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1

Diversion of methadone and buprenorphine from opioid substitution treatment: a staff perspective.  

PubMed

Opioid substitution treatment (OST) is still controversial, despite positive results. The issue of diversion to the illicit drug market is a cornerstone in the criticism typically voiced against the treatment. Little research is available concerning how professionals who work in OST view the issue of diversion. In this article, we discuss existing ideas and attitudes toward diversion of methadone and buprenorphine among OST staff in Sweden. The article is based on semi-structured interviews with 25 professionals working in eight OST-programs in southern Sweden. Diversion was seen as a deleterious phenomenon by the interviewees. Three problematic aspects were highlighted: medical risks in the form of overdose fatalities and the recruitment of new opiate/opioid users; negative consequences for the legitimacy of OST; and moral objections, since diversion means that the patients remain in a criminal environment. However, positive aspects were also highlighted. Illicit methadone or buprenorphine is perceived as safer than heroin. In this way, diversion can fulfill a positive function; for instance, if there is a shortage of access to regular treatment. Patients who share their medication with opioid-dependent friends are seen as less culpable than those who sell to anyone for money. PMID:25364995

Johnson, Björn; Richert, Torkel

2014-01-01

2

Naltrexone implant treatment for buprenorphine dependence - Mauritian case series.  

PubMed

Although substitution therapy with opiate agonist treatments such as methadone and buprenorphine has resulted in a reduction of illicit drug use related harm, such treatment has also resulted in severe problems in some countries where opioid-dependent individuals now inject illicitly sold buprenorphine or buprenorphine-naloxone instead of heroin. There is no approved treatment for buprenorphine dependence. Naltrexone is an opioid antagonist which has been used for the treatment of both alcohol and opioid dependencies. Although both buprenorphine and heroin resemble each other concerning their effects, buprenorphine has a higher affinity to opioid receptors than heroin. Therefore, it is not known if naltrexone can block the psychoactive effects of buprenorphine as it does for heroin. This paper presents observational case series data on the use of a sustained-release naltrexone implant for the treatment of buprenorphine dependence. To the authors' knowledge this is the first use of sustained-release naltrexone for this indication. PMID:24695742

Jhugroo, Anil; Ellayah, Darmen; Norman, Amanda; Hulse, Gary

2014-04-01

3

Buprenorphine substitution treatment in France: drug users' views of the doctor-user relationship  

PubMed Central

The French system for drug substitution, or maintenance treatment, established in 1996, differs from the often strict conditions attached to methadone clinics in other countries. Because of the predominant role of general practitioners and the flexible prescription rules for Subutex® in France, the relationship between the physician and the drug user becomes a central element in the treatment. This article deals with the expectations that these users have of the physician, and their perception of his or her attitude towards them. In order to identify possible reasons for the absence of treatment compliance and of Subutex® misuse, it focuses on the users’ assessment of the physician’s response to the problems they report. This study, based on a diversified sample of 28 persons in treatment, showed 4 patterns of relationships between physicians and users, which differed in their focus: a) dosage, b) compliance, c) the person and d) obtaining a prescription. In all four case types, users had difficulty reporting other drug use or intravenous Subutex® injection within this relationship in which the stigma attached to drug dependence seems to reappear. Moreover, the lack of clarity about the treatment objectives and time frame limits the users’ ability to integrate the treatment into their lives and to commit themselves to it. The heterogeneity and fragility of the users’ situations are elements related to dependence that, during contact with the physician, require regular assessment of the individual’s situation and of the treatment objectives. This constant reappraisal of the situation with the physician should help to optimize the treatment and avoid the hiatus that can generate or continue “misuse.” PMID:17442473

Guichard, Anne; Lert, France; Brodeur, Jean-Marc; Richard, Lucie

2007-01-01

4

The effects of chronic buprenorphine treatment on cocaine and food self-administration by rhesus monkeys.  

PubMed

The goal of this study was to determine if buprenorphine continues to reduce cocaine self-administration over long periods of treatment, or if tolerance develops to this effect. The effects of 30 to 120 days of buprenorphine treatment (0.32 mg/kg/day) on cocaine and food self-administration were examined in six rhesus monkeys. Saline control treatment was studied for 15 days before and after buprenorphine treatment. Intravenous cocaine (0.05 or 0.10 mg/kg) and food (1 g banana pellet) self-administration were maintained on a FR 4 (VR 16:S) schedule of reinforcement. Cocaine self-administration decreased significantly (P less than .0001) and remained 60 to 97% below saline treatment baseline levels (52 +/- 2 injections/day) throughout 120 days of buprenorphine treatment (P less than .01). After substitution of saline for buprenorphine, cocaine self-administration resumed and averaged between 21 (+/- 3.6) and 56 (+/- 6.5) injections per day over 20 days. Buprenorphine plasma levels averaged 18 (+/- 2.84) ng/ml (range 10.9-30 ng/ml) during buprenorphine treatment. Buprenorphine plasma levels usually decreased by 50% or more within 27 hr after the last buprenorphine dose. Low levels of buprenorphine (0.10-0.19 ng/ml) were measured for 30 to 74 days after abrupt termination of daily buprenorphine treatment. Food self-administration was initially reduced (P less than .01-.05), but tolerance to buprenorphine's suppression of food-maintained responding developed over 30 to 70 days of treatment. Food self-administration returned to and significantly exceeded (P less than .05-.01) saline treatment base-line levels, whereas cocaine self-administration remained significantly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1545386

Mello, N K; Lukas, S E; Kamien, J B; Mendelson, J H; Drieze, J; Cone, E J

1992-03-01

5

Smoking cessation treatment among office-based buprenorphine treatment patients.  

PubMed

Opioid-dependent patients smoke at high rates, and office-based buprenorphine treatment provides an opportunity to offer cessation treatment. We examined tobacco use and smoking cessation treatment patterns among office-based buprenorphine treatment patients. We reviewed records of 319 patients treated with buprenorphine from 2005 to 2010. We examined smoking status, cessation medication prescriptions, and factors associated with receipt of cessation prescriptions. Mean age was 43.9 years; most were men (74.2%) and Hispanic (70.9%). At buprenorphine initiation, 21.9% had no documentation of smoking status, while 67.4% were current, 10% former, and 0.9% never smokers. Of current smokers, 16.8% received smoking cessation prescriptions. Patients retained (vs. not retained) in buprenorphine treatment were more likely to receive smoking cessation medications (26.3% vs. 11.2%, p<0.005). We observed a high tobacco use prevalence among buprenorphine patients, and limited provision of cessation treatment. This is a missed opportunity to impact the high tobacco use burden in opioid-dependent persons. PMID:24912863

Nahvi, Shadi; Blackstock, Oni; Sohler, Nancy L; Thompson, Devin; Cunningham, Chinazo O

2014-08-01

6

Hypogonadism in men receiving methadone and buprenorphine maintenance treatment.  

PubMed

The aim of this study was to determine the prevalence and investigate the aetiology of hypogonadism in men on methadone or buprenorphine maintenance treatment (MMT, BMT). 103 men (mean age 37.6 +/- 7.9) on MMT (n = 84) or BMT (n = 19) were evaluated using hormone assays, body mass index (BMI), serological, biochemical, demographic and substance use measures. Overall 54% of men (methadone 65%; buprenorphine 28%) had total testosterone (TT) <12.0 nm; 34% (methadone 39%; buprenorphine 11%) had TT <8.0 nm. Both methadone- and buprenorphine-treated men had lower free testosterone, luteinising hormone and estradiol than age-matched reference groups. Methadone-treated men had lower TT than buprenorphine-treated men and reference groups. Prolactin did not differ between methadone, buprenorphine groups, and reference groups. Primary testicular failure was an uncommon cause of hypogonadism. Yearly percentage fall in TT by age across the patient group was 2.3%, more than twice that expected normally. There were no associations between TT and opioid dose, cannabis, alcohol and tobacco consumption, or chronic hepatitis C viraemia. On multiple regression higher TT was associated with higher alanine aminotransferase and lower TT with higher BMI. Men on MMT have high prevalence of hypogonadotrophic hypogonadism. The extent of hormonal changes associated with buprenorphine needs to be explored further in larger studies. Men receiving long term opioid replacement treatment, especially methadone treatment, should be screened for hypogonadism. Wide interindividual differences in methadone metabolism and tolerance may in a cross-sectional study obscure a methadone dose relationship to testosterone in individuals. Future studies of hypogonadism in opioid-treated men should examine the potential benefits of dose reduction, choice of opioid medication, weight loss, and androgen replacement. PMID:17971165

Hallinan, R; Byrne, A; Agho, K; McMahon, C G; Tynan, P; Attia, J

2009-04-01

7

Bringing Buprenorphine-Naloxone Detoxification to Community Treatment Providers: The NIDA Clinical Trials Network Field Experience  

PubMed Central

In October 2002, the U.S. Food and Drug Administration approved buprenorphine-naloxone (Suboxone®) sublingual tablets as an opioid dependence treatment available for use outside traditionally licensed opioid treatment programs. The NIDA Center for Clinical Trials Network (CTN) sponsored two clinical trials assessing buprenorphine-naloxone for short-term opioid detoxification. These trials provided an unprecedented field test of its use in twelve diverse community-based treatment programs. Opioid-dependent men and women were randomized to a thirteen-day buprenorphine-naloxone taper regimen for short-term opioid detoxification. The 234 buprenorphine-naloxone patients averaged 37 years old and used mostly intravenous heroin. Direct and rapid induction onto buprenorphine-naloxone was safe and well tolerated. Most patients (83%) received 8 mg buprenorphine-2 mg naloxone on the first day and 90% successfully completed induction and reached a target dose of 16mg buprenorphine-4 mg naloxone in three days. Medication compliance and treatment engagement was high. An average of 81% of available doses was ingested, and 68% of patients completed the detoxification. Most (80.3%) patients received some ancillary medications with an average of 2.3 withdrawal symptoms treated. The safety profile of buprenorphine-naloxone was excellent. Of eighteen serious adverse events reported, only one was possibly related to buprenorphine-naloxone. All providers successfully integrated buprenorphine-naloxone into their existing treatment milieus. Overall, data from the CTN field experience suggest that buprenorphine-naloxone is practical and safe for use in diverse community treatment settings, including those with minimal experience providing opioid-based pharmacotherapy and/or medical detoxification for opioid dependence. PMID:15204675

Amass, Leslie; Ling, Walter; Freese, Thomas E.; Reiber, Chris; Annon, Jeffrey J.; Cohen, Allan J.; M.F.T.; McCarty, Dennis; Reid, Malcolm S.; Brown, Lawrence S.; Clark, Cynthia; Ziedonis, Douglas M.; Krejci, Jonathan; Stine, Susan; Winhusen, Theresa; Brigham, Greg; Babcock, Dean; L.C.S.W.; Muir, Joan A.; Buchan, Betty J.; Horton, Terry

2005-01-01

8

Buprenorphine augmentation in the treatment of refractory obsessive–compulsive disorder  

PubMed Central

Background: OCD is often refractory to treatment. There is a need for the development of new, non-invasive treatments for severe OCD. Rationale: There is evidence that opiates can be a useful adjunctive treatment in OCD. We summarise our experience with sublingual buprenorphine augmentation of standard pharmacological management of severe OCD. Methods: Patients were recruited from a standard psychiatric outpatient clinic and gave their consent to the treatment trial. The severity of the OCD was rated with the Y-BOCS. The buprenorphine was introduced to their existing medication regime at a low dose and the dose increased according to response. In order to gauge the reproducibility of the response the buprenorphine was withdrawn and then reintroduced once symptoms had returned. Results: 4 out of 7 patients with treatment resistant OCD showed a 30% reduction in the Y-BOCS score following buprenorphine augmentation. 3 of the responders were comorbid for other Axis 1 diagnoses. All of the responders had shown some improvement with SSRIs or clomipramine. Non-responders had not shown any improvement with either antidepressant or antipsychotic drugs. Typically improvement appeared within 2 days of initiating buprenorphine and waned within 1 to 2 days of its discontinuation. The dose of buprenorphine required varied between 400 µg and 600 µg a day. One responder managed on alternate day dosing. Reintroduction of buprenorphine resulted in symptom control within 2 to 3 days. The buprenorphine treatment was not associated with significant side-effects and the improvement was maintained without progressive dose escalation. Conclusions: Buprenorphine augmentation of standard treatment for OCD can result in clinically meaningful improvement in a proportion of refractory OCD cases. Further treatment trials are indicated. PMID:23983988

Aziz, Victor; Briggs, Patrick; Kanakkehewa, Nimalee; Rawi, Omar

2013-01-01

9

Consensus statement on office-based treatment of opioid dependence using buprenorphine  

Microsoft Academic Search

Buprenorphine and buprenorphine\\/naloxone (BUP) are newly approved for office-based treatment of opioid dependence. Federal and non-federal regulatory and monitoring agencies, national and international researchers, national professional organizations, researchers involved in monitoring, opioid treatment programs and the pharmaceutical industry met to synthesize and disseminate practical information to guide training, practice, monitoring, regulation and evaluation efforts with these medications. We performed a

David A. Fiellin; Herbert Kleber; Jeanne G. Trumble-Hejduk; A. Thomas McLellan; Thomas R. Kosten

2004-01-01

10

Impact of research network participation on the adoption of buprenorphine for substance abuse treatment.  

PubMed

There is a growing body of research supporting the use of buprenorphine and other medication assisted treatments (MATs) for the rapidly accelerating opioid epidemic in the United States. Despite numerous advantages of buprenorphine (accessible in primary care, no daily dosing required, minimal stigma), implementation has been slow. As the field progresses, there is a need to understand the impact of participation in practitioner-scientist research networks on acceptance and uptake of buprenorphine. This paper examines the impact of research network participation on counselor attitudes toward buprenorphine addressing both counselor-level characteristics and program-level variables using hierarchical linear modeling (HLM) to account for nesting of counselors within treatment programs. Using data from the National Treatment Center Study, this project compares privately funded treatment programs (N=345) versus programs affiliated with the National Institute on Drug Abuse Clinical Trials Network (CTN) (N=198). Models included 922 counselors in 172 CTN programs and 1203 counselors in 251 private programs. Results of two-level HLM logistic (Bernoulli) models revealed that counselors with higher levels of education, larger caseloads, more buprenorphine-specific training, and less preference for 12-step treatment models were more likely to perceive buprenorphine as acceptable and effective. Furthermore, buprenorphine was 50% more likely to be perceived as effective among counselors working in CTN-affiliated programs as compared to private programs. This study suggests that research network affiliation positively impacts counselors' acceptance and perceptions of buprenorphine. Thus, research network participation can be utilized as a means to promote positive attitudes toward the implementation of innovations including medication assisted treatment. PMID:24594902

Rieckmann, Traci R; Abraham, Amanda J; Kovas, Anne E; McFarland, Bentson H; Roman, Paul M

2014-05-01

11

Revised Dose Schema of Sublingual Buprenorphine in the Treatment of the Neonatal Opioid Abstinence Syndrome  

PubMed Central

AIMS Over half of infants exposed to opioids in utero develop neonatal abstinence syndrome (NAS) of severity to require pharmacologic therapy. Current treatments are associated with prolonged hospitalization. We sought to optimize the dose of sublingual buprenorphine in the treatment of NAS. DESIGN Randomized, phase 1, open-label, active-control clinical trial comparing sublingual buprenorphine to oral morphine. SETTING Large, urban, tertiary care hospital. PARTICIPANTS Twenty-four term infants requiring pharmacological treatment for NAS. MEASUREMENTS Outcomes were neonatal safety, length of treatment, and length of hospitalization. FINDINGS Sublingual buprenorphine was safe and effective. Infants treated with buprenorphine had a 23-day length of treatment compared to 38 days for those treated with morphine (p=0.01), representing a 40% reduction. Length of hospital stay in the buprenorphine group was reduced 24%, from 42 to 32 days (p=0.05). CONCLUSIONS Sublingual buprenorphine was safe in NAS, with a substantial efficacy advantage over standard of care therapy with oral morphine. PMID:20925688

Kraft, Walter K.; Dysart, Kevin; Greenspan, Jay S.; Gibson, Eric; Kaltenbach, Karol; Ehrlich, Michelle E.

2010-01-01

12

Adoption of evidence-based clinical innovations: the case of buprenorphine use by opioid treatment programs.  

PubMed

This article examines changes from 2005 to 2011 in the use of an evidence-based clinical innovation, buprenorphine use, among a nationally representative sample of opioid treatment programs and identifies characteristics associated with its adoption. We apply a model of the adoption of clinical innovations that focuses on the work needs and characteristics of staff; organizations' technical and social support for the innovation; local market dynamics and competition; and state policies governing the innovation. Results indicate that buprenorphine use increased 24% for detoxification and 47% for maintenance therapy between 2005 and 2011. Buprenorphine use was positively related to reliance on private insurance and availability of state subsidies to cover its cost and inversely related to the percentage of clients who injected opiates, county size, and local availability of methadone. The results indicate that financial incentives and market factors play important roles in opioid treatment programs' decisions to adopt evidence-based clinical innovations such as buprenorphine use. PMID:24051897

Andrews, Christina M; D'Aunno, Thomas A; Pollack, Harold A; Friedmann, Peter D

2014-02-01

13

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

PubMed Central

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 ( ?22 = 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%; ?12 = 32.90, P < .001). During weeks 1 through 12, patients in the 12-week buprenorphine-naloxone group reported less opioid use ( ?12 = 18.45, P < .001), less injecting ( ?12 = 6.00, P = .01), and less nonstudy addiction treatment ( ?12 = 25.82, P < .001). High levels of opioid use occurred in both groups at follow-up. Four of 83 patients who tested negative for hepatitis C at baseline were positive for hepatitis C at week 12. Conclusions Continuing treatment with buprenorphine-naloxone improved outcome compared with short-term detoxification. Further research is necessary to assess the efficacy and safety of longer-term treatment with buprenorphine for young individuals with opioid dependence. PMID:18984887

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

14

A qualitative study of the adoption of buprenorphine for opioid addiction treatment.  

PubMed

Qualified physicians may prescribe buprenorphine to treat opioid dependence, but medication use remains controversial. We examined adoption of buprenorphine in two not-for-profit integrated health plans, over time, completing 101 semi-structured interviews with clinicians and clinician-administrators from primary and specialty care. Transcripts were reviewed, coded, and analyzed. A strong leader championing the new treatment was critical for adoption in both health plans. Once clinicians began using buprenorphine, patients' and other clinicians' experiences affected decisions more than did the champion. With experience, protocols developed to manage unsuccessful patients and changed to support maintenance rather than detoxification. Diffusion outside addiction and mental health settings was nonexistent; primary care clinicians cited scope-of-practice issues and referred patients to specialty care. With greater diffusion came questions about long-term use and safety. Recognizing how implementation processes develop may suggest where, when, and how to best expend resources to increase adoption of such treatments. PMID:24268947

Green, Carla A; McCarty, Dennis; Mertens, Jennifer; Lynch, Frances L; Hilde, Anadam; Firemark, Alison; Weisner, Constance M; Pating, David; Anderson, Bradley M

2014-03-01

15

Comment on "a comparison of buprenorphine + naloxone to buprenorphine and methadone in the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes".  

PubMed

In a recent article, Lund et al sought to compare maternal and neonatal outcomes of various treatment regimens for opioid dependence during pregnancy.1 In their background, discussion the authors state that "In the United States buprenorphine plus naloxone [Suboxone(®)] … has been the preferred form of prescribed buprenorphine due to its reduced abuse liability relative to buprenorphine alone [Subutex(®)]." This claim is certainly consistent with the view of the firm that has manufactured and sold both products, Reckitt Benckiser. In September of 2011, the company announced that it was "… discontinuing distribution and sale of Subutex(®) tablets as we believe that mono product (product containing buprenorphine alone with no naloxone) creates a greater risk of misuse, abuse and diversion …".2 Supporting evidence for the alleged "reduced abuse liability" appears to be lacking, however, and evidence cannot be located in the two references cited by Dr. Lund and his co-authors, which in fact are silent on the subject of abuse potential.3,4 In contrast, it has been reported that the transition to buprenorphine/naloxone from the mono formulation has been associated with "… no reduction in injection risk behaviors among IDUs."5. PMID:23772177

Newman, Robert G; Gevertz, Susan G

2013-01-01

16

Persistence During Stress-Challenge Associated With Lapse to Opioid Use During Buprenorphine Treatment  

PubMed Central

Objectives Lapse to opiate use after initiation of buprenorphine treatment is common and is a strong predictor of poor treatment retention and increased risk of chronic opiate use. Drug-cues and situations or events associated with distress are known to provoke craving and increase risk for lapse. The current study evaluated the predictive validity of a behavioral index of persistence during a stress-challenge among opiate users identified as affectively vulnerable to lapse risk due to elevated depressive symptoms. Methods Patients from on ongoing clinical trial (n=48) completed a stress-challenge task prior to receiving their first dose of buprenorphine. Results After controlling for levels of craving on their induction day, persistence on the stress-challenge task prior to initiating buprenorphine treatment was associated with successful transition to early abstinence, and lower rates of opiate use during the initial three months of buprenorphine treatment across antidepressant and placebo groups. Conclusions Results from this preliminary study suggest the promise of laboratory-based behavioral paradigms in facilitating understanding of important mechanisms of early lapse. Identifying individual behavioral responses to drug- and stress-cues prior to attempts at abstinence may facilitate delivery of adjunctive behavioral treatments to prevent early lapse. PMID:22864399

Strong, David R.; Brown, Richard A.; Sims, Meredith; Herman, Debra S.; Anderson, Bradley J.; Stein, Michael D.

2014-01-01

17

Developing and Implementing a New Prison-Based Buprenorphine Treatment Program  

ERIC Educational Resources Information Center

Research suggests that buprenorphine treatment may be a promising intervention for incarcerated individuals with heroin addiction histories. However, its implementation varies from corrections-based methadone because of unique challenges regarding dosing, administration, and regulation. Describing the first randomized clinical trial of…

Kinlock, Timothy W.; Gordon, Michael S.; Schwartz, Robert P.; Fitzgerald, Terrence T.

2010-01-01

18

Compliance with buprenorphine medication-assisted treatment and relapse to opioid use.  

PubMed

Opioid dependence (OD), often characterized as a chronic relapsing disorder, affects millions of people worldwide. The purpose of this study was to examine the effect of compliance with buprenorphine on reducing relapse among a sample of patients in treatment for OD. Patients new to buprenorphine (N?= 703) completed the Addiction Severity Index (ASI) at baseline, and at 1, 2, and 3 months postbaseline. The ASI is a semistructured interview designed to measure problem severity in seven functional areas known to be affected by alcohol and drug dependence. Compliance was defined as taking buprenorphine medication on at least 22 of the past 28 days (80%), while relapse classification was based on resumed use of opioids during the follow-up period (months 2 and 3). Relapse was regressed onto demographic indicators, baseline ASI composite scores, and compliance with buprenorphine. Noncompliant patients were over 10 times more likely to relapse than those who were compliant (exp ?= 10.55;?p?< .001). Neither demographics nor baseline ASI composite scores were predictive of relapse (p's > .05). Compliance with medication-assisted treatment supports abstinence, essential for patient recovery. Understanding the factors that drive treatment compliance and noncompliance may assist providers in supporting patient compliance and recovery.? PMID:22211347

Tkacz, Joseph; Severt, Jamie; Cacciola, John; Ruetsch, Charles

2012-01-01

19

Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40  

ERIC Educational Resources Information Center

This Treatment Improvement Protocol (TIP) addresses the clinical use of buprenorphine in the treatment of opioid addiction. TIPs are best-practice guidelines for the treatment of substance use disorders that make the latest research in substance abuse treatment available to counselors and educators. The content was generated by a panel of experts…

Boone, Margaret; Brown, Nancy J.; Moon, Mary A.; Schuman, Deborah J.; Thomas, Josephine; Wright, Denise L.

2004-01-01

20

Failure to identify or effectively manage prescription opioid dependence acted as a gateway to heroin use-buprenorphine/naloxone treatment and recovery in a surgical patient.  

PubMed

The prescribing of opioid pain medication has increased markedly in recent years, with strong opioid dispensing increasing 18-fold in Tayside, Scotland since 1995. Despite this, little data is available to quantify the problem of opioid pain medication dependence (OPD) and until recently there was little guidance on best-practice treatment. We report the case of a young mother prescribed dihydrocodeine for postoperative pain relief who became opioid dependent. When her prescription was stopped without support, she briefly used heroin to overcome her withdrawal. After re-exposure to dihydrocodeine following surgery 9?years later and treatment with methadone for dependency, she was transferred to buprenorphine/naloxone. In our clinical experience and in agreement with Department of Health and Royal College of General Practitioner guidance, buprenorphine/naloxone is the preferred opioid substitution treatment for OPD. Our patient remains within her treatment programme and has returned to work on buprenorphine 16?mg/naloxone 4?mg in conjunction with social and psychological support. PMID:25519865

Conroy, Stephen; Hill, Duncan

2014-01-01

21

Motivational Assessment of Non-Treatment Buprenorphine Research Participation in Heroin Dependent Individuals  

PubMed Central

Background Heroin abuse remains an important public health problem, particularly in economically disadvantaged areas. Insight into this problem is gained from interviewing addicted individuals. However, we lack systematic data on factors that motivate heroin users to participate in non-treatment research that offers both financial incentives (compensation) and non-financial incentives (e.g., short-term medication). Aim To better understand the relative importance of several types of personal motivations to participate in non-treatment buprenorphine research, and to relate self-motivations to social, economic, demographic and drug use factors. Methods Heroin dependent volunteers (N = 235 total; 57 female and 178 male; 136 African American, 86 Caucasian, and 13 Other) applied for non-therapeutic buprenorphine research in an urban outpatient setting from 2004–2008. We conducted a semi-structured behavioral economic interview, after which participants ranked 11 possible motivations for research participation. Results Although the study was repeatedly described as non-treatment research involving buprenorphine, participants often ranked some treatment-related motivations as important (wanting to reduce/stop heroin use, needing a medication to get stabilized/detoxify). Some motivations correlated with income, heroin use, and years since marketing of buprenorphine. Two dimensions emerged from principal component analysis of motivation rankings: (1) treatment motivation vs. greater immediate needs, and (2) commitment to trying alternatives vs. a more accepting attitude toward traditional interventions. In summary, heroin addicts’ self-motivations to engage in non-therapeutic research are complex – they value economic gain but not exclusively or primarily – and relate to variables such as socioeconomic factors and drug use. PMID:22137646

Papke, Gina; Greenwald, Mark K.

2011-01-01

22

Opioid substitution treatment in New Zealand: a 40 year perspective.  

PubMed

We provide an overview of the history and philosophy of the treatment for opioid dependence, which has been dominated by methadone substitution treatment for the past 40 years in New Zealand. Although changes in approach have occurred over this time, influenced by various sociopolitical events and changing ideologies, opioid substitution treatment has still "not come of age". It remains undermined by stigma and risk concerns associated with methadone and has struggled to be accessible and attractive to illicit opioid drug users, comprehensive and integrated into mainstream health care. However, the introduction in 2012 of Pharmac-subsidised buprenorphine combined with naloxone (Suboxone) in the context of an emerging trend towards a broader recovery and well-being orientation could signal a new era in treatment. The availability of buprenorphine-naloxone may also facilitate a further shift in treatment from primarily siloed specialist addiction services to integrated primary care services. This shift will help reduce stigma, promote patient self-management and community integration and align opioid substitution treatment with treatment for other chronic health conditions such as diabetes and asthma. PMID:24997702

Deering, Daryle; Sellman, J Douglas; Adamson, Simon

2014-07-01

23

[Buprenorphine transdermal patch (Norspan tape)].  

PubMed

Buprenorphine is a chemically synthesized opioid characterized as the partial mu agonist and kappa antagonist, and transdermal buprenorphine patch will be considered useful as a strong analgesic with fewer psychological side effects in the treatment of chronic non-cancer pain. Use of transdermal buprenorphine should be limited for pain relief of intractable muscle skeletal pain that cannot be alleviated with other analgesics. To avoid severe complication and drug abuse or addiction, assessment of pain and medical history including drug dependence by medical team are important before administration of transdermal buprenorphine. Moreover, side effects such as nausea, vomiting, constipation, erythema and itching, loss of appetite should be treated appropriately. When transdermal buprenorphine is administered to chronic pain patients, physicians must examine the condition of patients regularly at an outpatient clinic. Moreover, decreasing and discontinuation of opioid including transdermal buprenorphine should always be considered during the treatment. Most important objective of chronic pain treatment is to improve QOL and ADL of patients. PMID:23905402

Hamaguchi, Shinsuke; Ikeda, Tomohito

2013-07-01

24

Variation in use of Buprenorphine and Methadone Treatment by Racial, Ethnic and Income Characteristics of Residential Social Areas in New York City  

PubMed Central

National data indicate that patients treated with buprenorphine for opiate use disorders are more likely to be White, highly educated, and to have greater incomes than those receiving methadone, but patterns of buprenorphine dissemination across demographic areas have not been documented in major metropolitan areas where poverty, minority populations and injection heroin use are concentrated. Rates of buprenorphine and methadone treatment are compared among areas of New York City defined by their income and ethnic/racial composition. Residential social areas (hereinafter called social areas) were defined as aggregations of ZIP codes with similar race/ethnicity and income characteristics, and were formed based on clustering techniques. Treatment rates were obtained for each New York City ZIP code: buprenorphine treatment rates were based on the annual number of buprenorphine prescriptions written, and the methadone treatment rate on the number of methadone clinic visits for persons in each ZIP code. Treatment rates were correlated univariately with ethnicity and income characteristics of ZIP codes. Social area treatment rates were compared using individual ANOVA models for each rate. Buprenorphine and methadone treatment rates were significantly correlated with the ethnicity and income characteristics of ZIP codes, and treatment rates differed significantly across the social areas. Buprenorphine treatment rates were highest in the social area with the highest income and lowest percentage of Black and Hispanic residents. Conversely, the methadone treatment rate was highest in the social area with the highest percentage of low income and Hispanic residents. The uneven dissemination of 0pioid maintenance treatment in New York City may be reflective of the limited public health impact of buprenorphine in ethnic minority and low income areas. Specific policy and educational interventions to providers are needed to promote the use of buprenorphine for opiate use disorders in diverse populations. PMID:23702611

Hansen, Helena B.; Siegel, Carole E.; Case, Brady G.; Bertollo, David N.; DiRocco, Danae; Galanter, Marc

2013-01-01

25

Two-year Experience with Buprenorphine-naloxone (Suboxone) for Maintenance Treatment of Opioid Dependence Within a Private Practice Setting.  

PubMed

Office-based buprenorphine-naloxone (Suboxone) treatment in the United States has significantly improved access to safe and effective opioid-dependence therapy. Little data from physicians' experiences prescribing Suboxone in private offices have been available. This retrospective chart review describes a family practitioner's first 2 years of clinical experience prescribing Suboxone for opioid dependence to 71 patients in a private office. After directly observed rapid office dose induction, Suboxone prescriptions were given monthly after evidence of continued stability. Urine was screened regularly and patients were referred for counseling and other ancillary services. Patients averaged 32 years old, 4.3 years of opioid dependence, and were primarily white (93%) and employed (70%). Fifty-two percent used heroin primarily (most by injection), and 70% had no agonist substitution therapy history. Almost half (47%) paid for their own treatment. Compliance during dose induction was excellent. Suboxone maintenance doses averaged 10 (range, 2-24) mg per day. More than 80% of urine samples were opioid-negative after Suboxone treatment began, although urinalysis did not always include a test for oxycodone. Seventy-five percent had successful outcomes by remaining in Suboxone treatment (43%), tapering successfully (21%), transferring to methadone maintenance (7%), or inpatient treatment (4%). Fifty-eight percent reported receiving counseling. Almost all (85%) paid their fees on time. There were no safety, medication abuse, or diversion issues detected. Overall, office-based Suboxone therapy was easily implemented and the physician considered the experience excellent. Suboxone maintenance was associated with good treatment retention and significantly reduced opioid use, and it is helping to reach patients, including injection drug users, without histories of agonist substitution therapy. PMID:21768942

Finch, James W; Kamien, Jonathan B; Amass, Leslie

2007-06-01

26

Interactions of buprenorphine and dipotassium clorazepate on anxiety and memory functions in the mouse.  

PubMed

Buprenorphine, a partial mu-receptor agonist widely substituted for heroin in the treatment of addiction, is often misused in combination with benzodiazepines. Improved hedonic properties may result, but only at the cost of increased buprenorphine toxicity. In order to elucidate the appeal of the benzodiazepine-buprenorphine combination, the present study looked at its neuropsycho-pharmacological effects on various emotional and cognitive parameters in the mouse. On the basis of previous dose-response studies, the regimen used was buprenorphine 0.3mg/kg, s.c. plus dipotassium clorazepate 1, 4 and 16 mg/kg, i.p. Anxiety-like behaviour was assessed using the black and white test box, and memory processes were examined via the spontaneous alternation paradigm in the Y-maze, and passive avoidance tests. Spontaneous locomotor activity was also evaluated. High doses of clorazepate impaired buprenorphine-induced hyperactivity and anxiogenic-like effects. They also increased buprenorphine-induced spontaneous alternation impairment, but did not modify its impact on long-term memory processes. These results suggest that the positive reinforcement experienced with the buprenorphine-benzodiazepine combination may be attributable, at least in part, to an increase in buprenorphine's sedative effect associated with a decrease in anxiogenicity. PMID:16720083

Lelong-Boulouard, Véronique; Quentin, Thomas; Moreaux, Fabien; Debruyne, Danièle; Boulouard, Michel; Coquerel, Antoine

2006-11-01

27

Predictors of Abstinence: National Institute of Drug Abuse Multisite Buprenorphine/Naloxone Treatment Trial in Opioid-Dependent Youth  

ERIC Educational Resources Information Center

Objective: To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal)-assisted psychosocial treatment for opioid-dependent youth. Method: Secondary analyses were performed of data from 152 youth (15-21 years old) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification with weekly…

Subramaniam, Geetha A.; Warden, Diane; Minhajuddin, Abu; Fishman, Marc J.; Stitzer, Maxine L.; Adinoff, Bryon; Trivedi, Madhukar; Weiss, Roger; Potter, Jennifer; Poole, Sabrina A.; Woody, George E.

2011-01-01

28

Buprenorphine for opioid addiction  

PubMed Central

SUMMARY Buprenorphine is a partial opioid agonist of the µ-receptor, and is used as a daily dose sublingual tablet or filmstrip for managing opioid addiction. In the USA, the Drug Addiction Treatment Act of 2000 made buprenorphine the only opioid medication for opioid addiction that can be prescribed in an office-based setting. Owing to its high affinity for the µ-receptor, buprenorphine inhibits the reinforcing effect of exogenous opioids. The ceiling effect of buprenorphine's µ-agonist activity reduces the potential for drug overdose and confers low toxicity even at high doses. Buprenorphine pharmacotherapy has proven to be a treatment approach that supports recovery from addiction while reducing or curtailing the use of opioids. This article examines buprenorphine pharmacotherapy for opioid addiction, focusing on the situation in the USA, and is based on a review of pertinent literature, and the authors’ research and clinical experience. The references in this paper were chosen according to the authors’ judgment of quality and relevance, and with respect to their familiarity and involvement in related research. PMID:24654720

Ling, Walter; Mooney, Larissa; Torrington, Matthew

2014-01-01

29

Supply of buprenorphine waivered physicians: The influence of state policies.  

PubMed

Buprenorphine, an effective opioid use disorder treatment, can be prescribed only by buprenorphine-waivered physicians. We calculated the number of buprenorphine-waivered physicians/100,000 county residents using 2008-11 Buprenorphine Waiver Notification System data, and used multivariate regression models to predict number of buprenorphine-waivered physicians/100,000 residents in a county as a function of county characteristics, state policies and efforts to promote buprenorphine use. In 2011, 43% of US counties had no buprenorphine-waivered physicians and 7% had 20 or more waivered physicians. Medicaid funding, opioid overdose deaths, and specific state guidance for office-based buprenorphine use were associated with more buprenorphine-waivered physicians, while encouraging methadone programs to promote buprenorphine use had no impact. Our findings provide important empirical information to individuals seeking to identify effective approaches to increase the number of physicians able to prescribe buprenorphine. PMID:25218919

Stein, Bradley D; Gordon, Adam J; Dick, Andrew W; Burns, Rachel M; Pacula, Rosalie Liccardo; Farmer, Carrie M; Leslie, Douglas L; Sorbero, Mark

2015-01-01

30

Consensus statement on office-based treatment of opioid dependence using buprenorphine.  

PubMed

Buprenorphine and buprenorphine/naloxone (BUP) are newly approved for office-based treatment of opioid dependence. Federal and non-federal regulatory and monitoring agencies, national and international researchers, national professional organizations, researchers involved in monitoring, opioid treatment programs and the pharmaceutical industry met to synthesize and disseminate practical information to guide training, practice, monitoring, regulation and evaluation efforts with these medications. We performed a review of the literature, training curricula and practice guidelines and commissioned manuscripts describing recently completed, or still in progress, studies or field experiences with BUP treatment. A consensus process generated fifteen statements: (1) The federal government should collect baseline data on opioid-related deaths and morbidity to assess the effect of BUP on public health, (2) the patient limit for group practices should apply to individual physicians rather than group practices, (3 and 4) telephone and Internet-based physician and pharmacist support is needed, (5) clinicians who provide psychosocial services to opioid dependent patients should be informed of the role of BUP, (6) opioid-dependent patients should be instructed to present for induction in mild withdrawal, (7) the existing Center for Substance Abuse Treatment guidelines provide a reasonable induction protocol, (8) physicians should be prepared to use ancillary medications with BUP induction, (9) a physician or nurse must be available to the patient during the induction period, (10) concurrent counseling and support services are necessary, (11) detoxification without appropriate followup addiction treatment leads to rapid relapse and is not as effective as maintenance, (12) pregnant opioid-dependent women should be treated using good clinical practice including specialist addiction care and prenatal care, (13) BUP induction and withdrawal treatment may benefit from different designations for payment, (14) take-home medication options should be tailored to patients' needs, (15) there is a need for clinical and policy research in unique patient populations. PMID:15450648

Fiellin, David A; Kleber, Herbert; Trumble-Hejduk, Jeanne G; McLellan, A Thomas; Kosten, Thomas R

2004-09-01

31

Combined abuse of clonidine and amitriptyline in a patient on buprenorphine maintenance treatment.  

PubMed

Buprenorphine/naloxone maintenance therapy is often prescribed in primary care to treat opioid dependence. Previous reports have described concomitant abuse of opioids and clonidine. In this case, a primary care patient on buprenorphine/naloxone maintenance therapy demonstrating altered mental status, hallucinations, falls, and rebound hypertension was found to be concomitantly abusing clonidine and amitryptyline, which share metabolic pathways with buprenorphine. Clinicians should be aware of patients' combining amitryptyline, clonidine, and gabapentin with buprenorphine to achieve a mood altering state, avoid co-prescribing them if possible, and maintain communication with pharmacies and other providers when they are prescribed. PMID:25314340

Seale, J Paul; Dittmer, Trent; Sigman, Erika J; Clemons, Holly; Johnson, J Aaron

2014-01-01

32

Combined Abuse of Clonidine and Amitriptyline in a Patient on Buprenorphine Maintenance Treatment  

PubMed Central

Buprenorphine/naloxone maintenance therapy is often prescribed in primary care to treat opioid dependence. Previous reports have described concomitant abuse of opioids and clonidine. In this case, a primary care patient on buprenorphine/naloxone maintenance therapy demonstrating altered mental status, hallucinations, falls, and rebound hypertension was found to be concomitantly abusing clonidine and amitryptyline, which share metabolic pathways with buprenorphine. Clinicians should be aware of patients' combining amitryptyline, clonidine, and gabapentin with buprenorphine to achieve a mood altering state, avoid co-prescribing them if possible, and maintain communication with pharmacies and other providers when they are prescribed. PMID:25314340

Dittmer, Trent; Sigman, Erika J.; Clemons, Holly; Johnson, J. Aaron

2014-01-01

33

Buprenorphine Sublingual  

MedlinePLUS

... dependence (addiction to opioid drugs, including heroin and narcotic painkillers). Buprenorphine is in a class of medications ... other medications.do not take antidepressants ('mood elevators'), narcotic pain killers, sedatives, sleeping pills, or tranquilizers while ...

34

Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent youth?  

PubMed Central

Background In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment. Methods Opioid dependent adolescents and young adults (n=152), aged 15–21, were randomized to 12 weeks (BUP, n=74) or 2 weeks of detoxification (DETOX, n=78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment. Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression. Results In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition. Conclusions Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/ Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics. PMID:22626890

Warden, Diane; Subramaniam, Geetha A.; Carmody, Thomas; Woody, George E.; Minhajuddin, Abu; Poole, Sabrina A.; Potter, Jennifer; Fishman, Marc; Bogenschutz, Michael; Patkar, Ashwin; Trivedi, Madhukar H.

2012-01-01

35

Predictors of Abstinence: NIDA Multi-site Buprenorphine/Naloxone Treatment Trial in Opioid Dependent Youth  

PubMed Central

Objective To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal) assisted psychosocial treatment for opioid dependent youth Method Secondary analyses of data from 152 youth (ages 15–21) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification, both with weekly individual and group drug counseling. Logistic regression models were constructed to identify baseline and during-treatment predictors of opioid positive urines (OPU) at week-12. Predictors were selected based on significance or trend toward significance (i.e. p<0.1) and backward stepwise selection was used, controlling for treatment group, to produce final independent predictors at p ? 0.05. Results Youth presenting to treatment with past 30-day injection drug use (IDU) and more active medical/psychiatric problems were less likely to have a week-12 OPU. Those with early treatment opioid abstinence (i.e. weeks 1 and 2); and those who received additional non-study treatments during the study were less likely to have a week-12 OPU; and those not completing 12 weeks of treatment were more likely to have an OPU. Conclusions Youth with advanced illness (i.e. reporting IDU and additional health problems), and those receiving ancillary treatments to augment study treatment were more likely to have lower opioid use. Treatment success in the first 2 weeks and completion of 12 weeks of treatment were associated with lower rates of OPU. These findings suggest that youth with advanced illness respond well to Bup/Nal treatment, and identify options for tailoring treatment for opioid-dependent youth presenting at community-based settings. PMID:22024000

Subramaniam, Geetha A.; Warden, Diane; Minhajuddin, Abu; Fishman, Marc J.; Stitzer, Maxine L.; Adinoff, Bryon; Trivedi, Madhukar; Weiss, Roger; Potter, Jennifer; Poole, Sabrina A.; Woody, George E.

2013-01-01

36

Patient perspectives on buprenorphine/naloxone: a qualitative study of retention during the starting treatment with agonist replacement therapies (START) study.  

PubMed

This study examines the barriers and facilitators of retention among patients receiving buprenorphine/naloxone at eight community-based opioid treatment programs across the United States. Participants (n = 105) were recruited up to three and a half years after having participated in a randomized clinical trial comparing the effect of buprenorphine/naloxone and methadone on liver function. Semi-structured interviews were conducted with 67 patients provided with buprenorphine/naloxone who had terminated early and 38 patients who had completed at least 24 weeks of the trial. Qualitative data were analyzed using the constant comparison method. Barriers to buprenorphine/naloxone retention that emerged included factors associated with: (1) the design of the clinical trial; (2) negative medication or treatment experience; and (3) personal circumstances. The facilitators comprised: (1) positive experience with the medication; (2) personal determination and commitment to complete; and (3) staff encouragement and support. The themes drawn from interviews highlight the importance of considering patients' prior experience with buprenorphine/naloxone and methadone, medication preference, personal circumstances, and motivation to abstain from illicit use or misuse of opioids, as these may influence retention. Ongoing education of patients and staff regarding buprenorphine/naloxone, especially in comparison to methadone, and support from staff and peers are essential. PMID:25364994

Teruya, Cheryl; Schwartz, Robert P; Mitchell, Shannon Gwin; Hasson, Albert L; Thomas, Christie; Buoncristiani, Samantha H; Hser, Yih-Ing; Wiest, Katharina; Cohen, Allan J; Glick, Naomi; Jacobs, Petra; McLaughlin, Paul; Ling, Walter

2014-01-01

37

Patient Characteristics Associated with Buprenorphine/Naloxone Treatment Outcome for Prescription Opioid Dependence: Results from a Multisite Study  

PubMed Central

Background Prescription opioid dependence is a growing problem, but little research exists on its treatment, including patient characteristics that predict treatment outcome. Methods A secondary analysis of data from a large multisite, randomized clinical trial, the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study (POATS) was undertaken to examine baseline patient characteristics (N=360) associated with success during 12-week buprenorphine/naloxone treatment for prescription opioid dependence. Baseline predictor variables included self-reported demographic and opioid use history information, diagnoses assessed via the Composite International Diagnostic Interview, and historical opioid use and related information from the Pain And Opiate Analgesic Use History. Results In bivariate analyses, pre-treatment characteristics associated with successful opioid use outcome included older age, past-year or lifetime diagnosis of major depressive disorder, initially obtaining opioids with a medical prescription to relieve pain, having only used opioids by swallowing or sublingual administration, never having used heroin, using an opioid other than extended-release oxycodone most frequently, and no prior opioid dependence treatment. In multivariate analysis, age, lifetime major depressive disorder, having only used opioids by swallowing or sublingual administration, and receiving no prior opioid dependence treatment remained as significant predictors of successful outcome. Conclusions This is the first study to examine characteristics associated with treatment outcome in patients dependent exclusively on prescription opioids. Characteristics associated with successful outcome after 12 weeks of buprenorphine/naloxone treatment include some that have previously been found to predict heroin-dependent patients’ response to methadone treatment and some specific to prescription opioid-dependent patients receiving buprenorphine/naloxone. PMID:23333292

Dreifuss, Jessica A.; Griffin, Margaret L.; Frost, Katherine; Fitzmaurice, Garrett M.; Potter, Jennifer Sharpe; Fiellin, David A.; Selzer, Jeffrey; Hatch-Maillette, Mary; Sonne, Susan C.; Weiss, Roger D.

2012-01-01

38

Buprenorphine is protective against the depressive effects of norbuprenorphine on ventilation  

SciTech Connect

High dose buprenorphine is used as substitution treatment in heroin addiction. However, deaths have been reported in addicts using buprenorphine. The role of norbuprenorphine, an N-dealkyl metabolite of buprenorphine, was hypothesized to explain these fatal cases. We determined the median intravenous lethal dose (LD{sub 5}) of norbuprenorphine in male Sprague-Dawley rats. The effects of a single intravenous dose of 3 or 9 mg/kg norbuprenorphine alone on arterial blood gases were studied. Finally, the effect of pre- and post-administrations of buprenorphine on norbuprenorphine-induced changes on arterial blood gases were analyzed. Norbuprenorphine's LD{sub 5} was 10 mg kg{sup -1}. Norbuprenorphine 3 mg kg{sup -1} produces the rapid onset of sustained respiratory depression, as demonstrated at 20 min by a maximal significant increase in PaCO{sub 2} (8.4 {+-} 0.9 versus 5.7 {+-} 0.1 kPa), decrease in arterial pH (7.25 {+-} 0.06 versus 7.44 {+-} 0.01), and hypoxia (8.3 {+-} 0.6 versus 11.1 {+-} 0.2 kPa). Buprenorphine not only protected against the effects of 3 mg kg{sup -1} norbuprenorphine in a dose-dependent manner but also reversed the effects when given afterward. Binding experiments suggest a role for mu- and to a lesser extent for delta-opioid receptors in buprenorphine protective effect against norbuprenorphine-induced respiratory depression. In conclusion, our data clearly show that norbuprenorphine alone causes important deleterious effects on ventilation in rats. However, buprenorphine protective effect calls into question the role for norbuprenorphine in respiratory toxicity associated with buprenorphine use.

Megarbane, Bruno [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France) and Reanimation Medicale et Toxicologique, Hopital Lariboisiere, 2 Rue Ambroise Pare, 75010 Paris (France)]. E-mail: bruno-megarbane@wanadoo.fr; Marie, Nicolas [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France); Pirnay, Stephane [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France); Laboratoire de Toxicologie, Prefecture de Police de Paris, 75012 Paris (France); Borron, Stephen W. [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France) and Departments of Emergency Medicine and Medicine - Occupational and Environmental Health, George Washington University, Washington, DC 22052 (United States); Gueye, Papa N. [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France); Risede, Patricia [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France); Monier, Claire [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France); Noble, Florence [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France); Baud, Frederic J. [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France); Reanimation Medicale et Toxicologique, Hopital Lariboisiere, 2 Rue Ambroise Pare, 75010 Paris (France)

2006-05-01

39

Treatment Retention among Patients Randomized to Buprenorphine/Naloxone Compared to Methadone in A Multi-site Trial  

PubMed Central

Aims To examine patient and medication characteristics associated with retention and continued illicit opioid use in methadone (MET) versus buprenorphine/naloxone (BUP) treatment for opioid dependence. Design/Settings/Participants This secondary analysis included 1,267 opioid-dependent individuals participating in 9 opioid treatment programs between 2006 and 2009 and randomized to receive open-label BUP or MET for 24 weeks. Measurements The analyses included measures of patient characteristics at baseline (demographics; use of alcohol, cigarettes, and illicit drugs; self-rated mental and physical health), medication dose and urine drug screens during treatment, and treatment completion and days in treatment during the 24 week trial. Findings The treatment completion rate was 74% for MET vs. 46% for BUP (p<.01); the rate among MET participants increased to 80% when the maximum MET dose reached or exceeded 60mg/day. With BUP, the completion rate increased linearly with higher doses, reaching 60% with doses of 30–32mg/day. Of those remaining in treatment, positive opioid urine results were significantly lower (OR=0.63, 95%CI=0.52–0.76, p<.01) among BUP relative to MET participants during the first 9 weeks of treatment. Higher medication dose was related to lower opiate use, more so among BUP patients. A Cox proportional hazards model revealed factors associated with dropout: (1) BUP (vs. MET, HR=1.61, CI:1.20–2.15), (2) lower medication dose (<16mg for BUP, <60mg for MET; HR=3.09, CI:2.19–4.37), (3) the interaction of dose and treatment condition (those with higher BUP dose were 1.04 times more likely to drop out than those with lower MET dose, and (4) being younger, Hispanic, and using heroin or other substances during treatment. Conclusions Provision of methadone appears to be associated with better retention in treatment for opioid dependence than buprenorphine, as does use of provision of higher doses of both medications. Provision of buprenorphine is associated with lower continued use of illicit opioids. PMID:23961726

Hser, Yih-Ing; Saxon, Andrew J.; Huang, David; Hasson, Al; Thomas, Christie; Hillhouse, Maureen; Jacobs, Petra; Teruya, Cheryl; McLaughlin, Paul; Wiest, Katharina; Cohen, Allan; Ling, Walter

2013-01-01

40

Dosing considerations with transdermal formulations of fentanyl and buprenorphine for the treatment of cancer pain  

PubMed Central

Opioids continue to be first-line pharmacotherapy for patients suffering from cancer pain. Unfortunately, subtherapeutic dosage prescribing of pain medications remains common, and many cancer patients continue to suffer and experience diminished quality of life. A large variety of therapeutic options are available for cancer pain patients. Analgesic pharmacotherapy is based on the patient’s self-report of pain intensity and should be tailored to meet the requirements of each individual. Most, if not all, cancer pain patients will ultimately require modifications in their opioid pharmacotherapy. When changes in a patient’s medication regimen are needed, adequate pain control is best maintained through appropriate dosage conversion, scheduling immediate release medication for withdrawal prevention, and providing as needed dosing for breakthrough pain. Transdermal opioids are noninvasive, cause less constipation and sedation when compared to oral opioids, and may improve patient compliance. A relative potency of 100:1 is recommended when converting the patient from oral morphine to transdermal fentanyl. Based on the limited data available, there is significant interpatient variability with transdermal buprenorphine and equipotency recommendations from oral morphine of 75:1–110:1 have been suggested. Cancer patients may require larger transdermal buprenorphine doses to control their pain and may respond better to a more aggressive 75–100:1 potency ratio. This review outlines the prescribing of transdermal fentanyl and transdermal buprenorphine including how to safely and effectively convert to and use them for those with cancer pain. PMID:25170278

Skaer, Tracy L

2014-01-01

41

Outcomes among buprenorphine-naloxone primary care patients after Hurricane Sandy  

PubMed Central

Background The extent of damage in New York City following Hurricane Sandy in October 2012 was unprecedented. Bellevue Hospital Center (BHC), a tertiary public hospital, was evacuated and temporarily closed as a result of hurricane-related damages. BHC’s large primary care office-based buprenorphine clinic was relocated to an affiliate public hospital for three weeks. The extent of environmental damage and ensuing service disruption effects on rates of illicit drug, tobacco, and alcohol misuse, buprenorphine medication supply disruptions, or direct resource losses among office-based buprenorphine patients is to date unknown. Methods A quantitative and qualitative semi-structured survey was administered to patients in BHC’s primary care buprenorphine program starting one month after the hurricane. Survey domains included: housing and employment disruptions; social and economic support; treatment outcomes (buprenorphine adherence and ability to get care), and tobacco, alcohol, and drug use. Open-ended questions probed general patient experiences related to the storm, coping strategies, and associated disruptions. Results There were 132 patients enrolled in the clinic at the time of the storm; of those, 91 patients were recruited to the survey, and 89 completed (98% of those invited). Illicit opioid misuse was rare, with 7 respondents reporting increased heroin or illicit prescription opioid use following Sandy. Roughly half of respondents reported disruption of their buprenorphine-naloxone medication supply post-event, and self-lowering of daily doses to prolong supply was common. Additional buprenorphine was obtained through unscheduled telephone or written refills from relocated Bellevue providers, informally from friends and family, and, more rarely, from drug dealers. Conclusions The findings highlight the relative adaptability of public sector office-based buprenorphine treatment during and after a significant natural disaster. Only minimal increases in self-reported substance use were reported despite many disruptions to regular buprenorphine supplies and previous daily doses. Informal supplies of substitute buprenorphine from family and friends was common. Remote telephone refill support and a temporary back-up location that provided written prescription refills and medication dispensing for uninsured patients enabled some patients to maintain an adequate medication supply. Such adaptive strategies to ensure medication maintenance continuity pre/post natural disasters likely minimize poor treatment outcomes. PMID:24467734

2014-01-01

42

Barriers to Primary Care Physicians Prescribing Buprenorphine  

PubMed Central

PURPOSE Despite the efficacy of buprenorphine-naloxone for the treatment of opioid use disorders, few physicians in Washington State use this clinical tool. To address the acute need for this service, a Rural Opioid Addiction Management Project trained 120 Washington physicians in 2010–2011 to use buprenorphine. We conducted this study to determine what proportion of those trained physicians began prescribing this treatment and identify barriers to incorporating this approach into outpatient practice. METHODS We interviewed 92 of 120 physicians (77%), obtaining demographic information, current prescribing status, clinic characteristics, and barriers to prescribing buprenorphine. Residents and 7 physicians who were prescribing buprenorphine at the time of the course were excluded from the study. We analyzed the responses of the 78 remaining respondents. RESULTS Almost all respondents reported positive attitudes toward buprenorphine, but only 22 (28%) reported prescribing buprenorphine. Most (95%, n = 21) new prescribers were family physicians. Physicians who prescribed buprenorphine were more likely to have partners who had received a waiver to prescribe buprenorphine. A lack of institutional support was associated with not prescribing the medication (P = .04). A lack of mental health and psychosocial support was the most frequently cited barrier by both those who prescribe and who do not prescribe buprenorphine. CONCLUSION Interventions before and after training are needed to increase the number of physicians who offer buprenorphine for treatment of addiction. Targeting physicians in clinics that agree in advance to institute services, coupled with technical assistance after they have completed their training, their clinical teams, and their administrations is likely to help more physicians become active providers of this highly effective outpatient treatment. PMID:24615308

Hutchinson, Eliza; Catlin, Mary; Andrilla, C. Holly A.; Baldwin, Laura-Mae; Rosenblatt, Roger A.

