the effects of distribution through syringe exchange sites with and without secondary distribution, which refers to distribution of naloxone kits by laypersons within their social networks and enables ten additional laypersons to administer naloxone to reverse opioid overdose. Our baseline model with no naloxone distribution predicted there would be 167.9 deaths in a six month period. A single distribution site, even with 10 kits picked up per visit, decreased overdose deaths by only 8.3% relative to baseline. However, adding secondary distribution through social networks to a single site resulted in 42.5% fewer overdose deaths relative to baseline. That is slightly higher than the 39

RuO2 Thermometer for Ultra-Low Temperatures

NASA Technical Reports Server (NTRS)

Hait, Thomas; Shirron, Peter J.; DiPirro, Michael

2009-01-01

A small, high-resolution, low-power thermometer has been developed for use in ultra-low temperatures that uses multiple RuO2 chip resistors. The use of commercially available thick-film RuO2 chip resistors for measuring cryogenic temperatures is well known due to their low cost, long-term stability, and large resistance change.

Comparison of image quality, myocardial perfusion, and LV function between standard imaging and single-injection ultra-low-dose imaging using a high-efficiency SPECT camera: the MILLISIEVERT study

PubMed Central

Einstein, Andrew J.; Blankstein, Ron; Andrews, Howard; Fish, Mathews; Padgett, Richard; Hayes, Sean W.; Friedman, John D.; Qureshi, Mehreen; Rakotoarivelo, Harivony; Slomka, Piotr; Nakazato, Ryo; Bokhari, Sabahat; Di Carli, Marcello; Berman, Daniel S.

2015-01-01

SPECT myocardial perfusion imaging (MPI) plays a central role in coronary artery disease diagnosis; but concerns exist regarding its radiation burden. Compared to standard Anger-SPECT (A-SPECT) cameras, new high-efficiency (HE) cameras with specialized collimators and solid-state cadmium-zinc-telluride detectors offer potential to maintain image quality (IQ), while reducing administered activity and thus radiation dose to patients. No previous study has compared IQ, interpretation, total perfusion deficit (TPD), or ejection fraction (EF) in patients receiving both ultra-low-dose (ULD) imaging on a HE-SPECT camera and standard low-dose (SLD) A-SPECT imaging. Methods We compared ULD-HE-SPECT to SLD-A-SPECT imaging by dividing the rest dose in 101 patients at 3 sites scheduled to undergo clinical A-SPECT MPI using a same day rest/stress Tc-99m protocol. Patients received HE-SPECT imaging following an initial ~130 MBq (3.5mCi) dose, and SLD-A-SPECT imaging following the remainder of the planned dose. Images were scored visually by 2 blinded readers for IQ and summed rest score (SRS). TPD and EF were assessed quantitatively. Results Mean activity was 134 MBq (3.62 mCi) for ULD-HE-SPECT (effective dose 1.15 mSv) and 278 MBq (7.50 mCi, 2.39 mSv) for SLD-A-SPECT. Overall IQ was superior for ULD-HE-SPECT (p<0.0001), with twice as many studies graded excellent quality. Extracardiac activity and overall perfusion assessment were similar. Between-method correlations were high for SRS (r=0.87), TPD (r=0.91), and EF (r=0.88). Conclusion ULD-HE-SPECT rest imaging correlates highly with SLD-A-SPECT. It has improved image quality, comparable extracardiac activity, and achieves radiation dose reduction to 1 mSv for a single injection. PMID:24982439

An ultra-low power output capacitor-less low-dropout regulator with slew-rate-enhanced circuit

NASA Astrophysics Data System (ADS)

Cheng, Xin; Zhang, Yu; Xie, Guangjun; Yang, Yizhong; Zhang, Zhang

2018-03-01

An ultra-low power output-capacitorless low-dropout (LDO) regulator with a slew-rate-enhanced (SRE) circuit is introduced. The increased slew rate is achieved by sensing the transient output voltage of the LDO and then charging (or discharging) the gate capacitor quickly. In addition, a buffer with ultra-low output impedance is presented to improve line and load regulations. This design is fabricated by SMIC 0.18 μm CMOS technology. Experimental results show that, the proposed LDO regulator only consumes an ultra-low quiescent current of 1.2 μA. The output current range is from 10 μA to 200 mA and the corresponding variation of output voltage is less than 40 mV. Moreover, the measured line regulation and load regulation are 15.38 mV/V and 0.4 mV/mA respectively. Project supported by the National Natural Science Foundation of China (Nos. 61401137, 61404043, 61674049).

Whole-body ultra-low dose CT using spectral shaping for detection of osteolytic lesion in multiple myeloma.

PubMed

Suntharalingam, Saravanabavaan; Mikat, Christian; Wetter, Axel; Guberina, Nika; Salem, Ahmed; Heil, Philipp; Forsting, Michael; Nassenstein, Kai

2018-06-01

The aim of this study was to investigate the radiation dose and image quality of a whole-body low-dose CT (WBLDCT) using spectral shaping at 100 kV (Sn 100 kV) for the assessment of osteolytic lesions in patients with multiple myeloma. Thirty consecutive patients were retrospectively selected, who underwent a WBLDCT on a third-generation dual-source CT (DSCT) (Sn 100 kV, ref. mAs: 130). They were matched with patients, who were examined on a second-generation DSCT with a standard low-dose protocol (100 kV, ref. mAs: 111). Objective and subjective image quality, radiation exposure as well as the frequency of osteolytic lesions were evaluated. All scans were of diagnostic image quality. Subjective overall image quality was significantly higher in the study group (p = 0.0003). Objective image analysis revealed that signal intensities, signal-to-noise ratio and contrast-to-noise ratio of the bony structures were equal or significantly higher in the control group. There was no significant difference in the frequency of osteolytic lesions (p = 0.259). The median effective dose of the study protocol was significantly lower (1.45 mSv vs. 5.65 mSv; p < 0.0001). WBLDCT with Sn 100 kV can obtain sufficient image quality for the depiction of osteolytic lesions while reducing the radiation dose by approximately 74%. • Spectral shaping using tin filtration is beneficial for whole-body low-dose CT • Sn 100 kV yields sufficient image quality for depiction of osteolytic lesions • Whole-body low-dose CT can be performed with a median dose of 1.5 mSv.

Intranasal naloxone administration by police first responders is associated with decreased opioid overdose deaths.

PubMed

Rando, Jessica; Broering, Derek; Olson, James E; Marco, Catherine; Evans, Stephen B

2015-09-01

This study sought to answer the question, "Can police officers administer intranasal naloxone to drug overdose victims to decrease the opioid overdose death rate?" This prospective interventional study was conducted in Lorain County, OH, from January 2011 to October 2014. Starting October 2013, trained police officers administered naloxone to suspected opioid overdose victims through a police officer naloxone prescription program (NPP). Those found by the county coroner to be positive for opioids at the time of death and those who received naloxone from police officers were included in this study. The rate of change in the total number of opioid-related deaths in Lorain County per quarter year, before and after initiation of the NPP, and the trend in the survival rate of overdose victims who were given naloxone were analyzed by linear regression. Significance was established a priori at P < .05. Data from 247 individuals were eligible for study inclusion. Opioid overdose deaths increased significantly before initiation of the police officer NPP with average deaths per quarter of 5.5 for 2011, 15.3 for 2012, and 16.3 for the first 9 months of 2013. After initiation of the police officer NPP, the number of opioid overdose deaths decreased each quarter with an overall average of 13.4. Of the 67 participants who received naloxone by police officers, 52 (77.6%) survived, and 8 (11.9%) were lost to follow-up. Intranasal naloxone administration by police first responders is associated with decreased deaths in opioid overdose victims. Copyright © 2015 Elsevier Inc. All rights reserved.

Knowledge of naloxone and take-home naloxone programs among a sample of people who inject drugs in Australia: Variations across capital cities.

PubMed

Dietze, Paul M; Stare, Mark; Cogger, Shelley; Nambiar, Dhanya; Olsen, Anna; Burns, Lucinda; Lenton, Simon

2018-05-01

Take-home naloxone (THN) programs targeting people who inject drugs (PWID) have been running in some Australian states and territories since 2012. In this study, we aimed to determine the extent to which PWID in the capital cities of all Australian states and territories are aware of naloxone and THN programs, whether awareness of these programs has changed over time. Data were obtained from cross-sectional surveys of a total of 2088 PWID conducted annually as part of the Illicit Drug Reporting System from 2013 to 2015. Specific questions about THN added to the survey in 2013 allowed assessment of the extent to which sampled PWID were aware of naloxone and its function and THN programs in Australia and whether they had participated in a THN program. These main outcomes were examined over time and across states and territories using a mix of descriptive statistics and logistic regression. Over 80% of the sample reported having heard of naloxone across survey years. Less than half of the participants reported having heard of THN programs in 2013 (35%), but this increased to just over (52%) half in 2015 (P < 0.01). Changes over time differed across cities with increases in reports of having heard of THN occurring over time most clearly in those cities with operational THN programs. Around half of the PWID sampled for this study are aware of THN programs. Further work is needed to ensure widespread awareness of THN programs which should include implementing THN in all Australian states and territories. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Ultra-low dose quantitative CT myocardial perfusion imaging with sparse-view dynamic acquisition and image reconstruction: A feasibility study.

PubMed

Enjilela, Esmaeil; Lee, Ting-Yim; Hsieh, Jiang; Wisenberg, Gerald; Teefy, Patrick; Yadegari, Andrew; Bagur, Rodrigo; Islam, Ali; Branch, Kelley; So, Aaron

2018-03-01

We implemented and validated a compressed sensing (CS) based algorithm for reconstructing dynamic contrast-enhanced (DCE) CT images of the heart from sparsely sampled X-ray projections. DCE CT imaging of the heart was performed on five normal and ischemic pigs after contrast injection. DCE images were reconstructed with filtered backprojection (FBP) and CS from all projections (984-view) and 1/3 of all projections (328-view), and with CS from 1/4 of all projections (246-view). Myocardial perfusion (MP) measurements with each protocol were compared to those with the reference 984-view FBP protocol. Both the 984-view CS and 328-view CS protocols were in good agreements with the reference protocol. The Pearson correlation coefficients of 984-view CS and 328-view CS determined from linear regression analyses were 0.98 and 0.99 respectively. The corresponding mean biases of MP measurement determined from Bland-Altman analyses were 2.7 and 1.2ml/min/100g. When only 328 projections were used for image reconstruction, CS was more accurate than FBP for MP measurement with respect to 984-view FBP. However, CS failed to generate MP maps comparable to those with 984-view FBP when only 246 projections were used for image reconstruction. DCE heart images reconstructed from one-third of a full projection set with CS were minimally affected by aliasing artifacts, leading to accurate MP measurements with the effective dose reduced to just 33% of conventional full-view FBP method. The proposed CS sparse-view image reconstruction method could facilitate the implementation of sparse-view dynamic acquisition for ultra-low dose CT MP imaging. Copyright © 2017 Elsevier B.V. All rights reserved.

High-power all-fiber ultra-low noise laser

NASA Astrophysics Data System (ADS)

Zhao, Jian; Guiraud, Germain; Pierre, Christophe; Floissat, Florian; Casanova, Alexis; Hreibi, Ali; Chaibi, Walid; Traynor, Nicholas; Boullet, Johan; Santarelli, Giorgio

2018-06-01

High-power ultra-low noise single-mode single-frequency lasers are in great demand for interferometric metrology. Robust, compact all-fiber lasers represent one of the most promising technologies to replace the current laser sources in use based on injection-locked ring resonators or multi-stage solid-state amplifiers. Here, a linearly polarized high-power ultra-low noise all-fiber laser is demonstrated at a power level of 100 W. Special care has been taken in the study of relative intensity noise (RIN) and its reduction. Using an optimized servo actuator to directly control the driving current of the pump laser diode, we obtain a large feedback bandwidth of up to 1.3 MHz. The RIN reaches - 160 dBc/Hz between 3 and 20 kHz.

Low-dose estrogen therapy for prevention of osteoporosis: working our way back to monotherapy.

PubMed

Richman, Susan; Edusa, Valentine; Fadiel, Ahmed; Naftolin, Frederick

2006-01-01

The risks of low bone mineral density, osteoporosis and fractures, are major concerns in postmenopausal women. Although postmenopausal hormone therapy is effective for reducing these risks, safety issues have been raised by the results of studies such as the Women's Health Initiative. Although there are scientifically valid reasons to be wary of the general applicability of the Women's Health Initiative findings, the study has underscored the continuing need for research into new forms of menopausal hormone therapy. Low-dose transdermal estrogen monotherapy can preserve bone density while relieving vasomotor symptoms. Transdermal administration may offer advantages, including lack of first-pass liver metabolism, which permits the use of lower doses and avoids a negative impact on the lipid profile. Moreover, a recently published 2-year study of ultra-low-dose transdermal estrogen monotherapy in an older population similar to that of the WHI reported significant increases in bone mineral density, accompanied by significant reductions in markers of bone turnover, with no increased risk of endometrial hyperplasia or other side effects. Additional studies are warranted to shed further light on the possible benefits of low-dose estrogen monotherapy for the prevention of bone loss in postmenopausal women.

Opioid overdose prevention and naloxone rescue kits: what we know and what we don't know.

PubMed

Kerensky, Todd; Walley, Alexander Y

2017-01-07

The opioid use and overdose crisis is persistent and dynamic. Opioid overdoses were initially driven in the 1990s and 2000s by the increasing availability and misuse of prescription opioids. More recently, opioid overdoses are increasing at alarming rates due to wider use of heroin, which in some places is mixed with fentanyl or fentanyl derivatives. Naloxone access for opioid overdose rescue is one of the US Department of Health and Human Services' three priority areas for responding to the opioid crisis. This article summarizes the known benefits of naloxone access and details unanswered questions about overdose education and naloxone rescue kits. Hopefully future research will address these knowledge gaps, improve the effectiveness of opioid overdose education and naloxone distribution programs, and unlock the full promise of naloxone rescue kits.

Knowledge of Opioid Overdose and Attitudes to Supply of Take-Home Naloxone Among People with Chronic Noncancer Pain Prescribed Opioids.

PubMed

Nielsen, Suzanne; Peacock, Amy; Lintzeris, Nicholas; Bruno, Raimondo; Larance, Briony; Degenhardt, Louisa

2018-03-01

Take-home naloxone (THN) is recommended in response to pharmaceutical opioid-related mortality. Some health professionals are reluctant to discuss THN for fear of causing offense. The aims of this study were to assess knowledge of opioid overdose and attitudes toward THN for opioid overdose reversal in people with chronic noncancer pain (CNCP). Prospective cohort study. Australia, September to October 2015. A subset of participants (N = 208) from a cohort of people prescribed restricted opioids for CNCP. Questions added in the two-year telephone interviews examined knowledge of overdose symptoms and attitudes toward community supply of naloxone. Associations with overdose risk factors and naloxone supply eligibility criteria with attitudes toward naloxone were explored. Fourteen percent reported ever experiencing opioid overdose symptoms. Participants correctly identified fewer than half of the overdose signs and symptoms. After receiving information on naloxone, most participants (60%), thought it was a "good" or "very good" idea. Few participants reported that they would be "a little" (N = 21, 10%) or "very" offended (N = 7, 3%) if their opioid prescriber offered them naloxone. Positive attitudes toward THN were associated with male gender (odds ratio [OR] = 1.96, 95% confidence interval [CI] = 1.09-3.50), past year cannabis use (OR = 2.52, 95% CI = 1.03-6.16), and past year nicotine use (OR = 2.11, 95% CI = 1.14-3.91). Most participants had positive attitudes toward THN but low knowledge about opioid overdose symptoms. Strategies for educating patients and their caregivers on opioid toxicity are needed. THN may be best targeted toward those with risk factors in terms of overdose prevention and acceptability.

Ultra-low magnetic damping in metallic and half-metallic systems

NASA Astrophysics Data System (ADS)

Shaw, Justin

The phenomenology of magnetic damping is of critical importance to devices which seek to exploit the electronic spin degree of freedom since damping strongly affects the energy required and speed at which a device can operate. However, theory has struggled to quantitatively predict the damping, even in common ferromagnetic materials. This presents a challenge for a broad range of applications in magnonics, spintronics and spin-orbitronics that depend on the ability to precisely control the damping of a material. I will discuss our recent work to precisely measure the intrinsic damping in several metallic and half-metallic material systems and compare experiment with several theoretical models. This investigation uncovered a metallic material composed of Co and Fe that exhibit ultra-low values of damping that approach values found in thin film YIG. Such ultra-low damping is unexpected in a metal since magnon-electron scattering dominates the damping in conductors. However, this system possesses a distinctive feature in the bandstructure that minimizes the density of states at the Fermi energy n(EF). These findings provide the theoretical framework by which such ultra-low damping can be achieved in metallic ferromagnets and may enable a new class of experiments where ultra-low damping can be combined with a charge current. Half-metallic Heusler compounds by definition have a bandgap in one of the spin channels at the Fermi energy. This feature can also lead to exceptionally low values of the damping parameter. Our results show a strong correlation of the damping with the order parameter in Co2MnGe. Finally, I will provide an overview of the recent advances in achieving low damping in thin film Heusler compounds.

Evaluation of an Ultra-Low Power Reed Solomon Encoder for NASA's Space Technology 5 Mission

NASA Technical Reports Server (NTRS)

Lei, K. E.; Xapsos, M. A.; Poivey, C.; LaBel, K. A.; Stone, R. F.; Yeh, P-S.; Gambles, J.; Hass, J.; Maki, G.; Murguia, J.

2003-01-01

Radiation test results and analyses are presented for ultra-low power Reed Solomon encoder circuits that are being considered for use on the Space Technology 5 (ST5) mission. The total ionizing dose tolerance is in excess of 100 krad(Si) and is due to the low supply voltage and the use of back-bias, which suppresses radiation-induced leakage currents in the n-channel devices. The circuits do not latch-up for ion LET values of at least 90 MeV-sq cm/mg. A hardened-by-design approach to SEU has achieved an upset threshold of about 20 MeV-sq cm/mg. The SEU rate expected for these circuits in the geosynchronous transfer orbit of ST5 is low.

Opioid Overdose Reversal with Naloxone (Narcan, Evzio)

MedlinePlus

... Teens Search Connect with NIDA : Facebook LinkedIn Twitter YouTube Flickr RSS Menu Home Drugs of Abuse Commonly ... and no insurance. Where can I get naloxone? YouTube embedded video: https://www.youtube-nocookie.com/embed/ ...

Morphine, Endogenous Opioid Peptides, and Reproduction in the Male Rhesus Monkey

DTIC Science & Technology

1983-05-18

receptors are both antagonized at high dose levels, while at low doses , naloxone antagonizes only u-receptors (Kosterlitz, 1980). Studies of a...found witli the 20 ug/kg dose . As in the case of testosterone at the same dose , the LH pretreatment levels measured were unusually low (600 ng/dl vs...concentration of the dose of an- tagonist required to reduce agonistic potency by one-half. Due to differences in affinity, naloxone at low dose levels

Background characterization of an ultra-low background liquid scintillation counter

DOE PAGES

Erchinger, J. L.; Orrell, John L.; Aalseth, C. E.; ...

2017-01-26

The Ultra-Low Background Liquid Scintillation Counter developed by Pacific Northwest National Laboratory will expand the application of liquid scintillation counting by enabling lower detection limits and smaller sample volumes. By reducing the overall count rate of the background environment approximately 2 orders of magnitude below that of commercially available systems, backgrounds on the order of tens of counts per day over an energy range of ~3–3600 keV can be realized. Finally, initial test results of the ULB LSC show promising results for ultra-low background detection with liquid scintillation counting.

Ultra-thin smart acoustic metasurface for low-frequency sound insulation

NASA Astrophysics Data System (ADS)

Zhang, Hao; Xiao, Yong; Wen, Jihong; Yu, Dianlong; Wen, Xisen

2016-04-01

Insulating low-frequency sound is a conventional challenge due to the high areal mass required by mass law. In this letter, we propose a smart acoustic metasurface consisting of an ultra-thin aluminum foil bonded with piezoelectric resonators. Numerical and experimental results show that the metasurface can break the conventional mass law of sound insulation by 30 dB in the low frequency regime (<1000 Hz), with an ultra-light areal mass density (<1.6 kg/m2) and an ultra-thin thickness (1000 times smaller than the operating wavelength). The underlying physical mechanism of such extraordinary sound insulation performance is attributed to the infinite effective dynamic mass density produced by the smart resonators. It is also demonstrated that the excellent sound insulation property can be conveniently tuned by simply adjusting the external circuits instead of modifying the structure of the metasurface.

Tribological performance of ultra-low viscosity composite base fluid with bio-derived fluid

USDA-ARS?s Scientific Manuscript database

One obvious approach to increase efficiencies in many lubricated systems such as ICE and gearbox is the reduction in viscosity of oil lubricant. Indeed, ultra-low viscosity engine oils are now commercially available. One approach to the development of ultra-low viscosity lubricants without compromis...

Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria

There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated bymore » naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

Naloxone injections into CA3 disrupt pattern completion associated with relapse from cocaine seeking

PubMed Central

Kirk, Ryan A.; Clark, Jascha K.; Moore, Angela; Keefe, Kristen

2016-01-01

The goal of the present research was to assess the degree to which a pattern completion process operates in cue-induced relapse to cocaine-seeking behavior. Using a novel cue-preference version of the place preference task, rats were administered cocaine or saline, which resulted in a preference for the cocaine-paired cues. After 21 days of abstinence and prior to the preference test, for one group, PBS or naloxone was injected into the CA3 subregion of the hippocampus and for a second group, saline or naloxone was injected systemically. The results indicated that infusions of naloxone into CA3 or systemic injections produced a marked disruption for one and two cues, but had minimal disruptive effect for three or four cues, suggesting that naloxone injections disrupt CA3 function and trigger a deficit in a pattern completion process. Thus, it appears that cue-based activation of the dorsal CA3 might be a critical trigger via a pattern completion process. Based on additional analyses it appears that there is a disruption primarily for object touches for one cue naloxone injections into the CA3 or systemic injections, but no effect on time (spatial context). PMID:26815290

FORMULATING ULTRA-LOW-VOC WOOD FURNITURE COATINGS

EPA Science Inventory

The article discusses the formulation of ultra-low volatile organic compound (VOC) wood furniture coatings. The annual U.S. market for wood coatings is about 240, 000 cu m (63 million gal). In this basis, between 57 and 91 million kg (125 and 200 million lb) of VOCs are emitted i...

Prescription naloxone: a novel approach to heroin overdose prevention.

PubMed

Sporer, Karl A; Kral, Alex H

2007-02-01

The mortality and morbidity from heroin overdose have increased in the United States and internationally in the last decade. The lipid solubility allows the rapid deposition of heroin and its metabolites into the central nervous system and accounts for the "rush" experienced by users and for the toxicity. Risk factors for fatal and nonfatal heroin overdoses such as recent abstinence, decreased opiate tolerance, and polydrug use have been identified. Opiate substitution treatment such as methadone or buprenorphine is the only proven method of heroin overdose prevention. Death from a heroin overdose most commonly occurs 1 to 3 hours after injection at home in the company of other people. Numerous communities have taken advantage of this opportunity for treatment by implementing overdose prevention education to active heroin users, as well as prescribing naloxone for home use. Naloxone is a specific opiate antagonist without agonist properties or potential for abuse. It is inexpensive and nonscheduled and readily reverses the respiratory depression and sedation caused by heroin, as well as causing transient withdrawal symptoms. Program implementation considerations, legal ramifications, and research needs for prescription naloxone are discussed.

Nonprescription naloxone and syringe sales in the midst of opioid overdose and hepatitis C virus epidemics: Massachusetts, 2015.

PubMed

Stopka, Thomas J; Donahue, Ashley; Hutcheson, Marguerite; Green, Traci C

To determine the prevalence of nonprescription naloxone and sterile syringe sales, factors associated with nonprescription sales, geospatial access to nonprescription naloxone and syringe-selling pharmacies, and targets for potential interventions. Cross-sectional study. Massachusetts has experienced steep increases in reported opioid overdoses and hepatitis C virus cases in the past decade. Pharmacists have the potential to play a substantial role in increasing access to nonprescription naloxone and sterile syringes, which can reverse opioid overdoses and decrease hepatitis C virus transmission, respectively. We completed brief telephone surveys with 809 of 1042 retail pharmacies across Massachusetts (response rate = 77.6%) during 2015 to assess experience with nonprescription sales of naloxone and sterile syringes. Our primary outcomes were the stocking and selling of naloxone in the pharmacy (yes or no) for nonprescription sales and nonprescription syringe sales (yes or no). We conducted multivariable regression analyses and created maps using a geographic information system to identify factors associated with nonprescription sales of naloxone and sterile syringes, and to improve our understanding of geospatial access to pharmacy-based naloxone and syringe sales. More than 97% of pharmacies reported selling sterile syringes without requiring a prescription, and 45% of pharmacies reported stocking and selling naloxone. Factors associated with nonprescription sales included hours of operation, experience with and interest in harm reduction activities, and presence in an opioid overdose hotspot. Geographic access to nonprescription sale of sterile syringes is widespread, whereas geospatial access to naloxone is limited. Training to understand the benefits, applications, and distribution needs of naloxone is of interest to surveyed pharmacists. Access to sterile syringes through nonprescription sales is strong across Massachusetts, and although more than 350

Buprenorphine/naloxone treatment practices in Malaysia: Results of national surveys of physicians and patients.

PubMed

Vicknasingam, B; Dazali, M N M; Singh, D; Schottenfeld, R S; Chawarski, M C

2015-07-01

Medication assisted treatment with buprenorphine/naloxone (Bup/Nx), including prescribing and dispensing practices of general practitioners (GPs) in Malaysia and their patients' experiences with this treatment have not been systematically examined. The current study surveyed GPs providing Bup/Nx treatment and patients receiving office-based Bup/Nx treatment in Malaysia. Two cross-sectional surveys of GPs (N=115) providing outpatient Bup/Nx maintenance treatment and of patients (N=253) currently receiving Bup/Nx treatment throughout peninsular Malaysia. Physicians prescribed Bup/Nx dosages in the range of 2-4mg daily for 70% of patients and conducted urine testing in the past month on approximately 16% of their patients. In the patient survey, 79% reported taking daily Bup/Nx doses of 2mg or less; 82% reported that no urine toxicology testing had been conducted on them in the past month, 36% had an opiate positive urine test at the time of the survey, 43% reported illicit opiate use, 15% reported injection of heroin and 22% reported injection of Bup/Nx in the past month. Low daily Bup/Nx doses, lack of behavioral monitoring or counseling, and high rates of continued drug use, including injection of drugs and medications during Bup/Nx treatment in Malaysia, indicate continuing problems with implementation and less than optimal treatment effectiveness. High cost of Bup/Nx in Malaysia may deter patients from seeking treatment and contribute to taking low Bup/Nx dosages. Improved training of physicians and establishing standards for Bup/Nx dosing, routine toxicology testing, and counseling may be needed to improve care and treatment response. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Overdose Education and Naloxone for Patients Prescribed Opioids in Primary Care: A Qualitative Study of Primary Care Staff.

PubMed

Binswanger, Ingrid A; Koester, Stephen; Mueller, Shane R; Gardner, Edward M; Goddard, Kristin; Glanz, Jason M

2015-12-01

The rate of fatal unintentional pharmaceutical opioid poisonings has increased substantially since the late 1990s. Naloxone is an effective opioid antidote that can be prescribed to patients for bystander use in the event of an overdose. Primary care clinics represent settings in which large populations of patients prescribed opioids could be reached for overdose education and naloxone prescription. Our aim was to investigate the knowledge, attitudes and beliefs about overdose education and naloxone prescription among clinical staff in primary care. This was a qualitative study using focus groups to elucidate both clinic-level and provider-level barriers and facilitators. Ten primary care internal medicine, family medicine and infectious disease/HIV practices in three large Colorado health systems. A focus group guide was developed based on behavioral theory. Focus group transcripts were coded for manifest and latent meaning, and analyzed for themes using a recursive approach that included inductive and deductive analysis. Themes emerged in four content areas related to overdose education and naloxone prescription: knowledge, barriers, benefits and facilitators. Clinical staff (N = 56) demonstrated substantial knowledge gaps about naloxone and its use in outpatient settings. They expressed uncertainty about who to prescribe naloxone to, and identified a range of logistical barriers to its use in practice. Staff also described fears about offending patients and concerns about increased risk behaviors in patients prescribed naloxone. When considering naloxone, some providers reflected critically and with discomfort on their own opioid prescribing. These barriers were balanced by beliefs that prescribing naloxone could prevent death and result in safer opioid use behaviors. Findings from these qualitative focus groups may not be generalizable to other settings. In addition to evidence gaps, logistical and attitudinal barriers will need to be addressed to enhance

Ultra Low Energy Binary Decision Diagram Circuits Using Few Electron Transistors

NASA Astrophysics Data System (ADS)

Saripalli, Vinay; Narayanan, Vijay; Datta, Suman

Novel medical applications involving embedded sensors, require ultra low energy dissipation with low-to-moderate performance (10kHz-100MHz) driving the conventional MOSFETs into sub-threshold operation regime. In this paper, we present an alternate ultra-low power computing architecture using Binary Decision Diagram based logic circuits implemented using Single Electron Transistors (SETs) operating in the Coulomb blockade regime with very low supply voltages. We evaluate the energy - performance tradeoff metrics of such BDD circuits using time domain Monte Carlo simulations and compare them with the energy-optimized CMOS logic circuits. Simulation results show that the proposed approach achieves better energy-delay characteristics than CMOS realizations.

Preventing deaths from rising opioid overdose in the US – the promise of naloxone antidote in community-based naloxone take-home programs

PubMed Central

Straus, Michele M; Ghitza, Udi E; Tai, Betty

2013-01-01

The opioid overdose epidemic is an alarming and serious public health problem in the United States (US) that has been escalating for 11 years. The 2011 National Survey on Drug Use and Health (NSDUH) demonstrated that 1 in 20 persons in the US aged 12 or older reported nonmedical use of prescription painkillers in the past year. Prescription drug overdose is now the leading cause of accidental death in the United States – surpassing motor vehicle accidents. Great efforts have been initiated to curb the overdose crisis. Notable examples of these efforts are (1) the Drug Enforcement Administration’s (DEA) National Take-Back Initiative instituted in 2010; (2) the Prescription Drug Monitoring Programs (PDMPs) implemented in most US states to provide practitioners with point-of-care information regarding a patient’s controlled substance use; (3) the naloxone rescue programs initiated in the community to avert mortality resulting from overdose. The use of naloxone rescue strategies has gained traction as an effective measure to prevent fatal opioid overdose. Many US federal-government agencies are working to make these strategies more accessible to first responders and community participants. This new approach faces many challenges, such as accessibility to naloxone and the equipment and training needed to administer it, but none is more challenging than the fear of legal repercussions. US federal-government agencies, local governments, health care institutions, and community-based organizations have begun to tackle these barriers, and naloxone take-home programs have gained recognition as a feasible and sensible preventive strategy to avoid a fatal result from opioid overdose. Although many challenges still need to be overcome, it is important for federal government research agencies to initiate and support independent and rigorous evaluation of these programs to inform policymakers how effective these programs can be to save lives and curb the opioid overdose

Picrotoxin-induced behavioral tolerance and altered susceptibility to seizures: effects of naloxone.

PubMed

Thomas, J; Nores, W L; Pariser, R

1993-07-01

The role of opiate mechanisms in the development of tolerance and altered susceptibility to seizures after repeated injections of picrotoxin was investigated. Independent groups of rats were pretreated with naloxone (0.3, 1.0, 3.0, and 10.0 mg/kg) or the saline vehicle and then tested for seizures induced by picrotoxin. The procedure was performed on 3 days at 1-week intervals, for a total of 3 testing days. Latencies to different types of seizures, the duration of postseizure immobility, and the number of focal seizure episodes were scored. In the vehicle-treated group, repeated picrotoxin injections led to an increased susceptibility to myoclonic and focal seizures and to decreased duration of postseizure immobility. Naloxone pretreatment significantly decreased the duration of the postseizure akinetic periods in the 1.0- and 10.0-mg/kg groups across all days, suggesting that endogenous opiates are involved in postseizure immobility and that there are interactions between opiate and picrotoxin mechanisms in some seizure-related behaviors. Naloxone did not alter the development of tolerance or sensitivity, indicating that naloxone-insensitive opiate mechanisms or nonopiate mechanisms may be involved in these processes.

Ultra-Low-Power MEMS Selective Gas Sensors

NASA Technical Reports Server (NTRS)

Stetter, Joseph

2012-01-01

This innovation is a system for gas sensing that includes an ultra-low-power MEMS (microelectromechanical system) gas sensor, combined with unique electronic circuitry and a proprietary algorithm for operating the sensor. The electronics were created from scratch, and represent a novel design capable of low-power operation of the proprietary MEMS gas sensor platform. The algorithm is used to identify a specific target gas in a gas mixture, making the sensor selective to that target gas.

System and method for magnetic current density imaging at ultra low magnetic fields

DOEpatents

Espy, Michelle A.; George, John Stevens; Kraus, Robert Henry; Magnelind, Per; Matlashov, Andrei Nikolaevich; Tucker, Don; Turovets, Sergei; Volegov, Petr Lvovich

2016-02-09

Preferred systems can include an electrical impedance tomography apparatus electrically connectable to an object; an ultra low field magnetic resonance imaging apparatus including a plurality of field directions and disposable about the object; a controller connected to the ultra low field magnetic resonance imaging apparatus and configured to implement a sequencing of one or more ultra low magnetic fields substantially along one or more of the plurality of field directions; and a display connected to the controller, and wherein the controller is further configured to reconstruct a displayable image of an electrical current density in the object. Preferred methods, apparatuses, and computer program products are also disclosed.

Pharmacokinetics of Sublingual Buprenorphine and Naloxone in Subjects with Mild to Severe Hepatic Impairment (Child-Pugh Classes A, B, and C), in Hepatitis C Virus-Seropositive Subjects, and in Healthy Volunteers.

PubMed

Nasser, Azmi F; Heidbreder, Christian; Liu, Yongzhen; Fudala, Paul J

2015-08-01

Suboxone(®) is a sublingual tablet of buprenorphine/naloxone, approved for the treatment of opioid dependence. The objective of this study was to quantify the impact of hepatic impairment or hepatitis C virus infection on the pharmacokinetics of buprenorphine or naloxone and their major metabolites. Forty-three subjects received a single dose of a Suboxone 2.0/0.5-mg tablet. Blood samples were collected up to 168 h and pharmacokinetic parameters were calculated using non-compartmental analysis. Statistical analysis was performed using analysis of covariance. Pharmacokinetic parameters were derived from 33 subjects. Compared with healthy subjects, for patients with severe hepatic impairment, total and peak exposures increased to 281.4 % [90 % confidence interval 187.1-423.3] and 171.8 % [117.9-250.2] for buprenorphine, 1401.9 % [707.6-2777.5] and 1129.8 % [577.2-2211.4] for naloxone. For moderate hepatic impaired subjects, naloxone total and peak exposure increased to 317.6 % [164.9-611.5] and 270.0  % [141.9-513.9]. For buprenorphine, only total exposure increased to 163.9 % [110.8-242.3]. Changes in maximum observed plasma concentration, area under the plasma concentration-time curve from time zero to time of the last quantifiable concentration, and area under the plasma concentration-time curve from time zero to infinity of buprenorphine or naloxone in subjects with mild hepatic impairment or with hepatitis C virus infection were within twofold of those of healthy subjects. Serious adverse events were not observed. Severe and moderate hepatic impairment significantly increased exposure of naloxone and to a lesser extent of buprenorphine. Therefore, buprenorphine/naloxone combination products should generally be avoided in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment. However, buprenorphine/naloxone products may be used with caution for maintenance treatment in patients with moderate

Neighborhood-Level and Spatial Characteristics Associated with Lay Naloxone Reversal Events and Opioid Overdose Deaths.

