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1

Drug Education: A Position Paper  

ERIC Educational Resources Information Center

|New York State's drug education Position Paper clearly demonstrates a commitment to the youth of the State and certainly one that other states might consider for its youth. Many aspects of the program are presented in this paper which have implications for teachers, school administrators, and community leaders. (Author)|

Journal of Drug Education, 1971

1971-01-01

2

Clinical False-Positive Drug Test Results  

Microsoft Academic Search

A confirmed positive drug test reassures all the parties involved in the drug testing process that the reported positive result\\u000a is an analytical true positive and as such is evidence that the individual has been exposed to the drug. That individual may\\u000a not be a drug abuser and may have a valid alternative explanation for the positive result. In this

Tai C. Kwong

3

PERCEPTION OF DRUG ADDICTS-HIV POSITIVE TOWARDS DENTAL SERVICES  

Microsoft Academic Search

Many study worldwide showed that the HIV -positive individuals were discriminated on receiving dental care or treatment. A descriptive study to assess the perception of a group of Malaysian drug addicts who are HIV-positive toward dental care or treatment was conducted among drug addicts living in rehabilitation centres. The sampling frame of the study comprises drug addicts who are inmates

Sharol Lail Sujak; Rahimah Abdul Kadir; Roziah Omar

4

17. DETAIL VIEW OF ROLLER GATE (IN RAISED POSITION), SHOWING ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

17. DETAIL VIEW OF ROLLER GATE (IN RAISED POSITION), SHOWING GATE FLANGES, GATE HEATER (LEFT FOREGROUND), ROLLER TRACK, CHAIN AND BRIDGE GIRDER, LOOKING EAST - Upper Mississippi River 9-Foot Channel Project, Lock & Dam No. 3, Red Wing, Goodhue County, MN

5

5. UNIT VENTILATOR, MEN'S BATH HALL, SHOWING POSITION AGAINST WALL ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. UNIT VENTILATOR, MEN'S BATH HALL, SHOWING POSITION AGAINST WALL ABOVE THE BATHS. - Hot Springs National Park, Bathhouse Row, Ozark Bathhouse: Mechanical & Piping Systems, State Highway 7, 1 mile north of U.S. Highway 70, Hot Springs, Garland County, AR

6

Emerging Trends in Contextual Learning Show Positive Results for Students.  

ERIC Educational Resources Information Center

|This issue focuses on contextual learning (CL), in which students master rigorous academic content in real-world or work-based learning experiences. "Emerging Trends in CL Show Positive Results for Students" discusses CL as an important strategy for improving student achievement. It describes: how CL raises the bar for all students, challenging…

WorkAmerica, 2001

2001-01-01

7

49 CFR 219.605 - Positive drug test results; procedures.  

Code of Federal Regulations, 2012 CFR

...2012-10-01 2012-10-01 false Positive drug test results; procedures. 219.605 Section...DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.605 Positive drug...

2012-10-01

8

49 CFR 219.605 - Positive drug test results; procedures.  

Code of Federal Regulations, 2011 CFR

...2011-10-01 2011-10-01 false Positive drug test results; procedures. 219.605 Section...DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.605 Positive drug...

2011-10-01

9

MEK: A Single Drug Target Shows Promise in Multiple Cancers  

Cancer.gov

Drugs that block the MEK protein have shown promise in several cancers. Trametinib has had encouraging results in patients with advanced melanoma, and selumetinib has been tested in patients with advanced thyroid and ovarian cancers.

10

Stomach Cancer Drug, S-1, Shows Promise in Japanese Trial  

Cancer.gov

In this Japanese clinical trial, patients with advanced, inoperable stomach cancer who received combination therapy with cisplatin and a drug called S-1 lived about two months longer than patients treated with S-1 alone, according to the March 2008 Lancet Oncology.

11

New cancer drug shows promise for treating advanced melanoma  

Cancer.gov

Researchers from UCLA's Jonsson Comprehensive Cancer Center report that a new drug in preliminary tests has shown promising results with very manageable side effects for treating patients with melanoma, the deadliest form of skin cancer. The results were presented at the 2013 meeting of the American Society of Clinical Oncology today in Chicago by Dr. Antoni Ribas, professor of medicine in the UCLA division of hematology-oncology, who led the research. Following Ribas’ presentation, the study was published online ahead of press in the New England Journal of Medicine.

12

Neurotensin-deficient mice show altered responses to antipsychotic drugs  

PubMed Central

The peptide transmitter neurotensin (NT) exerts diverse neurochemical effects that resemble those seen after acute administration of antipsychotic drugs (APDs). These drugs also induce NT expression in the striatum; this and other convergent findings have led to the suggestion that NT may mediate some APD effects. Here, we demonstrate that the ability of the typical APD haloperidol to induce Fos expression in the dorsolateral striatum is markedly attenuated in NT-null mutant mice. The induction of Fos and NT in the dorsolateral striatum in response to typical, but not atypical, APDs has led to the hypothesis that the increased expression of these proteins is mechanistically related to the production of extrapyramidal side effects (EPS). However, we found that catalepsy, which is thought to reflect the EPS of typical APDs, is unaffected in NT-null mutant mice, suggesting that NT does not contribute to the generation of EPS. We conclude that NT is required for haloperidol-elicited activation of a specific population of striatal neurons but not haloperidol-induced catalepsy. These results are consistent with the hypothesis that endogenous NT mediates a specific subset of APD actions.

Dobner, Paul R.; Fadel, Jim; Deitemeyer, Nancy; Carraway, Robert E.; Deutch, Ariel Y.

2001-01-01

13

A Parent's Plea: To Keep Kids Off Drugs, Show Them Life's "Hard Realities."  

ERIC Educational Resources Information Center

|Having witnessed drug use, idleness, and dangerous driving, a parent urges school officials to encourage neighborhood vigilance, follow up on leads, use dogs to sniff out drugs, suspend hard cases, expose second offenders to drug victims in local hospitals, and provide students with positive role models and career goals. (PB)|

Gill, Kimberly

1983-01-01

14

Drinking and smoking as concurrent predictors of illicit drug use and positive drug attitudes in adolescents  

Microsoft Academic Search

The study investigates the relationship between smoking and drinking, and the use of illicit drugs in a cohort of London adolescents. A high prevalence of drug experimentation and positive attitudes to illicit drug use were characteristic of those who both drank alcohol and smoked cigarettes on a regular basis. There was then a clear hierarchy in which lower prevalence of

David Best; Salman Rawaf; Jenny Rowley; Karen Floyd; Victoria Manning; John Strang

2000-01-01

15

Crizotinib Continues to Show Promise for Some Lung Tumors, Faces Challenge of Drug Resistance  

Cancer.gov

New data from a phase I trial of crizotinib, a small-molecule drug that targets cancer-causing chromosomal rearrangements involving the gene ALK, in patients with non-small cell lung cancer add to positive results published October 28, 2010, in the New England Journal of Medicine.

16

Positive Urgency Predicts Illegal Drug Use and Risky Sexual Behavior  

PubMed Central

There are several different personality traits that dispose individuals to engage in rash action. One such trait is positive urgency: the tendency to act rashly when experiencing extremely positive affect. This trait may be relevant for college student risky behavior, because it appears that a great deal of college student risky behavior is undertaken during periods of intensely positive mood states. To test this possibility, the authors conducted a longitudinal study designed to predict increases in risky sexual behavior and illegal drug use over the course of the first year of college (n = 407). In a well-fitting structural model, positive urgency predicted increases in illegal drug use and risky sexual behavior, even after controlling for time 1 (T1) involvement in both risky behaviors, biological sex, and T1 scores on four other personality dispositions to rash action. The authors discuss the theoretical and practical implications of this finding.

Zapolski, Tamika C. B.; Cyders, Melissa A.; Smith, Gregory T.

2009-01-01

17

FOXP2 targets show evidence of positive selection in European populations.  

PubMed

Forkhead box P2 (FOXP2) is a highly conserved transcription factor that has been implicated in human speech and language disorders and plays important roles in the plasticity of the developing brain. The pattern of nucleotide polymorphisms in FOXP2 in modern populations suggests that it has been the target of positive (Darwinian) selection during recent human evolution. In our study, we searched for evidence of selection that might have followed FOXP2 adaptations in modern humans. We examined whether or not putative FOXP2 targets identified by chromatin-immunoprecipitation genomic screening show evidence of positive selection. We developed an algorithm that, for any given gene list, systematically generates matched lists of control genes from the Ensembl database, collates summary statistics for three frequency-spectrum-based neutrality tests from the low-coverage resequencing data of the 1000 Genomes Project, and determines whether these statistics are significantly different between the given gene targets and the set of controls. Overall, there was strong evidence of selection of FOXP2 targets in Europeans, but not in the Han Chinese, Japanese, or Yoruba populations. Significant outliers included several genes linked to cellular movement, reproduction, development, and immune cell trafficking, and 13 of these constituted a significant network associated with cardiac arteriopathy. Strong signals of selection were observed for CNTNAP2 and RBFOX1, key neurally expressed genes that have been consistently identified as direct FOXP2 targets in multiple studies and that have themselves been associated with neurodevelopmental disorders involving language dysfunction. PMID:23602712

Ayub, Qasim; Yngvadottir, Bryndis; Chen, Yuan; Xue, Yali; Hu, Min; Vernes, Sonja C; Fisher, Simon E; Tyler-Smith, Chris

2013-04-18

18

Anxiety positive subjects show altered processing in the anterior insula during anticipation of negative stimuli  

PubMed Central

Prior neuroimaging studies support the hypothesis that anticipation, an important component of anxiety, may be mediated by activation within the insular and medial prefrontal cortices including the anterior cingulate cortex. However, there is an insufficient understanding of how affective anticipation differs across anxiety groups in emotional brain loci and networks. We examined 14 anxiety positive (AP) and 14 anxiety normative (AN) individuals completing an affective picture anticipation task during functional magnetic resonance imaging (fMRI). Brain activation was examined across groups for cued anticipation (to aversive or pleasant stimuli). Both groups showed greater activation in the bilateral anterior insula during cued differential anticipation (i.e., aversive vs. pleasant) and activation on the right was significantly higher in AP compared to AN subjects. Functional connectivity showed that the left anterior insula was involved in a similar network during pleasant anticipation in both groups. The left anterior insula during aversive and the right anterior insula during all anticipation conditions co-activated with a cortical network consisting of frontal and parietal lobes in the AP group to a greater degree. These results are consistent with the hypothesis that anxiety is related to greater anticipatory reactivity in the brain and that there may be functional asymmetries in the brain that interact with psychiatric traits.

Simmons, Alan; Stein, Murray B.; Strigo, Irina A; Arce, Estibaliz; Hitchcock, Carla; Paulus, Martin P.

2011-01-01

19

Anxiety positive subjects show altered processing in the anterior insula during anticipation of negative stimuli.  

PubMed

Prior neuroimaging studies support the hypothesis that anticipation, an important component of anxiety, may be mediated by activation within the insular and medial prefrontal cortices including the anterior cingulate cortex. However, there is an insufficient understanding of how affective anticipation differs across anxiety groups in emotional brain loci and networks. We examined 14 anxiety positive (AP) and 14 anxiety normative (AN) individuals completing an affective picture anticipation task during functional magnetic resonance imaging (fMRI). Brain activation was examined across groups for cued anticipation (to aversive or pleasant stimuli). Both groups showed greater activation in the bilateral anterior insula during cued differential anticipation (i.e., aversive vs. pleasant), and activation on the right was significantly higher in AP compared to AN subjects. Functional connectivity showed that the left anterior insula was involved in a similar network during pleasant anticipation in both groups. The left anterior insula during aversive and the right anterior insula during all anticipation conditions coactivated with a cortical network consisting of frontal and parietal lobes in the AP group to a greater degree. These results are consistent with the hypothesis that anxiety is related to greater anticipatory reactivity in the brain and that there may be functional asymmetries in the brain that interact with psychiatric traits. PMID:21181800

Simmons, Alan N; Stein, Murray B; Strigo, Irina A; Arce, Estibaliz; Hitchcock, Carla; Paulus, Martin P

2010-12-22

20

Antiparkinson drug--Mucuna pruriens shows antioxidant and metal chelating activity.  

PubMed

Parkinson's disease is a neurodegenerative disorder for which no neurorestorative therapeutic treatment is currently available. Oxidative stress plays an important role in the pathophysiology of Parkinson's disease. The ancient Indian medical system, Ayurveda, traditionally uses Mucuna pruriens to treat Parkinson's disease. In our earlier studies, Mucuna pruriens has been shown to possess antiparkinson and neuroprotective effects in animal models of Parkinson's disease. The antioxidant activity of Mucuna pruriens was demonstrated by its ability to scavenge DPPH radicals, ABTS radicals and reactive oxygen species. Mucuna pruriens significantly inhibited the oxidation of lipids and deoxyribose sugar. Mucuna pruriens exhibited divalent iron chelating activity and did not show any genotoxic/mutagenic effect on the plasmid DNA. These results suggest that the neuroprotective and neurorestorative effect of Mucuna pruriens may be related to its antioxidant activity independent of the symptomatic effect. In addition, the drug appears to be therapeutically safe in the treatment of patients with Parkinson's disease. PMID:18064727

Dhanasekaran, Muralikrishnan; Tharakan, Binu; Manyam, Bala V

2008-01-01

21

Few Girls With Childhood Attention-Deficit\\/Hyperactivity Disorder Show Positive Adjustment During Adolescence  

Microsoft Academic Search

Employing data from 140 prospectively followed girls with attention-deficit\\/hyperactivity disorder (ADHD) and 88 age- and ethnicity-matched comparison girls, we adopted a person-centered analytic approach to assess rates of adolescent positive adjustment (PA) across six domains: ADHD symptoms, externalizing symptoms, internalizing symptoms, social skills, peer acceptance, and school achievement. During adolescence, between 19.8% and 61.1% of the girls with childhood ADHD

Elizabeth B. Owens; Stephen P. Hinshaw; Steve S. Lee; Benjamin B. Lahey

2009-01-01

22

Legal Position of School Personnel -- Drugs and Narcotics.  

ERIC Educational Resources Information Center

|California educators have been given broad discretionary powers to control students who misuse drugs or narcotics, and to develop drug education programs. This paper outlines and discusses legislation dealing with disciplinary actions against drug offenders, and delineates school responsibilities for developing and implementing effective drug

Shannon, Thomas A.

23

Drug abusers show impaired performance in a laboratory test of decision making  

Microsoft Academic Search

A defining feature of drug addiction is persistent drug use despite long-term adverse consequences. This study examined the performance of drug abusers on a neuropsychological test that requires evaluation of long-term outcomes in the presence of a complex set of mixed reward\\/punishment contingencies (the Gambling Task). In order to control for generalized deficits related to choice and planning, subjects were

Steven Grant; Carlo Contoreggi; Edythe D. London

2000-01-01

24

Male and Female Plasmodium falciparum Mature Gametocytes Show Different Responses to Antimalarial Drugs  

PubMed Central

It is the mature gametocytes of Plasmodium that are solely responsible for parasite transmission from the mammalian host to the mosquito. They are therefore a logical target for transmission-blocking antimalarial interventions, which aim to break the cycle of reinfection and reduce the prevalence of malaria cases. Gametocytes, however, are not a homogeneous cell population. They are sexually dimorphic, and both males and females are required for parasite transmission. Using two bioassays, we explored the effects of 20 antimalarials on the functional viability of both male and female mature gametocytes of Plasmodium falciparum. We show that mature male gametocytes (as reported by their ability to produce male gametes, i.e., to exflagellate) are sensitive to antifolates, some endoperoxides, methylene blue, and thiostrepton, with submicromolar 50% inhibitory concentrations (IC50s), whereas female gametocytes (as reported by their ability to activate and form gametes expressing the marker Pfs25) are much less sensitive to antimalarial intervention, with only methylene blue and thiostrepton showing any significant activity. These findings show firstly that the antimalarial responses of male and female gametocytes differ and secondly that the mature male gametocyte should be considered a more vulnerable target than the female gametocyte for transmission-blocking drugs. Given the female-biased sex ratio of Plasmodium falciparum (?3 to 5 females:1 male), current gametocyte assays without a sex-specific readout are unlikely to identify male-targeted compounds and prioritize them for further development. Both assays reported here are being scaled up to at least medium throughput and will permit identification of key transmission-blocking molecules that have been overlooked by other screening campaigns.

Ruecker, Andrea; Straschil, Ursula; Lelievre, Joel; Marques, Sara; Lopez-Barragan, Maria Jose; Herreros, Esperanza; Sinden, Robert E.

2013-01-01

25

Male and female Plasmodium falciparum mature gametocytes show different responses to antimalarial drugs.  