2014-01-01

43

Gender Differences Among Prisoners With Pre-Incarceration Heroin Dependence Participating in a Randomized Clinical Trial of Buprenorphine Treatment  

PubMed Central

The primary focus of the current study is to examine whether gender and other baseline characteristics were significantly associated with more severe patterns of drug use. It involves data from 260 male and female pre-release prison inmates with pre-incarceration heroin dependence who enrolled in a randomized clinical trial of prison-initiated buprenorphine. Three outcomes are examined: 1) Lifetime Intravenous drug use; 2) Lifetime number of drugs used; and 3) Heroin use in prison. Regarding lifetime intravenous drug use; race (p = .0001), education (p = .009), age (p = .0001), and psychological treatment (p = .028) were significant. Concerning lifetime number of drugs used; race (p =.0001) and age of first crime (p = .001) were significant. Finally, gender (p = .004), was the only significant variable in terms of using heroin while in prison. All of these differences may have important clinical, treatment, and research implications, which are discussed. PMID:23997546

Gordon, Michael S.; Kinlock, Timothy W.; Couvillion, Kathryn A.; Wilson, Monique E.; Schwartz, Robert P.; O’Grady, Kevin E.

2013-01-01

44

Comparative Effects of Vasectomy Surgery and Buprenorphine Treatment on Faecal Corticosterone Concentrations and Behaviour Assessed by Manual and Automated Analysis Methods in C57 and C3H Mice  

PubMed Central

Establishing effective cage-side pain assessment methods is essential if post-surgical pain is to be controlled effectively in laboratory animals. Changes to overall activity levels are the most common methods of assessment, but may not be the most appropriate for establishing the analgesic properties of drugs, especially in mice, due their high activity levels. Use of drugs that can affect activity (e.g. opioids) is also a problem. The relative merits of both manual and automated behaviour data collection methods was determined in two inbred mouse strains undergoing vasectomy following treatment with one of 2 buprenorphine dose rates. Body weights and the effects of surgery and buprenorphine on faecal corticosterone were also measured. Surgery caused abnormal behaviour and reduced activity levels, but high dose buprenorphine caused such large-scale increases in activity in controls that we could not establish analgesic effects in surgery groups. Only pain-specific behaviour scoring using the manual approach was effective in showing 0.05 mg/kg buprenorphine alleviated post-vasectomy pain. The C57 mice also responded better to buprenorphine than C3H mice, indicating they were either less painful, or more responsive to its analgesic effects. C3H mice were more susceptible to the confounding effects of buprenorphine irrespective of whether data were collected manually or via the automated approach. Faecal corticosterone levels, although variable, were higher in untreated surgery mice than in control groups, also indicating the presence of pain or distress. Pain-specific scoring was superior to activity monitoring for assessing the analgesic properties of buprenorphine in vasectomised mice. Buprenorphine (0.01 mg/kg), in these strains of male mice, for this procedure, provided inadequate analgesia and although 0.05 mg/kg was more effective, not completely so. The findings support the recommendation that analgesic dose rates should be adjusted in relation to the potential severity of the surgical procedure, the mouse strain, and the individual animals' response. PMID:24098748

Wright-Williams, Sian; Flecknell, Paul A.; Roughan, Johnny V.

2013-01-01

45

The effectiveness of opioid substitution treatments for patients with opioid dependence: a systematic review and multiple treatment comparison protocol  

PubMed Central

Background Opioids are psychoactive analgesic drugs prescribed for pain relief and palliative care. Due to their addictive potential, effort and vigilance in controlling prescriptions is needed to avoid misuse and dependence. Despite the effort, the prevalence of opioid use disorder continues to rise. Opioid substitution therapies are commonly used to treat opioid dependence; however, there is minimal consensus as to which therapy is most effective. Available treatments include methadone, heroin, buprenorphine, as well as naltrexone. This systematic review aims to assess and compare the effect of all available opioid substitution therapies on the treatment of opioid dependence. Methods/Design The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. The title, abstract, and full-text screening will be completed in duplicate. When appropriate, multiple treatment comparison Bayesian meta-analytic methods will be performed to deduce summary statistics estimating the effectiveness of all opioid substitution therapies in terms of retention and response to treatment (as measured through continued opioid abuse). Discussion Using evidence gained from this systematic review, we anticipate disseminating an objective review of the current available literature on the effectiveness of all opioid substitution therapies for the treatment of opioid use disorder. The results of this systematic review are imperative to the further enhancement of clinical practice in addiction medicine. Systematic review registration PROSPERO CRD42013006507. PMID:25239213

2014-01-01

46

Buprenorphine/Naloxone and Methadone Maintenance Treatment Outcomes for Opioid Analgesic, Heroin, and Combined Users: Findings From Starting Treatment With Agonist Replacement Therapies (START)  

PubMed Central

Objective: The objective of this secondary analysis was to explore differences in baseline clinical characteristics and opioid replacement therapy treatment outcomes by type (heroin, opioid analgesic [OA], or combined [heroin and OA]) and route (injector or non-injector) of opioid use. Method: A total of 1,269 participants (32.2% female) were randomized to receive one of two study medications (methadone or buprenorphine/naloxone [BUP]). Of these, 731 participants completed the 24-week active medication phase. Treatment outcomes were opioid use during the final 30 days of treatment (among treatment completers) and treatment attrition. Results: Non-opioid substance dependence diagnoses and injecting differentiated heroin and combined users from OA users. Non-opioid substance dependence diagnoses and greater heroin use differentiated injectors from non-injectors. Further, injectors were more likely to be using at end of treatment compared with non-injectors. OA users were more likely to complete treatment compared with heroin users and combined users. Non-injectors were more likely than injectors to complete treatment. There were no interactions between type of opioid used or injection status and treatment assignment (methadone or BUP) on either opioid use or treatment attrition. Conclusions: Findings indicate that substance use severity differentiates heroin users from OA users and injectors from non-injectors. Irrespective of medication, heroin use and injecting are associated with treatment attrition and opioid misuse during treatment. These results have particular clinical interest, as there is no evidence of superiority of BUP over methadone for treating OA users versus heroin users. PMID:23739025

Potter, Jennifer S.; Marino, Elise N.; Hillhouse, Maureen P.; Nielsen, Suzanne; Wiest, Katharina; Canamar, Catherine P.; Martin, Judith A.; Ang, Alfonso; Baker, Rachael; Saxon, Andrew J.; Ling, Walter

2013-01-01

47

Pain and Associated Substance Use among Opioid Dependent Individuals Seeking Office-Based Treatment with Buprenorphine-Naloxone: A Needs Assessment Study  

PubMed Central

Background and Objectives A paucity of studies has examined the pain experiences of opioid dependent individuals seeking office-based buprenorphine-naloxone treatment (BNT). We set out to examine, among those seeking BNT: (a) the prevalence of pain types (i.e., recent pain, chronic pain), (b) the characteristics of pain (intensity, frequency, duration, interference, location, and genesis), and (c) substance use to alleviate pain. Methods We surveyed 244 consecutive individuals seeking office-based buprenorphine-naloxone treatment (BNT) for opioid dependence about physical pain and associated substance use. Results Thirty-six percent of respondents reported chronic pain (CP) (i.e., pain lasting at least 3 months) and 36% reported “some pain” (SP) (i.e., past week pain not meeting the threshold for CP). In comparison to SP respondents, those with CP were, on average, older; reported greater current pain intensity, pain frequency, typical pain duration, typical pain intensity, and typical pain interference; were more likely to report shoulder or pelvis and less likely to report stomach or arms as their most bothersome pain location; and were more likely to report accident or nerve damage and less likely to report opioid withdrawal as the genesis of their pain. Both pain subgroups reported similarly high rates of past-week substance use to alleviate pain. Conclusions and Scientific Significance The high rates of pain and self-reported substance use to manage pain suggest the importance of assessing and addressing pain in BNT patients. PMID:23617861

Barry, Declan T.; Savant, Jonathan D.; Beitel, Mark; Cutter, Christopher J.; Moore, Brent A.; Schottenfeld, Richard S.; Fiellin, David A.

2012-01-01

48

Buprenorphine may not be as safe as you think: a pediatric fatality from unintentional exposure.  

PubMed

Buprenorphine is a partial ?-opioid receptor agonist that is approved for the treatment of opioid dependency. It is generally believed to be safer than methadone because of its ceiling effect on respiratory depression. As more adults in US households use buprenorphine, an increasing number of children are being exposed. We report a fatal exposure to buprenorphine in a small child that occurred after ingestion of a caretaker's buprenorphine/naloxone. Postmortem toxicology analysis showed free serum concentrations of 52 ng/mL and 39 ng/mL for buprenorphine and norbuprenorphine, respectively. No other drugs were detected. Autopsy did not find signs of injury or trauma. The theoretical safety provided by the ceiling effect in respiratory depression from buprenorphine may not apply to children, and buprenorphine may cause dose-dependent respiratory depression. PMID:23129079

Kim, Hong K; Smiddy, Monica; Hoffman, Robert S; Nelson, Lewis S

2012-12-01

49

Formulation of Buprenorphine for Sublingual Use in Neonates  

PubMed Central

OBJECTIVES The only medication used sublingually in the neonate is buprenorphine for the treatment of neonatal abstinence syndrome (NAS). Compared with morphine, buprenorphine reduces the length of treatment and length of hospitalization in neonates treated for NAS. The objective of this study was to characterize the stability of ethanolic buprenorphine for sublingual administration. METHODS Buprenorphine solution was prepared and stored in amber glass source bottles at either 68°F to 77°F (20°C-25°C) or 36°F to 46°F (2.2°C-7.8°C). Samples were collected from each of these batches on days 0, 3, 7, 14, and 30. Additional samples were withdrawn at baseline from each batch and placed in oral dispensing syringes for 3 and 7 days. Buprenorphine concentration was assessed by liquid chromatography–electrospray ionization–tandem mass spectrometry. RESULTS Neither storage temperature (p=0.65) nor storage time (p=0.24) significantly affected buprenorphine concentrations. All of the mean concentrations, regardless of storage temperature, were above 95% of the labeled concentration, and the potency was maintained for samples stored either in the original amber glass source bottles or in oral syringes. CONCLUSIONS An ethanolic buprenorphine solution is stable at room temperature for 30 days. PMID:22768012

Anagnostis, Ellena A.; Sadaka, Rania E.; Sailor, Linda A.; Moody, David E.; Dysart, Kevin C.; Kraft, Walter K.

2011-01-01

50

PREVALENCE AND CORRELATES OF STREET-OBTAINED BUPRENORPHINE USE AMONG CURRENT AND FORMER INJECTORS IN BALTIMORE, MARYLAND  

PubMed Central

Objectives There are few systematic assessments of street-obtained buprenorphine use from community-based samples in the United States. The objective of this study was to characterize the prevalence, correlates, and reasons for street-obtained buprenorphine use among current and former injection drug users (IDUs) in Baltimore, Maryland. Methods In 2008, participants of the ALIVE (AIDS Linked to the IntraVenous Experience) study, a community-based cohort of IDUs, were administered a survey on buprenorphine. Street-obtained buprenorphine represented self-reported use of buprenorphine obtained from the street or a friend in the prior three months. Results 602 respondents were predominantly male (65%), African-American (91%), and 30% were HIV-positive. Overall, nine percent reported recent street-obtained buprenorphine use, and only 2% reported using to get high. Among active opiate users, 23% reported recent use of street-obtained buprenorphine. Use of buprenorphine prescribed by a physician, injection and non-injection drug use, use of street-obtained methadone and prescription opiates, homelessness, and opioid withdrawal symptoms were positively associated, while methadone treatment, health insurance, outpatient care, and HIV-infection were negatively associated with recent street-obtained buprenorphine use in univariate analysis. After adjustment, active injection and heroin use were positively associated with street-obtained buprenorphine use. Ninety-one percent reported using street-obtained buprenorphine to manage withdrawal symptoms. Conclusions While 9% reported recent street-obtained buprenorphine use, only a small minority reported using buprenorphine to get high, with the majority reporting use to manage withdrawal symptoms. There is limited evidence of diversion of buprenorphine in this sample and efforts to expand buprenorphine treatment should continue with further monitoring. PMID:24018232

Genberg, Becky L.; Gillespie, Mirinda; Schuster, Charles R.; Johanson, Chris-Ellyn; Astemborski, Jacquie; Kirk, Gregory D.; Vlahov, David; Mehta, Shruti H.

2013-01-01

51

Structural Determinants of Opioid and NOP Receptor Activity in Derivatives of Buprenorphine  

PubMed Central

The unique pharmacological profile of buprenorphine has led to its considerable success as an analgesic and as a treatment agent for drug abuse. Activation of nociceptin/orphanin FQ peptide (NOP) receptors has been postulated to account for certain aspects of buprenorphine’s behavioural profile. In order to investigate the role of NOP activation further, a series of buprenorphine analogues has been synthesised with the aim of increasing affinity for the NOP receptor. Binding and functional assay data on these new compounds indicate that the area around C20 in the orvinols is key to NOP receptor activity, with several compounds displaying higher affinity than buprenorphine. One compound, 1b, was found to be a mu opioid receptor partial agonist of comparable efficacy to buprenorphine, but with higher efficacy at NOP receptors. PMID:21866885

Cami-Kobeci, Gerta; Polgar, Willma E.; Khroyan, Taline V; Toll, Lawrence; Husbands, Stephen M.

2011-01-01

52

Effects of intermittent buprenorphine administration on cocaine self-administration by rhesus monkeys.  

PubMed

In previous studies, daily buprenorphine administration significantly reduced cocaine self-administration by rhesus monkeys over 15 to 120 days (Mello et al., 1990, 1992). This report describes the effects of 60 days of intermittent buprenorphine (0.40 mg/kg) treatment once every 48 hr or 72 hr on cocaine and food self-administration by six rhesus monkeys. Cocaine (0.05 or 0.10 mg/kg/injection) and food (1-g banana pellet) self-administration were maintained on a fixed ratio 4, (variable ratio 16:S) reinforcement schedule. Intermittent buprenorphine treatment reduced cocaine self-administration significantly below saline treatment levels (P < .01). On the first day of buprenorphine treatment, cocaine self-administration averaged 53 and 60% below base line (P < .01-.0001). Cocaine self-administration remained significantly below base line on day 2 (P < .02-.0001) but usually returned to base-line levels by day 3. During buprenorphine treatment once every 48 hr, cocaine self-administration gradually increased over time in four monkeys (P < .001-.0005). These data suggest that intermittent buprenorphine treatment is less effective than daily buprenorphine treatment in reducing cocaine self-administration by rhesus monkeys. Food self-administration decreased by 23.6 and 12.7% from the saline base line during buprenorphine treatment every 48 and 72 hr, respectively. On the day of buprenorphine treatment, food self-administration was usually significantly lower than during the saline base line (P < .05-.0001), but usually returned to or exceeded base line levels by days 2 and 3. There were no significant changes in food self-administration over time with intermittent buprenorphine treatment every 48 hr. PMID:8437105

Mello, N K; Kamien, J B; Lukas, S E; Mendelson, J H; Drieze, J M; Sholar, J W

1993-02-01

53

Methadone and buprenorphine-naloxone are effective in reducing illicit buprenorphine and other opioid use, and reducing HIV risk behavior – Outcomes of a Randomized Trial  

PubMed Central

Aims Determine the extent to which buprenorphine injectors continue treatment with buprenorphine-naloxone or methadone, and the impact of these treatments on substance use and HIV risk in the Republic of Georgia. Methods Randomized controlled 12-week trial of daily-observed methadone or buprenorphine-naloxone followed by a dose taper, referral to ongoing treatment, and follow-up at week 20 at the Uranti Clinic in Tbilisi, Republic of Georgia. Eighty consenting treatment-seeking individuals (40/group) aged 25 and above who met ICD-10 criteria for opioid dependence with physiologic features and reported injecting buprenorphine 10 or more times in the past 30 days. Opioid use according to urine tests and self-reports, treatment retention, and HIV risk behavior as determined by the Risk Assessment Battery. Results Mean age of participants was 33.7 (SD5.7), 4 were female, mean history of opioid injection use was 5.8 years (SD4.6), none were HIV+ at intake or at the 12-week assessment and 73.4% were HCV+. Sixty-eight participants (85%) completed the 12-week medication phase (33 from methadone and 35 from buprenorphine/naloxone group); 37 (46%) were in treatment at the 20-week follow-up (21 from methadone and 16 from the buprenorphine/naloxone group). In both study arms, treatment resulted in a marked reduction in unprescribed buprenorphine, other opioid use, and HIV injecting risk behavior with no clinically significant differences between the two treatment arms. Conclusions Daily observed methadone or buprenorphine-naloxone are effective treatments for non-medical buprenorphine and other opioid use in the Republic of Georgia and likely to be useful for preventing HIV infection. PMID:23916321

Otiashvili, David; Piralishvili, Gvantsa; Sikharulidze, Zura; Kamkamidze, George; Poole, Sabrina; Woody, George E.

2013-01-01

54

ROAD TRAFFIC CRASHES AND PRESCRIBED METHADONE AND BUPRENORPHINE: A FRENCH REGISTRY-BASED CASE-  

E-print Network

functioning in healthy volunteers with no history of opioid abuse. Few or no significant effects have been-consumption of other substances (alcohol and benzodiazepines). Injured drivers exposed to buprenorphine or methadone of risky behaviors and treatments. Key words: methadone, buprenorphine, road traffic crashes 2 hal-01027574

Boyer, Edmond

55

New developments in the management of opioid dependence: focus on sublingual buprenorphine–naloxone  

PubMed Central

Opioid maintenance therapy is a well-established first-line treatment approach in opioid dependence. Buprenorphine, a partial opioid agonist, has been found by numerous studies to be an effective and safe medication in the treatment of opioid dependence. At present, buprenorphine is available as a monodrug or in a fixed 4:1 ratio combination with naloxone. A diminished risk of diversion and abuse for the buprenorphine–naloxone combination is likely but not firmly established. Conventional formulations are given sublingually to avoid the hepatic first-pass effect. A novel film tablet is available only in the US and Australia. Other novel, sustained-release formulations (implant, depot) are currently being developed and tested. Recent studies, including a Cochrane meta-analysis, suggest that the retention with buprenorphine is lower than for methadone, but that buprenorphine may be associated with less drug use. Higher doses of buprenorphine are associated with better retention rates. Buprenorphine has a ceiling effect at the opioid receptor with regard to respiratory depression, and may cause fewer fatal intoxications than methadone. Possible antidepressant effects of buprenorphine and its use in comorbid psychiatric patients has not been studied in much detail. Clinical implications are discussed. PMID:25610012

Soyka, Michael

2015-01-01

56

Buprenorphine Reduces Alcohol Drinking Through Activation of the Nociceptin/Orphanin FQ-NOP Receptor System  

PubMed Central

Background Activation of the NOP receptor by its endogenous ligand nociceptin/orphanin FQ reduces ethanol intake in genetically selected alcohol preferring Marchigian Sardinian alcohol preferring (msP) rats. Here we evaluated whether buprenorphine, a partial agonist at ?-opioid and NOP receptors, would reduce ethanol consumption in msP rats via activation of NOP receptors. Methods Marchigian Sardinian alcohol preferring rats trained to drink 10% alcohol 2 hours/day were injected with buprenorphine (.03, .3, 3.0, or 6.0 mg/kg intraperitoneally [IP]) 90 min before access to ethanol. Results Similar to prototypical ?-agonists, the two lowest doses of buprenorphine significantly increased ethanol consumption (p < .01); in contrast, the two highest doses reduced it (p < .05). Pretreatment with naltrexone (.25 mg/kg IP) prevented the increase of ethanol intake induced by .03 mg/kg of buprenorphine (p < .001) but did not affect the inhibition of ethanol drinking induced by 3.0 mg/kg of buprenorphine. Conversely, pretreatment with the selective NOP receptor antagonist UFP-101 (10.0 or 20.0 ?g/rat) abolished the suppression of ethanol drinking by 3.0 mg/kg of buprenorphine. Conclusions Buprenorphine has dualistic effects on ethanol drinking; low doses increase alcohol intake via stimulation of classic opioid receptors, whereas higher doses reduce it via activation of NOP receptors. We suggest that NOP agonistic properties of buprenorphine might be useful in the treatment of alcoholism. PMID:16533497

Ciccocioppo, Roberto; Economidou, Daina; Rimondini, Roberto; Sommer, Wolfgang; Massi, Maurizio; Heilig, Markus

2011-01-01

57

The Implementation of Buprenorphine/Naloxone in College Health Practice  

ERIC Educational Resources Information Center

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…

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

2008-01-01

58

Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity causing anti-reward and relapse potential?  

PubMed Central

Opiate addiction is associated with many adverse health and social harms, fatal overdose, infectious disease transmission, elevated health care costs, public disorder, and crime. Although community-based addiction treatment programs continue to reduce the harms of opiate addiction with narcotic substitution therapy such as methadone maintenance, there remains a need to find a substance that not only blocks opiate-type receptors (mu, delta, etc.) but also provides agonistic activity; hence the impetus arose for the development of a combination of narcotic antagonism and mu receptor agonist therapy. After three decades of extensive research the federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with addiction disorders by providing increased access to options for treatment. DATA allows physicians who complete a brief specialty-training course to become certified to prescribe buprenorphine and buprenorphine/naloxone (Subutex, Suboxone) for treatment of patients with opioid dependence. Clinical studies indicate buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and in reducing illicit opioid use. With that stated, we must consider the long-term benefits or potential toxicity attributed to Subutex or Suboxone. We describe a mechanism whereby chronic blockade of opiate receptors, in spite of only partial opiate agonist action, may ultimately block dopaminergic activity causing anti-reward and relapse potential. While the direct comparison is not as yet available, toxicity to buprenorphine can be found in the scientific literature. In considering our cautionary note in this commentary, we are cognizant that to date this is what we have available, and until such a time when the real magic bullet is discovered, we will have to endure. However, more than anything else this commentary should at least encourage the development of thoughtful new strategies to target the specific brain regions responsible for relapse prevention. PMID:21948099

Blum, Kenneth; Chen, Thomas JH; Bailey, John; Bowirrat, Abdulla; Femino, John; Chen, Amanda LC; Simpatico, Thomas; Morse, Siobhan; Giordano, John; Damle, Uma; Kerner, Mallory; Braverman, Eric R.; Fornari, Frank; Downs, B.William; Rector, Cynthia; Barh, Debmayla; Oscar-Berman, Marlene

2013-01-01

59

Novel depots of buprenorphine have a long-acting effect for the management of physical dependence to morphine.  

PubMed

Buprenorphine is a promising new pharmacotherapy for the management of physical dependence to opioids. The aim of the study was to evaluate the duration of action of several novel depots of buprenorphine in the treatment of physical dependence to morphine in mice. Following intramuscular injection, the duration of action of several novel oil-based depots of buprenorphine base in morphine-dependent mice were evaluated. The traditional dosage form of buprenorphine hydrochloride in saline was used as control. We found that the depot of buprenorphine base in sesame oil produced a dose-related long-lasting effect. On an equimolar basis of 6 micromol kg(-1), its effect was 5.7-fold longer than that of buprenorphine hydrochloride in saline. When prepared in several other oleaginous vehicles (castor oil, cottonseed oil, peanut oil and soybean oil), buprenorphine base also produced a long-lasting effect, which was similar to buprenorphine base in sesame oil. In conclusion, buprenorphine base, when prepared in oleaginous vehicles and injected intramuscularly in mice, produced a long-lasting effect on physical dependence to morphine. PMID:16536900

Liu, Kuo-Sheng; Kao, Cheng-Hsiung; Liu, Shyun-Yeu; Sung, K C; Kuei, Chun-Hsiung; Wang, Jhi-Joung

2006-03-01

60

Opioid Abstinence Reinforcement Delays Heroin Lapse during Buprenorphine Dose Tapering  

ERIC Educational Resources Information Center

A positive reinforcement contingency increased opioid abstinence during outpatient dose tapering (4, 2, then 0 mg/day during Weeks 1 through 3) in non-treatment-seeking heroin-dependent volunteers who had been maintained on buprenorphine (8 mg/day) during an inpatient research protocol. The control group (n = 12) received $4.00 for completing…

Greenwald, Mark K.

2008-01-01

61

Efficacy of daily and alternate-day dosing regimens with the combination buprenorphine–naloxone tablet  

Microsoft Academic Search

This study evaluated the efficacy of a combination tablet formulation of buprenorphine containing 8 mg of buprenorphine and 2 mg of naloxone for every other day treatment and whether increasing the daily maintenance dose was essential for maintaining an efficacious alternate-day treatment. Twenty-six opioid-dependent outpatients completing a 16-day baseline entered a double-blind, placebo-controlled, triple crossover trial. Twenty-one days of daily

Leslie Amass; Jonathan B Kamien; Susan K Mikulich

2000-01-01

62

Five Year Experience with Collaborative Care of Opioid Addicted Patients using Buprenorphine in Primary Care  

PubMed Central

Background Opioid addiction is a chronic disease treatable in primary care settings with buprenorphine, but this treatment remains underutilized. We describe a collaborative care model for managing opioid addiction with buprenorphine. Methods This is a cohort study of patients treated for opioid addiction utilizing collaborative care between nurse care managers and generalist physicians in an urban academic primary care practice over 5 years. We examine patient characteristics, 12-month treatment success (i.e., retention or taper after 6 months), and predictors of successful outcomes. Results From 2003 to 2008, 408 patients with opioid addiction were treated with buprenorphine. Twenty-six patients were excluded from analysis as they left treatment due to preexisting legal or medical conditions or a need for transfer to another buprenorphine program. At 12 months 51% of patients (196/382) underwent successful treatment. Of patients remaining in treatment at 3-, 6-, 9- and 12 months, 93% were no longer using illicit opioids or cocaine based on urine drug tests. On admission, patients who were older, employed, and used illicit buprenorphine had significantly higher odds of treatment success; those of African American or Hispanic race had significantly lower odds of treatment success. These outcomes were achieved with a model that facilitated physician involvement. Conclusions Collaborative care with nurse care managers in an urban primary care practice is an alternative and successful method of service delivery for the majority of patients with opioid addiction while effectively utilizing the time of physicians prescribing buprenorphine. PMID:21403039

Alford, Daniel P.; LaBelle, Colleen T.; Kretsch, Natalie; Bergeron, Alexis; Winter, Michael; Botticelli, Michael; Samet, Jeffrey H.

2010-01-01

63

Utilizing buprenorphine–naloxone to treat illicit and prescription-opioid dependence  

PubMed Central

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 ?-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

Mauger, Sofie; Fraser, Ronald; Gill, Kathryn

2014-01-01

64

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

PubMed

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

Hard, Bernadette

2014-01-01

65

Thienorphine is a potent long-acting partial opioid agonist: a comparative study with buprenorphine.  

PubMed

A strategy in the development of new treatment for opioid addiction is to find partial opioid agonists with properties of long duration of action and high oral bioavailability. In a search for such compounds, thienorphine, a novel analog of buprenorphine, was synthesized. Here, we reported that, like buprenorphine, thienorphine bound potently and nonselectively to mu-, delta-, and kappa-opioid receptors stably expressed in CHO (Chinese hamster ovary) cells and behaved as a partial agonist at mu-opioid receptor. However, some differences were observed between the pharmacological profiles of thienorphine and buprenorphine. In vitro, thienorphine was more potent than buprenorphine in inhibiting [3H]diprenorphine and stimulating guanosine 5'-O-(3-[35S]thio)triphosphate binding to rat mu-opioid receptor stably expressed in CHO cells. In vivo, thienorphine exhibited a less potent but more efficacious antinociceptive effect with an ED50 value of 0.25 mg/kg s.c. and more potent antimorphine effect with an ED50 value of 0.64 mg/kg intragastric, compared with buprenorphine. Additionally, the bioavailability of thienorphine was greatly higher than that of buprenorphine after oral administration. Moreover, compared with buprenorphine, thienorphine showed a similar long-lasting antinociceptive effect but a much longer antagonism of morphine-induced lethality (more than 15 days). These results indicate that thienorphine is a potent, long-acting partial opioid agonist with high oral bioavailability and may have possible application in treating addiction. PMID:16569757

Yu, Gang; Yue, Yong-Juan; Cui, Meng-Xun; Gong, Ze-Hui

2006-07-01

66

A randomized trial of buprenorphine maintenance for heroin dependence in a primary care clinic for substance users versus a methadone clinic  

Microsoft Academic Search

PURPOSE: Buprenorphine is an alternative to methadone for the maintenance treatment of heroine dependence and may be effective on a thrice weekly basis. Our objective was to evaluate the effect of thrice weekly buprenorphine maintenance for the treatment of heroin dependence in a primary care clinic on retention in treatment and illicit opioid use.SUBJECTS AND METHODS: Opioid-dependent patients were randomly

PatrickG O’Connor; AlisonH Oliveto; JuliaM Shi; ElisaG Triffleman; KathleenM Carroll; ThomasR Kosten; BruceJ Rounsaville; JulianaA Pakes; RichardS Schottenfeld

1998-01-01

67

[Necrosis of the glans penis: a complication of an injection of buprenorphin in a opioid abuser].  

PubMed

Necrosis of the penis glans is commonly described after circumcision or strangulation. We report the case of a patient, opioid abuser, who presented an isolated glans necrosis after an injection of buprenorphin. The buprenorphin (Subutex) is a sublingual partial mu-opioid agonist used for the treatment of heroin dependance. Its intravenous or subcutaneous abuse is associated with local infection. The patient require a surgical intervention. After the failure of a mucosal graft, a soft skin graft was done. PMID:19269730

Hornez, E; Laroche, J; Monchal, T; Bourgouin, S; Riviere, P; Fournier, R; Dantzer, E

2010-04-01

68

An Unusual Case of Death Probably Triggered by the Association of Buprenorphine at Therapeutic Dose with Ethanol and Benzodiazepines and with Very Low Norbuprenorphine Level.  

PubMed

Buprenorphine is largely prescribed for maintenance treatment in opioid dependence due to its safety profile. Nevertheless, fatalities at therapeutic dose have been described when associated with other central nervous system depressants, such as ethanol or benzodiazepines. Here, we report a case of death due to association of buprenorphine at therapeutic dose with benzodiazepines and ethanol. Although toxicity has been often attributed to its metabolite norbuprenorphine rather than to buprenorphine itself, in our case, norbuprenorphine was not detected in urine and bile and only in traces in blood. Moreover, the presence in blood of free buprenorphine but not of glucuronide metabolites argues for an unusual early death, at the beginning of buprenorphine metabolism. We propose that in the context of prior toxic impregnation, buprenorphine directly (and not via its metabolite norbuprenorphine) acted as a triggering factor by blocking the ventilatory response, rapidly leading to fatal respiratory depression. PMID:25348172

Bardy, Guillaume; Cathala, Philippe; Eiden, Céline; Baccino, Eric; Petit, Pierre; Mathieu, Olivier

2014-10-27

69

Differential activation of pregnane X receptor and constitutive androstane receptor by buprenorphine in primary human hepatocytes and HepG2 cells.  

PubMed

Buprenorphine is a partial ?-opioid receptor agonist used for the treatment of opioid dependence that has several advantages over methadone. The principal route of buprenorphine disposition has been well established; however, little is known regarding the potential for buprenorphine to influence the metabolism and clearance of other drugs by affecting the expression of drug-metabolizing enzymes (DMEs). Here, we investigate the effects of buprenorphine on the activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR), as well as the induction of DMEs, in both HepG2 cells and human primary hepatocytes (HPHs). In HepG2 cells, buprenorphine significantly increased human PXR-mediated CYP2B6 and CYP3A4 reporter activities. CYP2B6 reporter activity was also enhanced by buprenorphine in HepG2 cells cotransfected with a chemical-responsive human CAR variant. Real-time reverse transcription-polymerase chain reaction analysis revealed that buprenorphine strongly induced CYP3A4 expression in both PXR- and CAR-transfected HepG2 cells. However, treatment with the same concentrations of buprenorphine in HPHs resulted in literally no induction of CYP3A4 or CYP2B6 expression. Further studies indicated that buprenorphine could neither translocate human CAR to the nucleus nor activate CYP2B6/CYP3A4 reporter activities in transfected HPHs. Subsequent experiments to determine whether the differential response was due to buprenorphine's metabolic stability revealed a dramatically differential rate of elimination for buprenorphine between HPHs and HepG2 cells. Taken together, these studies indicate that metabolic stability of buprenorphine defines the differential induction of DMEs observed in HepG2 and HPHs, and the results obtained from PXR and CAR reporter assays in immortalized cell line require cautious interpretation. PMID:20829393

Li, Linhao; Hassan, Hazem E; Tolson, Antonia H; Ferguson, Stephen S; Eddington, Natalie D; Wang, Hongbing

2010-12-01

70

Pharmacokinetics of intravenous buprenorphine in children.  

PubMed Central

Buprenorphine (3 micrograms kg-1) was given intravenously as premedication to small children (age 4-7 years) undergoing minor surgery. Because of the rapid decline of the plasma buprenorphine concentrations, the terminal elimination half-life could not be estimated reliably. Given this constraint, values of clearance appeared to be higher than those in adults but values of Vss were similar. PMID:2775626

Olkkola, K T; Maunuksela, E L; Korpela, R

1989-01-01

71

Pregnancy under high-dose buprenorphine  

Microsoft Academic Search

ObjectiveThis study was first conducted to compare the consequences of the use of methadone and high-dose buprenorphine in pregnancy in France and secondly to describe the heterogeneity of women under high-dose buprenorphine. This paper focuses on the second point only.

Laurence Simmat-Durand; Claude Lejeune; Laurent Gourarier

2009-01-01

72

Buprenorphine and methadone for opioid addiction during pregnancy.  

PubMed

Buprenorphine and methadone are opioid-receptor agonists used as opioid substitution therapy during pregnancy to limit exposure of the fetus to cycles of opioid withdrawal and reduce the risk of infectious comorbidities of illicit opioid use. As part of a comprehensive care plan, such therapy may result in improved access to prenatal care, reduced illicit drug use, reduced exposure to infections associated with intravenous drug use, and improved maternal nutrition and infant birth weight. This article describes differences in patient selection between the two drugs, their relative safety during pregnancy, and changes in daily doses as a guide for prescribing clinicians. PMID:24845488

Mozurkewich, Ellen L; Rayburn, William F

2014-06-01

73

Correlations of maternal buprenorphine dose, buprenorphine, and metabolite concentrations in meconium with neonatal outcomes.  

PubMed

For the first time, relationships among maternal buprenorphine dose, meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted meconium concentrations or neonatal outcomes. Total buprenorphine meconium concentrations and buprenorphine/norbuprenorphine ratios were significantly related to neonatal abstinence syndrome (NAS) scores >4. As free buprenorphine concentration and percentage free buprenorphine increased, head circumference decreased. Thrice-weekly urine tests for opiates, cocaine, and benzodiazepines and self-reported smoking data from the mother were compared with data from analysis of the meconium to estimate in utero exposure. Time of last drug use and frequency of use during the third trimester were important factors associated with drug-positive meconium specimens. The results suggest that buprenorphine and metabolite concentrations in the meconium may predict the onset and frequency of NAS. PMID:18701886

Kacinko, S L; Jones, H E; Johnson, R E; Choo, R E; Huestis, M A

2008-11-01

74

A Double Blind, within Subject Comparison of Spontaneous Opioid Withdrawal from Buprenorphine versus Morphine  

PubMed Central

Preliminary evidence suggests that there is minimal withdrawal after the cessation of chronically administered buprenorphine and that opioid withdrawal symptoms are delayed compared with those of other opioids. The present study compared the time course and magnitude of buprenorphine withdrawal with a prototypical ?-opioid agonist, morphine. Healthy, out-of-treatment opioid-dependent residential volunteers (N = 7) were stabilized on either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses for 9 days. They then underwent an 18-day period of spontaneous withdrawal, during which four double-blind i.m. placebo injections were administered daily. Stabilization and spontaneous withdrawal were assessed for the second opioid using the same time course. Opioid withdrawal measures were collected eight times daily. Morphine withdrawal symptoms were significantly (P < 0.05) greater than those of buprenorphine withdrawal as measured by mean peak ratings of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), all subscales of the Profile of Mood States (POMS), sick and pain (0–100) Visual Analog Scales, systolic and diastolic blood pressure, heart rate, respiratory rate, and pupil dilation. Peak ratings on COWS and SOWS occurred on day 2 of morphine withdrawal and were significantly greater than on day 2 of buprenorphine withdrawal. Subjective reports of morphine withdrawal resolved on average by day 7. There was minimal evidence of buprenorphine withdrawal on any measure. In conclusion, spontaneous withdrawal from high-dose buprenorphine appears subjectively and objectively milder compared with that of morphine for at least 18 days after drug cessation. PMID:24227768

Smith, Michael T.; Mintzer, Miriam Z.; Campbell, Claudia M.; Strain, Eric C.

2014-01-01

75

Clinical efficacy of buprenorphine to minimize distress in MRL/lpr mice  

PubMed Central

MRL/MpJ-Faslpr (MRL/lpr) mice are an accepted animal model to study human systemic lupus erythematosus. We tested if a commonly used analgesic (buprenorphine hydrochloride) would reduce pain and distress in these mice without impacting the progression of autoimmune disease. Female MRL/lpr mice were randomly separated into four groups. Experimental groups received cyclophosphamide (25 mg/kg i.p. weekly), buprenorphine (0.09 mg/kg/mouse/day via drinking water), or cyclophosphamide + buprenorphine from 11 - 21 weeks of age. Controls received no treatments. Mice were monitored daily by a licensed veterinarian (blinded observer) and assigned a score weekly on parameters associated with pain and distress as well as progression of disease. Proteinuria was measured weekly, and serum anti-dsDNA antibody levels were determined at 11, 15, and 18 weeks of age. At 21 weeks of age, the animals were euthanized and the kidneys and spleens were removed for evaluation. Regardless of the parameter observed, buprenorphine did not significantly decrease distress when compared to the controls. Buprenorphine did not alter the progression of autoimmune disease, based on characteristics of splenic architecture and splenocyte cell profiles, development of lymphadenopathy, or kidney histology as compared to controls. This study indicates that buprenorphine at this dose and route of administration was ineffective in reducing distress associated with disease progression in the MRL/lpr strain. More studies are needed to determine if, at a different dose or route, buprenorphine would be useful as adjunctive therapy in reducing distress in MRL/lpr mice. PMID:17490635

Swenson, Julie; Olgun, Selen; Radjavi, Ali; Kaur, Taranjit; Reilly, Christopher M.

2007-01-01

76

Randomized controlled study transitioning opioid-dependent pregnant women from short-acting morphine to buprenorphine or methadone  

Microsoft Academic Search

This study compared the safety and withdrawal discomfort associated with transitioning pregnant opioid-dependent women from short-acting morphine onto buprenorphine or methadone under well-controlled double-blind conditions. Participants (n=18) were patients in a comprehensive treatment setting and were part of a larger randomized controlled trial comparing the neonatal abstinence syndrome in mothers treated with individualized doses of sublingual buprenorphine or oral methadone.

Hendree E. Jones; Rolley E. Johnson; Donald R. Jasinski; Lorraine Milio

2005-01-01

77

Management of opioid addiction with buprenorphine: French history and current management  

PubMed Central

The way in which opioid addiction is managed in France is unique, as it is based on the prescription of buprenorphine by general practitioners and is dispensed by retail pharmacies. This policy has had a direct, positive impact on the number of deaths caused by heroin overdose, which was reduced by four-fifths between 1994 and 2002. In addition, certain associated comorbidities, such as infection with the human immunodeficiency virus, have also been reduced; the incidence of acquired immune deficiency syndrome in intravenous drug users fell from 25% in the mid-1990s to 6% in 2010. Since the implementation of this French model of opioid management, major scientific progress has been made, leading to a better understanding of the pathophysiologic mechanisms of addiction and of the management modalities required for its treatment. However, despite notable advances in scientific knowledge and in the implementation of devices, opioid addiction remains a major public health care issue in France, with 275,000–360,000 “problem drug users” being reported in 2011. The situation is still particularly worrying due to psychoactive substance use and misuse of opioid substitution treatments. Since 2003, there has been a persistent increase in the number of deaths and comorbidities related to opioid addiction, principally hepatitis C virus infection, which affects up to 40% of intravenous drug users. In France, the direct involvement of general practitioners in the management of opioid addiction is indisputable. Nevertheless, management could be optimized through better understanding of the pathophysiologic mechanisms of the disease, better knowledge of the pharmacology of opioid substitution treatments, and clear definition of short-, medium- and long-term treatment objectives. Data related to the management of opioid addiction by general practitioners in France have been published in 2005. Since then, the context has changed, other drugs were launched on the market such as generics of buprenorphine, methadone capsule, and Suboxone. Thus, an update seems necessary. This paper provides a description of opioid addiction management objectives and treatment modalities for general practitioners, based on currently available knowledge. PMID:24623988

Poloméni, Pierre; Schwan, Raymund

2014-01-01

78

Antihyperalgesic effect of buprenorphine involves nociceptin/orphanin FQ peptide-receptor activation in rats with spinal nerve injury-induced neuropathy.  

PubMed

We evaluated the effect of buprenorphine, a mixed agonist for ?-opioid receptors and nociceptin/orphanin FQ peptide (NOP) receptors, in neuropathic rats, using the paw pressure test. Buprenorphine, administered i.p. at 50, but not 20, ?g/kg, exhibited naloxone-reversible analgesic activity in naïve rats. In contrast, buprenorphine at 0.5 - 20 ?g/kg produced a naloxonesensitive antihyperalgesic effect in the L5 spinal nerve-injured neuropathic rats. Intrathecal injection of [N-Phe(1)]nociceptin(1-13)NH2, a NOP-receptor antagonist, reversed the effect of buprenorphine in neuropathic rats, but not in naïve rats. Together, buprenorphine suppresses neuropathic hyperalgesia by activating NOP and opioid receptors, suggesting its therapeutic usefulness in treatment of neuropathic pain. PMID:23603932

Takahashi, Tomoko; Okubo, Kazumasa; Kojima, Shota; Nishikawa, Hiroyuki; Takemura, Motohide; Tsubota-Matsunami, Maho; Sekiguchi, Fumiko; Kawabata, Atsufumi

2013-01-01

79

The effect of an electronic medicine dispenser on diversion of buprenorphine-naloxone-experience from a medium-sized Finnish city.  

PubMed

Providing unobserved opioid substitution treatment (OST) safely is a major challenge. This study examined whether electronic medicine dispensers (EMDs) can reduce diversion of take-home buprenorphine-naloxone (BNX) in a medium-sized Finnish city. All BNX treated OST patients in Kuopio received their take-home BNX in EMDs for 4months. EMDs' effect on diversion was investigated using questionnaires completed by patients (n=37) and treatment staff (n=19), by survey at the local needle exchange service and by systematic review of drug screen data from the Kuopio University Hospital. The majority of patients (n=21, 68%) and treatment staff (n=11, 58%) preferred to use EMDs for the safe storage of tablets. Five patients (16%) declared that EMDs had prevented them from diverting BNX. However, EMDs had no detectable effect on the availability or origin of illegal BNX or on the hospital-treated buprenorphine-related health problems. EMDs may improve the safety of storage of take-home BNX, but their ability to prevent diversion needs further research. PMID:23433750

Uosukainen, Hanna; Pentikäinen, Hannu; Tacke, Ulrich

2013-07-01

80

Respiratory Rates and Arterial Blood-Gas Tensions in Healthy Rabbits Given Buprenorphine, Butorphanol, Midazolam, or Their Combinations  

PubMed Central

The objective of this study was to evaluate the respiratory effects of buprenorphine, butorphanol, midazolam, and their combinations in healthy conscious rabbits. Six adult female New Zealand white rabbits were anesthetized briefly with isoflurane by mask to allow placement of a catheter into the central ear artery. After a 60-min recovery period, a baseline arterial sample was obtained. Animals then were injected intramuscularly with either 0.9% NaCl (1 mL), buprenorphine (0.03 mg/kg), butorphanol (0.3 mg/kg), midazolam (2 mg/kg), buprenorphine + midazolam (0.03 mg/kg, 2 mg/kg), or butorphanol + midazolam (0.3 mg/kg, 2 mg/kg). Arterial blood gases were evaluated at 30, 60, 90, 120, 180, 240, and 360 min after drug administration. All drug treatments caused significant decreases in respiratory rate, compared with saline. Buprenorphine and the combinations of midazolam–butorphanol and midazolam–buprenorphine resulted in statistically significant decreases in pO2. No significant changes in pCO2 pressure were recorded for any treatment. Increases in blood pH were associated with administration of butorphanol, midazolam, and the combinations of midazolam–butorphanol and midazolam–buprenorphine. In light of these results, buprenorphine and the combinations of midazolam–buprenorphine and midazolam–butorphanol result in statistically significant hypoxemia in rabbits that breathe room air. The degree of hypoxemia is of questionable clinical importance in these healthy subjects. Hypoxemia resulting from these drug combinations may be amplified in rabbits with underlying pulmonary or systemic disease. PMID:21439214

Schroeder, Carrie A; Smith, Lesley J

2011-01-01

81

Tramadol versus buprenorphine for the management of acute heroin withdrawal: a retrospective matched cohort controlled study.  

PubMed

Many medications have been used over the past thirty years for the treatment of opioid withdrawal, including propoxyphene, methadone, clonidine, parenteral buprenorphine, and, more recently, sublingual buprenorphine. Each has been found to have clinical strengths and limitations. Tramadol is a centrally acting synthetic analgesic with opiate activity primarily due to the binding of a metabolite to the micro receptor. Despite this micro receptor activity, tramadol appears to have low abuse potential and is a non-scheduled analgesic. The pharmacologic profile of tramadol makes it a candidate for opiate withdrawal treatment. A chart review was undertaken to retrospectively compare treatment outcomes of heroin-dependent patients when detoxified with parenteral buprenorphine (1996-1997) versus tramadol (1999-2000). Inclusion criteria for this study were heroin as drug of choice, current opioid physical dependence (ie, withdrawal symptoms), no current abuse of oral opioid analgesics, and no alcohol or benzodiazepine withdrawal symptoms. Patient cases that met inclusion criteria were group-matched between buprenorphine and tramadol on the basis of age, sex, and amount of heroin used (bags/day). Charts were audited for patient demographics, daily heroin use at admission, withdrawal symptoms, and discharge status. In total, 129 patient charts were reviewed, and 115 met all inclusion criteria and were group-matched (45 patients in the buprenorphine group, seventy in the tramadol group). There were no differences in demographics between the two groups of patients. Fifty-six percent of the buprenorphine group and 71% of the tramadol group completed detoxification; tramadol-treated patients had significantly higher average withdrawal symptoms when compared to the buprenorphine group and a greater reduction in withdrawal symptoms over time. Finally, the number of side effects was small and did not differ between the groups. The results of this study are consistent with previous pilot reports that indicated few clinical differences between parenteral buprenorphine and oral tramadol protocols when used in the management of acute heroin withdrawal. As a consequence, tramadol shows some promise as an opioid withdrawal management medication. PMID:16595358

Threlkeld, Melinda; Parran, Theodore V; Adelman, Christopher A; Grey, Scott F; Yu, Jaehak

2006-01-01

82

Flunitrazepam variably alters morphine, buprenorphine, and methadone lethality in the rat  

Microsoft Academic Search

Opiates and substitution products are frequently abused, alone and in association with benzodiazepines. While this combination may result in severe respiratory depression and death, the quantitative relationship remains uncertain. We performed randomized, blinded intravenous median lethal dose (MLD) studies in Sprague–Dawley rats of morphine, buprenorphine, and methadone, alone and in combination with intraperitoneal flunitrazepam pretreatment. We employed the up-and-down method,

S W Borron; C Monier; P Risède; F J Baud

2002-01-01

83

The reinforcing and subjective effects of intravenous and intranasal buprenorphine in heroin users.  

PubMed

Abuse of buprenorphine (BUP) by the intravenous (IV) route has been documented in several studies, and reports of intranasal (IN) abuse are increasing. However, no studies have directly compared the effects of BUP when it is administered intranasally and intravenously. The present secondary analysis used data from two separate studies to compare the reinforcing and subjective effects of IV and IN buprenorphine. One study evaluated IV buprenorphine (N=13) and the other evaluated IN buprenorphine (N=12). Participants were maintained on 2 mg sublingual (SL) BUP and tested with each intranasal or intravenous buprenorphine test dose (0 mg, 2 mg, 4 mg, 8 mg, and 16 mg). During morning laboratory sessions, participants received money (US $20) and sample doses of IN or IV BUP, and then completed subjective effects questionnaires. Later that day, they completed a self-administration task to receive 10% portions of the drug and/or money they previously sampled. In general, positive subjective ratings for both IV and IN BUP were significantly greater than placebo, with IV BUP having a greater effect than IN BUP. All active BUP doses (IV and IN) maintained significantly higher progressive ratio breakpoint values than placebo, but breakpoint values for IV BUP were greater than for IN BUP. Buprenorphine is an effective maintenance treatment for opioid dependence, valued for its ability to reduce the positive subjective effects of other opioids. Nevertheless, the present data demonstrate that in participants maintained on a low dose of SL BUP, the medication itself has abuse liability when used intravenously or intranasally. PMID:24793093

Jones, Jermaine D; Madera, Gabriela; Comer, Sandra D

2014-07-01

84

A review of buprenorphine diversion and misuse: the current evidence base and experiences from around the world.  