PubMed

Rowe, Christopher; Santos, Glenn-Milo; Vittinghoff, Eric; Wheeler, Eliza; Davidson, Peter; Coffin, Philip O

2016-02-01

There were over 23,000 opioid overdose deaths in the USA in 2013, and opioid-related mortality is increasing. Increased access to naloxone, particularly through community-based lay naloxone distribution, is a widely supported strategy to reduce opioid overdose mortality; however, little is known about the ecological and spatial patterns of the distribution and utilization of lay naloxone. This study aims to investigate the neighborhood-level correlates and spatial relationships of lay naloxone distribution and utilization and opioid overdose deaths. We determined the locations of lay naloxone distribution sites and the number of unintentional opioid overdose deaths and reported reversal events in San Francisco census tracts (n = 195) from 2010 to 2012. We used Wilcoxon rank-sum tests to compare census tract characteristics across tracts adjacent and not adjacent to distribution sites and multivariable negative binomial regression models to assess the association between census tract characteristics, including distance to the nearest site, and counts of opioid overdose deaths and naloxone reversal events. Three hundred forty-two opioid overdose deaths and 316 overdose reversals with valid location data were included in our analysis. Census tracts including or adjacent to a distribution site had higher income inequality, lower percentage black or African American residents, more drug arrests, higher population density, more overdose deaths, and more reversal events (all p < 0.05). In multivariable analysis, greater distance to the nearest distribution site (up to a distance of 4000 m) was associated with a lower count of Naloxone reversals [incidence rate ratio (IRR) = 0.51 per 500 m increase, 95% CI 0.39-0.67, p < 0.001] but was not significantly associated with opioid overdose deaths. These findings affirm that locating lay naloxone distribution sites in areas with high levels of substance use and overdose risk facilitates reversals of opioid overdoses in those

Lay responder naloxone access and Good Samaritan law compliance: postcard survey results from 20 Indiana counties.

PubMed

Watson, Dennis P; Ray, Bradley; Robison, Lisa; Huynh, Philip; Sightes, Emily; Walker, La Shea; Brucker, Krista; Duwve, Joan

2018-04-06

To reduce fatal drug overdoses, two approaches many states have followed is to pass laws expanding naloxone access and Good Samaritan protections for lay persons with high likelihood to respond to an opioid overdose. Most prior research has examined attitudes and knowledge among lay responders in large metropolitan areas who actively use illicit substances. The present study addresses current gaps in knowledge related to this issue through an analysis of data collected from a broader group of lay responders who received naloxone kits from 20 local health departments across Indiana. Postcard surveys were included inside naloxone kits distributed in 20 Indiana counties, for which 217 returned cards indicated the person completing it was a lay responder. The survey captured demographic information and experiences with overdose, including the use of 911 and knowledge about Good Samaritan protections. Few respondents had administered naloxone before, but approximately one third had witnessed a prior overdose and the majority knew someone who had died from one. Those who knew someone who had overdosed were more likely to have obtained naloxone for someone other than themselves. Also, persons with knowledge of Good Samaritan protections or who had previously used naloxone were significantly more likely to have indicated calling 911 at the scene of a previously witnessed overdose. Primary reasons for not calling 911 included fear of the police and the person who overdosed waking up on their own. Knowing someone who has had a fatal or non-fatal overdose appears to be a strong motivating factor for obtaining naloxone. Clarifying and strengthening Good Samaritan protections, educating lay persons about these protections, and working to improve police interactions with the public when they are called to an overdose scene are likely to improve implementation and outcomes of naloxone distribution and opioid-related Good Samaritan laws.

Naloxone Distribution and Training for Patients with High-Risk Opioid Use in a Veterans Affairs Community-Based Primary Care Clinic.

PubMed

Raffel, Katie E; Beach, Leila Y; Lin, John; Berchuck, Jacob E; Abram, Shelly; Markle, Elizabeth; Patel, Shalini

2018-03-30

Naloxone distribution has historically been implemented in a community-based, expanded public health model; however, there is now a need to further explore primary care clinic-based naloxone delivery to effectively address the nationwide opioid epidemic. To create a general medicine infrastructure to identify patients with high-risk opioid use and provide 25% of this population with naloxone autoinjector prescription and training within a 6-month period. The quality improvement study was conducted at an outpatient clinic serving 1238 marginally housed veterans with high rates of comorbid substance use and mental health disorders. Patients at high risk of opioid-related adverse events were identified using the Stratification Tool for Opioid Risk Management and were contacted to participate in a one-on-one, 15-minute, hands-on naloxone training led by nursing staff. The number of patients identified at high risk and rates of naloxone training/distribution. There were 67 patients identified as having high-risk opioid use. None of these patients had been prescribed naloxone at baseline. At the end of the intervention, 61 patients (91%) had been trained in the use of naloxone. Naloxone was primarily distributed by licensed vocational nurses (42/61, 69%). This study demonstrates the feasibility of high-risk patient identification and of a primary care-based and nursing-championed naloxone distribution model. This delivery model has the potential to provide access to naloxone to a population of patients with opioid use who may not be engaged in mental health or specialty care.

Naloxone injections into CA3 disrupt pattern completion associated with relapse from cocaine seeking.

PubMed

Kesner, Raymond P; Kirk, Ryan A; Clark, Jascha K; Moore, Angela; Keefe, Kristen

2016-07-01

The goal of the present research was to assess the degree to which a pattern completion process operates in cue-induced relapse to cocaine-seeking behavior. Using a novel cue-preference version of the place preference task, rats were administered cocaine or saline, which resulted in a preference for the cocaine-paired cues. After 21 days of abstinence and prior to the preference test, for one group, PBS or naloxone was injected into the CA3 subregion of the hippocampus and for a second group, saline or naloxone was injected systemically. The results indicated that infusions of naloxone into CA3 or systemic injections produced a marked disruption for one and two cues, but had minimal disruptive effect for three or four cues, suggesting that naloxone injections disrupt CA3 function and trigger a deficit in a pattern completion process. Thus, it appears that cue-based activation of the dorsal CA3 might be a critical trigger via a pattern completion process. Based on additional analyses it appears that there is a disruption primarily for object touches for one cue naloxone injections into the CA3 or systemic injections, but no effect on time (spatial context). © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Extended vs short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial.

PubMed

Woody, George E; Poole, Sabrina A; Subramaniam, Geetha; Dugosh, Karen; Bogenschutz, Michael; Abbott, Patrick; Patkar, Ashwin; Publicker, Mark; McCain, Karen; Potter, Jennifer Sharpe; Forman, Robert; Vetter, Victoria; McNicholas, Laura; Blaine, Jack; Lynch, Kevin G; Fudala, Paul

2008-11-05

The usual treatment for opioid-addicted youth is detoxification and counseling. Extended medication-assisted therapy may be more helpful. To evaluate the efficacy of continuing buprenorphine-naloxone for 12 weeks vs detoxification for opioid-addicted youth. Clinical trial at 6 community programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were randomized to 12 weeks of buprenorphine-naloxone or a 14-day taper (detox). Patients in the 12-week buprenorphine-naloxone group were prescribed up to 24 mg per day for 9 weeks and then tapered to week 12; patients in the detox group were prescribed up to 14 mg per day and then tapered to day 14. All were offered weekly individual and group counseling. Opioid-positive urine test result at weeks 4, 8, and 12. The number of patients younger than 18 years was too small to analyze separately, but overall, patients in the detox group had higher proportions of opioid-positive urine test results at weeks 4 and 8 but not at week 12 (chi(2)(2) = 4.93, P = .09). At week 4, 59 detox patients had positive results (61%; 95% confidence interval [CI] = 47%-75%) vs 58 12-week buprenorphine-naloxone patients (26%; 95% CI = 14%-38%). At week 8, 53 detox patients had positive results (54%; 95% CI = 38%-70%) vs 52 12-week buprenorphine-naloxone patients (23%; 95% CI = 11%-35%). At week 12, 53 detox patients had positive results (51%; 95% CI = 35%-67%) vs 49 12-week buprenorphine-naloxone patients (43%; 95% CI = 29%-57%). By week 12, 16 of 78 detox patients (20.5%) remained in treatment vs 52 of 74 12-week buprenorphine-naloxone patients (70%; chi(2)(1) = 32.90, P < .001). During weeks 1 through 12, patients in the 12-week buprenorphine-naloxone group reported less opioid use (chi(2)(1) = 18.45, P < .001), less injecting (chi(2)(1) = 6.00, P = .01), and less nonstudy addiction treatment (chi(2)(1) = 25.82, P < .001). High levels of opioid use occurred in both groups at follow-up. Four of 83 patients who tested

Baclofen prevents the elevated plus maze behavior and BDNF expression during naloxone precipitated morphine withdrawal in male and female mice.

PubMed

Pedrón, Valeria T; Varani, André P; Balerio, Graciela N

2016-05-01

In previous studies we have shown that baclofen, a selective GABAB receptor agonist, prevents the somatic expression and reestablishes the dopamine and μ-opioid receptors levels, modified during naloxone-precipitated morphine withdrawal syndrome in male and female mice. There are no previous reports regarding sex differences in the elevated plus maze (EPM) and the expression of BDNF in morphine-withdrawn mice. The present study analyses the behavioral and biochemical variations during morphine withdrawal in mice of both sexes, and whether these variations are prevented with baclofen. Swiss-Webster albino prepubertal mice received morphine (2 mg/kg, i.p.) twice daily, for 9 consecutive days. On the 10th day, one group of morphine-treated mice received naloxone (opioid receptor antagonist; 6 mg/kg, i.p.) 1 h after the last dose of morphine to precipitate withdrawal. A second group received baclofen (2 mg/kg, i.p.) before naloxone administration. The EPM behavior was measured during 15 min after naloxone injection. The expression of BDNF-positive cells was determined by immunohistochemistry. Withdrawn male mice showed a higher percentage of time spent and number of entries to the open arms compared to withdrawn female mice. Baclofen prevented this behavior in both sexes. BDNF expression decreased in the AcbC, BNST, CeC, and CA3 of the hippocampus while increased in the BLA of morphine withdrawn male. Baclofen pretreatment prevented the BDNF expression observed in morphine withdrawn male mice in all the brain areas studied except in the CeC. Baclofen prevention of the EPM behavior associated to morphine withdrawal could be partially related to changes in BDNF expression. © 2016 Wiley Periodicals, Inc.

Reducing drug related deaths: a pre-implementation assessment of knowledge,barriers and enablers for naloxone distribution through general practice

PubMed Central

2014-01-01

Background The Scottish Naloxone Programme aims to reduce Scotland’s high number of drug-related deaths (DRDs) caused by opiate overdose. It is currently implemented through specialist drug services but General Practitioners (GPs) are likely to have contact with drug using patients and their families and are therefore in an ideal position to direct them to naloxone schemes, or provide it themselves. This research gathered baseline data on GP’s knowledge of and willingness to be involved in DRD prevention, including naloxone administration, prior to the implementation of primary care based delivery. Methods Mixed methods were used comprising a quantitative, postal survey and qualitative telephone interviews. A questionnaire was sent to 500 GPs across Scotland. An initial mailing was followed by a reminder. A shortened questionnaire containing seven key questions was posted as a final reminder. Telephone interviews were conducted with 17 GPs covering a range of demographic characteristics and drug user experience. Results A response rate of 55% (240/439) was achieved. There was some awareness of the naloxone programme but little involvement (3.3%), 9% currently provided routine overdose prevention, there was little involvement in displaying overdose prevention information (<20%). Knowledge of DRD risk was mixed. There was tentative willingness to be involved in naloxone prescribing with half of respondents willing to provide this to drug users or friends/family. However half were uncertain GP based naloxone provision was essential to reduce DRDs. Factors enabling naloxone distribution were: evidence of effectiveness, appropriate training, and adding to the local formulary. Interviewees had limited awareness of what naloxone distribution in primary care may involve and considered naloxone supply as a specialist service rather than a core GP role. Wider attitudinal barriers to involvement with this group were expressed. Conclusions There was poor awareness of the

Non-Prescription Naloxone and Syringe Sales in the Midst of Opioid Overdose and Hepatitis C Virus Epidemics: Massachusetts, 2015

PubMed Central

Stopka, Thomas J.; Donahue, Ashley; Hutcheson, Marguerite; Green, Traci C.

2017-01-01

Objectives To determine the prevalence of non-prescription naloxone and sterile syringe sales, factors associated with non-prescription sales, geospatial access to non-prescription naloxone and syringe selling pharmacies, and targets for potential interventions. Design Cross-sectional study. Setting and Participants Massachusetts has experienced steep increases in reported opioid overdoses and hepatitis C virus (HCV) cases in the past decade. Pharmacists have the potential to play a substantial role in increasing access to non-prescription naloxone and sterile syringes, which can reverse opioid overdoses and decrease HCV transmission, respectively. We completed brief telephone surveys with 809 of 1,042 retail pharmacies across Massachusetts (response rate=77.6%) during 2015 to assess experience with non-prescription sales of naloxone and sterile syringes. Outcome Measures Our primary outcomes were the stocking and selling of naloxone in the pharmacy (yes/no) for non-prescription sales, and non-prescription syringe sales (yes/no). We conducted multivariable regression analyses and created maps using a geographic information system (GIS) to identify factors associated with non-prescription sales of naloxone and sterile syringes, and to improve our understanding geospatial access to pharmacy-based naloxone and syringe sales. Results Over 97% of pharmacies reported selling sterile syringes without requiring a prescription and 45% of pharmacies reported stocking and selling naloxone. Factors associated with non-prescription sales included: hours of operation, experience with and interest in harm reduction activities, and presence in an opioid overdose hotspot. Geographic access to non-prescription sale of sterile syringes is wide-spread, while geospatial access to naloxone is more limited. Training to better understand the benefits, applications, and distribution needs of naloxone is of interest to surveyed pharmacists. Conclusion Access to sterile syringes through non

Messaging to Increase Public Support for Naloxone Distribution Policies in the United States: Results from a Randomized Survey Experiment.

PubMed

Bachhuber, Marcus A; McGinty, Emma E; Kennedy-Hendricks, Alene; Niederdeppe, Jeff; Barry, Colleen L

2015-01-01

Barriers to public support for naloxone distribution include lack of knowledge, concerns about potential unintended consequences, and lack of sympathy for people at risk of overdose. A randomized survey experiment was conducted with a nationally-representative web-based survey research panel (GfK KnowledgePanel). Participants were randomly assigned to read different messages alone or in combination: 1) factual information about naloxone; 2) pre-emptive refutation of potential concerns about naloxone distribution; and 3) a sympathetic narrative about a mother whose daughter died of an opioid overdose. Participants were then asked if they support or oppose policies related to naloxone distribution. For each policy item, logistic regression models were used to test the effect of each message exposure compared with the no-exposure control group. The final sample consisted of 1,598 participants (completion rate: 72.6%). Factual information and the sympathetic narrative alone each led to higher support for training first responders to use naloxone, providing naloxone to friends and family members of people using opioids, and passing laws to protect people who administer naloxone. Participants receiving the combination of the sympathetic narrative and factual information, compared to factual information alone, were more likely to support all policies: providing naloxone to friends and family members (OR: 2.0 [95% CI: 1.4 to 2.9]), training first responders to use naloxone (OR: 2.0 [95% CI: 1.2 to 3.4]), passing laws to protect people if they administer naloxone (OR: 1.5 [95% CI: 1.04 to 2.2]), and passing laws to protect people if they call for medical help for an overdose (OR: 1.7 [95% CI: 1.2 to 2.5]). All messages increased public support, but combining factual information and the sympathetic narrative was most effective. Public support for naloxone distribution can be improved through education and sympathetic portrayals of the population who stands to benefit from

Naloxone Distribution and Training for Patients with High-Risk Opioid Use in a Veterans Affairs Community-Based Primary Care Clinic

PubMed Central

Raffel, Katie E; Beach, Leila Y; Lin, John; Berchuck, Jacob E; Abram, Shelly; Markle, Elizabeth; Patel, Shalini

2018-01-01

Context Naloxone distribution has historically been implemented in a community-based, expanded public health model; however, there is now a need to further explore primary care clinic-based naloxone delivery to effectively address the nationwide opioid epidemic. Objective To create a general medicine infrastructure to identify patients with high-risk opioid use and provide 25% of this population with naloxone autoinjector prescription and training within a 6-month period. Design The quality improvement study was conducted at an outpatient clinic serving 1238 marginally housed veterans with high rates of comorbid substance use and mental health disorders. Patients at high risk of opioid-related adverse events were identified using the Stratification Tool for Opioid Risk Management and were contacted to participate in a one-on-one, 15-minute, hands-on naloxone training led by nursing staff. Main Outcome Measures The number of patients identified at high risk and rates of naloxone training/distribution. Results There were 67 patients identified as having high-risk opioid use. None of these patients had been prescribed naloxone at baseline. At the end of the intervention, 61 patients (91%) had been trained in the use of naloxone. Naloxone was primarily distributed by licensed vocational nurses (42/61, 69%). Conclusion This study demonstrates the feasibility of high-risk patient identification and of a primary care-based and nursing-championed naloxone distribution model. This delivery model has the potential to provide access to naloxone to a population of patients with opioid use who may not be engaged in mental health or specialty care. PMID:29616917

Diversion and injection of buprenorphine-naloxone film two years post-introduction in Australia.

PubMed

Larance, Briony; Mattick, Richard; Ali, Robert; Lintzeris, Nicholas; Jenkinson, Rebecca; White, Nancy; Kihas, Ivana; Cassidy, Rosemary; Degenhardt, Louisa

2016-01-01

We report 2 years of post-marketing surveillance of the diversion and injection of buprenorphine-naloxone (BNX) film following its introduction in 2011. Interviews were conducted with people who inject drugs regularly (PWID) (2004-2013), opioid substitution therapy clients (2013, n = 492) and key experts (n = 44). Key outcomes were unsanctioned removal of supervised doses, diversion, injection and street price. Prevalence of past 6-month injection among PWID was adjusted for background availability of opioid substitution therapy medications using sales data. Among out-of-treatment PWID, the levels of regular (weekly+) BNX film injection were comparable to methadone and BNX tablets, and lower than mono-buprenorphine, adjusting for background availability. Fewer BNX film clients [3%; 95% (CI) 1-5] regularly injected their medication than mono-buprenorphine clients (25%; 95% CI 11-39), but at levels equivalent to those among methadone (3%; 95% CI 1-6) and BNX tablet clients (2%; 95% CI 0-6). Key experts perceived BNX film needed less supervised dosing time as it dissolved rapidly and was harder to remove from the mouth than sublingual tablets; however, removal of supervised doses was higher among BNX film clients (15%; 95% CI: 10-20) than methadone clients (3%; 95% CI 1-6), and not significantly different from BNX tablet (11%; 95% CI 2-21) and mono-buprenorphine clients (31%; 95% CI 16-46). Two years post-introduction, levels of BNX film diversion and injection remained comparable with those for methadone and BNX tablets, and lower than mono-buprenorphine. We found no evidence that BNX film has lower non-adherence and diversion than the tablet formulation. [Larance B, Mattick R, Ali R, Lintzeris N, Jenkinson R, White N, Kihas I, Cassidy R, Degenhardt L. Diversion and injection of buprenorphine-naloxone film two years post-introduction in Australia. Drug Alcohol Rev 2015]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Noise thermometry at ultra-low temperatures.

PubMed

Rothfuss, D; Reiser, A; Fleischmann, A; Enss, C

2016-03-28

The options for primary thermometry at ultra-low temperatures are rather limited. In practice, most laboratories are using (195)Pt NMR thermometers in the microkelvin range. In recent years, current sensing direct current superconducting quantum interference devices (DC-SQUIDs) have enabled the use of noise thermometry in this temperature range. Such devices have also demonstrated the potential for primary thermometry. One major advantage of noise thermometry is the fact that no driving current is needed to operate the device and thus the heat dissipation within the thermometer can be reduced to a minimum. Ultimately, the intrinsic power dissipation is given by the negligible back action of the readout SQUID. For thermometry in low-temperature experiments, current noise thermometers and magnetic flux fluctuation thermometers have proved to be most suitable. To make use of such thermometers at ultra-low temperatures, we have developed a cross-correlation technique that reduces the amplifier noise contribution to a negligible value. For this, the magnetic flux fluctuations caused by the Brownian motion of the electrons in our noise source are measured inductively by two DC-SQUID magnetometers simultaneously and the signals from these two channels are cross-correlated. Experimentally, we have characterized a thermometer made of a cold-worked high-purity copper cylinder with a diameter of 5 mm and a length of 20 mm for temperatures between 42 μK and 0.8 K. For a given temperature, a measuring time below 1 min is sufficient to reach a precision of better than 1%. The extremely low power dissipation in the thermometer allows continuous operation without heating effects. © 2016 The Author(s).

Sex differences in opioid use and medical issues during buprenorphine/naloxone treatment.

PubMed

Barbosa-Leiker, Celestina; McPherson, Sterling; Layton, Matthew E; Burduli, Ekaterina; Roll, John M; Ling, Walter

2018-01-01

There are sex differences in buprenorphine/naloxone clinical trials for opioid use. While women have fewer opioid-positive urine samples, relative to men, a significant decrease in opioid-positive samples was found during treatment for men, but not women. In order to inform sex-based approaches to improve treatment outcomes, research is needed to determine if opioid use, and predictors of opioid use, differs between men and women during treatment. To test for sex differences in opioid use during a buprenorphine/naloxone clinical trial and determine if sex differences exist in the associations between addiction-related problem areas and opioid use over the course of the trial. This secondary data analysis of the National Drug Abuse Treatment Clinical Trials Network (CTN) 0003 examined sex differences (men = 347, women = 169) in opioid-positive samples in a randomized clinical trial comparing 7-day vs. 28-day buprenorphine/naloxone tapering strategies. Addiction-related problem areas were defined by Addiction Severity-Lite (ASI-L) domain composite scores. Women were more likely than men to use opioids during the course of the buprenorphine/naloxone clinical trial (B = .33, p = .01) and medical issues were positively related to submitting an opioid-positive sample during treatment for women (B = 1.67, p = .01). No ASI-L domain composite score was associated with opioid-positive samples during treatment for men. Women were more likely than men to use opioids during the course of the buprenorphine/naloxone clinical trial, and medical issues predicted opioid use during treatment for women but not men. Complementary treatment for medical problems during opioid replacement therapy may benefit women.

Influence of Ultra-Low-Dose and Iterative Reconstructions on the Visualization of Orbital Soft Tissues on Maxillofacial CT.

PubMed

Widmann, G; Juranek, D; Waldenberger, F; Schullian, P; Dennhardt, A; Hoermann, R; Steurer, M; Gassner, E-M; Puelacher, W

2017-08-01

Dose reduction on CT scans for surgical planning and postoperative evaluation of midface and orbital fractures is an important concern. The purpose of this study was to evaluate the variability of various low-dose and iterative reconstruction techniques on the visualization of orbital soft tissues. Contrast-to-noise ratios of the optic nerve and inferior rectus muscle and subjective scores of a human cadaver were calculated from CT with a reference dose protocol (CT dose index volume = 36.69 mGy) and a subsequent series of low-dose protocols (LDPs I-4: CT dose index volume = 4.18, 2.64, 0.99, and 0.53 mGy) with filtered back-projection (FBP) and adaptive statistical iterative reconstruction (ASIR)-50, ASIR-100, and model-based iterative reconstruction. The Dunn Multiple Comparison Test was used to compare each combination of protocols (α = .05). Compared with the reference dose protocol with FBP, the following statistically significant differences in contrast-to-noise ratios were shown (all, P ≤ .012) for the following: 1) optic nerve: LDP-I with FBP; LDP-II with FBP and ASIR-50; LDP-III with FBP, ASIR-50, and ASIR-100; and LDP-IV with FBP, ASIR-50, and ASIR-100; and 2) inferior rectus muscle: LDP-II with FBP, LDP-III with FBP and ASIR-50, and LDP-IV with FBP, ASIR-50, and ASIR-100. Model-based iterative reconstruction showed the best contrast-to-noise ratio in all images and provided similar subjective scores for LDP-II. ASIR-50 had no remarkable effect, and ASIR-100, a small effect on subjective scores. Compared with a reference dose protocol with FBP, model-based iterative reconstruction may show similar diagnostic visibility of orbital soft tissues at a CT dose index volume of 2.64 mGy. Low-dose technology and iterative reconstruction technology may redefine current reference dose levels in maxillofacial CT. © 2017 by American Journal of Neuroradiology.

Effect of naloxone on the antral motor response to solid food in man.

PubMed

Sharpe, G R; Rees, W D; Adrian, T E; Christofides, N D; Bloom, S R

1987-04-01

Antroduodenal motor activity was recorded in eight healthy subjects using perfused tubes connected to external strain gauge transducers. Each subject was studied over a 2.5-h period following ingestion of a solid meal, on 2 separate days. Intravenous saline was administered on one day and saline plus naloxone (40 micrograms kg-1 h-1) on the other, in randomized order. Naloxone markedly inhibited the antral motor response to food and this effect was due to decreased amplitude and contractile frequency. The duodenal motor response to solid food and the postprandial rise in serum gastrin and plasma pancreatic polypeptide were not altered by naloxone. These observations suggest that peripheral or central opiate receptors play a role in regulating the antral motor response to food.

21 CFR 522.1462 - Naloxone hydrochloride injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Naloxone hydrochloride injection. 522.1462 Section 522.1462 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... antagonist in dogs. (2) It is administered by intravenous, intramuscular, or subcutaneous injection at an...

21 CFR 522.1462 - Naloxone hydrochloride injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Naloxone hydrochloride injection. 522.1462 Section 522.1462 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... antagonist in dogs. (2) It is administered by intravenous, intramuscular, or subcutaneous injection at an...

Ultra-Low Noise Germanium Neutrino Detection system (ULGeN).

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cabrera-Palmer, Belkis; Barton, Paul

Monitoring nuclear power plant operation by measuring the antineutrino flux has become an active research field for safeguards and non-proliferation. We describe various efforts to demonstrate the feasibility of reactor monitoring based on the detection of the Coherent Neutrino Nucleus Scattering (CNNS) process with High Purity Germanium (HPGe) technology. CNNS detection for reactor antineutrino energies requires lowering the electronic noise in low-capacitance kg-scale HPGe detectors below 100 eV as well as stringent reduction in other particle backgrounds. Existing state- of-the-art detectors are limited to an electronic noise of 95 eV-FWHM. In this work, we employed an ultra-low capacitance point-contact detectormore » with a commercial integrated circuit preamplifier- on-a-chip in an ultra-low vibration mechanically cooled cryostat to achieve an electronic noise of 39 eV-FWHM at 43 K. We also present the results of a background measurement campaign at the Spallation Neutron Source to select the area with sufficient low background to allow a successful first-time measurement of the CNNS process.« less

Placebo-mediated, Naloxone-sensitive suggestibility of short-term memory performance.

PubMed

Stern, Jair; Candia, Victor; Porchet, Roseline I; Krummenacher, Peter; Folkers, Gerd; Schedlowski, Manfred; Ettlin, Dominik A; Schönbächler, Georg

2011-03-01

Physiological studies of placebo-mediated suggestion have been recently performed beyond their traditional clinical context of pain and analgesia. Various neurotransmitter systems and immunological modulators have been used in successful placebo suggestions, including Dopamine, Cholecystokinin and, most extensively, opioids. We adhered to an established conceptual framework of placebo research and used the μ-opioid-antagonist Naloxone to test the applicability of this framework within a cognitive domain (e.g. memory) in healthy volunteers. Healthy men (n=62, age 29, SD=9) were required to perform a task-battery, including standardized and custom-designed memory tasks, to test short-term recall and delayed recognition. Tasks were performed twice, before and after intravenous injection of either NaCl (0.9%) or Naloxone (both 0.15 mg/kg), in a double-blind setting. While one group was given neutral information (S-), the other was told that it might receive a drug with suspected memory-boosting properties (S+). Objective and subjective indexes of memory performance and salivary cortisol (as a stress marker) were recorded during both runs and differences between groups were assessed. Short-term memory recall, but not delayed recognition, was objectively increased after placebo-mediated suggestion in the NaCl-group. Naloxone specifically blocked the suggestion effect without interfering with memory performance. These results were not affected when changes in salivary cortisol levels were considered. No reaction time changes, recorded to uncover unspecific attentional impairment, were seen. Placebo-mediated suggestion produced a training-independent, objective and Naloxone-sensitive increase in memory performance. These results indicate an opioid-mediated placebo effect within a circumscribed cognitive domain in healthy volunteers. Copyright © 2011 Elsevier Inc. All rights reserved.

Pain therapy with oxycodone/naloxone prolonged-release combination: case report

PubMed Central

Droń, Aleksandra

2013-01-01

Pain afflicts patients suffering from many chronic diseases and is present in 80% of cases of patients with advanced cancer who suffer from persistent pain. The aim of the pain treatment is to achieve the maximum analgesic effect while minimizing side effects. The main analgesic agent – morphine is unfortunately a therapy associated with gastrointestinal side effects. It appears that the combination of oxycodone and naloxone available as Targin® (Mundipharma) is an alternative. The paper presents a case of a 45-year-old patient who was treated effectively with oxycodone/naloxone prolonged-release tablets. This treatment has proven to be effective in providing pain and constipation control. PMID:24592131

Pain therapy with oxycodone/naloxone prolonged-release combination: case report.

PubMed

Błaszczyk, Feliks; Droń, Aleksandra

2013-01-01

Pain afflicts patients suffering from many chronic diseases and is present in 80% of cases of patients with advanced cancer who suffer from persistent pain. The aim of the pain treatment is to achieve the maximum analgesic effect while minimizing side effects. The main analgesic agent - morphine is unfortunately a therapy associated with gastrointestinal side effects. It appears that the combination of oxycodone and naloxone available as Targin(®) (Mundipharma) is an alternative. The paper presents a case of a 45-year-old patient who was treated effectively with oxycodone/naloxone prolonged-release tablets. This treatment has proven to be effective in providing pain and constipation control.

Responsible Management and Use of a Personal Take-Home Naloxone Supply: A Pilot Project

ERIC Educational Resources Information Center

McAuley, Andrew; Lindsay, George; Woods, Maureen; Louttit, Derek

2010-01-01

Aims: To assess if Scottish drug users, their family and friends could be trained in critical incident management and the safe and effective administration of naloxone. The project also sought to monitor whether drug users can manage their own personal take-home naloxone (THN) supply and use it appropriately in an emergency opiate overdose…

Ultra-low-loss optical fiber nanotapers.

PubMed

Brambilla, Gilberto; Finazzi, Vittoria; Richardson, David

2004-05-17

Optical fiber tapers with a waist size larger than 1microm are commonplace in telecommunications and sensor applications. However the fabrication of low-loss optical fiber tapers with subwavelength diameters was previously thought to be impractical due to difficulties associated with control of the surface roughness and diameter uniformity. In this paper we show that very-long ultra-low-loss tapers can in fact be produced using a conventional fiber taper rig incorporating a simple burner configuration. For single-mode operation, the optical losses we achieve at 1.55microm are one order of magnitude lower than losses previously reported in the literature for tapers of a similar size. SEM images confirm excellent taper uniformity. We believe that these low-loss structures should pave the way to a whole range of fiber nanodevices.

Ultra-low-cost clinical pulse oximetry.

PubMed

Petersen, Christian L; Gan, Heng; MacInnis, Martin J; Dumont, Guy A; Ansermino, J Mark

2013-01-01

An ultra-low-cost pulse oximeter is presented that interfaces a conventional clinical finger sensor with a mobile phone through the headset jack audio interface. All signal processing is performed using the audio subsystem of the phone. In a preliminary volunteer study in a hypoxia chamber, we compared the oxygen saturation obtained with the audio pulse oximeter against a commercially available (and FDA approved) reference pulse oximeter (Nonin Xpod). Good agreement was found between the outputs of the two devices.

Incidence and Demographics of Post-Operative Naloxone Administration: A 13-Year Experience at a Major Tertiary Teaching Institution.

PubMed

Khelemsky, Yury; Kothari, Rishi; Campbell, Neville; Farnad, Shahbaz

2015-01-01

Perioperative use of opioids is associated with the risk of opioid-induced respiratory depression. Naloxone is a competitive opioid antagonist typically administered to reverse opioid-induced respiratory depression. Postoperative administration of naloxone may be considered a proxy for significant postoperative opioid-induced respiratory depression and data regarding its use may be utilized as a quality measure. Few large studies have been done to characterize the population and define an incidence of naloxone recipients in the postoperative inpatient setting. We aimed to characterize the demographics of patients receiving postoperative naloxone, as well as the incidence of administration in the first 72 post-operative hours at a large urban academic medical center in the United States. This is a retrospective cohort study. Major urban tertiary teaching institution. The robust electronic record database of The Department of Anesthesiology at The Icahn School of Medicine at Mount Sinai, as well as the institution's data warehouse were instrumental in allowing almost 450,000 surgical cases performed between 2001 and 2014 to be screened for naloxone administration within the first 72 postoperative hours. Organ harvests, outside of OR intubations, cancelled cases, and patients age less than or equal to 18 were excluded from the total case count. Naloxone was administered 433 times in a total of 442,699 postoperative cases. This yielded an incidence of 0.1%. Additionally, the demographics of the group receiving naloxone were described. The mean age was 60, mean body mass index (BMI) was 27, 60% were women, and the mean American Society of Anesthesiologists (ASA) status was 3. Average time to naloxone administration was 21 hours (standard deviation 7) after surgery. Thirteen percent of the cases were emergent. Breakdown of anesthetic technique revealed that 81% of the cases were performed under general anesthesia, 7% with monitored anesthesia care (MAC), and 12% under

Using compressive measurement to obtain images at ultra low-light-level

NASA Astrophysics Data System (ADS)

Ke, Jun; Wei, Ping

2013-08-01

In this paper, a compressive imaging architecture is used for ultra low-light-level imaging. In such a system, features, instead of object pixels, are imaged onto a photocathode, and then magnified by an image intensifier. By doing so, system measurement SNR is increased significantly. Therefore, the new system can image objects at ultra low-ligh-level, while a conventional system has difficulty. PCA projection is used to collect feature measurements in this work. Linear Wiener operator and nonlinear method based on FoE model are used to reconstruct objects. Root mean square error (RMSE) is used to quantify system reconstruction quality.

Ultra-low Temperature Curable Conductive Silver Adhesive with different Resin Matrix

NASA Astrophysics Data System (ADS)

Zhou, Xingli; Wang, Likun; Liao, Qingwei; Yan, Chao; Li, Xing; Qin, Lei

2018-03-01

The ultra-low temperature curable conductive silver adhesive with curing temperature less than 100 °C needed urgently for the surface conductive treatment of piezoelectric composite material due to the low thermal resistance of composite material and low adhesion strength of adhesive. An ultra-low temperature curable conductive adhesive with high adhesion strength was obtained for the applications of piezoelectric composite material. The microstructure, conductive properties and adhesive properties with different resin matrix were investigated. The conductive adhesive with AG-80 as the resin matrix has the shorter curing time (20min), lower curing temperature (90°C) and higher adhesion strength (7.6MPa). The resistivity of AG-80 sample has the lower value (2.13 × 10-4Ω·cm) than the 618 sample (4.44 × 10-4Ω·cm).

Ultrastructural Study on Ultra-Low Frequency Electromagnetic Fields and Transfer Factor Effects on Skin Ulcers

NASA Astrophysics Data System (ADS)

Cadena, M. S. Reyes; Chapul, L. Sánchez; Pérez, Javiér; García, M. N. Jiménez; López, M. A. Jiménez; Espíndola, M. E. Sánchez; Perez, R. Paniagua; Hernández, N. A.; Paniagua, G.; Uribe, F.; Nava, J. J. Godina; Segura, M. A. Rodríguez

2008-08-01

We determined the effect of 120Hz ultra low frequency electromagnetic field (ELF) on the healing process of skin in 20 Wistar rats distributed in four groups in which chronic dermal ulcers had been produced. The first two groups received a dose of the transfer factor and interferon-beta (IFN-β) every 24 h during 12 days. The third group (positive control) received only electromagnetic field (ELF) sessions, and in the fourth group (negative control), no treatment was applied. The electromagnetic field was applied through a Helmholtz coils; 30 Gauss of intensity. Results shown histological changes that improve the healing process in animals subjected to ELF together with the transfer factor.