PubMed

It is the mature gametocytes of Plasmodium that are solely responsible for parasite transmission from the mammalian host to the mosquito. They are therefore a logical target for transmission-blocking antimalarial interventions, which aim to break the cycle of reinfection and reduce the prevalence of malaria cases. Gametocytes, however, are not a homogeneous cell population. They are sexually dimorphic, and both males and females are required for parasite transmission. Using two bioassays, we explored the effects of 20 antimalarials on the functional viability of both male and female mature gametocytes of Plasmodium falciparum. We show that mature male gametocytes (as reported by their ability to produce male gametes, i.e., to exflagellate) are sensitive to antifolates, some endoperoxides, methylene blue, and thiostrepton, with submicromolar 50% inhibitory concentrations (IC50s), whereas female gametocytes (as reported by their ability to activate and form gametes expressing the marker Pfs25) are much less sensitive to antimalarial intervention, with only methylene blue and thiostrepton showing any significant activity. These findings show firstly that the antimalarial responses of male and female gametocytes differ and secondly that the mature male gametocyte should be considered a more vulnerable target than the female gametocyte for transmission-blocking drugs. Given the female-biased sex ratio of Plasmodium falciparum (?3 to 5 females:1 male), current gametocyte assays without a sex-specific readout are unlikely to identify male-targeted compounds and prioritize them for further development. Both assays reported here are being scaled up to at least medium throughput and will permit identification of key transmission-blocking molecules that have been overlooked by other screening campaigns. PMID:23629698

Delves, Michael J; Ruecker, Andrea; Straschil, Ursula; Leličvre, Jöel; Marques, Sara; López-Barragán, María José; Herreros, Esperanza; Sinden, Robert E

2013-04-29

26

Do rewardless orchids show a positive relationship between phenotypic diversity and reproductive success?  

PubMed

Among rewardless orchids, pollinator sampling behavior has been suggested to drive a positive relationship between population phenotypic variability and absolute reproductive success, and hence population fitness. We tested this hypothesis by constructing experimental arrays using the rewardless orchid Dactylorhiza sambucina, which is dimorphic for corolla color. We found no evidence that polymorphic arrays had higher mean reproductive success than monomorphic arrays for pollinia removal, pollen deposition, or fruit set. For pollinia removal, monomorphic yellow arrays had significantly greater reproductive success, and monomorphic red the least. A tendency for yellow arrays to have higher pollen deposition was also found. We argue that differential population fitness was most likely to reflect differential numbers of pollinators attracted to arrays, through preferential long-distance attraction to arrays with yellow inflorescences. Correlative studies of absolute reproductive success in 52 populations of D. sambucina supported our experimental results. To our knowledge this is the first study to suggest that attraction of a greater number of pollinators to rewardless orchids may be of greater functional importance to population fitness, and thus ecology and conservation, than are the behavioral sequences of individual pollinators. PMID:17479761

Smithson, Ann; Juillet, Nicolas; Macnair, Mark R; Gigord, Luc D B

2007-02-01

27

In Sloan-Kettering study, new drug shows promise for patients with advanced kidney cancer  

Cancer.gov

People with advanced kidney cancer may have a new alternative in their limited arsenal of treatment options that are both well tolerated and effective against the disease. New research led by Memorial Sloan-Kettering has shown that the investigational drug tivozanib is more effective than an approved targeted therapy called sorafenib (Nexavar®) in delaying the growth of their cancer.

28

Conditional drug screening shows that mitotic inhibitors induce AKT\\/PKB-insensitive apoptosis  

Microsoft Academic Search

The phosphatidylinositol 3-kinase (PI3K)\\/AKT pathway is frequently upregulated in human cancer. Activation of this pathway\\u000a has been reported to be associated with resistance to various chemotherapeutical agents. We here used a chemical biology\\/chemical\\u000a informatic approach to identify apoptotic mechanisms that are insensitive to activation of the PI3K\\/AKT pathway. The National\\u000a Cancer Institute (NCI) Mechanistic Set drug library was screened for

Maria Berndtsson; Emma Hernlund; Maria C. Shoshan; Stig Linder

2009-01-01

29

Drug-eluting stents show delayed healing: paclitaxel more pronounced than sirolimus  

Microsoft Academic Search

Aims To understand wound healing after drug-eluting stents (DES) placement in humans, we studied the histology of in-stent restenosis (ISR) tissue obtained by atherectomy from bare metal stents (BMS) and DES in comparison with de novo atherosclerosis. Methods and results The tissue was retrieved from ISR in ten sirolimus-eluting stents (SES) and nine paclitaxel-eluting stents (PES), six BMS, and nine

Heleen M. M. van Beusekom; Francesco Saia; Jaap D. Zindler; Pedro A. Lemos; Stijn L. Swager-ten Hoor; Maarten A. H. van Leeuwen; Pim J. de Feijter; Patrick W. Serruys; Willem J. van der Giessen

30

Studies show new drug to be effective in treating skin cancer  

Cancer.gov

A clinical study has demonstrated that a new drug, a targeted molecular therapy called vismodegib (trade name Erivedge), can dramatically shrink basal cell skin cancers and prevent the formation of new ones, in patients with basal cell nevus syndrome (BCNS). This rare genetic condition causes dozens, and sometimes hundreds or thousands, of skin cancers on each patient’s body. The primary treatment option is surgical removal. These study results are significant as they indicate the possibility of an alternative treatment with oral medication; although side effects remain a consideration.

31

HIV drug shows efficacy in treating mouse models of HER2+ breast cancer  

Cancer.gov

The HIV protease inhibitor, Nelfinavir, can be used to treat HER2-positive breast cancer in the same capacity and dosage regimen that it is used to treat HIV, according to a Johns Hopkins School of Medicine study published October 5 in the Journal of the National Cancer Institute. Johns Hopkins University is home to the Sidney Kimmel Comprehensive Cancer Center.

32

Sexual Risk Taking among HIV-Positive Injection Drug Users: Contexts, Characteristics, and Implications for Prevention  

ERIC Educational Resources Information Center

|HIV-positive injection drug users (IDUs) (N = 161) were recruited to complete a qualitative interview and a quantitative survey about sexual behavior and transmission risk. We identified two contexts in which exposure encounters occurred most commonly for HIV-positive IDUs: in intimate serodiscordant relationships and in the drug/sex economy.…

Knight, Kelly R.; Purcell, David; Dawson-Rose, Carol; Halkitis, Perry N.; Gomez, Cynthia A.

2005-01-01

33

Predicting Positive Attitudes About Quitting Drug and Alcohol Use Among Homeless Women  

Microsoft Academic Search

Two separate path models for alcohol and drugs were tested in which psychosocial, environmental, and sociodemographic variables predicted behavioral and substance abuse related factors as well as the key outcome of positive attitudes about quitting drugs (N = 620) or alcohol (N = 526) in a sample of 709 homeless women. A positive attitude about quitting alcohol was predicted by

Adeline M. Nyamathi; Judith A. Stein; Elizabeth Dixon; Douglas Longshore; Elisha Galaif

2003-01-01

34

Cost-effectiveness of methadone maintenance treatment for HIV-positive drug users in Vietnam  

Microsoft Academic Search

Methadone maintenance treatment (MMT) is efficacious in reducing drug use that may improve HIV\\/AIDS care and treatment outcomes. This study evaluated the incremental cost-effectiveness of MMT for HIV-positive drug users from the perspective of health service providers. A sample of 370 HIV-positive drug users (age: mean±SD: 29.5±5.9 years; 95.7% male) taking MMT in multi-sites was assessed at baseline, three, six

Bach Xuan Tran; Arto Ohinmaa; Anh Thuy Duong; Nhan Thi Do; Long Thanh Nguyen; Steve Mills; Stan Houston; Philip Jacobs

2012-01-01

35

Cost-effectiveness of methadone maintenance treatment for HIV-positive drug users in Vietnam  

Microsoft Academic Search

Methadone maintenance treatment (MMT) is efficacious in reducing drug use that may improve HIV\\/AIDS care and treatment outcomes. This study evaluated the incremental cost-effectiveness of MMT for HIV-positive drug users from the perspective of health service providers. A sample of 370 HIV-positive drug users (age: mean±SD: 29.5±5.9 years; 95.7% male) taking MMT in multi-sites was assessed at baseline, three, six

Bach Xuan Tran; Arto Ohinmaa; Anh Thuy Duong; Nhan Thi Do; Long Thanh Nguyen; Steve Mills; Stan Houston; Philip Jacobs

2011-01-01

36

Strut Position, Blood Flow, and Drug Deposition Implications for Single and Overlapping Drug-Eluting Stents  

Microsoft Academic Search

Background—The intricacies of stent design, local pharmacology, tissue biology, and rheology preclude an intuitive understanding of drug distribution and deposition from drug-eluting stents (DES). Methods and Results—A coupled computational fluid dynamics and mass transfer model was applied to predict drug deposition for single and overlapping DES. Drug deposition appeared not only beneath regions of arterial contact with the strut but

Brinda Balakrishnan; Abraham R. Tzafriri; Philip Seifert; Adam Groothuis; Campbell Rogers; Elazer R. Edelman

2010-01-01

37

Report Shows That "Bath Salts" Drugs Were Involved in Nearly 23,000 Emergency Department Visits in One Year  

MedlinePLUS

... Report shows that “Bath Salts” drugs were involved in nearly 23,000 emergency department visits in one year A new national report reveals that “ ... estimated 22,904 visits to hospital emergency departments in 2011. The report by the Substance Abuse and ...

38

Contamination of dietary supplements and positive drug tests in sport.  

PubMed

The use of dietary supplements is widespread in sport and most athletes competing at the highest level of competition use some form of dietary supplementation. Many of these supplements confer no performance or health benefit, and some may actually be detrimental to both performance and health when taken in high doses for prolonged periods. Some supplements contain excessive doses of potentially toxic ingredients, while others do not contain significant amounts of the ingredients listed on the label. There is also now evidence that some of the apparently legitimate dietary supplements on sale contain ingredients that are not declared on the label but that are prohibited by the doping regulations of the International Olympic Committee and of the World Anti-Doping Agency. Contaminants that have been identified include a variety of anabolic androgenic steroids (including testosterone and nandrolone as well as the pro-hormones of these compounds), ephedrine and caffeine. This contamination may in most cases be the result of poor manufacturing practice, but there is some evidence of deliberate adulteration of products. The principle of strict liability that applies in sport means that innocent ingestion of prohibited substances is not an acceptable excuse, and athletes testing positive are liable to penalties. Although it is undoubtedly the case that some athletes are guilty of deliberate cheating, some positive tests are likely to be the result of inadvertent ingestion of prohibited substances present in otherwise innocuous dietary supplements. PMID:16195040

Maughan, R J

2005-09-01

39

Differences in treatment outcome between male alcohol dependent offenders of domestic violence with and without positive drug screens.  

PubMed

Men who are violent toward their partners tend to have a dual problem with alcohol and drug use, yet little is known about differences between men with single rather than dual problems. This study was one of the first to evaluate differences between alcohol dependent men who were arrested for Intimate Partner Violence (IPV) with and without concurrent illicit drug use. Seventy-eight participants were randomly assigned to manual-guided group behavioral therapies (Cognitive Behavioral Therapy or Twelve Step Facilitation) and assessed across 12 weeks of treatment. Despite denying drug use at baseline, thirty-two clients (43%) tested positive for illicit drug use (cocaine and marijuana) during the 12 weeks of treatment. The study specifically addressed whether there were differences between clients using alcohol only versus individuals using both alcohol + drugs in terms of 1) baseline characteristics; 2) treatment compliance (e.g., attendance and substance use during treatment; and 3) treatment outcomes (alcohol, drug use, anger management, and aggression at the completion of treatment). The results showed that there were comparatively few differences between the alcohol versus the alcohol + drug using groups at baseline. Regarding treatment compliance and retention, alcohol + drug using participants attended significantly fewer sessions, had significantly fewer percent days abstinence from alcohol use, significantly more total days of positive breathalyzer results. Regarding treatment outcomes across anger management and aggression scores, the alcohol + drug using participants had significantly more impairments in anger management styles from pre- to post-treatment. However, there were no differences between the groups across verbal or physical aggression. Both groups improved in their verbal aggression from pre- to post-treatment. The findings suggest that alcohol dependent men who continue to use illicit drugs may require additional interventions to effectively control their drug use and, their anger management styles. PMID:17367953

Easton, Caroline J; Mandel, Dolores; Babuscio, Theresa; Rounsaville, Bruce J; Carroll, Kathleen M

2007-02-04

40

Protamine 3 shows evidence of weak, positive selection in mouse species (genus Mus)--but it is not a protamine.  

PubMed

Protamines are short and highly basic sperm-specific nuclear proteins that replace somatic histones during spermiogenesis in a process that is crucial for sperm formation and function. Many mammals have two protamine genes (PRM1 and PRM2) located in a gene cluster, which appears to evolve fast. Another gene in this cluster (designated protamine 3 [PRM3]) encodes a protein that is conserved among mammals but that does not seem to be involved in chromatin condensation. We have compared protein sequences and amino acid compositions of protamines in this gene cluster, searched for evidence of positive selection of PRM3, and examined whether sexual selection (sperm competition) may drive the evolution of the PRM3 gene. Nucleotide and amino acid analyses of mouse sequences revealed that PRM3 was very different from PRM1 and from both the precursor and the mature sequences of PRM2. Among 10 mouse species, PRM3 showed weak evidence of positive selection in two species, but there was no clear association with levels of sperm competition. In analyses from among mammalian species, no evidence of positive selection was found in PRM3. We conclude that PRM3 exhibits several clear differences from other protamines and, furthermore, that it cannot be regarded as a true protamine. PMID:20944085

Martin-Coello, Juan; Gomendio, Montserrat; Roldan, Eduardo R S

2010-10-13

41

Responses to Positive Results from Suspicionless Random Drug Tests in US Public School Districts  

ERIC Educational Resources Information Center

|Background: Little is known about the context in which school-based suspicionless random drug testing (SRDT) occurs. The primary purpose of the current study was to describe school districts' responses to students' first positive result in districts with SRDT programs. Methods: Data were collected in spring 2005 from 1612 drug prevention…

Ringwalt, Chris; Vincus, Amy A.; Ennett, Susan T.; Hanley, Sean; Bowling, J. Michael; Yacoubian, George S., Jr.; Rohrbach, Louise A.

2009-01-01

42

Physical activity in a cohort of HIV-positive and HIV-negative injection drug users  

Microsoft Academic Search

Physical activity is beneficial for persons with HIV infection but little is known about the relationships between physical activity, HIV treatment and injection drug use (IDU). This study compared physical activity levels between HIV-negative and HIV-positive injection drug users (IDUs) and between HIV-positive participants not on any treatment and participants on highly active antiretroviral therapy (HAART). Anthropometric measurements were obtained

E. Smit; C. J. Crespo; R. D. Semba; D. Jaworowicz; D. Vlahov; E. P. Ricketts; F. A. Ramirez-Marrero; A. M. Tang

2006-01-01

43

Drug poisoning deaths in Sweden show a predominance of ethanol in mono-intoxications, adverse drug–alcohol interactions and poly-drug use  

Microsoft Academic Search

Over a 10-year period (1998–2007) all deaths in Sweden classified by forensic pathologists as fatal drug poisonings (N=6894) were retrieved from a toxicology database (TOXBASE) belonging to the National Board of Forensic Medicine. The deaths were further classified as suicides N=2288 (33%), undetermined N=2260 (33%) and accidental N=2346 (34%). The average age (±SD) of all victims was 49.1±15.9 years and

A. W. Jones; F. C. Kugelberg; A. Holmgren; J. Ahlner

2011-01-01

44

Regions with higher Medicare Part D spending show better drug adherence, but not lower medicare costs for two diseases.  

PubMed

A quarter-century of research on geographic variation in Medicare costs has failed to find any positive association between high spending and better health outcomes. We conducted this study using a 5 percent random sample of Medicare beneficiaries with diabetes or heart failure in 2006 and 2007 to see whether there was any correlation between geographic variation in Part D spending and good medication-taking behavior-and, if so, whether that correlation resulted in reduced Medicare Parts A and B spending on diabetes and heart failure treatments. We found that beneficiaries residing in areas characterized by higher adjusted drug spending had significantly more "therapy days"-days with recommended medications on hand-than did beneficiaries in lower-spending areas. However, we did not find that this factor translated into short-term savings in Medicare treatment costs for these two diseases. This result might not be surprising, since returns from medication adherence can take years to manifest. At the same time, discovering which regional factors are responsible for differences in drug spending and medication practices should be a high priority. If the observed differences are related to poor physician communication or lack of good care coordination, then appropriately designed policy tools-including accountable care organizations, medical homes, and provider quality reporting initiatives-might help address them. PMID:23297279

Stuart, Bruce; Shoemaker, J Samantha; Dai, Mingliang; Davidoff, Amy J

2013-01-01

45

Oral fluid drug testing of chronic pain patients. I. Positive prevalence rates of licit and illicit drugs.  