PubMed

Outpatient opioid addiction treatment with sublingual buprenorphine pharmacotherapy has rapidly expanded in the United States and abroad, and, with this increase in medication availability, there have been increasing concerns about its diversion, misuse, and related harms. This narrative review defines the behaviors of diversion and misuse, examines how the pharmacology of buprenorphine alone and in combination with naloxone influence its abuse liability, and describes the epidemiological data on buprenorphine diversion and intravenous misuse, risk factors for its intravenous misuse, and the unintended consequences of misuse and diversion. Physician practices to prevent, screen for, and therapeutically respond to these behaviors, which are a form of medication nonadherence, are discussed, and gaps in knowledge are identified. Outpatient opioid addiction treatment with sublingual buprenorphine pharmacotherapy experiences from other countries that have varied health care systems, public policies, and access to addiction treatment are shared to make clear that diversion and misuse occur across the world in various contexts, for many different reasons, and are not limited to buprenorphine. Comparisons are made with other opioids with known abuse liability and medications with no known abuse. The objective was to facilitate understanding of diversion and misuse so that all factors influencing their expression (patient and provider characteristics and public policy) can be appreciated within a framework that also recognizes the benefits of addiction treatment. With this comprehensive perspective, further careful work can help determine how to minimize these behaviors without eroding the current benefits realized through improved addiction treatment access and expansion. PMID:25221984

Lofwall, Michelle R; Walsh, Sharon L

2014-01-01

85

Postcastration analgesia in ponies using buprenorphine hydrochloride.  

PubMed

Buprenorphine has recently obtained UK Marketing Authorisation for horses. The analgesic effects are long lasting, and have considerable potential for postoperative pain relief. This observer blinded, randomised study aimed to evaluate postsurgical analgesia in ponies premedicated with buprenorphine prior to castration under intravenous anaesthesia. Ponies received either 0.01 mg/kg bodyweight (BW) buprenorphine (group B) or an equivalent volume of 5 per cent glucose (group C) given intravenously before induction of anaesthesia. Pain was assessed and recorded using dynamic interactive visual analogue scores (DIVAS 0-100) and a Simple Descriptive Scale (SDS 0-3) (high scores=most pain) before and 1, 3, 6, 9, 12 and 24 hours after anaesthesia. Rescue analgesia was given if DIVAS>40 mm. Data were analysed using the Mann-Whitney U test at P<0.05. Median (range) areas under the curve for DIVAS were 63 (0-383) mm hour in group B and 209 (0-391) mm hour in group C (P=0.0348). The SDS was lower in group B than in group C (P=0.038). Three group B and five group C animals required rescue analgesia. Buprenorphine did not produce any serious adverse effects. Buprenorphine at 0.01 mg/kg BW intravenously administered before anaesthesia provided near-comprehensive postoperative analgesia after surgical castration in ponies. PMID:23736517

Love, E J; Taylor, P M; Whay, H R; Murrell, J

2013-06-15

86

Efficacy of daily and alternate-day dosing regimens with the combination buprenorphine-naloxone tablet.  

PubMed

This study evaluated the efficacy of a combination tablet formulation of buprenorphine containing 8 mg of buprenorphine and 2 mg of naloxone for every other day treatment and whether increasing the daily maintenance dose was essential for maintaining an efficacious alternate-day treatment. Twenty-six opioid-dependent outpatients completing a 16-day baseline entered a double-blind, placebo-controlled, triple crossover trial. Twenty-one days of daily combination tablet administration were compared to two different 21-day periods of alternate-day buprenorphine administration where subjects received either 8 or 16 mg of the combination tablet every other day with placebo on the interposed day. Fifty-four percent (14/26) of subjects completed the study, but only two subjects dropped out during the 16-mg alternate-day condition. Rates of medication compliance, illicit opioid use and subject- and observer-rated measures of opioid effects did not distinguish daily from alternate-day treatments in subjects completing the study. However, pupillary diameter was significantly increased during 8-mg alternate-day compared to the 8-mg daily or 16-mg alternate-day treatment. These data replicate earlier findings describing the acceptability of alternate-day buprenorphine treatment using multiples of the daily maintenance dose and extend these findings by establishing the clinical efficacy of daily and alternate-day dosing regimens with the combination buprenorphine naloxone tablet. This study also suggests slightly improved outcomes during alternate-day treatment using multiples of the daily dose. PMID:10669065

Amass, L; Kamien, J B; Mikulich, S K

2000-02-01

87

Effects of Buprenorphine and Hepatitis C on Liver Enzymes in Adolescents and Young Adults  

PubMed Central

Objective The purpose of this study was to explore changes in transaminase values associated with buprenorphine treatment and hepatitis C status among opioid dependent subjects aged 15–21. Methods 152 subjects seeking treatment for opioid dependence were randomized to 2-week detoxification with buprenorphine/naloxone (DETOX) or 12 weeks buprenorphine/naloxone (BUP). Liver chemistries including transaminases were obtained baseline and at 4, 8, and 12 weeks. 111 patients had at least one set of transaminases during treatment and were included in analyses of treatment effects. Results Overall, 8/60 BUP participants vs. 12/51 DETOX participants had at least one elevated ALT value during follow-up (Chi-square n.s.). 5/60 BUP participants vs. 11/51 DETOX participants had at least one elevated AST value (Chi-square = 3.194, p = .048). Twenty-eight out of 152 participants were hepatitis C (HCV) positive at baseline, and 4 seroconverted within 12 weeks, 2 in each group. HCV status was significantly associated with transaminase abnormalities (p = .009 and p = .006 for ALT an AST, respectively). HCV status had a strong effect on transaminase abnormalities among participants assigned to DETOX, but not among those assigned to BUP. Conclusions No evidence was found for hepatotoxicity of buprenorphine in this exploratory analysis. HCV was present in a significant minority of participants and was a significant predictor of transaminase elevation. Results suggest that stabilization on buprenorphine may decrease the frequency of transaminase abnormalities associated with HCV in opioid dependent young people. The high rate of seroconversion underscores the importance of effective treatment and prevention. PMID:21170166

Bogenschutz, Michael P.; Abbott, Patrick J.; Kushner, Robert; Tonigan, J. Scott; Woody, George E.

2010-01-01

88

[Opioid addiction: P300 assessment in treatment by methadone substitution].  

PubMed

The aim of this study was to assess cognitive functions in two clinical conditions, namely during heroin detoxification and during substitution treatment by methadone. Two groups of chronic heroin user inpatients, meeting DSM-III-R criteria for concurrent opiate dependence, were tested using an auditory oddball paradigm of P300. The first group (four women and six men) were drug-free and the second (five women, ten men) received methadone treatment. Patients were also compared to a control group of non-dependent healthy subjects (five women, nine men). The patients were recorded 6-10 days after the beginning of either detoxification or methadone treatment. There were significant P300 alterations in the two patient groups, with amplitude decrease and latency increase, at a time when self-reported signs of withdrawal were absent or minimal. Paradoxically, the reaction time was accelerated in the two groups of patients, who also showed increased discrimination errors. These abnormalities were found with a lesser degree in the methadone-treated group than in detoxification patients. PMID:11488228

Attou, A; Figiel, C; Timsit-Berthier, M

2001-06-01

89

Does buprenorphine maintenance improve the quality of life of opioid users?  

PubMed Central

Background & objectives: The quality of life (QOL) of substance abusers is known to be severely impaired. Information on impact of opioid maintenance treatment on the QOL of opioid dependent subjects though available from the developed countries, is lacking from India. This study was carried out to assess the impact of buprenorphine maintenance treatment on the quality of life (QOL) of opioid dependent subjects at nine months follow up. Methods: Based on specified inclusion criteria a total of 231 subjects were recruited from five participating centres across India. They received sublingual buprenorphine as a directly observed therapy along with brief psychosocial intervention (provided in groups of 8-10 subjects) after intake in to the study. The WHOQOL-BREF scale domain scores obtained at baseline were compared to domain scores at nine months follow up. Results: At nine months follow up, among the 64.1 per cent retained in buprenorphine maintenance, there was a significant (P<0.001) decline in opioid use from 24.9 ± 10.1 days at baseline to 1.7 ± 4.7 days at nine months follow up and improvements in score of the four WHOQOL-BREF domains (Physical, Psychological, Social relationships and Environment). Interpretation & conclusions: The results showed the beneficial effects of buprenorphine maintenance treatment in improving the QOL of opioid-dependent subjects at nine month follow up. These results point towards the need for an expanded nation-wide provision of buprenorphine maintenance treatment as a harm reduction strategy for the opioid dependent population. PMID:23481062

Dhawan, A.; Chopra, A.

2013-01-01

90

Benzodiazepines increase the reward effects of buprenorphine in a conditioned place preference test in the mouse.  

PubMed

Buprenorphine (BPN) is widely used as a substitution treatment for opioid addiction. Some cases of abuse and misuse, especially associated with various benzodiazepines (BZDs), have been described, and a previous study has shown that BZDs increase the sedative effect of BPN and decrease its anxiogenic properties. To investigate the reward effect that may lead to the abusive combination of BPN and BZD, we studied the influence of different doses of three BZDs extensively used with BPN by drug addicts on conditioned place preference behavior in mice. BPN (0.3, 1, 3 mg/kg) was injected subcutaneously into male mice alone or in combination with a BZD administered intraperitoneally: dipotassium clorazepate (CRZ; 1, 4, 16 mg/kg), diazepam (DAZ; 0.5, 1, 5 mg/kg), or bromazepam (BMZ; 0.5, 1, 3 mg/kg). Amphetamine (8 mg/kg) was used as a reference drug. Reward effects of BPN alone or in combination were measured in a conditioned place preference paradigm using an unbiased procedure. Our results showed that groups treated with BPN associated with different doses of diazepam and clorazepate, but not bromazepam, spent significantly more time in the drug-paired compartment compared to the group treated with BPN alone. Our study shows that joint consumption of diazepam and clorazepate, but not bromazepam, can increase the reward properties of BPN alone in mice. These results could help to explain the use of this type of drug combination in the drug addict population. PMID:24617653

Ma, Lin-Lin; Freret, Thomas; Lange, Mathilde; Bourgine, Joanna; Coquerel, Antoine; Lelong-Boulouard, Véronique

2014-12-01

91

Modulation of the discriminative-stimulus effects of cocaine by buprenorphine.  

PubMed

Modulation of the discriminative-stimulus effects of cocaine by the mixed-action opioid buprenorsphine was studied in squirrel monkeys trained to discriminate cocaine from saline, using a two-lever drug discrimination procedure. Lever pressing was maintained under a fixed-ratio 10 schedule of food presentation. During test sessions, monkeys received cumulative doses of cocaine after presession treatment with either saline or buprenorphine (0.001-0.01mg/kg). After pretreatment with saline, cocaine engendered dose-related increases in the percentage of cocaine-appropriate responses, reaching a maximum of 99-100 percent at doses of 0.3 or 1.0mg/kg. Pretreatment with buprenorphine shifted the cocaine dose-response function to the left, resulting in 98-100 percent cocaine-appropriate responding at doses of cocaine that previously engendered only saline-appropriate responding. When tested alone, buprenorphine did not occasion cocaine-appropriate responding at any dose. The results show that although buprenorphine does not itself have cocaine-like discriminative-stimulus effects, it can potentiate the discriminative-stimulus effects of cocaine. PMID:11224094

Kamien, J.B.; Spealman, R.D.

1991-12-01

92

Effects of Multimodal Analgesia with Low-Dose Buprenorphine and Meloxicam on Fecal Glucocorticoid Metabolites after Surgery in New Zealand White Rabbits (Oryctolagus cuniculus)  

PubMed Central

Despite the increasing use of rabbits as companion animals and models for biomedical research, rabbits have not been extensively studied to identify an efficacious postsurgical analgesic that does not cause systemic complications. The synergy of NSAID and systemic opioids is well-documented, and their combined use reduces the amount of either drug required for adequate analgesia. We measured fecal corticosterone metabolites (FCM) in rabbits after a minimally invasive vascular cut-down procedure. Rabbits received buprenorphine (0.03 mg/kg SC every 12 h for 3 d), meloxicam (0.2 mg/kg SC every 24 h for 3 d), buprenorphine–meloxicam (0.01 mg/kg–0.1 mg/kg SC every 24 h for 3 d), or a single dose of 0.5% bupivacaine (0.5 mL) infused locally at the incision site. By day 3 after surgery, buprenorphine, meloxicam, and bupivacaine groups showed elevated FCM levels, which continued to rise until day 7 and then gradually returned to baseline by day 28. In the buprenorphine–meloxicam group, FCM was relatively unchanged until day 3, when treatment was discontinued, and then began to rise. Rabbits in the buprenorphine–meloxicam group gained more weight over the 28-d study than did those in the other 3 treatment groups. This study shows that in rabbits low-dose buprenorphine administered with meloxicam effectively mitigates the FCM response that develops after surgery without the adverse effects associated with higher doses. PMID:24041213

Goldschlager, Gregg B; Gillespie, Virginia L; Palme, Rupert; Baxter, Mark G

2013-01-01

93

Effects of buprenorphine and an alternative nondrug reinforcer, alone and in combination on smoked cocaine self-administration in monkeys.  

PubMed

The abuse of smoked cocaine base, also known as 'crack', continues to be a major public health problem and to date the success of pharmacological or behavioral interventions has been limited. The purpose of this study was to evaluate the efficacy of a behavioral (alternative reinforcer-saccharin) and pharmacological (0.01 mg/kg buprenorphine) treatment alone and in combination. Five adult male rhesus monkeys self-administered cocaine base (1.0 mg/kg/delivery) via the smoking/inhalation route. Each day ten smoke deliveries were available contingent upon completion of a chained FR (lever press), FR (inhalation response) response schedule during 4 hr sessions. The data were analyzed using a behavioral economic framework in which the lever press response requirements were varied from 64 to 1024 to generate a demand function (consumption x FR) for cocaine under the following conditions: (1) buprenorphine pretreatment alone (0.01 mg/kg, i.m., 30 min presession); (2) concurrent access to saccharin alone (0.03% wt/vol); and (3) buprenorphine pretreatment in the presence of concurrent access to saccharin. Under all conditions, increases in the lever FR resulted in significant decreases in smoked cocaine base deliveries. Neither buprenorphine pretreatment alone nor concurrent saccharin alone produced significant decreases in smoked cocaine deliveries; however, the combination of buprenorphine pretreatment and concurrent saccharin significantly decreased the mean number of smoked cocaine deliveries from the no treatment baseline and from the buprenorphine alone condition. These data suggest that the combination of pharmacotherapy and alternative reinforcers may be an effective treatment strategy to alter smoked cocaine self-administration. PMID:9179503

Rodefer, J S; Mattox, A J; Thompson, S S; Carroll, M E

1997-04-14

94

The pharmacodynamic and pharmacokinetic profile of intranasal crushed buprenorphine and buprenorphine/naloxone tablets in opioid abusers  

PubMed Central

Aims Sublingual buprenorphine and buprenorphine/naloxone are efficacious opioid dependence pharmacotherapies, but there are reports of their diversion and misuse by the intranasal route. The study objectives were to characterize and compare their intranasal pharmacodynamic and pharmacokinetic profiles. Design A randomized, double-blind, placebo-controlled, crossover study. Setting An in-patient research unit at the University of Kentucky. Participants Healthy adults (n=10) abusing, but not physically dependent on, intranasal opioids. Measurements Six sessions (72 hours apart) tested five intranasal doses [0/0, crushed buprenorphine (2, 8 mg), crushed buprenorphine/naloxone (2/0.5, 8/2 mg)] and one intravenous dose (0.8 mg buprenorphine/0.2 mg naloxone for bioavailability assessment). Plasma samples, physiological, subject- and observer-rated measures were collected before and for up to 72 hours after drug administration. Findings Both formulations produced time- and dose-dependent increases on subjective and physiological mu-opioid agonist effects (e.g. ‘liking’, miosis). Subjects reported higher subjective ratings and street values for 8 mg compared to 8/2 mg, but these differences were not statistically significant. No significant formulation differences in peak plasma buprenorphine concentration or time-course were observed. Buprenorphine bioavailability was 38–44% and Tmax was 35–40 minutes after all intranasal doses. Naloxone bioavailability was 24% and 30% following 2/0.5 and 8/2 mg, respectively. Conclusions It is difficult to determine if observed differences in abuse potential between intranasal buprenorphine and buprenorphine/naloxone are clinically relevant at the doses tested. Greater bioavailability and faster onset of pharmacodynamic effects compared to sublingual administration suggests a motivation for intranasal misuse in non-dependent opioid abusers. However, significant naloxone absorption from intranasal buprenorphine/naloxone administration may deter the likelihood of intranasal misuse of buprenorphine/naloxone, but not buprenorphine, in opioid-dependent individuals. PMID:21395892

Middleton, L.S.; Nuzzo, P.A.; Lofwall, M.R.; Moody, D.E.; Walsh, S.L.

2011-01-01

95

The impact of recent cocaine use on plasma levels of methadone and buprenorphine in patients with and without HIV-infection.  

PubMed

Cocaine decreases methadone and buprenorphine plasma concentrations. HIV infection and/or antiretroviral medication use may impact these relationships. We sought to determine the association between recent cocaine use and methadone and buprenorphine concentrations in HIV-infected and uninfected subjects in clinical care. R- and S-methadone or buprenorphine and norbuprenorphine concentrations were assessed at 0.5, 1, 2, and 24hours after dosing in subjects with confirmed cocaine use and abstinence. We compared methadone and buprenorphine concentrations for cocaine use vs. abstinence, by HIV status in 16 subjects receiving methadone (6 HIV-infected) and 17 receiving buprenorphine (8 HIV-infected). With recent cocaine use, peak R-methadone (244 vs. 297ng/mL, p=0.03) and peak S-methadone (285 vs. 339ng/mL); p=0.03 concentrations were lower in HIV-uninfected subjects only. Peak buprenorphine and norbuprenorphine concentrations were unchanged regardless of cocaine use or HIV status. Cocaine may decrease methadone concentrations in HIV-uninfected subjects. HIV infection or its treatment may attenuate cocaine's effect on methadone. PMID:25480096

Tetrault, Jeanette M; McCance-Katz, Elinore F; Moody, David E; Fiellin, David A; Lruie, Bonnie S; DInh, An T; Fiellin, Lynn E

2014-11-01

96

The use of skin substitutes in the treatment of the hand and upper extremity.  

PubMed

The introduction of skin substitutes in the last decade has dramatically changed how we think about the concept of "non-healing" wounds. Their use has improved prognosis and reduced morbidity in the treatment of open wounds. This article aims to summarize the development of tissue-engineered skin substitutes, discuss their use, and highlight some specific applications in different clinical settings. PMID:24839416

Capo, John T; Kokko, Kyle P; Rizzo, Marco; Adams, Julie E; Shamian, Ben; Abernathie, Brenon; Melamed, Eitan

2014-06-01

97

Comparison of Buprenorphine and Butorphanol Analgesia in the Eastern Red-Spotted Newt (Notophthalmus viridescens)  

PubMed Central

The experimental use of amphibian models in biomedical research increases yearly, but there is a paucity of reports concerning analgesic use in many of these species. In this study, buprenorphine given by intracoelomic injection and butorphanol added to the tank water were compared for analgesic effect in the eastern red-spotted newt after bilateral forelimb amputations. Newts undergoing anesthesia but not surgery and newts having surgery but not given analgesia postoperatively were used as control groups. Animals were tested for food consumption, spontaneous movement, response to tapping on the tank, response to being touched, and body posture. Both buprenorphine by intracoelomic injection and butorphanol in tank water significantly promoted resumption of normal behavior after bilateral surgical amputation of the forelimbs. The difference between analgesic treatment and no analgesic treatment was maintained until 72 h after surgery. PMID:19383214

2009-01-01

98

Clinical pharmacology of buprenorphine: Ceiling effects at high doses  

Microsoft Academic Search

Objective: The purpose of this study was to characterize the acute effects of buprenorphine, an opioid partial (?-agonist, across a wide range of doses in comparison to methadone.Method: Healthy adult male volunteers, who had experience with but were not physically dependent on opioids, participated while residing on a closed research unit. Four subjects received buprenorphine (0, 1, 2, 4, 8,

Sharon L Walsh; Kenzie L Preston; Maxine L Stitzer; Edward J Cone; George E Bigelow

1994-01-01

99

Treatment of enchondromas of the hand with bone substitute  

Microsoft Academic Search

We report five patients with enchondromas of long bones in the hand. They were successfully treated by curettage and implantation of a biodegradable bone substitute (calcium phosphate). Bone regained normal X-ray appearance by 9 months. The full range of motion and normal function of the hand were restored. There were no complications and no recurrence at follow-up visits 28 months

P. Jacoulet; P. Faure

1997-01-01

100

Effects of buprenorphine and meloxicam analgesia on induced cerebral ischemia in C57BL/6 male mice.  

PubMed

Laboratory mice constitute an extensively used model to study the pathologic and functional outcomes of cerebral ischemic stroke. The middle cerebral artery occlusion (MCAO) model requires surgical intervention, which potentially can result in postsurgical pain and stress. In the present study, we investigated whether buprenorphine and meloxicam, at clinically relevant doses provided pain relief without altering infarct volume in male C57BL/6 mice. Common known side-effects of buprenorphine, including decreased food consumption, were noted after surgery in buprenorphine-treated mice, but these effects were brief and seen only during the treatment period. Fecal corticosterone metabolites did not differ significantly between the groups. In the present study, buprenorphine treatment did not alter infarction volume when compared with that of mice that did not receive analgesia. In contrast, meloxicam treatment significantly reduced infarct volume and may be a confounder if used as an analgesic during MCAO surgery. Furthermore, investigation of behavioral profiles by using an automated behavioral scoring system showed that rearing and sniffing behaviors decreased as infarct volume increased. This suggests that studies of exploratory behavior may aid in developing new markers of short-term stroke-related behavioral deficiencies in laboratory mice. PMID:23582417

Jacobsen, Kirsten R; Fauerby, Natasha; Raida, Zindy; Kalliokoski, Otto; Hau, Jann; Johansen, Flemming F; Abelson, Klas Sp

2013-04-01

101

Twelve reasons for considering buprenorphine as a frontline analgesic in the management of pain.  

PubMed

Buprenorphine is an opioid that has a complex and unique pharmacology which provides some advantages over other potent mu agonists. We review 12 reasons for considering buprenorphine as a frontline analgesic for moderate to severe pain: (1) Buprenorphine is effective in cancer pain; (2) buprenorphine is effective in treating neuropathic pain; (3) buprenorphine treats a broader array of pain phenotypes than do certain potent mu agonists, is associated with less analgesic tolerance, and can be combined with other mu agonists; (4) buprenorphine produces less constipation than do certain other potent mu agonists, and does not adversely affect the sphincter of Oddi; (5) buprenorphine has a ceiling effect on respiratory depression but not analgesia; (6) buprenorphine causes less cognitive impairment than do certain other opioids; (7) buprenorphine is not immunosuppressive like morphine and fentanyl; (8) buprenorphine does not adversely affect the hypothalamic-pituitary-adrenal axis or cause hypogonadism; (9) buprenorphine does not significantly prolong the QTc interval, and is associated with less sudden death than is methadone; (10) buprenorphine is a safe and effective analgesic for the elderly; (11) buprenorphine is one of the safest opioids to use in patients in renal failure and those on dialysis; and (12) withdrawal symptoms are milder and drug dependence is less with buprenorphine. In light of evidence for efficacy, safety, versatility, and cost, buprenorphine should be considered as a first-line analgesic. PMID:22809652

Davis, Mellar P

2012-01-01

102

Indicators of Buprenorphine and Methadone Use and Abuse: What Do We Know?  

PubMed Central

Abuse of prescription opioids is a growing problem. The number of methadone pain pills distributed now exceeds liquid methadone used in opioid treatment, and the increases in buprenorphine indicators provide evidence of the need to monitor and intervene to decrease the abuse of this drug. The need for additional and improved data to track trends is discussed, along with findings as to the characteristics of the users and combinations of drugs. Data on toxicities related to methadone or buprenorphine, particularly in combination with other prescribed drugs, are presented and clinical implications and considerations are offered. These findings underscore the need for physicians to be aware of potential toxicities and to educate their patients regarding these issues. PMID:20132124

Maxwell, Jane Carlisle; McCance-Katz, Elinore F.

2013-01-01

103

Psychiatric comorbidity, red flag behaviors, and associated outcomes among office-based buprenorphine patients following Hurricane Sandy.  

PubMed

In October 2012, Bellevue Hospital Center (Bellevue) in New York City was temporarily closed as a result of Hurricane Sandy, the largest hurricane in US history. Bellevue's primary care office-based buprenorphine program was temporarily closed and later relocated to an affiliate public hospital. Previous research indicates that the relationships between disaster exposure, substance use patterns, psychiatric symptoms, and mental health services utilization is complex, with often conflicting findings regarding post-event outcomes (on the individual and community level) and antecedent risk factors. In general, increased use of tobacco, alcohol, and illicit drugs is associated with both greater disaster exposure and the development or exacerbation of other psychiatric symptoms and need for treatment. To date, there is limited published information regarding post-disaster outcomes among patients enrolled in office-based buprenorphine treatment, as the treatment modality has only been relatively approved recently. Patients enrolled in the buprenorphine program at the time of the storm were surveyed for self-reported buprenorphine adherence and illicit substance and alcohol use, as well as disaster-related personal consequences and psychiatric sequelae post-storm. Baseline demographic characteristics and insurance status were available from the medical record. Analysis was descriptive (counts and proportions) and qualitative, coding open-ended responses for emergent themes. There were 132 patients enrolled in the program at the time of the storm; of those, 91 were contacted and 89 completed the survey. Almost half of respondents reported disruption of their buprenorphine supply. Unexpectedly, patients with psychiatric comorbidity were no more likely to report increased use/relapse as a result. Rather, major risk factors associated with increased use or relapse post-storm were: (1) shorter length of time in treatment, (2) exposure to storm losses such as buprenorphine supply disruption, (3) a pre-storm history of red flag behaviors (in particular, repeat opioid-positive urines), and (4) new-onset post-storm psychiatric symptoms. Our findings highlight the relative resilience of buprenorphine as an office-based treatment modality for patients encountering a disaster with associated unanticipated service disruption. In responding to future disasters, triaging patient contact and priority based on a history of red-flag behaviors, rather than a history of psychiatric comorbidity, will likely optimize resource allocation, especially among recently enrolled patients. Additionally, patients endorsing new-onset psychiatric manifestations following disasters may be an especially high-risk group for poor outcomes, warranting further study. PMID:24619775

Williams, Arthur R; Tofighi, Babak; Rotrosen, John; Lee, Joshua D; Grossman, Ellie

2014-04-01

104

Results of a Pilot Randomized Controlled Trial of Buprenorphine For Opioid Dependent Women in the Criminal Justice System  

PubMed Central

Aims Recent studies have demonstrated the efficacy of both methadone and buprenorphine when used with opioid dependent men transitioning from prison to the community, but no studies have been conducted with women in the criminal justice (CJ) system. The aim of this study was to determine the efficacy of buprenorphine for relapse prevention among opioid dependent women in the CJ system transitioning back to the community. Methods 36 women under CJ supervision were recruited from an inpatient drug treatment facility that treats CJ individuals returning back to the community. Nine were enrolled in an open label buprenorphine arm then 27 were randomized to buprenorphine (n=15) or placebo (n=12; double-blind). All women completed baseline measures and started study medication prior to release. Participants were followed weekly, provided urine drug screens (UDS), received study medication for 12 weeks, and returned for a 3 month follow-up. Intent-to-treat analyses were performed for all time points through end-of-treatment (EOT). Results The majority of participants were Caucasian (88.9%), young (M±SD=31.8±8.4 years), divorced/separated (59.2%) women with at least a high school/GED education (M±SD =12±1.7 years). GEE analyses showed that buprenorphine was efficacious in maintaining abstinence across time compared to placebo. At End of Treatment, 92% of placebo and 33% of active medication participants were positive for opiates on urine drug screen (Chi-Square = 10.9, df=1; p<0.001). However, by the three month follow-up point, no differences were found between the two groups, with 83% of participants at follow-up positive for opiates. Conclusions Women in the CJ system who received buprenorphine prior to release from a treatment facility had fewer opiate positive UDS through the 12-weeks of treatment compared to women receiving placebo. Initiating buprenorphine in a controlled environment prior to release appears to be a viable strategy to reduce opiate use when transitioning back to the community. PMID:21782352

Cropsey, Karen L.; Lane, Peter S.; Hale, Galen J.; Jackson, Dorothy O.; Clark, C. Brendan; Ingersoll, Karen S.; Islam, M. Aminul; Stitzer, Maxine L.

2011-01-01

105

Atipamezole Reverses Ketamine-Dexmedetomidine Anesthesia without Altering the Antinociceptive Effects of Butorphanol and Buprenorphine in Female C57BL/6J Mice.  

PubMed

Butorphanol and buprenorphine are common analgesics used in laboratory mice. Inadvertent attenuation of the antinociceptive effects of these analgesics via the administration of an anesthetic reversal agent could result in postprocedural pain and distress, with subsequent negative effects on animal welfare, study outcomes, and regulatory compliance. This study was undertaken to determine whether atipamezole reverses ketamine-dexmedetomidine anesthesia and alters the antinociceptive effects of butorphanol and buprenorphine in female C57BL/6J mice. Atipamezole reliably reversed the anesthetic effects of ketamine-dexmedetomidine, and mice were ambulatory 17.4 ± 30.6 min after administration of the ?2-adrenoreceptor antagonist. Atipamezole alone had no significant effect on tail-flick latency and did not alter the antinociceptive properties of butorphanol or low-dose (0.05 mg/kg) or high-dose (0.1 mg/kg) buprenorphine in female C57BL/6J mice. After reversal of ketamine-dexmedetomidine anesthesia, tail-flick latency at 30, 60, and 150 min after analgesic treatment differed significantly between mice treated with atipamezole alone and those given atipamezole followed by butorphanol or high-dose buprenorphine. These results suggest that the analgesic effects of butorphanol and buprenorphine are not affected by atipamezole. Buprenorphine (0.1 mg/kg) administered 30 min prior to or at the time of anesthesia resulted in a greater magnitude of antinociception after antagonism of anesthesia than when given at the time of reversal. Given these results, we recommend the use of ketamine-dexmedetomidine anesthesia with buprenorphine administered either preemptively or at the time of anesthetic induction to provide a defined period of surgical anesthesia that is effectively reversed by atipamezole. PMID:25650975

Izer, Jenelle M; Whitcomb, Tiffany L; Wilson, Ronald P

2014-01-01

106

Buprenorphine for Cancer Pain: Is It Ready for Prime Time?  

PubMed

Buprenorphine (BUP) is a semisynthetic derivative of the opium alkaloid thebaine found in the poppy Papaver somniferum. Its chemical structure contains the morphine structure but differs by having a cyclopropylmethyl group. Buprenorphine is a potent µ opioid agonist. Buprenorphine undergoes extensive first-pass metabolism in the liver and gut. The development of a transdermal BUP formulation in 2001 led to its evaluation in cancer pain. This article provides the practitioner with an update on the current role of BUP in cancer care. It highlights data suggesting effectiveness in various types of cancer pain. The article reviews pharmacology, routes of administration, adverse effects, drug interactions, and cost considerations. PMID:25163678

Prommer, Eric

2014-08-27

107

Acute Pain Management for Patients Receiving Maintenance Methadone or Buprenorphine Therapy  

PubMed Central

More patients with opioid addiction are receiving opioid agonist therapy (OAT) with methadone and buprenorphine. As a result, physicians will more frequently encounter patients receiving OAT who develop acutely painful conditions, requiring effective treatment strategies. Undertreatment of acute pain is suboptimal medical treatment, and patients receiving long-term OAT are at particular risk. This paper acknowledges the complex interplay among addictive disease, OAT, and acute pain management and describes 4 common misconceptions resulting in suboptimal treatment of acute pain. Clinical recommendations for providing analgesia for patients with acute pain who are receiving OAT are presented. Although challenging, acute pain in patients receiving this type of therapy can effectively be managed. PMID:16418412

Alford, Daniel P.; Compton, Peggy; Samet, Jeffrey H.

2007-01-01

108

The Effects of Maternally Administered Methadone, Buprenorphine and Naltrexone on Offspring: Review of Human and Animal Data  

PubMed Central

Most women using heroin are of reproductive age with major risks for their infants. We review clinical and experimental data on fetal, neonatal and postnatal complications associated with methadone, the current “gold standard”, and compare these with more recent, but limited, data on developmental effects of buprenorphine, and naltrexone. Methadone is a µ-opioid receptor agonist and is commonly recommended for treatment of opioid dependence during pregnancy. However, it has undesired outcomes including neonatal abstinence syndrome (NAS). Animal studies also indicate detrimental effects on growth, behaviour, neuroanatomy and biochemistry, and increased perinatal mortality. Buprenorphine is a partial µ-opioid receptor agonist and a ?-opioid receptor antagonist. Clinical observations suggest that buprenorphine during pregnancy is similar to methadone on developmental measures but is potentially superior in reducing the incidence and prognosis of NAS. However, small animal studies demonstrate that low doses of buprenorphine during pregnancy and lactation lead to changes in offspring behaviour, neuroanatomy and biochemistry. Naltrexone is a non-selective opioid receptor antagonist. Although data are limited, humans treated with oral or sustained-release implantable naltrexone suggest outcomes potentially superior to those with methadone or buprenorphine. However, animal studies using oral or injectable naltrexone have shown developmental changes following exposure during pregnancy and lactation, raising concerns about its use in humans. Animal studies using chronic exposure, equivalent to clinical depot formulations, are required to evaluate safety. While each treatment is likely to have maternal advantages and disadvantages, studies are urgently required to determine which is optimal for offspring in the short and long term. PMID:19305793

Farid, W.O; Dunlop, S.A; Tait, R.J; Hulse, G.K

2008-01-01

109

Caudal epidural buprenorphine for postoperative pain relief in children  

Microsoft Academic Search

Postoperative pain relief by caudal epidural buprenorphine, a highly lipid-soluble, semisynthetic derivative of thebaine, has not been reported in children. Over a period of 1 year, 58 children undergoing various surgical procedures were given 3 g\\/kg epidural buprenorphine via the caudal route. No serious side effects were encountered; on the contrary, the excellent and long-lasting pain relief (about 7 days)

A. N. Gangopadhyay; P. Bhattacharya; A. Sinhal; A. Digar; S. C. Gopall; G. D. Singhall

1992-01-01

110

Behavioral treatment of voyeurism and possible symptom substitution  

Microsoft Academic Search

Presents a case study that describes the relatively successful treatment of voyeuristic behaviors using behavioral techniques. A 44-yr-old black male had been a peeping tom since the age of 13. He was of borderline mental retardation with an IQ of 77. He and his wife were asked to keep a record of his peeping urges and fantasies and from this

John Stoudenmire

1973-01-01

111

Major bone defect treatment with an osteoconductive bone substitute  

Microsoft Academic Search

A bone defect can be provoked by several pathological conditions (e.g. bone tumours, infections, major trauma with bone stock\\u000a loss) or by surgical procedures, required for the appropriate treatment. Surgical techniques currently used for treating bone\\u000a defects may count on different alternatives, including autologous vascularized bone grafts, homologous bone graft provided\\u000a by musculoskeletal tissue bank, heterologous bone graft (xenograft), or

Stefania Paderni; S. Terzi; L. Amendola

2009-01-01

112

Bone graft substitutes for the treatment of traumatic fractures of the extremities  

PubMed Central

Health political and scientific background Bone graft substitutes are increasingly being used as supplements to standard care or as alternative to bone grafts in the treatment of traumatic fractures. Research questions The efficacy and cost-effectiveness of bone graft substitutes for the treatment of traumatic fractures as well as the ethical, social and legal implications of their use are the main research questions addressed. Methods A systematic literature search was conducted in electronic medical databases (MEDLINE, EMBASE etc.) in December 2009. Randomised controlled trials (RCT), where applicable also containing relevant health economic evaluations and publications addressing the ethical, social and legal aspects of using bone graft substitutes for fracture treatment were included in the analysis. After assessment of study quality the information synthesis of the medical data was performed using metaanalysis, the synthesis of the health economic data was performed descriptively. Results 14 RCT were included in the medical analysis, and two in the heath economic evaluation. No relevant publications on the ethical, social and legal implications of the bone graft substitute use were found. In the RCT on fracture treatment with bone morphogenetic protein-2 (BMP-2) versus standard care without bone grafting (RCT with an elevated high risk of bias) there was a significant difference in favour of BMP-2 for several outcome measures. The RCT of calcium phosphate (CaP) cement and bone marrow-based composite materials versus autogenous bone grafts (RCT with a high risk of bias) revealed significant differences in favour of bone graft substitutes for some outcome measures. Regarding the other bone graft substitutes, almost all comparisons demonstrated no significant difference. The use of BMP-2 in addition to standard care without bone grafting led in the study to increased treatment costs considering all patients with traumatic open fractures. However, cost savings through the additional use of BMP-2 were calculated in a patient subgroup with high-grade open fractures (Gustilo-Anderson grade IIIB). Cost-effectiveness for BMP-2 versus standard care with autologous bone grafts as well as for other bone graft substitutes in fracture treatment has not been determined yet. Discussion Although there were some significant differences in favour of BMP-2, due to the overall poor quality of the studies the evidence can only be interpreted as suggestive for efficacy. In the case of CaP cements and bone marrow-based bone substitute materials, the evidence is only weakly suggestive for efficacy. From an overall economic perspective, the transferability of the results of the health economic evaluations to the current situation in Germany is limited. Conclusions The current evidence is insufficient to evaluate entirely the use of different bone graft substitutes for fracture treatment. From a medical point of view, BMP-2 is a viable alternative for treatment of open fractures of the tibia, especially in cases where bone grafting is not possible. Autologous bone grafting is preferable comparing to the use of OP-1. Possible advantages of CaP cements and composites containing bone marrow over autogenous bone grafting should be taken into account in clinical decision making. The use of the hydroxyapatite material and allograft bone chips compared to autologous bone grafts cannot be recommended. From a health economic perspective, the use of BMP-2 in addition to standard care without bone grafting is recommended as cost-saving in patients with high-grade open fractures (Gustilo-Anderson grade IIIB). Based on the current evidence no further recommendations can be made regarding the use of bone graft substitutes for the treatment of fractures. To avoid legal implications, use of bone graft substitutes outside their approved indications should be avoided. PMID:22984371

Hagen, Anja; Gorenoi, Vitali; Schönermark, Matthias P.

2012-01-01

113

Shifts in opioid substitution treatment policy in Denmark from 2000-2011.  

PubMed

This article discusses how opioid substitution treatment policy has developed from 2000 to 2011 in Denmark. Empirically, it takes its point of departure in a stakeholder analysis including 17 qualitative interviews with stakeholders who have played important roles in this field. Analytically, it is inspired by Kingdon's concepts of agenda and policy window. Three major shifts are identified: a shift from psychosocial to medical thinking and practice, from an abstinence driven ideology to health care, and from perceptions of passive clients to user involvement. These shifts are discussed in relation to the legal context of substitute prescribing medicine. PMID:23952511

Frank, Vibeke Asmussen; Bjerge, Bagga; Houborg, Esben

2013-08-01

114

Effects of buprenorphine and an alternative nondrug reinforcer, alone and in combination on smoked cocaine self-administration in monkeys  

Microsoft Academic Search

The abuse of smoked cocaine base, also known as ‘crack’, continues to be a major public health problem and to date the success of pharmacological or behavioral interventions has been limited. The purpose of this study was to evaluate the efficacy of a behavioral (alternative reinforcer-saccharin) and pharmacological (0.01 mg\\/kg buprenorphine) treatment alone and in combination. Five adult male rhesus

Joshua S. Rodefer; Adande J. Mattox; Sherry S. Thompson; Marilyn E. Carroll

1997-01-01

115

Optimizing the dosing interval of buprenorphine in a multimodal postoperative analgesic strategy in the rat: minimizing side-effects without affecting weight gain and food intake.  

PubMed

Buprenorphine is commonly used as (part of) postoperative analgesic treatment with dosage dependent side-effects such as pica behaviour. No strict consensus exists about the optimal dosing interval of buprenorphine, as its duration of action has been described as being in the range of 6-12 h. In this study, dosing intervals of 8 h (thrice-a-day) and 12 h (twice-a-day) for buprenorphine in a multimodal analgesic strategy (concurrent administration of a non-steroidal anti-inflammatory drug) were compared on food intake, weight and side-effects (gnawing on plastic Petri dishes and growth rate, indicative of pica behaviour) in rats. The food intake and weight of both intervals were comparable, as the animals from the twice-a-day group did not lose more weight or consumed less food during the analgesic period. The rats from the thrice-a-day group suffered from more side-effects, as the growth rate was decreased and more plastic was gnawed on. It is recommended to carefully evaluate analgesic and side-effects when using buprenorphine. When side-effects are observed, the possibility of increasing the dosing interval of buprenorphine should be explored. In this study, increasing the dosing interval of buprenorphine in a multimodal analgesic regimen resulted in reduced unwanted side-effects, without increasing weight loss or decreasing food intake. Although this is suggestive of provision of comparable analgesia, future studies including more pain-related readout parameters to assess the effect of the dosing interval on analgesic efficacy are recommended. PMID:23097561

Schaap, Manon W H; Uilenreef, Joost J; Mitsogiannis, Manuela D; van 't Klooster, José G; Arndt, Saskia S; Hellebrekers, Ludo J

2012-10-01

116

Effect of ?-opioids morphine and buprenorphine on the development of adjuvant arthritis in rats  

Microsoft Academic Search

Objective and Design: On the basis that endogenous opioids play a role in the physiological response to inflammation, this\\u000a study tests the antiarthritic effects of a ?-opioid agonist, morphine and the partial ?-agonist, buprenorphine.\\u000a \\u000a Material: Male Lewis rats were used.\\u000a \\u000a \\u000a Treatment: Rats were innoculated subcutaneously with 0.05 ml of Freund's complete adjuvant (5 mg\\/ml) into the right hind paw\\u000a to

J. S. Walker; A. K. Chandler; J. L. Wilson; W. Binder; R. O. Day

1996-01-01

117

Predictors of Dropout from Inpatient Opioid Detoxification with Buprenorphine: A Chart Review  

PubMed Central

Inpatient withdrawal treatment (detoxification) is common in opioid dependence, although dropout against medical advice often limits its outcome. This study aimed to assess baseline predictors of dropout from inpatient opioid detoxification with buprenorphine, including age, gender, current substance use, and type of postdetoxification planning. A retrospective hospital chart review was carried out for inpatient standard opioid detoxifications using buprenorphine taper, in a detoxification ward in Malmö, Sweden (N = 122). Thirty-four percent of patients (n = 42) dropped out against medical advice. In multivariate logistic regression, dropout was significantly associated with younger age (OR 0.93 [0.89–0.97]) and negatively predicted by inpatient postdetoxification plan (OR 0.41 [0.18–0.94]), thus favouring an inpatient plan as opposed to outpatient treatment while residing at home. Dropout was unrelated to baseline urine toxicology. In opioid detoxification, patients may benefit from a higher degree of postdetoxification planning, including transition to residential treatment, in order to increase the likelihood of a successful detoxification and treatment entry. Young opioid-dependent patients may need particular attention in the planning of detoxification. PMID:25530903

Hallén, Emma

2014-01-01

118

Who prescribes buprenorphine for rural patients? The impact of specialty, location and practice type in Washington State?,??  

PubMed Central

We determined the specialty, geographic location, practice type and treatment capacity of waivered clinicians in Washington State. We utilized the April 2011 Drug Enforcement Agency roster of all waivered buprenorphine prescribers and cross-referenced the data with information from the American Medical Association and online resources. Waivered physicians, as compared to Washington State physicians overall, are more likely to be primary care providers, be older, less likely to be younger than 35years, and more likely to be female. Isolated rural areas have the lowest provider to population ratios. Ten counties lack either a buprenorphine provider or a methadone clinic. In rural areas, waivered physicians work predominately in federally-subsidized safety-net settings, which underscores the need for continued governmental support of primary care and mental health in these settings. PMID:22939650

Kvamme, Erik; Catlin, Mary; Banta-Green, Caleb; Roll, John; Rosenblatt, Roger

2013-01-01

119

Who prescribes buprenorphine for rural patients? The impact of specialty, location and practice type in Washington State.  

PubMed

We determined the specialty, geographic location, practice type and treatment capacity of waivered clinicians in Washington State. We utilized the April 2011 Drug Enforcement Agency roster of all waivered buprenorphine prescribers and cross-referenced the data with information from the American Medical Association and online resources. Waivered physicians, as compared to Washington State physicians overall, are more likely to be primary care providers, be older, less likely to be younger than 35 years, and more likely to be female. Isolated rural areas have the lowest provider to population ratios. Ten counties lack either a buprenorphine provider or a methadone clinic. In rural areas, waivered physicians work predominately in federally-subsidized safety-net settings, which underscores the need for continued governmental support of primary care and mental health in these settings. PMID:22939650

Kvamme, Erik; Catlin, Mary; Banta-Green, Caleb; Roll, John; Rosenblatt, Roger

2013-03-01

120

Buprenorphine versus morphine for patient-controlled analgesia after cholecystectomy.  

PubMed

Buprenorphine is an opioid agonist-antagonist that has emerged as an option for postoperative analgesia. We compared the postoperative hospital course of patients undergoing open cholecystectomy who received buprenorphine hydrochloride with those who received morphine sulfate. Patients in both groups administered the analgesic using a patient-controlled analgesia infusion device. Comparison of the two groups demonstrated no difference with respect to clinical indicators of intestinal motility, visual analog pain scores and hospitalization period. Postoperative nausea occurred more frequently in the buprenorphine group, but the difference was not significant. We concluded that the patient-controlled analgesia device is a valuable tool for comparing different analgesics. Both analgesics tested provide adequate analgesia with a similar postoperative course. PMID:8322143

Dingus, D J; Sherman, J C; Rogers, D A; DiPiro, J T; May, R; Bowden, T A

1993-07-01

121

Buprenorphine Response as a Function of Neurogenetic Polymorphic Antecedents: Can Dopamine Genes Affect Clinical Outcomes in Reward Deficiency Syndrome (RDS)?  

PubMed Central

There is a plethora of research indicating the successful treatment of opioid dependence with either buprenorphine alone or in combination with naloxone (Suboxone®). However, we encourage caution in long-term maintenance with these drugs, albeit, lack of any other FDA approved opioid maintenance compound to date. Our concern has been supported by severe withdrawal (even with tapering of the dosage of for example Suboxone® which is 40 times more potent than morphine) from low dose of buprenorphine (alone or with naloxone). In addition our findings of a long-term flat affect in chronic Suboxone® patients amongst other unwanted side effects including diversion and suicide attempts provides impetus to reconsider long-term utilization. However, it seems prudent to embrace genetic testing to reveal reward circuitry gene polymorphisms especially those related to dopaminergic pathways as well as opioid receptor(s) as a way of improving treatment outcomes. Understanding the interaction of reward circuitry involvement in buprenorphine effects and respective genotypes provide a novel framework to augment a patient's clinical experience and benefits during opioid replacement therapy. PMID:25664200

Blum, Kenneth; Oscar-Berman, Marlene; Jacobs, William; McLaughlin, Thomas; Gold, Mark S.

2014-01-01

122

Reversal of opioid overdose syndrome in morphine-dependent rats using buprenorphine.  

PubMed

The method of choice for reversal of opioid-toxicity is administration of naloxone. This treatment can be accompanied by complications including acute lung-injury, myocardial infarction, or withdrawal-syndrome (in dependent-patients). We aimed to evaluate the efficacy of buprenorphine in reversal of opioid-overdose syndrome in dependent-rats. A prospective case-control study was designed, in which a total of 30 rats were put on opioid-dependency protocol with 10mg/kg of intra-peritoneal morphine twice daily for 10 days. After confirmation of dependency by naloxone administration, the rats were overdosed by giving 16mg/kg of intra-peritoneal methadone. They were divided into four groups receiving naloxone (n=7; 2mg/kg) and buprenorphine(n=8, 8, and 7 with doses of 3mg/kg, 6mg/kg, and 10mg/kg), respectively. These four groups were compared regarding reversal of opioid signs/symptoms and development of withdrawal-syndrome. Rats in the first group showed signs/symptoms of opioid-withdrawal severely and with a higher frequency (P<0.001). In the groups 2-4, all doses recovered the intoxicated-rats without inducing signs/symptoms of withdrawal; however, the 3mg/kg dose reversed toxicity slower (P<0.001) and one rat in this group died later due to the re-development of signs of toxicity. Buprenorphine recovers opioid-overdose in morphine-dependent rats and bypasses the withdrawal-syndrome due to administration of naloxone. PMID:25510513

Zamani, Nasim; Hassanian-Moghaddam, Hossein; Bayat, Amir Hossein; Haghparast, Abbas; Shadnia, Shahin; Rahimi, Mitra; Hashemi Demaneh, Behrouz; Assar, Nasim

2015-02-01

123

Withdrawal from Buprenorphine/Naloxone and Maintenance with a Natural Dopaminergic Agonist: A Cautionary Note  

PubMed Central

Background While numerous studies support the efficacy of methadone and buprenorphine for the stabilization and maintenance of opioid dependence, clinically significant opioid withdrawal symptoms occur upon tapering and cessation of dosage. Methods We present a case study of a 35 year old Caucasian female (Krissie) who was prescribed increasing dosages of prescription opioids after carpel tunnel surgery secondary to chronic pain from reflex sympathetic dystrophy and fibromyalgia. Over the next 5 years, daily dosage requirements increased to over 80 mg of Methadone and 300 ug/hr Fentanyl transdermal patches, along with combinations of 12–14 1600 mcg Actig lollipop and oral 100 mg Morphine and 30 mg oxycodone 1–2 tabs q4-6hr PRN for breakthrough pain. Total monthly prescription costs including supplemental benzodiazepines, hypnotics and stimulants exceeded $50,000. The patient was subsequently transferred to Suboxone® in 2008, and the dosage was gradually tapered until her admission for inpatient detoxification with KB220Z a natural dopaminergic agonist. We carefully documented her withdrawal symptoms when she precipitously stopped taking buprenorphine/naloxone and during follow-up while taking KB220Z daily. We also genotyped the patient using a reward gene panel including (9 genes 18 alleles): DRD 2,3,4; MOA-A; COMT; DAT1; 5HTTLLR; OPRM1; and GABRA3. Findings At 432 days post Suboxone® withdrawal the patient is being maintained on KB220Z, has been urine tested and is opioid free. Genotyping data revealed a moderate genetic risk for addiction showing a hypodopaminergic trait. This preliminary case data suggest that the daily use of KB220Z could provide a cost effective alternative substitution adjunctive modality for Suboxone®. We encourage double-blind randomized –placebo controlled studies to test the proposition that KB220Z may act as a putative natural opioid substitution maintenance adjunct. PMID:24273683

Blum, Kenneth; Oscar-Berman, Marlene; Femino, John; Waite, Roger L; Benya, Lisa; Giordano, John; Borsten, Joan; Downs, William B; Braverman, Eric R; Loehmann, Raquel; Dushaj, Kristina; Han, David; Simpatico, Thomas; Hauser, Mary; Barh, Debmalya; McLaughlin, Thomas

2013-01-01

124

Comparison of the transcriptional responses induced by acute morphine, methadone and buprenorphine.  

PubMed

Despite their widespread use in opioid maintenance treatment and pain management, little is known about the intracellular effectors of methadone and buprenorphine and the transcriptional responses they induce. We therefore studied the acute effects of these two opioids in rats, comparing our observations with those for the reference molecule, morphine. We determined the analgesic ED50 of the three molecules in the tail flick test, to ensure that transcriptional effects were compared between doses of equivalent analgesic effect. We analysed changes in gene expression over time in three cerebral structures involved in several opioid behaviours-the dorsal striatum, thalamus and nucleus accumbens-by real-time quantitative PCR. We analysed the expression of genes encoding proteins of the endogenous opioid system in parallel with that of Fos, a marker of neuronal activation. The acute transcriptional effects of methadone resembled those of morphine more closely than did those of buprenorphine, in terms of kinetics and intensities. Our results provide the first evidence that these two drugs widely used in pain management and opioid maintenance treatment can disturb the regulation of endogenous opioid system genes and induce molecular outcomes different from those observed with morphine. PMID:23624329

Belkaï, Emilie; Crété, Dominique; Courtin, Cindie; Noble, Florence; Marie-Claire, Cynthia

2013-07-01

125

Changes in Quality of Life (WHOQOL-BREF) and Addiction Severity Index (ASI) among participants in Opioid Substitution Treatment (OST) in Low and Middle Income Countries: An International Systematic Review  

PubMed Central

Background Opioid substitution treatment (OST) can increase quality of life (WHOQOL-BREF) and reduce addiction severity index (ASI) scores among participants over time. OST program participants have noted that improvement in quality of life is one of the most important variables to their reduction in drug use. However, there is little systematic understanding of WHOQOL-BREF and ASI domain changes among OST participants in low and middle-income countries (LMIC). Methods Utilizing PRISMA guidelines we conducted a systematic literature search to identify OST program studies documenting changes in WHOQOL-BREF or ASI domains for participants in buprenorphine or methadone programs in LMIC. Standardized mean differences for baseline and follow-up domain scores were compared along with relationships between domain scores, OST dosage, and length of follow-up. Results There were 13 OST program studies with 1801 participants from seven countries eligible for inclusion in the review. Overall, statistically significant changes were noted in all four WHOQOL-BREF domain and four of the seven ASI domain scores (drug, psychological, legal, and family) documented in studies. Dosage of pharmacologic medication and length of follow-up did not affect changes in domain scores. Conclusion WHOQOL-BREF and ASI domain scoring is a useful tool in measuring overall quality of life and levels of addiction among OST participants. Coupled with measurements of blood-borne infection, drug use, relapse, and overdose, WHOQOL-BREF and ASI represent equally important tools for evaluating the effects of OST over time and should be further developed as integrated tools in the evaluation of participants in LMIC. PMID:24200104

Feelemyer, Jonathan P; Jarlais, Don C Des; Arasteh, Kamyar; Phillips, Benjamin W; Hagan, Holly

2013-01-01

126

Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis  

PubMed Central

Objective To quantify the effect of opiate substitution treatment in relation to HIV transmission among people who inject drugs. Design Systematic review and meta-analysis of prospective published and unpublished observational studies. Data sources Search of Medline, Embase, PsychINFO, and the Cochrane Library from the earliest year to 2011 without language restriction. Review methods We selected studies that directly assessed the impact of opiate substitution treatment in relation to incidence of HIV and studies that assessed incidence of HIV in people who inject drugs and that might have collected data regarding exposure to opiate substitution treatment but not have reported it. Authors of these studies were contacted. Data were extracted by two reviewers and pooled in a meta-analysis with a random effects model. Results Twelve published studies that examined the impact of opiate substitution treatment on HIV transmission met criteria for inclusion, and unpublished data were obtained from three additional studies. All included studies examined methadone maintenance treatment. Data from nine of these studies could be pooled, including 819 incident HIV infections over 23?608 person years of follow-up. Opiate substitution treatment was associated with a 54% reduction in risk of HIV infection among people who inject drugs (rate ratio 0.46, 95% confidence interval 0.32 to 0.67; P<0.001). There was evidence of heterogeneity between studies (I2=60%, ?2=20.12, P=0.010), which could not be explained by geographical region, site of recruitment, or the provision of incentives. There was weak evidence for greater benefit associated with longer duration of exposure to opiate substitution treatment. Conclusion Opiate substitution treatment provided as maintenance therapy is associated with a reduction in the risk of HIV infection among people who inject drugs. These findings, however, could reflect comparatively high levels of motivation to change behaviour and reduce injecting risk behaviour among people who inject drugs who are receiving opiate substitution treatment. PMID:23038795

2012-01-01

127

Overcoming policy and financing barriers to integrated buprenorphine and HIV primary care.  