Basic and Advanced EMS Providers Are Equally Effective in Naloxone Administration for Opioid Overdose in Northern New England.

PubMed

Gulec, Nazey; Lahey, Joseph; Suozzi, James C; Sholl, Matthew; MacLean, Charles D; Wolfson, Daniel L

2018-01-01

Overdose mortality from illicit and prescription opioids has reached epidemic proportions in the United States, especially in rural areas. Naloxone is a safe and effective agent that has been shown to successfully reverse the effects of opioid overdose in the prehospital setting. The National EMS Scope of Practice Model currently only recommends advanced life support (ALS) providers to administer naloxone; however, some individual states have expanded this scope of practice to include intranasal (IN) administration of naloxone by basic life support (BLS) providers, including the Northern New England states. This study compares the effectiveness and appropriateness of naloxone administration between BLS and ALS providers. All Vermont, New Hampshire, and Maine EMS patient encounters between April 1, 2014 and December 31, 2016 where naloxone was administered were examined and 3,219 patients were identified. The proportion of successful reversals of opioid overdose, based on improvement in the Glasgow Coma Scale (GCS), respiratory rate (RR), and provider global assessment (GA) of response to medication was compared between BLS and ALS providers using a Chi-Squared statistic, Fisher's exact or Wilcoxon rank-sum test. There was no significant difference in the percent improvement in GCS between BLS and ALS (64% and 64% P = 0.94). There was no significant difference in the percentage of improvement in RR between BLS and ALS (45% and 48% P = 0.43). There was a significant difference in the percentage of improvement of GA between BLS and ALS (80% and 67% P < 0.001). There was no significant difference in determining appropriate cases to administer naloxone where RR < 12 and GCS < 15 between BLS and ALS (42% and 43% P = 0.94). BLS providers were as effective as ALS providers in improving patient outcome measures after naloxone administration and in identifying patients for whom administration of naloxone is appropriate. These findings support expanding the National EMS Scope

Feasibility study of SiGHT: a novel ultra low background photosensor for low temperature operation

DOE PAGES

Wang, Y.; Fan, A.; Fiorillo, G.; ...

2017-02-27

Rare event search experiments, such as those searching for dark matter and observations of neutrinoless double beta decay, require ultra low levels of radioactive background for unmistakable identification. In order to reduce the radioactive background of detectors used in these types of event searches, low background photosensors are required, as the physical size of these detectors become increasing larger, and hence the number of such photosensors used also increases rapidly. Considering that most dark matter and neutrinoless double beta decay experiments are turning towards using noble liquids as the target choice, liquid xenon and liquid argon for instance, photosensors thatmore » can work well at cryogenic temperatures are required, 165 K and 87 K for liquid xenon and liquid argon, respectively. The Silicon Geiger Hybrid Tube (SiGHT) is a novel photosensor designed specifically for use in ultra low background experiments operating at cryogenic temperatures. It is based on the proven photocathode plus silicon photomultiplier (SiPM) hybrid technology and consists of very few other, but also ultra radio-pure, materials like fused silica and silicon for the SiPM. Lastly, the introduction of the SiGHT concept, as well as a feasibility study for its production, is reported in this article.« less

Buprenorphine and Buprenorphine/Naloxone Diversion, Misuse, and Illicit Use: An International Review

PubMed Central

Yokell, Michael A.; Zaller, Nickolas D.; Green, Traci C.; Rich, Josiah D.

2011-01-01

The diversion, misuse, and non-medically supervised use of buprenorphine and buprenorphine/naloxone by opioid users are reviewed. Buprenorphine and buprenorphine/naloxone are used globally as opioid analgesics and in the treatment of opioid dependency. Diversion of buprenorphine and buprenorphine/naloxone represents a complex medical and social issue, and has been widely documented in various geographical regions throughout the world. We first discuss the clinical properties of buprenorphine and its abuse potential. Second, we discuss its diversion and illicit use on an international level, as well as motivations for those activities. Third, we examine the medical risks and benefits of buprenorphine’s non-medically supervised use and misuse. These risks and benefits include the effect of buprenorphine’s use on HIV risk and the risk of its concomitant use with other medications and drugs of abuse. Finally, we discuss the implications of diversion, misuse, and non-medically supervised use (including potential measures to address issues of diversion); and potential areas for further research. PMID:21466501

Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scott, Bobby, R., Ph.D.

2003-06-27

OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase one¡¯s risk of cancer.more » Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based

Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence: A Randomized Clinical Noninferiority Trial.

PubMed

Tanum, Lars; Solli, Kristin Klemmetsby; Latif, Zill-E-Huma; Benth, Jurate Šaltyte; Opheim, Arild; Sharma-Haase, Kamni; Krajci, Peter; Kunøe, Nikolaj

2017-12-01

To date, extended-release naltrexone hydrochloride has not previously been compared directly with opioid medication treatment (OMT), currently the most commonly prescribed treatment for opioid dependence. To determine whether treatment with extended-release naltrexone will be as effective as daily buprenorphine hydrochloride with naloxone hydrochloride in maintaining abstinence from heroin and other illicit substances in newly detoxified individuals. A 12-week, multicenter, outpatient, open-label randomized clinical trial was conducted at 5 urban addiction clinics in Norway between November 1, 2012, and December 23, 2015; the last follow-up was performed on October 23, 2015. A total of 232 adult opioid-dependent (per DSM-IV criteria) individuals were recruited from outpatient addiction clinics and detoxification units and assessed for eligibility. Intention-to-treat analyses of efficacy end points were performed with all randomized participants. Randomization to either daily oral flexible dose buprenorphine-naloxone, 4 to 24 mg/d, or extended-release naltrexone hydrochloride, 380 mg, administered intramuscularly every fourth week for 12 weeks. Primary end points (protocol) were the randomized clinical trial completion rate, the proportion of opioid-negative urine drug tests, and number of days of use of heroin and other illicit opioids. Secondary end points included number of days of use of other illicit substances. Safety was assessed by adverse event reporting. Of 159 participants, mean (SD) age was 36 (8.6) years and 44 (27.7%) were women. Eighty individuals were randomized to extended-release naltrexone and 79 to buprenorphine-naloxone; 105 (66.0%) completed the trial. Retention in the extended-release naltrexone group was noninferior to the buprenorphine-naloxone group (difference, -0.1; with 95% CI, -0.2 to 0.1; P = .04), with mean (SD) time of 69.3 (25.9) and 63.7 (29.9) days, correspondingly (P = .33, log-rank test). Treatment with extended

The effect of naloxone and cyproheptadine on pulmonary platelet trapping, hypotension, and platelet aggregability in traumatized dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Almqvist, P.; Kuenzig, M.; Schwartz, S.I.

1983-05-01

Adult respiratory distress syndrome (ARDS) is a serious complication of trauma and sepsis. We have earlier shown naloxone, an opiate antagonist, and cyproheptadine, an antiserotonin drug, to be effective in reducing pulmonary platelet trapping (PPT), which is thought to play an important role in the evolution of ARDS in endotoxin-shocked dogs. Endorphins are implicated as pathophysiologic factors in shock, and serotonin is a possible mediator of their action. The present study shows naloxone and cyproheptadine to be equally effective in protecting against PPT in dogs subjected to trauma, and when naloxone is given before the trauma it also obviates themore » hypotension associated with trauma. In addition, the naloxone- and cyproheptadine-treated animals did not show the increased platelet aggregability usually seen in traumatized dogs.« less

A programmable ultra-low noise X-band exciter.

PubMed

MacMullen, A; Hoover, L R; Justice, R D; Callahan, B S

2001-07-01

A programmable ultra-low noise X-band exciter has been developed using commercial off-the-shelf components. Its phase noise is more than 10 dB below the best available microwave synthesizers. It covers a 7% frequency band with 0.1-Hz resolution. The X-band output at +23 dBm is a combination of signals from an X-band sapphire-loaded cavity oscillator (SLCO), a low noise UHF frequency synthesizer, and special-purpose frequency translation and up-conversion circuitry.

Development of a Low cost Ultra tiny Line Laser Range Sensor

DTIC Science & Technology

2016-12-01

Development of a Low-cost Ultra-tiny Line Laser Range Sensor Xiangyu Chen∗, Moju Zhao∗, Lingzhu Xiang†, Fumihito Sugai∗, Hiroaki Yaguchi∗, Kei Okada...and Masayuki Inaba∗ Abstract— To enable robotic sensing for tasks with require- ments on weight, size, and cost, we develop an ultra-tiny line laser ...view customizable using different laser lenses. The optimal measurement range of the sensor is 0.05[m] ∼ 2[m]. Higher sampling rates can be achieved

Training law enforcement to respond to opioid overdose with naloxone: Impact on knowledge, attitudes, and interactions with community members.

PubMed

Wagner, Karla D; Bovet, L James; Haynes, Bruce; Joshua, Alfred; Davidson, Peter J

2016-08-01

Training law enforcement officers (LEOs) to administer naloxone to opioid overdose victims is increasingly part of comprehensive efforts to reduce opioid overdose deaths. Such efforts could yield positive interactions between LEOs and community members and might ultimately help lower overdose death rates. We evaluated a pilot LEO naloxone program by (1) assessing opioid overdose knowledge and attitudes (competency in responding, concerns about naloxone administration, and attitudes towards overdose victims) before and after a 30min training on overdose and naloxone administration, and (2) conducting qualitative interviews with LEOs who used naloxone to respond to overdose emergencies after the training. Eighty-one LEOs provided pre- and post-training data. Nearly all (89%) had responded to an overdose while serving as an LEO. Statistically significant increases were observed in nearly all items measuring opioid overdose knowledge (p's=0.04 to <0.0001). Opioid overdose competencies (p<0.001) and concerns about naloxone administration (p<0.001) significantly improved after the training, while there was no change in attitudes towards overdose victims (p=0.90). LEOs administered naloxone 11 times; nine victims survived and three of the nine surviving victims made at least one visit to substance abuse treatment as a result of a LEO-provided referral. Qualitative data suggest that LEOs had generally positive experiences when they employed the skills from the training. Training LEOs in naloxone administration can increase knowledge and confidence in managing opioid overdose emergencies. Perhaps most importantly, training LEOs to respond to opioid overdose emergencies may have positive effects for LEOs and overdose victims. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ultra-low field nuclear magnetic resonance and magnetic resonance imaging to discriminate and identify materials

DOEpatents

Kraus, Robert H.; Matlashov, Andrei N.; Espy, Michelle A.; Volegov, Petr L.

2010-03-30

An ultra-low magnetic field NMR system can non-invasively examine containers. Database matching techniques can then identify hazardous materials within the containers. Ultra-low field NMR systems are ideal for this purpose because they do not require large powerful magnets and because they can examine materials enclosed in conductive shells such as lead shells. The NMR examination technique can be combined with ultra-low field NMR imaging, where an NMR image is obtained and analyzed to identify target volumes. Spatial sensitivity encoding can also be used to identify target volumes. After the target volumes are identified the NMR measurement technique can be used to identify their contents.

Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate.

PubMed

Crist, Richard C; Li, James; Doyle, Glenn A; Gilbert, Alex; Dechairo, Bryan M; Berrettini, Wade H

2018-01-01

Currently, no pharmacogenetic tests for selecting an opioid-dependence pharmacotherapy have been approved by the US Food and Drug Administration. Determine the effects of variants in 11 genes on dropout rate and dose in patients receiving methadone or buprenorphine/naloxone (ClinicalTrials.gov Identifier: NCT00315341). Variants in six pharmacokinetic genes (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4) and five pharmacodynamic genes (HTR2A, OPRM1, ADRA2A, COMT, SLC6A4) were genotyped in samples from a 24-week, randomized, open-label trial of methadone and buprenorphine/naloxone for the treatment of opioid dependence (n = 764; 68.7% male). Genotypes were then used to determine the metabolism phenotype for each pharmacokinetic gene. Phenotypes or genotypes for each gene were analyzed for association with dropout rate and mean dose. Genotype for 5-HTTLPR in the SLC6A4 gene was nominally associated with dropout rate when the methadone and buprenorphine/naloxone groups were combined. When the most significant variants associated with dropout rate were analyzed using pairwise analyses, SLC6A4 (5-HTTLPR) and COMT (Val158Met; rs4860) had nominally significant associations with dropout rate in methadone patients. None of the genes analyzed in the study was associated with mean dose of methadone or buprenorphine/naloxone. This study suggests that functional polymorphisms related to synaptic dopamine or serotonin levels may predict dropout rates during methadone treatment. Patients with the S/S genotype at 5-HTTLPR in SLC6A4 or the Val/Val genotype at Val158Met in COMT may require additional treatment to improve their chances of completing addiction treatment. Replication in other methadone patient populations will be necessary to ensure the validity of these findings.

Ibogaine interferes with motivational and somatic effects of naloxone-precipitated withdrawal from acutely administered morphine.

PubMed

Parke, Linda A; Burton, Page; McDonald, Robert V; Kim, Joseph A; Siegel, Shepard

2002-02-01

It has been reported that ibogaine interferes with somatic withdrawal reactions in rats chronically treated with morphine. The present experiments demonstrated that ibogaine also interferes with motivational withdrawal reactions and somatic withdrawal reactions in rats treated with morphine on only two occasions. On each of two conditioning trials, naloxone was administered 24 h following an injection of morphine. Four hours prior to each naloxone administration, rats were injected with either ibogaine or saline. In two experiments, ibogaine interfered with naloxone-precipitated withdrawal. In Experiment 1, ibogaine-treated rats displayed a weaker aversion to the withdrawal-paired chamber, and in Experiment 2, ibogaine-treated rats displayed fewer somatic withdrawal reactions than did saline treated rats.

Optimizing Parameters of Axial Pressure-Compounded Ultra-Low Power Impulse Turbines at Preliminary Design

NASA Astrophysics Data System (ADS)

Kalabukhov, D. S.; Radko, V. M.; Grigoriev, V. A.

2018-01-01

Ultra-low power turbine drives are used as energy sources in auxiliary power systems, energy units, terrestrial, marine, air and space transport within the confines of shaft power N td = 0.01…10 kW. In this paper we propose a new approach to the development of surrogate models for evaluating the integrated efficiency of multistage ultra-low power impulse turbine with pressure stages. This method is based on the use of existing mathematical models of ultra-low power turbine stage efficiency and mass. It has been used in a method for selecting the rational parameters of two-stage axial ultra-low power turbine. The article describes the basic features of an algorithm for two-stage turbine parameters optimization and for efficiency criteria evaluating. Pledged mathematical models are intended for use at the preliminary design of turbine drive. The optimization method was tested at preliminary design of an air starter turbine. Validation was carried out by comparing the results of optimization calculations and numerical gas-dynamic simulation in the Ansys CFX package. The results indicate a sufficient accuracy of used surrogate models for axial two-stage turbine parameters selection

CMOS Ultra Low Power Radiation Tolerant (CULPRiT) Microelectronics

NASA Technical Reports Server (NTRS)

Yeh, Penshu; Maki, Gary

2007-01-01

Space Electronics needs Radiation Tolerance or hardness to withstand the harsh space environment: high-energy particles can change the state of the electronics or puncture transistors making them disfunctional. This viewgraph document reviews the use of CMOS Ultra Low Power Radiation Tolerant circuits for NASA's electronic requirements.

Buprenorphine-naloxone buccal soluble film for the treatment of opioid dependence: current update.

PubMed

Soyka, Michael

2015-02-01

Opioid dependence is a severe medical disorder with a high psychiatric and somatic comorbidity and mortality rate. The opioid agonist methadone, mixed agonist-antagonist buprenorphine and the combination of buprenorphine with the opioid antagonist naloxone are the first-line maintenance treatments for opioid dependence. Risk of diversion and accidental intoxications, especially in children, are of great concern. To lower these risks, a novel buprenorphine-naloxone film has been developed and introduced in the USA and Australia. This review evaluates the available preclinical and clinical data on the novel buprenorphine-naloxone film for treatment of opioid dependence. Literature was identified through a comprehensive PubMed search. Data sources also included official FDA information and material made public by the manufacturer. Few preclinical and clinical data on safety and efficacy have been published. The pharmacological differences between the novel film and the conventional buprenorphine/naloxone are small. In an experimental study, the new formulation suppressed symptoms of opioid withdrawal. The spectrum of adverse events seems to be similar to that of the conventional sublingual tablet. Recent data show that patients prefer the novel film over the conventional sublingual tablet. Emerging surveillance data indicate a lower risk of accidental poisoning in children compared with the conventional formulation. Further clinical and preclinical data are needed to explore additional possible advantages of the new formulation.

Ultrastructural Study on Ultra-Low Frequency Electromagnetic Fields and Transfer Factor Effects on Skin Ulcers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cadena, M. S. Reyes; Chapul, L. Sanchez; Perez, Javier

2008-08-11

We determined the effect of 120Hz ultra low frequency electromagnetic field (ELF) on the healing process of skin in 20 Wistar rats distributed in four groups in which chronic dermal ulcers had been produced. The first two groups received a dose of the transfer factor and interferon-beta (IFN-{beta}) every 24 h during 12 days. The third group (positive control) received only electromagnetic field (ELF) sessions, and in the fourth group (negative control), no treatment was applied. The electromagnetic field was applied through a Helmholtz coils; 30 Gauss of intensity. Results shown histological changes that improve the healing process in animalsmore » subjected to ELF together with the transfer factor.« less

Controlling Low-Rate Signal Path Microdischarge for an Ultra-Low-Background Proportional Counter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mace, Emily K.; Aalseth, Craig E.; Bonicalzi, Ricco

2013-05-01

ABSTRACT Pacific Northwest National Laboratory (PNNL) has developed an ultra-low-background proportional counter (ULBPC) made of high purity copper. These detectors are part of an ultra-low-background counting system (ULBCS) in the newly constructed shallow underground laboratory at PNNL (at a depth of ~30 meters water-equivalent). To control backgrounds, the current preamplifier electronics are located outside the ULBCS shielding. Thus the signal from the detector travels through ~1 meter of cable and is potentially susceptible to high voltage microdischarge and other sources of electronic noise. Based on initial successful tests, commercial cables and connectors were used for this critical signal path. Subsequentmore » testing across different batches of commercial cables and connectors, however, showed unwanted (but still low) rates of microdischarge noise. To control this noise source, two approaches were pursued: first, to carefully validate cables, connectors, and other commercial components in this critical signal path, making modifications where necessary; second, to develop a custom low-noise, low-background preamplifier that can be integrated with the ULBPC and thus remove most commercial components from the critical signal path. This integrated preamplifier approach is based on the Amptek A250 low-noise charge-integrating preamplifier module. The initial microdischarge signals observed are presented and characterized according to the suspected source. Each of the approaches for mitigation is described, and the results from both are compared with each other and with the original performance seen with commercial cables and connectors.« less

Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice.

PubMed

Wu, Xian; Pang, Gang; Zhang, Yong-Mei; Li, Guangwu; Xu, Shengchun; Dong, Liuyi; Stackman, Robert W; Zhang, Gongliang

2015-10-21

Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an α2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Activation of serotonin 5-HT2C receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice

PubMed Central

Li, Guangwu; Xu, Shengchun; Dong, Liuyi; Stackman, Robert W.; Zhang, Gongliang

2015-01-01

Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an α2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction. PMID:26375926

The Acute Administration of the Selective Dopamine D3 Receptor Antagonist SB-277011A Reverses Conditioned Place Aversion Produced by Naloxone Precipitated Withdrawal From Acute Morphine Administration in Rats

PubMed Central

RICE, ONARAE V.; GARDNER, ELIOT L.; HEIDBREDER, CHRISTIAN A.; ASHBY, CHARLES R.

2014-01-01

We examined the effect of SB-277011A, a selective D3 receptor antagonist, on the conditioned place aversion (CPA) response associated with naloxone-induced withdrawal from acute morphine administration in male Sprague-Dawley rats. Morphine (5.6 mg/kg i.p.) was given, followed 4 hrs later by naloxone (0.3 mg/kg i.p.) and prior to placing the animals in one specific chamber of the test apparatus. All animals were subjected to 2 of these trials. A significant CPA occurred in animals that received an i.p. injection of vehicle 30 minutes prior to the measurement of chamber preference. The pretreatment of animals (30 minutes prior to testing) with 3 mg/kg i.p. of SB-277011A did not significantly alter the CPA compared to animals treated with vehicle (1 ml/kg i.p. of deionized distilled water). In contrast, the acute pretreatment of animals with 6, 12 or 24 mg/kg i.p. of SB-277011A significantly decreased the CPA compared to vehicle-treated animals. In fact, the 12 and 24 mg/kg doses of SB-277011A significantly increased the time spent in the chamber where animals were paired with morphine and naloxone. These results suggest that the selective antagonism of D3 receptors attenuates the CPA produced by a model of naloxone-induced withdrawal from acute morphine dependence. PMID:21905128

Ultra-Low Density Organic-Inorganic Composite Materials Possessing Thermally Insulating and Acoustic Damping Properties

DTIC Science & Technology

1992-05-07

Officer. Dr. Kenneth Wynne d. Brief Description of Project- We are investigating the design and synthesis of strong, ultra-low density xerogel and aerogel ...materials of this type would have applications in a broad range of areas including lightweight engine components, high temperature coatings, aircraft wings...we plan to investigate the formation of ultra-low density composites using supercritical universal drying (SCUD) techniques. SiO2 aerogel materials

Working together: Expanding the availability of naloxone for peer administration to prevent opioid overdose deaths in the Australian Capital Territory and beyond.

PubMed

Lenton, Simon; Dietze, Paul; Olsen, Anna; Wiggins, Nicole; McDonald, David; Fowlie, Carrie

2015-07-01

Since the mid-1990s, there have been calls to make naloxone, a prescription-only medicine in many countries, available to heroin and other opioid users and their peers and family members to prevent overdose deaths. In Australia there were calls for a trial of peer naloxone in 2000, yet at the end of that year, heroin availability and harm rapidly declined, and a trial did not proceed. In other countries, a number of peer naloxone programs have been successfully implemented. Although a controlled trial had not been conducted, evidence of program implementation demonstrated that trained injecting drug-using peers and others could successfully administer naloxone to reverse heroin overdose, with few, if any, adverse effects. In 2009 Australian drug researchers advocated the broader availability of naloxone for peer administration in cases of opioid overdose. Industrious local advocacy and program development work by a number of stakeholders, notably by the Canberra Alliance for Harm Minimisation and Advocacy, a drug user organisation, contributed to the rollout of Australia's first prescription naloxone program in the Australian Capital Territory (ACT). Over the subsequent 18 months, prescription naloxone programs were commenced in four other Australian states. The development of Australia's first take-home naloxone program in the ACT has been an 'ice-breaker' for development of other Australian programs. Issues to be addressed to facilitate future scale-up of naloxone programs concern scheduling and cost, legal protections for lay administration, prescribing as a barrier to scale-up; intranasal administration, administration by service providers and collaboration between stakeholders. © 2014 Australasian Professional Society on Alcohol and other Drugs.

Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury.

PubMed

Hochhauser, Edith; Lahat, Eylon; Sultan, Maya; Pappo, Orit; Waldman, Maayan; Sarne, Yosef; Shainberg, Asher; Gutman, Mordechai; Safran, Michal; Ben Ari, Ziv

2015-01-01

Ischemia/reperfusion (I/R) injury is the main cause of both primary graft dysfunction and primary non-function of liver allografts. Cannabinoids has been reported to attenuate myocardial, cerebral and hepatic I/R oxidative injury. Delta-9-tetrahydrocannabinol (THC), a cannabinoid agonist, is the active components of marijuana. In this study we examined the role of ultralow dose THC (0.002mg/kg) in the protection of livers from I/R injury. This extremely low dose of THC was previously found by us to protect the mice brain and heart from a variety of insults. C57Bl Mice were studied in in vivo model of hepatic segmental (70%) ischemia for 60min followed by reperfusion for 6 hours. THC administration 2h prior to the induction of hepatic I/R was associated with significant attenuated elevations of: serum liver transaminases ALT and AST, the hepatic oxidative stress (activation of the intracellular signaling CREB pathway), the acute proinflammatory response (TNF-α, IL-1α, IL-10 and c-FOS hepatic mRNA levels, and ERK signaling pathway activation). This was followed by cell death (the cleavage of the pro-apoptotic caspase 3, DNA fragmentation and TUNEL) after 6 hours of reperfusion. Significantly less hepatic injury was detected in the THC treated I/R mice and fewer apoptotic hepatocytes cells were identified by morphological criteria compared with untreated mice. A single ultralow dose THC can reduce the apoptotic, oxidative and inflammatory injury induced by hepatic I/R injury. THC may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation, liver resection and trauma. © 2015 S. Karger AG, Basel.

Homeless drug users' awareness and risk perception of peer "Take Home Naloxone" use – a qualitative study

PubMed Central

Wright, Nat; Oldham, Nicola; Francis, Katharine; Jones, Lesley

2006-01-01

Background Peer use of take home naloxone has the potential to reduce drug related deaths. There appears to be a paucity of research amongst homeless drug users on the topic. This study explores the acceptability and potential risk of peer use of naloxone amongst homeless drug users. From the findings the most feasible model for future treatment provision is suggested. Methods In depth face-to-face interviews conducted in one primary care centre and two voluntary organisation centres providing services to homeless drug users in a large UK cosmopolitan city. Interviews recorded, transcribed and analysed thematically by framework techniques. Results Homeless people recognise signs of a heroin overdose and many are prepared to take responsibility to give naloxone, providing prior training and support is provided. Previous reports of the theoretical potential for abuse and malicious use may have been overplayed. Conclusion There is insufficient evidence to recommend providing "over the counter" take home naloxone" to UK homeless injecting drug users. However a programme of peer use of take home naloxone amongst homeless drug users could be feasible providing prior training is provided. Peer education within a health promotion framework will optimise success as current professionally led health promotion initiatives are failing to have a positive impact amongst homeless drug users. PMID:17014725

Study on Structural and Dielectric Properties of Ultra-Low-Fire Integratable Dielectric Film for High-Frequency and Microwave Application

NASA Astrophysics Data System (ADS)

Qu, Sheng; Zhang, Jihua; Wu, Kaituo; Wang, Lei; Chen, Hongwei

2018-03-01

In this study, ultra-low-fire ceramic composites of Zn2Te3O8-30 wt.%TiTe3O8 (ZTT) were prepared by a solid-state reaction method. Densified at 600°C, the best microwave dielectric properties at 8.5 GHz were measured with the ɛ r , tan δ, Q × f, and τ f as 25.6, 1.5 × 10-4, 56191 GHz and 1.66 ppm/°C, respectively. Thin films of ultra-low-fire ZTT were prepared by a radio-frequency magnetron sputtering method. ZTT films which deposited on Au/NiCr/SiO2/Si (100) substrates at 200°C showed good adhesion. From ultra-low-fire ceramic to ultra-low-fire ZTT thin films, the latter maintained all the good high-frequency dielectric properties of the former: high dielectric constant ( ɛ r ˜ 25) and low dissipation factor (tan δ < 5×10-3), low leakage current density (˜ 10-9 A/cm2) and ultra low processing temperature. These excellent properties of the ultra-low-fire ZTT thin film make it possible to be integrated in MMIC and be applied in the research of GaN and GaAs MOSFET devices.

Reversal of overdose on fentanyl being illicitly sold as heroin with naloxone nasal spray: A case report.

PubMed

Fareed, Ayman; Buchanan-Cummings, Ann Marie; Crampton, Kelli; Grant, Angela; Drexler, Karen

2015-08-01

This is a case report describing a reversal of fentanyl overdose with naloxone nasal spray. The patient was not aware that he overdosed on fentanyl being sold as heroin. The Veterans Health Administration (VHA) has implemented an initiative to provide education for veterans, their families, friends and significant others about opioid overdose and use of naloxone reversal kits. The Atlanta VA Medical Center adopted this program to reduce the risk of opioid overdose in high risk patients. Over the past year, we provided educational sessions for 63 veterans and their families. We also prescribed 41 naloxone kits. We have received three reports of opioid overdose reversal with use of naloxone kits prescribed by the Atlanta VA Medical Center. The authors recommend that public health administrators and policy makers advocate for the implementation of these programs to reduce the rising number of overdose death in the United States and worldwide. © American Academy of Addiction Psychiatry.

Energy deposition evaluation for ultra-low energy electron beam irradiation systems using calibrated thin radiochromic film and Monte Carlo simulations.

PubMed

Matsui, S; Mori, Y; Nonaka, T; Hattori, T; Kasamatsu, Y; Haraguchi, D; Watanabe, Y; Uchiyama, K; Ishikawa, M

2016-05-01

For evaluation of on-site dosimetry and process design in industrial use of ultra-low energy electron beam (ULEB) processes, we evaluate the energy deposition using a thin radiochromic film and a Monte Carlo simulation. The response of film dosimeter was calibrated using a high energy electron beam with an acceleration voltage of 2 MV and alanine dosimeters with uncertainty of 11% at coverage factor 2. Using this response function, the results of absorbed dose measurements for ULEB were evaluated from 10 kGy to 100 kGy as a relative dose. The deviation between the responses of deposit energy on the films and Monte Carlo simulations was within 15%. As far as this limitation, relative dose estimation using thin film dosimeters with response function obtained by high energy electron irradiation and simulation results is effective for ULEB irradiation processes management.

EVALUATING AND DESIGNING ULTRA-LOW-COST SOLAR WATER HEATING SYSTEMS

EPA Science Inventory

This project will have three key outputs:

1. an evaluation of the thermal performance of ultra-low-cost solar components, with components being characterized by their absorbed solar energy per cost;
2. a built demonstration prototype of...

3. Ultra Low Temperature Instrumentation for Measurements in Astrophysics : ULTIMA

   DOE Office of Scientific and Technical Information (OSTI.GOV)

   Bunkov, Yu. M.; Elbs, J.; Godfrin, H.

   2006-09-07

   This paper reviews recent advances in particle detection using superfluid 3He at ultra-low temperature about 100 {mu}K, for application in large detector project ULTIMA for the search of non-baryonic Dark Matter. The unique advantages of 3He, and in particular of its superfluid state, for Dark Matter search are highlighted.

4. Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses

   PubMed Central

   Colborn, Theo; Hayes, Tyrone B.; Heindel, Jerrold J.; Jacobs, David R.; Lee, Duk-Hee; Shioda, Toshi; Soto, Ana M.; vom Saal, Frederick S.; Welshons, Wade V.; Zoeller, R. Thomas

   2012-01-01

   For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health. PMID:22419778

5. HIV testing and sexual risk reduction counseling in office-based buprenorphine/naloxone treatment.

   PubMed

   Edelman, E Jennifer; Moore, Brent A; Caffrey, Sarah; Sikkema, Kathleen J; Jones, Emlyn S; Schottenfeld, Richard S; Fiellin, David A; Fiellin, Lynn E

   2013-01-01

   We assessed the feasibility and preliminary efficacy of human immunodeficiency virus (HIV) testing with sexual risk reduction counseling for opioid-dependent patients initiating office-based buprenorphine/naloxone treatment. We conducted a 14-week randomized, controlled trial with 30 patients (original target of 114) assigned to receive buprenorphine/naloxone induction/stabilization and HIV testing with Brief Sexual Risk Management (BSRM) or Enhanced Sexual Risk Management (ESRM). We evaluated process measures and compared outcomes at baseline and during the 3-month follow-up. Similar proportions of patients receiving BSRM and ESRM underwent HIV testing (93% vs 80%; P = 0.28) and completed counseling sessions (80% vs 67%; P = 0.40). Brief Sexual Risk Management sessions were shorter than ESRM sessions (15.4 vs 23.4 minutes), with comparable manual adherence (P = 0.80). Outcomes did not vary by BSRM versus ESRM. Although the recruitment of opioid-dependent patients with sexual risk behaviors is challenging, HIV testing with sexual risk reduction counseling in office-based buprenorphine/naloxone treatment practice is feasible. Interventions to decrease sexual risk behaviors among a segment of this population are necessary.

6. Naloxone for heroin, prescription opioid, and illicitly made fentanyl overdoses: Challenges and innovations responding to a dynamic epidemic.

   PubMed

   Fairbairn, Nadia; Coffin, Phillip O; Walley, Alexander Y

   2017-08-01

   Community-based overdose prevention programs first emerged in the 1990's and are now the leading public health intervention for overdose. Key elements of these programs are overdose education and naloxone distribution to people who use opioids and their social networks. We review the evolution of naloxone programming through the heroin overdose era of the 1990's, the prescription opioid era of the 2000's, and the current overdose crisis stemming from the synthetic opioid era of illicitly manufactured fentanyl and its analogues in the 2010's. We present current challenges arising in this new era of synthetic opioids, including variable potency of illicit drugs due to erratic adulteration of the drug supply with synthetic opioids, potentially changing efficacy of standard naloxone formulations for overdose rescue, potentially shorter overdose response time, and reports of fentanyl exposure among people who use drugs but are opioid naïve. Future directions for adapting naloxone programming to the dynamic opioid epidemic are proposed, including scale-up to new venues and social networks, new standards for post-overdose care, expansion of supervised drug consumption services, and integration of novel technologies to detect overdose and deliver naloxone. Copyright © 2017 Elsevier B.V. All rights reserved.

7. Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke.

   PubMed

   Anderson, Craig S; Robinson, Thompson; Lindley, Richard I; Arima, Hisatomi; Lavados, Pablo M; Lee, Tsong-Hai; Broderick, Joseph P; Chen, Xiaoying; Chen, Guofang; Sharma, Vijay K; Kim, Jong S; Thang, Nguyen H; Cao, Yongjun; Parsons, Mark W; Levi, Christopher; Huang, Yining; Olavarría, Verónica V; Demchuk, Andrew M; Bath, Philip M; Donnan, Geoffrey A; Martins, Sheila; Pontes-Neto, Octavio M; Silva, Federico; Ricci, Stefano; Roffe, Christine; Pandian, Jeyaraj; Billot, Laurent; Woodward, Mark; Li, Qiang; Wang, Xia; Wang, Jiguang; Chalmers, John

   2016-06-16

   Thrombolytic therapy for acute ischemic stroke with a lower-than-standard dose of intravenous alteplase may improve recovery along with a reduced risk of intracerebral hemorrhage. Using a 2-by-2 quasi-factorial open-label design, we randomly assigned 3310 patients who were eligible for thrombolytic therapy (median age, 67 years; 63% Asian) to low-dose intravenous alteplase (0.6 mg per kilogram of body weight) or the standard dose (0.9 mg per kilogram); patients underwent randomization within 4.5 hours after the onset of stroke. The primary objective was to determine whether the low dose would be noninferior to the standard dose with respect to the primary outcome of death or disability at 90 days, which was defined by scores of 2 to 6 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]). Secondary objectives were to determine whether the low dose would be superior to the standard dose with respect to centrally adjudicated symptomatic intracerebral hemorrhage and whether the low dose would be noninferior in an ordinal analysis of modified Rankin scale scores (testing for an improvement in the distribution of scores). The trial included 935 patients who were also randomly assigned to intensive or guideline-recommended blood-pressure control. The primary outcome occurred in 855 of 1607 participants (53.2%) in the low-dose group and in 817 of 1599 participants (51.1%) in the standard-dose group (odds ratio, 1.09; 95% confidence interval [CI], 0.95 to 1.25; the upper boundary exceeded the noninferiority margin of 1.14; P=0.51 for noninferiority). Low-dose alteplase was noninferior in the ordinal analysis of modified Rankin scale scores (unadjusted common odds ratio, 1.00; 95% CI, 0.89 to 1.13; P=0.04 for noninferiority). Major symptomatic intracerebral hemorrhage occurred in 1.0% of the participants in the low-dose group and in 2.1% of the participants in the standard-dose group (P=0.01); fatal events occurred within 7 days in 0.5% and 1.5%, respectively

8. The Implementation of Buprenorphine/Naloxone in College Health Practice

   ERIC Educational Resources Information Center

   DeMaria, Peter A., Jr.; Patkar, Ashwin A.