PubMed

Oral fluid compliance monitoring of chronic pain patients is an analytical challenge because of the limited specimen volume and the number of drugs that require detection. This study evaluated oral fluid for monitoring pain patients and compared results to urine studies of similar populations. Oral fluid specimens were analyzed from 6441 pain patients from 231 pain clinics in 20 states. Specimens were screened with 14 ELISA assays and non-negative specimens were confirmed by LC-MS-MS for 40 licit and illicit drugs and metabolites. There was an 83.9% positive screening rate (n=5401) of which 98.7% (n=5329) were confirmed at ? LOQ concentrations for at least one analyte. The prevalence of confirmed positive drug groups was as follows: opiates > oxycodone > benzodiazepines > methadone ? carisoprodol > fentanyl > cannabinoids ? tramadol > cocaine > amphetamines ? propoxyphene ? buprenorphine > barbiturates > methamphetamine. Approximately 11.5% of the study population of pain patients apparently used one or more illicit drugs (cannabis, cocaine, methamphetamine and/or MDMA). Overall, the pattern of licit and illicit drugs and metabolites observed in oral fluid paralleled results reported earlier for urine, indicating that oral fluid is a viable option for use in compliance monitoring programs of chronic pain patients. PMID:22004671

Heltsley, Rebecca; DePriest, Anne; Black, David L; Robert, Tim; Marshall, Lucas; Meadors, Viola M; Caplan, Yale H; Cone, Edward J

2011-10-01

46

Impact of a positive hepatitis C diagnosis on homeless injecting drug users: a qualitative study  

PubMed Central

Background Increasing numbers of injecting drug users are presenting to primary care and a growing number of general practices are specifically providing care for homeless people. Injecting drug users are at the greatest risk of hepatitis C infection and homeless drug misusers, because of their drug-taking behaviour and patterns, have been identified as being at greater risk of harm of blood-borne diseases than the general population. However, little work has been conducted with injecting drug users or homeless people who have hepatitis C and little is known about how the virus may affect them. Aim To explore the impact of a positive hepatitis C diagnosis on homeless injecting drug users. Design of study This study employed qualitative research. In-depth interviews allowed the exploration of the impact of a potentially life-threatening diagnosis within the context of a person's expressed hierarchy of needs. Setting A primary care centre for homeless people in the north of England. Method In-depth interviews about the impact of a positive hepatitis C diagnosis on their lives were conducted with 17 homeless injecting drug users who had received a positive hepatitis C diagnosis. The interviews were audiotaped, transcribed, and analysed using the framework approach. Results Receiving a positive diagnosis for hepatitis C resulted in feelings of shock, devastation, disbelief, anger, and questioning. A positive diagnosis had lasting social, emotional, psychological, behavioural, and physical effects on homeless injecting drug users, even years after the initial diagnosis. Most responders were diagnosed by a doctor in primary care or by hospital staff; however, not all had sought testing and a number were tested while inpatients and were unaware that blood had been taken for hepatitis C virus serology. Conclusions The implications for clinical policy and primary care practice are discussed, including the issues of patient choice, confidentiality, and pre- and post-test discussions. Post-test discussions should be followed up with additional social, psychological, and medical support and counselling.

Tompkins, Charlotte NE; Wright, Nat MJ; Jones, Lesley

2005-01-01

47

Individuals Family History Positive for Alcoholism Show fMRI Differences in Reward Sensitivity that are Related to Impulsivity Factors  

PubMed Central

Background Substance abusing individuals tend to display abnormal reward processing and a vulnerability to being impulsive. Detoxified alcoholics show differences in regional brain activation during a monetary incentive delay (MID) task. However there is limited information on whether this uncharacteristic behavior represents a biological predisposition towards alcohol abuse, a consequence of chronic alcohol use, or both. Methods We investigated proposed neural correlates of substance disorder risk by examining reward system activity during a MID task with separate reward prospect, reward anticipation, and reward outcome phases in 30 individuals with and 19 without family histories of alcoholism. All subjects were healthy, lacked DSM-IV past or current alcohol or substance abuse histories, and were free of illegal substances as verified by a urine toxicology screening at the time of scanning. Additionally, we explored specific correlations between task-related nucleus accumbens (NAcc) activation and distinct factor analysis-derived domains of behavioral impulsivity. Results During reward anticipation, fMRI data confirmed blunted NAcc activation in family history positive subjects. In addition, we found atypical activation in additional reward-associated brain regions during additional task phases. We further found a significant negative correlation between NAcc activation during reward anticipation and an impulsivity construct. Conclusions Overall, results demonstrate that sensitivity of the reward circuit, including NAcc, is functionally different in alcoholism FHP individuals in multiple regards.

Andrews, Melissa M.; Meda, Shashwath A.; Thomas, Andre D.; Potenza, Marc N.; Krystal, John H; Worhunsky, Patrick; Stevens, Michael C.; O'Malley, Stephanie; Book, Gregory A.; Reynolds, Brady; Pearlson, Godfrey D.

2013-01-01

48

Gender, Drug Use, and Perceived Social Support Among HIV Positive Patients  

Microsoft Academic Search

We investigated the relationships among gender, drug use, and perceived social support in 176 HIV positive patients recruited\\u000a with their informal caregivers in HIV clinics. Perceived caregiver support, emotional support, tangible support, and conflict\\u000a were assessed. Current drug use was defined as heroin and\\/or cocaine use within 6 months prior to baseline. Gender was not\\u000a significantly associated with any of the

Gabriella Rothman; Bradley J. Anderson; Michael D. Stein

2008-01-01

49

Positive Youth Development: Helping Postsecondary Students Deal with Pressures To Use Alcohol and Other Drugs.  

ERIC Educational Resources Information Center

|Current research shows alcohol and other drugs to be a major problem on postsecondary campuses despite the fact that the purchase and use of alcohol is illegal for many college students and on most campuses. Little is known about drug and alcohol use levels among deaf students, many of whom come to college ill prepared to handle the pressures of…

Guthmann, Debra S.; Sandberg, Katherine A.

50

Thirsty heroin addicts show different fMRI activations when exposed to water-related and drug-related cues  

Microsoft Academic Search

Relapse to drug use is frequently preceded or caused by craving, an intense desire for drug. Advances in functional brain imaging techniques make it possible to directly investigate this special mental state in vivo and non-invasively. Extant imaging studies on craving have been mostly on cocaine which is the dominant drug abused in the U.S. Employing functional MRI, we examined

Zhuangwei Xiao; Tatia Lee; John X. Zhang; Qiulin Wu; Renhua Wu; Xuchu Weng; Xiaoping Hu

2006-01-01

51

Eczematous-type multiple drug allergy from isoniazid and ethambutol with positive patch test results.  

PubMed

Multiple drug allergy (MDA) is characterized by hypersensitivity to 2 or more chemically unrelated drugs. Multiple drug allergy from simultaneous use of antituberculosis drugs is a rare phenomenon that mainly presents as an urticarial or maculopapular eruption. This case report describes a 58-year-old man who developed a generalized eczematous eruption during the sixth week of oral therapy with 4 antituberculosis drugs-isoniazid, ethambutol, rifampicin, and morphazinamide-for treatment of suspected pleural tuberculosis. The eruption resolved after treatment with systemic corticosteroids and cessation of isoniazid and ethambutol. During a lesion-free period 6 months after cessation of the corticosteroids, patch testing with serial dilutions of isoniazid and ethambutol revealed positive reactions; irritant patch test reactions were excluded by testing with graded concentrations of each drug. The patient avoided the causative drugs and reported no new eruptions at 1-year follow-up. It is important for dermatologists to consider the value of patch testing in determining the causative drugs in suspected cases of eczematous-type MDA. PMID:24153138

Ozkaya, Esen

2013-09-01

52

Yersinia enterocolitica serotype O:9 cultured from Swedish sheep showing serologically false-positive reactions for Brucella melitensis  

PubMed Central

In a herd of 20 sheep in Sweden, a country where brucellosis has never been diagnosed in sheep or goats, a total of six sheep were found serologically positive to Brucella melitensis in two different rounds of sampling. Yersinia enterocolitica serotype O:9 could at the time of the second sampling be isolated from four sheep, one of them at the same time serologically positive for B. melitensis. The article describes the case and gives some background information on brucellosis and Y. enterocolitica in general as well as a more specific description of the Swedish surveillance program for B. melitensis and the test procedures used. The problem with false-positive reactions, in particular its implications for surveillance programs in low prevalence or officially brucellosis-free countries, is discussed.

Chenais, Erika; Bagge, Elisabeth; Lambertz, Susanne Thisted; Artursson, Karin

2012-01-01

53

Sexual Transmission Risk Behavior Reported Among Behaviorally Bisexual HIV-Positive Injection Drug-Using Men  

Microsoft Academic Search

Background: Few research studies have examined the HIV trans- mission risk behaviors of HIV-positive injection drug users (IDUs) who are men who have sex with men and women (MSMW). Methods: We compared unprotected vaginal or anal sex with an HIV-negative or unknown (UNK) status sexual partner of MSMW (n = 118) with men who have sex exclusively with women (MSW;

Kelly R. Knight; Starley B. Shade; David W. Purcell; Carol Dawson Rose; Lisa R. Metsch; Mary H. Latka; Carl A. Latkin; Cynthia A. Gomez

2007-01-01

54

Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis.  

PubMed

M. tuberculosis is evolving antibiotic resistance, threatening attempts at tuberculosis epidemic control. Mechanisms of resistance, including genetic changes favored by selection in resistant isolates, are incompletely understood. Using 116 newly sequenced and 7 previously sequenced M. tuberculosis whole genomes, we identified genome-wide signatures of positive selection specific to the 47 drug-resistant strains. By searching for convergent evolution-the independent fixation of mutations in the same nucleotide position or gene-we recovered 100% of a set of known resistance markers. We also found evidence of positive selection in an additional 39 genomic regions in resistant isolates. These regions encode components in cell wall biosynthesis, transcriptional regulation and DNA repair pathways. Mutations in these regions could directly confer resistance or compensate for fitness costs associated with resistance. Functional genetic analysis of mutations in one gene, ponA1, demonstrated an in vitro growth advantage in the presence of the drug rifampicin. PMID:23995135

Farhat, Maha R; Shapiro, B Jesse; Kieser, Karen J; Sultana, Razvan; Jacobson, Karen R; Victor, Thomas C; Warren, Robin M; Streicher, Elizabeth M; Calver, Alistair; Sloutsky, Alex; Kaur, Devinder; Posey, Jamie E; Plikaytis, Bonnie; Oggioni, Marco R; Gardy, Jennifer L; Johnston, James C; Rodrigues, Mabel; Tang, Patrick K C; Kato-Maeda, Midori; Borowsky, Mark L; Muddukrishna, Bhavana; Kreiswirth, Barry N; Kurepina, Natalia; Galagan, James; Gagneux, Sebastien; Birren, Bruce; Rubin, Eric J; Lander, Eric S; Sabeti, Pardis C; Murray, Megan

2013-09-01

55

Developing and implementing a positive behavioral reinforcement intervention in prison-based drug treatment: Project BRITE.  

PubMed

Within prison settings, the reliance on punishment for controlling inappropriate or noncompliant behavior is self-evident. What is not so evident is the similarity between this reliance on punishment and the use of positive reinforcements to increase desired behaviors. However, seldom do inmates receive positive reinforcement for engaging in prosocial behaviors or, for inmates receiving drug treatment, behaviors that are consistent with or support their recovery. This study provides an overview of the development and implementation of a positive behavioral reinforcement intervention in male and female prison-based drug treatment programs. The active involvement of institutional staff, treatment staff, and inmates enrolled in the treatment programs in the development of the intervention along with the successful branding of the intervention were effective at promoting support and participation. However, these factors may also have ultimately impacted the ability of the randomized design to reliably demonstrate the effectiveness of the intervention. PMID:22185038

Burdon, William M; St De Lore, Jef; Prendergast, Michael L

2011-09-01

56

Mucosal CD30-positive T-cell lymphoproliferations of the head and neck show a clinicopathologic spectrum similar to cutaneous CD30-positive T-cell lymphoproliferative disorders.  

PubMed

CD30-positive T-cell lymphoproliferative disorders are classified as cutaneous (primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis) or systemic. As extent of disease dictates prognosis and treatment, patients with skin involvement need clinical staging to determine whether systemic lymphoma also is present. Similar processes may involve mucosal sites of the head and neck, constituting a spectrum that includes both neoplasms and reactive conditions (eg, traumatic ulcerative granuloma with stromal eosinophilia). However, no standard classification exists for mucosal CD30-positive T-cell lymphoproliferations. To improve our understanding of these processes, we identified 15 such patients and examined clinical presentation, treatment and outcome, morphology, phenotype using immunohistochemistry, and genetics using gene rearrangement studies and fluorescence in situ hybridization. The 15 patients (11 M, 4 F; mean age, 57 years) had disease involving the oral cavity/lip/tongue (9), orbit/conjunctiva (3) or nasal cavity/sinuses (3). Of 14 patients with staging data, 7 had mucosal disease only; 2 had mucocutaneous disease; and 5 had systemic anaplastic large cell lymphoma. Patients with mucosal or mucocutaneous disease only had a favorable prognosis and none developed systemic spread (follow-up, 4-93 months). Three of five patients with systemic disease died of lymphoma after 1-48 months. Morphologic and phenotypic features were similar regardless of extent of disease. One anaplastic lymphoma kinase-positive case was associated with systemic disease. Two cases had rearrangements of the DUSP22-IRF4 locus on chromosome 6p25.3, seen most frequently in primary cutaneous anaplastic large cell lymphoma. Our findings suggest mucosal CD30-positive T-cell lymphoproliferations share features with cutaneous CD30-positive T-cell lymphoproliferative disorders, and require clinical staging for stratification into primary and secondary types. Primary cases have clinicopathologic features closer to primary cutaneous disease than to systemic anaplastic large cell lymphoma, including indolent clinical behavior. Understanding the spectrum of mucosal CD30-positive T-cell lymphoproliferations is important to avoid possible overtreatment resulting from a diagnosis of overt T-cell lymphoma. PMID:22388754

Sciallis, Andrew P; Law, Mark E; Inwards, David J; McClure, Rebecca F; Macon, William R; Kurtin, Paul J; Dogan, Ahmet; Feldman, Andrew L

2012-03-02

57

[SICI-GISE position paper on drug-coated balloon use in the coronary district].  

PubMed

Drug-coated balloons are a new tool for the treatment of patients with coronary artery disease. The main feature of this technology is a rapid and homogeneous transfer of an antiproliferative drug (paclitaxel) to the vessel wall just at the time of balloon inflation, when neointimal proliferation, in response to angioplasty, is the highest. Moreover, drug-coated balloons share adjunctive advantages over stents: the absence of permanent scaffold and polymer, the respect of the original coronary anatomy, and limited inflammatory stimuli, thereby allowing for short-term dual antiplatelet therapy. At present, a variety of devices are available in the market, with limited scientific data for the vast majority of them. Thus, the Italian Society of Interventional Cardiology (SICI-GISE) decided to coordinate the efforts of a group of renowned experts in this field, in order to produce a position paper on the correct use of drug-coated balloons in all settings of coronary artery disease, giving a class of indication to each one, based on clinical evidence. This position paper represents a quick reference for operators, investigators and manufacturers to promote the understanding and the correct use of the drug-coated balloon technology in everyday clinical practice. PMID:24121894

Cortese, Bernardo; Sgueglia, Gregory A; Berti, Sergio; Biondi-Zoccai, Giuseppe; Colombo, Antonio; Limbruno, Ugo; Bedogni, Francesco; Cremonesi, Alberto

2013-10-01

58

Cost-effectiveness of methadone maintenance treatment for HIV-positive drug users in Vietnam.  

PubMed

Methadone maintenance treatment (MMT) is efficacious in reducing drug use that may improve HIV/AIDS care and treatment outcomes. This study evaluated the incremental cost-effectiveness of MMT for HIV-positive drug users from the perspective of health service providers. A sample of 370 HIV-positive drug users (age: mean ± SD: 29.5 ± 5.9 years; 95.7% male) taking MMT in multi-sites was assessed at baseline, three, six and nine months. Costs of MMT services were analyzed and converted to the year 2009. Quality-adjusted life years (QALYs) were modeled from changes in health-related quality of life of patients using the modified World Health Organization Quality of Life - Brief Version (WHOQOL-BREF). Inverse probability-of-treatment weights, constructed using propensity score of non-responses, were applied to adjust for potential confounding. Over nine months, MMT substantially improved QALYs of HIV/AIDS patients (0.076 QALY [0.066-0.084]). The increments in QALY were large and stabilized in those patients taking antiretroviral treatment and abstinent to drug use. For one QALY gained, the MMT program would cost US$3745.3, approximately 3.2 times Vietnam GDP per capita in 2009. The cost-effectiveness of MMT intervention was robust against HIV advanced status or co-morbidity, e.g., TB treatment, but it might not be cost-effective for those patients who continued to use drug. Findings of this study indicate that providing MMT for HIV-positive drug users is a cost-effective intervention in Vietnam. Integrating MMT to HIV/AIDS care and treatment services would be beneficial in injection-driven HIV epidemics. PMID:21936718

Tran, Bach Xuan; Ohinmaa, Arto; Duong, Anh Thuy; Do, Nhan Thi; Nguyen, Long Thanh; Mills, Steve; Houston, Stan; Jacobs, Philip

2011-09-22

59

Inhibition of related JAK/STAT pathways with molecular targeted drugs shows strong synergy with ruxolitinib in chronic myeloproliferative neoplasm.  