PubMed

Treatment for substance abuse and human immunodeficiency virus (HIV) infection historically have come from different providers, often in separate locations, and have been reimbursed through separate funding streams. We describe policy and financing challenges faced by health care providers seeking to integrate buprenorphine, a new treatment for opioid dependence, into HIV primary care. Regulatory challenges include licensing and training restrictions imposed by the Drug Addiction Treatment Act of 2000 and confidentiality regulations for alcohol and drug treatment records. Potential responses include the development of local training programs and electronic medical records. Addressing the complexity of funding sources for integrated care will require administrative support, up-front investments, and federal and state leadership. A policy and financing research agenda should address evidence gaps in the rationales for regulatory restrictions and should include cost-effectiveness studies that quantify the "value for money" of investments in integrated care to improve health outcomes for HIV-infected patients with opioid dependence. PMID:17109311

Schackman, Bruce R; Merrill, Joseph O; McCarty, Dennis; Levi, Jeffrey; Lubinski, Christine

2006-12-15

128

Barriers to Opioid Substitution Treatment Access, Entry and Retention: A Survey of Opioid Users, Patients in Treatment, and Treating and Non-Treating Physicians  

Microsoft Academic Search

Background\\/Aims: Although the number of patients in opioid substitution treatment (OST) in Germany has increased in recent years, many dependent opioid users remain out of treatment. Project IMPROVE assessed attitudes and beliefs regarding barriers to OST. Methods: Data were collected from opioid-dependent individuals (using self-complete questionnaires) currently in treatment (n = 200) or not in treatment (n = 200), and

Heino Stöver

2011-01-01

129

Effect of steady-state faldaprevir on the pharmacokinetics of steady-state methadone and buprenorphine-naloxone in subjects receiving stable addiction management therapy.  

PubMed

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 has been registered at ClinicalTrials.gov under registration no. NCT01637922.). PMID:25385094

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

2015-01-01

130

[The impact of substitution treatment by methadone among opiate-dependent subjects evaluated by Addiction Severity Index and by urine tests].  

PubMed

Methadone maintenance treatment (MMT) has been evaluated in the United States and in a few other countries. MMT has been developed in France since 1995, and over 5 000 patients receive this treatment. However no French study has yet been published on the efficacy of MMT as assessed by a validated scale. Retention in treatment for one year has been considered as a threshold to define maintenance of treatment benefits after discharge from a methadone program; determination of retention predictors is important. Over a three year period, we evaluated patients at admission and during treatment using the Addiction Severity Index (ASI), and urine drug screening was performed weekly; 95 patients (66 males and 29 females) were evaluated at intake. Their mean age was 30.2 5.5, and they had used opioids for a mean of 10.6 5.7 years. Their ASI severity scores for drugs were over 5, showing a clear need for treatment. Female patients differed from males only in the employment-finances ASI score; 43 patients completed at least one year of treatment, after which their drug and legal composite scores significantly improved. No significant changes in their consumption of cocaine, alcohol, benzodiazepines or cannabis were found, but they smoked fewer cigarettes at 12 months. Demographics, ASI severity scores, and history of suicide attempts did not differentiate one-year completers from dropouts (n=16). However, dropouts had used more buprenorphine and less methadone in the 30 days preceding their admission, and they received a lower dose of methadone during treatment. Our population is comparable to other French MMT populations; they enter treatment after a long history of opioid dependence. The improvement found on the ASI composite scores is also similar to the improvement described in other international studies. Dropouts in our study seem to be more treatment-resistant patients, in the sense that they had used more buprenorphine before intake and were not stabilized with it; and they may have had a more negative attitude towards methadone. PMID:12386547

Trémeau, F; Darreye, A; Khidichian, F; Weibel, H; Kempf, M; Greth, Ph; Schneider, J L; Wantz, C; Weber, B; Stépien, S; Macher, J P

2002-01-01

131

[High-dose buprenorphine for outpatient palliative pain therapy].  

PubMed

The case of a 78-year-old patient with cancer-related pain and additionally mixed-pain syndrome is presented. Pain therapy with buprenorphine TTS 210 microg/h every 3 days was sufficient in the beginning, later the therapy was changed because of increasing problems of tape fixing during fever periods under chemotherapy to a continuous infusion of buprenorphine intravenously via an external medication pump. During the course of therapy it became necessary to increase the dose to 99.9 mg/day buprenorphine. Under this medication a sufficient pain reduction (median NRS 2-3) over a period of 135 days could be achieved. At the same time the patient was vigilant and cooperative without signs of intoxication until the end of life at home in the presence of his family.If no signs of intoxication occur under extreme opioid therapy and a sufficient pain therapy can be achieved, a rotation to another opioid is not necessary. However, outpatient palliative care requires a frequent adaptation to the individually varying opioid demand of the patient and time-consuming nursing care. PMID:19066981

Gastmeier, K; Freye, E

2009-04-01

132

Opioid Dependence Treatment: Options In Pharmacotherapy  

PubMed Central

The development of effective treatments for opioid dependence is of great importance given the devastating consequences of the disease. Pharmacotherapies for opioid addiction include opioid agonists, partial agonists, opioid antagonists, and alpha-2-adrenergic agonists, which are targeted toward either detoxification or long-term agonist maintenance. Agonist maintenance therapy is currently the recommended treatment for opioid dependence due to its superior outcomes relative to detoxification. Detoxification protocols have limited long term efficacy and patient discomfort remains a significant therapy challenge. Buprenorphine’s effectiveness relative to methadone remains a controversy and may be most appropriate for patients in need of low doses of agonist treatment. Buprenorphine appears superior to alpha-2 agonists, however, and office-based treatment with buprenorphine in the US is gaining support. Studies of sustained-release formulations of naltrexone suggest improved effectiveness for retention and sustained abstinence, however, randomized clinical trials are needed. PMID:19538000

Stotts, Angela L.; Dodrill, Carrie L.; Kosten, Thomas R.

2010-01-01

133

Crushed and Injected Buprenorphine Tablets: Characteristics of Princeps and Generic Solutions  

PubMed Central

Self-injection of high-dose buprenorphine is responsible for well-described complications. In 2011, we have been alerted by unusual but serious cutaneous complication among injection buprenorphine users. A prospective data collection identified 30 cases of necrotic cutaneous lesions after injection of filtered buprenorphine solution, among which 25 cases occurred following injection of buprenorphine generics. The main goal of our study was to put forward particularities that could explain the cutaneous complications, by qualitatively and quantitatively confronting particles present in Subutex and generics solutions. We used the same protocol that injected-buprenorphine users: generic or subutex tablets were crushed in sterile water and filtered through 2 filters commonly used (cotton-pad and sterifilt). Solutions were analyzed by laser granulometry, flow cytometry and scanning electron microscopy. We have highlighted the wide variation of the quantity and the size of the particles present in solution between the two drugs after cotton-pad filtration. The proportion of particles <10 µm is systematically higher in the generic solutions than with Subutex. All of the insoluble particles found in generic solutions contain silica, whereas non- organic element was to be identified in the insoluble particles of Subutex. One skin biopsy obtained from one patient who developed a necrotic lesion after intravenous injection of filtrated solution of buprenorphine generic, shows non-organic elements. Identification of particles in situ enables us to confirm the presence of silica in the biopsy. Actually the monitoring of patient receiving generic of buprenorphine must be strengthened. PMID:25474108

Bouquié, Régis; Wainstein, Laura; Pilet, Paul; Mussini, Jean-Marie; Deslandes, Guillaume; Clouet, Johann; Dailly, Eric; Jolliet, Pascale; Victorri-Vigneau, Caroline

2014-01-01

134

Dexamethasone hepatic induction in rats subsequently treated with high dose buprenorphine does not lead to respiratory depression  

SciTech Connect

In humans, asphyxic deaths and severe poisonings have been attributed to high-dosage buprenorphine, a maintenance therapy for heroin addiction. However, in rats, intravenous buprenorphine at doses up to 90 mg kg{sup -1} was not associated with significant effects on arterial blood gases. In contrast, norbuprenorphine, the buprenorphine major cytochrome P450 (CYP) 3A-derived metabolite, is a potent respiratory depressant. Thus, our aim was to study the consequences of CYP3A induction on buprenorphine-associated effects on resting ventilation in rats. We investigated the effects on ventilation of 30 mg kg{sup -1} buprenorphine alone or following cytochrome P450 (CYP) 3A induction with dexamethasone, using whole body plethysmography (N = 24) and arterial blood gases (N = 12). Randomized animals in 4 groups received sequential intraperitoneal dosing with: (dexamethasone [days 1-3] + buprenorphine [day 4]), (dexamethasone solvent [days 1-3] + buprenorphine [day 4]), (dexamethasone [days 1-3] + buprenorphine solvent [day 4]), or (dexamethasone solvent [days 1-3] + buprenorphine solvent [day 4]). Buprenorphine alone caused a significant rapid and sustained increase in the inspiratory time (P < 0.001), without significant effects on the respiratory frequency, the tidal volume, the minute volume, or arterial blood gases. In dexamethasone-pretreated rats, there was no significant alteration in the respiratory parameters, despite CYP3A induction and significant increase of the ratio of plasma norbuprenorphine-to-buprenorphine concentrations. In conclusion, dexamethasone did not modify the effects of 30 mg kg{sup -1} buprenorphine on rat ventilation. Our results suggest a limited role of drug-mediated CYP3A induction in the occurrence of buprenorphine-attributed respiratory depression in addicts.

Hreiche, Raymond [INSERM U705, CNRS UMR 7157, Universite Paris 7, Universite Paris 5, Hopital Fernand Widal, 75010 Paris (France); Megarbane, Bruno [INSERM U705, CNRS UMR 7157, Universite Paris 7, Universite Paris 5, Hopital Fernand Widal, 75010 Paris (France) and Assistance Publique-Hopitaux de Paris, Hopital Lariboisiere, Reanimation Medicale et Toxicologique, Universite Paris 7, 75010 Paris (France)]. E-mail: bruno-megarbane@wanadoo.fr; Pirnay, Stephane [INSERM U705, CNRS UMR 7157, Universite Paris 7, Universite Paris 5, Hopital Fernand Widal, 75010 Paris (France); Laboratoire de Toxicologie, Prefecture de Police de Paris, 75012 Paris (France); Borron, Stephen W. [INSERM U705, CNRS UMR 7157, Universite Paris 7, Universite Paris 5, Hopital Fernand Widal, 75010 Paris (France); Department of Surgery, University of Texas Health Science Center, San Antonio, TX 78229 (United States); Monier, Claire [INSERM U705, CNRS UMR 7157, Universite Paris 7, Universite Paris 5, Hopital Fernand Widal, 75010 Paris (France); Risede, Patricia [INSERM U705, CNRS UMR 7157, Universite Paris 7, Universite Paris 5, Hopital Fernand Widal, 75010 Paris (France); Milan, Nathalie [Laboratoire de Toxicologie, Prefecture de Police de Paris, 75012 Paris (France); Descatoire, Veronique [INSERM U481, Faculte de Medecine Xavier Bichat, 75018 Paris (France); Pessayre, Dominique [INSERM U481, Faculte de Medecine Xavier Bichat, 75018 Paris (France); Baud, Frederic J. [INSERM U705, CNRS UMR 7157, Universite Paris 7, Universite Paris 5, Hopital Fernand Widal, 75010 Paris (France); Assistance Publique-Hopitaux de Paris, Hopital Lariboisiere, Reanimation Medicale et Toxicologique, Universite Paris 7, 75010 Paris (France)

2006-12-15

135

The Severity, Frequency, and Variety of Crime in Heroin-Dependent Prisoners Enrolled in a Buprenorphine Clinical Trial  

PubMed Central

Data were obtained on four dimensions of criminal activity (frequency, variety, severity, and income) from male and female prisoners (N = 200) with preincarceration heroin dependence who participated in a randomized clinical trial of buprenorphine treatment. The article examines the above-mentioned dimensions of crime and their relationships with demographic characteristics, substance use, legitimate employment, drug treatment episodes, and psychological problems. Results largely show several important similarities to results on previous prison inmate cohorts with histories of heroin addiction, although the present sample may have more of a tendency toward violent crime than earlier cohorts of heroin-dependent offenders. This study’s findings may have implications for the design of appropriate treatment interventions for prisoners with preincarceration heroin dependence that address not only substance use but also criminal activity. PMID:25392564

Gordon, Michael S.; Kinlock, Timothy W.; Schwartz, Robert P.; Couvillion, Kathryn A.; O’Grady, Kevin E.

2014-01-01

136

The effects of prenatal exposure to buprenorphine or methadone on infant visual evoked potentials  

Microsoft Academic Search

This study compared the neurological development of 4month old infants exposed to buprenorphine or methadone during pregnancy to that of a control group of non-exposed infants. Participants were 30 buprenorphine-maintained women, 22 methadone-maintained women and 33 non opioid-dependent controls, and their infants. Women were enrolled during pregnancy as part of an open-label non-randomised flexible-dosing longitudinal study. Groups were matched for

Justine N. Whitham; Nicola J. Spurrier; Michael G. Sawyer; Peter A. Baghurst; John E. Taplin; Jason M. White; Andrea L. Gordon

2010-01-01

137

Evaluation of medetomidine, ketamine and buprenorphine for neutering feral cats.  

PubMed

A combination of medetomidine (M, 100 ?g/kg), ketamine (K, 10 mg/kg) and buprenorphine (B, 10 ?g/kg), administered by intramuscular injection, was evaluated for spaying and castration (neutering) of feral cats (n = 101). Eleven animals (11%) required supplemental anesthesia (isoflurane by mask) to maintain an adequate plane of surgical anesthesia. Atipamezole (A, 125 ?g/kg) was administered subcutaneously at the completion of surgery. All cats recovered from surgery and were released the following day. A hemoglobin saturation (SpO(2)) value of < 95% was recorded at least once during anesthesia in all cats. This MKB combination can be used in a feral cat sterilization clinic, but isoflurane supplementation may be necessary. Further research is indicated to determine the clinical significance of the low SpO(2) values associated with this anesthetic regimen. PMID:21885310

Harrison, Kelly A; Robertson, Sheilah A; Levy, Julie K; Isaza, Natalie M

2011-12-01

138

Opioid partial agonist buprenorphine dampens responses to psychosocial stress in humans.  

PubMed

Pre-clinical and clinical evidence indicates that opioid drugs have stress-dampening effects. In animal models, opioid analgesics attenuate responses to isolation distress, and in humans, opioids reduce stress related to anticipation of physical pain. The stress-reducing effects of opioid drugs may contribute to their abuse potential. Despite this evidence in laboratory animals, the effects of opioids on responses to psychosocial stress have not been determined in humans. Here we examined the effects of buprenorphine, a ?-opioid partial agonist used to treat opioid dependence and pain, on subjective and physiological responses to a stressful public speaking task in healthy adults. We hypothesized that buprenorphine would reduce subjective and physiological stress responses. Healthy adult volunteers (N=48) were randomly assigned to receive placebo, 0.2mg sublingual buprenorphine, or 0.4mg sublingual buprenorphine in a two-session study with a stressful speaking task (Trier Social Stress Test; TSST) and a non-stressful control task. During the sessions, the participants reported on their mood states, provided subjective appraisals of the task, and measures of salivary cortisol, heart rate, and blood pressure at regular intervals. Stress produced its expected effects, increasing heart rate, blood pressure, salivary cortisol, and subjective ratings of anxiety and negative mood. In line with our hypothesis, both doses of buprenorphine significantly dampened salivary cortisol responses to stress. On self-report ratings, buprenorphine reduced how threatening participants found the tasks. These results suggest that enhanced opioid signaling dampens responses to social stress in humans, as it does in laboratory animals. This stress-dampening effect of buprenorphine may contribute to the non-medical use of opioid drugs. PMID:25544740

Bershad, Anya K; Jaffe, Jerome H; Childs, Emma; de Wit, Harriet

2015-02-01

139

Community-Based Treatment for Opioid Dependent Offenders: A Pilot Study  

PubMed Central

Background Primary care opioid substitution treatment (OST) has not been compared to program-based OST for community-supervised offenders. Objective To compare primary care to specialist supervised OST for opioid dependent offenders in terms of substance use and HIV risk outcomes. This project randomly assigned 15 jail diversion participants to either: (1) primary care buprenorphine OST, (2) specialist facility buprenorphine OST, or (3) specialist facility methadone OST. Participation lasted 13.5 months (12 month active treatment plus a post-participation visit). Results All subjects endorsed 0 days of opioid use in the previous 14 at follow-up. Specialty care reduced HIV risk (Risk Assessment Battery composite score) over 6 months (?0.24±0.17) compared to primary care (0.02±0.14; p=0.032). Conclusion Findings support primary care OST feasibility for a community-supervised offender sample. Specialist care may facilitate improvements in secondary outcomes, such as HIV risk behaviors. Scientific significance Further research is needed to clarify (1) the role of primary care in addicted offender management, and (2) the matching of offenders, based upon history and co-morbidity, to care coordination conditions. PMID:23952897

Brown, Randy; Gassman, Michele; Hetzel, Scott; Berger, Lisa

2013-01-01

140

Effect of low-level laser treatment of tissue-engineered skin substitutes: contraction of collagen lattices  

NASA Astrophysics Data System (ADS)

Fibroblast-populated collagen lattices (FPCL) are widely used in tissue-engineered artificial skin substitutes, but their main drawback is that interaction of fibroblasts and matrix causes contraction of the lattice, reducing it to about 20% of its original area. The effect of low-level laser treatment (LLLT) on the behavior of 3T3 fibroblasts seeded in collagen lattices containing 20% chondroitin-6-sulphate was investigated to determine whether LLLT could control the contraction of FPCL. A He-Ne laser was used at 632.8 nm to deliver a 5-mW continuous wave with fluences from 1 to 4 J/cm2. Laser treatment at 3 J/cm2 increased contraction of collagen lattices in the absence of cells but decreased contraction of cell seeded lattices over a 7-day period. The effect was energy dependent and was not observed at 1, 2, or 4 J/cm2. There was no alteration in fibroblast viability, morphology, or mitochondrial membrane potential after any laser treatments, but the distribution of actin fibers within the cells and collagen fibers in the matrices was disturbed at 3 J/cm2. These effects contribute to the decrease in contraction observed. LLLT may offer a means to control contraction of FPCL used as artificial skin substitutes.

Ho, Gideon; Barbenel, Joseph; Grant, M. Helen

2009-05-01

141

Prenatal buprenorphine versus methadone exposure and neonatal outcomes: systematic review and meta-analysis.  

PubMed

Increasing rates of maternal opioid use during pregnancy and neonatal withdrawal, termed neonatal abstinence syndrome (NAS), are public health concerns. Prenatal buprenorphine maintenance treatment (BMT) versus methadone maintenance treatment (MMT) may improve neonatal outcomes, but associations vary. To summarize evidence, we used a random-effects meta-analysis model and estimated summary measures of BMT versus MMT on several outcomes. Sensitivity analyses evaluated confounding, publication bias, and heterogeneity. Subjects were 515 neonates whose mothers received BMT and 855 neonates whose mothers received MMT and who were born from 1996 to 2012 and who were included in 12 studies. The unadjusted NAS treatment risk was lower (risk ratio=0.90, 95% confidence interval (CI): 0.81, 0.98) and mean length of hospital stay shorter (-7.23 days, 95% CI: -10.64, -3.83) in BMT-exposed versus MMT-exposed neonates. In treated neonates, NAS treatment duration was shorter (-8.46 days, 95% CI: -14.48, -2.44) and morphine dose lower (-3.60 mg, 95% CI: -7.26, 0.07) in those exposed to BMT. BMT-exposed neonates had higher mean gestational age and greater weight, length, and head circumference at birth. Fewer women treated with BMT used illicit opioids near delivery (risk ratio=0.44, 95% CI: 0.28, 0.70). Simulations suggested that confounding by indication could account for some of the observed differences. Prenatal BMT versus MMT may improve neonatal outcomes, but bias may contribute to this protective association. Further evidence is needed to guide treatment choices. PMID:25150272

Brogly, Susan B; Saia, Kelley A; Walley, Alexander Y; Du, Haomo M; Sebastiani, Paola

2014-10-01

142

Antinociceptive efficacy of buprenorphine and hydromorphone in red-eared slider turtles (Trachemys scripta elegans).  

PubMed

Despite the frequent clinical use of buprenorphine in reptiles, its antinociceptive efficacy is not known. In a randomized, complete cross-over study, the antinociceptive efficacy of buprenorphine (0.2 mg/kg s.c.) was compared with hydromorphone (0.5 mg/kg s.c.), and saline (0.9% s.c. equivalent volume) in 11 healthy red-eared slider turtles (Trachemys scripta elegans). Additionally, buprenorphine at 0.1 and 1 mg/kg was compared with saline in six turtles. Hindlimb withdrawal latencies were measured after exposure to a focal, thermal noxious stimulus before and between 3 hr and up to 96 hr after drug administration. Buprenorphine did not significantly increase hindlimb withdrawal latencies at any time point compared with saline. In contrast, hydromorphone administration at 0.5 mg/kg significantly increased hindlimb withdrawal latencies for up to 24 hr. These results show that hydromorphone, but not buprenorphine, provides thermal antinociception in red-eared slider turtles. PMID:23082538

Mans, Christoph; Lahner, Lesanna L; Baker, Bridget B; Johnson, Stephen M; Sladky, Kurt K

2012-09-01

143

Acute and chronic administration of clorazepate modifies the cell surface regulation of mu opioid receptors induced by buprenorphine in specific regions of the rat brain.  

PubMed

The aim of the present study was to investigate the acute and chronic effects of clorazepate (CRZ) alone or in combination with buprenorphine (BPN) on binding of the selective mu opiate tritiated ligand [3H]-DAMGO in the rat brain. Using 0.1 to 5 nM [3H]-DAMGO concentrations and a beta-imager, Bmax (maximal receptor density) and K(D) (the dissociation constant) were directly determined at different regions of interest (ROI) in the brains of rats treated with BPN and/or CRZ administered either once or over 21 consecutive days. Differences in Bmax and K(D) were related to both treatment and location. Acute BPN induced a down-regulation (62% mean decrease in Bmax observed on the whole brain) of mu opiate receptors. CRZ induced a mean 39% decrease in Bmax associated with substantially decreased affinity, particularly after acute administration (136% mean K(D) increase). Addition of CRZ to BPN [mean Bmax decreases of 34% (acute) and 29% (chronic)] induced significantly less down-regulation than did BPN alone, while altering affinity. These changes were maximal in the amygdaloid nucleus. Significant and persistent decreases in Bmax and affinity were also detected in the hippocampus, hypothalamus and thalamus. In the thalamus, an opposite regulation of Bmax was observed that was maximal with the combination. As the regions where changes were greatest have been specifically implicated in memory and socio-emotional functions and/or vegetative and endocrine adaptations, there is reason to suspect that the addition of CRZ to BPN may have clinical consequences. On the one hand, it may have some impact on drug abuse and misuse behaviors towards treatments including heroin substitute and BZD, and on the other, amplify the BPN effect-particularly hedonic or toxic-mainly after sporadic BPN-BZD abuses. These pharmacodynamic findings may explain, at least in part, the well-established preference of patients for the BPN-benzodiazepine combination and the toxicity with which it is associated. PMID:16023087

Debruyne, Danièle; Quentin, Thomas; Poisnel, Géraldine; Lelong-Boulouard, Véronique; Barré, Louisa; Coquerel, Antoine

2005-08-01

144

Clinical efficacy of sustained-release buprenorphine with meloxicam for postoperative analgesia in beagle dogs undergoing ovariohysterectomy.  

PubMed

The goal of the current study was to compare the efficacy, adverse effects, and plasma buprenorphine concentrations of sustained-release buprenorphine (SRB) and buprenorphine after subcutaneous administration in dogs undergoing ovariohysterectomy. In a prospective, randomized, blinded design, 20 healthy adult female Beagle dogs underwent routine ovariohysterectomy and received multimodal analgesia consisting of meloxicam and one of two buprenorphine formulations. Dogs were randomly assigned to receive either SRB (0.2 mg/kg SC, once) or buprenorphine (0.02 mg/kg SC every 12 h for 3 d). Blinded observers assessed all dogs by using sedation scores, pain scores, temperature, HR, RR, and general wellbeing. Dogs were provided rescue analgesia with 0.02 mg/kg buprenorphine SC if the postoperative pain score exceeded a prede- termined threshold. Blood samples were collected, and mass spectrometry was used to determine plasma buprenorphine concentrations. Data were analyzed with a linear mixed model and Tukey-Kramer multiple comparison. Age, body weight, anesthetic duration, surgical duration, sevoflurane concentration, and cardiorespiratory variables did not differ significantly between groups. Dogs in both formulation groups had comparable postoperative sedation and pain scores. One dog from each formulation group had breakthrough pain requiring rescue analgesia. Plasma buprenorphine concentrations remained above a hypothesized therapeutic concentration of 0.6 ng/mL for 136.0 ± 11.3 and 10.67 ± 0.84 h for SRB and buprenorphine, respectively. Based on the results of this study, multimodal analgesic regimens consisting of meloxicam and either buprenorphine or SRB are equally efficacious in managing pain associated with an ovariohysterectomy and show comparable side effects. PMID:25255072

Nunamaker, Elizabeth A; Stolarik, DeAnne F; Ma, Junli; Wilsey, Amanda S; Jenkins, Gary J; Medina, Chris L

2014-09-01

145

40 CFR 268.3 - Dilution prohibited as a substitute for treatment.  

Code of Federal Regulations, 2011 CFR

...wastes in a CWA-equivalent treatment system, or which treat wastes...specified in § 268.40 as the treatment standard, or unless the waste is a D003 reactive cyanide wastewater or nonwastewater. (c...generation, or after any bona fide treatment such as cyanide...

2011-07-01

146

40 CFR 268.3 - Dilution prohibited as a substitute for treatment.  

Code of Federal Regulations, 2012 CFR

...wastes in a CWA-equivalent treatment system, or which treat wastes...specified in § 268.40 as the treatment standard, or unless the waste is a D003 reactive cyanide wastewater or nonwastewater. (c...generation, or after any bona fide treatment such as cyanide...

2012-07-01

147

40 CFR 268.3 - Dilution prohibited as a substitute for treatment.  

Code of Federal Regulations, 2010 CFR

...wastes in a CWA-equivalent treatment system, or which treat wastes...specified in § 268.40 as the treatment standard, or unless the waste is a D003 reactive cyanide wastewater or nonwastewater. (c...generation, or after any bona fide treatment such as cyanide...

2010-07-01

148

Sublingual Buprenorphine/Naloxone for Chronic Pain in At-Risk Patients: Development and Pilot Test of a Clinical Protocol  

PubMed Central

Objective Sublingual buprenorphine/naloxone (Bup/Nx) is approved for addiction treatment and may be useful for pain management, particularly in opioid-treated pain patients with nonadherence behaviors. The transition of opioid-treated pain patients to buprenorphine carries the risk of precipitated withdrawal and increased pain. This study convened pain and addiction specialists to develop and pilot a clinical protocol for safe transitioning to Bup/Nx. Design The protocol was revised three times based on outside expert review and pilot study observations. The pilot was conducted with a prospective cohort of 12 patients with moderate to severe chronic pain, who were receiving long-term opioid therapy with any full ?-agonist drug, and had exhibited one or more aberrant drug-related behaviors. Patients were followed up for 3 to 6 months with the expectation that they would experience few adverse events and report lower pain severity. Results The three patients on the highest baseline opioid dose (equivalent to 303–450 mg of oral morphine) and the three on the lowest doses (?20 mg) had early adverse events (AEs) when switched to Bup/Nx and did not complete the trial. Of the remaining six, one withdrew due to AEs; one responded well, then withdrew; and four completed a three-month trial. A mixed effects model controlling for dropouts found that average and worst pain significantly decreased after the switch to Bup/Nx (both p < .01). Conclusion Based on this experience, the protocol recommends Bup/Nx for pain only when baseline opioid doses are within bounds that reduce AEs at transition and incorporates dose flexibility to further reduce risks. This protocol warrants further testing. PMID:23264315

Rosenblum, Andrew; Cruciani, Ricardo A.; Strain, Eric C; Cleland, Charles M.; Joseph, Herman; Magura, Stephen; Marsch, Lisa A; McNicholas, Laura F; Savage, Seddon R; Sundaram, Arun; Portenoy, Russell K.

2013-01-01

149

A Marcus Treatment of Rate Constants for Protonation of Ring-Substituted ?-Methoxystyrenes  

PubMed Central

Rate and equilibrium constants were determined for protonation of ring-substituted ?-methoxystyrenes by hydronium ion and by carboxylic acids to form the corresponding ring-substituted ?-methyl ?-methoxybenzyl carbocations at 25 ° C and I = 1.0 (KCl). The thermodynamic barrier to carbocation formation increases by14.5 kcal/mol as the phenyl ring substituent(s) is changed from 4-MeO- to 3,5-di-NO2-, and as the carboxylic acid is changed from dichloroacetic to acetic acid. The Brønsted coefficient ? for protonation by carboxylic acids increases from 0.67 to 0.77 over this range of phenyl ring substituents and the Brønsted coefficient ? for proton transfer increases from 0.63 to 0.69 as the carboxylic acid is changed from dichloroacetic to acetic acid. The change in these Brønsted coefficients with changing reaction driving force, ?????Gavo=?????Gavo=1?8?=0.011 is used to calculate a Marcus intrinsic reaction barrier of ? = 11 kcal/mol which is close to the barrier of 13 kcal/mol for thermoneutral proton transfer between this series of acids and bases. The value of ? = 0.66 for thermoneutral proton transfer is greater than ? = 0.50 required by a reaction that follows the Marcus equation. This elevated value of ? may be due to an asymmetry in the reaction coordinate that arises from the difference in the intrinsic barriers for proton transfer at the oxygen acid reactant and resonance stabilized carbon acid product. PMID:17488079

Richard, John P.; Williams, Kathleen B.

2008-01-01

150

Production and validation of model iron-tannate dyed textiles for use as historic textile substitutes in stabilisation treatment studies  

PubMed Central

Background For millennia, iron-tannate dyes have been used to colour ceremonial and domestic objects shades of black, grey, or brown. Surviving iron-tannate dyed objects are part of our cultural heritage but their existence is threatened by the dye itself which can accelerate oxidation and acid hydrolysis of the substrate. This causes many iron-tannate dyed textiles to discolour and decrease in tensile strength and flexibility at a faster rate than equivalent undyed textiles. The current lack of suitable stabilisation treatments means that many historic iron-tannate dyed objects are rapidly crumbling to dust with the knowledge and value they hold being lost forever. This paper describes the production, characterisation, and validation of model iron-tannate dyed textiles as substitutes for historic iron-tannate dyed textiles in the development of stabilisation treatments. Spectrophotometry, surface pH, tensile testing, SEM-EDX, and XRF have been used to characterise the model textiles. Results On application to textiles, the model dyes imparted mid to dark blue-grey colouration, an immediate tensile strength loss of the textiles and an increase in surface acidity. The dyes introduced significant quantities of iron into the textiles which was distributed in the exterior and interior of the cotton, abaca, and silk fibres but only in the exterior of the wool fibres. As seen with historic iron-tannate dyed objects, the dyed cotton, abaca, and silk textiles lost tensile strength faster and more significantly than undyed equivalents during accelerated thermal ageing and all of the dyed model textiles, most notably the cotton, discoloured more than the undyed equivalents on ageing. Conclusions The abaca, cotton, and silk model textiles are judged to be suitable for use as substitutes for cultural heritage materials in the testing of stabilisation treatments. PMID:22616934

2012-01-01

151

Illicit use of methadone and buprenorphine among adolescents and young adults in Sweden  

PubMed Central

Background Illicit use of methadone and buprenorphine has been described as a growing problem in Sweden in recent years, and has been associated with an increased drug-related mortality. Critics claim that the substances have become popular among adolescents and that they function as a gateway to heroin use. The aim of this study is to investigate, firstly, the extent to which illicit use of methadone and buprenorphine occurs among adolescents and young adults in Sweden, and secondly, at what stage in a user’s drug career these substances tend to appear. Methods The study is based on surveys and structured interviews on drug use among various populations of young people, in addition to qualitative interviews with 86 informants who, in their professional capacity, encounter adolescents or young adults who are using illicit drugs. Results Illicit use of methadone and buprenorphine is rare among young people in Sweden. According to high school surveys, less than 0.1% have tried these substances. Among young drug users in general, few have tried the substances, and there is nothing to indicate that they act as gateway drugs. Among adolescents and young adults with severe drug problems, however, the illicit use of methadone and buprenorphine is more common (54% in a compulsory care sample). These substances normally enter the drug career late, and few use them as their main drug of choice. Other prescription drugs, like benzodiazepines and tramadol, are used by adolescents to a far greater extent. Diversion and illicit use of methadone and buprenorphine is not seen as a serious problem by the professionals interviewed. A general view is that the substances are mainly used by people with a heroin or polydrug addiction, often for “self-medication” purposes. However, several informants express concern that methadone and buprenorphine may cause fatalities among young drug users without an opioid tolerance. Conclusions Illicit use of methadone and buprenorphine among young drug users is not a widespread problem in Sweden. Harm-reduction measures should target drug users with more severe problems, among whom illicit use of methadone and buprenorphine is more common and pose a medical risk. Illicit use of other prescription drugs, which are less controlled and more widely used by young people, is an important issue for further research. PMID:24139199

2013-01-01

152

Buprenorphine versus methadone in pregnant opioid-dependent women: a prospective multicenter study  

Microsoft Academic Search

Patients and methods  In order to investigate the effects of exposure to buprenorphine compared with methadone during pregnancy, a prospective multicenter\\u000a study was conducted in collaboration with maternity hospitals, maintenance therapy centers, and general practitioners involved\\u000a in addiction care. Ninety pregnant women exposed to buprenorphine and 45 to metadone were selected for the study.\\u000a \\u000a \\u000a \\u000a \\u000a Results  During pregnancy, some women were exposed to

Isabelle Lacroix; Alain Berrebi; Daniel Garipuy; Laurent Schmitt; Yamina Hammou; Catherine Chaumerliac; Maryse Lapeyre-Mestre; Jean-Louis Montastruc; Christine Damase-Michel

153

Depression among entrants to treatment for heroin dependence in the Australian Treatment Outcome Study (ATOS): prevalence, correlates and treatment seeking  

Microsoft Academic Search

Aim: To determine the rate of current major depressive disorder (MDD) among entrants to treatment for heroin dependence in three treatment modalities and a non-treatment comparison group; and to ascertain factors associated with depression. Design: Cross sectional structured interview. Setting: Sydney, Australia. Participants: 615 current heroin users: 201 entering methadone\\/buprenorphine maintenance (MT), 201 entering detoxification (DTX), 133 entering drug free

Maree Teesson; Alys Havard; Sandra Fairbairn; Joanne Ross; Michael Lynskey; Shane Darke

2005-01-01

154

Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial  

Microsoft Academic Search

BACKGROUND: Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. METHODS: Open label randomised controlled trial in NHS Primary Care (General Practices), Leeds, UK. Sixty

Nat MJ Wright; Laura Sheard; Charlotte NE Tompkins; Clive E Adams; Victoria L Allgar; Nicola S Oldham

2007-01-01

155

Pharmacodynamic modelling of placebo and buprenorphine effects on event-related potentials in experimental pain.  

PubMed

The purpose of the study was to investigate placebo and buprenorphine effects on event-related potentials (ERPs) in experimental pain and the potential benefit of population pharmacodynamic modelling in data analysis. Nineteen healthy volunteers received transdermal placebo and buprenorphine in a cross-over study. Drug plasma concentrations and ERPs after electrical stimulation at the median nerve with intensity adjusted to pain detection threshold were recorded until 144 hrs after administration. Placebo and concentration-effect models were fitted to data using non-linear mixed-effects modelling implemented in NONMEM (V7.2.0.). Pharmacodynamic models were developed to adequately describe both placebo and buprenorphine ERP data. Models predicted significant placebo effects, but did not predict significant effects related to buprenorphine concentration. Models revealed that ERPs varied both between subjects and between study occasions. ERPs were found to be reproducible within subjects and occasions as population variance was found to be eight times higher than the unexplained variances. Between-subject variance accounted for more than 75% of the population variance. In conclusion, pharmacodynamic modelling was successfully implemented to allow for placebo and variability correction in ERP of experimental pain. Improved outcome of ERP studies can be expected if variation between subjects and study occasions can be identified and described. PMID:25163749

Juul, Rasmus V; Foster, David J R; Upton, Richard N; Andresen, Trine; Graversen, Carina; Drewes, Asbjørn M; Christrup, Lona L; Kreilgaard, Mads

2014-10-01

156

The effects of prenatal exposure to buprenorphine or methadone on infant visual evoked potentials.  

PubMed

This study compared the neurological development of 4 month old infants exposed to buprenorphine or methadone during pregnancy to that of a control group of non-exposed infants. Participants were 30 buprenorphine-maintained women, 22 methadone-maintained women and 33 non opioid-dependent controls, and their infants. Women were enrolled during pregnancy as part of an open-label non-randomised flexible-dosing longitudinal study. Groups were matched for maternal age, parity, gravida, and tobacco and alcohol use. Infant neurological development was assessed by measuring latency of pattern reversal visual evoked potentials (VEP). One-way between groups analyses of variance (ANOVA) were conducted to test the statistical significance of differences between the mean latencies of the peak response to two different sized checkerboard patterns (48' and 69' of retinal arc). Infants prenatally exposed to methadone had significantly prolonged latencies, compared with infants in the control group and infants prenatally exposed to buprenorphine, in response to checks of 48' and 69'. VEP latencies of infants prenatally exposed to buprenorphine did not differ significantly from controls for either check size. After adjustment for covariates, prenatal exposure to methadone remained a significant predictor of VEP response to checks of 48', but not 69'. Maternal self-reported used of marijuana during pregnancy made a significant unique contribution to the variance in P1 latencies for both check sizes. Data from this controlled, non-randomised study suggest that buprenorphine may confer an advantage over methadone as a maintenance drug during pregnancy in terms of infant neural development at 4 months of age. PMID:19751825

Whitham, Justine N; Spurrier, Nicola J; Sawyer, Michael G; Baghurst, Peter A; Taplin, John E; White, Jason M; Gordon, Andrea L

2010-01-01

157

Managing treatment resistant violent adolescents: a step forward by substituting seclusion for mechanical restraint?  

PubMed

Despite a growing consensus that seclusion or restraint should never be used with children or adolescents, there are a few patients who are resistant to treatment, and are persistently violent. The purpose of this study was to measure the efficacy of installing a padded seclusion room to decrease the use of mechanical restraints, a potentially more emotionally traumatic and dangerous intervention than seclusion. After padded room installation, the number of monthly mechanical restraint events per 1000 patient days decreased by 93.7%, from 21.2 to 1.3. A padded seclusion room may offer a safer, albeit a less than desirable alternative to mechanical restraint. PMID:18058220

Larson, Thomas C; Sheitman, Brian B; Kraus, John E; Mayo, James; Leidy, LuAnn

2008-05-01

158

Roles of ?-Opioid Receptors and Nociceptin/Orphanin FQ Peptide Receptors in Buprenorphine-Induced Physiological Responses in Primates  

PubMed Central

Buprenorphine is known as a ?-opioid peptide (MOP) receptor agonist, but its antinociception is compromised by the activation of nociceptin/orphanin FQ peptide (NOP) receptors in rodents. The aim of this study was to investigate the roles of MOP and NOP receptors in regulating buprenorphine-induced physiological responses in primates (rhesus monkeys). The effects of MOP antagonist (naltrexone), NOP antagonist [(±)-1-[(3R*,4R*)-1-(cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397)], and NOP agonists [(1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4.5] decan-4-one (Ro 64-6198) and 3-endo-8-[bis(2-methylphenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol (SCH 221510)] on buprenorphine were studied in three functional assays for measuring analgesia, respiratory depression, and itch in primates. Over the dose range of 0.01 to 0.1 mg/kg, buprenorphine dose-dependently produced antinociception, respiratory depression, and itch/scratching responses, and there was a ceiling effect at higher doses (0.1–1 mg/kg). Naltrexone (0.03 mg/kg) produced similar degrees of rightward shifts of buprenorphine's dose-response curves for all three endpoints. Mean pKB values of naltrexone (8.1–8.3) confirmed that MOP receptors mediated mainly buprenorphine-induced antinociception, respiratory depression, and itch/scratching. In contrast, J-113397 (0.1 mg/kg) did not change buprenorphine-induced physiological responses, indicating that there were no functional NOP receptors in buprenorphine-induced effects. More importantly, both NOP agonists, Ro 64-6198 and SCH 221510, enhanced buprenorphine-induced antinociception without respiratory depression and itch/ scratching. The dose-addition analysis revealed that buprenorphine in combination with the NOP agonist synergistically produced antinociceptive effects. These findings provided functional evidence that the activation of NOP receptors did not attenuate buprenorphine-induced antinociception in primates; instead, the coactivation of MOP and NOP receptors produced synergistic antinociception without other side effects. This study strongly supports the therapeutic potential of mixed MOP/NOP agonists as innovative analgesics. PMID:22743574

Cremeans, Colette M.; Gruley, Erin; Kyle, Donald J.

2012-01-01

159

Roles of ?-opioid receptors and nociceptin/orphanin FQ peptide receptors in buprenorphine-induced physiological responses in primates.  

PubMed

Buprenorphine is known as a ?-opioid peptide (MOP) receptor agonist, but its antinociception is compromised by the activation of nociceptin/orphanin FQ peptide (NOP) receptors in rodents. The aim of this study was to investigate the roles of MOP and NOP receptors in regulating buprenorphine-induced physiological responses in primates (rhesus monkeys). The effects of MOP antagonist (naltrexone), NOP antagonist [(±)-1-[(3R*,4R*)-1-(cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397)], and NOP agonists [(1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4.5] decan-4-one (Ro 64-6198) and 3-endo-8-[bis(2-methylphenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol (SCH 221510)] on buprenorphine were studied in three functional assays for measuring analgesia, respiratory depression, and itch in primates. Over the dose range of 0.01 to 0.1 mg/kg, buprenorphine dose-dependently produced antinociception, respiratory depression, and itch/scratching responses, and there was a ceiling effect at higher doses (0.1-1 mg/kg). Naltrexone (0.03 mg/kg) produced similar degrees of rightward shifts of buprenorphine's dose-response curves for all three endpoints. Mean pK(B) values of naltrexone (8.1-8.3) confirmed that MOP receptors mediated mainly buprenorphine-induced antinociception, respiratory depression, and itch/scratching. In contrast, J-113397 (0.1 mg/kg) did not change buprenorphine-induced physiological responses, indicating that there were no functional NOP receptors in buprenorphine-induced effects. More importantly, both NOP agonists, Ro 64-6198 and SCH 221510, enhanced buprenorphine-induced antinociception without respiratory depression and itch/ scratching. The dose-addition analysis revealed that buprenorphine in combination with the NOP agonist synergistically produced antinociceptive effects. These findings provided functional evidence that the activation of NOP receptors did not attenuate buprenorphine-induced antinociception in primates; instead, the coactivation of MOP and NOP receptors produced synergistic antinociception without other side effects. This study strongly supports the therapeutic potential of mixed MOP/NOP agonists as innovative analgesics. PMID:22743574

Cremeans, Colette M; Gruley, Erin; Kyle, Donald J; Ko, Mei-Chuan

2012-10-01

160

Human Split-Thickness Skin Allograft: Skin Substitute in the Treatment of Burn  

PubMed Central

Background: Human skin allograft has been used as wound coverage for a long time; it is one of the most successful and widely used dressings for burn wounds in the world. Objective: To prepare a freeze-dried human split-thickness skin allograft and evaluate its cytotoxicity, the structure and physical properties after processing methods and clinical efficacy in burn patients. Methods: After ensuring tissue safety, we lyophilized human cadaveric partial thickness skin and exposed it to gamma radiation. Histopathological and immunohistochemical properties, tensile strength and in vitro cytotoxicity were assayed for the skin samples. Then, we tested the samples in 11 patients with deep skin burn. Results: On histological and histopathological examinations, we found a normal skin structure. The tensile strength of the rehydrated freeze-dried human skin allograft was not lesser than the fresh human skin. Cell viability in MTT testing was more than 95%. None of our patients showed any signs of immunological reactions or complications. Conclusion: Gamma-irradiated freeze-dried human split-thickness skin is safe and non-toxic and can be used for the treatment of patients with deep skin burn. PMID:25013660

Mahdavi-Mazdeh, M.; Nozary Heshmati, B.; Tavakoli, S. A. H.; Ayaz, M.; Azmoudeh Ardalan, F.; Momeni, M.

2013-01-01

161

Evaluation of drug-drug interaction between daclatasvir and methadone or buprenorphine/naloxone  

PubMed Central

Introduction Daclatasvir (DCV) is a potent hepatitis C virus (HCV) NS5A replication complex inhibitor with pangenotypic (1–6) activity in vitro. Methadone (MET) and buprenorphine (BUP) are opioid medications used to treat opioid addiction; patients on HCV therapy may require MET or BUP treatment. The effect of DCV on the pharmacokinetics (PK) of MET or BUP/naloxone (NLX) was assessed in subjects on stable MET or BUP. Materials and Methods An open-label, two-part study assessed the effect of steady-state oral administration of DCV on the PK of MET (Part 1, P1) or BUP/NAL (Part 2, P2). Safety/tolerability and pharmacodynamics (PD, opioid withdrawal scales/overdose assessment) were also assessed. Subjects (P1, N=14; P2, N=11) received daily single-dose oral MET (40–120mg) or BUP/NLX (8/2–24/6mg) based on their prescribed stable dose throughout, in addition to DCV (60mg QD) on Days 2–9. Serial PK sampling occurred predose and postdose till 24 hours on Day 1 (MET/BUP) and Day 10 (MET/BUP/DCV). Noncompartmental PK were derived. Geometric mean ratios (GMR) and 90% confidence intervals (90% CI) for MET/BUP/norBUP Cmax and AUCTAU were derived from linear mixed effects models. Results Subjects were aged 19–39 years, mostly white (P1, 93%; P2, 100%) and male (P1, 71%; P2, 91%). All subjects completed the study. No clinically meaningful effect was demonstrated as the GMR and 90% CIs fell within the prespecified interval (P1, 0.7–1.4; P2, 0.5–2.0: see Table 1). DCV coadministration was well-tolerated: overall, six (43%) subjects had adverse events (AEs) (all mild and resolved without treatment). DCV had no clinically significant effect on the PD of MET or BUP/NLX. Conclusions Steady-state administration of DCV 60mg QD had no clinically meaningful effect on the PK of MET or BUP/NLX and was generally well-tolerated, suggesting that no dose adjustments will be required. PMID:25394132

Garimella, Tushar; Wang, Reena; Luo, Wen-Lin; Wastall, Philip; Kandoussi, Hamza; Demicco, Michael; Bruce, Douglas; Hwang, Carey; Bertz, Richard; Bifano, Marc

2014-01-01

162

Buprenorphine for pain relief in mice: repeated injections vs sustained-release depot formulation.  

PubMed

Sustained-release formulations of analgesic drugs are promising alternatives to repeated drug injections. Here, we compared a sustained-release formulation of buprenorphine (SB, 2.2?mg/kg) with a standard protocol of three injections of buprenorphine (Temgesic, 0.1?mg/kg/8?h) in mice. Buprenorphine serum concentration and analgesic action (thermal sensitivity) were determined in healthy mice. Additionally, the pain relief properties of both protocols were assessed after laparotomy using physiological and ethological measures of pain and recovery. Serum concentrations and thermal sensitivity tests indicated duration of action of at least 4?h (but less than 8?h) with the Temgesic protocol, and 24-48?h with SB. Behavioural and clinical parameters indicated at least partial pain relief after surgery for both protocols. Observed side-effects of buprenorphine independent of the protocol were increased activity, disturbed circadian rhythm and several abnormal behaviours. A tendency for decreased food and water intake as well as body weight reduction was also seen. Body weight decreased significantly in animals that received three injections of Temgesic, regardless of whether surgery was performed or not (P?=?0.015; P?=?0.023), hinting at a stress response towards this repeated intervention. In conclusion, an application interval of 8?h (Temgesic) appears too long and might lead to repeated periods with insufficient analgesia in animals undergoing lasting and/or substantial pain after surgery. In comparison to the standard protocol, SB provided a long-lasting, assured analgesia without possible stressful repeated injections in a standard surgical model, with only limited and acceptable behavioural side-effects. PMID:25488320

Jirkof, P; Tourvieille, A; Cinelli, P; Arras, M

2014-12-01

163

Double-blind evaluation of buprenorphine hydrochloride for post-operative pain  

Microsoft Academic Search

Summary and Conclusions  In a double-blind, random assignment study of four groups of 40 patients, relief of severe pain with buprenorphine hydrochloride\\u000a 0.2 mg or 0.4 mg was evaluated and compared with morphine sulphate 5 or 10 mg. Evaluations included pain intensity, pain relief,\\u000a sedation and other effects for up to 12 hours after drug administration, following recovery of wakefulness from

Allen B. Dobkin; Barbara Esposito; Carole Philbin

1977-01-01

164

The applicability of a gel delivery system for self-administration of buprenorphine to laboratory mice.  

PubMed

Oral administration of perioperative analgesia to laboratory mice is beneficial compared with administration by injection. The mice become less stressed when allowed to voluntarily ingest the drug in a palatable feed item and it results in high and long-lasting serum concentrations of the drug. We have previously demonstrated sticky nut and chocolate paste to be well-liked by mice and readily ingested in most cases. However, a disadvantage with nut and chocolate paste is its high content of fat and sugar, which may have undesirable effects in some experimental models. Alternatively, a delivery system using an aqueous gel may serve as a supplementary source of fluid post-operatively and as a vehicle for analgesic drugs. In the present study, we investigated the willingness of the mice to ingest a commercially available gel, by measuring the duration from introduction of the gel to first ingestion, as well as the amount ingested overnight. Furthermore, buprenorphine in two different concentrations (5 and 15?µg/mL) was mixed in the gel and the resulting serum concentrations of buprenorphine were investigated. The aqueous gel was ingested by the mice, but their willingness was low and did not increase over time. The serum concentrations of buprenorphine were similar to, or higher than, those following a subcutaneous injection (0.1?mg/kg body weight), but the variation was considerably higher. In conclusion, aqueous gel may serve as a relevant vehicle for the voluntary ingestion of buprenorphine in mice, but the willingness of the mice to ingest the gel needs to be improved. PMID:25193176

Hovard, Amb; Teilmann, Ac; Hau, J; Abelson, Ksp

2015-01-01

165

Determination of buprenorphine, fentanyl and LSD in whole blood by UPLC-MS-MS.  