   2008-01-01

   Opiate abuse and dependence have become important concerns for college healthcare providers. The passage of the Drug Addiction Treatment Act of 2000 and the approval of the combination buprenorphine/naloxone for office-based treatment of opiate dependence have increased the options available for college students and their healthcare providers. The…

9. Multidisciplinary European Low Dose Initiative (MELODI): strategic research agenda for low dose radiation risk research.

   PubMed

   Kreuzer, M; Auvinen, A; Cardis, E; Durante, M; Harms-Ringdahl, M; Jourdain, J R; Madas, B G; Ottolenghi, A; Pazzaglia, S; Prise, K M; Quintens, R; Sabatier, L; Bouffler, S

   2018-03-01

   MELODI (Multidisciplinary European Low Dose Initiative) is a European radiation protection research platform with focus on research on health risks after exposure to low-dose ionising radiation. It was founded in 2010 and currently includes 44 members from 18 countries. A major activity of MELODI is the continuous development of a long-term European Strategic Research Agenda (SRA) on low-dose risk for radiation protection. The SRA is intended to identify priorities for national and European radiation protection research programs as a basis for the preparation of competitive calls at the European level. Among those key priorities is the improvement of health risk estimates for exposures close to the dose limits for workers and to reference levels for the population in emergency situations. Another activity of MELODI is to ensure the availability of European key infrastructures for research activities, and the long-term maintenance of competences in radiation research via an integrated European approach for training and education. The MELODI SRA identifies three key research topics in low dose or low dose-rate radiation risk research: (1) dose and dose rate dependence of cancer risk, (2) radiation-induced non-cancer effects and (3) individual radiation sensitivity. The research required to improve the evidence base for each of the three key topics relates to three research lines: (1) research to improve understanding of the mechanisms contributing to radiogenic diseases, (2) epidemiological research to improve health risk evaluation of radiation exposure and (3) research to address the effects and risks associated with internal exposures, differing radiation qualities and inhomogeneous exposures. The full SRA and associated documents can be downloaded from the MELODI website ( http://www.melodi-online.eu/sra.html ).

10. The Low-Mass Stellar Initial Mass Function: Ultra-Faint Dwarf Galaxies Revisited

    NASA Astrophysics Data System (ADS)

    Platais, Imants

    2017-08-01

    The stellar Initial Mass Function plays a critical role in the evolution of the baryonic content of the Universe. The form of the low-mass IMF - stars of mass less than the solar mass - determines the fraction of baryons locked up for a Hubble time, and thus indicates how gas and metals are cycled through galaxies. Inferences from resolved stellar populations, where the low-mass luminosity function and associated IMF can be derived from direct star counts, generally favor an invariant and universal IMF. However, a recent study of ultra-faint dwarf galaxies Hercules and Leo IV indicates a bottom-lite IMF, over a narrow range of stellar mass (only 0.55-0.75 M_sun), correlated with the internal velocity dispersion and/or metallicity. We propose to obtain ultra-deep imaging for a significantly closer ultra-faint dwarf, Bootes I, which will allow us to construct the luminosity function down to M_v=+10 (equivalent to 0.35 solar mass). We will also re-analyze the HST archival observations for the Hercules and Leo IV dwarfs using the same updated techniques as for Bootes I. The combined datasets should provide a reliable answer to the question of how variable is the low-mass stellar IMF.

11. Comparison of the cardiovascular effects of meptazinol and naloxone following haemorrhagic shock in rats and cats.

    PubMed Central

    Chance, E.; Paciorek, P. M.; Todd, M. H.; Waterfall, J. F.

    1985-01-01

    The cardiovascular effects of the opioid mixed agonist-antagonist, meptazinol, and the opioid antagonist, naloxone, have been evaluated in conscious rats, anaesthetized rats and anaesthetized cats following the induction of haemorrhagic shock. The mean arterial pressure of conscious rats decreased by 17-29 mmHg following a haemorrhage of 20% of blood volume. Meptazinol (17 mg kg-1, i.m.) administered after haemorrhage evoked a rapid and sustained increase in mean arterial pressure to pre-haemorrhage levels. Naloxone (10 mg kg-1, i.v.) also increased mean arterial pressure to a level significantly higher than post-haemorrhage values. Neither haemorrhage nor subsequent drug treatments evoked significant changes in the heart rates of conscious rats. In anaesthetized rats, 20% haemorrhage evoked decreases in mean arterial pressure, heart rate and cardiac output. Blood flow to the heart, skin, skeletal muscle, kidneys, spleen and liver (arterial) was decreased. Meptazinol and naloxone increased blood pressure and total peripheral resistance, but did not significantly alter heart rate or cardiac output. Hepatic arterial flow decreased further in both drug and vehicle treated groups. In addition meptazinol slightly reduced skeletal muscle flow. In anaesthetized cats 40% haemorrhage decreased mean arterial pressure by 46 +/- 3 mmHg. An intravenous infusion of either meptazinol or naloxone (cumulative 2 mg kg-1, i.v.) partially restored blood pressure. In experimental animal models of haemorrhagic shock, meptazinol has a similar cardiovascular profile to naloxone. The established analgesic activity of meptazinol may confer an advantage in some shock states. PMID:4052729

12. Energy deposition evaluation for ultra-low energy electron beam irradiation systems using calibrated thin radiochromic film and Monte Carlo simulations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Matsui, S., E-mail: smatsui@gpi.ac.jp; Mori, Y.; Nonaka, T.

    2016-05-15

    For evaluation of on-site dosimetry and process design in industrial use of ultra-low energy electron beam (ULEB) processes, we evaluate the energy deposition using a thin radiochromic film and a Monte Carlo simulation. The response of film dosimeter was calibrated using a high energy electron beam with an acceleration voltage of 2 MV and alanine dosimeters with uncertainty of 11% at coverage factor 2. Using this response function, the results of absorbed dose measurements for ULEB were evaluated from 10 kGy to 100 kGy as a relative dose. The deviation between the responses of deposit energy on the films andmore » Monte Carlo simulations was within 15%. As far as this limitation, relative dose estimation using thin film dosimeters with response function obtained by high energy electron irradiation and simulation results is effective for ULEB irradiation processes management.« less

An ultra low power ECG signal processor design for cardiovascular disease detection.

PubMed

Jain, Sanjeev Kumar; Bhaumik, Basabi

2015-08-01

This paper presents an ultra low power ASIC design based on a new cardiovascular disease diagnostic algorithm. This new algorithm based on forward search is designed for real time ECG signal processing. The algorithm is evaluated for Physionet PTB database from the point of view of cardiovascular disease diagnosis. The failed detection rate of QRS complex peak detection of our algorithm ranges from 0.07% to 0.26% for multi lead ECG signal. The ASIC is designed using 130-nm CMOS low leakage process technology. The area of ASIC is 1.21 mm(2). This ASIC consumes only 96 nW at an operating frequency of 1 kHz with a supply voltage of 0.9 V. Due to ultra low power consumption, our proposed ASIC design is most suitable for energy efficient wearable ECG monitoring devices.

Effects of phenazepam on the behavior of C57BL/6 and BALB/c mice in the open field test after naloxone pretreatment.

PubMed

Seredenin, S B; Nadorova, A V; Kolik, L G; Yarkova, M A

2013-07-01

We studied the effects of phenazepam (0.075 mg/kg) after pretreatment (5 minutes before) with naloxone (10 mg/kg) on open-field behavior of C57Bl/6 and BALB/c mice. In ex vivo experiments, we studied the effects of naloxone (1 and 10 mg/kg) on receptor binding of [(3)H]-flunitrazepam by membranes of brain fraction (P1+P2) of C57Bl/6 and BALB/c mice. It was shown that naloxone increased motor activity in the open field in BALB/c mice and decreased this parameter in C57Bl/6 mice. During combined treatment, naloxone potentiated the activating effects of phenazepam on the open-field behavior of BALB/c mice and slightly increased the sedative effect of this drug in C57Bl/6 mice. Naloxone stimulated reception of [(3)H]-flunitrazepam in BALB/c mice and slightly increased radioligand binding in C57Bl/6 mice. These data attest to enhanced reception in benzodiazepine site of GABAA-receptor under conditions of opioid receptor blockade, the presence of anxiolytic or sedative (depending on the phenotype of the response to emotional stress) effect of naloxone, and co-directed effects of naloxone and benzodiazepine tranquilizer on open-field behavior of C57Bl/6 and BALB/c mice.

ULTRA-LOW POWER CO2 SENSOR FOR INTELLIGENT BUILDING CONTROL - PHASE I

EPA Science Inventory

The proposed EPA SBIR Phase I program will create a novel ultra-low power and low-cost microfabricated CO₂ sensor. The initial developments of sensor technology will serve the very large Demand Controlled Ventilation market that has been identified by KWJ and its...

Facilitators and Barriers to Naloxone Kit Use Among Opioid-Dependent Patients Enrolled in Medication Assisted Therapy Clinics in North Carolina.

PubMed

Khatiwoda, Prasana; Proeschold-Bell, Rae Jean; Meade, Christina S; Park, Lawrence P; Proescholdbell, Scott

2018-01-01

BACKGROUND Naloxone-an opioid antagonist that reverses the effects of opioids-is increasingly being distributed in non-medical settings. We sought to identify the facilitators of, and barriers to, opioid users using naloxone kits in North Carolina. METHODS In 2015, we administered a 15-item survey to a convenience sample of 100 treatment seekers at 4 methadone/buprenorphine Medication Assisted Therapy (MAT) clinics in North Carolina. RESULTS Seventy-four percent of participants reported having ever gotten a naloxone kit; this percentage was higher for females (81%) than males (63%) ( P = .06). The primary reason given for not having a kit was not knowing where to get one. Only 6% had heard of kits from the media and only 5% received one from a medical provider. Among kit recipients, 56% of both females and males reported mostly or sometimes carrying the kit, with additional participants reporting always. Reasons for not carrying a kit were no longer being around drugs, forgetting it, and the kit being too large. Men discussed the difficulties of carrying the naloxone kits, which are currently too large to fit in a pocket. Ninety-four percent of naloxone users reported intending to call emergency services in case of an overdose emergency. LIMITATIONS Study limitations included a small sample, participants limited to MAT clinics, and a predominantly white sample. CONCLUSIONS MAT treatment seekers reported a willingness to carry and use naloxone kits. Education, outreach, media, and medical providers need to promote naloxone kits. A smaller kit may increase the likelihood of men carrying one. ©2018 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.

Economic method for measuring ultra-low flow rates of fluids

NASA Technical Reports Server (NTRS)

Bogdanovic, J. A.; Keller, W. F.

1970-01-01

Capillary tube flowmeter measures ultra-low flows of very corrosive fluids /such as chlorine trifluoride and liquid fluorine/ and other liquids with reasonable accuracy. Flowmeter utilizes differential pressure transducer and operates on the principle that for laminar flow in the tube, pressure drop is proportional to flow rate.

Memantine improves buprenorphine/naloxone treatment for opioid dependent young adults.

PubMed

Gonzalez, Gerardo; DiGirolamo, Gregory; Romero-Gonzalez, Mauricio; Smelson, David; Ziedonis, Douglas; Kolodziej, Monika

2015-11-01

Opioid use disorders are considered a serious public health problem among young adults. Current treatment is limited to long-term opioid substitution therapy, with high relapse rates after discontinuation. This study evaluated the co-administration of memantine to brief buprenorphine pharmacotherapy as a treatment alternative. 13-week double-blind placebo-controlled trial evaluating 80 young adult opioid dependent participants treated with buprenorphine/naloxone 16-4mg/day and randomized to memantine (15mg or 30mg) or placebo. Primary outcomes were a change in the weekly mean proportion of opioid use, and cumulative abstinence rates after rapid buprenorphine discontinuation on week 9. Treatment retention was not significantly different between groups. The memantine 30mg group was significantly less likely to relapse and to use opioids after buprenorphine discontinuation. Among participants abstinent on week 8, those in the memantine 30mg group (81.9%) were significantly less likely to relapse after buprenorphine was discontinued compared to the placebo group (30%) (p<0.025). Also, the memantine 30mg group had significantly reduced opioid use (mean=0, SEM±0.00) compared to the placebo group (mean=0.33, SEM±0.35; p<0.004) during the last 2 weeks of study participation. Memantine 30mg significantly improved short-term treatment with buprenorphine/naloxone for opioid dependent young adults by reducing relapse and opioid use after buprenorphine discontinuation. Combined short-term treatment with buprenorphine/naloxone may be an effective alternative treatment to long-term methadone or buprenorphine maintenance in young adults. Published by Elsevier Ireland Ltd.

GRABGAM Analysis of Ultra-Low-Level HPGe Gamma Spectra

DOE Office of Scientific and Technical Information (OSTI.GOV)

Winn, W.G.

The GRABGAM code has been used successfully for ultra-low level HPGe gamma spectrometry analysis since its development in 1985 at Savannah River Technology Center (SRTC). Although numerous gamma analysis codes existed at that time, reviews of institutional and commercial codes indicated that none addressed all features that were desired by SRTC. Furthermore, it was recognized that development of an in-house code would better facilitate future evolution of the code to address SRTC needs based on experience with low-level spectra. GRABGAM derives its name from Gamma Ray Analysis BASIC Generated At MCA/PC.

"Once I'd done it once it was like writing your name": Lived experience of take-home naloxone administration by people who inject drugs.

PubMed

McAuley, Andrew; Munro, Alison; Taylor, Avril

2018-05-23

The supply of naloxone, the opioid antagonist, for peer administration ('take-home naloxone' (THN)) has been promoted as a means of preventing opioid-related deaths for over 20 years. Despite this, little is known about PWID experiences of take-home naloxone administration. The aim of this study was to advance the evidence base on THN by producing one of the first examinations of the lived-experience of THN use among PWID. Qualitative, face to face, semi-structured interviews were undertaken at a harm reduction service with individuals known to have used take-home naloxone in an overdose situation in a large urban area in Scotland. Interpretative Phenomenological Analysis (IPA) was then applied to the data from these in-depth accounts. The primary analysis involved a total of 8 PWID (seven male, one female) known to have used take-home naloxone. This paper focuses on the two main themes concerning naloxone administration: psychological impacts of peer administration and role perceptions. In the former, the feelings participants encounter at different stages of their naloxone experience, including before, during and after use, are explored. In the latter, the concepts of role legitimacy, role adequacy, role responsibility and role support are considered. This study demonstrates that responding to an overdose using take-home naloxone is complex, both practically and emotionally, for those involved. Although protocols exist, a multitude of individual, social and environmental factors shape responses in the short and longer terms. Despite these challenges, participants generally conveyed a strong sense of therapeutic commitment to using take-home naloxone in their communities. Copyright © 2018 Elsevier B.V. All rights reserved.

Assessing the Risk of Prehospital Administration of Naloxone with Subsequent Refusal of Care.

PubMed

Levine, Michael; Sanko, Stephen; Eckstein, Marc

2016-01-01

EMS providers frequently encounter opioid-toxic patients who receive naloxone and then refuse further medical care. Older studies revealed this practice to be safe. In light of the evolving patterns of opioid abuse, this study attempted to determine the safety of this practice. This is a retrospective review of all patient encounters by the Los Angeles Fire Department (LAFD) between July 1, 2011-December 31, 2013. All LAFD patient encounters are stored electronically. These electronic records were reviewed for subjects who received naloxone had a documented respiratory rate (RR) less than 12, and subsequently refused transport. Data abstracted included name, social security number (SSN), date of birth (DOB), date of EMS encounter, age, and treatment rendered. The names, SSN, and DOB, as available, were supplied to the coroner's office. The Coroner's records were reviewed to determine if a patient with the same or similar name (e.g., Jon vs. Jonathan) had died within 24 hours, 30 days, or 6 months of the initial EMS encounter. The abstractor was blinded to the study hypothesis. 205 subjects were identified; the median (IQR) age was 41 (29-53) years. 27 (13%) were female. One subject (0.49%) died within 24 hours of the initial EMS encounter. The cause of death (COD) was coronary artery disease and heroin use. Two additional subjects (1. %) died within 30 days. One of these subjects died 6 days later; the COD is unknown. The other subject died 20 days after the EMS encounter; the COD was cardiovascular disease and liver cirrhosis. No additional subjects were identified at the 6 month follow up. A third subject died of a heroin overdose 16 months after the initial EMS encounter, but was beyond the pre-defined follow up period. The practice of receiving pre-hospital naloxone by paramedics and subsequently refusing care is associated with an extremely low short- and intermediate-term mortality. Despite an evolving pattern of opioid abuse, the results of this study

Ultra-low noise supercontinuum source for ultra-high resolution optical coherence tomography at 1300 nm

NASA Astrophysics Data System (ADS)

Gonzalo, I. B.; Maria, M.; Engelsholm, R. D.; Feuchter, T.; Leick, L.; Moselund, P. M.; Podoleanu, A.; Bang, O.

2018-02-01

Supercontinuum (SC) sources are of great interest for many applications due to their ultra-broad optical bandwidth, good beam quality and high power spectral density [1]. In particular, the high average power over large bandwidths makes SC light sources excellent candidates for ultra-high resolution optical coherence tomography (UHR-OCT) [2-5]. However, conventional SC sources suffer from high pulse-to-pulse intensity fluctuations as a result of the noise-sensitive nonlinear effects involved in the SC generation process [6-9]. This intensity noise from the SC source can limit the performance of OCT, resulting in a reduced signal-to-noise ratio (SNR) [10-12]. Much work has been done to reduce the noise of the SC sources for instance with fiber tapers [7,8] or increasing the repetition rate of the pump laser for averaging in the spectrometer [10,12]. An alternative approach is to use all-normal dispersion (ANDi) fibers [13,14] to generate SC light from well-known coherent nonlinear processes [15-17]. In fact, reduction of SC noise using ANDi fibers compared to anomalous dispersion SC pumped by sub-picosecond pulses has been recently demonstrated [18], but a cladding mode was used to stabilize the ANDi SC. In this work, we characterize the noise performance of a femtosecond pumped ANDi based SC and a commercial SC source in an UHR-OCT system at 1300 nm. We show that the ANDi based SC presents exceptional noise properties compared to a commercial source. An improvement of 5 dB in SNR is measured in the UHR-OCT system, and the noise behavior resembles that of a superluminiscent diode. This preliminary study is a step forward towards development of an ultra-low noise SC source at 1300 nm for ultra-high resolution OCT.

International Workshop on Neuroimmunomodulation (2nd) Held in Dubrovnik (Yugoslavia) on 1-6 June 1986.

DTIC Science & Technology

1986-09-18

systemically with doses of reaction) were sharply reduced. Histo- naltrexone or naloxone and subsequently logically, the infiltration of the dermis...challenged with a lethal dose of antigen. with polymorphonuclear (Arthus reaction) Both naloxone and naltrexone were found and mononuclear cells (delayed...for Integrative Biomedical Research, Eb- roendocrine cell type present in low num- matingen, Switzerland) reported on the bers in the spleen, lymph

Intra-arterial Ultra-low-Dose CT Angiography of Lower Extremity in Diabetic Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Özgen, Ali, E-mail: draliozgen@hotmail.com; Sanioğlu, Soner; Bingöl, Uğur Anıl

2016-08-15

PurposeTo image lower extremity arteries by CT angiography using a very low-dose intra-arterial contrast medium in patients with high risk of developing contrast-induced nephropathy (CIN).Materials and MethodsThree cases with long-standing diabetes mellitus and signs of lower extremity atherosclerotic disease were evaluated by CT angiography using 0.1 ml/kg of the body weight of contrast medium given via 10-cm-long 4F introducer by puncturing the CFA. Images were evaluated by an interventional radiologist and a cardiovascular surgeon. Density values of the lower extremity arteries were also calculated. Findings in two cases were compared with digital subtraction angiography images performed for percutaneous revascularization. Blood creatininemore » levels were followed for possible CIN.ResultsIntra-arterial CT angiography images were considered diagnostic in all patients and optimal in one patient. No patient developed CIN after intra-arterial CT angiography, while one patient developed CIN after percutaneous intervention.ConclusionIntra-arterial CT angiography of lower extremity might be performed in selected patients with high risk of developing CIN. Our limited experience suggests that as low as of 0.1 ml/kg of the body weight of contrast medium may result in adequate diagnostic imaging.« less

Seizure and electroencephalographic changes in the newborn period induced by opiates and corrected by naloxone infusion.

PubMed

da Silva, O; Alexandrou, D; Knoppert, D; Young, G B

1999-03-01

To describe the association between opioid administration in the newborn period and neurologic abnormalities. Case reports of two infants who presented with seizure activity and abnormal electroencephalograms associated with opiate administration, and reversed by naloxone. The first was a preterm infant who developed a burst-suppression pattern on the electroencephalogram while receiving a continuous infusion of morphine and muscle paralysis. Naloxone injection during the electroencephalogram recording reversed the burst-suppression pattern. The second was a term infant receiving fentanyl infusion for pain control following surgery, who presented with motor seizure that was only partially controlled with barbiturates. An abnormal electroencephalogram recording during the opiate infusion improved with naloxone administration. Our observations indicate a potential for neurologic abnormalities, including induction of seizure activity and electroencephalogram abnormalities, suggesting caution when opiates are used for sedation and/or pain control in the newborn period.

Low-dose morphine elicits ventilatory excitant and depressant responses in conscious rats: Role of peripheral μ-opioid receptors.

PubMed

Henderson, Fraser; May, Walter J; Gruber, Ryan B; Young, Alex P; Palmer, Lisa A; Gaston, Benjamin; Lewis, Stephen J

2013-08-01

The systemic administration of morphine affects ventilation via a mixture of central and peripheral actions. The aims of this study were to characterize the ventilatory responses elicited by a low dose of morphine in conscious rats; to determine whether tolerance develops to these responses; and to determine the potential roles of peripheral μ-opioid receptors (μ-ORs) in these responses. Ventilatory parameters were monitored via unrestrained whole-body plethysmography. Conscious male Sprague-Dawley rats received an intravenous injection of vehicle or the peripherally-restricted μ-OR antagonist, naloxone methiodide (NLXmi), and then three successive injections of morphine (1 mg/kg) given 30 min apart. The first injection of morphine in vehicle-treated rats elicited an array of ventilatory excitant (i.e., increases in frequency of breathing, minute volume, respiratory drive, peak inspiratory and expiratory flows, accompanied by decreases in inspiratory time and end inspiratory pause) and inhibitory (i.e., a decrease in tidal volume and an increase in expiratory time) responses. Subsequent injections of morphine elicited progressively and substantially smaller responses. The pattern of ventilatory responses elicited by the first injection of morphine was substantially affected by pretreatment with NLXmi whereas NLXmi minimally affected the development of tolerance to these responses. Low-dose morphine elicits an array of ventilatory excitant and depressant effects in conscious rats that are subject to the development of tolerance. Many of these initial actions of morphine appear to involve activation of peripheral μ-ORs whereas the development of tolerance to these responses does not.

A low power cryocooled autonomous ultra-stable oscillator

NASA Astrophysics Data System (ADS)

Fluhr, C.; Dubois, B.; Grop, S.; Paris, J.; Le Tetû, G.; Giordano, V.

2016-12-01

We present the design and the preliminary evaluation of a cryostat equipped with a low power pulse-tube cryocooler intended to maintain near 5 K a high-Q factor sapphire microwave resonator. This cooled resonator constitutes the frequency reference of an ultra-stable oscillator presenting a short term fractional frequency stability of better than 1 ×10-15 . The proposed design enables to reach a state-of-the-art frequency stability with a cryogenic oscillator consuming only 3 kW of electrical power.

Ultra-low-power conversion and management techniques for thermoelectric energy harvesting applications

NASA Astrophysics Data System (ADS)

Fleming, Jerry W.

2010-04-01

Thermoelectric energy harvesting has increasingly gained acceptance as a potential power source that can be used for numerous commercial and military applications. However, power electronic designers have struggled to incorporate energy harvesting methods into their designs due to the relatively small voltage levels available from many harvesting device technologies. In order to bridge this gap, an ultra-low input voltage power conversion method is needed to convert small amounts of scavenged energy into a usable form of electricity. Such a method would be an enabler for new and improved medical devices, sensor systems, and other portable electronic products. This paper addresses the technical challenges involved in ultra-low-voltage power conversion by providing a solution utilizing novel power conversion techniques and applied technologies. Our solution utilizes intelligent power management techniques to control unknown startup conditions. The load and supply management functionality is also controlled in a deterministic manner. The DC to DC converter input operating voltage is 20mV with a conversion efficiency of 90% or more. The output voltage is stored into a storage device such as an ultra-capacitor or lithium-ion battery for use during brown-out or unfavorable harvesting conditions. Applications requiring modular, low power, extended maintenance cycles, such as wireless instrumentation would significantly benefit from the novel power conversion and harvesting techniques outlined in this paper.

From Evidence to Policy: The Scottish National Naloxone Programme

ERIC Educational Resources Information Center

McAuley, Andrew; Best, David; Taylor, Avril; Hunter, Carole; Robertson, Roy

2012-01-01

Drug-related death (DRD) is a major public health problem globally, with rates in Scotland higher than any other UK region and among the highest in Europe. One of the most important public health interventions to emerge aimed at tackling rising DRD rates is the distribution of naloxone, the opioid antagonist, for peer administration. The Scottish…

The effects of meptazinol in comparison with pentazocine, morphine and naloxone in a rat model of anaphylactic shock.

PubMed Central

Paciorek, P. M.; Todd, M. H.; Waterfall, J. F.

1985-01-01

The actions of meptazinol, pentazocine, morphine and naloxone on the cardiovascular changes accompanying anaphylactic shock were evaluated in ovalbumin-sensitized anaesthetized rats. Pretreatment with meptazinol and pentazocine prevented the fall in mean arterial pressure associated with antigen challenge, whereas morphine and naloxone attenuated but did not completely prevent, this change. None of the drugs significantly altered the antigen-induced decreases in heart rate. All the drugs partially reversed the fall in mean arterial pressure when given after antigen challenge although the activity of naloxone was less marked. Pretreatment with reserpine prevented the restoration of blood pressure by all drugs. Additional experiments with meptazinol showed that pretreatment with phentolamine prevented its pressor action. In pithed non-sensitized rats the frequency-pressor response curve to splanchnic stimulation was shifted to the left by meptazinol and shifted to the right by pentazocine, but the changes were small Morphine and naloxone had no significant effects. It was concluded that opioid mixed agonist-antagonists reverse the cardiovascular changes associated with anaphylactic shock. These effects appear to be mediated by facilitation of sympathetic neurotransmission. PMID:3978318

The effects of meptazinol in comparison with pentazocine, morphine and naloxone in a rat model of anaphylactic shock.

PubMed

Paciorek, P M; Todd, M H; Waterfall, J F

1985-02-01

The actions of meptazinol, pentazocine, morphine and naloxone on the cardiovascular changes accompanying anaphylactic shock were evaluated in ovalbumin-sensitized anaesthetized rats. Pretreatment with meptazinol and pentazocine prevented the fall in mean arterial pressure associated with antigen challenge, whereas morphine and naloxone attenuated but did not completely prevent, this change. None of the drugs significantly altered the antigen-induced decreases in heart rate. All the drugs partially reversed the fall in mean arterial pressure when given after antigen challenge although the activity of naloxone was less marked. Pretreatment with reserpine prevented the restoration of blood pressure by all drugs. Additional experiments with meptazinol showed that pretreatment with phentolamine prevented its pressor action. In pithed non-sensitized rats the frequency-pressor response curve to splanchnic stimulation was shifted to the left by meptazinol and shifted to the right by pentazocine, but the changes were small Morphine and naloxone had no significant effects. It was concluded that opioid mixed agonist-antagonists reverse the cardiovascular changes associated with anaphylactic shock. These effects appear to be mediated by facilitation of sympathetic neurotransmission.

Effect of Diluent on Ultra-low Temperature Curable Conductive Silver Adhesive

NASA Astrophysics Data System (ADS)

Zhou, Xingli; Wang, Likun; Liao, Qingwei; Yan, Chao; Du, Haibo; Qin, Lei

2018-03-01

The ultra-low temperature curable conductive silver adhesive needed urgently for the surface conductive treatment of piezoelectric composite material. The effect of diluent acetone on ultra-low temperature curable conductive silver adhesive were investigated for surface conductive treatment of piezoelectric composite material. In order to improve the operability and extend the life of the conductive adhesive, the diluent was added to dissolve and disperse conductive adhesive. With the increase of the content of diluent, the volume resistivity of conductive adhesive decreased at first and then increased, and the shear strength increased at first and then decreased. When the acetone content is 10%, the silver flaky bonded together, arranged the neatest, the smallest gap, the most closely connected, the surface can form a complete conductive network, and the volume resistivity is 2.37 × 10-4Ω · cm, the shear strength is 5.13MPa.

Radon Exposure and the Definition of Low Doses-The Problem of Spatial Dose Distribution.

PubMed

Madas, Balázs G

2016-07-01

Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses.

Cryogenic ultra-low-noise SiGe transistor amplifier.

PubMed

Ivanov, B I; Trgala, M; Grajcar, M; Il'ichev, E; Meyer, H-G

2011-10-01

An ultra-low-noise one-stage SiGe heterojunction bipolar transistor amplifier was designed for cryogenic temperatures and a frequency range of 10 kHz-100 MHz. A noise temperature T(N) ≈ 1.4 K was measured at an ambient temperature of 4.2 K at frequencies between 100 kHz and 100 MHz for a source resistance of ~50 Ω. The voltage gain of the amplifier was 25 dB at a power consumption of 720 μW. The input voltage noise spectral density of the amplifier is about 35 pV/√Hz. The low noise resistance and power consumption makes the amplifier suitable for readout of resistively shunted DC SQUID magnetometers and amplifiers.

Survival of tumor cells after proton irradiation with ultra-high dose rates

PubMed Central

2011-01-01

Background Laser acceleration of protons and heavy ions may in the future be used in radiation therapy. Laser-driven particle beams are pulsed and ultra high dose rates of >109 Gy s-1may be achieved. Here we compare the radiobiological effects of pulsed and continuous proton beams. Methods The ion microbeam SNAKE at the Munich tandem accelerator was used to directly compare a pulsed and a continuous 20 MeV proton beam, which delivered a dose of 3 Gy to a HeLa cell monolayer within < 1 ns or 100 ms, respectively. Investigated endpoints were G2 phase cell cycle arrest, apoptosis, and colony formation. Results At 10 h after pulsed irradiation, the fraction of G2 cells was significantly lower than after irradiation with the continuous beam, while all other endpoints including colony formation were not significantly different. We determined the relative biological effectiveness (RBE) for pulsed and continuous proton beams relative to x-irradiation as 0.91 ± 0.26 and 0.86 ± 0.33 (mean and SD), respectively. Conclusions At the dose rates investigated here, which are expected to correspond to those in radiation therapy using laser-driven particles, the RBE of the pulsed and the (conventional) continuous irradiation mode do not differ significantly. PMID:22008289

Analysis and Design of Rotors at Ultra-Low Reynolds Numbers

NASA Technical Reports Server (NTRS)

Kunz, Peter J.; Strawn, Roger C.

2003-01-01

Design tools have been developed for ultra-low Reynolds number rotors, combining enhanced actuator-ring / blade-element theory with airfoil section data based on two-dimensional Navier-Stokes calculations. This performance prediction method is coupled with an optimizer for both design and analysis applications. Performance predictions from these tools have been compared with three-dimensional Navier Stokes analyses and experimental data for a 2.5 cm diameter rotor with chord Reynolds numbers below 10,000. Comparisons among the analyses and experimental data show reasonable agreement both in the global thrust and power required, but the spanwise distributions of these quantities exhibit significant deviations. The study also reveals that three-dimensional and rotational effects significantly change local airfoil section performance. The magnitude of this issue, unique to this operating regime, may limit the applicability of blade-element type methods for detailed rotor design at ultra-low Reynolds numbers, but these methods are still useful for evaluating concept feasibility and rapidly generating initial designs for further analysis and optimization using more advanced tools.

Findings of a Naloxone Database and its Utilization to Improve Safety and Education in a Tertiary Care Medical Center.

PubMed

Rosenfeld, David M; Betcher, Jeffrey A; Shah, Ruby A; Chang, Yu-Hui H; Cheng, Meng-Ru; Cubillo, Efrain I; Griffin, Julia M; Trentman, Terrence L

2016-03-01

Analyzing hospital naloxone use may assist in identification of areas for quality and safety improvement. Our primary objective is to quantitate the incidence of hospital naloxone use and to assess certain patient populations at risk. During the years 2008 to 2011, each clinical scenario where naloxone was administered on an in-patient care ward was reviewed. The events were assessed to separate situations where naloxone rescue was effective in reversing opioid-induced intoxication vs. others. Further analysis was conducted to stratify patient populations at greatest risk. Naloxone was administered for well-defined opioid-induced respiratory depression and oversedation 61% of the time, the remainder used for patient deterioration of other etiology. Surgical populations are at risk with an incidence of 3.8/1,000 hospitalized patients, and this is the greatest within 24 hours of surgery. General surgical patients represent the highest surgical patient risk at 5.5/1,000. Medical patients represent lower risk at 2.0/1,000. Patients with patient-controlled analgesia and epidural opioid infusion are high risk at 12.1 and 13.1/1,000 patients, respectively. Many quality and safety interventions were gradually implemented in response to this data and are summarized. These include nursing and provider education, electronic medical record modification, and more stringent patient monitoring practices. Examination of naloxone use can assist in the identification and stratification of patients at risk for opioid-induced respiratory depression and oversedation and can serve as a driver for improvements in hospital patient safety. This information can also guide other institutions interested in similar improvements. © 2015 World Institute of Pain.

Study of ultra-low emittance design for SPEAR3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, M. -H.; Huang, X.; Safranek, J.

2015-09-17

Since its 2003 construction, the SPEAR3 synchrotron light source at SLAC has continuously improved its performance by raising beam current, top-off injection, and smaller emittance. This makes SPEAR3 one of the most productive light sources in the world. Now, to further enhance the performance of SPEAR3, we are looking into the possibility of converting SPEAR3 to an ultra-low emittance storage ring within its site constraint.

Design of nodes for embedded and ultra low-power wireless sensor networks

NASA Astrophysics Data System (ADS)

Xu, Jun; You, Bo; Cui, Juan; Ma, Jing; Li, Xin

2008-10-01

Sensor network integrates sensor technology, MEMS (Micro-Electro-Mechanical system) technology, embedded computing, wireless communication technology and distributed information management technology. It is of great value to use it where human is quite difficult to reach. Power consumption and size are the most important consideration when nodes are designed for distributed WSN (wireless sensor networks). Consequently, it is of great importance to decrease the size of a node, reduce its power consumption and extend its life in network. WSN nodes have been designed using JN5121-Z01-M01 module produced by jennic company and IEEE 802.15.4/ZigBee technology. Its new features include support for CPU sleep modes and a long-term ultra low power sleep mode for the entire node. In low power configuration the node resembles existing small low power nodes. An embedded temperature sensor node has been developed to verify and explore our architecture. The experiment results indicate that the WSN has the characteristic of high reliability, good stability and ultra low power consumption.

Ultra-low current biosensor output detection using portable electronic reader

NASA Astrophysics Data System (ADS)

Yahaya, N. A. N.; Rajapaksha, R. D. A. A.; Uda, M. N. Afnan; Hashim, U.

2017-09-01

Generally, the electrical biosensor usually shows extremely low current signal output around pico ampere to microampere range. In this research, electronic reader with amplifier has been demonstrated to detect ultra low current via the biosensor. The operational amplifier Burr-Brown OPA 128 and Arduino Uno board were used to construct the portable electronic reader. There are two cascaded inverting amplifier were used to detect ultra low current through the biosensor from pico amperes (pA) to nano amperes ranges (nA). A small known input current was form by applying variable voltage between 0.1V to 5.0V across a 5GΩ high resistor to check the amplifier circuit. The amplifier operation was measured with the high impedance current source and has been compared with the theoretical measurement. The Arduino Uno was used to convert the analog signal to digital signal and process the data to display on reader screen. In this project, Proteus software was used to design and test the circuit. Then it was implemented together with Arduino Uno board. Arduino board was programmed using C programming language to make whole circuit communicate each order. The current was measured then it shows a small difference values compared to theoretical values, which is approximately 14pA.