PubMed

This study aimed to assess the antitumour effects, molecular mechanisms of action, and potential synergy of ruxolitinib with sorafenib, KNK437, dasatinib, and perifosine, in Philadelphia-negative chronic myeloproliferative neoplasms (MPN). Cytotoxic and cytostatic effects of the different compounds were determined in the JAK2 V617F-positive cell lines, HEL and Ba/F3 (JAK2V617F EPOR) , and in primary mononuclear and bone marrow CD34-positive cells from 19 MPN patients. Ruxolitinib [50% inhibitory concentration (IC50 )(PV)  = 15 nmol/l], as well as sorafenib (IC50 PV=8?mol/l), KNK437 (IC50 PV=100?mol/l ), and perifosine (IC50 PV=15?mol/l ), were able to inhibit proliferation in cell line models and in primary cells from MPN patients. Dasatinib, KNK437, and sorafenib showed a strong synergistic effect in combination with ruxolitinib [combination index (CI)(PV)  < 0·3]. Western blot confirmed that ruxolitinib blocked ERK, and consequently STAT5 activation, sorafenib inhibited ERK, P38 and STAT5, dasatinib blocked SRC and STAT5, and KNK437 decreased the stability of the JAK2 protein, reducing its expression. Inhibiting JAK2-related proliferative pathways has the potential to inhibit cell proliferation in MPNs. Furthermore, the combination of ruxolitinib with inhibitors that target these pathways has a strong synergistic effect, which may be due to decreased activation of the common effector, STAT5. PMID:23560534

Barrio, Santiago; Gallardo, Miguel; Arenas, Alicia; Ayala, Rosa; Rapado, Inmaculada; Rueda, Daniel; Jimenez, Ana; Albizua, Enriqueta; Burgaleta, Carmen; Gilsanz, Florinda; Martinez-Lopez, Joaquin

2013-04-05

60

Nitric oxide (NO)-releasing statin derivatives, a class of drugs showing enhanced antiproliferative and antiinflammatory properties  

PubMed Central

Inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, namely statins, exert pleiotropic actions beyond lipid-lowering effects. Their pharmacological activity on atherosclerotic plaque stability and vascular inflammation appears to be mediated, at least in part, by nitric oxide (NO). With the aim of enhancing the nonlipid-lowering properties of selected statins, we introduced a NO-releasing moiety into the structure of pravastatin (NCX 6550) and fluvastatin (NCX 6553). NO release was evaluated as nitrosylhemoglobin adduct formation by using EPR spectroscopy in rat blood. Both compounds produced a linear time-dependent increase in nitrosylhemoglobin formation, which is consistent with slow NO release kinetics. In PC12 cells, unlike their native statins, both compounds stimulated cGMP formation (NCX 6550, EC50 = 2.3 ± 0.2 ?M; NCX 6553, EC50 = 2.7 ± 0.2 ?M). Moreover, NCX 6550 potently inhibited cell proliferation in rat aortic smooth muscle cells (IC50 = 2.2 ± 0.3 ?M) with a mechanism that involved both the polyamine and HMG-CoA reductase signaling pathways. Hence, mevalonate or putrescine partially reverted the effects of NCX 6550 and their combination was fully effective. In RAW 264.7 murine macrophage cells stimulated with lipopolysaccharide (1 ?g/ml), NCX 6550, but not pravastatin, significantly decreased inducible NO synthase and cyclooxygenase-2 protein expression as well as nitrite accumulation. All together, the data show that the previously undescribed NO-releasing statins retain HMG-CoA reductase inhibitory activity and release bioactive NO slowly. Among the additional properties, compared with native statins, the NO-releasing statins show enhanced antiinflammatory effects. Thus, NO-releasing statins represent an interesting class of drugs having potential in the therapy of disorders associated with endothelial dysfunction and vascular inflammation.

Ongini, Ennio; Impagnatiello, Francesco; Bonazzi, Albino; Guzzetta, Massimiliano; Govoni, Mirco; Monopoli, Angela; Del Soldato, Piero; Ignarro, Louis J.

2004-01-01

61

Nitric oxide (NO)-releasing statin derivatives, a class of drugs showing enhanced antiproliferative and antiinflammatory properties.  

PubMed

Inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, namely statins, exert pleiotropic actions beyond lipid-lowering effects. Their pharmacological activity on atherosclerotic plaque stability and vascular inflammation appears to be mediated, at least in part, by nitric oxide (NO). With the aim of enhancing the nonlipid-lowering properties of selected statins, we introduced a NO-releasing moiety into the structure of pravastatin (NCX 6550) and fluvastatin (NCX 6553). NO release was evaluated as nitrosylhemoglobin adduct formation by using EPR spectroscopy in rat blood. Both compounds produced a linear time-dependent increase in nitrosylhemoglobin formation, which is consistent with slow NO release kinetics. In PC12 cells, unlike their native statins, both compounds stimulated cGMP formation (NCX 6550, EC(50) = 2.3 +/- 0.2 microM; NCX 6553, EC(50) = 2.7 +/- 0.2 microM). Moreover, NCX 6550 potently inhibited cell proliferation in rat aortic smooth muscle cells (IC(50) = 2.2 +/- 0.3 microM) with a mechanism that involved both the polyamine and HMG-CoA reductase signaling pathways. Hence, mevalonate or putrescine partially reverted the effects of NCX 6550 and their combination was fully effective. In RAW 264.7 murine macrophage cells stimulated with lipopolysaccharide (1 microg/ml), NCX 6550, but not pravastatin, significantly decreased inducible NO synthase and cyclooxygenase-2 protein expression as well as nitrite accumulation. All together, the data show that the previously undescribed NO-releasing statins retain HMG-CoA reductase inhibitory activity and release bioactive NO slowly. Among the additional properties, compared with native statins, the NO-releasing statins show enhanced antiinflammatory effects. Thus, NO-releasing statins represent an interesting class of drugs having potential in the therapy of disorders associated with endothelial dysfunction and vascular inflammation. PMID:15173604

Ongini, Ennio; Impagnatiello, Francesco; Bonazzi, Albino; Guzzetta, Massimiliano; Govoni, Mirco; Monopoli, Angela; Del Soldato, Piero; Ignarro, Louis J

2004-06-01

62

Etoricoxib-induced fixed drug eruption with positive lesional patch tests.  

PubMed

Fixed drug eruption (FDE) is most commonly associated with antibiotics, anticonvulsants, and nonnarcotic analgens, including nonsteroidal anti-inflammatory drugs (NSAIDs). However, the newer cyclooxygenase 2 (COX-2) inhibitors have been rarely reported to cause FDE. We report the case of a 52-year-old Caucasian woman with erythematous pruritic plaques on the neck, left forearm, and second finger of the right hand, healing with hyperpigmentation and recurring in the same locations. The patient was sporadically taking oral etoricoxib 90 mg for her back pain and noticed the relation between administration of the drug and skin lesions, the time interval decreasing progressively from 1 week to 30 minutes. No other signs, symptoms, or drug intake was mentioned. The patch tests with etoricoxib 1% and 5% in petrolatum were positive at the location of the lesions and negative on the back (nonlesional skin). Standard European and NSAID series were negative. Patch tests of 10 healthy controls with etoricoxib 1% and 5% in petrolatum were negative. After the avoidance of the drug, no relapse was mentioned. The patch test was reliable for the diagnosis of FDE, avoiding the need for subsequent oral provocation testing and therefore preventing the possible adverse effects. Despite being regarded as a safe drug, the occurrence of cutaneous adverse reactions to etoricoxib should be considered, especially in the setting of its increasing use in pain control. PMID:21108578

Calistru, Ana Maria; Cunha, Ana Paula; Nogueira, Ana; Azevedo, Filomena

2010-11-26

63

Environment-mediated drug resistance in Bcr/Abl-positive acute lymphoblastic leukemia.  

PubMed

Although cure rates for acute lymphoblastic leukemia (ALL) have increased, development of resistance to drugs and patient relapse are common. The environment in which the leukemia cells are present during the drug treatment is known to provide significant survival benefit. Here, we have modeled this process by culturing murine Bcr/Abl-positive acute lymphoblastic leukemia cells in the presence of stroma while treating them with a moderate dose of two unrelated drugs, the farnesyltransferase inhibitor lonafarnib and the tyrosine kinase inhibitor nilotinib. This results in an initial large reduction in cell viability of the culture and inhibition of cell proliferation. However, after a number of days, cell death ceases and the culture becomes drug-tolerant, enabling cell division to resume. Using gene expression profiling, we found that the development of drug resistance was accompanied by massive transcriptional upregulation of genes that are associated with general inflammatory responses such as the metalloproteinase MMP9. MMP9 protein levels and enzymatic activity were also increased in ALL cells that had become nilotinib-tolerant. Activation of p38, Akt and Erk correlated with the development of environment-mediated drug resistance (EMDR), and inhibitors of Akt and Erk in combination with nilotinib reduced the ability of the cells to develop resistance. However, inhibition of p38 promoted increased resistance to nilotinib. We conclude that development of EMDR by ALL cells involves changes in numerous intracellular pathways. Development of tolerance to drugs such as nilotinib may therefore be circumvented by simultaneous treatment with other drugs having divergent targets. PMID:22934254

Feldhahn, Niklas; Arutyunyan, Anna; Stoddart, Sonia; Zhang, Bin; Schmidhuber, Sabine; Yi, Sun-Ju; Kim, Yong-Mi; Groffen, John; Heisterkamp, Nora

2012-08-01

64

Positive autoregulation of the yeast transcription factor Pdr3p, which is involved in control of drug resistance.  

PubMed Central

Simultaneous resistance to an array of drugs with different cytotoxic activities is a property of Saccharomyces cerevisiae, in which the protein Pdr3p has recently been shown to play a role as a transcriptional regulator. We provide evidence that the yeast PDR3 gene, which encodes a zinc finger transcription factor implicated in certain drug resistance phenomena, is under positive autoregulation by Pdr3p. DNase I footprinting analyses using bacterially expressed Pdr3p showed specific recognition by this protein of at least two upstream activating sequences in the PDR3 promoter. The use of lacZ reporter constructs, a mutational analysis of the upstream activating sequences, as well as band shift experiments enabled the identification of two 5'TC CGCGGA3' sequence motifs in the PDR3 gene as consensus elements for the binding of Pdr3p. Several similar sequence motifs can be found in the promoter of PDR5, a gene encoding an ATP-dependent drug pump whose Pdr3p-induced overexpression is responsible for drug resistance phenomena. Recently one of these sequence elements was shown to be the target of Pdr3p to elevate the level of PDR5 transcription. Finally, we provide evidence in the absence of PDR1 for a PDR3-controlled transcriptional induction of the drug pump by cycloheximide and propose a model for the mechanism governing the transcriptional autoregulation of Pdr3p.

Delahodde, A; Delaveau, T; Jacq, C

1995-01-01

65

Application of physiologically based pharmacokinetic modeling and clearance concept to drugs showing transporter-mediated distribution and clearance in humans  

Microsoft Academic Search

This review illustrates the concept of a rate-determining process in the overall hepatic elimination of anionic drugs that\\u000a involves transporters in the uptake process. A kinetic study in rats has demonstrated that uptake is the rate-determining\\u000a process for most anionic drugs, and this is likely to hold true for the hepatic elimination of statins in humans. To simulate\\u000a the effects

Takao Watanabe; Hiroyuki Kusuhara; Yuichi Sugiyama

2010-01-01

66

Student Drug Testing in the Context of Positive and Negative School Climates: Results from a National Survey  

ERIC Educational Resources Information Center

Positive school climates and student drug testing have been separately proposed as strategies to reduce student substance use in high schools. However, the effects of drug testing programs may depend on the favorability of school climates. This study examined the association between school drug testing programs and student substance use in schools…

Sznitman, Sharon R.; Dunlop, Sally M.; Nalkur, Priya; Khurana, Atika; Romer, Daniel

2012-01-01

67

Student Drug Testing in the Context of Positive and Negative School Climates: Results from a National Survey  

ERIC Educational Resources Information Center

|Positive school climates and student drug testing have been separately proposed as strategies to reduce student substance use in high schools. However, the effects of drug testing programs may depend on the favorability of school climates. This study examined the association between school drug testing programs and student substance use in…

Sznitman, Sharon R.; Dunlop, Sally M.; Nalkur, Priya; Khurana, Atika; Romer, Daniel

2012-01-01

68

Safe Syringe Disposal is Related to Safe Syringe Access among HIV-positive Injection Drug Users  

Microsoft Academic Search

We evaluated the effect of syringe acquisition on syringe disposal among HIV-positive injection drug users (IDUs) in Baltimore,\\u000a New York City, and San Francisco (N = 680; mean age 42 years, 62% male, 59% African-American, 21% Hispanic, 12% White). Independent predictors of safe disposal\\u000a were acquiring syringes through a safe source and ever visiting a syringe exchange program. Weaker predictors included living\\u000a in

Phillip O. Coffin; Mary H. Latka; Carl Latkin; Yingfeng Wu; David W. Purcell; Lisa Metsch; Cynthia Gomez; Marc N. Gourevitch

2007-01-01

69

Promotion as Prevention: Positive Youth Development as Protective against Tobacco, Alcohol, Illicit Drug, and Sex Initiation  

Microsoft Academic Search

The present study was designed to examine the association of positive youth development with the likelihood of tobacco, alcohol, marijuana, hard drug, and sex initiation between 5th and 10th grades. A national, largely middle-class sample of 5,305 adolescents, participating in a longitudinal study funded by the National 4-H Council (although not all participants were enrolled in 4-H or other after-school

Seth J. Schwartz; Erin Phelps; Jacqueline V. Lerner; Shi Huang; C. Hendricks Brown; Selva Lewin-Bizan; Yibing Li; Richard M. Lerner

2010-01-01

70

Kinetic analysis shows that vitamin A disposal rate in humans is positively correlated with vitamin A stores.  

PubMed

Vitamin A (VA) kinetics, storage, and disposal rate were determined in well-nourished Chinese and U.S. adults using model-based compartmental analysis. [(2)H(8)]Retinyl acetate (8.9 micromol) was orally administered to U.S. (n = 12; 59 +/- 9 y; mean +/- SD) and Chinese adults (n = 14; 54 +/- 4 y) and serum tracer and VA concentrations were measured from 3 h to 56 d. Using the Windows version of the Simulation, Analysis and Modeling software, we determined that the average time from dosing until appearance of labeled retinol in serum was greater in U.S. subjects (40.6 +/- 8.47 h) than in Chinese subjects (32.2 +/- 5.84 h; P < 0.01). Model-predicted total traced mass (898 +/- 637 vs. 237 +/- 109 micromol), disposal rate (14.7 +/- 5.87 vs. 5.58 +/- 2.04 micromol/d), and system residence time (58.9 +/- 28.7 vs. 42.9 +/- 14.6 d) were greater in U.S. than in Chinese subjects (P < 0.05). The model-predicted VA mass and VA mass estimated by deuterated retinol dilution at 3 and 24 d did not differ. VA disposal rate was positively correlated with VA traced mass in Chinese (R(2) = 0.556), U.S. (R(2) = 0.579), and all subjects (R(2) = 0.808). Additionally, VA disposal rate was significantly correlated with serum retinol pool size (R(2) = 0.227) and retinol concentration (R(2) = 0.330) in all subjects. Our results support the hypothesis that VA stores are the principle determinant of VA disposal rate in healthy, well-nourished adults. PMID:18424609

Cifelli, Christopher J; Green, Joanne B; Wang, Zhixu; Yin, Shian; Russell, Robert M; Tang, Guangwen; Green, Michael H

2008-05-01

71

The central nervous system of sea cucumbers (Echinodermata: Holothuroidea) shows positive immunostaining for a chordate glial secretion  

PubMed Central

Background Echinoderms and chordates belong to the same monophyletic taxon, the Deuterostomia. In spite of significant differences in body plan organization, the two phyla may share more common traits than was thought previously. Of particular interest are the common features in the organization of the central nervous system. The present study employs two polyclonal antisera raised against bovine Reissner's substance (RS), a secretory product produced by glial cells of the subcomissural organ, to study RS-like immunoreactivity in the central nervous system of sea cucumbers. Results In the ectoneural division of the nervous system, both antisera recognize the content of secretory vacuoles in the apical cytoplasm of the radial glia-like cells of the neuroepithelium and in the flattened glial cells of the non-neural epineural roof epithelium. The secreted immunopositive material seems to form a thin layer covering the cell apices. There is no accumulation of the immunoreactive material on the apical surface of the hyponeural neuroepithelium or the hyponeural roof epithelium. Besides labelling the supporting cells and flattened glial cells of the epineural roof epithelium, both anti-RS antisera reveal a previously unknown putative glial cell type within the neural parenchyma of the holothurian nervous system. Conclusion Our results show that: a) the glial cells of the holothurian tubular nervous system produce a material similar to Reissner's substance known to be synthesized by secretory glial cells in all chordates studied so far; b) the nervous system of sea cucumbers shows a previously unrealized complexity of glial organization. Our findings also provide significant clues for interpretation of the evolution of the nervous system in the Deuterostomia. It is suggested that echinoderms and chordates might have inherited the RS-producing radial glial cell type from the central nervous system of their common ancestor, i.e., the last common ancestor of all the Deuterostomia.