PubMed

A sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method has been developed and validated for the quantification of buprenorphine, fentanyl and lysergic acid diethylamide (LSD) in whole blood. Sample preparation was performed by liquid-liquid extraction (LLE) with methyl tert-butyl ether. UPLC-MS-MS analysis was performed with a mobile phase consisting of ammonium formate (pH 10.2) and methanol. Positive electrospray ionization MS-MS detection was performed with two multiple reaction monitoring transitions for each of the analytes and the deuterium labeled internal standards. Limit of detection values of buprenorphine, fentanyl and LSD were 0.28, 0.044 and 0.0097 ng/mL and limit of quantification values were 0.94, 0.14 and 0.036 ng/mL, respectively. Most phospholipids were removed during LLE. No or only minor matrix effects were observed. The method has been routinely used at the Norwegian Institute of Public Health since September 2011 for qualitative and quantitative detections of buprenorphine, fentanyl and/or LSD in more than 400 whole blood samples with two replicates per sample. PMID:23423312

Berg, Thomas; Jørgenrud, Benedicte; Strand, Dag Helge

2013-04-01

166

Subnanogram-concentration measurement of buprenorphine in human plasma by electron-capture capillary gas chromatography: application to pharmacokinetics of sublingual buprenorphine.  

PubMed

We describe a sensitive and specific method for the measurement of buprenorphine in human plasma. The method involves a structural analog as an internal calibrator, careful control of pH during sample extraction to maximize drug recovery, and back-extraction into acid followed by reextraction to eliminate endogenous interferences. After evaporation, sample residues are derivatized with heptafluorobutyric anhydride and analyzed by separation on a fused-silica polymethylsiloxane capillary column and electron-capture detection. Calibration curves were linear in the ranges 0.1-2.0 micrograms/L and 2.0-20 micrograms/L, with within-run CVs of 9.7% at 0.1 microgram/L to 5.0% at 20 micrograms/L, and total CVs of 15.9% at 0.1 microgram/L to 6.5% at 10 micrograms/L. The limit of quantification was 0.1 microgram/L. The method was utilized in studies to determine the absolute bioavailability of sublingual doses of 2 mg of buprenorphine in 1 mL of 300 mL/L ethanol and the bioequivalence of sublingual 8-mg tablet and 300 mL/L ethanol solution formulations. PMID:9439446

Everhart, E T; Cheung, P; Shwonek, P; Zabel, K; Tisdale, E C; Jacob, P; Mendelson, J; Jones, R T

1997-12-01

167

Effect of Rifampin and Nelfinavir on the Metabolism of Methadone and Buprenorphine in Primary Cultures of Human Hepatocytes  

PubMed Central

We tested the hypothesis that primary cultures of human hepatocytes could predict potential drug interactions with methadone and buprenorphine. Hepatocytes (five donors) were preincubated with dimethyl sulfoxide (DMSO) (vehicle), rifampin, or nelfinavir before incubation with methadone or buprenorphine. Culture media (0–60 min) was analyzed by liquid chromatography-tandem mass spectrometry for R- and S-methadone and R- and S-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) or for buprenorphine, norbuprenorphine, and their glucuronides [buprenorphine-3-glucuronide (B-3-G) and norbuprenorphine-3-glucuronide (N-3-G)]. R- and S-EDDP were detected in three of five, four of five, and five of five media from cells pretreated with DMSO, nelfinavir, and rifampin. R-EDDP increased 3.1- and 26.5-fold, and S-EDDP increased 2.5- and 21.3-fold after nelfinavir and rifampin. The rifampin effect was significant. B-3-G production was detected in media of all cells incubated with buprenorphine and accounted for most of the buprenorphine loss from culture media; it was not significantly affected by either pretreatment. Norbuprenorphine and N-3-G together were detected in three of five, four of five, and five of five donors pretreated with DMSO, nelfinavir and rifampin, and norbuprenorphine in one of five, one of five, and two of five donors. Although there was a trend for norbuprenorphine (2.8- and 4.9-fold) and N-3-G (1.7- and 1.9-fold) to increase after nelfinavir and rifampin, none of the changes were significant. To investigate low norbuprenorphine production, buprenorphine was incubated with human liver and small intestine microsomes fortified to support both N-dealkylation and glucuronidation; N-dealkylation predominated in small intestine and glucuronidation in liver microsomes. These studies support the hypothesis that methadone metabolism and its potential for drug interactions can be predicted with cultured human hepatocytes, but for buprenorphine the combined effects of hepatic and small intestinal metabolism are probably involved. PMID:19773542

Fang, Wenfang B.; Lin, Shen-Nan; Weyant, Denise M.; Strom, Stephen C.; Omiecinski, Curtis J.

2009-01-01

168

Comparison of Intrathecal Dexmedetomidine with Buprenorphine as Adjuvant to Bupivacaine in Spinal Asnaesthesia  

PubMed Central

Background: The supplementation of local anaesthetics with adjuvants to improve the efficacy of subarachnoid block has been recognised since long. The most preferred drug has been opioids, but newer drugs like dexmedetomidine has also been introduced and investigated as an effective adjuvant. Aim: This study was conducted to evaluate and compare the characteristics of subarachnoid blockade, hemodynamic stability and adverse effects of intrathecal buprenorphine and intrathecal dexmedetomidine as an adjuvant to 0.5% hyperbaric bupivacaine for lower abdominal surgeries. Materials and Methods: The present study included 60 patients aged between 18-60 years classified as American Society of Anesthesiologists (ASA) Physical Status (PS) I/II scheduled for elective lower abdominal surgeries. The patients were randomly allotted to two groups to receive intrathecal 3ml of 0.5% bupivacine with 60µg of buprenorphine (Group B; n=30) or 3ml of 0.5% bupivacaine with 5µg of dexmedetomidine (Group D; n=30). The onset time to peak sensory level, motor block, sedation, Haemodynamic variables, duration of motor block, analgesia and any adverse effects were noted. Results: There was no significant difference between groups regarding demographic characteristics and type of surgery. The motor, sensory blockade and time of rescue analgesia were significantly prolonged in Group D compared to Group B. The sedation level was higher in Group D compared to Group B. There was no significant difference in haemodynamic variables although Group B had lower Heart Rate (HR) than Group D. Conclusion: Intrathecal dexmedetomidine when compared to intrathecal buprenorphine causes prolonged anaesthesia and analgesia with reduced need for sedation and rescue analgesics. PMID:24701498

Gupta, Mahima; Shailaja, S.; Hegde, K. Sudhir

2014-01-01

169

Transcutaneous cranial electrical stimulation (Limoge's currents) decreases early buprenorphine analgesic requirements after abdominal surgery.  

PubMed

Transcutaneous cranial electrical stimulation with Limoge's currents (TCES) consists of high frequency, low intensity currents which decreased anesthetic requirements during elective surgery. This action is likely to be mediated by the release of central endogenous opioids. In the present study, we hypothesized that TCES applied intraoperatively may decrease early postoperative narcotic requirements. Thirty-nine ASA physical status I and II patients undergoing elective abdominal surgery were enrolled in this prospective, randomized, double-blind, placebo-controlled study. Just before induction of anesthesia, patients were connected to the electrical stimulator and randomly allocated to be either stimulated (TCES group, n = 20) or not (control group, n = 19) during surgery. The managing anesthesiologist was unaware of which group the patient was assigned. Postoperatively, patients were given a patient-controlled analgesia (PCA) device delivering buprenorphine for the first four postoperative hours. The recorded variables included postoperative buprenorphine requirements, pain scores (0-10 visual analog scale [VAS]), sedation (0-4 scale), and intraoperative isoflurane requirements. Patients were comparable with respect to age, sex ratio, weight, duration of surgery, intraoperative hemodynamics, fentanyl requirements, and time from skin closure to tracheal extubation. Buprenorphine requirements were significantly reduced in the TCES group versus the control group (2.36 vs 3.43 micrograms.kg-1.h-1; P = 0.002). Intraoperative isoflurane anesthetic requirements, as well as hourly postoperative scores for pain and sedation, were the same for the two groups. These data indicate that TCES reduces narcotic requirements for early postoperative analgesia. This technique might have potential to facilitate early postoperative analgesia in patients undergoing elective abdominal surgery. PMID:8831319

Mignon, A; Laudenbach, V; Guischard, F; Limoge, A; Desmonts, J M; Mantz, J

1996-10-01

170

Skin Substitutes  

PubMed Central

In a relatively short timespan, a wealth of new skin substitutes made of synthetic and biologically derived materials have arisen for the purpose of wound healing of various etiologies. This review article focuses on providing an overview of skin substitutes including their indications, contraindications, benefits, and limitations. The result of this overview was an appreciation of the vast array of options available for clinicians, many of which did not exist a short time ago. Yet, despite the rapid expansion this field has undergone, no ideal skin substitute is currently available. More research in the field of skin substitutes and wound healing is required not only for the development of new products made of increasingly complex biomolecular material, but also to compare the existing skin substitutes. PMID:25371771

Howe, Nicole; Cohen, George

2014-01-01

171

Combination Interventions to Prevent HCV Transmission Among People Who Inject Drugs: Modeling the Impact of Antiviral Treatment, Needle and Syringe Programs, and Opiate Substitution Therapy  

PubMed Central

Background.?Interventions such as opiate substitution therapy (OST) and high-coverage needle and syringe programs (HCNSP) cannot substantially reduce hepatitis C virus (HCV) prevalence among people who inject drugs (PWID). HCV antiviral treatment may prevent onward transmission. We project the impact of combining OST, HCNSP, and antiviral treatment on HCV prevalence/incidence among PWID. Methods.?An HCV transmission model among PWID was used to project the combinations of OST, HCNSP, and antiviral treatment required to achieve different prevalence and incidence reductions within 10 years for 3 chronic prevalence scenarios and the impact of HCV treatment if only delivered through OST programs. Multivariate and univariate sensitivity analyses were performed. Results.?Large reductions (>45%) in HCV chronic prevalence over 10 years require HCV antiviral treatment. Scaling up OST and HCNSP substantially reduces the treatment rate required to achieve specific HCV prevalence reductions. If OST and HCNSP coverage were increased to 40% each (no coverage at baseline), then annually treating 10, 23, or 42 per 1000 PWID over 10 years would halve prevalence for 20%, 40%, or 60% baseline chronic HCV prevalences, respectively. Approximately 30% fewer treatments are necessary with new direct-acting antivirals. If coverage of OST and HCNSP is 50% at baseline, similar prevalence reductions require higher treatment rates for the same OST and HCNSP coverage. Conclusions.?Combining antiviral treatment with OST with HCNSP is critical for achieving substantial reductions (>50%) in HCV chronic prevalence over 10 years. Empirical studies are required on how best to scale up antiviral treatment and combine treatment with other interventions. PMID:23884064

Martin, Natasha K.; Hickman, Matthew; Hutchinson, Sharon J.; Goldberg, David J.; Vickerman, Peter

2013-01-01

172

Hemodynamic and Behavioral Differences after Administration of Meloxicam, Buprenorphine, or Tramadol as Analgesics for Telemeter Implantation in Mice  

PubMed Central

Cannulation of the common carotid artery for chronic, continuous radiotelemetric recording of aortic hemodynamic properties in mice is a highly invasive recovery surgery. Radiotelemetric recording, by its continuous nature, gives the most accurate measurements of hemodynamic variables in experimental animals, and is widely used in the study of cardiovascular diseases including hypertension. The American Heart Association has recommended data acquisition by radiotelemetric recording but did not provide guidelines regarding postoperative analgesic support. We assessed hemodynamic parameters, locomotor activity, food intake, and weight loss in radiotransmitter-implanted CD1 female mice receiving analgesic support during the first 48 h after surgery. The efficacy of analgesic support from the NSAID meloxicam was compared with that of the widely used opioid agonist buprenorphine and the related compound, tramadol. Meloxicam-treated mice recovered lost body weight more rapidly than did tramadol- or buprenorphine-treated mice. Furthermore, meloxicam-treated mice maintained circadian rhythm after surgery and had tighter regulation of mean arterial pressure than did tramadol- or buprenorphine-treated mice. Meloxicam was also superior with regard to food intake, locomotor activity, and limiting variance in hemodynamic parameters. This study indicates that when compared with buprenorphine and tramadol, meloxicam should be the postoperative analgesic of choice for radiotelemeter implantation in mice. PMID:24041211

Rätsep, Matthew T; Barrette, Valerie F; Winterborn, Andrew; Adams, Michael A; Croy, B Anne

2013-01-01

173

Executive function in preschool children prenatally exposed to methadone or buprenorphine.  

PubMed

Although an increasing number of children are born with prenatal methadone or buprenorphine exposure, little is still known about the potential long-term effects of these opioids. The aim of this study was to investigate executive function (EF) in children of women in opioid maintenance therapy (OMT). A total of 66 children (aged 48-57 months) participated in the study, 35 of which had histories of prenatal methadone or buprenorphine exposure. EF was measured using a battery of neuropsychological tests and the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Results showed that children of women in OMT perform lower on tasks of short-term memory and inhibition compared to nonexposed children, which was mainly associated with lower maternal education and employment rate. The OMT group scored significantly lower on all EF tasks compared to the nonexposed group, although scores fell within the average range on all measures. The development of these children should be monitored to assess for the possible problem behaviors and to promote optimal outcomes. PMID:25354916

Konijnenberg, Carolien; Melinder, Annika

2014-10-30

174

Rectal absorption and mucosal irritation of rectal gels containing buprenorphine hydrochloride prepared with water-soluble dietary fibers, xanthan gum and locust bean gum  

Microsoft Academic Search

Rectal gels prepared with water-soluble dietary fibers, xanthan gum and locust bean gum, were evaluated as a vehicle for the rectal administration of buprenorphine hydrochloride (BN-HCI) in rabbits. The maximum plasma concentration of buprenorphine (BN) gradually decreased with increase in the gum concentration. The values of the mean residence time (MRT0–2) increased in proportion to increasing gum concentration. The absorption

Kazunori Watanabe; Shigeru Yakou; Kozo Takayama; Koichi Isowa; Tsuneji Nagai

1996-01-01

175

Thrice-weekly supervised dosing with the combination buprenorphine-naloxone tablet is preferred to daily supervised dosing by opioid-dependent humans  

Microsoft Academic Search

A sublingual tablet formulation of buprenorphine combining 8 mg of buprenorphine with 2 mg of naloxone is being targeted for use in settings where less than daily dosing strategies and\\/or prescription-based dispensing will likely be employed. This study determined patient preferences for, and clinical outcomes during, daily and 3-day per week supervised dosing schedules using the combination tablet. Twenty-four opioid-dependent

Leslie Amass; Jonathan B Kamien; Susan K Mikulich

2001-01-01

176

Pilot study of a social network intervention for heroin users in opiate substitution treatment: study protocol for a randomized controlled trial  

PubMed Central

Background Research indicates that 3% of people receiving opiate substitution treatment (OST) in the UK manage to achieve abstinence from all prescribed and illicit drugs within 3 years of commencing treatment, and there is concern that treatment services have become skilled at engaging people but not at helping them to enter a stage of recovery and drug abstinence. The National Treatment Agency for Substance Misuse recommends the involvement of families and wider social networks in supporting drug users’ psychological treatment, and this pilot randomized controlled trial aims to evaluate the impact of a social network-focused intervention for patients receiving OST. Methods and design In this two-site, early phase, randomized controlled trial, a total of 120 patients receiving OST will be recruited and randomized to receive one of three treatments: 1) Brief Social Behavior and Network Therapy (B-SBNT), 2) Personal Goal Setting (PGS) or 3) treatment as usual. Randomization will take place following baseline assessment. Participants allocated to receive B-SBNT or PGS will continue to receive the same treatment that is routinely provided by drug treatment services, plus four additional sessions of either intervention. Outcomes will be assessed at baseline, 3 and 12 months. The primary outcome will be assessment of illicit heroin use, measured by both urinary analysis and self-report. Secondary outcomes involve assessment of dependence, psychological symptoms, social satisfaction, motivation to change, quality of life and therapeutic engagement. Family members (n = 120) of patients involved in the trial will also be assessed to measure the level of symptoms, coping and the impact of the addiction problem on the family member at baseline, 3 and 12 months. Discussion This study will provide experimental data regarding the feasibility and efficacy of implementing a social network intervention within routine drug treatment services in the UK National Health Service. The study will explore the impact of the intervention on both patients receiving drug treatment and their family members. Trial registration Trial Registration Number: ISRCTN22608399 ISRCTN22608399 registration: 27/04/2012 Date of first randomisation: 14/08/2012 PMID:23958332

2013-01-01

177

Pharmacokinetic Comparison of Sustained-Release and Standard Buprenorphine in Mice  

PubMed Central

Effective pain medication is important for animal stewardship and valid research results. We compared the pharmacokinetic assessments of standard, immediate-release buprenorphine (Bup IR) and a sustained-release buprenorphine formulation (Bup SR Lab) in male C57BL/6J mice, a mouse strain commonly used in biomedical research. We postulated that the administration of Bup SR Lab would achieve a more persistent blood drug concentration (>1 ng/mL) compared with single-dose Bup IR. The study assumed a blood buprenorphine concentration of 1 ng/mL as the minimum that may result in adequate analgesia, as previously reported. The 7 experimental groups included Bup IR (0.03, 0.05, 0.1, and 2 mg/kg), Bup SR Lab (0.3 and 1.2 mg/kg), and saline placebo (0.7 mL/100 g). Blood sampling occurred at 0.5, 1, 3, 6, 12, 24, 48, and 72 h for evaluation by using a forensic ELISA. Bup IR at 0.03 and 0.05 mg/kg and Bup SR Lab at 0.3 mg/kg failed to obtain maximal blood concentrations (Cmax) above 1 ng/mL. All other doses (0.1 and 2 mg/kg Bup IR and 1.2 mg/kg Bup SR Lab) reached a Cmax above 1 ng/mL within 3 h after injection. In addition, 1.2 mg/kg Bup SR Lab and 2 mg/kg Bup IR provided blood concentrations above 1 ng/mL for up to 12 h, and 0.1 mg/kg Bup IR achieved this criterion for as long as 3 h. In conclusion, Bup SR Lab at 1.2 mg/kg and Bup IR at 0.1 or 2.0 mg/kg achieve or surpass the published threshold for adequate analgesia in mice. PMID:25199095

Clark, Tannia S; Clark, David D; Jr, Robert F Hoyt

2014-01-01

178

Environmental assessment of nutrient recycling from biological pig slurry treatment--impact of fertilizer substitution and field emissions.  

PubMed

Pig slurry treatment is an important means in reducing nitrogen loads applied to farmland. Solid phase separation prior to biological treatment further allows for recovering phosphorus with the solid phase. The organic residues from the pig slurry treatment can be applied as organic fertilizers to farmland replacing mineral fertilizers. The environmental impacts of nutrient recycling from aerobic, biological pig slurry treatment were evaluated applying the life cycle assessment (LCA) methodology. LCA results revealed that direct field emissions from organic fertilizer application and the amount of avoided mineral fertilizers dominated the environmental impacts. A modified plant available nitrogen calculation (PAN) was introduced taking into account calculated nitrogen emissions from organic fertilizer application. Additionally, an equation for calculating the quantity of avoided mineral fertilizers based on the modified PAN calculation was proposed, which accounted for nitrogen emissions from mineral fertilizer application. PMID:24821206

Brockmann, Doris; Hanhoun, Mary; Négri, Ophélie; Hélias, Arnaud

2014-07-01

179

Rifampin reduces oral morphine absorption: a case of transdermal buprenorphine selection based on morphine pharmacokinetics.  

PubMed

A 51-year-old male was referred to the Stratton Veterans Affairs Medical Center Pain Service after hospital admission for endocarditis with a history of heroin use and chronic low back pain. During his hospital stay he experienced a reduction in his serum morphine level ostensibly as a result of concomitant rifampin administration. We hypothesize that diminished absorption was from rifampin-mediated intestinal P-glycoprotein induction, ultimately decreasing serum free morphine and metabolites. The case became more complex in an attempt to balance managed pain, history of substance abuse, completion of antibiotic therapy, and a reasonable pain regimen upon discharge. Ultimately, the patient was titrated onto a buprenorphine transdermal patch, the initiation of which was based on serum free morphine and an extrapolated oral morphine dose by calculation. PMID:23216174

Fudin, Jeffrey; Fontenelle, Dania Vanesta; Payne, Annette

2012-12-01

180

Relative efficacy of cash versus vouchers in engaging opioid substitution treatment clients in survey-based research.  

PubMed

Concerns that cash payments to people who inject drugs (PWID) to reimburse research participation will facilitate illicit drug purchases have led some ethical authorities to mandate department store/supermarket vouchers as research reimbursement. To examine the relative efficacy of the two forms of reimbursement in engaging PWID in research, clients of two public opioid substitution therapy clinics were invited to participate in a 20-30 min, anonymous and confidential interview about alcohol consumption on two separate occasions, 4 months apart. Under the crossover design, at Time 1, clients of Clinic 1 were offered $A20 cash as reimbursement, while clients of Clinic 2 were offered an $A20 voucher; at Time 2, the form of reimbursement was reversed. Using clinic records to determine the denominator (number of clients dosed), we found that compared with clients offered a voucher, a significantly higher proportion of clients who were offered cash participated in the survey (58% (139/241) vs 74% (186/252); ?(2)=14.27; p=0.0002). At first participation, respondents most commonly reported planning to purchase food/drinks/groceries (68%), cigarettes (21%) and transport/fuel (11%) with their payments, with those reimbursed in cash more likely to report planning to fund transport/fuel (19% vs 1%; p<.01) and less likely to report planning to purchase food/drinks/groceries (62% vs 76%; p=0.02). Just three out of 155 cash participants reported planning to purchase illicit drugs with their payment. Results demonstrate that modest cash payments enhanced recruitment of this group, an important consideration given the challenges of delineating the parameters of a population defined by illegal activity, seemingly without promoting excessive additional drug use. PMID:23236087

Topp, Libby; Islam, M Mofizul; Day, Carolyn Ann

2013-04-01

181

Effect of Heat Treatments on the Structural and Magnetic Properties of La-Co Substituted Strontium Ferrite Films  

NASA Astrophysics Data System (ADS)

A sputter-deposited strontium ferrite film with perpendicular anisotropy has been developed. The film, composed of La0.33Sr0.67Co0.25Fe11.75O19, has been fabricated directly on quartz glass substrates by radio frequency magnetron sputtering with various heat treatments. The structural and magnetic property dependence of those films on heat treatments has also been studied. The optimized condition is the heat treatment of in situ heating at 400°C and post-annealing at 850°C-900°C. When post-annealing temperature exceeds 900°C, parasitic phases of ?-Fe2O3 and LaFeO3 appear and gradually increase; meanwhile, the magneto plumbite phase gradually decreases. High c-axis perpendicularly oriented films with the coercivity (4148 Oe), remanence squareness ratio (0.89) and perpendicular magnetic anisotropy energy density (1.65 × 106 erg/cm3) are achieved, which is attributed to the single magneto plumbite phase with compact platelet grains and almost complete (0 0 l) texture of the c-axis normal to the film plane.

Hui, Yajuan; Cheng, Weiming; Lin, Gengqi; Miao, Xiangshui

2014-09-01

182

Effects of concurrent saccharin availability and buprenorphine pretreatment on demand for smoked cocaine base in rhesus monkeys  

Microsoft Academic Search

The effects of saccharin and the opioid partial agonist buprenorphine on cocaine base smoking were evaluated in five male rhesus monkeys. Monkeys completed a sequence of responding consisting of lever-press responses maintained under a fixed-ratio (FR) schedule followed by inhalation responses (FR5) on a smoking spout to gain access to a single delivery of volatilized cocaine base (1.0 mg\\/kg per

Sandra D. Comer; Vincent R. Hunt; Marilyn E. Carroll

1994-01-01

183

Effect of partial substitution of invert sugar for sucrose in combination with Duraphat treatment on caries development in preschool children: the Malmö Study.  

PubMed

The aim was to study the effect of substitution of invert sugar for sucrose, in combination with fluoride varnish (Duraphat) treatment twice a year, on caries development in preschool children. One hundred and eighty-seven 4-years-olds were divided randomly into four sugar groups: (1) sucrose (S), (2) sucrose-Duraphat (SD), (3) invert sugar (I), and (4) invert sugar-Duraphat (ID). All families were asked to buy beverages, biscuits, breakfast cereals, marmalade, ice cream, jam, ketchup, sweets and table sugar, totally 32 different food items, sweetened with invert sugar or sucrose. The substitution was, thus, restricted to a number of sugar-rich between-meal products. The study was carried out double-blind for 2 years. The children of those parents who did not want to participate in the sugar groups were divided randomly into one of the following two groups: (5) Duraphat (D), and control (C). Because of lack of cooperation, only 114 of the 187 children (61%) were considered to have completed the study. The mean caries increment, including initial lesions, was 3.86 dmfs in the combined groups S and SD (n = 63) and 3.10 dmfs in the combined groups I and ID (n = 51) during the 2 years (p = 0.34). The corresponding values for the 2nd year only were 1.84 and 0.67 dmfs, respectively (p = 0.09). The mean caries increment was 2.86 dmfs in group D (n = 113) and 4.10 dmfs (p = 0.08) in group C (n = 93). If initial caries lesions were excluded from the index, the difference between groups D and C was significant (p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1913770

Frostell, G; Birkhed, D; Edwardsson, S; Goldberg, P; Petersson, L G; Priwe, C; Winholt, A S

1991-01-01

184

Substitute Teachers  

NSDL National Science Digital Library

Our lives are ones of uncertainty and surprise, yin and yang existences. Some things we can control and others we are powerless to command, even with the best intentions. Teachers are not exempt from emergencies, jury duty, and illness. Luckily, most schools plan for such incidents by having willing substitutes on hand. Teachers need to follow the Scout's motto to "be prepared" and keep the classroom running smoothly and efficiently for students and subs.

Swango, C. J.; Steward, Sally B.

2003-01-01

185

2011 Media Reports of Buprenorphine Diversion and Misuse U n i v e r s i t y o f M a r y l a n d , C o l l e g e P a r k  

E-print Network

of buprenorphine diversion/trafficking & buprenorphine in jail trafficking ("Drug Meant to Treat Heroin Users Being ("When Children's Scribbles Hide a Prison Drug," New York Times) 5/26/11 WV trafficking Firefighter in Operation Postage Stamp," States News Service) 3/16/11 NY trafficking Drug ring sold Suboxone and Lortab

Milchberg, Howard

186

Differential involvement of P-glycoprotein (ABCB1) in permeability, tissue distribution, and antinociceptive activity of methadone, buprenorphine, and diprenorphine: in vitro and in vivo evaluation.  

PubMed

Conclusions based on either in vitro or in vivo approach to evaluate the P-gp affinity status of opioids may be misleading. For example, in vitro studies indicated that fentanyl is a P-gp inhibitor while in vivo studies indicated that it is a P-gp substrate. Quite the opposite was evident for meperidine. The objective of this study was to evaluate the P-gp affinity status of methadone, buprenorphine and diprenorphine to predict P-gp-mediated drug-drug interactions and to determine a better candidate for management of opioid dependence. Two in vitro (P-gp ATPase and monolayer efflux) assays and two in vivo (tissue distribution and antinociceptive evaluation in mdr1a/b (-/-) mice) assays were used. Methadone stimulated the P-gp ATPase activity only at higher concentrations, while verapamil and GF120918 inhibited its efflux (p < 0.05). The brain distribution and antinociceptive activity of methadone were enhanced (p < 0.05) in P-gp knockout mice. Conversely, buprenorphine and diprenorphine were negative in all assays. P-gp can affect the PK/PD of methadone, but not buprenorphine or diprenorphine. Our report is in favor of buprenorphine over methadone for management of opioid dependence. Buprenorphine most likely is not a P-gp substrate and concerns regarding P-gp-mediated drug-drug interaction are not expected. PMID:19370547

Hassan, Hazem E; Myers, Alan L; Coop, Andrew; Eddington, Natalie D

2009-12-01

187

Faculty Development in Small-Group Teaching Skills Associated with a Training Course on Office-Based Treatment of Opioid Dependence  

ERIC Educational Resources Information Center

The Drug Addiction Treatment Act of 2000 (DATA-2000) allows qualified physicians to treat opioid-dependent patients with schedule III-V medications, such as buprenorphine, in practices separate from licensed, accredited opioid treatment programs. Physicians may attain this qualification by completing 8-hours of training in treating opioid…

Wong, Jeffrey G.; Holmboe, Eric S.; Becker, William C.; Fiellin, David A.; Jara, Gail B.; Martin, Judith

2005-01-01

188

Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model: a double-blind, randomized, placebo-controlled, five-arm crossover study  

PubMed Central

Purpose Opioid therapy is associated with the development of tolerance and paradoxically increased sensitivity to pain. It has been suggested that buprenorphine is associated with a higher antihyperalgesia/analgesia ratio than ?-opioid receptor agonists. The primary outcome of this study was therefore to investigate relative differences in antihyperalgesia and analgesia effects between morphine and buprenorphine in an inflammatory pain model in volunteers. The secondary outcome was to examine the relationship between pain sensitivity and opioid-induced effects on analgesia, antihyperalgesia, and descending pain modulation. Subjects and methods Twenty-eight healthy subjects were included. The study was a double-blind, randomized, placebo-controlled, five-arm crossover study with a multimodal (electrical, mechanical, and thermal stimuli) testing technique. After baseline assessments, intravenous infusions of morphine (10/20 mg), buprenorphine (0.3/0.6 mg), or placebo (normal saline) were administered over a 210-minute period, during which a cold pressor test, heat injury (47°C, 7 minutes, 12.5 cm2), and the first postburn assessment were done. After completion of the drug infusions, two additional postburn assessments were done. The subjects were monitored during each 8-hour session by an anesthesiologist. Results For nearly all tested variables, significant dose-dependent analgesic effects were demonstrated. The median antihyperalgesia/analgesia ratio (secondary hyperalgesia/heat injury relative to placebo) for low-dose morphine was 0.01 (interquartile range: ?6.2; 9.9), 0.00 (?2.4; 2.1) for high-dose morphine, 0.03 (?1.8; 2.1) for low-dose buprenorphine, and 0.00 (?3.2; 1.1) for high-dose buprenorphine (P > 0.466). There were no significant differences in opioid responses between high and low pain-sensitive subjects (P > 0.286). High-dose buprenorphine, compared to placebo, was associated with a significantly enhanced action of the descending inhibitory pain control system (P = 0.004). Conclusion The present study, using multimodal testing technique, could not demonstrate any significant differences between morphine and buprenorphine in the profiles of antihyperalgesia and analgesia. Only high-dose buprenorphine was associated with a significant effect on the descending inhibitory pain control system. PMID:23359655

Ravn, Pernille; Secher, Erik L; Skram, Ulrik; Therkildsen, Trine; Christrup, Lona L; Werner, Mads U

2013-01-01

189

Clorazepate affects cell surface regulation of delta and kappa opioid receptors, thereby altering buprenorphine-induced adaptation in the rat brain.  

PubMed

Concomitant abuse of buprenorphine (BPN) and benzodiazepines (BZD) may relate to a pharmacodynamic interaction between the two. The objective of the present work was to investigate the acute and chronic effects of clorazepate (CRZ) alone or in combination with BPN on selective kappa opiate tritiated ligand [3H]-U69 593 and delta opiate radioligand [3H]-deltorphine II binding in the rat brain. Bmax (maximal receptor density) and Kd (the dissociation constant) were directly determined at different brain regions of interest (ROI) selected for high densities of kappa and/or delta receptors in rats treated with BPN and/or CRZ. The agents were administered either once or for 21 consecutive days. Differences in Bmax and Kd (for both specific ligands) were related to drug treatment and receptor location. Globally, single BPN administration induced no changes in kappa or delta opiate receptor binding, whereas repeated BPN administration up-regulated kappa receptor density and decreased delta affinity. At the kappa receptor level, repeated administration of CRZ acted only on Kd, whereas the delta receptor was up-regulated. Repeated addition of CRZ to BPN had no effect on kappa receptor Bmax versus chronic controls. By significantly decreasing Bmax, CRZ nullified the effect of chronic BPN on the kappa receptor. The modifications were strongest in the nucleus accumbens, where both types of receptor occur. Treatments had region-selective effects in some brain areas, such as the amygdala, periaqueductal gray matter, hypothalamus and caudate putamen. Increased mu and delta receptor densities would be expected to provide reinforcement by enhancing reward, and impairment of kappa receptor availability would be expected to decrease aversion. The effects described are likely to influence addictive behavior among people abusing BZD and BPN. PMID:16269137

Quentin, Thomas; Debruyne, Daniele; Lelong-Boulouard, Veronique; Poisnel, Geraldine; Barre, Louisa; Coquerel, Antoine

2005-11-23

190

Investigation of Cross-Species Translatability of Pharmacological MRI in Awake Nonhuman Primate - A Buprenorphine Challenge Study  

PubMed Central

Background Pharmacological MRI (phMRI) is a neuroimaging technique where drug-induced hemodynamic responses can represent a pharmacodynamic biomarker to delineate underlying biological consequences of drug actions. In most preclinical studies, animals are anesthetized during image acquisition to minimize movement. However, it has been demonstrated anesthesia could attenuate basal neuronal activity, which can confound interpretation of drug-induced brain activation patterns. Significant efforts have been made to establish awake imaging in rodents and nonhuman primates (NHP). Whilst various platforms have been developed for imaging awake NHP, comparison and validation of phMRI data as translational biomarkers across species remain to be explored. Methodology We have established an awake NHP imaging model that encompasses comprehensive acclimation procedures with a dedicated animal restrainer. Using a cerebral blood volume (CBV)-based phMRI approach, we have determined differential responses of brain activation elicited by the systemic administration of buprenorphine (0.03 mg/kg i.v.), a partial µ-opioid receptor agonist, in the same animal under awake and anesthetized conditions. Additionally, region-of-interest analyses were performed to determine regional drug-induced CBV time-course data and corresponding area-under-curve (AUC) values from brain areas with high density of µ-opioid receptors. Principal Findings In awake NHPs, group-level analyses revealed buprenorphine significantly activated brain regions including, thalamus, striatum, frontal and cingulate cortices (paired t-test, versus saline vehicle, p<0.05, n?=?4). This observation is strikingly consistent with µ-opioid receptor distribution depicted by [6-O-[11C]methyl]buprenorphine ([11C]BPN) positron emission tomography imaging study in baboons. Furthermore, our findings are consistent with previous buprenorphine phMRI studies in humans and conscious rats which collectively demonstrate the cross-species translatability of awake imaging. Conversely, no significant change in activated brain regions was found in the same animals imaged under the anesthetized condition. Conclusions Our data highlight the utility and importance of awake NHP imaging as a translational imaging biomarker for drug research. PMID:25337714

Seah, Stephanie; Asad, Abu Bakar Ali; Baumgartner, Richard; Feng, Dai; Williams, Donald S.; Manigbas, Elaine; Beaver, John D.; Reese, Torsten; Henry, Brian; Evelhoch, Jeffrey L.; Chin, Chih-Liang

2014-01-01

191

Attempted suicide among entrants to three treatment modalities for heroin dependence in the Australian Treatment Outcome Study (ATOS): prevalence and risk factors  

Microsoft Academic Search

Aims: To determine the lifetime and recent histories of attempted suicide among entrants to treatment for heroin dependence in three treatment modalities and a non-treatment comparison group; and to ascertain factors associated with a recent history of attempted suicide. Design: Cross-sectional structured interview. Setting: Sydney, Australia. Participants: Six hundred and fifteen current heroin users: 201 entering methadone\\/buprenorphine maintenance (MT), 201

Shane Darke; Joanne Ross; Michael Lynskey; Maree Teesson

2004-01-01

192

Buprenorphine Medication versus Voucher Contingencies in Promoting Abstinence from Opioids and Cocaine  

PubMed Central

This study compared the relative efficacy of two contingency management (CM) interventions versus standard care. During a 12-week intervention, opioid dependent participants (N = 120) were maintained on thrice-a-week (M, W, F) buprenorphine plus therapist and computer-based counseling. They were randomized to receive: (a) medication contingencies (MC= thrice weekly dosing schedule vs. daily attendance and single-day 50% dose reduction imposed upon submission of an opioid and/or cocaine positive urine sample); (b) voucher contingency (VC=escalating schedule for opioid and/or cocaine negative samples with reset for drug-positive samples); or (c) standard care (SC), with no programmed consequences for urinalysis results. Voucher reinforcement resulted in better 12-week retention (85%) compared to contingent medication (58%; p=0.009), but neither differed from standard care (76% retained). The groups submitted a similar overall percentage of opioid and cocaine-free urines (MC = 79%, VC = 76%, SC = 69%). After adjusting for baseline differences in employment, the medication contingency group achieved 1.5 more continuous weeks of combined opioid/cocaine abstinence than standard care (p=0.030), while the voucher group had 2 more total weeks of abstinence than standard care (p=0.048). Drug use results suggest that the two interventions were both efficacious, with effects seen primarily in opioid rather than cocaine test results. Findings should be interpreted in light of the greater attrition associated with medication-based contingencies versus the greater monetary costs of voucher-based contingencies. PMID:19653788

Chopra, Mohit P.; Landes, Reid D.; Gatchalian, Kirstin M; Jackson, Lisa C.; Buchhalter, August R; Stitzer, Maxine L.; Marsch, Lisa A.; Bickel, Warren K.

2010-01-01

193

Skin Substitutes and Wound Healing  

Microsoft Academic Search

Medical science has vastly improved on the means and methods available for the treatment of wounds in the clinic. The production and use of various types of skin substitutes has led to dramatic improvements in the odds of survival for severely burned patients, but they have also shown promise for many other applications, including cases involving chronic wounds that are

F. A. Auger; D. Lacroix; L. Germain

2009-01-01

194

Antinociceptive effects of sustained-release buprenorphine in a model of incisional pain in rats (Rattus norvegicus).  

PubMed

Effective management of postoperative pain is an essential component of the care and welfare of laboratory animals. A sustained-release formulation of buprenorphine (Bup-SR) has recently been introduced to the veterinary market and has been reported to provide analgesia for as long as 72 h. Using evoked mechanical and thermal hypersensitivity tests, we here evaluated the antinociceptive effects of Bup-SR in a model of incisional pain in rats. Paw withdrawal responses were obtained before and 1 through 4 d after surgery. Rats are assigned to receive Bup-SR (0.3, 1.2, or 4.5 mg/kg SC once) or buprenorphine HCl (Bup HCl, 0.05 mg/kg SC twice daily for 3 d). Responses to mechanical and thermal stimuli in the 1.2 and 4.5 Bup-SR groups did not differ from those of rats in the Bup HCl group. Thermal latency on day 3 in rats that received 0.3 mg/kg Bup-SR was significantly different from baseline, indicating that this dose effectively decreased thermal hypersensitivity for at least 48 h. Marked sedation occurred in rats in the 4.5 Bup-SR group. Our findings indicate that Bup-SR at 0.3 or 1.2 mg/kg SC is effective in minimizing hypersensitivity with minimal sedation for at least 48 h (thermal hypersensitivity) and 72 h, respectively, in the incisional pain model in rats. PMID:24602547

Chum, Helen H; Jampachairsri, Katechan; McKeon, Gabriel P; Yeomans, David C; Pacharinsak, Cholawat; Felt, Stephen A

2014-03-01

195

Antinociceptive Effects of Sustained-Release Buprenorphine in a Model of Incisional Pain in Rats (Rattus norvegicus)  

PubMed Central

Effective management of postoperative pain is an essential component of the care and welfare of laboratory animals. A sustained-release formulation of buprenorphine (Bup-SR) has recently been introduced to the veterinary market and has been reported to provide analgesia for as long as 72 h. Using evoked mechanical and thermal hypersensitivity tests, we here evaluated the antinociceptive effects of Bup-SR in a model of incisional pain in rats. Paw withdrawal responses were obtained before and 1 through 4 d after surgery. Rats are assigned to receive Bup-SR (0.3, 1.2, or 4.5 mg/kg SC once) or buprenorphine HCl (Bup HCl, 0.05 mg/kg SC twice daily for 3 d). Responses to mechanical and thermal stimuli in the 1.2 and 4.5 Bup-SR groups did not differ from those of rats in the Bup HCl group. Thermal latency on day 3 in rats that received 0.3 mg/kg Bup-SR was significantly different from baseline, indicating that this dose effectively decreased thermal hypersensitivity for at least 48 h. Marked sedation occurred in rats in the 4.5 Bup-SR group. Our findings indicate that Bup-SR at 0.3 or 1.2 mg/kg SC is effective in minimizing hypersensitivity with minimal sedation for at least 48 h (thermal hypersensitivity) and 72 h, respectively, in the incisional pain model in rats. PMID:24602547

Chum, Helen H; Jampachairsri, Katechan; McKeon, Gabriel P; Yeomans, David C; Pacharinsak, Cholawat; Felt, Stephen A

2014-01-01

196

Novel pharmacotherapeutic strategies for treatment of opioid-induced neonatal abstinence syndrome  

PubMed Central

Summary The non-medical use of prescription drugs, in general, and opioids, in particular, is a national epidemic, resulting in enormous addiction rates, healthcare expenditures, and overdose deaths. Prescription opioids are overly prescribed, illegally trafficked, and frequently abused, all of which have created a new opioid addiction pathway, adding to the number of opioid-dependent newborns requiring treatment for neonatal abstinence syndrome (NAS), and contributing to challenges in effective care in maternal and fetal/neonatal (M-F/N) medicine. The standard of care for illicit or prescription opioid dependence during pregnancy is opioid agonist (methadone or buprenorphine) substitution therapy, which are also frequently abused. The next generation of pharmacotherapies for the treatment of illicit or prescription opioid addiction in the M-F/N interactional dyad must take into consideration the interplay between genetic, epigenetic, and environmental factors. Addiction to illicit drugs during pregnancy presents unique challenges to effectively treat the mother, and the developing fetus and infant after delivery. New pharmacotherapies should be safe to the developing fetus, effective in treating the physical and psychological consequences of addiction in the mother, and reduce the incidence and severity of NAS in the infant after birth. More pharmacotherapeutic options should be available to the physician such that a more individualized rather than a one-drug/strategy-fits-all approach can be used. A myriad of new and exciting pharmacotherapeutic strategies for the treatment of opioid dependence and addiction are on the horizon. This review focuses on such three strategies: (i) pharmacotherapeutic targeting of the serotoninergic system; (ii) mixed opioid immunotherapeutics (vaccines); (iii) pharmacogenomics as a therapeutic strategy to insure personalized care. We review and discuss how these strategies may offer additional treatment modalities for the treatment of M-F/N during pregnancy and the treatment of the infant after birth. PMID:23059064

McLemore, Gabrielle L.; Lewis, Tamorah; Jones, Catherine H.; Gauda, Estelle B.

2014-01-01

197

Novel pharmacotherapeutic strategies for treatment of opioid-induced neonatal abstinence syndrome.  

PubMed

The non-medical use of prescription drugs, in general, and opioids, in particular, is a national epidemic, resulting in enormous addiction rates, healthcare expenditures, and overdose deaths. Prescription opioids are overly prescribed, illegally trafficked, and frequently abused, all of which have created a new opioid addiction pathway, adding to the number of opioid-dependent newborns requiring treatment for neonatal abstinence syndrome (NAS), and contributing to challenges in effective care in maternal and fetal/neonatal (M-F/N) medicine. The standard of care for illicit or prescription opioid dependence during pregnancy is opioid agonist (methadone or buprenorphine) substitution therapy, which are also frequently abused. The next generation of pharmacotherapies for the treatment of illicit or prescription opioid addiction in the M-F/N interactional dyad must take into consideration the interplay between genetic, epigenetic, and environmental factors. Addiction to illicit drugs during pregnancy presents unique challenges to effectively treat the mother, and the developing fetus and infant after delivery. New pharmacotherapies should be safe to the developing fetus, effective in treating the physical and psychological consequences of addiction in the mother, and reduce the incidence and severity of NAS in the infant after birth. More pharmacotherapeutic options should be available to the physician such that a more individualized rather than a one-drug/strategy-fits-all approach can be used. A myriad of new and exciting pharmacotherapeutic strategies for the treatment of opioid dependence and addiction are on the horizon. This review focuses on such three strategies: (i) pharmacotherapeutic targeting of the serotonergic system; (ii) mixed opioid immunotherapeutics (vaccines); (iii) pharmacogenomics as a therapeutic strategy to insure personalized care. We review and discuss how these strategies may offer additional treatment modalities for the treatment of M-F/N during pregnancy and the treatment of the infant after birth. PMID:23059064

McLemore, Gabrielle L; Lewis, Tamorah; Jones, Catherine H; Gauda, Estelle B

2013-02-01

198

The effect of statutory limitations on the authority of substitute decision makers on the care of patients in the intensive care unit: case examples and review of state laws affecting withdrawing or withholding life-sustaining treatment.  

PubMed

While the ethics and critical care literature is replete with discussion of medical futility and the ethics of end-of-life care decisions in the intensive care unit, little attention is paid to the effect of statutory limitations on the authority of substitute decision makers during the course of treatment of patients in the critical care setting. In many jurisdictions, a clear distinction is made between the authority of a health care power of attorney, who is legally designated by a competent adult to make decisions regarding withholding or withdrawing life-sustaining treatment, and of next-of-kin, who are limited in this regard. However, next-of-kin are often relied upon to consent to necessary procedures to advance a patient's medical care. When conflicts arise between critical care physicians and family members regarding projected patient outcome and functional status, these statutory limitations on decision-making authority by next of kin can cause paralysis in the medical care of severely ill patients, leading to practical and ethical impasses. In this article, we will provide case examples of how statutory limitations on substitute decision making authority for next of kin can impede the care of patients. We will also review the varying jurisdictional limitations on the authority of substitute decision makers and explore their implications for patient care in the critical care setting. Finally, we will review possible ethical and legal solutions to resolve these impasses. PMID:22257784

Venkat, Arvind; Becker, Julianna

2014-01-01

199

Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone).  

PubMed

SUMMARY OF CONSENSUS: 1. The use of opioids in cancer pain: The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities--including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia--and patient functional status need to be taken carefully into account when addressing pain in the elderly. World Health Organization step III opioids are the mainstay of pain treatment for cancer patients and morphine has been the most commonly used for decades. In general, high level evidence data (Ib or IIb) exist, although many studies have included only few patients. Based on these studies, all opioids are considered effective in cancer pain management (although parts of cancer pain are not or only partially opioid sensitive), but no well-designed specific studies in the elderly cancer patient are available. Of the 2 opioids that are available in transdermal formulation--fentanyl and buprenorphine--fentanyl is the most investigated, but based on the published data both seem to be effective, with low toxicity and good tolerability profiles, especially at low doses. 2. The use of opioids in noncancer-related pain: Evidence is growing that opioids are efficacious in noncancer pain (treatment data mostly level Ib or IIb), but need individual dose titration and consideration of the respective tolerability profiles. Again no specific studies in the elderly have been performed, but it can be concluded that opioids have shown efficacy in noncancer pain, which is often due to diseases typical for an elderly population. When it is not clear which drugs and which regimes are superior in terms of maintaining analgesic efficacy, the appropriate drug should be chosen based on safety and tolerability considerations. Evidence-based medicine, which has been incorporated into best clinical practice guidelines, should serve as a foundation for the decision-making processes in patient care; however, in practice, the art of medicine is realized when we individualize care to the patient. This strikes a balance between the evidence-based medicine and anecdotal experience. Factual recommendations and expert opinion both have a value when applying guidelines in clinical practice. 3. The use of opioids in neuropathic pain: The role of opioids in neuropathic pain has been under debate in the

Pergolizzi, Joseph; Böger, Rainer H; Budd, Keith; Dahan, Albert; Erdine, Serdar; Hans, Guy; Kress, Hans-Georg; Langford, Richard; Likar, Rudolf; Raffa, Robert B; Sacerdote, Paola

2008-01-01

200

Opioid use in Albuquerque, New Mexico: a needs assessment of recent changes and treatment availability  

PubMed Central

Background New Mexico has consistently high rates of drug-induced deaths, and opioid-related treatment admissions have been increasing over the last two decades. Youth in New Mexico are at particular risk: they report higher rates of nonmedical prescription opioid use than those over age 25, are more likely than their national counterparts to have tried heroin, and represent an increasing proportion of heroin overdoses. Methods Commissioned by the City of Albuquerque, semistructured interviews were conducted from April to June of 2011 with 24 substance use treatment agencies and eight key stakeholders in Albuquerque to identify recent changes in the treatment-seeking population and gaps in treatment availability. Themes were derived using template analysis and data were analyzed using NVivo 9 software. Results Respondents reported a noticeable increase in youth seeking treatment for opioid use and a general increase in nonmedical prescription opioid use. Most noted difficulties with finding buprenorphine providers and a lack of youth services. Additionally, stigma, limited interagency communication and referral, barriers to prescribing buprenorphine, and a lack of funding were noted as preventing opioid users from quickly accessing effective treatment. Conclusions Recommendations for addressing these issues include developing youth-specific treatment programs, raising awareness about opioid use among youth, increasing the availability of buprenorphine through provider incentives and education, developing a resource guide for individuals seeking treatment in Albuquerque, and prioritizing interagency communication and referrals. PMID:24942534

2014-01-01

201

The multi-site prescription opioid addiction treatment study: 18-month outcomes.  

PubMed

Despite the high prevalence of prescription opioid dependence in the U.S., little is known about the course of this disorder and long-term response to treatment. We therefore examined 18-month post-randomization outcomes of participants in the Prescription Opioid Addiction Treatment Study, a multi-site, randomized controlled trial examining varying durations of buprenorphine-naloxone treatment and different intensities of counseling for prescription opioid dependence. Thus the current follow-up study provides a unique contribution to the field by reporting longer-term outcomes of a well-characterized population of treatment-seeking prescription opioid dependent patients. Participants from the treatment trial (N=252/653) completed an 18-month follow-up telephone assessment. Multivariable analyses examined associations between participant characteristics and key indicators of month-18 status: opioid abstinence, DSM-IV opioid dependence, and opioid agonist treatment. Overall, participants showed improvement from baseline to month 18: 49.6% were abstinent in the previous 30days, with only 16.3% opioid-dependent. Some participants, however, had initiated past-year heroin use (n=9) or opioid injection (n=17). Most participants (65.9%) engaged in substance use disorder treatment during the past year, most commonly opioid agonist therapy (48.8%). Of particular interest in this population, multivariable analysis showed that greater pain severity at baseline was associated with opioid dependence at 18months. In conclusion, although opioid use outcomes during the treatment trial were poor immediately following a buprenorphine-naloxone taper compared to those during 12weeks of buprenorphine-naloxone stabilization, opioid use outcomes at 18-month follow-up showed substantial improvement over baseline and were comparable to the rate of successful outcomes during buprenorphine-naloxone stabilization in the treatment trial. PMID:25189089

Potter, Jennifer Sharpe; Dreifuss, Jessica A; Marino, Elise N; Provost, Scott E; Dodd, Dorian R; Rice, Lindsay S; Fitzmaurice, Garrett M; Griffin, Margaret L; Weiss, Roger D

2015-01-01

202

Substitute Addiction: A Concern for Researchers and Practitioners  

ERIC Educational Resources Information Center

An understanding of the role of substitute addictions remains unclear. This article examines the range and possible reward functions of substitute addictions. We suggest that prevention education and treatment need to take into account substitute addictions as an influential aspect of recovery. Research is needed to better understand the…

Sussman, Steve; Black, David S.

2008-01-01

203

A comparative study of the use of bioactive glass S53P4 and antibiotic-loaded calcium-based bone substitutes in the treatment of chronic osteomyelitis: a retrospective comparative study.  

PubMed

The treatment of chronic osteomyelitis often includes surgical debridement and filling the resultant void with antibiotic-loaded polymethylmethacrylate cement, bone grafts or bone substitutes. Recently, the use of bioactive glass to treat bone defects in infections has been reported in a limited series of patients. However, no direct comparison between this biomaterial and antibiotic-loaded bone substitute has been performed. In this retrospective study, we compared the safety and efficacy of surgical debridement and local application of the bioactive glass S53P4 in a series of 27 patients affected by chronic osteomyelitis of the long bones (Group A) with two other series, treated respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were also used in all groups. After comparable periods of follow-up, the control of infection was similar in the three groups. In particular, 25 out of 27 (92.6%) patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a reduced wound complication rate. Our results show that patients treated with a bioactive glass without local antibiotics achieved similar eradication of infection and less drainage than those treated with two different antibiotic-loaded calcium-based bone substitutes. PMID:24891588

Romanò, C L; Logoluso, N; Meani, E; Romanò, D; De Vecchi, E; Vassena, C; Drago, L

2014-06-01

204

Execution of control among 'non-compliant', imprisoned individuals in opioid maintenance treatment.  