Role of vagal afferents in the ventilatory response to naloxone during loaded breathing in the rabbit.

PubMed

Delpierre, S; Pugnat, C; Duté, N; Jammes, Y

1995-02-15

It was previously shown that inspiratory resistive loading (IRL) increases the cerebrospinal fluid (CSF) level of beta endorphin in awake goats, and also that the slower ventilation induced by injection of this substance into the CSF of anesthetized dogs is suppressed after vagotomy. In the present study, performed on anesthetized rabbits, we evaluated the part played by vagal afferents in the ventilatory response to IRL after opioid receptor blockade by naloxone. During unloaded breathing, naloxone injection did not modify baseline ventilation. Conversely, naloxone partially reversed IRL-induced hypoventilation through an increase in respiratory rate. This effect was abolished after either vagotomy or cold blockade of large vagal fibers, but it persisted after procaine blockade of thin vagal fibers. These results suggest that pulmonary stretch receptors, which are connected to some large vagal afferent fibers, would play a major role in the ventilatory response to IRL under opioid receptor inhibition.

[Reparative Osteogenesis and Angiogenesis in Low Intensity Electromagnetic Radiation of Ultra-High Frequency].

PubMed

Iryanov, Y M; Kiryanov, N A

2015-01-01

Non-drug correction of reparative bone tissue regeneration in different pathological states - one of the most actual problems of modern medicine. Our aim was to conduct morphological analysis of the influence of electromagnetic radiation of ultra-high frequency and low intensity on reparative osteogenesis and angiogenesis in fracture treatment under transosseous osteosynthesis. A controlled nonrandomized study was carried out. In the experiment conducted on rats we modeled tibial fracture with reposition and fixation of the bone fragments both in control and experimental groups. In the animals of the experimental group the fracture zone was exposed to low intensity electromagnetic radiation of ultra-high frequency. Exposure simulation was performed in the control group. The operated bones were examined using radiography, light and electronic microscopy, X-ray electronic probe microanalysis. It has been established that electromagnetic radiation of ultra-high frequency sessions in fracture treatment stimulate secretory activity and degranulation of mast cells, produce microcirculatory bed vascular permeability increase, endotheliocyte migration phenotype expression, provide endovascular endothelial outgrowth formation, activate reparative osteogenesis and angiogenesis while fracture reparation becomes the one of the primary type. The full periosteal, intermediary and intraosteal bone union was defined in 28 days. Among the therapeutic benefits of electromagnetic radiation of ultra-high frequency in fracture treatment we can detect mast cell secretorv activity stimulation and endovascular anziozenesis activation.

Development of Ultra-Low-Noise TES Bolometer Arrays

NASA Astrophysics Data System (ADS)

Suzuki, T.; Khosropanah, P.; Ridder, M. L.; Hijmering, R. A.; Gao, J. R.; Akamatsu, H.; Gottardi, L.; van der Kuur, J.; Jackson, B. D.

2016-07-01

SRON is developing ultra-low-noise transition edge sensors (TESs) based on a superconducting Ti/Au bilayer on a suspended SiN island with SiN legs for SAFARI aboard SPICA. We have two major concerns about realizing TESs with an ultra-low NEP of 2× 10^{-19} hbox {W}/√{{ {Hz}}}: achieving lower thermal conductance and no excess noise with respect to the phonon noise. To realize TESs with phonon-noise-limited NEPs, we need to make thinner ({<}0.25 \\upmu hbox {m}) and narrower ({<}1 \\upmu hbox {m}) SiN legs. With deep reactive-ion etching, three types of TESs were fabricated in combination with different SiN island sizes and the presence or absence of an optical absorber. Those TESs have a thin (0.20 \\upmu hbox {m}), narrow (0.5-0.7 \\upmu hbox {m}), and long (340-460 \\upmu hbox {m}) SiN legs and show Tc of {˜ }93 hbox {mK} and Rn of {˜ }158 hbox {m}{Ω }. These TESs were characterized under AC bias using our frequency-division multiplexing readout (1-3 MHz) system. TESs without the absorber show NEPs as low as 1.1 × 10^{-19} hbox {W}/√{{ {Hz}}} with a reasonable response speed ({<}1 hbox {ms}), which achieved the phonon noise limit. For TESs with the absorber, we confirmed a higher hbox {NEP}_{el} ({˜ }5 × 10^{-19} hbox {W}/√{{ {Hz}}}) than that of TESs without the absorber likely due to stray light. The lowest NEP can make the new version of SAFARI with a grating spectrometer feasible.

Ultra-Low-Power Cryogenic SiGe Low-Noise Amplifiers: Theory and Demonstration

NASA Astrophysics Data System (ADS)

Montazeri, Shirin; Wong, Wei-Ting; Coskun, Ahmet H.; Bardin, Joseph C.

2016-01-01

Low-power cryogenic low-noise amplifiers (LNAs) are desired to ease the cooling requirements of ultra-sensitive cryogenically cooled instrumentation. In this paper, the tradeoff between power and noise performance in silicon-germanium LNAs is explored to study the possibility of operating these devices from low supply voltages. A new small-signal heterojunction bipolar transistor noise model applicable to both the forward-active and saturation regimes is developed from first principles. Experimental measurements of a device across a wide range of temperatures are then presented and the dependence of the noise parameters on collector-emitter voltage is described. This paper concludes with the demonstration of a high-gain 1.8-3.6-GHz cryogenic LNA achieving a noise temperature of 3.4-5 K while consuming just 290 μW when operating at 15-K physical temperature.

Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Qaisieh, Bashar; Mason, Josh, E-mail: joshua.mason@nhs.net; Bownes, Peter

2015-07-15

Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focalmore » (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm{sup 3} was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a

Naloxone-blocked depriming effect of anxiolytic selank on apomorphine-induced behavioral manifestations of hyperfunction of dopamine system.

PubMed

Meshavkin, V K; Kost, N V; Sokolov, O Yu; Zolotarev, Yu A; Myasoedov, N F; Zozulya, A A

2006-11-01

Peptide anxiolytic selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) applied intraperitoneally in doses of 0.01, 0.1, 1.0, and 10.0 mg/kg to mice reduces behavioral manifestations of dopaminergic system induced by apomorphine in the verticalization test. This effect was comparable to that of atypical antipsychotic olanzapine in near-therapeutic doses (0.1 and 1.0 mg/kg, intraperitoneally) and was blocked with nonselective opioid receptor antagonist naloxone (10 mg/kg, intraperitoneally). Radioreceptor assay showed that selank did not displace nonselective D2-dopamine receptor antagonist (3)H-spiperone (EC50>100 microM) and delta- and micro-opioid receptor ligand 3H-DADLE (EC50>40 microM) from specific binding sites on rat brain membranes. It is hypothesized that the revealed behavioral effect of selank is mediated by its modulating effect on the endogenous opioid system and specifically, by its effect on activity of enkephalin-degrading enzymes.

Carbon transfer from magnesia-graphite ladle refractories to ultra-low carbon steel

NASA Astrophysics Data System (ADS)

Russo, Andrew Arthur

Ultra-low carbon steels are utilized in processes which require maximum ductility. Increases in interstitial carbon lower the ductility of steel; therefore, it is important to examine possible sources of carbon. The refractory ladle lining is one such source. Ladle refractories often contain graphite for its desirable thermal shock and slag corrosion resistance. This graphite is a possible source of carbon increase in ultra-low carbon steels. The goal of this research is to understand and evaluate the mechanisms by which carbon transfers to ultra-low carbon steel from magnesia-graphite ladle refractory. Laboratory dip tests were performed in a vacuum induction furnace under an argon atmosphere to investigate these mechanisms. Commercial ladle refractories with carbon contents between 4-12 wt% were used to investigate the effect of refractory carbon content. Slag-free dip tests and slag-containing dip tests with varying MgO concentrations were performed to investigate the influence of slag. Carbon transfer to the steel was controlled by steel penetrating into the refractory and dissolving carbon in dip tests where no slag was present. The rate limiting step for this mechanism is convective mass transport of carbon into the bulk steel. No detectable carbon transfer occurred in dip tests with 4 and 6 wt%C refractories without slag because no significant steel penetration occurred. Carbon transfer was controlled by the corrosion of refractory by slag in dip tests where slag was present.

Ultra-Shallow Junctions Fabrication by Plasma Immersion Implantation on PULSION registered Followed by Laser Thermal Processing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Torregrosa, Frank; Etienne, Hasnaa; Sempere, Guillaume

In order to achieve the requirements for P+/N junctions for <45 nm ITRS nodes, ultra low energy and high dose implantations are needed. Classical beamline implantation is now limited in low energies, compared to Plasma Immersion Ion Implantation (PIII) which efficiency is no more to prove for the realization of Ultra-Shallow Junctions (USJ) in semiconductor applications : this technique allows to get ultimate shallow profiles (as implanted) due to no lower limitation of energy and high dose rate. Electrical activation is also a big issue since it has to afford high electrical activation rate with very low diffusion. Laser annealingmore » is one of the candidates for the 45 nm node. This paper presents electrical and physico-chemical characterizations of junctions realized with BF3 PIII followed by laser thermal processing with aim to obtain ultra-shallow junctions. Different implantation conditions (acceleration voltage/dose) and laser conditions (laser types, fluence/number of shots) are used for this study. Pre-amorphization is also used to confine the junction depth, and is shown to have a positive effect on junction depth but leads in higher junction leakage due to the remaining of EOR defects. The characterization is done using Optical characterization tool (SEMILAB) for sheet resistance and junction leakage measurements. SIMS is used for Boron profile and junction depth.« less

Patient perspectives on an opioid overdose education and naloxone distribution program in the U.S. Department of Veterans Affairs.

PubMed

Oliva, Elizabeth M; Nevedal, Andrea; Lewis, Eleanor T; McCaa, Matthew D; Cochran, Michael F; Konicki, P Eric; Davis, Corey S; Wilder, Christine

2016-01-01

In an effort to prevent opioid overdose mortality among Veterans, Department of Veterans Affairs (VA) facilities began implementing opioid overdose education and naloxone distribution (OEND) in 2013 and a national program began in 2014. VA is the first national health care system to implement OEND. The goal of this study is to examine patient perceptions of OEND training and naloxone kits. Four focus groups were conducted between December 2014 and February 2015 with 21 patients trained in OEND. Participants were recruited from a VA residential facility in California with a substance use disorder treatment program (mandatory OEND training) and a homeless program (optional OEND training). Data were analyzed using matrices and open and closed coding approaches to identify participants' perspectives on OEND training including benefits, concerns, differing opinions, and suggestions for improvement. Veterans thought OEND training was interesting, novel, and empowering, and that naloxone kits will save lives. Some veterans expressed concern about using syringes in the kits. A few patients who never used opioids were not interested in receiving kits. Veterans had differing opinions about legal and liability issues, whether naloxone kits might contribute to relapse, and whether and how to involve family in training. Some veterans expressed uncertainty about the effects of naloxone. Suggested improvements included active learning approaches, enhanced training materials, and increased advertisement. OEND training was generally well received among study participants, including those with no indication for a naloxone kit. Patients described a need for OEND and believed it could save lives. Patient feedback on OEND training benefits, concerns, opinions, and suggestions provides important insights to inform future OEND training programs both within VA and in other health care settings. Training is critical to maximizing the potential for OEND to save lives, and this study

[Effects of naloxone on the expression of stem cell factor and C-kit receptor in combined oxygen-glucose deprivation of primary cultured human embryonic neuron in vitro].

PubMed

Zhu, Bo; Li, Lan-ying; Lü, Guo-yi; Xue, Yu-liang; Ye, Tie-hu

2010-04-01

To explore the effects of naloxone on the expression of c-kit receptor (c-kit R) and its ligand stem cell factor (SCF) in human embryo neuronal hypoxic injury. Serum-free cerebral cortical cultures prepared from embryonic human brains were deprived of both oxygen and glucose which would set up an environment more likely with that of in vivo ischemic injury. Neurons in 24-well culture plates were randomly divided into four groups: control group, hypoxia group, naloxone 0.5 microg/ml group and naloxone 10 microg/ml group. MTT assay and biological analysis were performed to study the cell death and the changes of extracellular concentrations of lactate dehydrogenase (LDH) after combined oxygen-glucose deprivation. Neurons in 25 ml culture flasks were also randomly allocated into four groups as previously described. Intracellular total RNA were extracted at different time points: pre-hypoxia, immediately after hypoxia, and 3, 6, 12, and 24 hours after reoxygenation. The changes of SCF/c-kit R mRNA expression in hypoxic neurons treated with different concentrations of naloxone pre and post oxygen-glucose deprivation were determined with RT-PCR. The cell vitality detected by MTT assay decreased significantly in hypoxia group and naloxone 0.5 microg/ml group when compared with control group (P<0.01), while no significant difference was found between naloxone 0.5 microg/ml group and hypoxia group or between naloxone 10 microg/ml group and control group. Extracellular concentration of LDH significantly increased in hypoxia group (P<0.05), while no difference was found between naloxone 0.5 microg/ml group and control group, between naloxone 0.5 microg/ml and hypoxia group, or between naloxone 10 microg/ml and control group (all P>0.05). Immediately after oxygen-glucose deprivation, the expression of SCF/c-kit R mRNA increased significantly (P<0.01). Among those the expression of SCF presented a distribution of double-peak value within 24 hours. After treated with different

Effectiveness and cost-effectiveness of unsupervised buprenorphine-naloxone for the treatment of heroin dependence in a randomized waitlist controlled trial.

PubMed

Dunlop, Adrian J; Brown, Amanda L; Oldmeadow, Christopher; Harris, Anthony; Gill, Anthony; Sadler, Craig; Ribbons, Karen; Attia, John; Barker, Daniel; Ghijben, Peter; Hinman, Jennifer; Jackson, Melissa; Bell, James; Lintzeris, Nicholas

2017-05-01

Access to opioid agonist treatment can be associated with extensive waiting periods with significant health and financial burdens. This study aimed to determine whether patients with heroin dependence dispensed buprenorphine-naloxone weekly have greater reductions in heroin use and related adverse health effects 12-weeks after commencing treatment, compared to waitlist controls and to examine the cost-effectiveness of this strategy. An open-label waitlist RCT was conducted in an opioid treatment clinic in Newcastle, Australia. Fifty patients with DSM-IV-TR heroin dependence (and no other substance dependence) were recruited. The intervention group (n=25) received take-home self-administered sublingual buprenorphine-naloxone weekly (mean dose, 22.7±5.7mg) and weekly clinical review. Waitlist controls (n=25) received no clinical intervention. The primary outcome was heroin use (self-report, urine toxicology verified) at weeks four, eight and 12. The primary cost-effectiveness outcome was incremental cost per additional heroin-free-day. Outcome data were available for 80% of all randomized participants. Across the 12-weeks, treatment group heroin use was on average 19.02days less/month (95% CI -22.98, -15.06, p<0.0001). A total 12-week reduction in adjusted costs including crime of $A5,722 (95% CI 3299, 8154) in favor of treatment was observed. Excluding crime, incremental cost per heroin-free-day gained from treatment was $A18.24 (95% CI 4.50, 28.49). When compared to remaining on a waitlist, take-home self-administered buprenorphine-naloxone treatment is associated with significant reductions in heroin use for people with DSM-IV-TR heroin dependence. This cost-effective approach may be an efficient strategy to enhance treatment capacity. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Intravenous nicotine self-administration in rats: effects of mecamylamine, hexamethonium and naloxone.

PubMed

DeNoble, Victor J; Mele, Paul C

2006-03-01

The rate and pattern of lever pressing were studied in 18 rats during 24-h sessions in which responding resulted in intravenous infusions of nicotine. There were four indications of the positive reinforcing effect of nicotine: (1) a greater number of lever presses when nicotine was response-contingent compared to when saline was available; (2) a greater number of responses on the lever resulting in an infusion of nicotine than on the control lever; (3) systematic decreases in the number of contingent nicotine infusions when nicotine was delivered noncontingently; and (4) systematic changes in the frequency of lever pressing as a function of dose. Under a fixed ratio 1 (FR 1) schedule, the number of infusions first increased and then decreased as the dose of nicotine was decreased (64, 32, 16, and 8 microg/kg infusion) and nicotine intake (mg/kg every 24 h) was directly related to the infusion dose. As the FR size was increased from 1 to 6, the number of lever presses increased and the number of infusions (32 microg/kg) remained stable. At FR values greater than 6, both the number of lever presses and infusions decreased. Presession injections of mecamylamine (0.75, 1.5, and 3.0 mg/kg, s.c.) decreased the number of infusions in a dose-related manner. Presession injections of hexamethonium (1.5 and 3.0 mg/kg, s.c.) or naloxone (0.75, 1.5, and 3.0 mg/kg, s.c.) did not alter the within- or between-session patterns of nicotine self-administration. Under the conditions of the present experiment, nicotine served as an effective reinforcer and the behavior was shown to be sensitive to both FR size and infusion dose. In addition, the results suggest that nicotine self-administration involves central nicotinic receptors and that opioid receptor antagonism has no effect on nicotine's reinforcing effects in rats.

The effects of oxotremorine, epibatidine, atropine, mecamylamine and naloxone in the tail-flick, hot-plate, and formalin tests in the naked mole-rat (Heterocephalus glaber).

PubMed

Dulu, Thomas D; Kanui, Titus I; Towett, Philemon K; Maloiy, Geoffrey M; Abelson, Klas S P

2014-01-01

The naked mole-rat (Heterocephalus glaber) is a promising animal model for the study of pain mechanisms, therefore a thorough characterization of this species is essential. The aim of the present study was to establish the naked mole-rat as a model for studying the cholinergic receptor system in antinociception by investigating the involvement of muscarinic, nicotinic and opioid receptors in nociceptive tests in this species. The effects of systemic administration of the muscarinic receptor agonist oxotremorine and the nicotinic receptor agonist epibatidine were investigated in the tail-flick, the hot-plate, and the formalin tests. The effects of co-administration of the muscarinic receptor antagonist atropine, the nicotinic receptor antagonist mecamylamine, and the opioid receptor antagonist naloxone were also investigated. Oxotremorine and epibatidine induced a significant, dose-dependent antinociceptive effect in the tail-flick, hot-plate, and formalin tests, respectively. The effects of oxotremorine and epibatidine were blocked by atropine and mecamylamine, respectively. In all three nociceptive tests, naloxone in combination with oxotremorine or epibatidine enhanced the antinociceptive effects of the drugs. The present study demonstrated that stimulation of muscarinic and nicotinic receptors produces antinociceptive effects in the naked-mole rat. The reversal effect of atropine and mecamylamine suggests that this effect is mediated by cholinergic receptors. As naloxone increases the antinociceptive effects of cholinergic agonists, it is suggested that the cholinergic antinociception acts via a gateway facilitated by opioid receptor blockage; however, the precise interaction between these receptor systems needs further investigation.

A flexible nanobrush pad for the chemical mechanical planarization of Cu/ultra-low-к materials

NASA Astrophysics Data System (ADS)

Han, Guiquan; Liu, Yuhong; Lu, Xinchun; Luo, Jianbin

2012-10-01

A new idea of polishing pad called flexible nanobrush pad (FNP) has been proposed for the low down pressure chemical mechanical planarization (CMP) process of Cu/ultra-low-к materials. The FNP was designed with a surface layer of flexible brush-like nanofibers which can `actively' carry nanoscale abrasives in slurry independent of the down pressure. Better planarization performances including high material removal rate, good planarization, good polishing uniformity, and low defectivity are expected in the CMP process under the low down pressure with such kind of pad. The FNP can be made by template-assisted replication or template-based synthesis methods, which will be driven by the development of the preparation technologies for ordered nanostructure arrays. The present work would potentially provide a new solution for the Cu/ultra-low-к CMP process.

[Electric traction magnetic fields of ultra-low frequency as an occupational risk factor of ischemic heart disease].

PubMed

Ptitsyna, N G; Kudrin, V A; Villorezi, D; Kopytenko, Iu A; Tiasto, M I; Kopytenko, E A; Bochko, V A; Iuchchi, N

1996-01-01

The study was inspired by earlier results that displayed influence of variable natural geomagnetic field (0.005-10 Hz range-ultra-low frequencies) on circulatory system, indicated possible correlation between industrial ultra-low frequency fields and prevalence of myocardial infarction. The authors conducted unique measurements of ultra-low frequency fields produced by electric engines. The results were compared with data on morbidity among railway transport workers. The findings are that level of magnetic variations in electric locomotive cabin can exceed 280 micro Tesla, whereas that in car sections reaches 50 micro Tesla. Occurrence of coronary heart disease among the locomotive operators appeared to be 2.0 + 0.2 times higher than that among the car section operators. Higher risk of coronary heart disease in the locomotive operators is associated with their increased occupational magnetic load.

An Ultra Low Cost Wireless Communications Laboratory for Education and Research

ERIC Educational Resources Information Center

Linn, Y.

2012-01-01

This paper presents an ultra-low-cost wireless communications laboratory that is based on a commercial off-the-shelf field programmable gate array (FPGA) development board that is both inexpensive and available worldwide. The total cost of the laboratory is under USD $200, but it includes complete transmission, channel emulation, reception…

Retrospective Analysis of Opioid Medication Incidents Requiring Administration of Naloxone

PubMed Central

Neil, Katherine; Marcil, Allison; Kosar, Lynette; Dumont, Zack; Ruda, Lisa; McMillan, Kaitlyn

2013-01-01

Background: Opioid analgesics are high-alert medications known to cause adverse drug events. Objectives: The purpose of this study was to determine the cause of opioid incidents requiring administration of naloxone, an opioid reversal agent. The specific objectives were to determine the number of opioid incidents and the proportion of incidents documented through occurrence reporting and to characterize the incidents by phase in the medication-use process, by type of incident, and by drug responsible for toxic effects. Methods: A retrospective chart analysis was conducted using records from 2 acute care centres in the Regina Qu’Appelle Health Region. The study included inpatients who received naloxone for reversal of opioid toxicity resulting from licit, in-hospital opioid use. Cases were classified as preventable or nonpreventable. Preventable cases were analyzed to determine the phase of the medication-use process during which the incident occurred. These cases were also grouped thematically by the type of incident. The drug most likely responsible for opioid toxicity was determined for each case. The proportion of cases documented by occurrence reporting was also noted. Results: Thirty-six cases involving administration of naloxone were identified, of which 29 (81%) were deemed preventable. Of these 29 preventable cases, the primary medication incident occurred most frequently in the prescribing phase (23 [79%]), but multiple phases were often involved. The cases were grouped into 6 themes according to the type of incident. Morphine was the drug that most frequently resulted in toxic effects (18 cases [50%]). Only two of the cases (5.6%) were documented by occurrence reports. Conclusion: Preventable opioid incidents occurred in the acute care centres under study. A combination of medication safety initiatives involving multiple disciplines may be required to decrease the incidence of these events and to better document their occurrence. PMID:24159230

Ultra-low-mass flexible planar solar arrays using 50-micron-thick solar cells

NASA Technical Reports Server (NTRS)

Costogue, E. N.; Rayl, G.

1978-01-01

A conceptual design study has been completed which has shown the feasibility of ultra-low-mass planar solar arrays with specific power of 200 watts/kilogram. The beginning of life (BOL) power output of the array designs would be 10 kW at 1 astronomical unit (AU) and a 55C deg operating temperature. Two designs were studied: a retractable rollout design and a non-retractable fold-out. The designs employed a flexible low-mass blanket and low-mass structures. The blanket utilized 2 x 2 cm high-efficiency (13.5% at 28C deg AM0), ultra-thin (50 micron), silicon solar cells protected by thin (75 micron) plastic encapsulants. The structural design utilized the 'V'-stiffened approach which allows a lower mass boom to be used. In conjunction with the conceptual design, modules using the thin cells and plastic encapsulant were designed and fabricated.

Accuracy of lung nodule volumetry in low-dose CT with iterative reconstruction: an anthropomorphic thoracic phantom study.

PubMed

Doo, K W; Kang, E-Y; Yong, H S; Woo, O H; Lee, K Y; Oh, Y-W

2014-09-01

The purpose of this study was to assess accuracy of lung nodule volumetry in low-dose CT with application of iterative reconstruction (IR) according to nodule size, nodule density and CT tube currents, using artificial lung nodules within an anthropomorphic thoracic phantom. Eight artificial nodules (four diameters: 5, 8, 10 and 12 mm; two CT densities: -630 HU that represents ground-glass nodule and +100 HU that represents solid nodule) were randomly placed inside a thoracic phantom. Scans were performed with tube current-time product to 10, 20, 30 and 50 mAs. Images were reconstructed with IR and filtered back projection (FBP). We compared volume estimates to a reference standard and calculated the absolute percentage error (APE). The APE of all nodules was significantly lower when IR was used than with FBP (7.5 ± 4.7% compared with 9.0 ±6.9%; p < 0.001). The effect of IR was more pronounced for smaller nodules (p < 0.001). IR showed a significantly lower APE than FBP in ground-glass nodules (p < 0.0001), and the difference was more pronounced at the lowest tube current (11.8 ± 5.9% compared with 21.3 ± 6.1%; p < 0.0001). The effect of IR was most pronounced for ground-glass nodules in the lowest CT tube current. Lung nodule volumetry in low-dose CT by application of IR showed reliable accuracy in a phantom study. Lung nodule volumetry can be reliably applicable to all lung nodules including small, ground-glass nodules even in ultra-low-dose CT with application of IR. IR significantly improved the accuracy of lung nodule volumetry compared with FBP particularly for ground-glass (-630 HU) nodules. Volumetry in low-dose CT can be utilized in patient with lung nodule work-up, and IR has benefit for small, ground-glass lung nodules in low-dose CT.

Qualitative assessment of take-home naloxone program participant and law enforcement interactions in British Columbia.

PubMed

Deonarine, Andrew; Amlani, Ashraf; Ambrose, Graham; Buxton, Jane A

2016-05-21

The British Columbia take-home naloxone (BCTHN) program has been in operation since 2012 and has resulted in the successful reversal of over 581 opioid overdoses. The study aims to explore BCTHN program participant perspectives about the program, barriers to participants contacting emergency services (calling "911") during an overdose, and perspectives of law enforcement officials on naloxone administration by police officers. Two focus groups and four individual interviews were conducted with BCTHN program participants; interviews with two law enforcement officials were also conducted. Qualitative analysis of all transcripts was performed. Positive themes about the BCTHN program from participants included easy to understand training, correcting misperceptions in the community, and positive interactions with emergency services. Potential barriers to contacting emergency services during an overdose include concerns about being arrested for outstanding warrants or for other illegal activities (such as drug possession) and confiscation of kits. Law enforcement officials noted that warrants were complex situational issues, kits would normally not be confiscated, and admitted arrests for drug possession or other activities may not serve the public good in an overdose situation. Law enforcement officials were concerned about legal liability and jurisdictional/authorization issues if naloxone administration privileges were expanded to police. Program participants and law enforcement officials expressed differing perspectives about warrants, kit confiscation, and arrests. Facilitating communication between BCTHN program participants and other stakeholders may address some of the confusion and remove potential barriers to further improving program outcomes. Naloxone administration by law enforcement would require policies to address jurisdiction/authorization and liability issues.

Implementing take-home naloxone in an urban community pharmacy.

PubMed

Akers, Joshua L; Hansen, Ryan N; Oftebro, Ryan D

Morbidity and mortality associated with opioid use have increased across the nation, growing into what can only be described as an epidemic. In Washington State between 2002 and 2004, the statewide death rate attributed to any opioid was 6.6 per 100,000 people, but between 2011 and 2013 it increased to 8.6 per 100,000 people. Pharmacies provide a unique access point for harm reduction services to patients due to their ease of accessibility in the community. In development of a take-home naloxone (THN) program, there were multiple areas that needed to be considered. These included product selection, collaborative practice agreements, training format and materials, managing patient and provider expectations, partnerships, and community perception of the service. Initial demographics from our experience of people obtaining THN showed a significant difference in the median age from other available programs in the area (57 years vs. 34, 35, and 31). These people tended to be bystanders, instead of end users of opioids, which led to redirecting marketing of our program. We provided community and group trainings for various organizations around the greater Seattle area. We have trained approximately 1400 unique individuals on how to recognize and respond to an opioid overdose, and how to administer naloxone. One organization reports 20 successful overdose rescues from 99 kits (100% intranasal route) dispensed by our pharmacy (20.2% rescue rate). Since 2012 when our THN program began, we have seen growth of these programs across the state. Based on data through 2015, deaths from heroin in King County have decreased for the first time in the last 7 years, and the number of people seeking treatment for heroin addiction has increased. Take-home naloxone programs can be successfully implemented into community pharmacies to increase access and awareness of opioid overdose recognition and response. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc

Low-dose effects of hormones and endocrine disruptors.

PubMed

Vandenberg, Laura N

2014-01-01

Endogenous hormones have effects on tissue morphology, cell physiology, and behaviors at low doses. In fact, hormones are known to circulate in the part-per-trillion and part-per-billion concentrations, making them highly effective and potent signaling molecules. Many endocrine-disrupting chemicals (EDCs) mimic hormones, yet there is strong debate over whether these chemicals can also have effects at low doses. In the 1990s, scientists proposed the "low-dose hypothesis," which postulated that EDCs affect humans and animals at environmentally relevant doses. This chapter focuses on data that support and refute the low-dose hypothesis. A case study examining the highly controversial example of bisphenol A and its low-dose effects on the prostate is examined through the lens of endocrinology. Finally, the chapter concludes with a discussion of factors that can influence the ability of a study to detect and interpret low-dose effects appropriately. © 2014 Elsevier Inc. All rights reserved.

Raman micro-spectroscopy analysis of human lens epithelial cells exposed to a low-dose-range of ionizing radiation.

PubMed

Allen, Christian Harry; Kumar, Achint; Qutob, Sami; Nyiri, Balazs; Chauhan, Vinita; Murugkar, Sangeeta

2018-01-09

Recent findings in populations exposed to ionizing radiation (IR) indicate dose-related lens opacification occurs at much lower doses (<2 Gy) than indicated in radiation protection guidelines. As a result, research efforts are now being directed towards identifying early predictors of lens degeneration resulting in cataractogenesis. In this study, Raman micro-spectroscopy was used to investigate the effects of varying doses of radiation, ranging from 0.01 Gy to 5 Gy, on human lens epithelial (HLE) cells which were chemically fixed 24 h post-irradiation. Raman spectra were acquired from the nucleus and cytoplasm of the HLE cells. Spectra were collected from points in a 3  ×  3 grid pattern and then averaged. The raw spectra were preprocessed and principal component analysis followed by linear discriminant analysis was used to discriminate between dose and control for 0.25, 0.5, 2, and 5 Gy. Using leave-one-out cross-validation accuracies of greater than 74% were attained for each dose/control combination. The ultra-low doses 0.01 and 0.05 Gy were included in an analysis of band intensities for Raman bands found to be significant in the linear discrimination, and an induced repair model survival curve was fit to a band-difference-ratio plot of this data, suggesting HLE cells undergo a nonlinear response to low-doses of IR. A survival curve was also fit to clonogenic assay data done on the irradiated HLE cells, showing a similar nonlinear response.

Raman micro-spectroscopy analysis of human lens epithelial cells exposed to a low-dose-range of ionizing radiation

NASA Astrophysics Data System (ADS)

Allen, Christian Harry; Kumar, Achint; Qutob, Sami; Nyiri, Balazs; Chauhan, Vinita; Murugkar, Sangeeta

2018-01-01

Recent findings in populations exposed to ionizing radiation (IR) indicate dose-related lens opacification occurs at much lower doses (<2 Gy) than indicated in radiation protection guidelines. As a result, research efforts are now being directed towards identifying early predictors of lens degeneration resulting in cataractogenesis. In this study, Raman micro-spectroscopy was used to investigate the effects of varying doses of radiation, ranging from 0.01 Gy to 5 Gy, on human lens epithelial (HLE) cells which were chemically fixed 24 h post-irradiation. Raman spectra were acquired from the nucleus and cytoplasm of the HLE cells. Spectra were collected from points in a 3  ×  3 grid pattern and then averaged. The raw spectra were preprocessed and principal component analysis followed by linear discriminant analysis was used to discriminate between dose and control for 0.25, 0.5, 2, and 5 Gy. Using leave-one-out cross-validation accuracies of greater than 74% were attained for each dose/control combination. The ultra-low doses 0.01 and 0.05 Gy were included in an analysis of band intensities for Raman bands found to be significant in the linear discrimination, and an induced repair model survival curve was fit to a band-difference-ratio plot of this data, suggesting HLE cells undergo a nonlinear response to low-doses of IR. A survival curve was also fit to clonogenic assay data done on the irradiated HLE cells, showing a similar nonlinear response.

A flexible nanobrush pad for the chemical mechanical planarization of Cu/ultra-low-к materials

PubMed Central

2012-01-01

A new idea of polishing pad called flexible nanobrush pad (FNP) has been proposed for the low down pressure chemical mechanical planarization (CMP) process of Cu/ultra-low-к materials. The FNP was designed with a surface layer of flexible brush-like nanofibers which can ‘actively’ carry nanoscale abrasives in slurry independent of the down pressure. Better planarization performances including high material removal rate, good planarization, good polishing uniformity, and low defectivity are expected in the CMP process under the low down pressure with such kind of pad. The FNP can be made by template-assisted replication or template-based synthesis methods, which will be driven by the development of the preparation technologies for ordered nanostructure arrays. The present work would potentially provide a new solution for the Cu/ultra-low-к CMP process. PMID:23110959

Naloxone administration for suspected opioid overdose: An expanded scope of practice by a basic life support collegiate-based emergency medical services agency.

PubMed

Jeffery, Ryan M; Dickinson, Laura; Ng, Nicholas D; DeGeorge, Lindsey M; Nable, Jose V

2017-04-01

Opioid abuse is a growing and significant public health concern in the United States. Naloxone is an opioid antagonist that can rapidly reverse the respiratory depression associated with opioid toxicity. Georgetown University's collegiate-based emergency medical services (EMS) agency recently adopted a protocol, allowing providers to administer intranasal naloxone for patients with suspected opioid overdose. While normally not within the scope of practice of basic life support prehospital agencies, the recognition of an increasing epidemic of opioid abuse has led many states, including the District of Columbia, to expand access to naloxone for prehospital providers of all levels of training. In particular, intranasal naloxone is a method of administering this medication that potentially avoids needlestick injuries among EMS providers. Universities with collegiate-based EMS agencies are well positioned to provide life-saving treatments for patients acutely ill from opioid overdose.

Ultra-low-power wearable biopotential sensor nodes.

PubMed

Yazicioglu, R F; Torfs, T; Penders, J; Romero, I; Kim, H; Merken, P; Gyselinckx, B; Yoo, H J; Van Hoof, C

2009-01-01

This paper discusses ultra-low-power wireless sensor nodes intended for wearable biopotential monitoring. Specific attention is given to mixed-signal design approaches and their impact on the overall system power dissipation. Examples of trade-offs in power dissipation between analog front-ends and digital signal processing are also given. It is shown how signal filtering can further reduce the internal power consumption of a node. Such power saving approaches are indispensable as real-life tests of custom wireless ECG patches reveal the need for artifact detection and correction. The power consumption of such additional features has to come from power savings elsewhere in the system as the overall power budget cannot increase.