Mashanov, Vladimir S; Zueva, Olga R; Heinzeller, Thomas; Aschauer, Beate; Naumann, Wilfried W; Grondona, Jesus M; Cifuentes, Manuel; Garcia-Arraras, Jose E

2009-01-01

72

Influence of lower body positive pressure on upper airway cross-sectional area in drug-resistant hypertension.  

PubMed

We previously showed that in hypertensive patients the amount of fluid displaced from the legs overnight is directly related to the severity of obstructive sleep apnea and that the rostral fluid shift was greater in drug-resistant hypertensive patients. The findings suggested that this fluid redistribution increases upper airway collapsibility, yet more direct evidence is lacking. The present study examines the effects of graded lower body positive pressure on leg fluid volume, upper airway cross-sectional area, and neck circumference in patients with drug-resistant hypertension (n=25) and controlled hypertension (n=15). In both groups, the reduction in mean upper airway cross-sectional area and oropharyngeal junction area, assessed by acoustic pharyngometry, and the increase in neck circumference, determined by mercury strain gauge plethysmography, were related to the amount of fluid displaced from the legs (R(2)=0.41, P<0.0001; R(2)=0.42, P<0.0001; and R(2)=0.47, P<0.0001, respectively). Displacement of leg fluid volume was significantly greater in patients with drug-resistant hypertension than in controlled hypertension (P<0.0001), and as a consequence, the former experienced greater reductions in mean upper airway cross-sectional area and oropharyngeal junction area (P=0.001 and P<0.0001, respectively). The findings support the concept that in hypertensive subjects, rostral fluid displacement may participate in the pathogenesis of obstructive sleep apnea by narrowing the upper airway and making it more susceptible to collapse during sleep. The exaggerated fluid volume displacement from the legs and upper airway response to lower body positive pressure in patients with drug-resistant hypertension provide additional evidence of an important link between drug-resistant hypertension and obstructive sleep apnea. PMID:23150515

Friedman, Oded; Bradley, T Douglas; Logan, Alexander G

2012-11-12

73

Efficacy and safety of anti-tuberculosis drugs in HIV-positive patients: A prospective study  

PubMed Central

Objectives: To assess the efficacy and safety of anti-tuberculosis drugs in HIV-positive patients at a tertiary care teaching hospital. Materials and Methods: As a part of an ongoing study of opportunistic infections (OIs) in HIV-positive patients, drug treatment in patients suffering from tuberculosis was assessed to determine its efficacy and safety. Based on prevalence data for last three years, a purposive sampling of study population was carried out in this observational, prospective, single centre study. Tuberculosis (TB) was the most common OI observed. The selected patients were followed up for a period of one year to evaluate the clinical course and outcome of OIs, and the efficacy and safety of drugs used was checked. Results: Tuberculosis was observed in 89 out of 134 enrolled patients. These included 79 adults and 10 children. Males (66.2%) were commonly affected. Extra pulmonary TB (73%) was the most common manifestation with abdominal TB observed in 55 (61.7%) patients. All patients were treated in accordance with the Revised National Tuberculosis Control Programme (RNTCP) guidelines as recommended by National AIDS Control Organization (NACO), India. Outcome of TB was assessable in 70 patients. Majority (82.8%) of the patients were cured, while 12 patients (17.1%) died during the course of treatment. A total of 149 ADRs were observed in 67 (75.2%) patients. Majority of ADRs (n = 147) were non-serious and did not warrant a change in therapy. Discoloration of urine was the most common ADR observed. Conclusion: TB is the most common opportunistic infection in HIV-positive patients with abdominal TB being the most common manifestation. RNTCP and NACO guidelines are adhered to in these patients. Anti-tuberculosis drugs are well tolerated and effective in majority of the patients.

Kapadia, Jigar D.; Desai, Chetna K.; Solanki, Manish N.; Shah, Asha N.; Dikshit, R. K.

2013-01-01

74

Cutaneous T-cell Lymphoma-like Drug Eruption in an Hiv-positive Patient Taking Vancomycin and Rifampin.  

PubMed

Background:Cutaneous T-cell pseudolymphoma (CTPL) is a benign reactive T-cell lymphoproliferative subtype of pseudolymphoma. Some variants of CTPL can resemble the plaques of mycosis fungoides (MF). The vast majority of drug-induced cases have been associated with anticonvulsants. There is only one report in the literature documenting a case of vancomycin-induced CTPL.Methods:We report a cutaneous T-cell lymphoma-like eruption in a human immunodeficiency virus (HIV)-positive patient recently started on vancomycin and rifampin.Results:A skin biopsy showed several histologic features of MF with immunohistochemical and T-cell receptor gene rearrangement studies suggestive of CTPL. This atypical T-cell reaction mimicking MF completely resolved on cessation of rifampin followed by vancomycin.Conclusion:Considering drug-induced causes of MF-like histologic changes is crucial to prevent unnecessary treatment for MF. PMID:24138984

Macisaac, Jennifer L; Ward, Chloé E; Pratt, Melanie

75

Environmental and biological monitoring of platinum-containing drugs in two hospital pharmacies using positive air pressure isolators.  

PubMed

Environmental and biological monitoring of platinum containing drugs was implemented in two French hospital pharmacies using positive air pressure isolators and having similar working procedures when preparing antineoplastic drugs. Wipe sampling of surfaces, gloves, and vials was performed in the preparation room and in storage areas. All employees involved in the preparation of antineoplastic drugs were tested for urinary platinum on Monday before work and Friday after shift. Only traces of platinum were detected on surfaces in the preparation room outside the isolators (less than 1.61 pg cm(-2)). However, in one center, significant contamination was found in the storage area of the drug vials, which can most likely be linked to the rupture of a platinum vial and due to inefficient cleaning procedures. Surfaces inside the isolators were found to be contaminated (maximum: 198.4 pg cm(-2)). A higher level of contamination was detected in one pharmacy and could be explained by the lack of overgloving with regular changes during the preparation process. Nitrile gloves used during drug handling outside the isolator showed the highest platinum concentration (maximum: 5.86 ng per pair). With regards to platinum urine concentration, no significant difference was found between exposed and unexposed pharmacy personnel. Isolator technology combined with individual protective measures seems to be efficient to protect workers from occupational exposure to antineoplastic drugs, whereas specific individual protective procedures implemented were focussing on the risk of handling vials outside the isolator (e.g. high frequency of glove changing). Moreover, overgloving inside the isolator would contribute to substantially decrease inner surface contamination and should be recommended in order to limit the transfer of chemical contamination to the end products. PMID:23091112

Kopp, Bettina; Crauste-Manciet, Sylvie; Guibert, Agnčs; Mourier, Wilhelmine; Guerrault-Moro, Marie-Noelle; Ferrari, Sylvie; Jomier, Jean-Yves; Brossard, Denis; Schierl, Rudolf

2012-10-22

76

Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened  

PubMed Central

Objective We screened commonly used prescription drugs for possible carcinogenic effects. Methods In a large health care program we identified 105 commonly used drugs, not previously screened. Recipients were followed for up to 12˝ years for incident cancer. Nested case-control analyses of 55 cancer sites and all combined included up to ten matched controls per case, with lag of at least two years between drug dispensing and cancer. Positive associations entailed a relative risk (RR) of 1.50, with p? 0.01 and higher risk for three or more, than for one prescription. Evaluation included further analyses, searches of the literature, and clinical judgment. Results There were 101 associations of interest for 61 drugs. Sixty-six associations were judged to have involved substantial confounding. We found evidence that of the remaining 35, the following associations may not be due to chance: sulindac with gallbladder cancer and leukemia, hyoscyamine with non-Hodgkin lymphoma, nortriptyline with esophageal and hepatic cancer, oxazepam with lung cancer, both fluoxetine and paroxetine with testicular cancer, hydrochlorothiazide with renal and lip cancer, and nifedipine with lip cancer. Conclusions These preliminary findings suggest that further studies are indicated regarding sulindac, hyoscyamine, nortriptyline, oxazepam, fluoxetine, paroxetine, hydrochlorothiazide and nifedipine.

Friedman, Gary D.; Udaltsova, Natalia; Chan, James; Quesenberry, Charles P; Habel, Laurel A.

2010-01-01

77

Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo.  

PubMed

In the continuing search for effective cancer treatments, we report the rational engineering of a multifunctional nanoparticle that combines traditional chemotherapy with cell targeting and anti-adhesion functionalities. Very late antigen-4 (VLA-4) mediated adhesion of multiple myeloma (MM) cells to bone marrow stroma confers MM cells with cell-adhesion-mediated drug resistance (CAM-DR). In our design, we used micellar nanoparticles as dynamic self-assembling scaffolds to present VLA-4-antagonist peptides and doxorubicin (Dox) conjugates, simultaneously, to selectively target MM cells and to overcome CAM-DR. Dox was conjugated to the nanoparticles through an acid-sensitive hydrazone bond. VLA-4-antagonist peptides were conjugated via a multifaceted synthetic procedure for generating precisely controlled number of targeting functionalities. The nanoparticles were efficiently internalized by MM cells and induced cytotoxicity. Mechanistic studies revealed that nanoparticles induced DNA double-strand breaks and apoptosis in MM cells. Importantly, multifunctional nanoparticles overcame CAM-DR, and were more efficacious than Dox when MM cells were cultured on fibronectin-coated plates. Finally, in a MM xenograft model, nanoparticles preferentially homed to MM tumors with ?10 fold more drug accumulation and demonstrated dramatic tumor growth inhibition with a reduced overall systemic toxicity. Altogether, we demonstrate the disease driven engineering of a nanoparticle-based drug delivery system, enabling the model of an integrative approach in the treatment of MM. PMID:22829966

Kiziltepe, T; Ashley, J D; Stefanick, J F; Qi, Y M; Alves, N J; Handlogten, M W; Suckow, M A; Navari, R M; Bilgicer, B

2012-04-20

78

Handling reactive metabolite positives in drug discovery: What has retrospective structure-toxicity analyses taught us?  

PubMed

Because of the inability to predict and quantify the risk of idiosyncratic adverse drug reactions (IADRs) and because reactive metabolites (RMs) as opposed to the parent molecules from which they are derived are thought to be responsible for the pathogenesis of some IADRs, procedures (RM trapping/covalent binding) are being incorporated into the discovery screening funnel early-on to assess the risk of RM formation. Utility of the methodology in structure-toxicity relationships and scope in abrogating RM formation at the lead optimization stage are discussed in this article. Interpretation of the output from RM assessment assays, however, is confounded by the fact that many successfully marketed drugs are false positives. Therefore, caution must be exercised in deprioritizing a compound based on a positive result, so that the development of a useful and potentially profitable compound won't be unnecessarily halted. Risk mitigation strategies (e.g., competing detoxication pathways, low daily dose, etc.) when selecting RM positives for clinical development are also reviewed. PMID:20833160

Kalgutkar, Amit S

2010-09-15

79

Sensitivity of individual items of the Positive and Negative Syndrome Scale (PANSS) and items subgroups to differentiate between placebo and drug treatment in schizophrenia.  

PubMed

Lack of hard clinical endpoints is an essential problem in schizophrenia research. Disease state and treatment outcomes are measured using rating scales, e.g. Positive and Negative Syndrome Scale (PANSS). However, the PANSS score cannot always differentiate between placebo and drug treatment, even for established antipsychotics. The goal of this study was to identify the individual items of PANSS and subscales of selected items which are most sensitive to differentiate between placebo and drug effect. We analysed data from seven clinical trials of different antipsychotics. "Mini-PANSS" scales consisting of the most sensitive items were created and analysed statistically. The power of these scales to show a significant difference between placebo and drug treatment was compared with the power of total PANSS. Furthermore, pharmacokinetic-pharmacodynamic analysis was performed to determine which of these scales shows the highest drug effect on top of the placebo effect. The results reveal that all 30 items of the PANSS scale show a therapeutic drug effect. The magnitude of placebo effect was not predictive for the power to detect drug effect. Mini-PANSS scales consisting of items with the largest drug treatment response and the scale with the largest mean-to-SD ratio are somewhat better in differentiating between placebo and drug treatment than the total PANSS. However, the difference between these scales and total PANSS is small. Therefore, our analysis does not support replacement of the total PANSS by a reduced scale in the analysis of primary endpoints. PMID:23434198

Kozielska, Magdalena; Pilla Reddy, Venkatesh; Johnson, Martin; de Ridder, Filip; Vermeulen, An; Liu, Jing; Groothuis, Geny M M; Danhof, Meindert; Proost, Johannes H

2013-02-20

80

Student Drug Testing in the Context of Positive and Negative School Climates: Results from a National Survey  

Microsoft Academic Search

Positive school climates and student drug testing have been separately proposed as strategies to reduce student substance\\u000a use in high schools. However, the effects of drug testing programs may depend on the favorability of school climates. This\\u000a study examined the association between school drug testing programs and student substance use in schools with different climates.\\u000a The analysis was based on

Sharon R. SznitmanSally; Sally M. Dunlop; Priya Nalkur; Atika Khurana; Daniel Romer

81

Drug Abuse in North Central New Mexico. Problems and Suggested Responses. A NorCHaP Position Statement.  

National Technical Information Service (NTIS)

The drug abuse problem in the seven-county area served by the North Central New Mexico Comprehensive Health Planning Council is examined in a position statement prepared by a task force comprised of persons who regularly deal with the problems of drug abu...

1975-01-01

82

The Drug User's Identity and How It Relates to Being Hepatitis C Antibody Positive: A Qualitative Study  

ERIC Educational Resources Information Center

|The increasing health problem of hepatitis C virus infection has only recently attracted the attention of psychosocial research, especially among subjects at higher risk (e.g. injecting drug users). There is a lack of information about the knowledge, perceptions and feelings that injecting drug users hold about their hepatitis C antibody positive

Copeland, Lorraine

2004-01-01

83

Different Requirements for cAMP Response Element Binding Protein in Positive and Negative Reinforcing Properties of Drugs of Abuse  

Microsoft Academic Search

Addiction is a complex process that relies on the ability of an organism to integrate positive and negative properties of drugs of abuse. Therefore, studying the reinforcing as well as aversive components of drugs of abuse in a single model system will enable us to understand the role of final common mediators, such as cAMP response element-binding protein (CREB), in

Carrie L. Walters; Julie A. Blendy

2001-01-01

84

A case of HER-2-positive recurrent breast cancer showing a clinically complete response to trastuzumab-containing chemotherapy after primary treatment of triple-negative breast cancer  

PubMed Central

We report a case of HER-2-positive recurrent breast cancer showing a clinically complete response to trastuzumab-containing chemotherapy 6 years after primary treatment of triple-negative breast cancer. The primary tumor was negative for HER-2 as determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) (1+, and ratio, 1.1), but examination of the recurrent lymph node metastasis showed positivity for HER-2 by FISH (ratio, 5.2). No lesions were detected in either her left breast or in other organs, and the patient was diagnosed as having HER-2-positive recurrent disease. Combination chemotherapy using weekly paclitaxel and trastuzumab was initiated, and a clinically complete response was achieved. This report suggests the benefit of routine evaluation of HER-2 status in recurrent breast cancer with the introduction of HER-2-targeting agents.

2011-01-01

85

Sodium azide is less suitable as a positive control of drug-induced lethality for in vitro clonogenic assays.  

PubMed

Sodium azide (6 mg/ml) was used as a positive control for drug-induced lethality in an in vitro clonogenic assay. Petri dishes containing control and sodium azide treated cultures of WiDr cells were placed together in a large Petri dish and incubated at 37 degrees C in an atmosphere of 10% CO2 in air. No growth was observed. Control cells formed colonies only when the dishes were separated from the sodium azide dishes. Using a microtiter plate the toxic effect was inversely related to the distance of the test cultures from the sodium azide treated cultures. These results suggested the formation of a toxic gas or vapour from sodium azide under cell culture conditions, probably an azide. Chemical analysis was based on characteristic reactions, such as the production of a precipitate with silver ions or formation of a red-coloured complex with ferric salts. On a microtiter plate, a gradient of the expected precipitate or red colour was observed, the highest amounts adjacent to the wells containing sodium azide. These results show that sodium azide acts as a positive control of drug-induced lethality for in vitro clonogenic assays. However, the formation of a highly toxic vapour, most likely hydrazaic acid, makes it a less suitable standard. PMID:3583644

Lelieveld, P; Aapro, M S; van Lambalgen, R; van den Berg, K J

1986-01-01

86

Meta-analysis shows similar risk of thrombosis after drug-eluting stent, bare-metal stent, or angioplasty.  