PubMed

Strict control routines of prescribed opiate intake in opioid maintenance treatment, OMT, are used to reduce the risk of diversion and non-prescribed methadone and buprenorphine use. While maintaining a focus on aspects of control, this article explores motivations for and practices of methadone and buprenorphine use, both inside and outside of prison and among imprisoned individuals in OMT. The participants in this qualitative study were subjected to tight external control regimes in their opioid maintenance schemes in prison, as they were prior to imprisonment due to varying degrees of 'non-compliance'. We nevertheless found them to exhibit a considerable amount of self-control, self-regulation and/or self-initiation of external control. Among the participants, a ceaseless surveillance of processes associated with methadone and buprenorphine use throughout diverse situations, relations and contexts was encountered. We conclude that, in opioid maintenance treatment, some individuals might know what particular configurations of internal and external control they need in order to achieve their own treatment goals. The drug users' capacities for execution of control, as well as their delegations of control to others, may be seen as resources throughout the course of treatment. PMID:24594221

Havnes, Ingrid Amalia; Clausen, Thomas; Middelthon, Anne-Lise

2014-05-01

205

A combined liquid three-phase micro-extraction and differential pulse voltammetric method for preconcentration and detection of ultra-trace amounts of buprenorphine using a modified pencil electrode.  

PubMed

A combination of polytetrafluorethylene membrane-based liquid three-phase micro-extraction and voltammetry was used for the micro-separation and determination of buprenorphine. Type of the organic solvent used, pH levels of the donor and acceptor phases, salt concentration, extraction time, stirring rate, and electrochemical parameters as the essential factors affecting the liquid three-phase micro-extraction of buprenorphine were investigated. Differential pulse voltammetry exhibited two linear dynamic ranges of 1.0-109.0 pmol L(-1) and 0.109 nmol L(-1)-0.11 µmol L(-1) of buprenorphine and the detection limit was found to be as low as 0.6 pmol L(-1) of buprenorphine. Also, the effects of a number of common substances potentially interfering with selectivity were studied. The results indicate that the proposed method is highly selective and sensitive for buprenorphine detection in real samples such as human urine and plasma of both drug-addict and non-addict human subjects. PMID:24148523

Ensafi, Ali A; Khoddami, Elaheh; Rezaei, B

2013-11-15

206

Review of Bone Substitutes  

PubMed Central

Bone substitutes are being increasingly used in craniofacial surgery and craniomaxillofacial trauma. We will review the history of the biomaterials and describe the ideal characteristics of bone substitutes, with a specific emphasis on craniofacial reconstruction. Some of the most commonly used bone substitutes are discussed in more depth, such as calcium phosphate and hydroxyapatite ceramics and cements, bioactive glass, and polymer products. Areas of active research and future directions include tissue engineering, with an increasing emphasis on bioactivity of the implant. PMID:22110809

Pryor, Landon S.; Gage, Earl; Langevin, Claude-Jean; Herrera, Fernando; Breithaupt, Andrew D.; Gordon, Chad R.; Afifi, Ahmed M.; Zins, James E.; Meltzer, Hal; Gosman, Amanda; Cohen, Steve R.; Holmes, Ralph

2009-01-01

207

Bone substitutes: new concepts  

Microsoft Academic Search

The filling of bone defects resulting from trauma or surgical resections of tumors requires bone grafts or bone substitutes. Bone substitute must be biocompatible, osteoconductive, and must present good mechanical properties. Among biomaterials classicaly used, calcium phosphate ceramic appear to be suitable alternatives to bone grafts. Calcium phosphate are known able to promote new bone formation on contact and have

D. Heymann; N. Passuti

1999-01-01

208

Sustainability and substitutability.  

PubMed

Developing a quantitative science of sustainability requires bridging mathematical concepts from fields contributing to sustainability science. The concept of substitutability is central to sustainability but is defined differently by different fields. Specifically, economics tends to define substitutability as a marginal concept while fields such as ecology tend to focus on limiting behaviors. We explain how to reconcile these different views. We develop a model where investments can be made in knowledge to increase the elasticity of substitution. We explore the set of sustainable and optimal trajectories for natural capital extraction and built and knowledge capital accumulation. Investments in substitutability through knowledge stock accumulation affect the value of natural capital. Results suggest that investing in the knowledge stock, which can enhance substitutability, is critical to desirable sustainable outcomes. This result is robust even when natural capital is not managed optimally. This leads us to conclude that investments in the knowledge stock are of first order importance for sustainability. PMID:24789570

Fenichel, Eli P; Zhao, Jinhua

2015-02-01

209

Synthesis of 2-(substituted anilino) 4-(substituted phenyl)thiazoles.  

PubMed

2-(Substituted anilino) 4-(substituted phenyl)thiazoles were synthesized by condensing 2-haloketones with substituted thioureas. The biological screening of some compounds indicated hypoglycemic and hyperglycemic activity. PMID:641782

Thakar, K A; Goswami, D D; Choudhari, S R

1978-04-01

210

Alcohol Use Disorders in Opioid Maintenance Therapy: Prevalence, Clinical Correlates and Treatment.  

PubMed

Maintenance therapy with methadone or buprenorphine is an established and first-line treatment for opioid dependence. Clinical studies indicate that about a third of patients in opioid maintenance therapy show increased alcohol consumption and alcohol use disorders. Comorbid alcohol use disorders have been identified as a risk factor for clinical outcome and can cause poor physical and mental health, including liver disorders, noncompliance, social deterioration and increased mortality risk. The effects of opioid maintenance therapy on alcohol consumption are controversial and no clear pattern has emerged. Most studies have not found a change in alcohol use after initiation of maintenance therapy. Methadone and buprenorphine appear to carry little risk of liver toxicity, but further research on this topic is required. Recent data indicate that brief intervention strategies may help reduce alcohol intake, but the existing evidence is still limited. This review discusses further clinical implications of alcohol use disorders in opioid dependence. © 2014 S. Karger AG, Basel. PMID:25413371

Soyka, Michael

2014-11-19

211

Presence of illicit drugs and metabolites in influents and effluents of 25 sewage water treatment plants and map of drug consumption in France.  

PubMed

Consumption of illicit drugs is a new concern for water management that must be considered not only because of the social and public health aspects but also in an environmental context in relation with the contamination of surface waters. Indeed, sewage treatment plant (STP) effluents contain drug residues that have not been eliminated since STP treatments are not completely efficient in their removal. We developed and validated an HPLC-MS/MS analytical method to assess the concentrations of 17 illicit drugs and metabolites in raw urban wastewaters: cocaine and its metabolites, amphetamine and amphetamine-likes (methamphetamine, MDMA, MDEA, MDA), opiates and opiate substitutes (methadone and buprenorphine), and THC-COOH cannabis metabolite. This method has been applied to the analysis of influent and effluent samples from 25 STPs located in France all over the country. The results allowed evaluating the drug consumption in the areas connected to the STPs and the efficiency of the treatment technology implied. We selected STPs according to their volume capacity, their treatment technologies (biofilters, activated sludges, MBR) and their geographical location. In influents, the concentrations varied between 6 ng/L for EDDP (main metabolite of methadone) and 3050 ng/L for benzoylecgonine (cocaine metabolite). Consumption maps were drawn for cocaine, MDMA, opiates, cannabis and amphetamine-like compounds. Geographical significant differences were observed and highlighted the fact that drug consumption inside a country is not homogeneous. In parallel, comparisons between STP technology processes showed differences of efficiency. More, some compounds appear very resistant to STP processes leading to the contamination of receiving water. PMID:23770552

Nefau, Thomas; Karolak, Sara; Castillo, Luis; Boireau, Véronique; Levi, Yves

2013-09-01

212

Sugar substitutes during pregnancy  

PubMed Central

Abstract Question I have a pregnant patient who regularly consumes sugar substitutes and she asked me if continuing their use would affect her pregnancy or child. What should I tell her, and are there certain options that are better for use during pregnancy? Answer Although more research is required to fully determine the effects of in utero exposure to sugar substitutes, the available data do not suggest adverse effects in pregnancy. However, it is recommended that sugar substitutes be consumed in moderate amounts, adhering to the acceptable daily intake standards set by regulatory agencies. PMID:25392440

Pope, Eliza; Koren, Gideon; Bozzo, Pina

2014-01-01

213

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.  

Code of Federal Regulations, 2010 CFR

...naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721...naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance...naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is...

2010-07-01

214

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.  

Code of Federal Regulations, 2013 CFR

...naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721...naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance...naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is...

2013-07-01

215

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.  

...naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721...naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance...naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is...

2014-07-01

216

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.  

Code of Federal Regulations, 2011 CFR

...naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721...naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance...naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is...

2011-07-01

217

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.  

Code of Federal Regulations, 2012 CFR

...naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721...naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance...naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is...

2012-07-01

218

Sugar Substitutes: Aspartame  

MedlinePLUS

... sugar substitute. It is a combination of 2 amino acids, aspartic acid and phenylalanine. It is about 220 ... bodies are unable to metabolize one of the amino acids in aspartame, phenylalanine. Benefits of aspartame Does not ...

219

Pharmacological characterization and therapeutic potential for the treatment of opioid abuse with ATPM-ET, an N-ethyl substituted aminothiazolomorphinan with ? agonist and ? agonist/antagonist activity.  

PubMed

We previously reported that the ? agonists with mixed ? activity could attenuate heroin self-administration with less potential to develop tolerance. The present study further investigated the effects of (-)-3-N-Ethylamino-thiazolo[5,4-b]-N-cyclopropylmethylmorphinan hydrochloride (ATPM-ET), a ? agonist and ? agonist/antagonist, on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP), heroin self-administration and heroin-primed reinstatement of drug-seeking behavior. We found that ATPM-ET produced a longer duration of potent antinociceptive effects with less side effect of sedation. More importantly, ATPM-ET attenuated the acquisition of morphine-induced CPP, without affecting the reinstatement of morphine CPP. Furthermore, ATPM-ET significantly inhibited heroin self-administration and the reinstatement of heroin primed drug-seeking behavior. Taken together, ATPM-ET, a novel ? agonist and ? agonist/antagonist may have utility for the treatment of drug dependence. PMID:24998879

Sun, Jian-Feng; Wang, Yu-Hua; Chai, Jing-Rui; Li, Fu-Ying; Hang, Ai; Lu, Gang; Tao, Yi-Min; Cheng, Yun; Chi, Zhi-Qiang; Neumeyer, John L; Zhang, Ao; Liu, Jing-Gen; Wang, Yu-Jun

2014-10-01

220

Convenient synthesis of amino-substituted pyranopyranones  

Microsoft Academic Search

Treatment of kojic acid and triacetic acid lactone with arylmethylenemalononitrile derivatives in the presence of piperidine in ethanol, respectively, furnished the corresponding amino-substituted new 4H,8H-pyrano[3,2-b]pyran-4-ones and 4H,5H-pyrano[4,3-b]pyran-5-ones in high yields.

Ming-Zhu Piao; Kimiaki Imafuku

1997-01-01

221

Introduction Many steels contain substitutional solutes which have a  

E-print Network

for a mixture of iron and substitutional solute atoms and X stands for interstitial solute atoms. In practiceIntroduction Many steels contain substitutional solutes which have a strong affinity for carbon or nitrogen. Such steels can be hardened by heat treatment which induces the precipitation of fine alloy

Cambridge, University of

222

Simultaneous analysis of buprenorphine, methadone, cocaine, opiates and nicotine metabolites in sweat by liquid chromatography tandem mass spectrometry.  

PubMed

A liquid chromatography tandem mass spectrometry method for buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine, ecgonine methyl ester (EME), morphine, codeine, 6-acetylmorphine, heroin, 6-acetylcodeine, cotinine, and trans-3'-hydroxycotinine quantification in sweat was developed and comprehensively validated. Sweat patches were mixed with 6 mL acetate buffer at pH 4.5, and supernatant extracted with Strata-XC-cartridges. Reverse-phase separation was achieved with a gradient mobile phase of 0.1% formic acid and acetonitrile in 15 min. Quantification was achieved by multiple reaction monitoring of two transitions per compound. The assay was a linear 1-1,000 ng/patch, except EME 5-1,000 ng/patch. Intra-, inter-day and total imprecision were <10.1%CV, analytical recovery 87.2-107.7%, extraction efficiency 35.3-160.9%, and process efficiency 25.5-91.7%. Ion suppression was detected for EME (-63.3%) and EDDP (-60.4%), and enhancement for NBUP (42.6%). Deuterated internal standards compensated for these effects. No carryover was detected, and all analytes were stable for 24 h at 22 °C, 72 h at 4 °C, and after three freeze/thaw cycles. The method was applied to weekly sweat patches from an opioid-dependent BUP-maintained pregnant woman; 75.0% of sweat patches were positive for BUP, 93.8% for cocaine, 37.5% for opiates, 6.3% for methadone and all for tobacco biomarkers. This method permits a fast and simultaneous quantification of 14 drugs and metabolites in sweat patches, with good selectivity and sensitivity. PMID:21125263

Concheiro, Marta; Shakleya, Diaa M; Huestis, Marilyn A

2011-04-01

223

The substitutability of reinforcers.  

PubMed

Substitutability is a construct borrowed from microeconomics that describes a continuum of possible interactions among the reinforcers in a given situation. Highly substitutable reinforcers, which occupy one end of the continuum, are readily traded for each other due to their functional similarity. Complementary reinforcers, at the other end of the continuum, tend to be consumed jointly in fairly rigid proportion, and therefore cannot be traded for one another except to achieve that proportion. At the center of the continuum are reinforcers that are independent with respect to each other; consumption of one has no influence on consumption of another. Psychological research and analyses in terms of substitutability employ standard operant conditioning paradigms in which humans and nonhumans choose between alternative reinforcers. The range of reinforcer interactions found in these studies is more readily accommodated and predicted when behavior-analytic models of choice consider issues of substitutability. New insights are gained into such areas as eating and drinking, electrical brain stimulation, temporal separation of choice alternatives, behavior therapy, drug use, and addictions. Moreover, the generalized matching law (Baum, 1974) gains greater explanatory power and comprehensiveness when measures of substitutability are included. PMID:16812696

Green, Leonard; Freed, Debra E

1993-07-01

224

Thrice-weekly supervised dosing with the combination buprenorphine-naloxone tablet is preferred to daily supervised dosing by opioid-dependent humans.  

PubMed

A sublingual tablet formulation of buprenorphine combining 8 mg of buprenorphine with 2 mg of naloxone is being targeted for use in settings where less than daily dosing strategies and/or prescription-based dispensing will likely be employed. This study determined patient preferences for, and clinical outcomes during, daily and 3-day per week supervised dosing schedules using the combination tablet. Twenty-four opioid-dependent subjects completing a 16-day baseline entered an outpatient triple crossover trial. Twenty-one days of daily dosing were compared to two different 21-day periods of 3-day per week supervised dosing: a 3-day per week clinic schedule and a 3-day per week take-home schedule in which tablets were provided to subjects to take at home on days between clinic visits. Thirteen patients completed the study. Significantly more doses were ingested under the 3-day per week schedules. Illicit drug use did not differ across conditions and 45% of urine samples tested positive for illicit opioids. Subjects 'liked' both 3-day per week schedules more than the daily schedule, and ratings of feeling 'good' were higher for the 3-day take-home as opposed to 3-day clinic condition. Almost all subjects (91%) rated 3-day take-home as the most preferred schedule. Overall, reducing clinic attendance improved medication compliance and increased client satisfaction without impacting illicit drug use. PMID:11137282

Amass, L; Kamien, J B; Mikulich, S K

2001-01-01

225

Aryl substitution of pentacenes  

PubMed Central

Summary A series of 11 new pentacene derivatives has been synthesized, with unsymmetrical substitution based on a trialkylsilylethynyl group at the 6-position and various aryl groups appended to the 13-position. The electronic and physical properties of the new pentacene chromophores have been analyzed by UV–vis spectroscopy (solution and thin films), thermoanalytical methods (DSC and TGA), cyclic voltammetry, as well as X-ray crystallography (for 8 derivatives). X-ray crystallography has been specifically used to study the influence of unsymmetrical substitution on the solid-state packing of the pentacene derivatives. The obtained results add to our ability to better predict substitution patterns that might be helpful for designing new semiconductors for use in solid-state devices. PMID:25161729

Waterloo, Andreas R; Sale, Anna-Chiara; Lehnherr, Dan; Hampel, Frank

2014-01-01

226

Bone graft substitutes.  

PubMed

Replacement of missing bone stock is a reconstructive challenge to upper extremity surgeons and decision-making with regards to available choices remains difficult. Preference is often given to autograft in the form of cancellous, cortical, or corticocancellous grafts from donor sites. However, the available volume from such donor sites is limited and fraught with potential complications. Advances in surgical management and medical research have produced a wide array of potential substances that can be used for bone graft substitute. Considerations in selecting bone grafts and substitutes include characteristic capabilities, availability, patient morbidity, immunogenicity, potential disease transmission, and cost variability. PMID:23101596

Bhatt, Reena A; Rozental, Tamara D

2012-11-01

227

Linsky, Quine, and Substitutivity  

E-print Network

LINSKYi QUINE, AND SUBSTITUTIVITY Charles Schlee It has been argued by Linsky that the principle of inter-substitutivity salva veritate of co-referential sin­ gular terms in sentences (PS) 1B "just false," that it is such that "no two terms obey... it" ([l ] i 100). What Linsky has criticized is a characterization of PS provided by Quine in "Reference and Modality" ([il], 139). An alter­ native characterization of PS has been employed by Quine in Word and Object ([ill], 1^3). I will argue...

Schlee, Charles

1975-11-01

228

Performing Substitute Teaching  

ERIC Educational Resources Information Center

Formal education is both a right and an obligation bestowed on young people in most all nations of the world. Teachers (adults) and students (youth) form a co-present dyadic contract that must be maintained within the classroom. Substitute teachers fill a role in sustaining the integrity of this teacher-student link, whenever teachers are absent.…

Bletzer, Keith V.

2010-01-01

229

Sulfur Substitution in Oxyanions.  

NASA Astrophysics Data System (ADS)

Sulfide can react with oxyanions in two ways. In anions such as chromate, iodate or permanganate, the central metal(loid) is reduced rapidly. In anions such as molybdate, arsenate or antimonate, sulfur atoms substitute for oxygen atoms in the first coordination sphere. In the latter cases, the central metal(loid) often retains its high oxidation state in the final thioanion; however lower valent species, which tend to be coordinatively more labile, may be important reaction intermediates. Replacement of oxygen by sulfur "softens" oxyanions, in some cases making them strong binders of soft metals, like Cu, Ag, Au and Hg. These changes also can profoundly affect the geochemical fate of the metal(loids). Sulfur substitution in oxyanions can be extremely sluggish. Recently, computational chemistry has begun to yield information about sulfur substitution reactions that are too slow to be studied experimentally but yet are potentially important in geochemistry. Thioperrhenates, thiovanadates and thiotungstates are species whose geochemical roles, if any, remain to be determined. It is possible that sulfur substitution reactions are more important under hydrothermal conditions than at ambient temperatures. For example, germanate dominates the ambient-temperature chemistry of Ge, but in hydrothermal deposits this element occurs commonly in sulfide minerals.

Helz, G. R.

2008-12-01

230

The Age of Substitutability  

ERIC Educational Resources Information Center

Dwindling mineral resources might cause a shift from nonrenewable resources to renewable resources and inexhaustible elements such as iron and aluminum. Alternative energy sources such as breeder, fusion, solar, and geothermal power must be developed for production and recycling of materials. Substitution and, hence, living standards ultimately…

Goeller, H. E.; Weinberg, Alvin M.

1976-01-01

231

Clarifying substituted judgement: the endorsed life approach.  

PubMed

A primary goal of clinical practice is to respect patient autonomy. To promote this goal for patients who have lost the ability to make their own decisions, commentators recommend that surrogates make their treatment decisions based on the substituted judgment standard. This standard is commonly interpreted as directing surrogates to make the decision the patient would have made in the circumstances, if the patient were competent. However, recent commentators have argued that this approach-attempting to make the decision the patient would have made if competent-is theoretically problematic, practically infeasible, and ignores the interests of the patient's family and loved ones. These commentators conclude that the substituted judgment standard should be revised significantly, or abandoned altogether. While this response would avoid the cited problems, it also would require substantial changes to clinical practice and would raise significant problems of its own. The present paper thus considers the possibility that the criticisms do not point to problems with the substituted judgment standard itself; instead, they point to problems with the way it is most commonly interpreted. This analysis suggests that the substituted judgment standard need not be dramatically revised or abandoned. Instead, it should be interpreted in a way that effectively promotes respect for the autonomy of incompetent patients. The 'endorsed life' interpretation described here helps clinicians and surrogates to achieve this important goal. To clarify this approach, we explain how it differs from three other recently proposed alternatives to the standard interpretation of the substituted judgment standard. PMID:25360029

Phillips, John; Wendler, David

2014-10-30

232

Pipelined Backward Substitution The backward substitution is inherently  

E-print Network

Pipelined Backward Substitution (cont.) Step 2. x 0 + a 0;1 x 1 + a 0;2 x 2 = ¯ y 0 \\Gamma a 0;3 x 3 = ~ y 0 2 = ~ y 3 x 3 = ¯ y 3 x 4 = y 4 Pipelined Backward Substitution (cont.) Step 4. x 0 = y 0 \\Gamma a 0Pipelined Backward Substitution The backward substitution is inherently sequential, but may

Zhang, Jun

233

SUBSTITUTION REACTIONS FOR THE DETOXIFICATION OF HAZARDOUS CHEMICALS  

EPA Science Inventory

Chemical Treatment is one of several treatment techniques used for the remediation of toxic and hazardous chemicals. Chemical treatment in this report is defined as substitution of halogens by hydrogens for the conversion of halogenated organic toxicant into its native hydrocarb...

234

U.S. Food and Drug Administration approval summary: Erlotinib for the first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution mutations.  

PubMed

On May 14, 2013, the U.S. Food and Drug Administration approved erlotinib (Tarceva, Astellas Pharma Inc., Northbrook, IL, http://www.us.astellas.com/) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. This indication for erlotinib was approved concurrently with the cobas EGFR Mutation Test (Roche Molecular Systems, Inc., Basel, Switzerland, http://www.molecular.roche.com), a companion diagnostic test for patient selection. The approval was based on clinically important improvements in progression-free survival (PFS) and objective response rate (ORR) and an acceptable toxicity profile demonstrated in a multicenter, open label trial enrolling 174 patients with metastatic NSCLC whose tumors had EGFR mutations as determined by a laboratory-developed test. Patients were randomized (1:1) to receive erlotinib (150 mg/day) or platinum-based doublet chemotherapy. The primary endpoint was investigator-assessed PFS. Secondary endpoints included overall survival (OS) and ORR. Superior PFS (hazard ratio [HR] 0.34; 95% confidence interval [CI]: 0.23, 0.49; p < .001) and ORR (65% vs. 16%) were observed in the erlotinib arm. Median PFS was 10.4 months and 5.2 months in the erlotinib and chemotherapy arms, respectively. There was no difference in OS (HR 0.93; 95% CI: 0.64, 1.35) with median OS of 22.9 months and 19.5 months in the erlotinib and chemotherapy arms, respectively. The most frequent (?30%) adverse reactions in the erlotinib-treated patients were rash, diarrhea, asthenia, cough, dyspnea, and decreased appetite. The most frequent (?5%) grade 3 and 4 adverse reactions were rash and diarrhea. PMID:24868098

Khozin, Sean; Blumenthal, Gideon M; Jiang, Xiaoping; He, Kun; Boyd, Karen; Murgo, Anthony; Justice, Robert; Keegan, Patricia; Pazdur, Richard

2014-07-01

235

U.S. Food and Drug Administration Approval Summary: Erlotinib for the First-Line Treatment of Metastatic Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Exon 19 Deletions or Exon 21 (L858R) Substitution Mutations  

PubMed Central

On May 14, 2013, the U.S. Food and Drug Administration approved erlotinib (Tarceva, Astellas Pharma Inc., Northbrook, IL, http://www.us.astellas.com/) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. This indication for erlotinib was approved concurrently with the cobas EGFR Mutation Test (Roche Molecular Systems, Inc., Basel, Switzerland, http://www.molecular.roche.com), a companion diagnostic test for patient selection. The approval was based on clinically important improvements in progression-free survival (PFS) and objective response rate (ORR) and an acceptable toxicity profile demonstrated in a multicenter, open label trial enrolling 174 patients with metastatic NSCLC whose tumors had EGFR mutations as determined by a laboratory-developed test. Patients were randomized (1:1) to receive erlotinib (150 mg/day) or platinum-based doublet chemotherapy. The primary endpoint was investigator-assessed PFS. Secondary endpoints included overall survival (OS) and ORR. Superior PFS (hazard ratio [HR] 0.34; 95% confidence interval [CI]: 0.23, 0.49; p < .001) and ORR (65% vs. 16%) were observed in the erlotinib arm. Median PFS was 10.4 months and 5.2 months in the erlotinib and chemotherapy arms, respectively. There was no difference in OS (HR 0.93; 95% CI: 0.64, 1.35) with median OS of 22.9 months and 19.5 months in the erlotinib and chemotherapy arms, respectively. The most frequent (?30%) adverse reactions in the erlotinib-treated patients were rash, diarrhea, asthenia, cough, dyspnea, and decreased appetite. The most frequent (?5%) grade 3 and 4 adverse reactions were rash and diarrhea. PMID:24868098

Blumenthal, Gideon M.; Jiang, Xiaoping; He, Kun; Boyd, Karen; Murgo, Anthony; Justice, Robert; Keegan, Patricia; Pazdur, Richard

2014-01-01

236

40 CFR 721.10497 - Substituted alkyl ester, hydrolysis products with silica and substituted silane (generic).  

... false Substituted alkyl ester, hydrolysis products with silica and substituted...10497 Substituted alkyl ester, hydrolysis products with silica and substituted...generically as substituted alkyl ester, hydrolysis products with silica and...

2014-07-01

237

40 CFR 721.10497 - Substituted alkyl ester, hydrolysis products with silica and substituted silane (generic).  

Code of Federal Regulations, 2013 CFR

... false Substituted alkyl ester, hydrolysis products with silica and substituted...10497 Substituted alkyl ester, hydrolysis products with silica and substituted...generically as substituted alkyl ester, hydrolysis products with silica and...

2013-07-01

238

Maternal stress and behavioral adaptation in methadone- or buprenorphine-exposed toddlers.  

PubMed

The current study examined the relationship between early interaction, parenting stress, maternal psychological distress symptoms, and behavior problems and health-related quality of life among children born to mothers in opioid maintenance treatment (OMT) in Norway during the period 2005-2007 (N = 36). This group was compared with a normative sample of mothers without substance abuse problems and their children (N = 36). There were significant group differences (p < .01) in perceived child problems in toddlerhood. In a regression model, mothers' self-reported psychological distress symptoms in terms of depression and anxiety symptoms significantly predicted child behavior problems (p < .01) and health-related quality of life (p < .01) rather than parenting stress. No significant, unique effect of exposure was found after controlling for other factors that could influence developmental outcomes. These findings add to the growing evidence on the importance of maternal psychological well-being for child development, and underscore the need to address opioid-maintained women's personal maladjustment and the constellation of stress experienced by mothers in recovery. PMID:23999378

Sarfi, Monica; Sundet, Jon Martin; Waal, Helge

2013-12-01

239

Polyimides comprising substituted benzidines  

NASA Technical Reports Server (NTRS)

A new class of polyimides and copolyimides made from substituted benzidines and aromatic dianhydrides and other aromatic diamines. The polyimides obtained with said diamines are distinguished by excellent thermal, excellent solubility, excellent electrical properties such as very low dielectric constants, excellent clarity and mechanical properties making the polyimides ideally suited as coating materials for microelectronic apparatii, as membranes for selective molecular or gas separation, as fibers in molecular composites, as high tensile strength, high compression strength fibers, as film castable coatings, or as fabric components.

Harris, Frank W. (Inventor)

1991-01-01

240

Sustained Release d-Amphetamine Reduces Cocaine but not ‘Speedball’-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine\\/Heroin Polydrug Abusers  

Microsoft Academic Search

The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid\\/cocaine combination (‘speedball’-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg\\/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg\\/day maintenance and double-blind ascending SR-AMP weekly doses of 0,

Mark K Greenwald; Leslie H Lundahl; Caren L Steinmiller

2010-01-01

241

Improvement in Psychopathology Among Opioid-Dependent Adolescents During Behavioral-Pharmacological Treatment  

PubMed Central

Objective To examine changes in behavioral and emotional problems among opioid-dependent adolescents during a four week combined behavioral and pharmacological treatment. Methods We examined scales of behavioral and emotional problems in youth using the Youth Self Report (YSR) measure at the time of substance abuse treatment intake and changes in scale scores during treatment Participants were 36 adolescents (ages 13–18 eligible) who met DSM-IV criteria for opioid dependence. Participants received a 28-day outpatient, medication-assisted withdrawal with either buprenorphine, or clonidine, as part of a double-blind, double-dummy comparison of these medications. All participants received a common behavioral intervention, composed of three individual counseling sessions per week, and incentives contingent on opioid-negative urine samples (collected three times/week) attendance and completion of weekly assessments. Results: Although a markedly greater number of youth who received buprenorphine remained in treatment relative to those who received clonidine, youth who remained in treatment showed significant reductions during treatment on two YSR grouping scales (Internalizing Problems and Total Problems) and four of the empirically based syndrome scales (Somatic, Social, Attention and Thought). On YSR competence and adaptive scales, no significant changes were observed. There was no evidence that changes in any scales differed across medication condition. Conclusions Youth who were retained demonstrated substantive improvements in a number of clinically meaningful behavioral and emotional problems, irrespective of pharmacotherapy provided to them. PMID:22107875

Moore, Sarah K.; Marsch, Lisa A.; Badger, Gary J.; Solhkhah, Ramon; Hofstein, Yariv

2011-01-01

242

Explicit Substitutions and All That  

NASA Technical Reports Server (NTRS)

Explicit substitution calculi are extensions of the lambda-calculus where the substitution mechanism is internalized into the theory. This feature makes them suitable for implementation and theoretical study of logic-based tools such as strongly typed programming languages and proof assistant systems. In this paper we explore new developments on two of the most successful styles of explicit substitution calculi: the lambda sigma- and lambda S(e)-calculi.

Ayala-Rincon, Mauricio; Munoz, Cesar

2000-01-01

243

40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...  

Code of Federal Regulations, 2011 CFR

... false Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega...10214 Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega...generically as poly(oxyalkylenediyl),.alpha.-substituted...

2011-07-01

244

A history of sexual, emotional, or physical abuse predicts adjustment during opioid maintenance treatment.  

PubMed

This study examined how having a history of sexual, physical, or emotional abuse is related to overall functioning as assessed by the Addiction Severity Index during short-term opioid maintenance treatment with either buprenorphine/naloxone or methadone. Furthermore, the relation between abuse history and overall functioning by sex was explored. Participants (N = 268) were opioid-dependent adults entering an outpatient randomized clinical trial with buprenorphine/naloxone and methadone. Latent growth modeling indicated that females with an abuse history entered treatment with more problems in the psychiatric and family domains as compared with females without an abuse history. Over the course of treatment, a history of abuse predicted problems in the psychiatric and alcohol domains. Furthermore, a history of abuse predicted slower recovery times and less recovery overall for females in some domains. Males with an abuse history entered treatment with more severe psychiatric and family problems as compared with males with no history of abuse. Victims of abuse may present to substance abuse treatment with weaknesses in the areas of family relations, psychiatric status, and alcohol use. The nature of these problems and their trajectory over time differed by sex. PMID:17596905

Branstetter, Steven A; Bower, Emily H; Kamien, Jonathan; Amass, Leslie

2008-03-01

245

Referential and nonreferential substitutional quantifiers  

Microsoft Academic Search

It is common to find philosophers claiming that it is possible to free the quantifiers - especially the particular (or so-called existential) quantifier - from questions of reference, existence, and ontology, by having recourse to what is now referred to as the substitutional interpretation of the quantifiers. Although there may be ontologically neutral uses of the substitutional interpretation, it is

Alex Orenstein

1984-01-01

246

Thermal decomposition of substituted phenols in supercritical water  

SciTech Connect

The thermal decomposition of cresols, hydroxybenzaldehydes, nitrophenols, and benzenediols was studied in dilute aqueous solutions and in the absence of oxygen at 460 C and 250 atm for residence times around 10 s. Thermolysis under these conditions produced conversions of less than 10% for o-, m-, and p-cresol, whereas hydroxybenzaldehydes and nitrophenols were much more reactive. Global rate expressions are reported for the thermolysis of each hydroxybenzaldehyde and nitrophenol isomer. Phenol was a major product from the decomposition of all of the substituted phenols studied. For a given substituent, ortho-substituted phenols reacted more rapidly than the other isomers. For a given substituted position, nitrophenols reacted more rapidly than hydroxybenzaldehydes, which in turn reacted more rapidly than cresols. These results demonstrate that the treatment of CHO- and NO{sub 2}-substituted phenols by oxidation in supercritical water will involve the oxidation of thermal decomposition products in addition to the oxidation of the original compounds.

Martino, C.J.; Savage, P.E. [Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Chemical Engineering] [Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Chemical Engineering

1997-05-01

247

Orthopaedic applications of bone graft & graft substitutes: a review.  

PubMed

Treatment of delayed union, malunion, and nonunion is a challenge to the orthopaedic surgeons in veterinary and human fields. Apart from restoration of alignment and stable fixation, in many cases adjunctive measures such as bone-grafting or use of bone-graft substitutes are of paramount importance. Bone-graft materials usually have one or more components: an osteoconductive matrix, which acts as scaffold to new bone growth; osteoinductive proteins, which support mitogenesis of undifferentiated cells; and osteogenic cells, which are capable of forming bone in the appropriate environment. Autologous bone remains the "gold standard" for stimulating bone repair and regeneration, but its availability may be limited and the procedure to harvest the material is associated with complications. Bone-graft substitutes can either substitute autologous bone graft or expand an existing amount of autologous bone graft. We review the currently available bone graft and graft substitutes for the novel therapeutic approaches in clinical setting of orthopaedic surgery. PMID:20693585

Nandi, S K; Roy, S; Mukherjee, P; Kundu, B; De, D K; Basu, D

2010-07-01

248

40 CFR 721.10626 - 1,4-Butanediol, polymer with substituted alkane and substituted methylene biscarbomonocycle, 2...  

...4-Butanediol, polymer with substituted alkane and substituted methylene biscarbomonocycle...4-Butanediol, polymer with substituted alkane and substituted methylene biscarbomonocycle...4-butanediol, polymer with substituted alkane and substituted methylene...

2014-07-01

249

40 CFR 721.10626 - 1,4-Butanediol, polymer with substituted alkane and substituted methylene biscarbomonocycle, 2...  

Code of Federal Regulations, 2013 CFR

...4-Butanediol, polymer with substituted alkane and substituted methylene biscarbomonocycle...4-Butanediol, polymer with substituted alkane and substituted methylene biscarbomonocycle...4-butanediol, polymer with substituted alkane and substituted methylene...

2013-07-01

250

40 CFR 721.323 - Substituted acrylamide.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Substituted acrylamide. 721.323 Section 721.323 ...Substances § 721.323 Substituted acrylamide. (a) Chemical substance and significant...generically identified as substituted acrylamide (PMN P-90-1687) is subject...

2010-07-01

251

40 CFR 721.323 - Substituted acrylamide.  

...2014-07-01 false Substituted acrylamide. 721.323 Section 721.323 ...Substances § 721.323 Substituted acrylamide. (a) Chemical substance and significant...generically identified as substituted acrylamide (PMN P-90-1687) is subject...

2014-07-01

252

40 CFR 721.323 - Substituted acrylamide.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Substituted acrylamide. 721.323 Section 721.323 ...Substances § 721.323 Substituted acrylamide. (a) Chemical substance and significant...generically identified as substituted acrylamide (PMN P-90-1687) is subject...

2013-07-01

253

40 CFR 721.323 - Substituted acrylamide.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 false Substituted acrylamide. 721.323 Section 721.323 ...Substances § 721.323 Substituted acrylamide. (a) Chemical substance and significant...generically identified as substituted acrylamide (PMN P-90-1687) is subject...

2012-07-01

254

40 CFR 721.1372 - Substituted nitrobenzene.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Substituted nitrobenzene. 721.1372 Section 721.1372...Substances § 721.1372 Substituted nitrobenzene. (a) Chemical substance and significant...substance identified as a substituted nitrobenzene (PMN P-92-1125) is...

2010-07-01

255

40 CFR 721.1372 - Substituted nitrobenzene.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 false Substituted nitrobenzene. 721.1372 Section 721.1372...Substances § 721.1372 Substituted nitrobenzene. (a) Chemical substance and significant...substance identified as a substituted nitrobenzene (PMN P-92-1125) is...

2011-07-01

256

40 CFR 721.4280 - Substituted hydrazine.  

Code of Federal Regulations, 2010 CFR

... 2010-07-01 false Substituted hydrazine. 721.4280 Section 721.4280...Substances § 721.4280 Substituted hydrazine. (a) Chemical substance and significant...identified generically as substituted hydrazine (PMN P-90-594) is subject...

2010-07-01

257

Substance Abuse Treatment Facility Locator  

MedlinePLUS

... Health Services Locator Buprenorphine Physician Locator Find a Facility in Your State To locate the drug and ... Service . Privacy Policy . Home | About the Locator | Find Facilities Near You | Find Facilities by City, County, State ...

258

Synthesis and evaluation of three structurally related ¹?F-labeled orvinols of different intrinsic activities: 6-O-[¹?F]fluoroethyl-diprenorphine ([¹?F]FDPN), 6-O-[¹?F]fluoroethyl-buprenorphine ([¹?F]FBPN), and 6-O-[¹?F]fluoroethyl-phenethyl-orvinol ([¹?F]FPEO).  

PubMed

We report the synthesis and biological evaluation of a triplet of 6-O-(18)F-fluoroethylated derivatives of structurally related orvinols that span across the full range of intrinsic activities, the antagonist diprenorphine, the partial agonist buprenorphine, and the full agonist phenethyl-orvinol. [(18)F]fluoroethyl-diprenorphine, [(18)F]fluoroethyl-buprenorphine, and [(18)F]fluoroethyl-phenethyl-orvinol were prepared in high yields and quality from their 6-O-desmethyl-precursors. The results indicate suitable properties of the three 6-O-(18)F-fluoroethylated derivatives as functional analogues to the native carbon-11 labeled versions with similar pharmacological properties. PMID:24933507

Schoultz, Bent W; Hjørnevik, Trine; Reed, Brian J; Marton, János; Coello, Christopher S; Willoch, Frode; Henriksen, Gjermund

2014-06-26

259

Thermogram No Substitute for Mammogram  

MedlinePLUS

... Products Vaccines, Blood & Biologics Articulos en Espanol Thermogram No Substitute for Mammogram Search the Consumer Updates Section ... by mammography. The problem is that FDA has no evidence to support these claims. "Mammography is still ...

260

A pharmaceutical industry perspective on the economics of treatments for alcohol and opioid use disorders.  

PubMed

Individuals with alcohol and/or drug use disorders often fail to receive care, or evidence-based care, yet the literature shows health economic benefits. Comparative effectiveness research is emerging that examines approved approaches in terms of real, total healthcare cost/utilization. Comprehensive retrospective insurance claims analyses are few but tend to be nationally distributed and large. The emerging pattern is that, while treatment in general is cost effective, specific therapeutics can yield different health economic outcomes. Cost/utilization data consistently show greater savings with pharmacotherapies (despite their costs) versus psychosocial treatment alone. All FDA-approved addiction pharmacotherapies (oral naltrexone, extended-release naltrexone, acamprosate, disulfiram, buprenorphine, buprenorphine/naloxone, and methadone) are intended for use in conjunction with psychosocial management, not as stand-alone therapeutics; hence, pharmacotherapy costs must offer benefits in addition to abstinence alone or psychological therapy. Patient persistence is problematic, and (despite its cost) extended-release pharmacotherapy may be associated with lower or no greater total healthcare cost, mostly due to reduced hospitalization. The reviewed studies use rigorous case-mix adjustment to balance treatment cohorts but lack the randomization that clinical trials use to protect against confounding. Unlike trials, however, these studies can offer generalizability to diverse populations, providers, and payment models--and are of particular salience to payers. PMID:25236185

Gastfriend, David R

2014-10-01

261

A pharmaceutical industry perspective on the economics of treatments for alcohol and opioid use disorders  

PubMed Central

Individuals with alcohol and/or drug use disorders often fail to receive care, or evidence-based care, yet the literature shows health economic benefits. Comparative effectiveness research is emerging that examines approved approaches in terms of real, total healthcare cost/utilization. Comprehensive retrospective insurance claims analyses are few but tend to be nationally distributed and large. The emerging pattern is that, while treatment in general is cost effective, specific therapeutics can yield different health economic outcomes. Cost/utilization data consistently show greater savings with pharmacotherapies (despite their costs) versus psychosocial treatment alone. All FDA-approved addiction pharmacotherapies (oral naltrexone, extended-release naltrexone, acamprosate, disulfiram, buprenorphine, buprenorphine/naloxone, and methadone) are intended for use in conjunction with psychosocial management, not as stand-alone therapeutics; hence, pharmacotherapy costs must offer benefits in addition to abstinence alone or psychological therapy. Patient persistence is problematic, and (despite its cost) extended-release pharmacotherapy may be associated with lower or no greater total healthcare cost, mostly due to reduced hospitalization. The reviewed studies use rigorous case-mix adjustment to balance treatment cohorts but lack the randomization that clinical trials use to protect against confounding. Unlike trials, however, these studies can offer generalizability to diverse populations, providers, and payment models—and are of particular salience to payers. PMID:25236185

Gastfriend, David R

2014-01-01

262

Laser Vascular Lesion Treatment  

MedlinePLUS

... this site constitutes acceptance of Skinsight's terms of service and privacy policy. The material on this site is for informational purposes only, and is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

263

Substitutional-interstitial G.P. zones in nitrided Fe-Mo alloys  

Microsoft Academic Search

Constant-activity nitriding of Fe-2·9 at. % Mo at 580°C produces mixed substitutional-interstitial solute-atom G.P. zones on {100} planes. Nitrogen can then be continuously removed from the clusters by hydrogen treatment to leave solely substitutional Mo zones on {100} planes. Results are discussed briefly in terms of possible clustering mechanisms for Mo in Fe.

J. H. Driver; D. C. Unthank; K. H. Jack

1972-01-01

264

Partitioning the Variation in Mammalian Substitution Rates  

Microsoft Academic Search

We have used analysis of variance to partition the variation in synonymous and amino acid substitution rates between three effects (gene, lineage, and a gene-by-lineage interaction) in mammalian nuclear and mitochondrial genes. We find that gene effects are stronger for amino acid substitution rates than for synonymous substitution rates and that lineage effects are stronger for synonymous substitution rates than

Nick G. C. Smith; Adam Eyre-Walker

2003-01-01

265

Tetra-Substituted Pyridinylimidazoles As Dual Inhibitors of p38? Mitogen-Activated Protein Kinase and c-Jun N-Terminal Kinase 3 for Potential Treatment of Neurodegenerative Diseases.  

PubMed

Tetra-substituted imidazoles were designed as dual inhibitors of c-Jun N-terminal kinase (JNK) 3 and p38? mitogen-activated protein (MAP) kinase. A library of 45 derivatives was prepared and evaluated in a kinase activity assay for their ability to inhibit both kinases, JNK3 and p38? MAP kinase. Dual inhibitors with IC50 values down to the low double-digit nanomolar range at both enzymes were identified. The best balanced dual JNK3/p38? MAP kinase inhibitors are 6m (IC50: JNK3, 18 nM; p38?, 30 nM) and 14d (IC50: JNK3, 26 nM; p38?, 34 nM) featuring both excellent solubility and metabolic stability. They may serve as useful tool compounds for preclinical proof-of-principle studies in order to validate the synergistic role of both kinases in the progression of Huntington's disease. PMID:25475894

Muth, Felix; Günther, Marcel; Bauer, Silke M; Döring, Eva; Fischer, Sabine; Maier, Julia; Drückes, Peter; Köppler, Jürgen; Trappe, Jörg; Rothbauer, Ulrich; Koch, Pierre; Laufer, Stefan A

2015-01-01

266

Magnesium substitution in brushite cements.  

PubMed

The use of magnesium-doped ceramics has been described to modify brushite cements and improve their biological behavior. However, few studies have analyzed the efficiency of this approach to induce magnesium substitution in brushite crystals. Mg-doped ceramics composed of Mg-substituted ?-TCP, stanfieldite and/or farringtonite were reacted with primary monocalcium phosphate (MCP) in the presence of water. The cement setting reaction has resulted in the formation of brushite and newberyite within the cement matrix. Interestingly, the combination of SAED and EDX analyses of single crystal has indicated the occurrence of magnesium substitution within brushite crystals. Moreover, the effect of magnesium ions on the structure, and mechanical and setting properties of the new cements was characterized as well as the release of Ca(2+) and Mg(2+) ions. Further research would enhance the efficiency of the system to incorporate larger amounts of magnesium ions within brushite crystals. PMID:25428098

Alkhraisat, Mohammad Hamdan; Cabrejos-Azama, Jatsue; Rodríguez, Carmen Rueda; Jerez, Luis Blanco; Cabarcos, Enrique López

2013-01-01

267

40 CFR 721.1555 - Substituted phenyl azo substituted benzenediazonium salt.  

...phenyl azo substituted benzenediazonium salt. 721.1555 Section 721.1555 ...phenyl azo substituted benzenediazonium salt. (a) Chemical substance and significant...phenyl azo substituted benzenediazonium salt (PMN P-92-652) is subject to...

2014-07-01

268

40 CFR 721.1555 - Substituted phenyl azo substituted benzenediazonium salt.  

Code of Federal Regulations, 2010 CFR

...phenyl azo substituted benzenediazonium salt. 721.1555 Section 721.1555 ...phenyl azo substituted benzenediazonium salt. (a) Chemical substance and significant...phenyl azo substituted benzenediazonium salt (PMN P-92-652) is subject to...

2010-07-01

269

40 CFR 721.9545 - Substituted phenyl azo substituted sulfocarbopolycle, sodium salt.  

Code of Federal Regulations, 2012 CFR

...azo substituted sulfocarbopolycle, sodium salt. 721.9545 Section 721.9545 ...azo substituted sulfocarbopolycle, sodium salt. (a) Chemical substance and significant...azo substituted sulfocarbopolycle, sodium salt (PMN P-96-1263) is subject to...

2012-07-01

270

40 CFR 721.1555 - Substituted phenyl azo substituted benzenediazonium salt.  

Code of Federal Regulations, 2013 CFR

...phenyl azo substituted benzenediazonium salt. 721.1555 Section 721.1555 ...phenyl azo substituted benzenediazonium salt. (a) Chemical substance and significant...phenyl azo substituted benzenediazonium salt (PMN P-92-652) is subject to...

2013-07-01

271

40 CFR 721.2577 - Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine...  

...substituted phenyl) disulfonaphthyl azo, amine salt (generic). 721.2577 Section 721...substituted phenyl) disulfonaphthyl azo, amine salt (generic). Link to an amendment published...substituted phenyl) disulfonaphthyl azo, amine salt (PMNs P-00-0364 and...

2014-07-01

272

Syntheses and antimalarial activities of N-substituted 11-azaartemisinins.  

PubMed

A two-step reaction sequence between artemisinin and methanolic ammonia followed by treatment with Amberlyst 15 yielded 11-azaartemisinin in 65% yield. Substituting a variety of primary alkyl- and heteroaromatic amines for ammonia in the reaction sequence yields N-substituted 11-azaartemisinins in similar or greater yield. When Amberlyst 15 is replaced by a mixture of sulfuric acid/silica gel, both 11-azaartemisinin and the expected metabolite, 10-azadesoxyartemisinin, are formed in 45% and 15% yields, respectively. In vitro and in vivo test data for a number of novel N-substituted 11-azaartemisinins, against drug-resistant strains of Plasmodium falciparum, show they possess antimalarial activities equal to or greater than that of artemisinin. The most active derivative, N-(2'-acetaldehydo)-11-azaartemisinin, 17, was 26 times more active in vitro and 4 times more active in vivo than artemisinin. PMID:8544181

Torok, D S; Ziffer, H; Meshnick, S R; Pan, X Q; Ager, A

1995-12-22

273

Dual functional selenium-substituted hydroxyapatite  

PubMed Central

Hydroxyapatite (HA) doped with trace elements has attracted much attention recently owing to its excellent biological functions. Herein, we use a facile co-precipitation method to incorporate selenium into HA by adding sodium selenite during synthesis. The obtained selenium-substituted HA products are needle-like nanoparticles which have  size and crystallinity that are similar to those of the pure HA nanoparticles (HANs) when the selenium content is low. HANs are found to have the ability to induce the apoptosis of osteosarcoma cells, and the anti-tumour effects are enhanced after incorporation of selenium. Meanwhile, the nanoparticles can also support the growth of bone marrow stem cells. Furthermore, the flow cytometric results indicate that the apoptosis induction of osteosarcoma cells is caused by the increased reactive oxygen species and decreased mitochondrial membrane potential. These results show that the selenium-substituted HANs are potentially promising bone graft materials in osteosarcoma treatment due to their dual functions of supporting normal cell growth and inducing tumour cell apoptosis. PMID:23741613

Wang, Yanhua; Ma, Jun; Zhou, Lei; Chen, Jin; Liu, Yonghui; Qiu, Zhiye; Zhang, Shengmin

2012-01-01

274

Dual functional selenium-substituted hydroxyapatite.  

PubMed

Hydroxyapatite (HA) doped with trace elements has attracted much attention recently owing to its excellent biological functions. Herein, we use a facile co-precipitation method to incorporate selenium into HA by adding sodium selenite during synthesis. The obtained selenium-substituted HA products are needle-like nanoparticles which have  size and crystallinity that are similar to those of the pure HA nanoparticles (HANs) when the selenium content is low. HANs are found to have the ability to induce the apoptosis of osteosarcoma cells, and the anti-tumour effects are enhanced after incorporation of selenium. Meanwhile, the nanoparticles can also support the growth of bone marrow stem cells. Furthermore, the flow cytometric results indicate that the apoptosis induction of osteosarcoma cells is caused by the increased reactive oxygen species and decreased mitochondrial membrane potential. These results show that the selenium-substituted HANs are potentially promising bone graft materials in osteosarcoma treatment due to their dual functions of supporting normal cell growth and inducing tumour cell apoptosis. PMID:23741613

Wang, Yanhua; Ma, Jun; Zhou, Lei; Chen, Jin; Liu, Yonghui; Qiu, Zhiye; Zhang, Shengmin

2012-06-01

275

Substitute consent in women with psychosis.  

PubMed

When treating patients with schizophrenia, substitute consent for treatment is often needed because of the patient's decisional incapacity. The goal of this article is to illustrate the potential problems involved in surrogate decision-making in a mental health service for women. A composite case vignette that highlights these issues is presented. The vignette was developed based on files from a women's clinic for psychosis and a selective literature review. The quality of the relationship between marriage partners and the possibility of pregnancy, motherhood, and child custody disputes all complicate the ethics of next- of-kin surrogate decision-making. The concept of "best interests" (the mother's or the child's) is not straightforward. A related ethical issue is whether/when to disclose psychiatric information to spouses. It is hoped that this paper will engender further discussion in medicine, cultural studies, ethics, and the law. PMID:25406056

Seeman, Mary V

2014-11-01

276

Preparation of Some Substituted Terephthalic Acids  

E-print Network

Preparation of Some Substituted Terephthalic Acids Susanna Branion and Vladimir Benin Department substituted terephthalic acids: 2-sulfomethylterephthalic acid (1) and 2-phosphonoterephthalic acid (2 for construction of acid-pendant polymer chains. Keywords: Acid-pendant polymers, arenephosphonic acids

Benin, Vladimir

277

Student Expectations and the Substitute Teacher.  

ERIC Educational Resources Information Center

Examines the problems substitute teachers have with conducting regular lessons when the class is unruly and offers a student questionnaire that gives an idea of what substitutes face as one solution. (JC)

Benedict, K. C.

1987-01-01

278

40 CFR 721.1643 - Benzenesulfonic acid, amino substituted phenylazo-.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 false Benzenesulfonic acid, amino substituted phenylazo-. 721... § 721.1643 Benzenesulfonic acid, amino substituted phenylazo-. ...generically as a benzenesulfonic acid, amino substituted phenylazo-...

2011-07-01

279

40 CFR 721.1643 - Benzenesulfonic acid, amino substituted phenylazo-.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Benzenesulfonic acid, amino substituted phenylazo-. 721... § 721.1643 Benzenesulfonic acid, amino substituted phenylazo-. ...generically as a benzenesulfonic acid, amino substituted phenylazo-...

2010-07-01

280

40 CFR 721.1643 - Benzenesulfonic acid, amino substituted phenylazo-.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Benzenesulfonic acid, amino substituted phenylazo-. 721... § 721.1643 Benzenesulfonic acid, amino substituted phenylazo-. ...generically as a benzenesulfonic acid, amino substituted phenylazo-...

2013-07-01

281

40 CFR 721.1643 - Benzenesulfonic acid, amino substituted phenylazo-.  

...2014-07-01 false Benzenesulfonic acid, amino substituted phenylazo-. 721... § 721.1643 Benzenesulfonic acid, amino substituted phenylazo-. ...generically as a benzenesulfonic acid, amino substituted phenylazo-...