Ultra low-cost, portable smartphone optosensors for mobile point-of-care diagnostics

NASA Astrophysics Data System (ADS)

Wang, Li-Ju; Chang, Yu-Chung; Sun, Rongrong; Li, Lei

2018-02-01

Smartphone optosensors with integrated optical components make mobile point-of-care (MPoC) diagnostics be done near patients' side. It'll especially have a significant impact on healthcare delivery in rural or remote areas. Current FDA-approved PoC devices achieving clinical level are still at high cost and not affordable in rural hospitals. We present a series of ultra low-cost smartphone optical sensing devices for mobile point-of-care diagnosis. Aiming different targeting analytes and sensing mechanisms, we developed custom required optical components for each smartphone optosensros. These optical devices include spectrum readers, colorimetric readers for microplate, lateral flow device readers, and chemiluminescence readers. By integrating our unique designed optical components into smartphone optosening platform, the anlaytes can be precisely detected. Clinical testing results show the clinical usability of our smartphone optosensors. Ultra low-cost portable smartphone optosensors are affordable for rural/remote doctors.

Why is it so hard to implement change? A qualitative examination of barriers and facilitators to distribution of naloxone for overdose prevention in a safety net environment.

PubMed

Drainoni, Mari-Lynn; Koppelman, Elisa A; Feldman, James A; Walley, Alexander Y; Mitchell, Patricia M; Ellison, Jacqueline; Bernstein, Edward

2016-10-18

The increase in opioid overdose deaths has become a national public health crisis. Naloxone is an important tool in opioid overdose prevention. Distribution of nasal naloxone has been found to be a feasible, and effective intervention in community settings and may have potential high applicability in the emergency department, which is often the initial point of care for persons at high risk of overdose. One safety net hospital introduced an innovative policy to offer take-home nasal naloxone via a standing order to ensure distribution to patients at risk for overdose. The aims of this study were to examine acceptance and uptake of the policy and assess facilitators and barriers to implementation. After obtaining pre-post data on naloxone distribution, we conducted a qualitative study. The PARiHS framework steered development of the qualitative guide. We used theoretical sampling in order to include the range of types of emergency department staff (50 total). The constant comparative method was initially used to code the transcripts and identify themes; the themes that emerged from the coding were then mapped back to the evidence, context and facilitation constructs of the PARiHS framework. Acceptance of the policy was good but uptake was low. Primary themes related to facilitators included: real-world driven intervention with philosophical, clinician and leadership support; basic education and training efforts; availability of resources; and ability to leave the ED with the naloxone kit in hand. Barriers fell into five general categories: protocol and policy; workflow and logistical; patient-related; staff roles and responsibilities; and education and training. The actual implementation of a new innovation in healthcare delivery is largely driven by factors beyond acceptance. Despite support and resources, implementation was challenging, with low uptake. While the potential of this innovation is unknown, understanding the experience is important to improve uptake

Ultra-Low Background Measurements Of Decayed Aerosol Filters

NASA Astrophysics Data System (ADS)

Miley, H.

2009-04-01

To experimentally evaluate the opportunity to apply ultra-low background measurement methods to samples collected, for instance, by the Comprehensive Test Ban Treaty International Monitoring System (IMS), aerosol samples collected on filter media were measured using HPGe spectrometers of varying low-background technology approaches. In this way, realistic estimates of the impact of low-background methodology can be assessed on the Minimum Detectable Activities obtained in systems such as the IMS. The current measurement requirement of stations in the IMS is 30 microBq per cubic meter of air for 140Ba, or about 106 fissions per daily sample. Importantly, this is for a fresh aerosol filter. Decay varying form 3 days to one week reduce the intrinsic background from radon daughters in the sample. Computational estimates of the improvement factor for these decayed filters for underground-based HPGe in clean shielding materials are orders of magnitude less, even when the decay of the isotopes of interest is included.

Low-Dose Radiation 3D Intraoperative Imaging: How Low Can We Go? An O-Arm, CT Scan, Cadaveric Study.

PubMed

Sarwahi, Vishal; Payares, Monica; Wendolowski, Stephen; Maguire, Kathleen; Thornhill, Beverly; Lo, Yungtai; Amaral, Terry D

2017-11-15

MINI: The objective of this study was to evaluate the accuracy and reliability of pedicle screw placement using O-Arm at dosages below the manufactured recommended dose. O-Arm at reduced dose showed a 90% accuracy when compared with computed tomography; however, about 30% medial breaches were misclassified. Cadaveric study. The objective was to evaluate O-Arm's ability at low-dose (LD) settings to assess intraoperative screw placement. Accurate placement of pedicle screws is crucial because of proximity to vital structures. Malposition of screws may result in significant morbidity and potential mortality. O-arm provides real-time, intraoperative imaging of patient's anatomy and provides higher accuracy in scoliosis surgeries, avoiding risk to vital structures. We hypothesize using LD or ultra-low doses (ULDs) to obtain intraoperative images allow for accurate assessment of screw placement, both minimizing radiation exposure and preventing screw misplacement. Eight cadavers were instrumented with pedicle screws bilaterally from T1 to S1. Screws were randomly placed using O-arm navigation into three positions: contained within the bone, OUT-anterior/lateral, and OUT-medial. O-arm images were obtained at three dosage settings: LD (kVp120/mAs125-lowest manufacturer recommended), very-low dose (VLD) (kVp120/mAs63), and ULD (kVp120/mAs39). Computed tomography (CT) scan was performed using institution's LD protocol (kVp100/mAs50) and gross dissection to identify screw positions. LD, VLD, ULD, and CT for identifying "IN" screws relative to gross dissection had, a mean (standard deviation) sensitivity of 84.2% (±5.7), specificity of 76.1% (±9.3), and accuracy of 79.9% (±3.1) from all three observers. Across the three observers, the interobserver agreement was 0.67 (0.61-0.72) for LD, 0.74 (0.69-0.79) for VLD, 0.61 (0.56-0.66) for ULD, and 0.79 (0.74-0.84) for CT. Effective doses of radiation (mSV) for LD O-arm scan was 2.16, VLD 1.08, ULD 0.68, and our LD CT protocol was

Pharmaceutical and pharmacokinetic characterization of a novel sublingual buprenorphine/naloxone tablet formulation in healthy volunteers.

PubMed

Fischer, Andreas; Jönsson, Martin; Hjelmström, Peter

2015-01-01

Bitter taste, as well as dissolve time, presents a significant challenge for the acceptability of formulations for oral transmucosal drug delivery. To characterize a novel sublingual tablet formulation of buprenorphine/naloxone with regards to pharmacokinetics, dissolve time and formulation acceptability. Dry mixing techniques were employed to produce a small and fast dissolving buprenorphine/naloxone sublingual tablet formulation, OX219 (Zubsolv®), using sucralose and menthol as sweetener and flavor to mask the bitter taste of the active ingredients. Two cross-over studies were performed in healthy volunteers to evaluate pharmacokinetics, dissolve time and acceptability of OX219 5.7/1.4 mg tablets compared to the commercially available buprenorphine/naloxone formulations Suboxone® tablets and films (8/2 mg). Buprenorphine exposure was equivalent in OX219 and Suboxone tablets. Sublingual dissolve times were significantly shorter for OX219 than for Suboxone tablets and were similar to Suboxone films. The OX219 formulation received significantly higher subjective ratings for taste and overall acceptability than both Suboxone formulations. OX219 was preferred over Suboxone tablet and film formulations by 77.4% and 88.9% of subjects, respectively. A sublingual tablet formulation with an improved acceptability has been successfully developed.

Central effects of some peptide and non-peptide opioids and naloxone on thermoregulation in the rabbit

NASA Technical Reports Server (NTRS)

Kandasamy, S. B.; Williams, B. A.

1983-01-01

The effects of several peptide and non-peptide opiods and naloxone on induced hyperthermia is studied in rabbits. The effect of tyical mu, kappa, and sigma receptor antagonists (morphine, ketocyclazcine and SKF 10,0 10, 047) and some opioid peptides (Beta-endorphin /BE/, methionine-enkaphalin /ME/, and D-Ala2-methionine-enkaphalin-amide /DAME/ are determined. The role of prostaglandins (PG), cAMP, and norepinephrine (NE) in morphine, BE, and DAME induced hyperthermia is investigated. In addition, the effect of naloxone on pyrogen, arachidonic acid, PGE2, prostacyclin, dibutyryl cAMP, and NE induced hyperthermia is determined. Among other results, it is found that the three receptor antagonists induced hyperthermia in rabbits. BE, ME, and DAME were also found to cause hyperthermia, and it is suggested that they act on the same type of receptor. It is also determined that neither NE nor cAMP is involved in the hyperthermia due to morphine, BE, and DAME. It is suggested that an action of endogenous peptides on naloxone sensitive receptors plays little role in normal thermoregulation or in hyperthermia.

Comparative analysis of gas and coal-fired power generation in ultra-low emission condition using life cycle assessment (LCA)

NASA Astrophysics Data System (ADS)

Yin, Libao; Liao, Yanfen; Liu, Guicai; Liu, Zhichao; Yu, Zhaosheng; Guo, Shaode; Ma, Xiaoqian

2017-05-01

Energy consumption and pollutant emission of natural gas combined cycle power-generation (NGCC), liquefied natural gas combined cycle power-generation (LNGCC), natural gas combined heat and power generation (CHP) and ultra-supercritical power generation with ultra-low gas emission (USC) were analyzed using life cycle assessment method, pointing out the development opportunity and superiority of gas power generation in the period of coal-fired unit ultra-low emission transformation. The results show that CO2 emission followed the order: USC>LNGCC>NGCC>CHP the resource depletion coefficient of coal-fired power generation was lower than that of gas power generation, and the coal-fired power generation should be the main part of power generation in China; based on sensitivity analysis, improving the generating efficiency or shortening the transportation distance could effectively improve energy saving and emission reduction, especially for the coal-fired units, and improving the generating efficiency had a great significance for achieving the ultra-low gas emission.

Development of an underground HPGe array facility for ultra low radioactivity measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sala, E.; Kang, W. G.; Kim, Y. D.

Low Level Counting techniques using low background facilities are continuously under development to increase the possible sensitivity needed for rare physics events experiments. The CUP (Center for Underground Physics) group of IBS is developing, in collaboration with Canberra, a ultra low background instrument composed of two arrays facing each other with 7 HPGe detectors each. The low radioactive background of each detector has been evaluated and improved by the material selection of the detector components. Samples of all the building materials have been provided by the manufacturer and the contaminations had been measured using an optimized low background 100% HPGemore » with a dedicated shielding. The evaluation of the intrinsic background has been performed using MonteCarlo simulations and considering the contribution of each material with the measured contamination. To further reduce the background, the instrument will be placed in the new underground laboratory at YangYang exploiting the 700m mountain coverage and radon-free air supplying system. The array has been designed to perform various Ultra Low background measurements; the sensitivity we are expecting will allow not only low level measurements of Ra and Th contaminations in Copper or other usually pure materials, but also the search for rare decays. In particular some possible candidates and configurations to detect the 0νECEC (for example {sup 106}Cd and {sup 156}Dy) and rare β decays ({sup 96}Zr, {sup 180m}Ta , etc ) are under study.« less

Low-dose vaporized cannabis significantly improves neuropathic pain.

PubMed

Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-02-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

Dose-effect relationships, epidemiological analysis and the derivation of low dose risk.

PubMed

Leenhouts, H P; Chadwick, K H

2011-03-01

This paper expands on our recent comments in a letter to this journal about the analysis of epidemiological studies and the determination of low dose RBE of low LET radiation (Chadwick and Leenhouts 2009 J. Radiol. Prot. 29 445-7). Using the assumption that radiation induced cancer arises from a somatic mutation (Chadwick and Leenhouts 2011 J. Radiol. Prot. 31 41-8) a model equation is derived to describe cancer induction as a function of dose. The model is described briefly, evidence is provided in support of it, and it is applied to a set of experimental animal data. The results are compared with a linear fit to the data as has often been done in epidemiological studies. The article presents arguments to support several related messages which are relevant to epidemiological analysis, the derivation of low dose risk and the weighting factor of sparsely ionising radiations. The messages are: (a) cancer incidence following acute exposure should, in principle, be fitted to a linear-quadratic curve with cell killing using all the data available; (b) the acute data are dominated by the quadratic component of dose; (c) the linear fit of any acute data will essentially be dependent on the quadratic component and will be unrelated to the effectiveness of the radiation at low doses; consequently, (d) the method used by ICRP to derive low dose risk from the atomic bomb survivor data means that it is unrelated to the effectiveness of the hard gamma radiation at low radiation doses; (e) the low dose risk value should, therefore, not be used as if it were representative for hard gamma rays to argue for an increased weighting factor for tritium and soft x-rays even though there are mechanistic reasons to expect this; (f) epidemiological studies of chronically exposed populations supported by appropriate cellular radiobiological studies have the best chance of revealing different RBE values for different sparsely ionising radiations.

Assessment of dose and DNA damages in individuals exposed to low dose and low dose rate ionizing radiations during computed tomography imaging.

PubMed

Kanagaraj, Karthik; Abdul Syed Basheerudeen, Safa; Tamizh Selvan, G; Jose, M T; Ozhimuthu, Annalakshmi; Panneer Selvam, S; Pattan, Sudha; Perumal, Venkatachalam

2015-08-01

Computed tomography (CT) is a frequently used imaging modality that contributes to a tenfold increase in radiation exposure to the public when compared to other medical imaging modalities. The use of radiation for therapeutic need is always rationalized on the basis of risk versus benefit thereby increasing concerns on the dose received by patients undergoing CT imaging. Therefore, it was of interest to us to investigate the effects of low dose and low dose-rate X-irradiation in patients who underwent CT imaging by recording the doses received by the eye, forehead and thyroid, and to study the levels of damages in the lymphocytes in vivo. Lithium manganese borate doped with terbium (LMB:Tb) thermo luminescence dosimeters (TLD) were used to record the doses in the patient's (n = 27) eye, forehead, and thyroid and compared with the dose length product (DLP) values. The in vivo DNA damages measured were compared before and after CT imaging using chromosomal aberration (CA) and micronucleus (MN) assays. The overall measured organ dose ranged between 2 ± 0.29 and 520 ± 41.63 mGy for the eye, 0.84 ± 0.29 and 210 ± 20.50 mGy for the forehead, and 1.79 ± 0.43 and 185 ± 0.70 mGy for the thyroid. The in vivo damages measured from the blood lymphocytes of the subjects showed an extremely significant (p < 0.0001) increase in CA frequency and significant (p < 0.001) increase in MN frequency after exposure, compared to before exposure. The results suggest that CT imaging delivers a considerable amount of radiation dose to the eye, forehead, and thyroid, and the observed increase in the CA and MN frequencies show low dose radiation effects calling for protective regulatory measures to increase patient's safety. This study is the first attempt to indicate the trend of doses received by the patient's eye, forehead and thyroid and measured directly in contrast to earlier values obtained by extrapolation from phantoms, and to assess the in vivo low dose effects in an Indian

Ultra-low profile Ovation device: is it the definitive solution for EVAR?

PubMed

de Donato, G; Setacci, F; Sirignano, P; Galzerano, G; Borrelli, M P; di Marzo, L; Setacci, C

2014-02-01

When Juan Parodi implanted an endograft in a human body for the first time on September 7, 1990 in Buenos Aires, Argentina, the delivery system of the handmade device was primitive, extremely rigid, and had a bulky profile of 27 French (F). Since then, stent-graft technology has evolved rapidly, limitations of earlier-generation devices have been overtaken, and endovascular aneurysm repair (EVAR) eligibility has increased enormously. Nevertheless (still) challenging aortoiliac anatomy such as short and complex proximal aortic neck seal zones and narrow access vessels are responsible for EVAR ineligibility in up to 50% of cases. The Ovation Prime abdominal stent-graft system (TriVascular, Inc., Santa Rosa, CA, USA) is a trimodular device designed with the aortic body delivered via a flexible, hydrophilic-coated, ultra-low profile catheter (14-F outer diameter - OD). The aortic body is provided with a suprarenal nitinol stent with anchors that provide active fixation, while a network of rings and channels that are inflated with a low-viscosity radiopaque polymer during stent-graft deployment, provides effective sealing. The previous EVAR technology aimed to both anchor and seal using stents combined with fabric, with neither optimized for their roles and each forced to compete for the same space within their delivery catheters, which inevitably led to larger profile of the delivery system. The technical revolution of the Ovation endograft includes the idea to truly uncouple the stages of stent-graft fixation and seal during the procedure. In the Ovation endograft platform, stent and fabric are not competing the same space within the delivery system and an ultra-low profile delivery can be achieved without compromise. With such a low-profile delivery catheter, approximately 90% of men and 70% of women with abdominal aortic aneurysm have access vessel diameters considered fit for endovascular repair. The aim of this review paper was to analyze the main properties of

Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

PubMed Central

Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-01-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

Low dose irradiation facilitates hepatocellular carcinoma genesis involving HULC.

PubMed

Li, Yuan; Ge, Chang; Feng, Guoxing; Xiao, Huiwen; Dong, Jiali; Zhu, Changchun; Jiang, Mian; Cui, Ming; Fan, Saijun

2018-03-24

Irradiation exposure positive correlates with tumor formation, such as breast cancer and lung cancer. However, whether low dose irradiation induces hepatocarcinogenesis and the underlying mechanism remain poorly defined. In the present study, we reported that low dose irradiation facilitated the proliferation of hepatocyte through up-regulating HULC in vitro and in vivo. Low dose irradiation exposure elevated HULC expression level in hepatocyte. Deletion of heightened HULC erased the cells growth accelerated following low dose irradiation exposure. CDKN1, the neighbor gene of HULC, was down-regulated by overexpression of HULC following low dose irradiation exposure via complementary base pairing, resulting in promoting cell cycle process. Thus, our findings provide new insights into the mechanism of low dose irradiation-induced hepatocarcinogenesis through HULC/CDKN1 signaling, and shed light on the potential risk of low dose irradiation for the development of hepatocellular carcinoma in pre-clinical settings. © 2018 Wiley Periodicals, Inc.

A novel ultrafast-low-dose computed tomography protocol allows concomitant coronary artery evaluation and lung cancer screening.

PubMed

Gaudio, Carlo; Petriello, Gennaro; Pelliccia, Francesco; Tanzilli, Alessandra; Bandiera, Alberto; Tanzilli, Gaetano; Barillà, Francesco; Paravati, Vincenzo; Pellegrini, Massimo; Mangieri, Enrico; Barillari, Paolo

2018-05-08

Cardiac computed tomography (CT) is often performed in patients who are at high risk for lung cancer in whom screening is currently recommended. We tested diagnostic ability and radiation exposure of a novel ultra-low-dose CT protocol that allows concomitant coronary artery evaluation and lung screening. We studied 30 current or former heavy smoker subjects with suspected or known coronary artery disease who underwent CT assessment of both coronary arteries and thoracic area (Revolution CT, General Electric). A new ultrafast-low-dose single protocol was used for ECG-gated helical acquisition of the heart and the whole chest. A single IV iodine bolus (70-90 ml) was used. All patients with CT evidence of coronary stenosis underwent also invasive coronary angiography. All the coronary segments were assessable in 28/30 (93%) patients. Only 8 coronary segments were not assessable in 2 patients due to motion artefacts (assessability: 98%; 477/485 segments). In the assessable segments, 20/21 significant stenoses (> 70% reduction of vessel diameter) were correctly diagnosed. Pulmonary nodules were detected in 5 patients, thus requiring to schedule follow-up surveillance CT thorax. Effective dose was 1.3 ± 0.9 mSv (range: 0.8-3.2 mSv). Noteworthy, no contrast or radiation dose increment was required with the new protocol as compared to conventional coronary CT protocol. The novel ultrafast-low-dose CT protocol allows lung cancer screening at time of coronary artery evaluation. The new approach might enhance the cost-effectiveness of coronary CT in heavy smokers with suspected or known coronary artery disease.

GaN on Diamond with Ultra-Low Thermal Barrier Resistance

DTIC Science & Technology

2016-03-31

GaN-on-Diamond with Ultra-Low Thermal Barrier Resistance Xing Gu1, Cathy Lee1, Jinqiao Xie1, Edward Beam1, Michael Becker2, Timothy A. Grotjohn2...Bristol BS8 1TL, UK Abstract: We investigated the effective thermal boundary resistance (TBReff) of GaN-on-Diamond interfaces for diamond growth... thermal boundary resistance; TBReff , interfacial layers; high density dielectric Introduction While GaN-based RF transistors, typically on SiC

Lateral topography for reducing effective dose in low-dose chest CT.

PubMed

Bang, Dong-Ho; Lim, Daekeon; Hwang, Wi-Sub; Park, Seong-Hoon; Jeong, Ok-man; Kang, Kyung Wook; Kang, Hohyung

2013-06-01

The purposes of this study were to assess radiation exposure during low-dose chest CT by using lateral topography and to compare the lateral topographic findings with findings obtained with anteroposterior topography alone and anteroposterior and lateral topography combined. From November 2011 to February 2012, 210 male subjects were enrolled in the study. Age, weight, and height of the men were recorded. All subjects were placed into one of three subgroups based on the type of topographic image obtained: anteroposterior topography, lateral topography, and both anteroposterior and lateral topography. Imaging was performed with a 128-MDCT scanner. CT, except for topography, was the same for all subjects. A radiologist analyzed each image, recorded scan length, checked for any insufficiencies in the FOV, and calculated the effective radiation dose. One-way analysis of variance and multiple comparisons were used to compare the effective radiation exposure and scan length between groups. The mean scan length in the anteroposterior topography group was significantly greater than that of the lateral topography group and the combined anteroposterior and lateral topography group (p < 0.001). The mean effective radiation dose for the lateral topography group (0.735 ± 0.033 mSv) was significantly lower than that for the anteroposterior topography group (0.763 ± 0.038 mSv) and the combined anteroposterior and lateral topography group (0.773 ± 0.038) (p < 0.001). Lateral topographic low-dose CT was associated with a lower effective radiation dose and scan length than either anteroposterior topographic low-dose chest CT or low-dose chest CT with both anteroposterior and lateral topograms.

Effectiveness of indoor ultra-low volume application of Aqua Reslin® Super during an emergency.

PubMed

Ordóñez González, José Genaro; Thirion, Jaime; García Orozco, Abel; Rodríguez, Américo D

2011-06-01

Indoor ultra-low volume (ULV) applications of Aqua Reslin Super (Permethrin + s-bioallethrin) were carried out using portable Solo Port 423 sprayers in an urban area of Reforma, Chiapas, Mexico. Sprayers were calibrated to discharge a flow rate of 110 ml/min with a dose range of approximately 0.55 to 0.792 mg Al/m3 space. Entomological evaluation, based on 3 cages per house, each containing 15 sugar-fed, 2-4-day-old Aedes aegypti females and placed in hidden locations in 4 randomly selected houses for 15 min, showed 98.8% to 100% mortality. After the spraying, ovitrap data showed no mosquito adults present 4 days after the applications, and only 1 ovitrap out of 60 positive 8 days after the intervention. This evaluation suggests that indoor ULV application can be useful during emergencies after disasters, during dengue outbreaks, or to prevent mosquito population outbreaks before rainy seasons and, therefore, the onset of dengue transmission in Mexican dengue transmission risk areas.

Effects of naloxone opiate blockade on the immunomodulation induced by exercise in rats.

PubMed

Bouix, O; elMezouini, M; Orsetti, A

1995-01-01

The purpose of this study was to examine the possible involvement of the endogenous opiate system in the changes in immune competence induced by isolated exercise. Male untrained rats were subjected to a 2.5 hours swimming exercise bout. Animals were killed 15 min after the end of the exercise. The concentration of leukocytes, lymphocytes, monocytes and granulocytes and T4 (T-helper), T8 (T-suppressor/cytotoxic), interleukin-2 receptor (IL-2R) and transferrin receptor (TrfR) positive lymphocytes were determined both in peripheral blood and spleen by flow cytometric analysis. Exercise resulted in a significant decrease in 1) blood lymphocyte and splenic granulocyte number (p < 0.05), 2) blood and splenic T4 positive lymphocytes and T4/T8 ratio (p < 0.05), and 3) blood and splenic IL-2R and TrfR positive lymphocytes (p < 0.05). The injection of the opiate blocker naloxone to exercising rats induced a decrease in the concentration and proportion of T8 positive lymphocytes, thereby restoring a normal T4/T8 ratio both in peripheral blood and spleen. Naloxone had no effect in control animals. The concentration and proportion of IL-2R and TrfR positive lymphocytes were not affected by naloxone. The mechanisms of the immunomodulation induced by isolated intense exercise are unclear. These data suggest that endogenous opiates participate in the alteration of cell-mediated immunity associated with exercise by modulating the T8 (suppressor/cytotoxic)-cell activity.

Naloxone decreases the inhibitory effect of alprazolam on the release of adrenocorticotropin/cortisol induced by physical exercise in man

PubMed Central

Coiro, Vittorio; Volpi, Riccardo; Casti, Amos; Maffei, Maria Ludovica; Stella, Adriano; Volta, Elio; Chiodera, Paolo

2011-01-01

AIMS To establish the possible involvement of alprazolam (ALP) and/or opiates in the mechanism underlying the ACTH/cortisol response to physical exercise. METHODS Tests were carried out under basal conditions (exercise control test), exercise plus ALP (50 µg at time −90 min), naloxone (10 mg at time 0) or ALP plus naloxone. Plasma ACTH and serum cortisol concentrations were evaluated in blood samples taken before, during and after the bicycle ergometer tests. RESULTS ACTH and cortisol concentrations rose significantly after physical exercise. Maximum peak at time 15 min (P≤ 0.01 vs. baseline) for ACTH and at time 30 min (P≤ 0.01 vs. baseline) for cortisol. In the presence of naloxone, the ACTH and cortisol responses were significantly increased (maximum peak at time 20 min, P≤ 0.02 vs. control test for ACTH, and at time 30 min (P≤ 0.01 vs. baseline) for cortisol) whereas they were abolished by ALP. When ALP and naloxone were given together, the inhibitory effect of ALP was partial. CONCLUSIONS These data demonstrate an inhibitory effect of ALP in the regulation of the ACTH/cortisol response to physical exercise in man and suggest that GABAergic receptor activating benzodiazepines and opioids interact in the neuroendocrine secretion of ACTH/cortisol. PMID:21564163

Expectancy Effects on Conditioned Pain Modulation Are Not Influenced by Naloxone or Morphine.

PubMed

France, Christopher R; Burns, John W; Gupta, Rajnish K; Buvanendran, Asokumar; Chont, Melissa; Schuster, Erik; Orlowska, Daria; Bruehl, Stephen

2016-08-01

Recent studies suggest that participant expectations influence pain ratings during conditioned pain modulation testing. The present study extends this work by examining expectancy effects among individuals with and without chronic back pain after administration of placebo, naloxone, or morphine. This study aims to identify the influence of individual differences in expectancy on changes in heat pain ratings obtained before, during, and after a forearm ischemic pain stimulus. Participants with chronic low back pain (n = 88) and healthy controls (n = 100) rated heat pain experience (i.e., "test stimulus") before, during, and after exposure to ischemic pain (i.e., "conditioning stimulus"). Prior to testing, participants indicated whether they anticipated that their heat pain would increase, decrease, or remain unchanged during ischemic pain. Analysis of the effects of expectancy (pain increase, decrease, or no change), drug (placebo, naloxone, or morphine), and group (back pain, healthy) on changes in heat pain revealed a significant main effect of expectancy (p = 0.001), but no other significant main effects or interactions. Follow-up analyses revealed that individuals who expected lower pain during ischemia reported significantly larger decreases in heat pain as compared with those who expected either no change (p = 0.004) or increased pain (p = 0.001). The present findings confirm that expectancy is an important contributor to conditioned pain modulation effects, and therefore significant caution is needed when interpreting findings that do not account for this individual difference. Opioid mechanisms do not appear to be involved in these expectancy effects.

Experiments on Quantum Hall Topological Phases in Ultra Low Temperatures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Rui-Rui

2015-02-14

This project is to cool electrons in semiconductors to extremely low temperatures and to study new states of matter formed by low-dimensional electrons (or holes). At such low temperatures (and with an intense magnetic field), electronic behavior differs completely from ordinary ones observed at room temperatures or regular low temperature. Studies of electrons at such low temperatures would open the door for fundamental discoveries in condensed matter physics. Present studies have been focused on topological phases in the fractional quantum Hall effect in GaAs/AlGaAs semiconductor heterostructures, and the newly discovered (by this group) quantum spin Hall effect in InAs/GaSb materials.more » This project consists of the following components: 1) Development of efficient sample cooling techniques and electron thermometry: Our goal is to reach 1 mK electron temperature and reasonable determination of electron temperature; 2) Experiments at ultra-low temperatures: Our goal is to understand the energy scale of competing quantum phases, by measuring the temperature-dependence of transport features. Focus will be placed on such issues as the energy gap of the 5/2 state, and those of 12/5 (and possible 13/5); resistive signature of instability near 1/2 at ultra-low temperatures; 3) Measurement of the 5/2 gaps in the limit of small or large Zeeman energies: Our goal is to gain physics insight of 5/2 state at limiting experimental parameters, especially those properties concerning the spin polarization; 4) Experiments on tuning the electron-electron interaction in a screened quantum Hall system: Our goal is to gain understanding of the formation of paired fractional quantum Hall state as the interaction pseudo-potential is being modified by a nearby screening electron layer; 5) Experiments on the quantized helical edge states under a strong magnetic field and ultralow temperatures: our goal is to investigate both the bulk and edge states in a quantum spin Hall insulator

[The study of the role of the water medium in the mechanism of action of peptides in low and ultra low doses].

PubMed

Grigor'ev, E I; Khavinson, V Kh; Malinin, V V; Grigor'ev, A E; Kochnev, I N; Kudriavtseva, T A

2003-01-01

The correlation between the structures and conformations of short peptides KE, EW, AEDG and other, their influence on the dynamic properties of water and dose/biologic effect dependencies in a wide range of concentrations were regarded. Their effects on the dynamic properties of water were studied by temperature dependencies (5-45 degrees C) of infrared spectra of the solutions in the near (5180 cm-1) and far (200 cm-1). In vitro biotesting included the determination of the proliferative activity of thymocytes, a bimodal curve with the second maximum were detected at super-low doses (10(-17)-10(-15) mol/l). Authors propose a hypothesis that for superlow concentrations the formation and distance transmission of a signal from ligand to a target cell without the formation of any ligand-receptor complex take place. An active role in this model belongs to water medium acting according to the solution mechanism.

Calibration of an Ultra-Low-Background Proportional Counter for Measuring 37Ar

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seifert, Allen; Aalseth, Craig E.; Bonicalzi, Ricco

Abstract. An ultra-low-background proportional counter (ULBPC) design has been developed at Pacific Northwest National Laboratory (PNNL) using clean materials, primarily electrochemically-purified copper. This detector, along with an ultra-low-background counting system (ULBCS), was developed to complement a new shallow underground laboratory (30 meters water-equivalent) constructed at PNNL. The ULBCS design includes passive neutron and gamma shielding, along with an active cosmic-veto system. This system provides a capability for making ultra-sensitive measurements to support applications like age-dating soil hydrocarbons with 14C/3H, age-dating of groundwater with 39Ar, and soil-gas assay for 37Ar to support On-Site Inspection (OSI). On-Site Inspection is a key componentmore » of the verification regime for the Comprehensive Nuclear-Test-Ban Treaty (CTBT). Measurements of radionuclides created by an underground nuclear explosion are valuable signatures of a Treaty violation. For OSI, the 35-day half-life of 37Ar, produced from neutron interactions with calcium in soil, provides both high specific activity and sufficient time for inspection before decay limits sensitivity. This work describes the calibration techniques and analysis methods developed to enable quantitative measurements of 37Ar samples over a broad range of pressures. These efforts, along with parallel work in progress on gas chemistry separation, are expected to provide a significant new capability for 37Ar soil gas background studies.« less

100 nm AlSb/InAs HEMT for ultra-low-power consumption, low-noise applications.

PubMed

Gardès, Cyrille; Bagumako, Sonia; Desplanque, Ludovic; Wichmann, Nicolas; Bollaert, Sylvain; Danneville, François; Wallart, Xavier; Roelens, Yannick

2014-01-01

We report on high frequency (HF) and noise performances of AlSb/InAs high electron mobility transistor (HEMT) with 100 nm gate length at room temperature in low-power regime. Extrinsic cut-off frequencies fT/f max of 100/125 GHz together with minimum noise figure NF(min) = 0.5 dB and associated gain G(ass) = 12 dB at 12 GHz have been obtained at drain bias of only 80 mV, corresponding to 4 mW/mm DC power dissipation. This demonstrates the great ability of AlSb/InAs HEMT for high-frequency operation combined with low-noise performances in ultra-low-power regime.

The extramedical use and diversion of opioid substitution medications and other medications in prison settings in Australia following the introduction of buprenorphine-naloxone film.

PubMed

White, Nancy; Ali, Robert; Larance, Briony; Zador, Deborah; Mattick, Richard P; Degenhardt, Louisa

2016-01-01

Around 65% of people incarcerated in prisons in Australia, America and Europe have a history of drug dependence, sometimes treated with opioid substitution treatment (OST) medications. Studies report that those in treatment in prison do engage in some level of diversion to others, whether on a voluntary or coerced basis. We aimed to examine the use of prescribed and non-prescribed OST medications by those in prisons, especially buprenorphine-naloxone film (BNX-F); the extent of non-adherence and diversion and reasons for such practices; and the impact of the introduction of BNX-F into the prison system. Mixed methods study drawing on: (i) structured interviews with current OST clients (n = 60) who reported being incarcerated in the 12 months prior to being interviewed and (ii) qualitative interviews with key experts working in corrections and prison (or justice) health settings. The majority were prescribed OST medications in prison, with 25% removing all or part of their supervised dose on at least one occasion, and 44% reporting use of non-prescribed medications. Some reported intravenous use (14% injected). One-third of OST recipients reported selling/sharing OST medications with others in prison. The introduction of BNX-F into the prison system saw different diversion methods used and removal from dosing within prison. Despite prison being a highly regulated and controlled environment, some level of diversion and sharing of psychoactive medication occurs among prisoners. The buprenorphine formulations used in OST present particular challenges with respect to supervised dosing in this setting. [White N, Ali R, Larance B, Zador D, Mattick RP, Degenhardt L. The extramedical use and diversion of opioid substitution medications and other medications in prison settings in Australia following the introduction of buprenorphine-naloxone film. Drug Alcohol Rev 2015;●●:●●-●●]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Development of UItra-Low Temperature Motor Controllers: Ultra Low Temperatures Evaluation and Characterization of Semiconductor Technologies For The Next Generation Space Telescope

NASA Technical Reports Server (NTRS)

Elbuluk, Malik E.

2003-01-01

Electronics designed for low temperature operation will result in more efficient systems than room temperature. This improvement is a result of better electronic, electrical, and thermal properties of materials at low temperatures. In particular, the performance of certain semiconductor devices improves with decreasing temperature down to ultra-low temperature (-273 'C). The Low Temperature Electronics Program at the NASA Glenn Research Center focuses on research and development of electrical components and systems suitable for applications in deep space missions. Research is being conducted on devices and systems for use down to liquid helium temperatures (-273 'C). Some of the components that are being characterized include semiconductor switching devices, resistors, magnetics, and capacitors. The work performed this summer has focused on the evaluation of silicon-, silicon-germanium- and gallium-Arsenide-based (GaAs) bipolar, MOS and CMOS discrete components and integrated circuits (ICs), from room temperature (23 'C) down to ultra low temperatures (-263 'C).

Low-dose intradermal and intramuscular vaccination against hepatitis B.

PubMed

Bryan, J P; Sjogren, M H; Perine, P L; Legters, L J

1992-03-01

Hepatitis B and its sequelae are global problems preventable by immunization. Expense limits the use of hepatitis B vaccines, but low-dose intradermal immunization has been evaluated as a cost-saving strategy in numerous studies. With few exceptions, low-dose intradermal plasma-derived vaccines have elicited protective levels of antibody in 82%-100% of young healthy adults--a proportion similar to that noted with full-dose regimens; peak levels of antibody to hepatitis B surface antigen (HBsAg) are lower with reduced doses, however. Although children respond well to low-dose intradermal immunization, this procedure is technically difficult in neonates and should not be used for those born to HBsAg-positive mothers. For persons at high risk, antibody to HBsAg must be assessed after immunization to determine the need for a booster dose. A fourth dose 1-2 years after the initial series substantially increases antibody concentrations. In low intradermal doses, recombinant vaccine elicits lower rates of seroconversion than plasma-derived vaccine. However, low intramuscular doses of recombinant vaccine give favorable results. In short, low-dose intradermal or intramuscular immunization offers protection against hepatitis B at significant savings and may be useful for mass immunization of populations at high risk.