PubMed

Coronary stent thrombosis remains an important problem after the implantation of different stent types. This study investigates the risk of stent thrombosis associated with the use of drug-eluting stents (DESs), bare-metal stents (BMSs) compared to balloon angioplasty. A meta-analysis of 28 randomized trials involving 5612 versus 7639 versus 2994 patients with coronary heart disease treated with DES, BMS, or balloon angioplasty was therefore performed. Comparing the implantation of DES versus BMS, DES was not found to increase the hazard for thrombosis up to 15 months (odds ratio [OR] = 0.86, 95% confidence interval [CI] 0.58 to 1.3, p < .48). There was also no significant difference in the hazard for subacute thrombosis (SAT) or late stent thrombosis (LST) in the DES versus BMSs group (OR = 0.86, 95% CI 0.50 to 1.5, p < .6 and OR = 0.92, 95% CI 0.50 to 1.68, p < .78, respectively). Comparing incidences of stent thromboses in patients receiving balloon angioplasty or implantation of BMS, the rate of SAT in the balloon angioplasty group (1.7% SAT) versus BMS group (1.8% SAT) was also similar (OR = 0.93, 95% CI 0.61 to 1.4, p < .71). Finally, there was no significant difference in the occurrence of stent thrombosis for the different coatings of DESs. In conclusion, the use of DES was not observed to have a significant effect on stent thrombosis events, compared with the implantation of BMS or balloon angioplasty. PMID:18568949

Fuchs, Alexandra Theresia; Kuehnl, Andreas; Pelisek, Jaroslav; Rolland, Pierre Henri; Mekkaoui, Choukri; Netz, Heinrich; Nikol, Sigrid

87

Co-occurring psychiatric symptoms and drug dependence or heavy drinking among HIV-positive people.  

PubMed

This study sought to establish population-based estimates of the prevalence of co-occurring psychiatric symptoms and either or both drug dependence symptoms or heavy drinking among individuals who test positive for the human immunodeficiency virus (HIV) and to identify the factors associated with such comorbidity. Data from the HIV Cost and Services Utilization Study (HCSUS), a nationally representative sample of HIV-infected adults receiving medical care in the U.S. in 1996 (N = 2,864), were used to estimate the prevalence of comorbidity. Logistic regression was used to identify the independent influences of sociodemographic and HIV-related variables on comorbidity. The authors estimate that 13% of people with HIV receiving care in the U.S. in 1996 had co-occurring psychiatric symptoms and either or both drug dependence symptoms or heavy drinking. The odds of having a comorbid condition were higher for males, heterosexuals, and people with more HIV-related symptoms. The odds were lower for people living with AIDS, African Americans, people who were gay or sexually abstinent, those living with a spouse, those aged 50 years or older, and those with private insurance. Sixty-nine percent of those with a substance-related condition also had psychiatric symptoms; 27% of those with psychiatric symptoms also had a substance-related condition. PMID:12825758

Galvan, Frank H; Burnam, M Audrey; Bing, Eric G

2003-05-01

88

Role of Catheter's Position for Final Results in Intrathecal Drug Delivery. Analysis Based on CSF Dynamics and Specific Drugs Profiles  

PubMed Central

Intrathecal drug delivery is an effective and safe option for the treatment of chronic pathology refractory to conventional pain therapies. Typical intrathecal administered drugs are opioids, baclofen, local anesthetics and adjuvant medications. Although knowledge about mechanisms of action of intrathecal drugs are every day more clear many doubt remain respect the correct location of intrathecal catheter in order to achieve the best therapeutic result. We analyze the factors that can affect drug distribution within the cerebrospinal fluid. Three categories of variables were identified: drug features, cerebrospinal fluid (CSF) dynamics and patients features. First category includes physicochemical properties and pharmacological features of intrathecal administered drugs with special attention to drug lipophilicity. In the second category, the variables in CSF flow, are considered that can modify the drug distribution within the CSF with special attention to the new theories of liquoral circulation. Last category try to explain inter-individual difference in baclofen response with difference that are specific for each patients such as the anatomical area to treat, patient posture or reaction to inflammatory stimulus. We conclude that a comprehensive evaluation of the patients, including imaging techniques to study the anatomy and physiology of intrathecal environment and CSF dynamics, could become essential in the future to the purpose of optimize the clinical outcome of intrathecal therapy.

Luciano, Perotti; Vicente, Villanueva; Juan Marcos, Asensio Samper; Gustavo, Fabregat-Cid

2013-01-01

89

Weighing the Consequences: Self-Disclosure of HIV-Positive Status among African American Injection Drug Users  

ERIC Educational Resources Information Center

|Theorists posit that personal decisions to disclose being HIV positive are made based on the perceived consequences of that disclosure. This study examines the perceived costs and benefits of self-disclosure among African American injection drug users (IDUs). A total of 80 African American IDUs were interviewed in-depth subsequent to testing HIV…

Valle, Maribel; Levy, Judith

2009-01-01

90

Weighing the Consequences: Self-Disclosure of HIV-Positive Status among African American Injection Drug Users  

ERIC Educational Resources Information Center

Theorists posit that personal decisions to disclose being HIV positive are made based on the perceived consequences of that disclosure. This study examines the perceived costs and benefits of self-disclosure among African American injection drug users (IDUs). A total of 80 African American IDUs were interviewed in-depth subsequent to testing HIV…

Valle, Maribel; Levy, Judith

2009-01-01

91

A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment  

PubMed Central

Increasing evidence suggests that specific physiological measures may serve as biomarkers for successful treatment to alleviate symptoms of pathological anxiety. Studies of autonomic function investigating parameters such as heart rate (HR), HR variability and blood pressure (BP) indicated that HR variability is consistently reduced in anxious patients, whereas HR and BP data show inconsistent results. Therefore, HR and HR variability were measured under various emotionally challenging conditions in a mouse model of high innate anxiety (high anxiety behaviour; HAB) vs. control normal anxiety-like behaviour (NAB) mice. Baseline HR, HR variability and activity did not differ between mouse lines. However, after cued Pavlovian fear conditioning, both elevated tachycardia and increased fear responses were observed in HAB mice compared to NAB mice upon re-exposure to the conditioning stimulus serving as the emotional stressor. When retention of conditioned fear was tested in the home cage, HAB mice again displayed higher fear responses than NAB mice, while the HR responses were similar. Conversely, in both experimental settings HAB mice consistently exhibited reduced HR variability. Repeated administration of the anxiolytic NK1 receptor antagonist L-822429 lowered the conditioned fear response and shifted HR dynamics in HAB mice to a more regular pattern, similar to that in NAB mice. Additional receiver-operating characteristic (ROC) analysis demonstrated the high specificity and sensitivity of HR variability to distinguish between normal and high anxiety trait. These findings indicate that assessment of autonomic response in addition to freezing might be a useful indicator of the efficacy of novel anxiolytic treatments.

Gaburro, Stefano; Stiedl, Oliver; Giusti, Pietro; Sartori, Simone B.; Landgraf, Rainer; Singewald, Nicolas

2011-01-01

92

A case of HER2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a clinically complete response to concurrent trastuzumab and paclitaxel treatment  

Microsoft Academic Search

We report a case of HER-2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a complete\\u000a response to trastuzumab and paclitaxel treatment. A 37-year-old woman was referred to our hospital for right breast swelling\\u000a with broad skin redness and right axillary tumor. Ipsilateral infraclavicular and contralateral axillary lymph nodes swelling\\u000a were also recognized. The histopathological findings of core-needle biopsy

Hideo ShigematsuYoshiaki; Yoshiaki Nakamura; Kimihiro Tanaka; Satoko Shiotani; Chinami Koga; Hidetoshi Kawaguchi; Sumiko Nishimura; Kenichi Taguchi; Kenichi Nishiyama; Shinji Ohno

2010-01-01

93

Construction of an Integrated Positive Youth Development Conceptual Framework for the Prevention of the Use of Psychotropic Drugs among Adolescents  

PubMed Central

This is a theoretical paper with an aim to construct an integrated conceptual framework for the prevention of adolescents' use and abuse of psychotropic drugs. This paper first reports the subjective reasons for adolescents' drug use and abuse in Hong Kong and reviews the theoretical underpinnings. Theories of drug use and abuse, including neurological, pharmacological, genetic predisposition, psychological, and sociological theories, were reviewed. It provides a critical re-examination of crucial factors that support the construction of a conceptual framework for primary prevention of adolescents' drug use and abuse building on, with minor revision, the model of victimization and substance abuse among women presented by Logan et al. This revised model provides a comprehensive and coherent framework synthesized from theories of drug abuse. This paper then provides empirical support for integrating a positive youth development perspective in the revised model. It further explains how the 15 empirically sound constructs identified by Catalano et al. and used in a positive youth development program, the Project P.A.T.H.S., relate generally to the components of the revised model to formulate an integrated positive youth development conceptual framework for primary prevention of adolescent drug use. Theoretical and practical implications as well as limitations and recommendations are discussed.

Lee, Tak Yan

2011-01-01

94

Field, Genetic, and Modeling Approaches Show Strong Positive Selection Acting upon an Insecticide Resistance Mutation in Anopheles gambiae s.s.  

PubMed Central

Alleles subject to strong, recent positive selection will be swept toward fixation together with contiguous sections of the genome. Whether the genomic signatures of such selection will be readily detectable in outbred wild populations is unclear. In this study, we employ haplotype diversity analysis to examine evidence for selective sweeps around knockdown resistance (kdr) mutations associated with resistance to dichlorodiphenyltrichloroethane and pyrethroid insecticides in the mosquito Anopheles gambiae. Both kdr mutations have significantly lower haplotype diversity than the wild-type (nonresistant) allele, with kdr L1014F showing the most pronounced footprint of selection. We complement these data with a time series of collections showing that the L1014F allele has increased in frequency from 0.05 to 0.54 in 5 years, consistent with a maximum likelihood–fitted selection coefficient of 0.16 and a dominance coefficient of 0.25. Our data show that strong, recent positive selective events, such as those caused by insecticide resistance, can be identified in wild insect populations.

Lynd, Amy; Weetman, David; Barbosa, Susana; Egyir Yawson, Alexander; Mitchell, Sara; Pinto, Joao; Hastings, Ian; Donnelly, Martin J.

2010-01-01

95

Estrogen receptor positive breast cancer identified by 95-gene classifier as at high risk for relapse shows better response to neoadjuvant chemotherapy.  

PubMed

A 95-gene classifier (95-GC) recently developed by us can predict the risk of relapse for ER-positive and node-negative breast cancer patients with high accuracy. This study investigated association of risk classification by 95-GC with response to neoadjuvant chemotherapy (NAC). Tumor biopsy samples obtained preoperatively from 72 patients with ER-positive breast cancer were classified by 95-GC into high-risk and low-risk for relapse. Pathological complete response (pCR) rate was numerically higher for high-risk (15.8%) than low-risk patients (8.8%) although the difference was not statistically significant. Pathological response evaluated in terms of the pathological partial response (pPR) rate (loss of tumor cells in more than two-thirds of the primary tumor) showed a significant association (P=0.005) between the high-risk patients and a high pPR rate. Besides, external validation study using the public data base (GSE25066) showed that the pCR rate (16.4%) for high-risk patients (n=128) was significantly (P=0.003) higher than for low-risk patients (5.7%) (n=159). These results demonstrate that the high-risk patients for relapse show a higher sensitivity to chemotherapy and thus are likely to benefit more from adjuvant chemotherapy. PMID:22546287

Tsunashima, Ryo; Naoi, Yasuto; Kishi, Kazuki; Baba, Yosuke; Shimomura, Atsushi; Maruyama, Naomi; Nakayama, Takahiro; Shimazu, Kenzo; Kim, Seung Jin; Tamaki, Yasuhiro; Noguchi, Shinzaburo

2012-04-27

96

49 CFR 655.46 - Return to duty following refusal to submit to a test, verified positive drug test result and/or...  

Code of Federal Regulations, 2012 CFR

...positive drug test result and/or breath alcohol test result of 0.04 or greater. 655...DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT...positive drug test result and/or breath alcohol test result of 0.04 or greater....

2012-10-01

97

49 CFR 655.46 - Return to duty following refusal to submit to a test, verified positive drug test result and/or...  

Code of Federal Regulations, 2011 CFR

...to submit to a test, verified positive drug test result and/or breath alcohol test...PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Types of Testing...to submit to a test, verified positive drug test result and/or breath alcohol...

2011-10-01

98

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...  

Code of Federal Regulations, 2012 CFR

...when an employee has a verified positive drug test result or has a confirmed alcohol...PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Consequences...when an employee has a verified positive drug test result or has a confirmed...

2012-10-01

99

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...  

Code of Federal Regulations, 2011 CFR

...when an employee has a verified positive drug test result or has a confirmed alcohol...PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Consequences...when an employee has a verified positive drug test result or has a confirmed...

2011-10-01

100

A case of HER-2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a clinically complete response to concurrent trastuzumab and paclitaxel treatment.  

PubMed

We report a case of HER-2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a complete response to trastuzumab and paclitaxel treatment. A 37-year-old woman was referred to our hospital for right breast swelling with broad skin redness and right axillary tumor. Ipsilateral infraclavicular and contralateral axillary lymph nodes swelling were also recognized. The histopathological findings of core-needle biopsy specimens from primary breast tumor and ipsilateral axillary lymph node were invasive ductal carcinoma with a micropapillary component. Immunohistochemical examination gave a negative result for estrogen receptor (ER)/progesterone receptor (PgR), and overexpression of HER-2 (Hercep Test 3+). Advanced inflammatory breast cancer with an invasive micropapillary component was diagnosed (T4d N3 M1 (LYM), stage IV). The patient was treated with combination chemotherapy using weekly paclitaxel and trastuzumab. After administration of three courses, the breast swelling, skin redness, and lymph node swelling disappeared completely. She maintained complete remission of disease for 12 months and was judged to have a clinically complete response by the RECIST criteria. Invasive micropapillary carcinoma is known to be an aggressive histological type associated with a high incidence of lymph node metastasis and poor prognosis. This is the first reported case of advanced inflammatory breast cancer with an invasive micropapillary component showing a clinically complete response to trastuzumab-containing treatment. This report suggests trastuzumab-containing chemotherapy is a promising therapy for HER-2-positive advanced invasive micropapillary carcinoma. PMID:20473628

Shigematsu, Hideo; Nakamura, Yoshiaki; Tanaka, Kimihiro; Shiotani, Satoko; Koga, Chinami; Kawaguchi, Hidetoshi; Nishimura, Sumiko; Taguchi, Kenichi; Nishiyama, Kenichi; Ohno, Shinji

2010-05-15

101

False-Positive Tests for Syphilis Associated with Human Immunodeficiency Virus and Hepatitis B Virus Infection among Intravenous Drug Abusers  

Microsoft Academic Search

The role of HIV, hepatitis C virus, and hepatitis B virus infections in the production of biological false-positive reactions\\u000a for syphilis was evaluated in two large samples of intravenous drug abusers and homosexual men attending AIDS prevention centers\\u000a in Spain. A significantly increased odds ratio (OR) for false-positive tests for syphilis [OR 2.23, 95% confidence intervals\\u000a (CI) 1.76–2.83] was observed

I. Hernández-Aguado; F. Bolumar; R. Moreno; F. J. Pardo; N. Torres; J. Belda; A. Espacio

1998-01-01

102

Positive and negative ion mode ESI-MS and MS/MS for studying drug-DNA complexes  

NASA Astrophysics Data System (ADS)

We report systematic investigation of duplex DNA complexes with minor groove binders (Hoechsts 33258 and 33342, netropsin and DAPI) and intercalators (daunomycin, doxorubicin, actinomycin D, ethidium, cryptolepine, neocryptolepine, m-Amsacrine, proflavine, ellipticine and mitoxantrone) by ESI-MS and ESI-MS/MS in the negative ion mode and in the positive ion mode. The apparent solution phase equilibrium binding constants can be determined by measuring relative intensities in the ESI-MS spectrum. While negative ion mode gives reliable results, positive ion mode gives a systematic underestimation of the binding constants and even a complete suppression of the complexes for intercalators lacking functional groups capable of interacting in the grooves. In the second part of the paper we systematically compare MS/MS fragmentation channels and breakdown curves in the positive and the negative modes, and discuss the possible uses and caveats of MS/MS in drug-DNA complexes. In the negative mode, the drugs can be separated in three groups: (1) those that leave the complex with no net charge; (2) those that leave the complex with a negative charge; and (3) those that remain attached on the strands upon dissociation of the duplex due to their positive charge. In the positive ion mode, all complexes fragment via the loss of protonated drug. Information on the stabilization of the complex by drug-DNA noncovalent interactions can be obtained straightforwardly only in the case of neutral drug loss. In all other cases, proton affinity (in the positive ion mode), gas-phase basicity (in the negative ion mode) and coulombic repulsion are the major factors influencing the fragmentation channel and the dissociation kinetics.

Rosu, Frédéric; Pirotte, Sophie; Pauw, Edwin De; Gabelica, Valérie

2006-07-01

103

College on Problems of Drug Dependence taskforce on prescription opioid non-medical use and abuse: position statement  

Microsoft Academic Search

This position paper from the College on Problems of Drug Dependence addresses the issues related to non-medical use and abuse of prescription opioids. A central theme throughout is the need to strike a balance between risk management strategies to prevent and deter prescription opioid abuse and the need for physicians and patients to have appropriate access to opioid pharmaceuticals for

James Zacny; George Bigelow; Peggy Compton; Kathleen Foley; Martin Iguchi; Christine Sannerud

2003-01-01

104

Positive family relationships and religious affiliation as mediators between negative environment and illicit drug symptoms in American Indian adolescents  

Microsoft Academic Search

The present study tests how positive family relationships and religious affiliation mediate between negative familial and social environments, and adolescent illicit drug abuse\\/dependence symptoms. The theoretical framework is based on an integration of two theories: the ecological model of human development (Bronfenbrenner, 1979) and the social development model (Hawkins & Weis, 1985). We used a stratified random sample of 401

ManSoo Yu; Arlene R. Stiffman

2010-01-01

105

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...  