2014-07-01

282

40 CFR 721.1643 - Benzenesulfonic acid, amino substituted phenylazo-.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 false Benzenesulfonic acid, amino substituted phenylazo-. 721... § 721.1643 Benzenesulfonic acid, amino substituted phenylazo-. ...generically as a benzenesulfonic acid, amino substituted phenylazo-...

2012-07-01

283

Substitutes for School Nurses in Illinois  

ERIC Educational Resources Information Center

The purpose of this descriptive study was to explore utilization of nurse substitutes in the school setting in Illinois. The literature described personnel who staff the school health office in the absence of the school nurse and the barriers to obtaining nurse substitutes. There were no empirical studies conducted on school nurse substitutes in…

Vollinger, Linda Jeno; Bergren, Martha Dewey; Belmonte-Mann, Frances

2011-01-01

284

Expectations and Experiences of Substitute Teachers  

ERIC Educational Resources Information Center

This article explores the expectations of support for and the experiences of substitute teachers in an urban school division in Saskatchewan. Data were collected in semistructured interviews with seven substitute teachers. The purpose of the study was to explore how substitute teachers frame their professional experiences and construct their roles…

Duggleby, Patricia; Badali, Sal

2007-01-01

285

Bone substitutes and bone formation  

Microsoft Academic Search

Summary  \\u000a Prompted by severe problems in autogeneic and allogeneic bone transplantation, intensive efforts were made to find sufficient\\u000a substitutes. A main demand on these materials, especially in healing of osseous defects, is to achieve results comparable\\u000a to those of auto- or allografts. These must be related to their biomechanical and particularly to their biological properties,\\u000a i. e. the ability to

H. Stützle; K. Hallfeldt; H. Mandelkow; S. Keßler; L. Schweiberer

1998-01-01

286

Iridium-Catalyzed Allylic Substitution  

NASA Astrophysics Data System (ADS)

Iridium-catalyzed asymmetric allylic substitution has become a valuable method to prepare products from the addition of nucleophiles at the more substituted carbon of an allyl unit. The most active and selective catalysts contain a phosphoramidite ligand possessing at least one arylethyl substituent on the nitrogen atom of the ligand. In these systems, the active catalyst is generated by a base-induced cyclometalation at the methyl group of this substituent to generate an iridium metalacycle bound by the COD ligand of the [Ir(COD)Cl]2 precursor and one additional labile dative ligand. Such complexes catalyze the reactions of linear allylic esters with alkylamines, arylamines, phenols, alcohols, imides, carbamates, ammonia, enolates and enolate equivalents, as well as typical stabilized carbon nucleophiles generated from malonates and cyanoesters. Iridium catalysts for enantioselective allylic substitution have also been generated from phosphorus ligands with substituents bound by heteroatoms, and an account of the studies of such systems, along with a description of the development of iridium catalysts is included.

Hartwig, John F.; Pouy, Mark J.

287

Resonant photodissociation in substituted benzenes  

NASA Astrophysics Data System (ADS)

Cyclic aromatic molecules are abundant in organic chemistry, with a wide variety of applications, including pharmacology, pollution studies and genetic research. Among the simplest of these molecules is benzene (C6H6), with many relevant molecules being benzene-like with a single atomic substitution. In such a substitution, the substituent determines a characteristic perturbation of the electronic structure of the molecule. We discuss the substitution of halogens into the ring (C6H5X), and its effects on the dynamics of ionization and dissociation of the molecule without the focal volume effect [1]. In particular, using 800-nm, 50-fs laser pulses, we present results in the dissociation of fluorobenzene, chlorobenzene, bromobenzene and iodobenzene into the phenyl ring (C6H5) and the atomic halogen, and the subsequent ionization of these fragments. The impact of the ``heavy atom effect'' on a ^1(?,?*) -> ^3(n,?*) singlet-triplet intersystem crossing will be emphasized. Currently under investigation is whether such a dissociation can be treated as an effective source of the neutral substituent.[4pt] [1] J. Strohaber and C. Uiterwaal, Phys. Rev. Lett. 100 023002 (2008).

Scarborough, Tim; McAcy, Collin; Foote, David; Uiterwaal, Cornelis

2011-06-01

288

Analgesics and ENT surgery. A clinical comparison of the intraoperative, recovery and postoperative effects of buprenorphine, diclofenac, fentanyl, morphine, nalbuphine, pethidine and placebo given intravenously with induction of anaesthesia.  

PubMed Central

1. Vomiting and restlessness following ENT and eye surgery are undesirable, and may be related to the emetic and analgesic effects of any analgesic given to augment anaesthesia during surgery. 2. To rationalise the choice of analgesic for routine ENT surgery we examined the intraoperative, recovery and postoperative effects following the administration of either buprenorphine (3.0 to 4.5 micrograms kg-1), diclofenac (1 mg kg-1), fentanyl (1.5 to 2.0 micrograms kg-1), morphine (0.1 to 0.15 mg kg-1), nalbuphine (0.1 to 0.15 mg kg-1), pethidine (1.0 to 1.5 mg kg-1) or saline (as control) given with the induction of anaesthesia in 374 patients. A standardised anaesthetic technique with controlled ventilation using 0.6-0.8% isoflurane in nitrous oxide and oxygen was employed. The study population constituted 7 similar groups of patients. 3. Intraoperatively, their effects on heart rate and blood pressure, airway pressure and intraocular pressure, were similar. This implies, most surprisingly, that neither their analgesic nor their histamine releasing effects were clinically evident during surgery. By prolonging the time to extubation at the end of anaesthesia, only buprenorphine, fentanyl, morphine and pethidine provided evidence of intraoperative respiratory depression. 4. Postoperatively, buprenorphine was associated with severe respiratory depression, prolonged somnolence, profound analgesia and the highest emesis rate. Diclofenac exhibited no sedative, analgesic, analgesic sparing, emetic or antipyretic effects. Fentanyl provided no sedative or analgesic effects, but was mildly emetic. Morphine provided poor sedation and analgesia, delayed the requirement for re-medication and was highly emetic. Nalbuphine and pethidine produced sedation with analgesia during recovery, a prolonged time to re-medication and a mild emetic effect. None provided evidence, from analysis of postoperative re-medication times and analgesic consumption, of any pre-emptive analgesic effect. 5. We conclude that nalbuphine (mean dose 0.13 mg kg-1) and pethidine (mean dose 1.35 mg kg-1), given individually as a single i.v. bolus during induction of anaesthesia, are the most efficacious analgesics for routine in-patient ENT surgery. PMID:7888292

van den Berg, A A; Honjol, N M; Prabhu, N V; Datta, S; Rozario, C J; Muraleedaran, R; Savva, D

1994-01-01

289

A prospective, randomised, controlled, multi-centre comparative effectiveness study of healing using dehydrated human amnion/chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers.  

PubMed

A prospective, randomised, controlled, parallel group, multi-centre clinical trial was conducted at three sites to compare the healing effectiveness of treatment of chronic lower extremity diabetic ulcers with either weekly applications of Apligraf® (Organogenesis, Inc., Canton, MA), EpiFix® (MiMedx Group, Inc., Marietta, GA), or standard wound care with collagen-alginate dressing. The primary study outcome was the percent change in complete wound healing after 4 and 6?weeks of treatment. Secondary outcomes included percent change in wound area per week, velocity of wound closure and a calculation of the amount and cost of Apligraf or EpiFix used. A total of 65 subjects entered the 2-week run-in period and 60 were randomised (20 per group). The proportion of patients in the EpiFix group achieving complete wound closure within 4 and 6?weeks was 85% and 95%, significantly higher (all adjusted P-values???0·003) than for patients receiving Apligraf (35% and 45%), or standard care (30% and 35%). After 1?week, wounds treated with EpiFix had reduced in area by 83·5% compared with 53·1% for wounds treated with Apligraf. Median time to healing was significantly faster (all adjusted P-values??0·001) with EpiFix (13?days) compared to Apligraf (49?days) or standard care (49?days). The mean number of grafts used and the graft cost per patient were lower in the EpiFix group campared to the Apligraf group, at 2·15 grafts at a cost of $1669 versus 6·2 grafts at a cost of $9216, respectively. The results of this study demonstrate the clinical and resource utilisation superiority of EpiFix compared to Apligraf or standard of care, for the treatment of diabetic ulcers of the lower extremities. PMID:25424146

Zelen, Charles M; Gould, Lisa; Serena, Thomas E; Carter, Marissa J; Keller, Jennifer; Li, William W

2014-11-26

290

Use This Test to Spruce Up Your Substitute Teacher Program.  

ERIC Educational Resources Information Center

Presents and interprets an 18-question test to determine how well a school's substitute teacher program functions. Topics covered include substitute teacher screening and preparation, lists of substitutes, lesson plans, staff and student evaluation of substitutes, substitutes' salaries, legal considerations, and making substitutes feel needed.…

Sendor, Elizabeth

1982-01-01

291

Sensory substitution as an artificially acquired synaesthesia.  

PubMed

In this review we explore the relationship between synaesthesia and sensory substitution and argue that sensory substitution does indeed show properties of synaesthesia. Both are associated with atypical perceptual experiences elicited by the processing of a qualitatively different stimulus to that which normally gives rise to that experience. In the most common forms of sensory substitution, perceptual processing of an auditory or tactile signal (which has been converted from a visual signal) is experienced as visual-like in addition to retaining auditory/tactile characteristics. We consider different lines of evidence that support, to varying degrees, the assumption that sensory substitution is associated with visual-like experiences. We then go on to analyse the key similarities and differences between sensory substitution and synaesthesia. Lastly, we propose two testable predictions: firstly that, in an expert user of a sensory substitution device, the substituting modality should not be lost. Secondly that stimulation within the substituting modality, but by means other than a sensory substitution device, should still produce sensation in the normally substituted modality. PMID:22885223

Ward, Jamie; Wright, Thomas

2014-04-01

292

Toxicity of N-substituted aromatics to acetoclastic methanogenic activity in granular sludge  

Microsoft Academic Search

N-substituted aromatics are important priority pollutants entering the environment primarily through anthropogenic activities associated with the industrial production of dyes, explosives, pesticides, and phar- maceuticals. Anaerobic treatment of wastewaters discharged by these industries could potentially be problem- atical as a result of the high toxicity of N-substituted aromatics. The objective of this study was to examine the structure-toxicity relationships of

BRIAN A. DONLON; ELIAS RAZO-FLORES; JIM A. FIELD; G. Lettinga

1995-01-01

293

Orally active 7-substituted (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitriles as active-site inhibitors of sphingosine 1-phosphate lyase for the treatment of multiple sclerosis.  

PubMed

Sphingosine 1-phosphate (S1P) lyase has recently been implicated as a therapeutic target for the treatment of multiple sclerosis (MS), based on studies in a genetic mouse model. Potent active site directed inhibitors of the enzyme are not known so far. Here we describe the discovery of (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitrile 5 in a high-throughput screen using a biochemical assay, and its further optimization. This class of compounds was found to inhibit catalytic activity of S1PL by binding to the active site of the enzyme, as seen in the cocrystal structure of derivative 31 with the homodimeric human S1P lyase. 31 induces profound reduction of peripheral T cell numbers after oral dosage and confers pronounced protection in a rat model of multiple sclerosis. In conclusion, this novel class of direct S1P lyase inhibitors provides excellent tools to further explore the therapeutic potential of T cell-targeted therapies in multiple sclerosis and other autoimmune and inflammatory diseases. PMID:24809814

Weiler, Sven; Braendlin, Nadine; Beerli, Christian; Bergsdorf, Christian; Schubart, Anna; Srinivas, Honnappa; Oberhauser, Berndt; Billich, Andreas

2014-06-26

294

Cement from magnesium substituted hydroxyapatite.  

PubMed

Brushite cement may be used as a bone graft material and is more soluble than apatite in physiological conditions. Consequently it is considerably more resorbable in vivo than apatite forming cements. Brushite cement formation has previously been reported by our group following the mixture of nanocrystalline hydroxyapatite and phosphoric acid. In this study, brushite cement was formed from the reaction of nanocrystalline magnesium-substituted hydroxyapatite with phosphoric acid in an attempt to produce a magnesium substituted brushite cement. The presence of magnesium was shown to have a strong effect on cement composition and strength. Additionally the presence of magnesium in brushite cement was found to reduce the extent of brushite hydrolysis resulting in the formation of HA. By incorporating magnesium ions in the apatite reactant structure the concentration of magnesium ions in the liquid phase of the cement was controlled by the dissolution rate of the apatite. This approach may be used to supply other ions to cement systems during setting as a means to manipulate the clinical performance and characteristics of brushite cements. PMID:15875256

Lilley, K J; Gbureck, U; Knowles, J C; Farrar, D F; Barralet, J E

2005-05-01

295

The reuse of municipal solid waste incinerator fly ash slag as a cement substitute  

Microsoft Academic Search

The results of the treatment of fly ash from a municipal solid waste incinerator (MSWI) by melting are described, and the safety and the effectiveness of using the slag produced by this melting treatment are studied. The properties of the MSWI fly ash slag were analyzed, to evaluate the feasibility of its reuse as a substitute for part of the

K. L Lin; K. S Wang; B. Y Tzeng; C. Y Lin

2003-01-01

296

Polycyclic Aromatic Triptycenes: Oxygen Substitution Cyclization Strategies  

E-print Network

The cyclization and planarization of polycyclic aromatic hydrocarbons with concomitant oxygen substitution was achieved through acid catalyzed transetherification and oxygen-radical reactions. The triptycene scaffold ...

VanVeller, Brett

297

Exfoliation and thermal transformations of Nb-substituted layered titanates  

NASA Astrophysics Data System (ADS)

Single-layer Nb-substituted titanate nanosheets of ca. 1 nm thickness were obtained by exfoliating tetrabutylammonium (TBA)-intercalated Nb-substituted titanates in water. AFM images and turbidity measurements reveal that the exfoliated nanosheets crack and corrugate when sonicated. Upon heating, the thermal transformation into anatase and further to rutile is retarded. This suppression of the phase transition upon higher valent substitution may promote technological applications of anatase thin films, hereunder development of films with TCO properties. Depending on the oxygen partial pressure during the transformation, the Nb-substitution into TiO 2 provokes different defect situations and also electronic properties. At reducing conditions, Nb is incorporated as Nb V and an equivalent amount of Ti IV is transformed to Ti III as evidenced by XPS. Magnetic susceptibility data show accordingly paramagnetic behavior. For samples heated in air Ti IV and Nb V cations prevail, the latter is compensated by cation vacancies. 93Nb MAS NMR data prove that Nb is finely dispersed into the transformed (Ti,Nb)O 2 oxide matrices without sign of Nb 2O 5 (nano)precipitates. The Nb-O-Ti bonds and defects at cation sites are considered key factors for increasing the transformation temperatures for conversion of the nanosheets to anatase and finally into rutile. It is further tempting to link the delay in crystallization to morphology limitations originating from the nanosheets. The present work shows that layered Nb-titanates are appropriate precursors for formation of highly oriented Nb-substituted anatase thin films via delamination, reconstruction and subsequent heat treatment.

Song, Haiyan; Sjåstad, Anja O.; Fjellvåg, Helmer; Okamoto, Hiroshi; Vistad, Ørnulv B.; Arstad, Bjørnar; Norby, Poul

2011-12-01

298

Dihydro-3-(triphenylphosphoranylidene)-2,5-thiophendione: A Convenient Synthon for the Preparation of Substituted 1,4-Thiazepin-5-ones and Piperidinones via the Intermediacy of Thioacids.  

PubMed

Reaction of thiomaleic anhydride with triphenylphosphine gives the title compound which undergoes reaction with a variety of aldehydes to give a range of alkylidene thiomaleic anhydrides (substituted monothio itaconic anhydrides). Subsequent treatment with tert-butoxycarbonylamino-substituted thiols, or under radical conditions with tert-butoxycarbonylamino-substituted alkyl halides results in a series of substituted monothiomaleic anhydrides, that on exposure to trifluoroacetic acid and then base lead to thiocarboxyl substituted 1,4-thiazepin-5-ones and piperidinones, respectively, that are ultimately trapped by reaction with 2,4-dinitrobenzenesulfonamides to give the corresponding amides. PMID:21170150

Crich, David; Rahaman, Md Yeajur

2010-08-14

299

Pharmacological maintenance treatments of opiate addiction.  

PubMed

For people seeking treatment, the course of heroin addiction tends to be chronic and relapsing, and longer duration of treatment is associated with better outcomes. Heroin addiction is strongly associated with deviant behaviour and crime, and the objectives in treating heroin addiction have been a blend of humane support, rehabilitation, public health intervention and crime control. Reduction in street heroin use is the foundation on which all these outcomes are based. The pharmacological basis of maintenance treatment of dependent individuals is to minimize withdrawal symptoms and attenuate the reinforcing effects of street heroin, leading to reduction or cessation of street heroin use. Opioid maintenance treatment can be moderately effective in suppressing heroin use, although deviations from evidence-based approaches, particularly the use of suboptimal doses, have meant that treatment as delivered in practice may have resulted in poorer outcomes than predicted by research. Methadone treatment has been 'programmatic', with a one-size-fits-all approach that in part reflects the perceived need to impose discipline on deviant individuals. However, differences in pharmacokinetics and in side-effects mean that many patients do not respond optimally to methadone. Injectable diamorphine (heroin) provides a more reinforcing medication for some 'nonresponders' and can be a valuable option in the rehabilitation of demoralized, socially excluded individuals. Buprenorphine, a partial agonist, is a less reinforcing medication with different side-effects and less risk of overdose. Not only is it a different medication, but also it can be used in a different paradigm of treatment, office-based opioid treatment, with less structure and offering greater patient autonomy. PMID:23210630

Bell, James

2014-02-01

300

Pharmacological maintenance treatments of opiate addiction  

PubMed Central

For people seeking treatment, the course of heroin addiction tends to be chronic and relapsing, and longer duration of treatment is associated with better outcomes. Heroin addiction is strongly associated with deviant behaviour and crime, and the objectives in treating heroin addiction have been a blend of humane support, rehabilitation, public health intervention and crime control. Reduction in street heroin use is the foundation on which all these outcomes are based. The pharmacological basis of maintenance treatment of dependent individuals is to minimize withdrawal symptoms and attenuate the reinforcing effects of street heroin, leading to reduction or cessation of street heroin use. Opioid maintenance treatment can be moderately effective in suppressing heroin use, although deviations from evidence-based approaches, particularly the use of suboptimal doses, have meant that treatment as delivered in practice may have resulted in poorer outcomes than predicted by research. Methadone treatment has been ‘programmatic’, with a one-size-fits-all approach that in part reflects the perceived need to impose discipline on deviant individuals. However, differences in pharmacokinetics and in side-effects mean that many patients do not respond optimally to methadone. Injectable diamorphine (heroin) provides a more reinforcing medication for some ‘nonresponders’ and can be a valuable option in the rehabilitation of demoralized, socially excluded individuals. Buprenorphine, a partial agonist, is a less reinforcing medication with different side-effects and less risk of overdose. Not only is it a different medication, but also it can be used in a different paradigm of treatment, office-based opioid treatment, with less structure and offering greater patient autonomy. PMID:23210630

Bell, James

2014-01-01

301

Asymmetric Synthesis of Substituted Tropinones using the Intramolecular Mannich Cyclization Reaction and Acyclic N-Sulfinyl ?-Amino Ketone Ketals  

PubMed Central

Sulfinimine-derived, enantiopure N-sulfinyl ?-amino ketone ketals on hydrolysis give dehydropyrrolidine ketones that on treatment with (Boc)2O/DMAP afford substituted tropinones in good yield. PMID:19278245

Davis, Franklin A.; Theddu, Naresh; Gaspari, Paul M.

2009-01-01

302

Effects of generic substitution on refill adherence to statin therapy: a nationwide population-based study.  

PubMed

BackgroundSeveral countries have introduced generic substitution, but few studies have assessed its effect on refill adherence. This study aimed to analyse whether generic substitution influences refill adherence to statin treatment.MethodsBetween 1 July 2006 and 30 June 2007, new users of simvastatin (n¿=¿108,806) and atorvastatin (n¿=¿7,464) were identified in the Swedish Prescribed Drug Register . The present study included atorvastatin users as an unexposed control group because atorvastatin was patent-protected and thus not substitutable. We assessed refill adherence using continuous measure of medication acquisition (CMA). To control for potential confounders, we used analysis of covariance (ANCOVA). Differences in CMA associated with generic substitution and generic substitution at first-time statin purchase were analysed.ResultsNine of ten simvastatin users were exposed to generic substitution during the study period, and their adherence rate was higher than that of patients without substitution [84.6% (95% CI 83.5-85.6) versus 59.9% (95% CI 58.4-61.4), p¿<¿0.001]. CMA rose with increasing age (60¿69 years 16.7%, p < 0.0001 and 70¿79 years 17.8%, p < 0.0001, compared to 18¿39 years) and secondary prevention (12.8%, p < 0.0001). CMA was lower among patients who were exposed to generic substitution upon initial purchase, compared to those who were exposed to a generic substitution subsequently [80.4% (95% CI 79.4-90.9) versus 89.8% (88.7-90.9), p < 0.001]. This difference decreased when those with only one statin purchase were excluded.ConclusionsStatin refill adherence was higher among patients who exposed to generic substitution compared to those who were not. Increasing age and previous cardiovascular disease affected refill adherence. PMID:25475416

Trusell, Henrik; Andersson Sundell, Karolina

2014-12-01

303

What happened to blood substitutes?  

PubMed

Concerns about the safety and adequacy of the blood supply have fostered twenty years of research into the so-called "blood substitutes" among them the oxygen carriers based on modified hemoglobin. Although none of these materials has yet been licensed for use in North America or Europe, the results of research and clinical trials have increased our understanding of oxygen delivery and its regulation. In particular, the examination of the basis for the vasoactivity observed with some of the hemoglobin based oxygen carriers has led to the insight that several colligative properties of hemoglobin solutions, such as their diffusion coefficient for oxygen, viscosity and colloid oncotic pressure, are important determinants of efficacy. PMID:16326128

Stowell, C P

2005-11-01

304

Material substitution and path dependence: empirical evidence on the substitution of copper for aluminum  

Microsoft Academic Search

Adopting an evolutionary perspective, this paper argues that path dependence plays a major role in material use and substitution such that it might delay or even prevent substitution despite the occurrence of significant relative price changes. After elucidating the importance of material substitution from an ecological-economic point of view and after explaining the meaning of path dependence from an evolutionary

Frank Messner

2002-01-01

305

SIMILARITY NETWORK FOR SEMANTIC WEB SERVICES SUBSTITUTION  

E-print Network

SIMILARITY NETWORK FOR SEMANTIC WEB SERVICES SUBSTITUTION Chantal Cherifi LE2I Laboratory, Burgundy is performed on a benchmark of semantically annotated Web services. Results show that this approach allows a more detailed analysis of substitutable Web services. Keywords - Semantic Web services, Functional

Paris-Sud XI, Université de

306

Educators Take Another Look at Substitutes  

ERIC Educational Resources Information Center

The mythology surrounding the substitute teacher is not a pretty one: Paper airplanes, lost learning, bullying. But as schools collect more information about teacher absenteeism and its consequences, districts and schools are exploring ways to professionalize substitute teaching--or experiment with alternative ways of coping with teacher absences.…

Zubrzycki, Jaclyn

2012-01-01

307

Amino acid substitution matrices from protein blocks  

Microsoft Academic Search

Methods for alignment of protein sequences typically measure similarity by using a substitution matrix with scores for all possible exchanges of one amino acid with another. The most widely used matrices are based on the Dayhoff model of evolutionary rates. Using a different approach, we have derived substitution matrices from about 2000 blocks of aligned sequence segments characterizing more than

Steven Henikoff; Jorja G. Henikoff

1992-01-01

308

Carboranylmethylene-substituted phosphazenes and polymers thereof  

NASA Technical Reports Server (NTRS)

Carboranylmethylene-substituted cyclophosphazenes are described which can be thermally polymerized into carboranylmethylene-substituted phosphazene polymers. The polymers are useful as thermally stable coatings. Also, due to the characteristics of these polymers in acting as a ligand for transition metals, metalocarboranylmethylene phosphazene polymers are described which can act as immobilized catalyst systems, and are electrically conductive and superconductive.

Allcock, H. R.; Scopelianos, A. G. (inventors)

1984-01-01

309

Savvy Substitutions. Tricks of the Trade.  

ERIC Educational Resources Information Center

Provides ideas for using throwaways and substitutions, such as homemade objects and everyday items, as art supplies and other resources in the art classroom. Throwaways and substitutions are a way to be environmentally caring, to extend meager supplies, and to supplement art budgets. (CMK)

Guhin, Paula

2000-01-01

310

Substitute Your Way to a Real Job  

ERIC Educational Resources Information Center

For some, substitute teaching is a career choice. However, for the majority of new teachers, it is often a necessary gateway to landing a first job. Either way, it is a great way to sharpen one's skills. This article presents tips from principals, teachers, and human resource directors to make the most of the substitute teaching experience…

Stephens, Cathy

2013-01-01

311

Toxicity of N-substituted aromatics to acetoclastic methanogenic activity in granular sludge.  

PubMed Central

N-substituted aromatics are important priority pollutants entering the environment primarily through anthropogenic activities associated with the industrial production of dyes, explosives, pesticides, and pharmaceuticals. Anaerobic treatment of wastewaters discharged by these industries could potentially be problematical as a result of the high toxicity of N-substituted aromatics. The objective of this study was to examine the structure-toxicity relationships of N-substituted aromatic compounds to acetoclastic methanogenic bacteria. The toxicity was assayed in serum flasks by measuring methane production in granular sludge. Unacclimated cultures were used to minimize the biotransformation of the toxic organic chemicals during the test. The nature and the degree of the aromatic substitution were observed to have a profound effect on the toxicity of the test compound. Nitroaromatic compounds were, on the average, over 500-fold more toxic than their corresponding aromatic amines. Considering the facile reduction of nitro groups by anaerobic microorganisms, a dramatic detoxification of nitroaromatics towards methanogens can be expected to occur during anaerobic wastewater treatment. While the toxicity exerted by the N-substituted aromatic compounds was closely correlated with compound apolarity (log P), it was observed that at any given log P, N-substituted phenols had a toxicity that was 2 orders of magnitude higher than that of chlorophenols and alkylphenols. This indicates that toxicity due to the chemical reactivity of nitroaromatics is much more important than partitioning effects in bacterial membranes. PMID:8526501

Donlon, B A; Razo-Flores, E; Field, J A; Lettinga, G

1995-01-01

312

40 CFR 721.320 - Acrylamide-substituted epoxy.  

...2014-07-01 2014-07-01 false Acrylamide-substituted epoxy. 721.320 ...Chemical Substances § 721.320 Acrylamide-substituted epoxy. (a) Chemical...chemical substance identified generically as acrylamide-substituted epoxy (PMN...

2014-07-01

313

40 CFR 721.320 - Acrylamide-substituted epoxy.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Acrylamide-substituted epoxy. 721.320 ...Chemical Substances § 721.320 Acrylamide-substituted epoxy. (a) Chemical...chemical substance identified generically as acrylamide-substituted epoxy (PMN...

2013-07-01

314

40 CFR 721.10254 - Substituted acrylamide (generic).  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Substituted acrylamide (generic). 721.10254 Section...Substances § 721.10254 Substituted acrylamide (generic). (a) Chemical substance...identified generically as substituted acrylamide (PMN P-09-390) is subject...

2013-07-01

315

40 CFR 721.10254 - Substituted acrylamide (generic).  

...2014-07-01 false Substituted acrylamide (generic). 721.10254 Section...Substances § 721.10254 Substituted acrylamide (generic). (a) Chemical substance...identified generically as substituted acrylamide (PMN P-09-390) is subject...

2014-07-01

316

40 CFR 721.320 - Acrylamide-substituted epoxy.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 false Acrylamide-substituted epoxy. 721.320 ...Chemical Substances § 721.320 Acrylamide-substituted epoxy. (a) Chemical...chemical substance identified generically as acrylamide-substituted epoxy (PMN...

2010-07-01

317

40 CFR 721.10254 - Substituted acrylamide (generic).  

Code of Federal Regulations, 2012 CFR

...2012-07-01 false Substituted acrylamide (generic). 721.10254 Section...Substances § 721.10254 Substituted acrylamide (generic). (a) Chemical substance...identified generically as substituted acrylamide (PMN P-09-390) is subject...

2012-07-01

318

40 CFR 721.320 - Acrylamide-substituted epoxy.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 2012-07-01 false Acrylamide-substituted epoxy. 721.320 ...Chemical Substances § 721.320 Acrylamide-substituted epoxy. (a) Chemical...chemical substance identified generically as acrylamide-substituted epoxy (PMN...

2012-07-01

319

40 CFR 721.320 - Acrylamide-substituted epoxy.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 2011-07-01 false Acrylamide-substituted epoxy. 721.320 ...Chemical Substances § 721.320 Acrylamide-substituted epoxy. (a) Chemical...chemical substance identified generically as acrylamide-substituted epoxy (PMN...

2011-07-01

320

40 CFR 721.2025 - Substituted phenylimino carbamate derivative.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Substituted phenylimino carbamate derivative. 721.2025 Section 721...721.2025 Substituted phenylimino carbamate derivative. (a) Chemical substance...generically as a substituted phenylimino carbamate derivative (PMN P-91-487)...

2013-07-01

321

40 CFR 721.2025 - Substituted phenylimino carbamate derivative.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 false Substituted phenylimino carbamate derivative. 721.2025 Section 721...721.2025 Substituted phenylimino carbamate derivative. (a) Chemical substance...generically as a substituted phenylimino carbamate derivative (PMN P-91-487)...

2011-07-01

322

40 CFR 721.2025 - Substituted phenylimino carbamate derivative.  

...2014-07-01 false Substituted phenylimino carbamate derivative. 721.2025 Section 721...721.2025 Substituted phenylimino carbamate derivative. (a) Chemical substance...generically as a substituted phenylimino carbamate derivative (PMN P-91-487)...

2014-07-01

323

40 CFR 721.2025 - Substituted phenylimino carbamate derivative.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 false Substituted phenylimino carbamate derivative. 721.2025 Section 721...721.2025 Substituted phenylimino carbamate derivative. (a) Chemical substance...generically as a substituted phenylimino carbamate derivative (PMN P-91-487)...

2012-07-01

324

40 CFR 721.4596 - Diazo substituted carbomonocyclic metal complex.  

Code of Federal Regulations, 2010 CFR

...Diazo substituted carbomonocyclic metal complex. 721.4596 Section 721.4596 ...Diazo substituted carbomonocyclic metal complex. (a) Chemical substance and significant...diazo substituted carbomonocyclic metal complex (PMN P-94-1039) is subject...

2010-07-01

325

40 CFR 721.1760 - Substituted benzotriazole derivatives.  

Code of Federal Regulations, 2010 CFR

... false Substituted benzotriazole derivatives. 721.1760 Section 721.1760...721.1760 Substituted benzotriazole derivatives. (a) Chemical substances and significant...generically as substituted benzotriazole derivatives (PMNs P-93-374 and...

2010-07-01

326

40 CFR 721.2025 - Substituted phenylimino carbamate derivative.  

Code of Federal Regulations, 2010 CFR

... Substituted phenylimino carbamate derivative. 721.2025 Section 721.2025... Substituted phenylimino carbamate derivative. (a) Chemical substance and significant...as a substituted phenylimino carbamate derivative (PMN P-91-487) is subject...

2010-07-01

327

40 CFR 721.2527 - Substituted diphenylazo dye (generic name).  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Substituted diphenylazo dye (generic name). 721.2527 Section... § 721.2527 Substituted diphenylazo dye (generic name). (a) Chemical substance...generically as a substituted diphenylazo dye (PMN P-95-514) is subject to...

2010-07-01

328

40 CFR 721.5278 - Substituted naphthalenesulfonic acid, alkali salt.  

...Substituted naphthalenesulfonic acid, alkali salt. 721.5278 Section 721.5278 ...Substituted naphthalenesulfonic acid, alkali salt. (a) Chemical substance and significant...substituted naphthalenesulfonic acid, alkali salt (PMN P-95-85) is subject to...

2014-07-01

329

40 CFR 721.5278 - Substituted naphthalenesulfonic acid, alkali salt.  

Code of Federal Regulations, 2011 CFR

...Substituted naphthalenesulfonic acid, alkali salt. 721.5278 Section 721.5278 ...Substituted naphthalenesulfonic acid, alkali salt. (a) Chemical substance and significant...substituted naphthalenesulfonic acid, alkali salt (PMN P-95-85) is subject to...

2011-07-01

330

40 CFR 721.8900 - Substituted halogenated pyridinol, alkali salt.  

Code of Federal Regulations, 2010 CFR

...Substituted halogenated pyridinol, alkali salt. 721.8900 Section 721.8900 ...Substituted halogenated pyridinol, alkali salt. (a) Chemical substances and significant...substituted halogenated pyridinols, alkali salts (PMNs P-88-1271 and...

2010-07-01

331

40 CFR 721.8900 - Substituted halogenated pyridinol, alkali salt.  

Code of Federal Regulations, 2013 CFR

...Substituted halogenated pyridinol, alkali salt. 721.8900 Section 721.8900 ...Substituted halogenated pyridinol, alkali salt. (a) Chemical substances and significant...substituted halogenated pyridinols, alkali salts (PMNs P-88-1271 and...

2013-07-01

332

40 CFR 721.640 - Amine substituted metal salts.  

...2014-07-01 false Amine substituted metal salts. 721.640 Section 721.640 Protection... § 721.640 Amine substituted metal salts. (a) Chemical substance and significant...identified generically as amine substituted metal salts (PMNs...

2014-07-01

333

40 CFR 721.3565 - Ethylenediamine, substituted, sodium salt.  

Code of Federal Regulations, 2011 CFR

... Ethylenediamine, substituted, sodium salt. 721.3565 Section 721.3565 ...Ethylenediamine, substituted, sodium salt. (a) Chemical substance and significant...as ethylenediamine, substituted, sodium salt (PMN P-97-328) is subject to...

2011-07-01

334

40 CFR 721.8670 - Alkylcyano substituted pyridazo benzoate.  

Code of Federal Regulations, 2010 CFR

...false Alkylcyano substituted pyridazo benzoate. 721.8670 Section 721.8670...8670 Alkylcyano substituted pyridazo benzoate. (a) Chemical substance and significant...as an alkylcyano substituted pyridazo benzoate (PMN P-94-1129) is subject...

2010-07-01

335

Substituted Hydroxyapatites with Antibacterial Properties  

PubMed Central

Reconstructive surgery is presently struggling with the problem of infections located within implantation biomaterials. Of course, the best antibacterial protection is antibiotic therapy. However, oral antibiotic therapy is sometimes ineffective, while administering an antibiotic at the location of infection is often associated with an unfavourable ratio of dosage efficiency and toxic effect. Thus, the present study aims to find a new factor which may improve antibacterial activity while also presenting low toxicity to the human cells. Such factors are usually implemented along with the implant itself and may be an integral part of it. Many recent studies have focused on inorganic factors, such as metal nanoparticles, salts, and metal oxides. The advantages of inorganic factors include the ease with which they can be combined with ceramic and polymeric biomaterials. The following review focuses on hydroxyapatites substituted with ions with antibacterial properties. It considers materials that have already been applied in regenerative medicine (e.g., hydroxyapatites with silver ions) and those that are only at the preliminary stage of research and which could potentially be used in implantology or dentistry. We present methods for the synthesis of modified apatites and the antibacterial mechanisms of various ions as well as their antibacterial efficiency. PMID:24949423

Kolmas, Joanna; Groszyk, Ewa; Kwiatkowska-Ró?ycka, Dagmara

2014-01-01

336

Electrophoretic deposition of zinc-substituted hydroxyapatite coatings.  

PubMed

Zinc-substituted hydroxyapatite nanoparticles synthesized by the co-precipitation method were used to coat stainless steel plates by electrophoretic deposition in n-butanol with triethanolamine as a dispersant. The effect of zinc concentration in the synthesis on the morphology and microstructure of coatings was investigated. It is found that the deposition current densities significantly increase with the increasing zinc concentration. The zinc-substituted hydroxyapatite coatings were analyzed by X-ray diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy. It is inferred that hydroxyapatite and triethanolamine predominate in the chemical composition of coatings. With the increasing Zn/Ca ratios, the contents of triethanolamine decrease in the final products. The triethanolamine can be burnt out by heat treatment. The tests of adhesive strength have confirmed good adhesion between the coatings and substrates. The formation of new apatite layer on the coatings has been observed after 7days of immersion in a simulated body fluid. In summary, the results show that dense, uniform zinc-substituted hydroxyapatite coatings are obtained by electrophoretic deposition when the Zn/Ca ratio reaches 5%. PMID:24863199

Sun, Guangfei; Ma, Jun; Zhang, Shengmin

2014-06-01

337

Synthesis and reactivity of 4-amino-substituted furfurals.  

PubMed

?-Hydroxy ?,?-unsaturated acetylenic ketones have been converted to 4-amino-substituted furfurals by reaction with secondary amines followed by treatment with acid in a mixture of THF and water. The stability of the furfurals depends to some extent on the nature of the amino group, whereas the reactivity has been shown to be reagent-dependent. When treated with phosphorus ylids, the expected alkenes are formed with E configuration in high yields, but when exposed to nitroalkanes under basic conditions (the Henry reaction) abnormal transformations appear to occur, and 2-acylated furans are obtained, albeit in low yield, instead of nitroalkanols. PMID:24393100

Erdenebileg, Uranbaatar; Høstmark, Inger; Polden, Karina; Sydnes, Leiv K

2014-02-01

338

A users' guide to understanding therapeutic substitutions.  

PubMed

Therapeutic substitutions are common at the level of ministries of health, clinicians, and pharmacy dispensaries. Guidance in determining whether drugs offer similar risk-benefit profiles is limited. Those making decisions on therapeutic substitutions should be aware of potential biases that make differentiating therapeutic agents difficult. Readers should consider whether the biological mechanisms and doses are similar across agents, whether the evidence is sufficiently valid across agents, and whether the safety and therapeutic effects of each drug are similar. This article uses a problem-based format to address the biological mechanism, validity, and results of a scenario in which therapeutic substitutions may be considered. PMID:24291506

Mills, Edward J; Gardner, David; Thorlund, Kristian; Briel, Matthias; Bryan, Stirling; Hutton, Brian; Guyatt, Gordon H

2014-03-01

339

40 CFR 721.10199 - Substituted aliphatic amine (generic).  

Code of Federal Regulations, 2010 CFR

40 Protection of Environment 30...Substituted aliphatic amine (generic). 721...Section 721.10199 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...Substituted aliphatic amine (generic)....

2010-07-01

340

Emerging drugs of abuse: current perspectives on substituted cathinones  

PubMed Central

Substituted cathinones are synthetic analogs of cathinone that can be considered as derivatives of phenethylamines with a beta-keto group on the side chain. They appeared in the recreational drug market in the mid-2000s and now represent a large class of new popular drugs of abuse. Initially considered as legal highs, their legal status is variable by country and is rapidly changing, with government institutions encouraging their control. Some cathinones (such as diethylpropion or pyrovalerone) have been used in a medical setting and bupropion is actually indicated for smoking cessation. Substituted cathinones are widely available from internet websites, retail shops, and street dealers. They can be sold under chemical, evocative or generic names, making their identification difficult. Fortunately, analytical methods have been developed in recent years to solve this problem. Available as powders, substituted cathinones are self-administered by snorting, oral injestion, or intravenous injection. They act as central nervous system stimulants by causing the release of catecholamines (dopamine, noradrenaline, and serotonin) and blocking their reuptake in the central and peripheral nervous system. They may also decrease dopamine and serotonin transporter function as nonselective substrates or potent blockers and may inhibit monoamine oxidase effects. Nevertheless, considerable differences have been found in the potencies of the different substituted cathinones in vitro. Desired effects reported by users include increased energy, empathy, and improved libido. Cardiovascular (tachycardia, hypertension) and psychiatric/neurological signs/symptoms (agitation, seizures, paranoia, and hallucinations) are the most common adverse effects reported. Severe toxicity signs compatible with excessive serotonin activity, such as hyperthermia, metabolic acidosis, and prolonged rhabdomyolysis, have also been observed. Reinforcing potential observed in animals predicts a high potential for addiction and abuse in users. In case of overdose, no specific antidote exists and no curative treatment has been approved by health authorities. Therefore, management of acute toxic effects is mainly extrapolated from experience with cocaine/amphetamines. PMID:24966713

Paillet-Loilier, Magalie; Cesbron, Alexandre; Le Boisselier, Reynald; Bourgine, Joanna; Debruyne, Danièle

2014-01-01

341

Substitutions into propositional tautologies Jan Krajcek #+#  

E-print Network

Substitutions into propositional tautologies Jan Krajâ??�Ÿcek #+# Isaac Newton Institute, Cambridge University, Prague. # The paper was written while at the Isaac Newton Institute in Cambridge (Logic

Krajíèek, Jan

342

Processed bovine dentine as a bone substitute  

Microsoft Academic Search

ObjectivesDifferent forms of allogenic dentine have been studied for their potential use as bone substitutes. We report a new method for processing bovine dentine that results in a sterile bioactive material for repair and regeneration of bone.

Keyvan Moharamzadeh; Christine Freeman; Keith Blackwood

2008-01-01

343

24 CFR 221.252 - Substitute mortgagors.  

Code of Federal Regulations, 2010 CFR

...PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES LOW COST AND MODERATE INCOME MORTGAGE INSURANCE-SAVINGS CLAUSE Contract Rights and Obligations-Low Cost Homes § 221.252 Substitute mortgagors. (a)...

2010-04-01

344

24 CFR 221.252 - Substitute mortgagors.  

Code of Federal Regulations, 2013 CFR

...PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES LOW COST AND MODERATE INCOME MORTGAGE INSURANCE-SAVINGS CLAUSE Contract Rights and Obligations-Low Cost Homes § 221.252 Substitute mortgagors. (a)...

2013-04-01

345

24 CFR 221.252 - Substitute mortgagors.  

Code of Federal Regulations, 2011 CFR

...PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES LOW COST AND MODERATE INCOME MORTGAGE INSURANCE-SAVINGS CLAUSE Contract Rights and Obligations-Low Cost Homes § 221.252 Substitute mortgagors. (a)...

2011-04-01

346

24 CFR 221.252 - Substitute mortgagors.  

Code of Federal Regulations, 2012 CFR

...PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES LOW COST AND MODERATE INCOME MORTGAGE INSURANCE-SAVINGS CLAUSE Contract Rights and Obligations-Low Cost Homes § 221.252 Substitute mortgagors. (a)...

2012-04-01

347

24 CFR 221.252 - Substitute mortgagors.  

...PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES LOW COST AND MODERATE INCOME MORTGAGE INSURANCE-SAVINGS CLAUSE Contract Rights and Obligations-Low Cost Homes § 221.252 Substitute mortgagors. (a)...

2014-04-01

348

Nutrient-substituted hydroxyapatites: synthesis and characterization  

NASA Technical Reports Server (NTRS)

Incorporation of Mg, S, and plant-essential micronutrients into the structure of synthetic hydroxyapatite (HA) may be advantageous for closed-loop systems, such as will be required on Lunar and Martian outposts, because these apatites can be used as slow-release fertilizers. Our objective was to synthesize HA with Ca, P, Mg, S, Fe, Cu, Mn, Zn, Mo, B, and Cl incorporated into the structure, i.e., nutrient-substituted apatites. Hydroxyapatite, carbonate hydroxyapatite (CHA), nutrient-substituted hydroxyapatite (NHA), and nutrient-substituted carbonate hydroxyapatite (NCHA) were synthesized by precipitating from solution. Chemical and mineralogical analysis of precipitated samples indicated a considerable fraction of the added cations were incorporated into HA, without mineral impurities. Particle size of the HA was in the 1 to 40 nm range, and decreased with increased substitution of nutrient elements. The particle shape of HA was elongated in the c-direction in unsubstituted HA and NHA but more spherical in CHA and NCHA. The substitution of cations and anions in the HA structure was confirmed by the decrease of the d[002] spacing of HA with substitution of ions with an ionic radius less than that of Ca or P. The DTPA-extractable Cu ranged from 8 to 8429 mg kg-1, Zn ranged from 57 to 1279 mg kg-1, Fe from 211 to 2573 mg kg-1, and Mn from 190 to 1719 mg kg-1, depending on the substitution level of each element in HA. Nutrient-substituted HA has the potential to be used as a slow-release fertilizer to supply micronutrients, S, and Mg in addition to Ca and P.

Golden, D. C.; Ming, D. W.

1999-01-01

349

Rapid hydrothermal flow synthesis and characterisation of carbonate- and silicate-substituted calcium phosphates  

PubMed Central

A range of crystalline and nano-sized carbonate- and silicate-substituted hydroxyapatite has been successfully produced by using continuous hydrothermal flow synthesis technology. Ion-substituted calcium phosphates are better candidates for bone replacement applications (due to improved bioactivity) as compared to phase-pure hydroxyapatite. Urea was used as a carbonate source for synthesising phase pure carbonated hydroxyapatite (CO3-HA) with ?5?wt% substituted carbonate content (sample 7.5CO3-HA) and it was found that a further increase in urea concentration in solution resulted in biphasic mixtures of carbonate-substituted hydroxyapatite and calcium carbonate. Transmission electron microscopy images revealed that the particle size of hydroxyapatite decreased with increasing urea concentration. Energy-dispersive X-ray spectroscopy result revealed a calcium deficient apatite with Ca:P molar ratio of 1.45 (±0.04) in sample 7.5CO3-HA. For silicate-substituted hydroxyapatite (SiO4-HA) silicon acetate was used as a silicate ion source. It was observed that a substitution threshold of ?1.1?wt% exists for synthesis of SiO4-HA in the continuous hydrothermal flow synthesis system, which could be due to the decreasing yields with progressive increase in silicon acetate concentration. All the as-precipitated powders (without any additional heat treatments) were analysed using techniques including Transmission electron microscopy, X-ray powder diffraction, Differential scanning calorimetry, Thermogravimetric analysis, Raman spectroscopy and Fourier transform infrared spectroscopy. PMID:22983020

Knowles, Jonathan C; Rehman, Ihtesham; Darr, Jawwad A

2013-01-01

350

Thermomigration in alloys for which substitutional-vacancy and interstitial-vacancy mechanisms are operative  

Microsoft Academic Search

The theoretical treatments of alloy diffusion in a temperature gradient by the substitutional-vaoanoy mechanism and by the interstitial-vacancy mechanism have been combined, and two types of thermomigration experiments which differ in initial condition have been analysed. It is shown that these experiments, as for measurements of the impurity heat of transport, are apparently incapable of distinguishing between the two mechanisms

B. A. McKee

1977-01-01

351

The effect of particle size on the osteointegration of injectable silicate-substituted calcium phosphate bone substitute materials  

PubMed Central

Calcium phosphate (CaP) particles as a carrier in an injectable bone filler allows less invasive treatment of bony defects. The effect of changing granule size within a poloxamer filler on the osteointegration of silicate-substituted calcium phosphate (SiCaP) bone substitute materials was investigated in an ovine critical-sized femoral condyle defect model. Treatment group (TG) 1 consisted of SiCaP granules sized 1000–2000 ?m in diameter (100 vol %). TG2 investigated a granule size of 250–500 ?m (75 vol %), TG3 a granule size of 90–125 ?m (75 vol %) and TG4 a granule size of 90–125 ?m (50 vol %). Following a 4 and 8 week in vivo period, bone area, bone-implant contact, and remaining implant area were quantified within each defect. At 4 weeks, significantly increased bone formation was measured in TG2 (13.32% ± 1.38%) when compared with all other groups (p = 0.021 in all cases). Bone in contact with the bone substitute surface was also significantly higher in TG2. At 8 weeks most new bone was associated within defects containing the smallest granule size investigated (at the lower volume) (TG4) (42.78 ± 3.36%) however this group was also associated with higher amounts of fragmented SiCaP. These smaller particles were phagocytosed by macrophages and did not appear to have a negative influence on healing. In conclusion, SiCaP granules of 250–500 ?m in size may be a more suitable scaffold when used as an injectable bone filler and may be a convenient method for treating bony defects. © 2013 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 902–910, 2013 PMID:23362131

Coathup, Melanie J; Cai, Qian; Campion, Charlie; Buckland, Thomas; Blunn, Gordon W

2013-01-01

352

Water/Wastewater Treatment Plant Operator Qualifications.  

ERIC Educational Resources Information Center

This article summarizes in tabular form the U.S. and Canadian programs for classification of water and wastewater treatment plant personnel. Included are main characteristics of the programs, educational and experience requirements, and indications of requirement substitutions. (CS)

Water and Sewage Works, 1979

1979-01-01

353

Prescription opioid abuse among enrollees into methadone maintenance treatment.  

PubMed

A multi-state survey of 5663 opioid dependent persons enrolling in 72 methadone maintenance treatment programs (MMTPs) was conducted to determine the prevalence of prescription opioid (PO) abuse, factors associated with PO abuse and sources for POs. Regions where PO abuse was believed to be prevalent were oversampled; primary opioid was defined as the drug used the most before coming to the MMTP. Among primary heroin abusers, 69% reported abusing POs. Opioid abuse frequencies among primary PO abusers were oxycodone (79%), hydrocodone (67%), methadone (40%), morphine (29%), heroin (13%), hydromorphone (16%), fentanyl (9%) and buprenorphine (1%). Correlates (p < or = .01) of PO abuse, using general estimating equations, were: low urbanicity (MMTPs located in comparatively low population density counties), white ethnicity, no history of injecting primary drug, no previous methadone treatment, younger age, chronic pain, and pain as a reason for enrollment. The most frequent sources of POs were dealer, friend or relative, and doctor's prescription; least frequent were Internet and forged prescription. One-third of PO abusers reported a history of injecting their primary drug. PO abuse is highly prevalent among MMTP patients. Future studies should describe HIV/HCV needle injection practices, characteristics that predict treatment outcomes, and factors that contribute to higher prevalence of persistent pain among PO abusers. PMID:17386981

Rosenblum, Andrew; Parrino, Mark; Schnoll, Sidney H; Fong, Chunki; Maxwell, Carleen; Cleland, Charles M; Magura, Stephen; Haddox, J David

2007-09-01

354

Structural characterization of microwave-synthesized zinc-substituted cobalt ferrite nanoparticles  

Microsoft Academic Search

Microwave combustion technique modified by post treatment procedure is used to synthesize single-phase spinel ferrites of\\u000a cobalt, zinc, and substituted magnetic nanoparticles of typical size 390 Å. The post treatment does not alter the crystal\\u000a structure but increases the crystallinity. This is confirmed by powder x-ray diffraction and Fourier Transform Infrared (FTIR)\\u000a studies. Citric acid is used as a fuel.

Harshida Parmar; Rucha Desai; R. V. Upadhyay

2011-01-01

355

Characterization of mutagenic activity in grain-based coffee-substitute blends and instant coffees  

SciTech Connect

Several grain-based coffee-substitute blends and instant coffees showed a mutagenic response in the Ames/Salmonella test using TA98, YG1024 and YG1O29 with metabolic activation. The beverage powders contained 150 to 500 TA98 and 1150 to 4050 YG1024 revertant colonies/gram, respectively. The mutagenic activity in the beverage powders was shown to be stable to heat and the products varied in resistance to acid nitrite treatment. Characterization of the mutagenic activity, using HPLC-and the Ames test of the collected fractions, showed the coffee-substitutes and instant coffees contain several mutagenic compounds, which are most likely aromatic amines.

Johansson, M.A.E.; Knize, M.G.; Felton, J.S.; Jagerstad, M.

1994-06-01

356

Substituting telecommunications for travel - Feasible or desirable  

NASA Technical Reports Server (NTRS)

This paper reviews recent advances in telecommunications and examines the detailed structure of travel to estimate the feasibility of substituting telecommunications for various travel objectives. The impact of travel is analyzed from a social, economic, energy, and pollution standpoint to assess the desirability of substitution. Perhaps 35-50% of the nation's travel could, in theory, be replaced by very advanced telecommunications (such as a much improved large-screen teleconferencing network), but public resistance would be massive. Much economic dislocation would result since, for example, over 25% of retail sales are travel-related. The energy savings would be modest since only 25% of the nation's energy is consumed by transportation. However, all pollution would be reduced substantially since transportation accounts for 75% of the carbon monoxide, 60% of the hydrocarbon, and 55% of the nitrogen oxide pollution in the nation. Problems related to the implementation of large-scale substitution are discussed.

Van Vleck, E. M.