Pharmaceutical and pharmacokinetic characterization of a novel sublingual buprenorphine/naloxone tablet formulation in healthy volunteers

PubMed Central

Fischer, Andreas; Hjelmström, Peter

2015-01-01

Abstract Context Bitter taste, as well as dissolve time, presents a significant challenge for the acceptability of formulations for oral transmucosal drug delivery. Objective To characterize a novel sublingual tablet formulation of buprenorphine/naloxone with regards to pharmacokinetics, dissolve time and formulation acceptability. Methods Dry mixing techniques were employed to produce a small and fast dissolving buprenorphine/naloxone sublingual tablet formulation, OX219 (Zubsolv®), using sucralose and menthol as sweetener and flavor to mask the bitter taste of the active ingredients. Two cross-over studies were performed in healthy volunteers to evaluate pharmacokinetics, dissolve time and acceptability of OX219 5.7/1.4 mg tablets compared to the commercially available buprenorphine/naloxone formulations Suboxone® tablets and films (8/2 mg). Results Buprenorphine exposure was equivalent in OX219 and Suboxone tablets. Sublingual dissolve times were significantly shorter for OX219 than for Suboxone tablets and were similar to Suboxone films. The OX219 formulation received significantly higher subjective ratings for taste and overall acceptability than both Suboxone formulations. OX219 was preferred over Suboxone tablet and film formulations by 77.4% and 88.9% of subjects, respectively. Conclusions A sublingual tablet formulation with an improved acceptability has been successfully developed. PMID:24099551

Accuracy of lung nodule volumetry in low-dose CT with iterative reconstruction: an anthropomorphic thoracic phantom study

PubMed Central

Doo, K W; Yong, H S; Woo, O H; Lee, K Y; Oh, Y-W

2014-01-01

Objective: The purpose of this study was to assess accuracy of lung nodule volumetry in low-dose CT with application of iterative reconstruction (IR) according to nodule size, nodule density and CT tube currents, using artificial lung nodules within an anthropomorphic thoracic phantom. Methods: Eight artificial nodules (four diameters: 5, 8, 10 and 12 mm; two CT densities: −630 HU that represents ground-glass nodule and +100 HU that represents solid nodule) were randomly placed inside a thoracic phantom. Scans were performed with tube current–time product to 10, 20, 30 and 50 mAs. Images were reconstructed with IR and filtered back projection (FBP). We compared volume estimates to a reference standard and calculated the absolute percentage error (APE). Results: The APE of all nodules was significantly lower when IR was used than with FBP (7.5 ± 4.7% compared with 9.0 ±6.9%; p < 0.001). The effect of IR was more pronounced for smaller nodules (p < 0.001). IR showed a significantly lower APE than FBP in ground-glass nodules (p < 0.0001), and the difference was more pronounced at the lowest tube current (11.8 ± 5.9% compared with 21.3 ± 6.1%; p < 0.0001). The effect of IR was most pronounced for ground-glass nodules in the lowest CT tube current. Conclusion: Lung nodule volumetry in low-dose CT by application of IR showed reliable accuracy in a phantom study. Lung nodule volumetry can be reliably applicable to all lung nodules including small, ground-glass nodules even in ultra-low-dose CT with application of IR. Advances in knowledge: IR significantly improved the accuracy of lung nodule volumetry compared with FBP particularly for ground-glass (−630 HU) nodules. Volumetry in low-dose CT can be utilized in patient with lung nodule work-up, and IR has benefit for small, ground-glass lung nodules in low-dose CT. PMID:25026866

Descriptive Epidemiology for Community-wide Naloxone Administration by Police Officers and Firefighters Responding to Opioid Overdose.

PubMed

Heavey, Sarah Cercone; Delmerico, Alan M; Burstein, Gale; Moore, Cheryll; Wieczorek, William F; Collins, R Lorraine; Chang, Yu-Ping; Homish, Gregory G

2018-04-01

Recently implemented New York State policy allows police and fire to administer intranasal naloxone when responding to opioid overdoses. This work describes the geographic distribution of naloxone administration (NlxnA) by police and fire when responding to opioid overdoses in Erie County, NY, an area of approximately 920,000 people including the City of Buffalo. Data are from opioid overdose reports (N = 800) filed with the Erie County Department of Health (July 2014-June 2016) by police/fire and include the overdose ZIP code, reported drug(s) used, and NlxnA. ZIP code data were geocoded and mapped to examine spatial patterns of NlxnA. The highest NlxnA rates (range: 0.01-84.3 per 10,000 population) were concentrated within the city and first-ring suburbs. Within 3 min 27.3% responded to NlxnA and 81.6% survived the overdose. The average individual was male (70.3%) and 31.4 years old (SD = 10.3). Further work is needed to better understand NlxnA and overdose, including exploring how the neighborhood environment creates a context for drug use, and how this context influences naloxone use and overdose experiences.

Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor(®)) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhibitors: pharmacokinetic, safety, and efficacy phase I clinical study.

PubMed

Donders, Gilbert; Neven, Patrick; Moegele, Maximilian; Lintermans, Anneleen; Bellen, Gert; Prasauskas, Valdas; Grob, Philipp; Ortmann, Olaf; Buchholz, Stefan

2014-06-01

Phase I pharmacokinetic (PK) study assessed circulating estrogens in breast cancer (BC) patients on a non-steroidal aromatase inhibitor (NSAI) with vaginal atrophy using vaginal ultra-low-dose 0.03 mg estriol (E3) and Lactobacillus combination vaginal tablets (Gynoflor(®)). 16 women on NSAI with severe vaginal atrophy applied a daily vaginal tablet of Gynoflor(®) for 28 days followed by a maintenance therapy of 3 tablets weekly for 8 weeks. Primary outcomes were serum concentrations and PK of E3, estradiol (E2), and estrone (E1) using highly sensitive gas chromatography-mass spectrometry. Secondary outcomes were clinical measures for efficacy and side effects; microscopic changes in vaginal epithelium and microflora; and changes in serum FSH, LH, and sex hormone-binding globulin. Compared with baseline, serum E1 and E2 did not increase in any of the women at any time following vaginal application. Serum E3 transiently increased after the first application in 15 of 16 women, with a maximum of 168 pg/ml 2-3 h post-insertion. After 4 weeks, serum E3 was slightly increased in 8 women with a maximum of 44 pg/ml. The vaginal atrophy resolved or improved in all women. The product was well tolerated, and discontinuation of therapy was not observed. The low-dose 0.03 mg E3 and Lactobacillus acidophilus vaginal tablets application in postmenopausal BC patients during AI treatment suffering from vaginal atrophy lead to small and transient increases in serum E3, but not E1 or E2, and therefore can be considered as safe and efficacious for treatment of atrophic vaginitis in BC patients taking NSAIs.

Low Dose MDCT with Tube Current Modulation: Role in Detection of Urolithiasis and Patient Effective Dose Reduction

PubMed Central

Kakkar, Chandan; Sripathi, Smiti; Parakh, Anushri; Shrivastav, Rajendra

2016-01-01

Introduction Urolithiasis is one of the major, recurring problem in young individuals and CT being the commonest diagnostic modality used. In order to reduce the radiation dose to the patient who are young and as stone formation is a recurring process; one of the simplest way would be, low dose CT along with tube current modulation. Aim Aim of this study was to compare the sensitivity and specificity of low dose (70mAs) with standard dose (250mAs) protocol in detecting urolithiasis and to define the tube current and mean effective patient dose by these protocols. Materials and Methods A prospective study was conducted in 200 patients over a period of 2 years with acute flank pain presentation. CT was performed in 100 cases with standard dose and another 100 with low dose protocol using tube current modulation. Sensitivity and specificity for calculus detection, percentage reduction of dose and tube current with low dose protocol was calculated. Results Urolithiasis was detected in 138 patients, 67 were examined by high dose and 71 were by low dose protocol. Sensitivity and Specificity of low dose protocol was 97.1% and 96.4% with similar results found in high BMI patients. Tube current modulation resulted in reduction of effective tube current by 12.17%. The mean effective patient dose for standard dose was 10.33 mSv whereas 2.92 mSv for low dose with 51.13–53.8% reduction in low dose protocol. Conclusion The study has reinforced that low-dose CT with tube current modulation is appropriate for diagnosis of urolithiasis with significant reduction in tube current and patient effective dose. PMID:27437322

Low Dose MDCT with Tube Current Modulation: Role in Detection of Urolithiasis and Patient Effective Dose Reduction.

PubMed

Koteshwar, Prakashini; Kakkar, Chandan; Sripathi, Smiti; Parakh, Anushri; Shrivastav, Rajendra

2016-05-01

Urolithiasis is one of the major, recurring problem in young individuals and CT being the commonest diagnostic modality used. In order to reduce the radiation dose to the patient who are young and as stone formation is a recurring process; one of the simplest way would be, low dose CT along with tube current modulation. Aim of this study was to compare the sensitivity and specificity of low dose (70mAs) with standard dose (250mAs) protocol in detecting urolithiasis and to define the tube current and mean effective patient dose by these protocols. A prospective study was conducted in 200 patients over a period of 2 years with acute flank pain presentation. CT was performed in 100 cases with standard dose and another 100 with low dose protocol using tube current modulation. Sensitivity and specificity for calculus detection, percentage reduction of dose and tube current with low dose protocol was calculated. Urolithiasis was detected in 138 patients, 67 were examined by high dose and 71 were by low dose protocol. Sensitivity and Specificity of low dose protocol was 97.1% and 96.4% with similar results found in high BMI patients. Tube current modulation resulted in reduction of effective tube current by 12.17%. The mean effective patient dose for standard dose was 10.33 mSv whereas 2.92 mSv for low dose with 51.13-53.8% reduction in low dose protocol. The study has reinforced that low-dose CT with tube current modulation is appropriate for diagnosis of urolithiasis with significant reduction in tube current and patient effective dose.

Systemic effects of low-dose dopamine during administration of cytarabine.

PubMed

Connelly, James; Benani, Dina J; Newman, Matthew; Burton, Bradley; Crow, Jessica; Levis, Mark

2017-09-01

Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m 2 /dose or greater, with or without dopamine at ≤5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low-dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function.

Distribution of naloxone for overdose prevention to chronic pain patients.

PubMed

Coe, Marion A; Walsh, Sharon L

2015-11-01

In this commentary, we reflect on the growing opioid overdose epidemic and propose that chronic pain patients prescribed opioids are contributing to growing mortality rates. We advocate for expanding naloxone access and overdose prevention training, which has historically been directed when available to injection drug users, to chronic pain patients who may be at high risk for accidental opioid overdose. Copyright © 2015 Elsevier Inc. All rights reserved.

Patient Simulation for Assessment of Layperson Management of Opioid Overdose with Intranasal Naloxone in a Recently-Released Prisoner Cohort

PubMed Central

Kobayashi, Leo; Green, Traci C.; Bowman, Sarah E.; Ray, Madeline C.; McKenzie, Michelle S.; Rich, Josiah D.

2016-01-01

Introduction Investigators applied simulation to an experimental program that educated, trained and assessed at-risk, volunteering prisoners on opioid overdose (OD) prevention, recognition and layperson management with intranasal (IN) naloxone. Methods Consenting inmates were assessed for OD-related experience and knowledge then exposed on-site to standardized didactics and educational DVD (without simulation). Subjects were provided with IN naloxone kits at time of release and scheduled for post-release assessment. At follow-up, subjects were evaluated for their performance of layperson opioid OD resuscitative skills during video-recorded simulations. Two investigators independently scored each subject’s resuscitative actions with a 21-item checklist; post-hoc video reviews were separately completed to adjudicate subjects’ interactions for overall benefit or harm. Results One hundred and three prisoners completed the baseline assessment and study intervention then were prescribed IN naloxone kits. One-month follow-up and simulation data were available for 85 subjects (82.5% of trained recruits) who had been released and resided in the community. Subjects’ simulation checklist median score was 12.0 (IQR 11.0–15.0) out of 21 total indicated actions. Forty-four participants (51.8%) correctly administered naloxone; 16 additional subjects (18.8%) suboptimally administered naloxone. Non-indicated actions, primarily chest compressions, were observed in 49.4% of simulations. Simulated resuscitative actions by 80 subjects (94.1%) were determined post-hoc to be beneficial overall for patients overdosing on opioids. Conclusions As part of an opioid OD prevention research program for at-risk inmates, investigators applied simulation to 1-month follow-up assessments of knowledge retention and skills acquisition in post-release participants. Simulation supplemented traditional research tools for investigation of layperson OD management. PMID:28146450

Preventing death among the recently incarcerated: an argument for naloxone prescription before release.

PubMed

Wakeman, Sarah E; Bowman, Sarah E; McKenzie, Michelle; Jeronimo, Alexandra; Rich, Josiah D

2009-01-01

Death from opiate overdose is a tremendous source of mortality, with a heightened risk in the weeks following incarceration. The goal of this study is to assess overdose experience and response among long-term opiate users involved in the criminal justice system. One hundred thirty-seven subjects from a project linking opiate-dependent individuals being released from prison with methadone maintenance programs were asked 73 questions regarding overdose. Most had experienced and witnessed multiple overdoses; 911 was often not called. The majority of personal overdoses occurred within 1 month of having been institutionalized. Nearly all participants expressed an interest in being trained in overdose prevention with Naloxone. The risk of death from overdose is greatly increased in the weeks following release from prison. A pre-release program of overdose prevention education, including Naloxone prescription, for inmates with a history of opiate addiction would likely prevent many overdose deaths.

Circuit design advances for ultra-low power sensing platforms

NASA Astrophysics Data System (ADS)

Wieckowski, Michael; Dreslinski, Ronald G.; Mudge, Trevor; Blaauw, David; Sylvester, Dennis

2010-04-01

This paper explores the recent advances in circuit structures and design methodologies that have enabled ultra-low power sensing platforms and opened up a host of new applications. Central to this theme is the development of Near Threshold Computing (NTC) as a viable design space for low power sensing platforms. In this paradigm, the system's supply voltage is approximately equal to the threshold voltage of its transistors. Operating in this "near-threshold" region provides much of the energy savings previously demonstrated for subthreshold operation while offering more favorable performance and variability characteristics. This makes NTC applicable to a broad range of power-constrained computing segments including energy constrained sensing platforms. This paper explores the barriers to the adoption of NTC and describes current work aimed at overcoming these obstacles in the circuit design space.

Limiting CT radiation dose in children with craniosynostosis: phantom study using model-based iterative reconstruction.

PubMed

Kaasalainen, Touko; Palmu, Kirsi; Lampinen, Anniina; Reijonen, Vappu; Leikola, Junnu; Kivisaari, Riku; Kortesniemi, Mika

2015-09-01

Medical professionals need to exercise particular caution when developing CT scanning protocols for children who require multiple CT studies, such as those with craniosynostosis. To evaluate the utility of ultra-low-dose CT protocols with model-based iterative reconstruction techniques for craniosynostosis imaging. We scanned two pediatric anthropomorphic phantoms with a 64-slice CT scanner using different low-dose protocols for craniosynostosis. We measured organ doses in the head region with metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters. Numerical simulations served to estimate organ and effective doses. We objectively and subjectively evaluated the quality of images produced by adaptive statistical iterative reconstruction (ASiR) 30%, ASiR 50% and Veo (all by GE Healthcare, Waukesha, WI). Image noise and contrast were determined for different tissues. Mean organ dose with the newborn phantom was decreased up to 83% compared to the routine protocol when using ultra-low-dose scanning settings. Similarly, for the 5-year phantom the greatest radiation dose reduction was 88%. The numerical simulations supported the findings with MOSFET measurements. The image quality remained adequate with Veo reconstruction, even at the lowest dose level. Craniosynostosis CT with model-based iterative reconstruction could be performed with a 20-μSv effective dose, corresponding to the radiation exposure of plain skull radiography, without compromising required image quality.

Chromatic dispersion effects in ultra-low coherence interferometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lychagov, V V; Ryabukho, V P

2015-06-30

We consider the properties of an interference signal shift from zero-path-difference position in the presence of an uncompensated dispersive layer in one of the interferometer arms. It is experimentally shown that in using an ultra-low coherence light source, the formation of the interference signal is also determined by the group velocity dispersion, which results in a nonlinear dependence of the position of the interference signal on the geometrical thickness of the dispersive layer. The discrepancy in the dispersive layer and compensator refractive indices in the third decimal place is experimentally shown to lead to an interference signal shift that ismore » an order of magnitude greater than the pulse width. (interferometry)« less

Preincisional and postoperative epidural morphine, ropivacaine, ketamine, and naloxone treatment for postoperative pain management in upper abdominal surgery.

PubMed

Lai, Hou-Chuan; Hsieh, Chung-Bao; Wong, Chih-Shung; Yeh, Chun-Chang; Wu, Zhi-Fu

2016-09-01

Previous studies have shown that preincisional epidural morphine, bupivacaine, and ketamine combined with epidural anesthesia (EA) and general anesthesia (GA) provided pre-emptive analgesia for upper abdominal surgery. Recent studies reported that ultralow-dose naloxone enhanced the antinociceptive effect of morphine in rats. This study investigated the benefits of preincisional and postoperative epidural morphine + ropivacaine + ketamine + naloxone (M + R + K + N) treatment for achieving postoperative pain relief in upper abdominal surgery. Eighty American Society of Anesthesiology I-II patients scheduled for major upper abdominal surgery were allocated to four groups in a randomized, single-blinded study. All patients received combined GA and EA with a continuous epidural infusion of 2% lidocaine (6-8 mL/h) 30 minutes after pain regimen. After GA induction, in Group I, an epidural pain control regimen (total 10 mL) was administered using 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg; M + R); in Group II, 1% lidocaine 8 (mL) + morphine (2 mg) + ropivacaine (20 mg) + ketamine (20 mg; M + R + K); in Group III, 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg) + naloxone (2 μg; M + R + N); and in Group IV, 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg) + ketamine (20 mg) + naloxone (2 μg; M + R + K + N), respectively. All patients received patient-controlled epidural analgesia (PCEA) with different pain regimens to control subsequent postoperative pain for 3 days following surgery. During the 3-day period following surgery, PCEA consumption (mL), numerical rating scale (NRS) score while cough/moving, and analgesic-related adverse effects were recorded. Total PCEA consumption for the 3-day observation period was 161.5±17.8 mL, 103.2±21.7 mL, 152.4±25.6 mL, and 74.1±16.9 mL for Groups I, II, III, and IV, respectively. (p < 0.05). The cough/moving NRS

Performance study of personal inhalable aerosol samplers at ultra-low wind speeds.

PubMed

Sleeth, Darrah K; Vincent, James H

2012-03-01

The assessment of personal inhalable aerosol samplers in a controlled laboratory setting has not previously been carried out at the ultra-low wind speed conditions that represent most modern workplaces. There is currently some concern about whether the existing inhalable aerosol convention is appropriate at these low wind speeds and an alternative has been suggested. It was therefore important to assess the performance of the most common personal samplers used to collect the inhalable aerosol fraction, especially those that were designed to match the original curve. The experimental set-up involved use of a hybrid ultra-low speed wind tunnel/calm air chamber and a rotating, heating breathing mannequin to measure the inhalable fraction of aerosol exposure. The samplers that were tested included the Institute of Occupational Medicine (IOM), Button, and GSP inhalable samplers as well as the closed-face cassette sampler that has been (and still is) widely used by occupational hygienists in many countries. The results showed that, down to ∼0.2 m s(-1), the samplers matched the current inhalability criterion relatively well but were significantly greater than this at the lowest wind speed tested. Overall, there was a significant effect of wind speed on sampling efficiency, with lower wind speeds clearly associated with an increase in sampling efficiency.

100 nm AlSb/InAs HEMT for Ultra-Low-Power Consumption, Low-Noise Applications

PubMed Central

Bagumako, Sonia; Desplanque, Ludovic; Wichmann, Nicolas; Bollaert, Sylvain; Danneville, François; Wallart, Xavier

2014-01-01

We report on high frequency (HF) and noise performances of AlSb/InAs high electron mobility transistor (HEMT) with 100 nm gate length at room temperature in low-power regime. Extrinsic cut-off frequencies f T/f max of 100/125 GHz together with minimum noise figure NFmin = 0.5 dB and associated gain G ass = 12 dB at 12 GHz have been obtained at drain bias of only 80 mV, corresponding to 4 mW/mm DC power dissipation. This demonstrates the great ability of AlSb/InAs HEMT for high-frequency operation combined with low-noise performances in ultra-low-power regime. PMID:24707193

Impulse Excitation Internal Friction Study of Dislocation and Point Defect Interactions in Ultra-Low Carbon Bake-Hardenable Steel

NASA Astrophysics Data System (ADS)

Jung, Il-Chan; Kang, Deok-Gu; De Cooman, Bruno C.

2014-04-01

The simultaneous presence of interstitial solutes and dislocations in an ultra-low carbon bake-hardenable steel gives rise to two characteristic peaks in the internal friction (IF) spectrum: the dislocation-enhanced Snoek peak and the Snoek-Kê-Köster peak. These IF peaks were used to study the dislocation structure developed by the pre-straining and the static strain aging effect of C during the bake-hardening process. A Ti-stabilized interstitial-free steel was used to ascertain the absence of a γ-peak in the IF spectrum of the deformed ultra-low carbon steel. The analysis of the IF data shows clearly that the bake-hardening effect in ultra-low carbon steel is entirely due to atmosphere formation, with the dislocation segment length being the main parameter affecting the IF peak amplitude. Recovery annealing experiments showed that the rearrangement of the dislocation structure lead to the elimination of the C atmosphere.

Utilizing buprenorphine–naloxone to treat illicit and prescription-opioid dependence

PubMed Central

Mauger, Sofie; Fraser, Ronald; Gill, Kathryn

2014-01-01

Objectives To review current evidence on buprenorphine–naloxone (bup/nx) for the treatment of opioid-use disorders, with a focus on strategies for clinical management and office-based patient care. Quality of evidence Medline and the Cochrane Database of Systematic Reviews were searched. Consensus reports, guidelines published, and other authoritative sources were also included in this review. Apart from expert guidelines, data included in this review constitute level 1 evidence. Findings Bup/nx is a partial μ-opioid agonist combined with the opioid antagonist naloxone in a 4:1 ratio. It has a lower abuse potential, carries less stigma, and allows for more flexibility than methadone. Bup/nx is indicated for both inpatient and ambulatory medically assisted withdrawal (acute detoxification) and long-term substitution treatment (maintenance) of patients who have a mild-to-moderate physical dependence. A stepwise long-term substitution treatment with regular monitoring and follow-up assessment is usually preferred, as it has better outcomes in reducing illicit opioid use, minimizing concomitant risks such as human immunodeficiency virus and hepatitis C transmission, retaining patients in treatment and improving global functioning. Conclusion Bup/nx is safe and effective for opioid detoxification and substitution treatment. Its unique pharmaceutical properties make it particularly suitable for office-based maintenance treatment of opioid-use disorder. PMID:24741316

Using MOF-74 for Hg{sup 2+} removal from ultra-low concentration aqueous solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiong, Yang Yang; Li, Jian Qiang; Gong, Le Le

Mercury (Hg{sup 2+}) ions have very high toxicity and widely spread as environmental pollutants. At present, many efforts have been taken to remove the hazardous materials of mercury(II) by adsorption, and it is highly desirable to develop a novel adsorbent with high adsorptive capacities. However it is still a big challenge to remove the ultra-low-concentration mercury ions from water. In this paper, MOF-74-Zn is explored for such function, showing high removal rate of Hg(II) from water without any pretreatment, especially for the ultra-trace Hg(II) ions in the ppb magnitude with the removal rate reaching to 54.48%, 69.71%, 72.26% when themore » initial concentration of Hg(II) is 20ppb, 40ppb, 50ppb, respectively. - Graphical abstract: The absorption of mercury ions on MOF-74-Zn is due to somewhat weak interactions between MOF skeleton that is composed of carboxylate and hydroxy group and Hg2+ ions. - Highlights: • MOF-74-Zn shows high removal rate of Hg(II) from water without any pretreatment. • The MOF-74-Zn has a notable performance at ultra-low concentration of Hg(II). • MOF-74-Zn shows the potential for Hg(II) removal from industrial waste water.« less

Ultra-low-loss and broadband mode converters in Si3N4 technology

NASA Astrophysics Data System (ADS)

Mu, Jinfeng; Dijkstra, Meindert; de Goede, Michiel; Yong, Yean-Sheng; García-Blanco, Sonia M.

2017-02-01

Si3N4 grown by low pressure chemical vapor deposition (LPCVD) on thermally oxidized silicon wafers is largely utilized for creating integrated photonic devices due to its ultra-low propagation loss and large transparency window (400 nm to 2350 nm). In this paper, an ultra-low-loss and broadband mode converter for monolithic integration of different materials onto the passive Si3N4 photonic technology platform is presented. The mode size converter is constructed with a vertically tapered Si3N4 waveguide that is then buried by a polymer or an Al2O3 waveguide. The influence of the various design parameters on the converter characteristics are investigated. Optimal designs are proposed, in which the thickness of the Si3N4 waveguide is tapered from 200 nm to 40 nm. The calculated losses of the mode converters at 976 nm and 1550 nm wavelengths are well below 0.1 dB for the Si3N4-polymer coupler and below 0.3 dB for the Si3N4-Al2O3 coupler. The preliminary experimental results show good agreement with the design values, indicating that the mode converters can be utilized for the low-loss integration of different materials.

Ultra-low-head hydroelectric technology: A review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Daqing; Deng, Zhiqun

In recent years, distributed renewable energy-generation technologies, such as wind and solar, have developed rapidly. Nevertheless, the utilization of ultra-low-head (ULH) water energy (i.e., situations where the hydraulic head is less than 3 m or the water flow is more than 0.5 m/s with zero head) has received little attention. We believe that, through technological innovations and cost reductions, ULH hydropower has the potential to become an attractive, renewable, and sustainable resource. This paper investigates potential sites for ULH energy resources, the selection of relevant turbines and generators, simplification of civil works, and project costs. This review introduces the currentmore » achievements on ULH hydroelectric technology to stimulate discussions and participation of stakeholders to develop related technologies for further expanding its utilization as an important form of renewable energy.« less

High-dose Versus Low-dose Tranexamic Acid to Reduce Transfusion Requirements in Pediatric Scoliosis Surgery.

PubMed

Johnson, Daniel J; Johnson, Christine C; Goobie, Susan M; Nami, Nina; Wetzler, Joshua A; Sponseller, Paul D; Frank, Steven M

2017-12-01

Our objective was to quantify blood loss and transfusion requirements for high-dose and low-dose tranexamic acid (TXA) dosing regimens in pediatric patients undergoing spinal fusion for correction of idiopathic scoliosis. Previous investigators have established the efficacy of TXA in pediatric scoliosis surgery; however, the dosing regimens vary widely and the optimal dose has not been established. We retrospectively analyzed electronic medical records for 116 patients who underwent spinal fusion surgery for idiopathic scoliosis by a single surgeon and were treated with TXA. In total, 72 patients received a 10 mg/kg loading dose with a 1 mg/kg/h maintenance dose (low-dose) and 44 patients received 50 mg/kg loading dose with a 5 mg/kg/h maintenance dose (high-dose). Estimated blood loss and transfusion requirements were compared between dosing groups. Patient characteristics were nearly identical between the 2 groups. Compared with the low-dose TXA group, the high-dose TXA group had decreased estimated blood loss (695 vs. 968 mL, P=0.01), and a decrease in both intraoperative (0.3 vs. 0.9 units, P=0.01) and whole hospitalization (0.4 vs. 1.0 units, P=0.04) red blood cell transfusion requirements. The higher-dose TXA was associated with decreased intraoperative (P=0.01), and whole hospital transfusion (P=0.01) requirements, even after risk-adjustment for potential confounding variables. High-dose TXA is more effective than low-dose TXA in reducing blood loss and transfusion requirements in pediatric idiopathic scoliosis patients undergoing surgery. Level-III, retrospective cohort study.

Treatment of Hailey-Hailey Disease With Low-Dose Naltrexone.

PubMed

Albers, Lauren N; Arbiser, Jack L; Feldman, Ron J

2017-10-01

Hailey-Hailey disease is a severe genetic blistering disease of intertriginous skin locations that can lead to poor quality of life and increased morbidities. Multiple therapies are available with inconsistent outcomes and potentially severe adverse effects. To determine whether low-dose naltrexone is an effective treatment for Hailey-Hailey disease. This study was a case series performed at a dermatology outpatient clinic of 3 patients with severe Hailey-Hailey disease recalcitrant to at least 4 therapies. Low-dose naltrexone, 3 mg nightly, titrated to 4.5 mg nightly in 2 patients. Reduction in size of lesions as well as subjective improvement of symptoms. All 3 patients noted significant healing of erosions and plaques starting from the peripheral aspect within 1 to 2 weeks of treatment, and clinical resolution of lesions within 2 months. Discontinuation of low-dose naltrexone resulted in flaring of symptoms, which cleared within 2 to 3 days on rechallenge with low-dose naltrexone. We present herein 3 cases of patients with severe Hailey-Hailey disease treated with low-dose naltrexone who achieved clinical resolution of symptoms. The success of these cases suggests low-dose naltrexone as a novel therapy for Hailey-Hailey disease. The possible mechanism may involve low-dose naltrexone influencing opioid or toll-like receptor signaling to improve calcium mobilization and improve keratinocyte differentiation and wound healing. Future studies are needed to clarify the mechanism and to define the role of low-dose naltrexone for treatment of Hailey-Hailey disease.

Persistence and healthcare utilization associated with the use of buprenorphine/naloxone film and tablet formulation therapy in adults with opioid dependence.

PubMed

Clay, Emilie; Khemiri, Amine; Zah, Vladimir; Aballéa, Samuel; Ruby, Jane; Asche, Carl V

2014-09-01

Buprenorphine/naloxone film was developed to improve retention in treatment and reduce public health risks over the tablet formulation for opioid dependence. To compare patient persistence and resource utilization between formulations for the treatment of opioid dependence. A longitudinal, retrospective cohort analysis was conducted to compare persistence and healthcare costs in a private US insurance claims database. Previously untreated patients, who initiated treatment with buprenorphine/naloxone following the introduction of the film, were classified in two groups according to the initial prescription. Persistence was defined as the proportion of patients continuing treatment for at least 6 months. Resource utilization and related costs were calculated over the 6- and 12-month periods after treatment initiation. Film and tablet groups included 2796 and 1510 patients enrolled over 9.76 and 13.76 months on average, respectively, from initiation of treatment. Patient characteristics were similar between groups. Mean prescribed doses were 14.62 and 14.26 mg/day in film and tablet groups. Among patients enrolled for at least 6 months from the initial treatment, persistence rates were 63.78% with film vs 58.13% with tablet. Time to treatment discontinuation was longer in the film group, with a hazard ratio of 0.818 (p = 0.0005, 95% CI = [0.730;0.916]) adjusted for baseline characteristics. Patients treated with film had significantly more outpatient visits (+4%, p = 0.0185) and lower probability to be hospitalized (-17%, p = 0.0158), resulting in lower total healthcare costs over the 12-month period after initiation (-27%, p < 0.0001). Patients treated with the film formulation of buprenorphine/naloxone appeared to stay longer on treatment, have a lower probability of hospital admission, and lower health care costs compared to patients treated with the tablet. This study, based on insurance claims data, has the advantage of reflecting real-world practice, but one

Enhancing acupuncture by low dose naltrexone.

PubMed

Hesselink, Jan M Keppel; Kopsky, David J

2011-06-01

To find appropriate and effective treatment options for chronic pain syndromes is a challenging task. Multimodal treatment approach has been gaining acceptance for chronic pain. However, combining treatments, such as acupuncture, with rational pharmacology is still in its infancy. Acupuncture influences the opioid and cannabinoid system through releasing endogenous receptor ligands. Low dose naltrexone also acts on both these systems, and upregulates the opioid and cannabinoid receptors. The authors hypothesise that low dose naltrexone could enhance the pain-relieving effect of acupuncture.

Effects of naloxone distribution alone or in combination with addiction treatment with or without pre-exposure prophylaxis for HIV prevention in people who inject drugs: a cost-effectiveness modelling study.

PubMed

Uyei, Jennifer; Fiellin, David A; Buchelli, Marianne; Rodriguez-Santana, Ramon; Braithwaite, R Scott

2017-03-01

In the USA, an epidemic of opioid overdose deaths is occurring, many of which are from heroin. Combining naloxone distribution with linkage to addiction treatment or pre-exposure prophylaxis (PrEP) for HIV prevention through syringe service programmes has the potential to save lives and be cost-effective. We estimated the outcomes and cost-effectiveness of five alternative strategies: no additional intervention, naloxone distribution, naloxone distribution plus linkage to addiction treatment, naloxone distribution plus PrEP, and naloxone distribution plus linkage to addiction treatment and PrEP. We developed a decision analytical Markov model to simulate opioid overdose, HIV incidence, overdose-related deaths, and HIV-related deaths in people who inject drugs in Connecticut, USA. Model input parameters were derived from published sources. We compared each strategy with no intervention, as well as simultaneously considering all strategies. Sensitivity analysis was done for all variables. Linkage to addiction treatment was referral to an opioid treatment programme for methadone. Endpoints were survival, life expectancy, quality-adjusted life-years (QALYs), number and percentage of overdose deaths averted, number of HIV-related deaths averted, total costs (in 2015 US$) associated with each strategy, and incremental cost per QALY gained. In the base-case analysis, compared with no additional intervention, the naloxone distribution strategy yielded an incremental cost-effectiveness ratio (ICER) of $323 per QALY, and naloxone distribution plus linkage to addiction treatment was cost saving compared with no additional intervention (greater effectiveness and less expensive). The most efficient strategies (ie, those conferring the greatest health benefit for a particular budget) were naloxone distribution combined with linkage to addiction treatment (cost saving), and naloxone distribution combined with PrEP and linkage to addiction treatment (ICER $95 337 per QALY) at a

78 FR 34108 - Determination That SUBOXONE (Buprenorphine Hydrochloride and Naloxone Hydrochloride) Sublingual...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... naloxone HCl) sublingual tablets, 2 mg/0.5 mg and 8 mg/2 mg, are the subject of NDA 20-733, held by Reckitt Benckiser Pharmaceuticals, Inc. (Reckitt), and initially approved on October 8, 2002. SUBOXONE is indicated...,'' http://www.rb.com/site/rkbr/templates/mediainvestorsgeneral2.aspx?pageid=1332&cc=GB , Reckitt Benckiser...

Orienting patients to greater opioid safety: models of community pharmacy-based naloxone.

PubMed

Green, Traci C; Dauria, Emily F; Bratberg, Jeffrey; Davis, Corey S; Walley, Alexander Y

2015-08-06

The leading cause of adult injury death in the U.S.A. is drug overdose, the majority of which involves prescription opioid medications. Outside of the U.S.A., deaths by drug overdose are also on the rise, and overdose is a leading cause of death for drug users. Reducing overdose risk while maintaining access to prescription opioids when medically indicated requires careful consideration of how opioids are prescribed and dispensed, how patients use them, how they interact with other medications, and how they are safely stored. Pharmacists, highly trained professionals expert at detecting and managing medication errors and drug-drug interactions, safe dispensing, and patient counseling, are an under-utilized asset in addressing overdose in the U.S. and globally. Pharmacies provide a high-yield setting where patient and caregiver customers can access naloxone-an opioid antagonist that reverses opioid overdose-and overdose prevention counseling. This case study briefly describes and provides two US state-specific examples of innovative policy models of pharmacy-based naloxone, implemented to reduce overdose events and improve opioid safety: Collaborative Pharmacy Practice Agreements and Pharmacy Standing Orders.