Code of Federal Regulations, 2010 CFR

...ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Consequences § 655.61 Action...a verified positive drug test result or has...alcohol test result of 0.04 or...

2009-10-01

106

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...  

Code of Federal Regulations, 2010 CFR

...ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Consequences § 655.61 Action...a verified positive drug test result or has...alcohol test result of 0.04 or...

2010-10-01

107

Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes.  

PubMed

To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify "toxic" and "non-toxic" drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. PMID:23811329

Nadanaciva, Sashi; Aleo, Michael D; Strock, Christopher J; Stedman, Donald B; Wang, Huijun; Will, Yvonne

2013-06-26

108

Drug testing welfare recipients—false positives, false negatives, unanticipated opportunities  

Microsoft Academic Search

Substance abuse and dependence are among the most common psychiatric disorders among pregnant and parenting women. These disorders among welfare recipients have attracted special concern. Chemical testing has been proposed to identify illicit drug use in this population. This analysis scrutinizes the potential value of drug testing, using recent data from the Women’s Employment Study and the National Household Survey

Harold A Pollack; Sheldon Danziger; Rukmalie Jayakody; Kristin S Seefeldt

2002-01-01

109

Drug disposition in patients with HB s Ag-positive chronic liver disease  

Microsoft Academic Search

Chronic infection with hepatitis B virus (HBV) results in a spectrum of hepatic abnormalities ranging from minimal liver dysfunction to severe liver failure. These patients provide an opportunity to examine the relationship between the evolution of the liver disease and the ability to metabolize drugs. We have examined hepatic drug disposition in patients with chronic persistent hepatitis, chronic active hepatitis,

J. P. Villeneuve; M. J. Thibeault; M. Ampelas; H. Fortunet-Fouin; L. LaMarre; J. Côté; G. Pomier-Layrargues; P.-M. Huet

1987-01-01

110

The Yeast Hrs1 Gene Is Involved in Positive and Negative Regulation of Transcription and Shows Genetic Characteristics Similar to Sin4 and Gal11  

PubMed Central

We provide genetic evidence that HRS1/PGD1, a yeast gene previously identified as a suppressor of the hyper-recombination phenotype of hpr1, has positive and negative roles in transcriptional regulation. We have analyzed three differently regulated promoters, GAL1, PHO5 and HSP26, by ?-galactosidase assays of lacZ-fused promoters and by Northern analysis of the endogenous genes. Transcription of these promoters was derepressed in hrs1? mutants under conditions in which it is normally repressed in wild type. Under induced conditions it was either strongly reduced or significantly enhanced depending on the promoter system analyzed. Constitutive transcription was not affected, as determined in ADH1 and TEF2. In addition, Hrs1p was required for mating-factor expression, telomere-linked DNA silencing and DNA supercoiling of plasmids. Furthermore, hrs1? suppressed Ty-insertion mutations and conferred a Gal(-) phenotype. Many of these phenotypes also result from mutations in GAL11, SIN4 or RGR1, which encode proteins of the RNA polII mediator. We also show that gal11? and sin4? partially suppress the hyper-rec phenotype of hpr1 mutants, although to a lesser extent than hrs1?. Our results provide new evidence for the connection between hpr1?-induced deletions and transcription. We discuss the possibility that Hrs1p might be a component of the RNA polII transcription machinery.

Piruat, J. I.; Chavez, S.; Aguilera, A.

1997-01-01

111

Genotype and growing environment interaction shows a positive correlation between substrates of raffinose family oligosaccharides (RFO) biosynthesis and their accumulation in chickpea ( Cicer arietinum L.) seeds.  

PubMed

To develop genetic improvement strategies to modulate raffinose family oligosaccharides (RFO) concentration in chickpea ( Cicer arietinum L.) seeds, RFO and their precursor concentrations were analyzed in 171 chickpea genotypes from diverse geographical origins. The genotypes were grown in replicated trials over two years in the field (Patancheru, India) and in the greenhouse (Saskatoon, Canada). Analysis of variance revealed a significant impact of genotype, environment, and their interaction on RFO concentration in chickpea seeds. Total RFO concentration ranged from 1.58 to 5.31 mmol/100 g and from 2.11 to 5.83 mmol/100 g in desi and kabuli genotypes, respectively. Sucrose (0.60-3.59 g/100 g) and stachyose (0.18-2.38 g/100 g) were distinguished as the major soluble sugar and RFO, respectively. Correlation analysis revealed a significant positive correlation between substrate and product concentration in RFO biosynthesis. In chickpea seeds, raffinose, stachyose, and verbascose showed a moderate broad sense heritability (0.25-0.56), suggesting the use of a multilocation trials based approach in chickpea seed quality improvement programs. PMID:23621405

Gangola, Manu P; Khedikar, Yogendra P; Gaur, Pooran M; Bĺga, Monica; Chibbar, Ravindra N

2013-05-13

112

Tenofovir Plasma Concentrations According to Companion Drugs: a Cross-Sectional Study of HIV-Positive Patients with Normal Renal Function  

PubMed Central

As the risk of tenofovir-associated renal toxicity has been found to be proportional to the drug plasma concentration, our aim was to measure the determinants of tenofovir plasma exposure in HIV-positive patients with normal renal function. A cross-sectional analysis was conducted in HIV-positive patients chronically receiving tenofovir-containing highly active antiretroviral therapies (HAARTs). Patients on tenofovir-containing antiretroviral regimens, presenting 22 to 26 h after drug intake, having estimated glomerular filtration rates above 60 ml/min, reporting high adherence to antiretroviral medications (above 95% of the doses), and signing a written informed consent were included. Plasma tenofovir concentrations were measured through a validated high-performance liquid chromatography–mass spectrometry (HPLC/LC-MS) method. The tenofovir trough concentrations in 195 patients (median, 50 ng/ml, and interquartile range, 35 to 77 ng/ml) were significantly associated with the estimated glomerular filtration rate, body mass index, and third-drug class (protease-containing versus protease-sparing regimens) (with the highest exposure in unboosted-atazanavir recipients). The results of multivariate analysis showed that the third-drug class and the weight/creatinine ratio were independent predictors of tenofovir trough concentrations. This cross-sectional study shows that tenofovir trough concentrations are predicted by the weight/creatinine ratio and by the coadministered antiretrovirals, with protease inhibitors (whether boosted or unboosted) being associated with the highest plasma exposure. These data, previously available in healthy subjects or for some drugs only, could be useful for designing strategies to manage tenofovir-associated toxicity, since this toxicity has been reported to be dose dependent.

Gonzalez de Requena, D.; Simiele, M.; D'Avolio, A.; Tettoni, M. C.; Salassa, B.; Orofino, G.; Bramato, C.; Libanore, V.; Motta, I.; Bigliano, P.; Orsucci, E.; Di Perri, G.; Bonora, S.

2013-01-01

113

Tenofovir plasma concentrations according to companion drugs: a cross-sectional study of HIV-positive patients with normal renal function.  

PubMed

As the risk of tenofovir-associated renal toxicity has been found to be proportional to the drug plasma concentration, our aim was to measure the determinants of tenofovir plasma exposure in HIV-positive patients with normal renal function. A cross-sectional analysis was conducted in HIV-positive patients chronically receiving tenofovir-containing highly active antiretroviral therapies (HAARTs). Patients on tenofovir-containing antiretroviral regimens, presenting 22 to 26 h after drug intake, having estimated glomerular filtration rates above 60 ml/min, reporting high adherence to antiretroviral medications (above 95% of the doses), and signing a written informed consent were included. Plasma tenofovir concentrations were measured through a validated high-performance liquid chromatography-mass spectrometry (HPLC/LC-MS) method. The tenofovir trough concentrations in 195 patients (median, 50 ng/ml, and interquartile range, 35 to 77 ng/ml) were significantly associated with the estimated glomerular filtration rate, body mass index, and third-drug class (protease-containing versus protease-sparing regimens) (with the highest exposure in unboosted-atazanavir recipients). The results of multivariate analysis showed that the third-drug class and the weight/creatinine ratio were independent predictors of tenofovir trough concentrations. This cross-sectional study shows that tenofovir trough concentrations are predicted by the weight/creatinine ratio and by the coadministered antiretrovirals, with protease inhibitors (whether boosted or unboosted) being associated with the highest plasma exposure. These data, previously available in healthy subjects or for some drugs only, could be useful for designing strategies to manage tenofovir-associated toxicity, since this toxicity has been reported to be dose dependent. PMID:23380733

Calcagno, A; Gonzalez de Requena, D; Simiele, M; D'Avolio, A; Tettoni, M C; Salassa, B; Orofino, G; Bramato, C; Libanore, V; Motta, I; Bigliano, P; Orsucci, E; Di Perri, G; Bonora, S

2013-02-04

114

Intrathyroid epithelial thymoma (ITET) and carcinoma showing thymus-like differentiation (CASTLE): CD5-positive neoplasms mimicking squamous cell carcinoma of the thyroid.  

PubMed

Carcinoma of possible thymic epithelial origin may occur within the thyroid gland, which was first reported by Miyauchi et al. as intrathyroid epithelial thymoma (ITET). ITET is a rare tumor comprising about 0.08% of all primary thyroid malignancies. It is a low-grade thyroid carcinoma with squamous cell differentiation whose overall survival rate was found to be 71%. Lymph node metastasis at surgery was found in 40% and hematogenous metastases developed in bones, liver and lungs. This tumor grows within the thyroid gland and invades into the thyroid parenchyma as well as into the extrathyroid structures. It is a well-circumscribed solid tumor with a sharp tumor border, but is not capsulated. After fixation, the cut surface of the tumor is gray-white in color and is a solid tumor with lobulation. Tumor calcification was not detected in our 15 cases. The tumor cells show solid sheets of growth with occasional keratinization without follicular or papillary structures. Lymphocytic infiltration in the stroma is one of the most characteristic features of this tumor. The tumor cells are polygonal epithelial cells with distinct nucleoli and ill-defined cell border. Positive immunoreactivity for CD5 is a key feature to differentiate it from undifferentiated carcinoma, poorly differentiated carcinoma, medullary (C cell) carcinoma and high-grade squamous cell carcinoma (so-called primary squamous cell carcinoma) of the thyroid. Negative immunoreactivity for calcitonin, TTF1 and thyroglobulin, and positive immunoreactivity for p63 and KIT are also helpful for differential diagnosis. Nuclear atypia is mild and mitoses are less frequent, with an intermediate proliferation index (MIB-1 labeling index is usually less than 20%), which are also helpful to differentiate it from high-grade primary squamous cell carcinoma of the thyroid. The tumors in our 15 cases demonstrate 3 histological subtypes: keratinizing squamous cell carcinoma type, non-keratinizing basaloid cell carcinoma (lymphoepithelioma-like) type and neuroendocrine carcinoma type, which correspond to subtypes of the mediastinal thymic carcinomas. PMID:23233417

Kakudo, Kennichi; Bai, Yanhua; Ozaki, Takashi; Homma, Kei-ichi; Ito, Yasuhiro; Miyauchi, Akira

2012-12-11

115

Using Positive Youth Development Constructs to Design a Drug Education Curriculum for Junior Secondary Students in Hong Kong  

PubMed Central

This paper outlines the design of a new curriculum for positive youth development (P.A.T.H.S. II) in Hong Kong. The paper discusses the conceptual base for designing a drug-education curriculum for junior-secondary students using four positive youth development constructs—cognitive competence, emotional competence, beliefs in the future, and self-efficacy. The program design is premised on the belief that adolescents do have developmental assets; therefore, the curriculum is designed to develop their psychosocial competencies. The goal of the curriculum is to develop the selfhood of these youths and ultimately achieve the goal of successful adolescent development.

Lam, Ching Man; Lau, Patrick S. Y.; Law, Ben M. F.; Poon, Y. H.

2011-01-01

116

Sodium azide is less suitable as a positive control of drug-induced lethality for in vitro clonogenic assays  

Microsoft Academic Search

Sodium azide (6 mg\\/ml) was used as a positive control for drug-induced lethality in an in vitro clonogenic assay. Petri dishes containing control and sodium azide treated cultures of WiDr cells were placed together in a large Petri dish and incubated at 37°C in an atmosphere of 10% CO2 in air. No growth was observed. Control cells formed colonies only

Peter Lelieveld; Matti S. Aapro; Rob Lambalgen; Kor J. Berg

1986-01-01

117

Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened  

Microsoft Academic Search

Objective  To screen commonly used prescription drugs for possible carcinogenic effects.\\u000a \\u000a \\u000a \\u000a Methods  In a large health care program we identified 105 commonly used drugs, not previously screened. Recipients were followed for\\u000a up to 12˝ years for incident cancer. Nested case–control analyses of 55 cancer sites and all combined included up to ten matched\\u000a controls per case, with lag of at least 2 years between

Gary D. Friedman; Natalia Udaltsova; James Chan; Charles P. Quesenberry Jr; Laurel A. Habel

2009-01-01

118

Unprotected Sexual Behavior Among Heterosexual HIV-Positive Injection Drug Using Men: Associations by Partner Type and Partner Serostatus  

PubMed Central

Few studies have examined sexual risk behaviors of HIV-positive, heterosexual, injection drug using (IDU) men. We investigated such behaviors and associations with risk among sexually active, HIV-positive IDU men who reported only female sex partners in the 3 months prior to baseline interview. We examined associations separately for four non-exclusive groups of men by crossing partner type (main or casual) and partner serostatus (HIV-positive or HIV-negative/unknown). Of 732 male participants, 469 (64%) were sexually active with only female partners. Of these 469 men, 155 (33%) reported sex with HIV-positive main partners, 127 (27%) with HIV-negative or unknown serostatus main partners, 145 (31%) with HIV-positive casual partners, and 192 (41%) with HIV-negative/unknown serostatus casual partners. Significant multivariate associations for unprotected sex with HIV-negative or unknown serostatus main partners were less self-efficacy to use condoms, weaker partner norms supporting condoms, and more negative condom beliefs. Similar correlates were found for unprotected sex with HIV-positive main and casual partners. In addition, alcohol or drug use during sex was a significant correlate of unprotected sex with HIV-positive main partners, while depression was significant for HIV-positive casual partners. For unprotected sex with HIV-negative/unknown status casual partners, self-efficacy for condom use, sex trade, and education were significant multivariate correlates. A combination of broad and tailored intervention strategies based on the relationship pattern of men's lives may provide the most benefit for reducing unprotected sex with female partners.

Mizuno, Yuko; Metsch, Lisa R.; Garfein, Richard; Tobin, Karin; Knight, Kelly; Latka, Mary H.

2006-01-01

119

Positively charged polymeric nanoparticle reservoirs of terbinafine hydrochloride: preclinical implications for controlled drug delivery in the aqueous humor of rabbits.  

PubMed

Frequent instillation of terbinafine hydrochloride (T HCl) eye drops (0.25%, w/v) is necessary to maintain effective aqueous humor concentrations for treatment of fungal keratitis. The current approach aimed at developing potential positively charged controlled-release polymeric nanoparticles (NPs) of T HCl. The estimation of the drug pharmacokinetics in the aqueous humor following ocular instillation of the best-achieved NPs in rabbits was another goal. Eighteen drug-loaded (0.50%, w/v) formulae were fabricated by the nanopreciptation method using Eudragit® RS100 and chitosan (0.25%, 0.5%, and 1%, w/v). Soybean lecithin (1%, w/v) and Pluronic® F68 (0.5%, 1%, and 1.5%, w/v) were incorporated in the alcoholic and aqueous phases, respectively. The NPs were evaluated for particle size, zeta potential, entrapment efficiency percentage (EE%), morphological examination, drug release in simulated tear fluid (pH 7.4), Fourier-transform IR (FT-IR), X-ray diffraction (XRD), physical stability (2 months, 4°C and 25°C), and drug pharmacokinetics in the rabbit aqueous humor relative to an oily drug solution. Spherical, discrete NPs were successfully developed with mean particle size and zeta potential ranging from 73.29 to 320.15 nm and +20.51 to +40.32 mV, respectively. Higher EE% were achieved with Eudragit® RS100-based NPs. The duration of drug release was extended to more than 8 h. FT-IR and XRD revealed compatibility between inactive formulation ingredients and T HCl and permanence of the latter's crystallinity, respectively. The NPs were physically stable, for at least 2 months, when refrigerated. F5-NP suspension significantly (P<0.05) increased drug mean residence time and improved its ocular bioavailability; 1.657-fold. PMID:23615773

Tayel, Saadia Ahmed; El-Nabarawi, Mohamed Ahmed; Tadros, Mina Ibrahim; Abd-Elsalam, Wessam Hamdy

2013-04-25

120

German national drug information service: user satisfaction and potential positive patient outcomes  

Microsoft Academic Search

Objective  The pharmacist-run national German drug information service (DIS) has operated since 1988. Answering a steadily increasing\\u000a demand over the past decade, our centre has, in total, provided information in more than 14,000 cases, mainly for community\\u000a pharmacists. Information on user’s satisfaction and on possible direct or indirect benefits for patients is as yet scarce.\\u000a Our objectives were to assess user’s

Thilo Bertsche; Andrea Hämmerlein; Martin Schulz

2007-01-01

121

Are phylogenetic position, virulence, drug susceptibility and in vivo response to treatment in mycobacteria interrelated?  