1974-01-01

357

Anisotropic Ferromagnetism in Substituted Zinc Oxide  

Microsoft Academic Search

Room-temperature ferromagnetism is observed in (110) oriented ZnO films\\u000acontaining 5 at % of Sc, Ti, V, Fe, Co or Ni, but not Cr, Mn or Cu ions. There\\u000aare large moments, 1.9 and 0.5 muB\\/atom for Co- and Ti-substituted oxides,\\u000arespectively. Sc-substituted ZnO shows also a moment of 0.3 muB\\/Sc.\\u000aMagnetization is very anisotropic, with variations of up to

M. Venkatesan; C. B. Fitzgerald; J. G. Lunney; J. M. D. Coey

2004-01-01

358

Asymmetric synthesis of substituted tropinones using the intramolecular mannich cyclization reaction and acyclic N-sulfinyl beta-amino ketone ketals.  

PubMed

Sulfinimine-derived, enantiopure N-sulfinyl beta-amino ketone ketals on hydrolysis give dehydropyrrolidine ketones that on treatment with (Boc)(2)O/DMAP afford substituted tropinones in good yield. PMID:19278245

Davis, Franklin A; Theddu, Naresh; Gaspari, Paul M

2009-04-01

359

40 CFR Appendix G to Subpart G of... - Substitutes Subject to Use Restrictions and Unacceptable Substitutes Listed in the March 3, 1999...  

Code of Federal Regulations, 2010 CFR

Appendix G to Subpart G of Part 82—Substitutes Subject to Use Restrictions and Unacceptable Substitutes Listed in the March 3, 1999, Final rule, Effective April 2, 1999. Refrigerants Unacceptable Substitutes End-use Substitute Decision...

2010-07-01

360

Asymmetric synthesis of highly substituted azapolycyclic compounds via 2-alkenyl sulfoximines: potential scaffolds for peptide mimetics.  

PubMed

The application of metalated, enantiomerically pure acyclic and cyclic 2-alkenyl sulfoximines for the synthesis of highly substituted aza(poly)cyclic ring systems is described. The method relies on a one-pot combination of a reagent-controlled allyl transfer reaction to alpha- or beta-amino aldehydes, followed by a Michael-type cyclization of the intermediate vinyl sulfoximines generated in the first step. The sulfur-free target compounds are preferentially obtained by samarium iodide treatment of the sulfonimidoyl substituted heterocycles. In addition to this methodological work, initial results on the biological activity of selected examples are reported. Furthermore, a concept for the transformation of peptidic lead structures into non-peptide mimetics is described, and the relevance of the new approach to highly substituted azaheterocycles in this context is discussed. PMID:16551111

Reggelin, Michael; Junker, Bernd; Heinrich, Timo; Slavik, Stefan; Bühle, Philipp

2006-03-29

361

Electronic structures of graphane sheets with foreign atom substitutions  

NASA Astrophysics Data System (ADS)

Using first-principles calculations, we investigate the electronic structures of the recently synthesized hydrogenated graphene, called graphane, with substitutional B, N, P, and Al atoms. We find that both the n-type and p-type substitutions can cause the semiconductor-to-metal transitions in graphane sheets. The substitutional B and Al atoms induce magnetic moments of nearby carbon atoms. Moreover, the B-substituted graphane sheets have the concentration-dependent magnetic properties, while the Al-substituted ones exhibit robust half-metallic behaviors. Our studies demonstrate that the substituted graphane sheets have potential applications in nanoelectronics and spintronics.

Wang, Yanli; Ding, Yi; Shi, Siqi; Tang, Weihua

2011-04-01

362

Syntheses of novel substituted-boranophosphate nucleosides.  

PubMed

A number of substituted (borano) nucleic acids, 3'-[diethylphosphite(cyano, carboxy, or carbamoyl) borano] deoxynucleosides (3a-4c) and 5'-[diethylphosphite(cyano or carboxy) borano] deoxynucleosides (6a-7d) were prepared by a variety of synthetic procedures. The syntheses of the pyrophosphates (2a-2c), as precursors for 3a-4c, are also described. PMID:12484452

Vyakaranam, Kamesh; Rana, Geeta; Spielvogel, Bernard F; Maguire, John A; Hosmane, Narayan S

2002-01-01

363

Eliminating the Substitution Axiom from UNITY Logic  

Microsoft Academic Search

The UNITY substitution axiom, “if (x=y) is an invariant of a program, then x can be replaced by y in any property of the program”, is problematic for several reasons. In this paper, dual predicate transformerssst andwst are introduced that allow the strongest invariant of a program to be expressed, and these are used to give new definitions for the

Beverly A. Sanders

1991-01-01

364

Plant breeding Production of intervarietal substitution lines  

E-print Network

attempted to improve its crossability with rye. The Courtot chromosomes 5A, 5B, 5D were replaced the degree of crossability estimated in BC1. wheat /rye / triticale / crossability genes/substitution lines to combine the hardi- ness of rye (Secale cereale L) with the pro- ductivity of common wheat (Triticum

Boyer, Edmond

365

The Substitution-Elimination Mechanistic Disc Method  

ERIC Educational Resources Information Center

A method designed to facilitate prediction of mechanism and products by developing critical thinking skills and reducing memorization is presented. The mechanistic disc method requiring students to utilize their understanding of charge stabilization, structural organic chemistry, and the fundamental mechanisms of aliphatic substitution and…

Buonora, Paul T.; Yu Jin Lim

2004-01-01

366

A Partial Taxonomy of Substitutability and Interchangeability  

E-print Network

Substitutability, interchangeability and related concepts in Constraint Programming were introduced approximately twenty years ago and have given rise to considerable subsequent research. We survey this work, classify, and relate the different concepts, and indicate directions for future work, in particular with respect to making connections with research into symmetry breaking. This paper is a condensed version of a larger work in progress.

Karakashian, Shant; Choueiry, Berthe Y; Prestwhich, Steven; Freuder, Eugene C

2010-01-01

367

Control of Angiogenesis with Synthetic Heparin Substitutes  

Microsoft Academic Search

Many diseases are dominated by persistent growth of capillary blood vessels. Tumor growth is also angiogenesis-dependent. Safe and effective angiogenesis inhibitors are needed to determine whether control of angiogenesis would be therapeutic. Heparin and certain steroids, administered together, can inhibit angiogenesis in a synergistic manner. This ``pair'' effect suggested that specific hydrophilic cycloamyloses may be suitable heparin substitutes. beta -Cyclodextrin

Judah Folkman; Paul B. Weisz; Madeleine M. Joullie; William W. Li; William R. Ewing

1989-01-01

368

Perfluorinated blood substitutes and artificial oxygen carriers  

Microsoft Academic Search

Blood transfusion is a remarkably safe, routine clinical procedure. However, the need for sophisticated blood processing, storage and cross-matching, coupled with increasing concerns about the safety of blood products, has fuelled the search for safe and efficacious substitutes. Candidate materials based on modified haemoglobin (including recombinant molecules) or highly inert, respiratory gas-dissolving perfluorinated liquids (perfluorochemicals) have been developed. The latter

K. C. Lowe

1999-01-01

369

Polycyclic Aromatic Triptycenes: Oxygen Substitution Cyclization Strategies  

PubMed Central

The cyclization and planarization of polycyclic aromatic hydrocarbons with concomitant oxygen substitution was achieved through acid catalyzed transetherification and oxygen-radical reactions. The triptycene scaffold enforces proximity of the alcohol and arene reacting partners and confers significant rigidity to the resulting ? system, expanding the tool set of iptycenes for materials applications. PMID:22510100

VanVeller, Brett; Schipper, Derek J.; Swager, Timothy M.

2012-01-01

370

Haemorrhage associated with silastic dural substitute.  

PubMed Central

Three cases of haemorrhage after the use of a silastic dural substitute are presented. In all cases the implant was removed and further haemorrhage has not occurred. Published work is reviewed and the implications for the continued use of silastic are discussed. Images PMID:8201348

Thompson, D; Taylor, W; Hayward, R

1994-01-01

371

Balances for xed points of primitive substitutions  

E-print Network

Balances for #12;xed points of primitive substitutions Boris Adamczewski Institut de Math#19. Abstract An in#12;nite word de#12;ned over a #12;nite alphabet A is balanced if for any pair (!; ! 0 generalize this notion and introduce a measure of balance for an in#12;nite sequence. In the case of #12;xed

Provence Aix-Marseille I, Université de

372

Sustained Release d-Amphetamine Reduces Cocaine but not ‘Speedball'-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine/Heroin Polydrug Abusers  

PubMed Central

The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination (‘speedball'-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8?mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8?mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60?mg/day, respectively. After 3 days (Saturday–Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30?mg administered at 0700 and 1225 each day), on Tuesday–Friday mornings (0900–1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100?mg+saline); hydromorphone (COC 4?mg+HYD 24?mg); ‘speedball' (COC 100?mg+HYD 24?mg); and placebo (COC 4?mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy. PMID:20881947

Greenwald, Mark K; Lundahl, Leslie H; Steinmiller, Caren L

2010-01-01

373

Hollow fiber liquid-phase microextraction combined with ultra-high performance liquid chromatography-tandem mass spectrometry for the simultaneous determination of naloxone, buprenorphine and norbuprenorphine in human plasma.  

PubMed

A hollow fiber liquid phase microextraction (HF-LPME) combined with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the extraction and determination of naloxone (NLX), buprenorphine (BP) and its major metabolite norbuprenorphine (NBP) in human plasma. The optimum extraction conditions of HF-LPME were: the porous of polyvinylidene fluoride (PVDF) hollow fiber was full of component solvent (1-octanol/chloroform/toluene, 2/4/4), the pH of donor phase was 8.7, the extraction time was 30min and stirring speed was 1000 revolutions per minute (rpm). The UHPLC-MS/MS method was performed with Waters ACQUITY UPLCTM BEH C18, 50mm×2.1mm, 1.7?m, using methanol-0.2%formic acid as mobile phase with a gradient elution at a flow rate of 0.25mL/min. The target compounds were detected under a tandem quadrupole mass spectrometer in positive electrospray ionization (ESI) mode, then analyzed in multiple reaction monitoring (MRM) mode and the isotope internal standard method was used for quantification. The results showed that linearities were in the range of 0.1-25ng/mL (R>0.996). The limits of detection (LOD) of BP/NBP/NLX were 0.05/0.05/0.025ng/mL and the limits of quantitation (LOQ) of BP/NBP/NLX were 0.1/0.1/0.05ng/mL, respectively. The spiked recoveries were in the range of 92.1-106.0% with relative standard deviation (RSD) values were less than 15%. This method was simple, inexpensive, sensitive and has been successfully used to quantify plasma samples from patients included in a clinical pharmacogenetic study. PMID:24566267

Sun, Wenjun; Qu, Shuping; Du, Zhenxia

2014-03-01

374

Synthesis and cytostatic evaluation of some 2-(5-substituted-2-oxoindolin-3-ylidene)- N -substituted hydrazine carbothioamide  

Microsoft Academic Search

Various substituted 2-(5-substituted-2-oxoindolin-3-ylidene)-N-substituted hydrazine carbothioamide 4a–g and 2-(5-substituted-1-(4-substituted benzyl)-2-oxoindolin-3-ylidene)-N-substituted hydrazine carbothioamide 5a–k were synthesized. The compounds were evaluated for their cytostatic activity against human Molt4\\/C8 and CEM T-lymphocytes\\u000a as well as murine L1210 leukemia cells. Several of these compounds were endowed with low micromolar 50%-inhibitory concentration\\u000a (IC50) values, and some were virtually equally potent as melphalan. The most potent inhibitors

Subhas S. Karki; Amol Kulkarni; Nishith Teraiya; Erik De Clercq; Jan Balzarini

375

Injectability of brushite-forming Mg-substituted and Sr-substituted ?-TCP bone cements  

Microsoft Academic Search

The influence of magnesium- and strontium-substitutions on injectability and mechanical performance of brushite-forming ?-TCP\\u000a cements has been evaluated in the present work. The effects of Mg- and Sr-substitutions on crystalline phase composition and\\u000a lattice parameters were determined through quantitative X-ray phase analysis and structural Rietveld refinement of the starting\\u000a calcium phosphate powders and of the hardened cements. A noticeable dependence

S. Pina; P. M. C. Torres; J. M. F. Ferreira

2010-01-01

376

New substituted amides and hydrazides of pectic acid  

SciTech Connect

Structural variants of pectin amides and hydrazides are of practical value as flocculants in water treatment. The purpose of this work was to further investigate the synthesis of substituted amides and hydrazides of pectic acid and to study their activity as flocculants. They used pectin, methylation products of pectin, pectic acid, and methyl pectates. The synthesized analogs of pectinic materials containing nitrogen are essentially copolymers of hydrazido (amido) and carboxyl (methoxyl) derivatives of D-galacturonic acid. The flocculant activity of the new polymers was monitored with simulated drainage water containing kaolin or abrasive powder (for glass manufacture) in the presence of polyvalent metal ions. The use of the new ampholytic flocculants in the purification of water from suspended impurities permits a high degree of clarification with a sharp decrease in reagent consumption.

Lapenko, V.L.; Potapova, L.B.; Slivkin, A.I.; Razumnaya, Z.A.

1988-05-10

377

N3-substituted thymidine bioconjugates for cancer therapy and imaging  

PubMed Central

The compound class of 3-carboranyl thymidine analogues (3CTAs) are boron delivery agents for boron neutron capture therapy (BNCT), a binary treatment modality for cancer. Presumably, these compounds accumulate selectively in tumor cells via intracellular trapping, which is mediated by hTK1. Favorable in vivo biodistribution profiles of 3CTAs led to promising results in preclinical BNCT of rats with intracerebral brain tumors. This review presents an overview on the design, synthesis, and biological evaluation of first- and second-generation 3CTAs. Boronated nucleosides developed prior to 3CTAs for BNCT and non-boronated N3-substituted thymidine conjugates for other areas of cancer therapy and imaging are also described. In addition, basic features of carborane clusters, which are used as boron moieties in the design and synthesis of 3CTAs, and the biological and structural features of TK1-like enzymes, which are the molecular targets of 3CTAs, are discussed. PMID:23617430

Khalil, Ahmed; Ishita, Keisuke; Ali, Tehane; Tjarks, Werner

2013-01-01

378

Practical Linguistic Steganography using Contextual Synonym Substitution and a  

E-print Network

Practical Linguistic Steganography using Contextual Synonym Substitution and a Novel Vertex Coding steganography is concerned with hiding information in natural language text. One of the major transformations used in linguistic steganography is synonym substitution. However, few existing studies have studied

379

40 CFR 721.6060 - Alkylaryl substituted phosphite.  

Code of Federal Regulations, 2011 CFR

... false Alkylaryl substituted phosphite. 721.6060 Section 721.6060 Protection of Environment ENVIRONMENTAL PROTECTION...New Uses for Specific Chemical Substances § 721.6060 Alkylaryl substituted phosphite. (a)...

2011-07-01

380

40 CFR 721.6060 - Alkylaryl substituted phosphite.  

Code of Federal Regulations, 2012 CFR

... false Alkylaryl substituted phosphite. 721.6060 Section 721.6060 Protection of Environment ENVIRONMENTAL PROTECTION...New Uses for Specific Chemical Substances § 721.6060 Alkylaryl substituted phosphite. (a)...

2012-07-01

381

40 CFR 721.6060 - Alkylaryl substituted phosphite.  

... false Alkylaryl substituted phosphite. 721.6060 Section 721.6060 Protection of Environment ENVIRONMENTAL PROTECTION...New Uses for Specific Chemical Substances § 721.6060 Alkylaryl substituted phosphite. (a)...

2014-07-01

382

40 CFR 721.6060 - Alkylaryl substituted phosphite.  

Code of Federal Regulations, 2013 CFR

... false Alkylaryl substituted phosphite. 721.6060 Section 721.6060 Protection of Environment ENVIRONMENTAL PROTECTION...New Uses for Specific Chemical Substances § 721.6060 Alkylaryl substituted phosphite. (a)...

2013-07-01

383

40 CFR 721.6060 - Alkylaryl substituted phosphite.  

Code of Federal Regulations, 2010 CFR

... false Alkylaryl substituted phosphite. 721.6060 Section 721.6060 Protection of Environment ENVIRONMENTAL PROTECTION...New Uses for Specific Chemical Substances § 721.6060 Alkylaryl substituted phosphite. (a)...

2010-07-01

384

47 CFR 54.646 - Site and service substitutions.  

...SERVICE Universal Service Support for Health Care Providers Healthcare Connect Fund § 54.646 Site and service substitutions...care provider and the service is an eligible service under the Healthcare Connect Fund; (3) The substitution does not...

2014-10-01

385

47 CFR 54.646 - Site and service substitutions.  

Code of Federal Regulations, 2013 CFR

...SERVICE Universal Service Support for Health Care Providers Healthcare Connect Fund § 54.646 Site and service substitutions...care provider and the service is an eligible service under the Healthcare Connect Fund; (3) The substitution does not...

2013-10-01

386

Signalization and stimulus-substitution in Pavlov's theory of conditioning.  

PubMed

The concept of conditioning as signalization proposed by Ivan P. Pavlov (1927, 1928) is studied in relation to the theory of stimulus-substitution, which is also attributed to him. In the so-called theory of stimulus-substitution a distinction must be made between an empirical principle of substitution and an actual theory of substitution, which can adopt different forms. The Pavlovian theory of substitution--which conceives substitution as a substitution of the unconditioned stimulus (US) by the conditioned stimulus (CS) in the activation of the representation of the former--can be understood as an explanation or model of signalization. Signalization and substitution are answers to different questions, and the level of analysis to which signalization corresponds, is that which concerns the nature of conditioning as an operation of the animal in the environment. PMID:14628703

García-Hoz, Víctor

2003-11-01

387

76 FR 8666 - Substitution in Case of Death of Claimant  

Federal Register 2010, 2011, 2012, 2013

...unraised theory of entitlement, such...not add the issue of or file a claim...connection for post-traumatic stress disorder. Although a substitute...clarify the scope of substitution and...conflict with VA's definitions of...

2011-02-15

388

40 CFR 721.4133 - Dimethyl-3-substituted heteromonocyclic amine.  

Code of Federal Regulations, 2010 CFR

40 Protection of Environment 30...Dimethyl-3-substituted heteromonocyclic amine. 721.4133 Section 721.4133 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...Dimethyl-3-substituted heteromonocyclic amine. (a)...

2010-07-01

389

40 CFR 721.640 - Amine substituted metal salts.  

Code of Federal Regulations, 2010 CFR

40 Protection of Environment 30...2010-07-01 false Amine substituted metal...Section 721.640 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...Substances § 721.640 Amine substituted...

2010-07-01

390

SUBSTITUTING CADMIUM CYANIDE ELECTROPLATING WITH ZINC CHLORIDE ELECTROPLATING  

EPA Science Inventory

The environmental and economic implications of substituting zinc chloride electroplating for cadmium cyanide electroplating were evaluated. he process substitution was successful in achieving product quality to satisfy the customer requirements for corrosion resistance. orrosion ...

391

40 CFR 721.10517 - Alkyl methacrylates, polymer with substituted carbomonocycle, hydroxymethyl acrylamide and...  

...substituted carbomonocycle, hydroxymethyl acrylamide and fluorinatedalkyl acrylate (generic...substituted carbomonocycle, hydroxymethyl acrylamide and fluorinatedalkyl acrylate (generic...substituted carbomonocycle, hydroxymethyl acrylamide and fluorinatedalkyl acrylate...

2014-07-01

392

40 CFR 721.10517 - Alkyl methacrylates, polymer with substituted carbomonocycle, hydroxymethyl acrylamide and...  

Code of Federal Regulations, 2013 CFR

...substituted carbomonocycle, hydroxymethyl acrylamide and fluorinatedalkyl acrylate (generic...substituted carbomonocycle, hydroxymethyl acrylamide and fluorinatedalkyl acrylate (generic...substituted carbomonocycle, hydroxymethyl acrylamide and fluorinatedalkyl acrylate...

2013-07-01

393

40 CFR 721.7770 - Alkylphenoxypoly(oxyethylene) sulfuric acid ester, substituted amine salt.  

Code of Federal Regulations, 2011 CFR

...Alkylphenoxypoly(oxyethylene) sulfuric acid ester, substituted amine salt...Alkylphenoxypoly(oxyethylene) sulfuric acid ester, substituted amine salt...alkyl phenoxypoly(oxyethylene) sulfuric acid ester, substituted amine...

2011-07-01

394

40 CFR 721.7770 - Alkylphenoxypoly(oxyethylene) sulfuric acid ester, substituted amine salt.  

Code of Federal Regulations, 2013 CFR

...Alkylphenoxypoly(oxyethylene) sulfuric acid ester, substituted amine salt...Alkylphenoxypoly(oxyethylene) sulfuric acid ester, substituted amine salt...alkyl phenoxypoly(oxyethylene) sulfuric acid ester, substituted amine...

2013-07-01

395

40 CFR 721.7770 - Alkylphenoxypoly(oxyethylene) sulfuric acid ester, substituted amine salt.  

...Alkylphenoxypoly(oxyethylene) sulfuric acid ester, substituted amine salt...Alkylphenoxypoly(oxyethylene) sulfuric acid ester, substituted amine salt...alkyl phenoxypoly(oxyethylene) sulfuric acid ester, substituted amine...

2014-07-01

396

40 CFR 721.321 - Substituted acrylamides and acrylic acid copolymer (generic).  

Code of Federal Regulations, 2010 CFR

...false Substituted acrylamides and acrylic acid copolymer (generic). 721...321 Substituted acrylamides and acrylic acid copolymer (generic). (a...as substituted acrylamides and acrylic acid copolymer (PMN...

2010-07-01

397

Synthesis of Al-substituted 11 A tobermorite from newsprint recycling residue: a feasibility study  

SciTech Connect

Newsprint recycling is responsible for significant volumes of secondary waste material for which further reprocessing and market development would be beneficial. In response to this problem, a layer lattice, ion exchange material, Al-substituted 11 A tobermorite, has been synthesised from newsprint recycling residue comprising gehlenite (Ca{sub 2}Al{sub 2}SiO{sub 7}), akermanite (Ca{sub 2}MgSi{sub 2}O{sub 7}), {beta}-dicalcium silicate (Ca{sub 2}SiO{sub 4}) and anorthite (CaAl{sub 2}Si{sub 2}O{sub 8}) under hydrothermal conditions at 100 deg. C in the presence of NaOH. The hydrogarnet phase, katoite (Ca{sub 3}Al{sub 2}SiO{sub 12}H{sub 8}), was also formed. Similar treatment regimes in the presence of LiOH and KOH did not yield significant quantities of Al-substituted 11 A tobermorite. A batch sorption study confirmed that the Al-substituted 11 A tobermorite-bearing product was effective in the exclusion of Cd{sup 2+}, Pb{sup 2+} and Zn{sup 2+} from acidified aqueous media. The potential to enhance the yield of Al-substituted 11 A tobermorite relative to that of katoite and thus optimise the ion exchange efficiency of the product is discussed with respect to its application to heavy metal-contaminated wastewater treatment.

Coleman, Nichola J.; Brassington, David S

2003-02-20

398

Cesium selectivity of (Al+Na)-substituted tobermorite  

Microsoft Academic Search

Several synthetic tobermorites with different levels of [Al+Na] substitution were prepared from two different types of starting materials and their cation exchange and cesium selective properties were investigated. The substituted tobermorites were found to have high cation exchange capacities and very high selectivities for Cs[sup +] ion. Cesium selectivity of the substituted tobermorites was demonstrated in the presence of divalent

O. P. Shrivastava; S. Komarneni

1994-01-01

399

Two types of amino acid substitutions in protein evolution  

Microsoft Academic Search

Summary The frequency of amino acid substitutions, relative to the frequency expected by chance, decreases linearly with the increase in physico-chemical differences between amino acid pairs involved in a substitution. This correlation does not apply to abnormal human hemoglobins. Since abnormal hemoglobins mostly reflect the process of mutation rather than selection, the correlation manifest during protein evolution between substitution frequency

Takashi Miyata; Sanzo Miyazawa; Teruo Yasunaga

1979-01-01

400

40 CFR 721.4594 - Substituted azo metal complex dye.  

Code of Federal Regulations, 2010 CFR

... false Substituted azo metal complex dye. 721.4594 Section 721.4594 Protection...721.4594 Substituted azo metal complex dye. (a) Chemical substance and significant...generically as a substituted azo metal complex dye (PMN P-94-499) is subject to...

2010-07-01

401

40 CFR 721.562 - Substituted alkylamine salt.  

...2014-07-01 false Substituted alkylamine salt. 721.562 Section 721.562 Protection... § 721.562 Substituted alkylamine salt. (a) Chemical substance and significant...generically as a substituted alkylamine salt (PMN P-85-941) is subject to...

2014-07-01

402

40 CFR 721.10087 - Substituted alkyl phosphine oxide (generic).  

Code of Federal Regulations, 2011 CFR

...2011-07-01 false Substituted alkyl phosphine oxide (generic). 721.10087 Section 721...721.10087 Substituted alkyl phosphine oxide (generic). (a) Chemical substance...generically as substituted alkyl phosphine oxide (PMN P-06-332) is subject to...

2011-07-01

403

40 CFR 721.10087 - Substituted alkyl phosphine oxide (generic).  

Code of Federal Regulations, 2012 CFR

...2012-07-01 false Substituted alkyl phosphine oxide (generic). 721.10087 Section 721...721.10087 Substituted alkyl phosphine oxide (generic). (a) Chemical substance...generically as substituted alkyl phosphine oxide (PMN P-06-332) is subject to...

2012-07-01

404

40 CFR 721.562 - Substituted alkylamine salt.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Substituted alkylamine salt. 721.562 Section 721.562 Protection... § 721.562 Substituted alkylamine salt. (a) Chemical substance and significant...generically as a substituted alkylamine salt (PMN P-85-941) is subject to...

2013-07-01

405

40 CFR 721.562 - Substituted alkylamine salt.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Substituted alkylamine salt. 721.562 Section 721.562 Protection... § 721.562 Substituted alkylamine salt. (a) Chemical substance and significant...generically as a substituted alkylamine salt (PMN P-85-941) is subject to...

2010-07-01

406

40 CFR 721.562 - Substituted alkylamine salt.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 false Substituted alkylamine salt. 721.562 Section 721.562 Protection... § 721.562 Substituted alkylamine salt. (a) Chemical substance and significant...generically as a substituted alkylamine salt (PMN P-85-941) is subject to...

2012-07-01

407

Peer-Reviewed Articles Substitutability in Recreational Fishing  

Microsoft Academic Search

The authors wanted to know the extent to which anglers were willing to make substitution decisions when constrained, and identify explanatory variables for substitution decisions. Anglers were asked if there were other outdoor recreation activities that would provide them with the same satisfaction and enjoyment they received from fishing. About 51% said yes. The most fre- quently identified substitutes were

ROBERT B. DITTON; STEPHEN G. SUTTON

2004-01-01

408

Reducing CO 2 emissions by substituting biomass for fossil fuels  

Microsoft Academic Search

Replacing fossil fuels with sustainably-produced biomass will reduce the net flow of CO2 to the atmosphere. We express the efficiency of this substitution in reduced emissions per unit of used land or biomass and in costs of the substitution per tonne of C. The substitution costs are calculated as the cost difference between continued use of fossil fuels at current

Leif Gustavsson; Pål Börjesson; Bengt Johansson; Per Svenningsson

1995-01-01

409

40 CFR 721.3435 - Butoxy-substituted ether alkane.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Butoxy-substituted ether alkane. 721.3435 Section 721.3435 ...721.3435 Butoxy-substituted ether alkane. (a) Chemical substance and significant...generically as butoxy-substituted ether alkane (PMN P-92-755) is subject to...

2013-07-01

410

40 CFR 721.10704 - Aryl-substituted alkane.  

...2014-07-01 false Aryl-substituted alkane. 721.10704 Section 721.10704...Substances § 721.10704 Aryl-substituted alkane. (a) Chemical substance and significant...identified generically as an aryl-substituted alkane (PMN P-12-548) is subject to...

2014-07-01

411

40 CFR 721.3435 - Butoxy-substituted ether alkane.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 false Butoxy-substituted ether alkane. 721.3435 Section 721.3435 ...721.3435 Butoxy-substituted ether alkane. (a) Chemical substance and significant...generically as butoxy-substituted ether alkane (PMN P-92-755) is subject to...

2012-07-01

412

40 CFR 721.3435 - Butoxy-substituted ether alkane.  

...2014-07-01 false Butoxy-substituted ether alkane. 721.3435 Section 721.3435 ...721.3435 Butoxy-substituted ether alkane. (a) Chemical substance and significant...generically as butoxy-substituted ether alkane (PMN P-92-755) is subject to...

2014-07-01

413

40 CFR 721.3435 - Butoxy-substituted ether alkane.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Butoxy-substituted ether alkane. 721.3435 Section 721.3435 ...721.3435 Butoxy-substituted ether alkane. (a) Chemical substance and significant...generically as butoxy-substituted ether alkane (PMN P-92-755) is subject to...

2010-07-01

414

40 CFR 721.3435 - Butoxy-substituted ether alkane.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 false Butoxy-substituted ether alkane. 721.3435 Section 721.3435 ...721.3435 Butoxy-substituted ether alkane. (a) Chemical substance and significant...generically as butoxy-substituted ether alkane (PMN P-92-755) is subject to...

2011-07-01

415

76 FR 39062 - Substitution in Case of Death of Claimant  

Federal Register 2010, 2011, 2012, 2013

...RIN 2900-AN91 Substitution in Case of Death of Claimant AGENCY: Department of Veterans...proposed rule, ``Substitution in Case of Death of Claimant'' (76 FR 8666), published...2900-AN91--Substitution in Case of Death of Claimant.'' Copies of comments...

2011-07-05

416

Substitutional alloy of Ce and Al  

PubMed Central

The formation of substitutional alloys has been restricted to elements with similar atomic radii and electronegativity. Using high-pressure at 298 K, we synthesized a face-centered cubic disordered alloy of highly dissimilar elements (large Ce and small Al atoms) by compressing the Ce3Al intermetallic compound >15 GPa or the Ce3Al metallic glass >25 GPa. Synchrotron X-ray diffraction, Ce L3-edge absorption spectroscopy, and ab initio calculations revealed that the pressure-induced Kondo volume collapse and 4f electron delocalization of Ce reduced the differences between Ce and Al and brought them within the Hume-Rothery (HR) limit for substitutional alloying. The alloy remained after complete release of pressure, which was also accompanied by the transformation of Ce back to its ambient 4f electron localized state and reversal of the Kondo volume collapse, resulting in a non-HR alloy at ambient conditions. PMID:19188608

Zeng, Qiao-Shi; Ding, Yang; Mao, Wendy L.; Luo, Wei; Blomqvist, Andreas; Ahuja, Rajeev; Yang, Wenge; Shu, Jinfu; Sinogeikin, Stas V.; Meng, Yue; Brewe, Dale L.; Jiang, Jian-Zhong; Mao, Ho-kwang

2009-01-01

417

Heat of segregation of single substitutional impurities  

NASA Technical Reports Server (NTRS)

The method of Bozzolo, Ferrante and Smith (BFS) is applied for the calculation of the heat of segregation of single substitutional impurities in fcc metals. A simple equation for predicting the heat of segregation is derived for the rigid case (no atomic relaxations). The results of including atomic relaxation using a Monte Carlo method are also presented and the results compared with a number of experimental and theoretical results.

Bozzolo, Guillermo; Good, Brian; Ferrante, John

1993-01-01

418

Convergence substitution for paralysed horizontal gaze.  

PubMed Central

Three patients with paralysed horizontal gaze are presented. Involuntary use of convergence to assist horizontal gaze was noted as a late feature. All patients showed (1) unilateral or bilateral horizontal gaze palsy (two patients had one and a half syndrome, the other had bilateral nuclear sixth nerve palsies), (2) adduction of both eyes on attempted gaze into the paralysed field, (3) miosis which coincided with adduction. Convergence substitution should be considered in the differential diagnosis of gaze induced strabismus. Images PMID:7703199

Beigi, B; O'Keeffe, M; Logan, P; Eustace, P

1995-01-01

419

Substitutional Semantics and Natural Language Quantification  

E-print Network

sharpening of certain points came out of discussion of these issues with Noam Chomsky and Norbert Hornstein. Finally, I would like to thank the MIT Department of Linguistics and Philosophy for making their facilities available to me during my tenure as a... Visiting Scholar. 'For example. Dale Gottlieb, Ontoloqical Economy; Substitutional Quantification and Mathematics, (Oxford: Oxford University Press, I960). 'Noam Chomsky has suggested to me that it is ille­ gitimate to suppose that natural language...

Ludlow, Peter

420

Abuse Liability Profile of Three Substituted Tryptamines  

PubMed Central

The abuse liability profile of three synthetic hallucinogens, N,N-diisopropyltryptamine (DIPT), 5-N,N-diethyl-5-methoxytryptamine (5-MeO-DET), and 5-methoxy-?-methyltryptamine (5-MeO-AMT), was tested in rats trained to discriminate hallucinogenic and psychostimulant compounds, including cocaine, methamphetamine, 3,4-methylenedioxymethylamphetamine (MDMA), lysergic acid diethylamide (LSD), (?)-2,5-dimethoxy-4-methylamphetamine (DOM), and dimethyltryptamine (DMT). Because abused hallucinogens act at 5-hydroxytryptamine 1A (5-HT1A) and 5-HT2A receptors, and abused psychostimulants act at monoamine transporters, binding and functional activities of DIPT, 5-MeO-DET, and 5-MeO-AMT at these sites were also tested. DIPT fully substituted in rats trained to discriminate DMT (ED50 = 1.71 mg/kg) and DOM (ED50 = 1.94 mg/kg), but produced only 68% LSD-appropriate responding. 5-MeO-DET fully substituted for DMT (ED50 = 0.41 mg/kg) and produced 59% MDMA-appropriate responding. 5-MeO-AMT did not fully substitute for any of the training drugs, but produced 67% LSD-appropriate responding. None of the compounds produced substitution in rats trained to discriminate cocaine or methamphetamine. All three compounds showed activity at 5-HT1A and 5-HT2A receptors as well as blockade of reuptake by the serotonin transporter. In addition, 5-MeO-AMT produced low levels of serotonin release and low potency blockade of dopamine uptake. DIPT, 5-MeO-DET, and 5-MeO-AMT produced behavioral and receptor effects similar to those of abused hallucinogens, but were not similar to those of psychostimulants. DIPT and 5-MeO-DET may have abuse liability similar to known hallucinogens and may be hazardous because high doses produced activity and lethality. PMID:21474568

Forster, Michael J.; Janowsky, Aaron; Eshleman, Amy J.

2011-01-01

421

Regiospecific biotransformation of substituted norbornanones by microorganisms  

Microsoft Academic Search

Summary The regiospecific biotransformation of (±) 5-acetoxy-7-fluoronorbornan-2-one into the equivalent bridgehead lactone of use as a source of substituted cyclopentane synthons containing four successive chiral centres has been demonstrated using washed-cell suspensions of cyclohexanol-grownAcinetobacter sp NCIB 9871. Conditions to optimise production of such 2-oxabicyclooctanones (substrate concentration<25mM, pH 7.35, 30°C) have been characterised.

Melissa Levitt; Helen Sandey; Andrew Willetts

1990-01-01

422

40 CFR 721.5930 - Phenylenebis[imino (chlorotriazinyl)imino(substituted naphthyl)azo(substituted phenyl)azo, sodium...  

Code of Federal Regulations, 2011 CFR

...azo(substituted phenyl)azo, sodium salt (generic name). 721.5930 Section...azo(substituted phenyl)azo, sodium salt (generic name). (a) Chemical substance...azo (substituted phenyl) azo, sodium salt (PMN P-95-274) is subject to...

2011-07-01

423

40 CFR 721.5930 - Phenylenebis[imino (chlorotriazinyl)imino(substituted naphthyl)azo(substituted phenyl)azo, sodium...  

Code of Federal Regulations, 2013 CFR

...azo(substituted phenyl)azo, sodium salt (generic name). 721.5930 Section...azo(substituted phenyl)azo, sodium salt (generic name). (a) Chemical substance...azo (substituted phenyl) azo, sodium salt (PMN P-95-274) is subject to...

2013-07-01

424

40 CFR 721.5930 - Phenylenebis[imino (chlorotriazinyl)imino(substituted naphthyl)azo(substituted phenyl)azo, sodium...  

Code of Federal Regulations, 2010 CFR

...azo(substituted phenyl)azo, sodium salt (generic name). 721.5930 Section...azo(substituted phenyl)azo, sodium salt (generic name). (a) Chemical substance...azo (substituted phenyl) azo, sodium salt (PMN P-95-274) is subject to...

2010-07-01

425

Study of In Vitro Capillary-Like Structures in Psoriatic Skin Substitutes  

PubMed Central

Abstract Angiogenesis is one of the important hallmarks of psoriasis. The extension of the superficial microvascular structure and activated pro-angiogenic mediators in psoriasis seem to be important factors involved in the pathology. According to the changes of superficial microvasculature in psoriatic lesions, anti-angiogenic treatment could be a promising therapeutic strategy for psoriasis. The aim of this study was to construct an in vitro vascularized psoriatic skin substitute for fundamental research. Psoriatic fibroblasts and keratinocytes were isolated from psoriatic plaque biopsies, while healthy fibroblasts and keratinocytes, as well as microvascular endothelial cells, were isolated from healthy skin biopsies of cosmetic breast surgery. Psoriatic and healthy skin substitutes with and without endothelial cells were produced using the self-assembly approach. Afterward the substitutes were examined by histology, immunofluorescence studies, and three-dimensional (3D) confocal microscopy. Histological analysis and immunofluorescence staining of specific markers for endothelial cells (von Willebrand, PECAM-1 [CD31], and VE-cadherin [CD144]) and basement membrane component (collagen IV) demonstrated that endothelial cells have the ability to form capillary-like tubes. Moreover, the 3D branched structure of the capillary-like structures and an eagle eye view of them were observed by confocal microscopy. Also the semiquantification of capillary-like tubes (CLTs) was carried out with a 3D eagle eye view of substitutes, and more CLTs were observed in psoriatic substitutes. These results suggest that it is possible to observe 3D capillary-like structures in the self-assembled psoriatic skin substitutes, which could become a good in vitro testing model for anti-angiogenic drug research, and facilitate the study of this complex pathology, which links angiogenesis to its development. PMID:25371856

Ayata, Raif Eren; Bouhout, Sara; Auger, Michèle

2014-01-01

426

The substitution of nickel for cobalt in hot isostatically pressed powder metallurgy UDIMET 700 alloys  

Microsoft Academic Search

Nickel was substituted in various proportions for cobalt in a series of five hot-isostatically-pressed powder metallurgy alloys based on the UDIMET 700 composition. These alloys were given 5-step heat treatments appropriate for use in turbine engine disks. The resultant microstructures displayed three distinct sizes of gamma' particles in a gamma matrix. The higher cobalt-content alloys contained larger amounts of the

Fredric H. Harf

1985-01-01

427

The substitution of nickel for cobalt in hot isostatically pressed powder metallurgy UDIMET 700 alloys  

Microsoft Academic Search

Nickel was substituted in various proportions for cobalt in a series of five hot-isostatically-pressed powder metallurgy alloys\\u000a based on the UDIMET 700 composition. These alloys were given 5-step heat treatments appropriate for use in turbine engine\\u000a disks. The resultant microstructures displayed three distinct sizes of ?? particles in a ? matrix. The higher cobalt-content\\u000a alloys contained larger amounts of the

Fredric H. Harf

1985-01-01

428

Incontinence Treatment: Surgical Treatments  

MedlinePLUS

... Stories Who We Are Contact Us Donate Incontinence Treatment: Surgical Treatments Jump to Topic Lifestyle changes Dietary changes Medication ... July 8, 2014 at 09:36:27 AM Treatment Lifestyle Changes Dietary Tips Medication Bowel Management Biofeedback ...

429

Mechanisms of Action of Substituted ?-Amino Alkanols on Leishmania donovani.  

PubMed

Leishmaniasis is the protozoan disease second in importance for human health, superseded only by malaria; however, the options for chemotherapeutic treatment are increasingly limited due to drug resistance and toxicity. Under this perspective, a quest for new chemical compounds is urgently needed. An N-substituted 2-aminoalkan-1-ol scaffold has been shown to be a versatile scaffold for antiparasitic activity. Knowledge about its mechanism of action is still rather limited. In this work, we endeavored to define the leishmanicidal profile of such ?-amino alkanol derivatives using a set of 15 N-mono- and disubstituted surrogates, tested on Leishmania donovani promastigotes and intracellular amastigotes. The best compound (compound 5), 2-ethylaminododecan-1-ol, had a 50% effective concentration (EC50) of 0.3 ?M and a selectivity index of 72 for infected THP-1 cells and was selected for further elucidation of its leishmanicidal mechanism. It induced fast depletion of intracellular ATP content in promastigotes in the absence of vital dye intracellular entry, ruling out plasma membrane permeabilization as its origin. Confocal and transmission electron microscopy analyses showed that compound 5 induced severe mitochondrial swelling and vesiculation. Polarographic analysis using an oxygen electrode demonstrated that complex II of the respiratory chain (succinate reductase) was strongly inhibited by compound 5, identifying this complex as one of the primary targets. Furthermore, for other ?-amino alkanols whose structures differed subtly from that of compound 5, plasma membrane permeabilization or interference with membrane traffic was also observed. In all, N-substituted ?-amino alkanols were shown as appealing leishmanicidal candidates deserving further exploration. PMID:25487805

Abengózar, María Ángeles; Bustos, Luis A; García-Hernández, Raquel; Fernández de Palencia, Pilar; Escarcena, Ricardo; Castanys, Santiago; Del Olmo, Esther; Gamarro, Francisco; San Feliciano, Arturo; Rivas, Luis

2015-02-01

430

A Modified Rabbit Ulna Defect Model for Evaluating Periosteal Substitutes in Bone Engineering: A Pilot Study  

PubMed Central

The present work defines a modified critical size rabbit ulna defect model for bone regeneration in which a non-resorbable barrier membrane was used to separate the radius from the ulna to create a valid model for evaluation of tissue-engineered periosteal substitutes. Eight rabbits divided into two groups were used. Critical defects (15?mm) were made in the ulna completely eliminating periosteum. For group I, defects were filled with a nanohydroxyapatite poly(ester urethane) scaffold soaked in PBS and left as such (group Ia) or wrapped with a tissue-engineered periosteal substitute (group Ib). For group II, an expanded-polytetrafluoroethylene (e-PTFE) (GORE-TEX®) membrane was inserted around the radius then the defects received either scaffold alone (group IIa) or scaffold wrapped with periosteal substitute (group IIb). Animals were euthanized after 12–16?weeks, and bone regeneration was evaluated by radiography, computed microtomography (?CT), and histology. In the first group, we observed formation of radio-ulnar synostosis irrespective of the treatment. This was completely eliminated upon placement of the e-PTFE (GORE-TEX®) membrane in the second group of animals. In conclusion, modification of the model using a non-resorbable e-PTFE membrane to isolate the ulna from the radius was a valuable addition allowing for objective evaluation of the tissue-engineered periosteal substitute. PMID:25610828

El Backly, Rania M.; Chiapale, Danilo; Muraglia, Anita; Tromba, Giuliana; Ottonello, Chiara; Santolini, Federico; Cancedda, Ranieri; Mastrogiacomo, Maddalena

2014-01-01

431

LEAD SUBSTITUTION AND ELIMINATION STUDY, PART II  

SciTech Connect

Within the Nuclear Materials Technology Division of Los Alamos National Laboratory, lead is used as shielding for a variety of operations, including actinide chemistry, weapons production, radiochemistry, and analytical chemistry. In this study, waste minimization issues associated with replacing lead shielding with non-hazardous materials are addressed. These include institutional program available to support this effort, the hazards and accompanying controls grouped with lead shielding, operations that use lead bricks and how this effects the selection of the substitute. Life cycle management issues are also examined. As a final step, an approach to get buy-in from both technical and budget minded employees is presented.

T. MARTINEZ; M. COURNOYER

2001-01-01

432

Cation radicals of N-substituted phenothiazines  

Microsoft Academic Search

The reaction of N-substituted phenothiazines with certain acceptors (halogenated solvents CHCl3, CH2Br2, CCl4, o-chloranil, AlCl3, SnCl4, concentrated H2SO4, concentrated HNO3 in HClO4) has been studied by EPR spectroscopy. The hyperfine structure in the EPR spectra of the cation radicals is analyzed. To interpret the EPR spectra obtained in terms of the MNDO-PM3 method we carried out a calculation of the

O. B. Tomilin; E. P. Konovalova; V. N. Yuzhalkin; L. V. Ryabkina; É. P. Sanaeva

1996-01-01

433

Mental Symptoms and Drug Use in Maintenance Treatment with Slow-Release Oral Morphine Compared to Methadone: Results of a Randomized Crossover Study.  

PubMed

Background: Opioid maintenance treatment is the option of choice to stabilize opioid-dependent patients. Whilst efficacy of methadone and buprenorphine has been studied extensively, fewer data on slow-release oral morphine are available. Aims: This study analyzes the effects of slow-release oral morphine compared to methadone with regard to self-reported mental symptoms, drug use and satisfaction with treatment. Methods: The study was carried out as an open-label randomized crossover trial in 14 treatment sites in Switzerland and Germany. It comprised 2 crossover periods of 11 weeks each. For measuring mental symptoms, the Symptom Checklist-27 (SCL-27) was used. Drug and alcohol use was assessed by the number of consumption days, and treatment satisfaction by a visual analogue scale. Results: A total of 157 patients were included for the analyses (per-protocol sample). Statistically significantly better outcomes for morphine as compared to methadone treatment were found for overall severity of mental symptoms (SCL-27 Global Severity Index), as well as 5 of the 6 syndrome groups of the SCL-27, and for treatment satisfaction. There were no statistically significant differences with regard to drug or alcohol use between groups. Conclusions: This study supports positive effects of slow-release oral morphine compared to methadone on patient-reported outcomes such as mental symptoms and treatment satisfaction with comparable effects on concomitant drug use. Slow-release oral morphine represents a meaningful alternative to methadone for treatment of opioid dependence. © 2014 S. Karger AG, Basel. PMID:25427944

Verthein, Uwe; Beck, Thilo; Haasen, Christian; Reimer, Jens

2014-11-22

434

The solubility of substitutional atoms in ordered substitutional-intrestitial solid solutions  

NASA Astrophysics Data System (ADS)

The solubility of substitutional impurities in ordered bcc A-B-(C) solid solutions has been calculated in a static approximation. The effect of the energy splitting of geometrically equivalent interstitial sites into interstitial sites of two types during ordering was taken into account. The solubility has been determined as a function of temperature, alloy composition, and long-range order parameter.

Masharov, S. I.

2010-12-01

435

Patient Perspectives of an Integrated Program of Medical Care and Substance Use Treatment  

PubMed Central

Abstract The benefits of integrating primary care and substance use disorder treatment are well known, yet true integration is difficult. We developed and evaluated a team-based model of integrated care within the primary care setting for HIV-infected substance users and substance users at risk for contracting HIV. Qualitative data were gathered via focus groups and satisfaction surveys to assess patients' views of the program, evaluate key elements for success, and provide recommendations for other programs. Key themes related to preferences for the convenience and efficiency of integrated care; support for a team-based model of care; a feeling that the program requirements offered needed structure; the importance of counseling and education; and how provision of concrete services improved overall well-being and quality of life. For patients who received buprenorphine/naloxone for opioid dependence, this was viewed as a major benefit. Our results support other studies that theorize integrated care could be of significant value for hard-to-reach populations and indicate that having a clinical team dedicated to providing substance use disorder treatment, HIV risk reduction, and case management services integrated into primary care clinics has the potential to greatly enhance the ability to serve a challenging population with unmet treatment needs. PMID:24428768

Farrell, Caitlin; Sorensen-Alawad, Amy; Palmisano, Joseph N.; Chaisson, Christine; Walley, Alexander Y.

2014-01-01

436

Medication-assisted treatment for opioid use disorders in correctional settings: an ethics review.  

PubMed

Opioid use disorders are a pressing health concern that disproportionately impacts the United States (U.S.) correctional population. Medication-assisted treatment (MAT) is an evidence-based standard of care for opioid use disorders. Despite its availability in the community, MAT and MAT medications (buprenorphine and methadone) are largely unavailable and/or inaccessible for the treatment of opioid use disorders in U.S. prisons and jails. Given that the ethical principles have served as justification for limiting access to MAT on "moral" grounds, this article examines the implications of current correctional policies through the ethical principles of: (1) beneficence/non-maleficence; (2) distributive justice (equivalence-of-care); and (3) autonomy (informed consent). Special attention is paid to the five components of informed consent (capacity, disclosure, understanding, voluntariness, and access), as this facet has been used most often to justify policies that limit access to MAT in the past. Findings highlight that these core ethical principles support the adoption of correctional policies that include MAT. Furthermore, our findings demonstrate that autonomy is maximized during the informed consent process when MAT is available as a treatment option. PMID:25249444

Ludwig, Ariel S; Peters, Roger H

2014-11-01

437

Infrared spectra of substituted polycylic aromatic hydrocarbons  

NASA Technical Reports Server (NTRS)

Calculations are carried out using density functional theory (DFT) to determine the harmonic frequencies and intensities of 1-methylanthracene, 9-methylanthracene, 9-cyanoanthracene, 2-aminoanthracene, acridine, and their positive ions. The theoretical data are compared with matrix-isolation spectra for these species also reported in this work. The theoretical and experimental frequencies and relative intensities for the neutral species are in generally good agreement, whereas the positive ion spectra are only in qualitative agreement. Relative to anthracene, we find that substitution of a methyl or CN for a hydrogen does not significantly affect the spectrum other than to add the characteristic methyl C-H and C triple bond N stretches near 2900 and 2200 cm-1, respectively. However, addition of NH2 dramatically affects the spectrum of the neutral. Not only are the NH2 modes themselves strong, but this electron-withdrawing group induces sufficient partial charge on the ring to give the neutral molecule spectra characteristics of the anthracene cation. The sum of the absolute intensities is about four times larger for 2-aminoanthracene than those for 9-cyanoanthracene. Substituting nitrogen in the ring at the nine position (acridine) does not greatly alter the spectrum compared with anthracene.

Langhoff, S. R.; Bauschlicher, C. W. Jr; Hudgins, D. M.; Sandford, S. A.; Allamandola, L. J.

1998-01-01

438

Coal to gas substitution using coal?!  

NASA Astrophysics Data System (ADS)

Substitution of carbon-intensive coal with less carbon-intensive natural gas for energy production is discussed as one main pillar targeting reduction of antrophogenic greenhouse gas emissions by means of climate change mitigation. Other pillars are energy efficiency, renewable energies, carbon capture and storage as well as further development of nuclear energy. Taking into account innovative clean coal technologies such as UCG-CCS (underground coal gasification with carbon capture and storage), in which coal deposits are developed using directional drilling technologies and subsequently converted into a synthesis gas of high calorific value, the coupled conceptual approach can provide a synergetic technology for coal utilization and mitigation of carbon emissions. This study aims at the evaluation of UC? s carbon mitigation potentials and the review of the economical boundary conditions. The analytical models applied within this study are based on data available from world-wide UCG projects and extensive laboratory studies. In summary, scenarios considering costs and carbon storage potentials are economically feasible and thus competitive with less carbon-intensive energy generation technologies such as natural gas. Thus, coal to gas substitution can be one of the coal based options.

Kempka, Thomas; Schlüter, Ralph

2010-05-01

439

Sucrose substitutes and their role in caries prevention.  

PubMed

Many non- or low-cariogenic sucrose substitutes are currently available and are found as ingredients of a variety of candy, chewing gum, and drinks. Recently the role of sugar alcohols in promoting remineralisation of enamel has attracted much attention. Thus, the dental profession needs to understand the general characteristics and features of sugar substitutes to provide advice on oral health to patients as well as the general public. There are two critical requirements for sucrose substitutes, namely, being nutritionally appropriate and not being detrimental to the overall general health of the individual. The use of a greater variety of confectionary containing sucrose substitutes and the development of new substitutes with high nutritional value are essential in the battle against caries. In this paper we review in detail the characteristics of sucrose substitutes currently in use, their role in caries prevention and promotion of oral health. PMID:16826877

Matsukubo, Takashi; Takazoe, Ichiro

2006-06-01

440

A study of photon interaction parameters in lung tissue substitutes  

PubMed Central

The study of photon interaction with different composite materials has become a topic of prime importance for radiation physicists. Some parameters of dosimetric interest are the mass attenuation coefficient, effective atomic number, and electron density; these help in the basic understanding of photon interactions with composite materials. The photon interaction parameters such as mass attenuation coefficient (?/?), effective atomic number (Zeff), and effective electron density (Nel) must be identical for the phantom material and their tissue. In the present study, we have evaluated the photon interaction parameters such as (?/?), Zeff and Nel of 13 lung tissue substitutes. The variations of these parameters of lung tissue substitutes with photon energy are graphically represented. The photon interaction parameters of lung tissue substitutes are compared with that of lung tissue. The variation of photon interaction parameters of the studied lung tissue substitutes is similar that of the lung. Logically, it can be shown that Alderson lung is good substitute for lung than the other substitutes. PMID:24872609

Manjunatha, H. C.

2014-01-01