Deep learning for low-dose CT

NASA Astrophysics Data System (ADS)

Chen, Hu; Zhang, Yi; Zhou, Jiliu; Wang, Ge

2017-09-01

Given the potential risk of X-ray radiation to the patient, low-dose CT has attracted a considerable interest in the medical imaging field. Currently, the main stream low-dose CT methods include vendor-specific sinogram domain filtration and iterative reconstruction algorithms, but they need to access raw data whose formats are not transparent to most users. Due to the difficulty of modeling the statistical characteristics in the image domain, the existing methods for directly processing reconstructed images cannot eliminate image noise very well while keeping structural details. Inspired by the idea of deep learning, here we combine the autoencoder, deconvolution network, and shortcut connections into the residual encoder-decoder convolutional neural network (RED-CNN) for low-dose CT imaging. After patch-based training, the proposed RED-CNN achieves a competitive performance relative to the-state-of-art methods. Especially, our method has been favorably evaluated in terms of noise suppression and structural preservation.

Austrian Mirrors: Development of Ultra-Low-Loss Cryogenic Crystalline Coatings (DARPA)

DTIC Science & Technology

2016-07-13

AFRL-AFOSR-UK-TR-2016-0013 Austrian Mirrors: Development of ultra-low- loss cryogenic crystalline coatings (DARPA) Garrett Cole Crystalline Mirror...REPORT DOCUMENTATION PAGE Form ApprovedOMB No . 0704-0188 The public reporting burden for this collection of information is estimated to average 1 hour...that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information   if

Preoperative assessment of pleural adhesion by Four-Dimensional Ultra-Low-Dose Computed Tomography (4D-ULDCT) with Adaptive Iterative Dose Reduction using Three-Dimensional processing (AIDR-3D).

PubMed

Hashimoto, Masayuki; Nagatani, Yukihiro; Oshio, Yasuhiko; Nitta, Norihisa; Yamashiro, Tsuneo; Tsukagoshi, Shinsuke; Ushio, Noritoshi; Mayumi, Masayuki; Kimoto, Tatsuya; Igarashi, Tomoyuki; Yoshigoe, Makoto; Iwai, Kyohei; Tanaka, Koki; Sato, Shigetaka; Sonoda, Akinaga; Otani, Hideji; Murata, Kiyoshi; Hanaoka, Jun

2018-01-01

To assess the feasibility of Four-Dimensional Ultra-Low-Dose Computed Tomography (4D-ULDCT) for distinguishing pleural aspects with localized pleural adhesion (LPA) from those without. Twenty-seven patients underwent 4D-ULDCT during a single respiration with a 16cm-coverage of the body axis. The presence and severity of LPA was confirmed by their intraoperative thoracoscopic findings. A point on the pleura and a corresponding point on the outer edge of the costal bone were placed in identical axial planes at end-inspiration. The distance of the two points (PCD), traced by automatic tracking functions respectively, was calculated at each respiratory phase. The maximal and average change amounts in PCD (PCD MCA and PCD ACA ) were compared among 110 measurement points (MPs) without LPA, 16MPs with mild LPA and 10MPs with severe LPA in upper lung field cranial to the bronchial bifurcation (ULF), and 150MPs without LPA, 17MPs with mild LPA and 9MPs with severe LPA in lower lung field caudal to the bronchial bifurcation (LLF) using the Mann-Whitney U test. In the LLF, PCD ACA as well as PCD MCA demonstrated a significant difference among non-LPA, mild LPA and severe LPA (18.1±9.2, 12.3±6.2 and 5.0±3.3mm) (p<0.05). Also in the ULF, PCD ACA showed a significant difference among three conditions (9.2±5.5, 5.7±2.8 and 2.2±0.4mm, respectively) (p<0.05), whereas PCD MCA for mild LPA was similar to that for non-LPA (12.3±5.9 and 17.5±11.0mm). Four D-ULDCT could be a useful non-invasive preoperative assessment modality for the detection of the presence or severity of LPA. Copyright © 2017 Elsevier B.V. All rights reserved.

Super-low dose endotoxin pre-conditioning exacerbates sepsis mortality.

PubMed

Chen, Keqiang; Geng, Shuo; Yuan, Ruoxi; Diao, Na; Upchurch, Zachary; Li, Liwu

2015-04-01

Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditionings with super-low or low dose endotoxin lipopolysaccharide (LPS) cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP). This is in opposite to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET) in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a novel mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks.

Rotatable Small Permanent Magnet Array for Ultra-Low Field Nuclear Magnetic Resonance Instrumentation: A Concept Study.

PubMed

Vogel, Michael W; Giorni, Andrea; Vegh, Viktor; Pellicer-Guridi, Ruben; Reutens, David C

2016-01-01

We studied the feasibility of generating the variable magnetic fields required for ultra-low field nuclear magnetic resonance relaxometry with dynamically adjustable permanent magnets. Our motivation was to substitute traditional electromagnets by distributed permanent magnets, increasing system portability. The finite element method (COMSOL®) was employed for the numerical study of a small permanent magnet array to calculate achievable magnetic field strength, homogeneity, switching time and magnetic forces. A manually operated prototype was simulated and constructed to validate the numerical approach and to verify the generated magnetic field. A concentric small permanent magnet array can be used to generate strong sample pre-polarisation and variable measurement fields for ultra-low field relaxometry via simple prescribed magnet rotations. Using the array, it is possible to achieve a pre-polarisation field strength above 100 mT and variable measurement fields ranging from 20-50 μT with 200 ppm absolute field homogeneity within a field-of-view of 5 x 5 x 5 cubic centimetres. A dynamic small permanent magnet array can generate multiple highly homogeneous magnetic fields required in ultra-low field nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) instruments. This design can significantly reduce the volume and energy requirements of traditional systems based on electromagnets, improving portability considerably.

[Competitive study of the effects of naloxone and of almitrine on fentanyl analgesia in the anesthetized dog: effects on the muzzle opening reflex and blood gases].

PubMed

Dauthier, C; Gaudy, J H; Willer, J C

1980-01-01

The search for a technique making it possible to dissociate the analgesia and ventilatory depression of central analgesics led to a comparison of the effects of naloxone, a specific morphinomimetic antagonist, with almitrine, a ventilatory stimulant with a peripheral action, on muzzle opening reflex and blood gases. Five male dogs (Beagles, aged one year), anaesthetised with Alfetesine were treated separately with the two drugs used alone and after fentanyl analgesia (injection of fractionnated doses up to the threshold of apnoea). The association of the two drugs was also tested in tyhe dog after analgesia. The parameters studied were muzzle opening reflex, as an indication of analgesia, and blood gases, and were observed for 45 minutes, including 15 minutes control. 1 - The intravenous injection of 1,2 mg of naloxone had the effect of increasing the surface area of muscle potentials with a maximum of 7 per cent (p 0.001) at the 15 th minute. By contrast, no significant change in blood gases was seen. In the same dogs given fentanyl analgesia, naloxone not only reversed respiratory depression but had a stimulatory effect on MOR reaching 7 per cent (p 0.001) at the 30 th minute. 2 - The effects of 1 mg.kg-1 of almitrine were characterised by a fall in MOR for a period equal to that of the study and a minimum of 7.8 per cent (p 0.001) at the 20 th minute. At the same time, marked ventilatory stimulation was seen. PO2 rose by 22.7 per cent (p 0.02) at the 5 th minute. PCO2 fell during the 30 minutes studied with a minimum of 39.6 per cent (p 0.01) at the 20 th minute. Almitrine did not antagonise the depression of MOR caused by fentanyl but reversed the respiratory depression of the analgesic, increasing PO2 by 26 per cent (p 0.01) and decreasing PCO2 by 25.7 per cent (p 0.01). 3 - The combination of both drugs cancelled out the abolition of the reflex by fentanyl then facilitated it up to 24.7 per cent (p 0.001) in comparison with the animal not receiving any

Restored low-dose digital breast tomosynthesis: a perception study

NASA Astrophysics Data System (ADS)

Borges, Lucas R.; Bakic, Predrag R.; Maidment, Andrew D. A.; Vieira, Marcelo A. C.

2018-03-01

This work investigates the perception of noise from restored low-dose digital breast tomosynthesis (DBT) images. First, low-dose DBT projections were generated using a dose reduction simulation algorithm. A dataset of clinical images from the Hospital of the University of Pennsylvania was used for this purpose. Low-dose projections were then denoised with a denoising pipeline developed specifically for DBT images. Denoised and noisy projections were combined to generate images with signal-to-noise ratio comparable to the full-dose images. The quality of restored low-dose and full-dose projections were first compared in terms of an objective no-reference image quality metric previously validated for mammography. In the second analysis, regions of interest (ROIs) were selected from reconstructed full-dose and restored low-dose slices, and were displayed side-by-side on a high-resolution medical display. Five medical physics specialists were asked to choose the image containing less noise and less blur using a 2-AFC experiment. The objective metric shows that, after the proposed image restoration framework was applied, images with as little as 60% of the AEC dose yielded similar quality indices when compared to images acquired with the full-dose. In the 2-AFC experiments results showed that when the denoising framework was used, 30% reduction in dose was possible without any perceived difference in noise or blur. Note that this study evaluated the observers perception to noise and blur and does not claim that the dose of DBT examinations can be reduced with no harm to the detection of cancer. Future work is necessary to make any claims regarding detection, localization and characterization of lesions.

The Impact of Take-Home Naloxone Distribution and Training on Opiate Overdose Knowledge and Response: An Evaluation of the THN Project in Wales

ERIC Educational Resources Information Center

Bennett, Trevor; Holloway, Katy

2012-01-01

Aims: To determine the impact of naloxone training on knowledge of opiate overdose and confidence and willingness to take appropriate action and to examine the use of naloxone and other harm-reduction actions at the time of overdose events. Methods: The evaluation was based on a repeated-measure design, whereby clients were tested before and after…

Simultaneous measurement of tritium and radiocarbon by ultra-low-background proportional counting.

PubMed

Mace, Emily; Aalseth, Craig; Alexander, Tom; Back, Henning; Day, Anthony; Hoppe, Eric; Keillor, Martin; Moran, Jim; Overman, Cory; Panisko, Mark; Seifert, Allen

2017-08-01

Use of ultra-low-background capabilities at Pacific Northwest National Laboratory provide enhanced sensitivity for measurement of low-activity sources of tritium and radiocarbon using proportional counters. Tritium levels are nearly back to pre-nuclear test backgrounds (~2-8 TU in rainwater), which can complicate their dual measurement with radiocarbon due to overlap in the beta decay spectra. We present results of single-isotope proportional counter measurements used to analyze a dual-isotope methane sample synthesized from ~120mg of H 2 O and present sensitivity results. Copyright © 2017 Elsevier Ltd. All rights reserved.

Simultaneous measurement of tritium and radiocarbon by ultra-low-background proportional counting

DOE PAGES

Mace, Emily; Aalseth, Craig; Alexander, Tom; ...

2016-12-21

Use of ultra-low-background capabilities at Pacific Northwest National Laboratory provide enhanced sensitivity for measurement of low-activity sources of tritium and radiocarbon using proportional counters. Tritium levels are nearly back to pre-nuclear test backgrounds (~2-8 TU in rainwater), which can complicate their dual measurement with radiocarbon due to overlap in the beta decay spectra. In this paper, we present results of single-isotope proportional counter measurements used to analyze a dual-isotope methane sample synthesized from ~120 mg of H 2O and present sensitivity results.

Super non-linear RRAM with ultra-low power for 3D vertical nano-crossbar arrays.

PubMed

Luo, Qing; Xu, Xiaoxin; Liu, Hongtao; Lv, Hangbing; Gong, Tiancheng; Long, Shibing; Liu, Qi; Sun, Haitao; Banerjee, Writam; Li, Ling; Gao, Jianfeng; Lu, Nianduan; Liu, Ming

2016-08-25

Vertical crossbar arrays provide a cost-effective approach for high density three-dimensional (3D) integration of resistive random access memory. However, an individual selector device is not allowed to be integrated with the memory cell separately. The development of V-RRAM has impeded the lack of satisfactory self-selective cells. In this study, we have developed a high performance bilayer self-selective device using HfO2 as the memory switching layer and a mixed ionic and electron conductor as the selective layer. The device exhibits high non-linearity (>10(3)) and ultra-low half-select leakage (<0.1 pA). A four layer vertical crossbar array was successfully demonstrated based on the developed self-selective device. High uniformity, ultra-low leakage, sub-nA operation, self-compliance, and excellent read/write disturbance immunity were achieved. The robust array level performance shows attractive potential for low power and high density 3D data storage applications.

Ultra compact 45 GHz CMOS compatible Germanium waveguide photodiode with low dark current.

PubMed

DeRose, Christopher T; Trotter, Douglas C; Zortman, William A; Starbuck, Andrew L; Fisher, Moz; Watts, Michael R; Davids, Paul S

2011-12-05

We present a compact 1.3 × 4 μm2 Germanium waveguide photodiode, integrated in a CMOS compatible silicon photonics process flow. This photodiode has a best-in-class 3 dB cutoff frequency of 45 GHz, responsivity of 0.8 A/W and dark current of 3 nA. The low intrinsic capacitance of this device may enable the elimination of transimpedance amplifiers in future optical data communication receivers, creating ultra low power consumption optical communications.

Low-dose radiation attenuates chemical mutagenesis in vivo.

PubMed

Kakinuma, Shizuko; Yamauchi, Kazumi; Amasaki, Yoshiko; Nishimura, Mayumi; Shimada, Yoshiya

2009-09-01

The biological effects of low-dose radiation are not only of social concern but also of scientific interest. The radioadaptive response, which is defined as an increased radioresistance by prior exposure to low-dose radiation, has been extensively studied both in vitro and in vivo. Here we briefly review the radioadaptive response with respect to mutagenesis, survival rate, and carcinogenesis in vivo, and introduce our recent findings of cross adaptation in mouse thymic cells, that is, the suppressive effect of repeated low-dose radiation on mutation induction by the alkylating agent N-ethyl-N-nitrosourea.

Ultra-low loss Si3N4 waveguides with low nonlinearity and high power handling capability.

PubMed

Tien, Ming-Chun; Bauters, Jared F; Heck, Martijn J R; Blumenthal, Daniel J; Bowers, John E

2010-11-08

We investigate the nonlinearity of ultra-low loss Si3N4-core and SiO2-cladding rectangular waveguides. The nonlinearity is modeled using Maxwell's wave equation with a small amount of refractive index perturbation. Effective n2 is used to describe the third-order nonlinearity, which is linearly proportional to the optical intensity. The effective n2 measured using continuous-wave self-phase modulation shows agreement with the theoretical calculation. The waveguide with 2.8-μm wide and 80-nm thick Si3N4 core has low loss and high power handling capability, with an effective n2 of about 9×10(-16) cm2/W.

Ultra-low-loss tapered optical fibers with minimal lengths

NASA Astrophysics Data System (ADS)

Nagai, Ryutaro; Aoki, Takao

2014-11-01

We design and fabricate ultra-low-loss tapered optical fibers (TOFs) with minimal lengths. We first optimize variations of the torch scan length using the flame-brush method for fabricating TOFs with taper angles that satisfy the adiabaticity criteria. We accordingly fabricate TOFs with optimal shapes and compare their transmission to TOFs with a constant taper angle and TOFs with an exponential shape. The highest transmission measured for TOFs with an optimal shape is in excess of 99.7 % with a total TOF length of only 23 mm, whereas TOFs with a constant taper angle of 2 mrad reach 99.6 % transmission for a 63 mm TOF length.

Effect of naloxone on plasma insulin, insulin-like growth factor I, and its binding protein 1 in patients with polycystic ovarian disease.

PubMed

Laatikainen, T; Anttila, L; Suikkari, A M; Ruutiainen, K; Erkkola, R; Seppälä, M

1990-09-01

Insulin and insulin-like growth factors (IGFs) stimulate ovarian steroidogenesis, and hyperinsulinemia is often accompanied by hyperandrogenemia in women with polycystic ovarian disease (PCOD). Because opioid peptides are involved in the regulation of insulin secretion, we studied the effect of naloxone-induced opiate receptor blockade on the circulating levels of insulin, IGF-I, and IGF binding protein 1 (IGFBP-1) in 13 nonobese and 7 obese PCOD patients and in 6 healthy subjects. In obese PCOD patients, the mean basal insulin concentration was significantly higher and the IGFBP-1 concentration lower than in nonobese PCOD patients. Plasma IGF-I levels were elevated both in obese and nonobese PCOD patients. After an intravenous bolus of 10 mg naloxone, no significant changes were found in the circulating insulin or IGF-I levels, whereas IGFBP-1 levels decreased in nonobese PCOD patients and remained low in obese PCOD patients. No significant decrease was found in healthy subjects. These results suggest that, in addition to insulin, endogenous opioids are involved in the regulation of serum IGFBP-1 level.

Ultra low-level measurements of actinides by sector field ICP-MS.

PubMed

Pointurier, F; Baglan, N; Hémet, P

2004-01-01

In the present work, a double-focusing sector field inductively coupled plasma-mass spectrometer was optimised for ultra trace and isotopic analyses of actinide long-lived isotopes in low concentration solutions of the fgml(-1) to the ngml(-1) range. Sensitivities of about 3GHz/(microgml(-1)), with as low a background as 0.1cps, were obtained for U using a conventional concentric pneumatic nebuliser. Detection limits are below the fg range for 239Pu and 240Pu. With natural U, a precision lower than 0.5% RSD is currently obtained for 235U/238U isotopic ratio at the 200pgml(-1) level.

Early study on the application of Nexcera ultra low thermal expansion ceramic to space telescopes

NASA Astrophysics Data System (ADS)

Kamiya, Tomohiro; Sugawara, Jun; Mizutani, Tadahito; Yasuda, Susumu; Kitamoto, Kazuya

2017-09-01

Optical mirrors for space telescopes, which require high precision and high thermal stability, have commonly been made of glass materials such as ultra low expansion glass (e.g. ULE®) or extremely low expansion glassceramic (e.g. ZERODUR® or CLEARCERAM®). These materials have been well-known for their reliability due to their long history of achievements in many space applications.

Monitoring of ULF (ultra-low-frequency) Geomagnetic Variations Associated with Earthquakes

PubMed Central

Hayakawa, Masashi; Hattori, Katsumi; Ohta, Kenji

2007-01-01

ULF (ultra-low-frequency) electromagnetic emission is recently recognized as one of the most promising candidates for short-term earthquake prediction. This paper reviews previous convincing evidence on the presence of ULF emissions before a few large earthquakes. Then, we present our network of ULF monitoring in the Tokyo area by describing our ULF magnetic sensors and we finally present a few, latest results on seismogenic electromagnetic emissions for recent large earthquakes with the use of sophisticated signal processings.

Low Dose Risk, Decisions, and Risk Communication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flynn, James

The overall research objective was to establish new levels of information about how people, groups, and communities respond to low dose radiation exposure. This is basic research into the social psychology of individual, group, and community responses to radiation exposures. The results of this research are directed to improving risk communication and public participation in management of environmental problems resulting from low dose radiation.

Successful management of drug-induced hypercapnic acidosis with naloxone and noninvasive positive pressure ventilation.

PubMed

Agrafiotis, Michalis; Tryfon, Stavros; Siopi, Demetra; Chassapidou, Georgia; Galanou, Artemis; Tsara, Venetia

2015-02-01

A 74-year-old man was referred to our hospital due to deteriorating level of consciousness and desaturation. His Glasgow Coma Scale was 6, and his pupils were constricted but responded to light. Chest radiograph was negative for significant findings. Arterial blood gas evaluation on supplemental oxygen revealed severe acute on chronic respiratory acidosis: pH 7.15; PCO2, 133 mm Hg; PO2,64 mm Hg; and HCO3, 31 mmol/L. He regained full consciousness (Glasgow Coma Scale, 15) after receiving a 0.4 mg dose of naloxone, but because of persistent severe respiratory acidosis (pH 7.21; PCO2, 105 mm Hg), he was immediately commenced on noninvasive positive pressure ventilation (NIV) displaying a remarkable improvement in arterial blood gas values within the next few hours. However, in the days that followed, he remained dependent on NIV, and he was finally discharged on a home mechanical ventilation prescription. In cases of drug-induced respiratory depression, NIV should be regarded as an acceptable treatment, as it can provide ventilatory support without the increased risks associated with invasive mechanical ventilation.

An ultra low-power CMOS automatic action potential detector.

PubMed

Gosselin, Benoit; Sawan, Mohamad

2009-08-01

We present a low-power complementary metal-oxide semiconductor (CMOS) analog integrated biopotential detector intended for neural recording in wireless multichannel implants. The proposed detector can achieve accurate automatic discrimination of action potential (APs) from the background activity by means of an energy-based preprocessor and a linear delay element. This strategy improves detected waveforms integrity and prompts for better performance in neural prostheses. The delay element is implemented with a low-power continuous-time filter using a ninth-order equiripple allpass transfer function. All circuit building blocks use subthreshold OTAs employing dedicated circuit techniques for achieving ultra low-power and high dynamic range. The proposed circuit function in the submicrowatt range as the implemented CMOS 0.18- microm chip dissipates 780 nW, and it features a size of 0.07 mm(2). So it is suitable for massive integration in a multichannel device with modest overhead. The fabricated detector succeeds to automatically detect APs from underlying background activity. Testbench validation results obtained with synthetic neural waveforms are presented.

The feasibility of employing a home healthcare model for education and treatment of opioid overdose using a naloxone auto-injector in a private practice pain medicine clinic.

PubMed

Dragovich, Anthony; Brason, Fred; Beltran, Thomas; McCoart, Amy; Plunkett, Anthony R

2018-04-18

The purpose of this study was to determine if employing a home healthcare model for education and treatment of opioid overdose using Evzio® (Naloxone)* auto-injector in a private practice pain clinic. A prospective survey was used to determine the feasibility of integrating a naloxone auto-injector within the patient's home with a home care training model. Twenty moderate or high-risk patients were enrolled from our chronic pain clinic. Patients who were moderate or high risk completed an evaluation survey. The naloxone auto-injector was dispensed to all patients meeting criteria. The treating provider after prescribing the naloxone auto-injector then consulted home health per standard clinical practice. All patients had home health consulted to perform overdose identification and rescue training. A Cochran's Q test was conducted to examine differences in patient knowledge pre and post training. The post training test was done 2-4 weeks later. Forty subjects enrolled after meeting inclusion/exclusion criteria. Twenty withdrew because their insurance declined coverage for the naloxone auto-injector. Those completing home health showed a statistically significant difference in their ability to correctly identify the steps needed to effectively respond to an overdose p = 0.03 Discussion: Preliminary evidence would suggest training on overdose symptom recognition and proper use of prescription naloxone for treatment in the home setting by home health staff would prove more beneficial than the clinic setting, but feasibility was hindered by unaffordable costs related to insurance coverage limitations.

Transfer of Low Dose Aspirin Into Human Milk.

PubMed

Datta, Palika; Rewers-Felkins, Kathleen; Kallem, Raja Reddy; Baker, Teresa; Hale, Thomas W

2017-05-01

Aspirin has antipyretic and anti-inflammatory properties and is frequently used by pregnant and lactating women. However, its transfer in human milk when administered at low dose has not been reported. Research aim: This study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite, salicylic acid, into human milk following the use of low dose aspirin. In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours from seven breastfeeding women after a steady-state daily dose of 81 mg of aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined by liquid chromatography-tandem mass spectrometry. Acetylsalicylic acid levels were below the limit of quantification (0.61 ng/ml) in all the milk samples, whereas salicylic acid was detected at very low concentrations. The average concentration of salicylic acid observed was 24 ng/ml and the estimated relative infant dose was 0.4%. Acetylsalicylic acid transfer into milk is so low that it is undetectable even by highly sophisticated methodology. Salicylic acid does appear in the human milk in comparatively low amounts, which are probably subclinical in infants. Thus, the daily use of an 81-mg dose of aspirin should be considered safe during lactation.

Restoration of low-dose digital breast tomosynthesis

NASA Astrophysics Data System (ADS)

Borges, Lucas R.; Azzari, Lucio; Bakic, Predrag R.; Maidment, Andrew D. A.; Vieira, Marcelo A. C.; Foi, Alessandro

2018-06-01

In breast cancer screening, the radiation dose must be kept to the minimum necessary to achieve the desired diagnostic objective, thus minimizing risks associated with cancer induction. However, decreasing the radiation dose also degrades the image quality. In this work we restore digital breast tomosynthesis (DBT) projections acquired at low radiation doses with the goal of achieving a quality comparable to that obtained from current standard full-dose imaging protocols. A multiframe denoising algorithm was applied to low-dose projections, which are filtered jointly. Furthermore, a weighted average was used to inject a varying portion of the noisy signal back into the denoised one, in order to attain a signal-to-noise ratio comparable to that of standard full-dose projections. The entire restoration framework leverages a signal-dependent noise model with quantum gain which varies both upon the projection angle and on the pixel position. A clinical DBT system and a 3D anthropomorphic breast phantom were used to validate the proposed method, both on DBT projections and slices from the 3D reconstructed volume. The framework is shown to attain the standard full-dose image quality from data acquired at 50% lower radiation dose, whereas progressive loss of relevant details compromises the image quality if the dosage is further decreased.

Effects of Low-Dose and Very Low-Dose Ketamine among Patients with Major Depression: a Systematic Review and Meta-Analysis.

PubMed

Xu, Ying; Hackett, Maree; Carter, Gregory; Loo, Colleen; Gálvez, Verònica; Glozier, Nick; Glue, Paul; Lapidus, Kyle; McGirr, Alexander; Somogyi, Andrew A; Mitchell, Philip B; Rodgers, Anthony

2016-04-01

Several recent trials indicate low-dose ketamine produces rapid antidepressant effects. However, uncertainty remains in several areas: dose response, consistency across patient groups, effects on suicidality, and possible biases arising from crossover trials. A systematic search was conducted for relevant randomized trials in Medline, Embase, and PsycINFO databases up to August 2014. The primary endpoints were change in depression scale scores at days 1, 3 and 7, remission, response, suicidality, safety, and tolerability. Data were independently abstracted by 2 reviewers. Where possible, unpublished data were obtained on treatment effects in the first period of crossover trials. Nine trials were identified, including 201 patients (52% female, mean age 46 years). Six trials assessed low-dose ketamine (0.5 mg/kg i.v.) and 3 tested very low-dose ketamine (one trial assessed 50 mg intra-nasal spray, another assessed 0.1-0.4 mg/kg i.v., and another assessed 0.1-0.5 mg/kg i.v., intramuscular, or s.c.). At day 3, the reduction in depression severity score was less marked in the very low-dose trials (P homogeneity <.05) and among bipolar patients. In analyses excluding the second period of crossover trials, response rates at day 7 were increased with ketamine (relative risk 3.4, 95% CI 1.6-7.1, P=.001), as were remission rates (relative risk 2.6, CI 1.2-5.7, P=.02). The absolute benefits were large, with day 7 remission rates of 24% vs 6% (P=.02). Seven trials provided unpublished data on suicidality item scores, which were reduced on days 1 and 3 (both P<.01) but not day 7. Low-dose ketamine appears more effective than very low dose. There is substantial heterogeneity in clinical response, with remission among one-fifth of patients at 1 week but most others having benefits that are less durable. Larger, longer term parallel group trials are needed to determine if efficacy can be extended and to further assess safety. © The Author 2015. Published by Oxford University

Effects of Low-Dose and Very Low-Dose Ketamine among Patients with Major Depression: a Systematic Review and Meta-Analysis

PubMed Central

Xu, Ying; Hackett, Maree; Carter, Gregory; Gálvez, Verònica; Glozier, Nick; Glue, Paul; Lapidus, Kyle; McGirr, Alexander; Somogyi, Andrew A.; Mitchell, Philip B.; Rodgers, Anthony

2016-01-01

Background: Several recent trials indicate low-dose ketamine produces rapid antidepressant effects. However, uncertainty remains in several areas: dose response, consistency across patient groups, effects on suicidality, and possible biases arising from crossover trials. Methods: A systematic search was conducted for relevant randomized trials in Medline, Embase, and PsycINFO databases up to August 2014. The primary endpoints were change in depression scale scores at days 1, 3 and 7, remission, response, suicidality, safety, and tolerability. Data were independently abstracted by 2 reviewers. Where possible, unpublished data were obtained on treatment effects in the first period of crossover trials. Results: Nine trials were identified, including 201 patients (52% female, mean age 46 years). Six trials assessed low-dose ketamine (0.5mg/kg i.v.) and 3 tested very low-dose ketamine (one trial assessed 50mg intra-nasal spray, another assessed 0.1–0.4mg/kg i.v., and another assessed 0.1–0.5mg/kg i.v., intramuscular, or s.c.). At day 3, the reduction in depression severity score was less marked in the very low-dose trials (P homogeneity <.05) and among bipolar patients. In analyses excluding the second period of crossover trials, response rates at day 7 were increased with ketamine (relative risk 3.4, 95% CI 1.6–7.1, P=.001), as were remission rates (relative risk 2.6, CI 1.2–5.7, P=.02). The absolute benefits were large, with day 7 remission rates of 24% vs 6% (P=.02). Seven trials provided unpublished data on suicidality item scores, which were reduced on days 1 and 3 (both P<.01) but not day 7. Conclusion: Low-dose ketamine appears more effective than very low dose. There is substantial heterogeneity in clinical response, with remission among one-fifth of patients at 1 week but most others having benefits that are less durable. Larger, longer term parallel group trials are needed to determine if efficacy can be extended and to further assess safety. PMID

Evaluation of knowledge and confidence following opioid overdose prevention training: A comparison of types of training participants and naloxone administration methods.

PubMed

Ashrafioun, Lisham; Gamble, Stephanie; Herrmann, Michele; Baciewicz, Gloria

2016-01-01

The purpose of the current study was to assess the effect of opioid overdose prevention training on participants' knowledge about opioid overdose and confidence to recognize and respond to opioid overdose situations as a function of naloxone administration (i.e., injection vs. intranasal spray) and participant type (friend/family, provider, "other"). Opioid overdose prevention trainings were offered throughout a mid-sized metropolitan area in the northeast. Participants (n = 428) were trained to administer naloxone via intramuscular injection (n = 154) or intranasal spray (n = 274). All training participants were given pre-post assessments of knowledge about opioid overdose and confidence to recognize and respond to opioid overdose situations. Participants' overall knowledge and confidence increased significantly from pre- to post-training (ps < .001). There was no significant association between knowledge and route of administration or participant type. Knowledge significantly increased from pre- to post-training in all participant types (ps < .001). Confidence improved significantly from pre- to post-training across both routes of administration (ps < .001). However, confidence was higher among those who were trained using the intranasal naloxone compared to those who were trained using the intramuscular injection naloxone at pre- (p = .011) and post-training (p < .001). Confidence increased from pre- to post-training in each of the participant types (ps < .001). Post-hoc tests revealed that confidence was higher among providers and friends/family members compared to "other" participants, such as first responders, only at post-training (p < .05). Opioid overdose trainings are effective in increasing knowledge and confidence related to opioid overdose situations. Findings suggest that trainees are more confident administering naloxone via intranasal spray compared to injection. Future research should attempt to identify other factors that may increase the

High-resolution low-dose scanning transmission electron microscopy.

PubMed

Buban, James P; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D; Stahlberg, Henning

2010-01-01

During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM.

High- to low-dose extrapolation: critical determinants involved in the dose response of carcinogenic substances.

PubMed

Swenberg, J A; Richardson, F C; Boucheron, J A; Deal, F H; Belinsky, S A; Charbonneau, M; Short, B G

1987-12-01

Recent investigations on mechanism of carcinogenesis have demonstrated important quantitative relationships between the induction of neoplasia, the molecular dose of promutagenic DNA adducts and their efficiency for causing base-pair mismatch, and the extent of cell proliferation in target organ. These factors are involved in the multistage process of carcinogenesis, including initiation, promotion, and progression. The molecular dose of DNA adducts can exhibit supralinear, linear, or sublinear relationships to external dose due to differences in absorption, biotransformation, and DNA repair at high versus low doses. In contrast, increased cell proliferation is a common phenomena that is associated with exposures to relatively high doses of toxic chemicals. As such, it enhances the carcinogenic response at high doses, but has little effect at low doses. Since data on cell proliferation can be obtained for any exposure scenario and molecular dosimetry studies are beginning to emerge on selected chemical carcinogens, methods are needed so that these critical factors can be utilized in extrapolation from high to low doses and across species. The use of such information may provide a scientific basis for quantitative risk assessment.

What predicts performance in ultra-triathlon races? – a comparison between Ironman distance triathlon and ultra-triathlon

PubMed Central

Knechtle, Beat; Zingg, Matthias Alexander; Rosemann, Thomas; Stiefel, Michael; Rüst, Christoph Alexander

2015-01-01

Objective This narrative review summarizes recent intentions to find potential predictor variables for ultra-triathlon race performance (ie, triathlon races longer than the Ironman distance covering 3.8 km swimming, 180 km cycling, and 42.195 km running). Results from studies on ultra-triathletes were compared to results on studies on Ironman triathletes. Methods A literature search was performed in PubMed using the terms “ultra”, “triathlon”, and “performance” for the aspects of “ultra-triathlon”, and “Ironman”, “triathlon”, and “performance” for the aspects of “Ironman triathlon”. All resulting papers were searched for related citations. Results for ultra-triathlons were compared to results for Ironman-distance triathlons to find potential differences. Results Athletes competing in Ironman and ultra-triathlon differed in anthropometric and training characteristics, where both Ironmen and ultra-triathletes profited from low body fat, but ultra-triathletes relied more on training volume, whereas speed during training was related to Ironman race time. The most important predictive variables for a fast race time in an ultra-triathlon from Double Iron (ie, 7.6 km swimming, 360 km cycling, and 84.4 km running) and longer were male sex, low body fat, age of 35–40 years, extensive previous experience, a fast time in cycling and running but not in swimming, and origins in Central Europe. Conclusion Any athlete intending to compete in an ultra-triathlon should be aware that low body fat and high training volumes are highly predictive for overall race time. Little is known about the physiological characteristics of these athletes and about female ultra-triathletes. Future studies need to investigate anthropometric and training characteristics of female ultra-triathletes and what motivates women to compete in these races. Future studies need to correlate physiological characteristics such as maximum oxygen uptake (VO2max) with ultra

Induced Mitogenic Activity in AML-12 Mouse Hepatocytes Exposed to Low-dose Ultra-Wideband Electromagnetic Radiation

PubMed Central

Dorsey, W. C.; Ford, B. D.; Roane, L.; Haynie, D. T.; Tchounwou, P. B.

2005-01-01

Ultra–wideband (UWB) technology has increased with the use of various civilian and military applications. In the present study, we hypothesized that low-dose UWB electromagnetic radiation (UWBR) could elicit a mitogenic effect in AML-12 mouse hepatocytes, in vitro. To test this hypothesis, we exposed AML-12 mouse hepatocytes, to UWBR in a specially constructed gigahertz transverse electromagnetic mode (GTEM) cell. Cells were exposed to UWBR for 2 h at a temperature of 23°C, a pulse width of 10 ns, a repetition rate of 1 kHz, and field strength of 5–20 kV/m. UWB pulses were triggered by an external pulse generator for UWBR exposure but were not triggered for the sham exposure. We performed an MTT Assay to assess cell viability for UWBR-treated and sham-exposed hepatocytes. Data from viability studies indicated a time-related increase in hepatocytes at time intervals from 8–24 h post exposure. UWBR exerted a statistically significant (p < 0.05) dose-dependent response in cell viability in both serum-treated and serum free medium (SFM) -treated hepatocytes. Western blot analysis of hepatocyte lysates demonstrated that cyclin A protein was induced in hepatocytes, suggesting that increased MTT activity after UWBR exposure was due to cell proliferation. This study indicates that UWBR has a mitogenic effect on AML-12 mouse hepatocytes and implicates a possible role for UWBR in hepatocarcinoma. PMID:16705798

PerSEUS: Ultra-Low-Power High Performance Computing for Plasma Simulations