PubMed

Phylogenetic analyses on the basis of multiple house-keeping genes and whole genome sequences have offered new insights in the phylogeny of the genus Mycobacterium. This genus yields obligate pathogens, the M. tuberculosis complex and M. leprae, as well as opportunistic pathogens (e.g. M. avium, M. intracellulare, M. kansasii, M. marinum, M. malmoense) and saprophytes (e.g. M. phlei, M. sphagni, M. gordonae). The most virulent mycobacteria, the M. tuberculosis complex, M. leprae and the M. kansasii-M. szulgai-M. marinum-M. ulcerans group are phylogenetically related and infections by these organisms are better treatable than those caused by less virulent and phylogenetically more distantly related Mycobacterium species. The most virulent Mycobacterium species are also characterized by high levels of natural drug susceptibility. In this paper, we review studies of phylogeny, drug susceptibility, and clinical significance to support our hypothesis that drug susceptibility in mycobacteria is acquired and reflects the low level of competition in -and adaptation to- a closer-to-human (environmental) niche. In turn, mycobacteria that inhabit the most competitive environmental niches are the least adapted to humans, thus of low clinical significance, but most tolerant to antibiotics derived from microbes with which they share their habitat, lowering the chances of cure in case of infection. PMID:22036704

van Ingen, Jakko; Boeree, Martin J; van Soolingen, Dick; Iseman, Michael D; Heifets, Leonid B; Daley, Charles L

2011-10-20

122

10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.  

Code of Federal Regulations, 2013 CFR

...707.7 Energy DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES Procedures § 707.7...designated positions. (a)(1) Each workplace substance abuse program will provide for random testing for...

2013-01-01

123

Canada refuses to issue a visa to an HIV-positive worker on antiretroviral drugs.  

PubMed

Citizenship and Immigration Canada has denied an application for a visa from an HIV-positive man even though he is in good health. The man was seeking to fill a two-year work term in Canada. The case raises concerns about Canada's immigration policies for people with HIV and about the ability of organizations working in AIDS to hire HIV-positive foreign workers. PMID:14719488

Garmaise, David

2002-12-01

124

Drug susceptibility testing of Mycobacterium tuberculosis by a nitrate reductase assay applied directly on microscopy-positive sputum samples.  

PubMed

Current methods for drug susceptibility testing of Mycobacterium tuberculosis are either costly or slow. As the prevalence of multidrug-resistant strains increases, the need for fast, reliable, and inexpensive methods that can also be applied in settings with scarce resources is obvious. We evaluated a rapid colorimetric nitrate reductase assay (NRA) for direct drug susceptibility testing of M. tuberculosis directly from clinical sputum samples with positive microscopy results for acid-fast bacilli with more than 10 acid-fast bacilli per high-power field. We have saved valuable time by omitting the preisolation step. The sensitivity (ability to detect true drug resistance) and specificity (ability to detect true drug susceptibility) of the direct NRA, using the direct proportion method as the reference, were 100 and 100%, 93 and 100%, 76 and 100%, and 55 and 99% for rifampin, isoniazid, streptomycin, and ethambutol, respectively, when tested on M. tuberculosis strains present in 121 samples. The results were in most cases available in 14 days. The direct NRA could be used as a rapid, inexpensive, and accurate method to determine rifampin and isoniazid susceptibility directly from sputum. The technique might become a valid alternative to traditional methods, especially in low-income countries. PMID:16000429

Musa, Humberto R; Ambroggi, Marta; Souto, Alejandro; Angeby, K A Kristian

2005-07-01

125

Beliefs that Condoms Reduce Sexual Pleasure--Gender Differences in Correlates Among Heterosexual HIV-Positive Injection Drug Users (IDUs)  

PubMed Central

Studies consistently find that negative condom beliefs or attitudes are significantly associated with less condom use in various populations, including HIV-positive injection drug users (IDUs). As part of efforts to reduce sexual risk among HIV-positive IDUs, one of the goals of HIV interventions should be the promotion of positive condom beliefs. In this paper we sought to identify the correlates of negative condom beliefs and examined whether such correlates varied by gender, using a subsample (those with an opposite-sex main partner; n?=?348) of baseline data collected as part of a randomized controlled study of HIV-positive IDUs. In multivariate analyses, we found more significant correlates for women than for men. With men, perception that their sex partner is not supportive of condom use (negative partner norm) was the only significant correlate (Beta?=??0.30; p?positive condom beliefs among HIV-positive IDUs.

Purcell, David W.; Latka, Mary H.; Metsch, Lisa R.; Gomez, Cynthia A.; Latkin, Carl A.

2007-01-01

126

Drugs  

Center for Drug Evaluation (CDER)

... Print; Share; E-mail. Home; Drugs. -. Increased risk of death from IV Tygacil. ... Information highlights risk of hepatitis B reactivation; hepatitis B reactivation ... More results from www.fda.gov/drugs

127

Agents of change: peer mentorship as HIV prevention among HIV-positive injection drug users.  

PubMed

This paper presents a qualitative investigation of peer mentoring among HIV seropositive injection drug users in a randomized controlled trial, the INSPIRE study. Qualitative analyses of 68 in-depth open-ended interviews conducted in 2005 in Baltimore, New York, Miami, and San Francisco revealed that these individuals conceptualized themselves as change agents through the identity of peer mentor at the three related domains of individual, interpersonal, and community-level change. Implications for program development and future research of peer mentoring as a mechanism for HIV prevention are discussed. This study was funded by the Centers for Disease Control and Prevention and Health Resources and Services Administration (HRSA). PMID:22428820

Mackenzie, Sonja; Pearson, Charles; Frye, Victoria; Gómez, Cynthia A; Latka, Mary H; Purcell, David W; Knowlton, Amy R; Metsch, Lisa R; Tobin, Karin E; Valverde, Eduardo E; Knight, Kelly R

2012-04-01

128

Positive Control Mutations in the MyoD Basic Region Fail to Show Cooperative DNA Binding and Transcriptional Activation in vitro  

NASA Astrophysics Data System (ADS)

An in vitro transcription system from HeLa cells has been established in which MyoD and E47 proteins activate transcription both as homodimers and heterodimers. However, heterodimers activate transcription more efficiently than homodimers, and function synergistically from multiple binding sites. Positive control mutants in the basic region of MyoD that have previously been shown to be defective in initiating the myogenic program, can bind DNA but have lost their ability to function as transcriptional activators in vitro. Additionally, positive control mutants, unlike wild-type MyoD, fail to bind cooperatively to DNA. We propose that binding of MyoD complexes to high affinity MyoD binding sites induces conformational changes that facilitate cooperative binding to multiple sites and promote transcriptional activation.

Bengal, Eyal; Flores, Osvaldo; Rangarajan, Pundi N.; Chen, Amy; Weintraub, Harold; Verma, Inder M.

1994-06-01

129

TetZ, a New Tetracycline Resistance Determinant Discovered in Gram-Positive Bacteria, Shows High Homology to Gram-Negative Regulated Efflux Systems  

Microsoft Academic Search

The complete nucleotide sequence of the tetracycline resistance plasmid pAG1 from the gram-positive soil bacterium Corynebacterium glutamicum 22243 (formerly Corynebacterium melassecola 22243) was determined. The R-plasmid has a size of 19,751 bp and contains at least 18 complete open reading frames. The resistance determinant of pAG1 revealed homology to gram-negative tetracycline efflux and repressor systems of Tet classes A through

Andreas Tauch; Alfred Pühler; Jörn Kalinowski; Georg Thierbach

2000-01-01

130

Sexual risk behavior among injection drug-using human immunodeficiency virus positive clients.  

PubMed

This study examined sexual risk behavior of 154 seropositive Hispanic injection drug-using clients who were a subsample of a larger study. The results revealed that while nearly 71% followed safe sex practices at a 6-month follow-up, the other 29% were following risky sexual behaviors. Among males who were 25 years of age or younger, slightly over 58% were practicing unsafe sex. Among females, those in the 31-35 age group were all following risky sexual behaviors. Generally, those who lived with their sexual partners, females, and younger clients tended to follow risky sexual behaviors. These findings are very significant in the light of the heterosexual transmission of Human Immunodeficiency Virus (HIV). Educational and case management programs are needed to provide such clients with an understanding of the possibility of HIV transmission to their sexual partners and to their children in case of pregnancies. PMID:8349390

Singh, B K; Koman, J J; Catan, V M; Souply, K L; Birkel, R C; Golaszewski, T J

1993-06-01

131

Recurrent deep venous thrombosis in an HIV-positive and injecting drug user woman  

PubMed Central

We report a case of recurrent deep venous thrombosis in a 44-year-old woman, intravenous drug user and HIV-infected, who injected cocaine in the groins and veins of the dorsum of the feet. She suffered several episodes of deep venous thrombosis and soft-tissue infections in the lower limbs. Images of Doppler ultrasound scan revealed thrombosis in the right popliteal vein with partial recanalization and calcified thrombi in the territory of the right femoral vein. After use of heparin and oral anticoagulation, her clinical evolution was uneventful, and she was asymptomatic at the occasion of the hospital discharge. This report calls for better awareness about injections in the groins and superficial femoral veins, which are part of the deep venous system. Thrombosis related to HIV infection is highlighted.

dos Santos, Vitorino Modesto; Teles, Ludmila Thommen; Leao, Carlos Eduardo Silva; Lopes, Janio Wagner Pinheiro; Fastudo, Custodio Abel; Lima, Regina Lucas Machada

2012-01-01

132

Ehrlichia ruminantium Major Antigenic Protein Gene (map1) Variants Are Not Geographically Constrained and Show No Evidence of Having Evolved under Positive Selection Pressure  

PubMed Central

In a search for tools to distinguish antigenic variants of Ehrlichia ruminantium, we sequenced the major antigenic protein genes (map1 genes) of 21 different isolates and found that the sequence polymorphisms were too great to permit the design of probes which could be used as markers for immunogenicity. Phylogenetic comparison of the 21 deduced MAP1 sequences plus another 9 sequences which had been previously published did not reveal any geographic clustering among the isolates. Maximum likelihood analysis of codon and amino acid changes over the phylogeny provided no statistical evidence that the gene is under positive selection pressure, suggesting that it may not be important for the evasion of host immune responses.

Allsopp, M. T. E. P.; Dorfling, C. M.; Maillard, J. C.; Bensaid, A.; Haydon, D. T.; van Heerden, H.; Allsopp, B. A.

2001-01-01

133

"The Show"  

ERIC Educational Resources Information Center

|For the past 16 years, the blue-collar city of Huntington, West Virginia, has rolled out the red carpet to welcome young wrestlers and their families as old friends. They have come to town chasing the same dream for a spot in what many of them call "The Show". For three days, under the lights of an arena packed with 5,000 fans, the state's best…

Gehring, John

2004-01-01

134

Forfeiture of illegally acquired assets of drug traffickers: the position in India.  

PubMed

Trafficking in drugs and other related crimes generates huge illicit funds which are used to support other criminal activity, corruption, illicit arms trading, the smuggling of goods and currency, and other economic offences. The traditional enforcement techniques aimed only at carriers and confiscation of the seized contraband no longer provide a sufficient deterrent. The problem is international in scope and requires close cooperation of all the agencies concerned. In 1976, India enacted specific legislation providing for the forfeiture of the property and assets of smugglers, including traffickers and foreign-exchange manipulators. This legislation, known as the "Smugglers and Foreign-Exchange Manipulators (Forfeiture of Property) Act, 1976", enables the enforcement authorities to confiscate all property, both movable and immovable, illegally acquired or accumulated, or for which investment is made from unlawful earnings resulting from smuggling and foreign exchange racketeering. It covers all such property held, not only in the names of smugglers and traffickers themselves, but their relatives and associates as well. The Act provides for principles of natural justice to be followed for all forfeiture proceedings and for appeals to a high tribunal. The legislation has enabled forfeiture action in 2,297 cases, covering properties valued at $US 40 million, during the last six years. PMID:6556075

Gujral, B B

135

Pollen-Specific, but Not Sperm-Specific, Genes Show Stronger Purifying Selection and Higher Rates of Positive Selection Than Sporophytic Genes in Capsella grandiflora.  

PubMed

Selection on the gametophyte can be a major force shaping plant genomes as 7-11% of genes are expressed only in that phase and 60% of genes are expressed in both the gametophytic and sporophytic phases. The efficacy of selection on gametophytic tissues is likely to be influenced by sexual selection acting on male and female functions of hermaphroditic plants. Moreover, the haploid nature of the gametophytic phase allows selection to be efficient in removing recessive deleterious mutations and fixing recessive beneficial mutations. To assess the importance of gametophytic selection, we compared the strength of purifying selection and extent of positive selection on gametophyte- and sporophyte-specific genes in the highly outcrossing plant Capsella grandiflora. We found that pollen-exclusive genes had a larger fraction of sites under strong purifying selection, a greater proportion of adaptive substitutions, and faster protein evolution compared with seedling-exclusive genes. In contrast, sperm cell-exclusive genes had a smaller fraction of sites under strong purifying selection, a lower proportion of adaptive substitutions, and slower protein evolution compared with seedling-exclusive genes. Observations of strong selection acting on pollen-expressed genes are likely explained by sexual selection resulting from pollen competition aided by the haploid nature of that tissue. The relaxation of selection in sperm might be due to the reduced influence of intrasexual competition, but reduced gene expression may also be playing an important role. PMID:23997108

Arunkumar, Ramesh; Josephs, Emily B; Williamson, Robert J; Wright, Stephen I

2013-08-30

136

Various adiposity measures show similar positive associations with type 2 diabetes in Caucasians, Native Hawaiians, and Japanese Americans: The Multiethnic Cohort  

PubMed Central

We evaluated the association of body mass index (BMI), waist (WC) and hip circumferences (HC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) with diabetes in Caucasians, Native Hawaiians, and Japanese Americans aged 45–75 years in the Multiethnic Cohort. Diabetes cases were obtained from self-reports and by linkages with health insurance plans. We estimated adjusted prevalence odds ratios (POR) and compared the area under the receiver operating characteristic curves (AUC). All measures were positively associated with diabetes prevalence; the PORs were 1.24–1.64 in men and 1.52–1.83 in women. In all 3 ethnic groups, the AUCs in men were greater for BMI than for the other measures, while in women the AUCs were greater for combined models than for BMI alone, but the differences were small and not clinically significant. It does not appear that one anthropometric measure best reflects diabetes prevalence or performs better in one ethnic group than in another.

Steinbrecher, A; Heak, S; Morimoto, Y; Grandinetti, A; Kolonel, LN; Maskarinec, G

2013-01-01

137

Amyotrophic lateral sclerosis with dementia: an autopsy case showing many Bunina bodies, tau-positive neuronal and astrocytic plaque-like pathologies, and pallido-nigral degeneration.  

PubMed

We report the case of a 54-year-old woman with mental retardation who developed frontotemporal dementia and amyotrophic lateral sclerosis (ALS) in the presenium. She presented with dementia at age 48, and motor neuron signs developed at age 53. She had no family history of dementia or ALS. Postmortem examination disclosed histopathological features of ALS, including pyramidal tract degeneration, mild loss of motor neurons, and many Bunina bodies immunoreactive for cystatin C, but not ubiquitin-positive inclusions. Unusual features of this case included severe neuronal loss in the substantia nigra and medial globus pallidus. The subthalamic nucleus, limbic system, and cerebral cortex were well preserved. In addition, neurofibrillary tangles (NFTs) were found in the frontal, temporal, insular, and cingulate cortices, nucleus basalis of Meynert, and locus coeruleus, and to a lesser degree, in the dentate nucleus, cerebellum, hippocampus, and amygdala. No ballooned neurons, tufted astrocytes, or astrocytic plaques were found. Tau immunostaining demonstrated many pretangles rather than NFTs and glial lesions resembling astrocytic plaques in the frontal and temporal cortices. This glial tau pathology predominantly developed in the middle to deep layers in the primary motor cortex, and was frequently associated with the walls of blood vessels. NFTs were immunolabeled with 3-repeat and 4-repeat specific antibodies against tau, respectively. Although the pathophysiological relationship between tau pathology and the selective involvement of motor neurons, substantia nigra, and globus pallidus was unclear, we considered that it might be more than coincidental. PMID:17021751

Yokota, Osamu; Tsuchiya, Kuniaki; Oda, Tatsurou; Ishihara, Takeshi; de Silva, Rohan; Lees, Andrew J; Arai, Tetsuaki; Uchihara, Toshiki; Ishizu, Hideki; Kuroda, Shigetoshi; Akiyama, Haruhiko

2006-09-26

138

Mutation at Positively Selected Positions in the Binding site for HLA-C Shows KIR2DL1 is a More Refined but Less Adaptable NK cell Receptor than KIR2DL31  

PubMed Central

Through recognition of HLA class I, killer cell immunoglobulin-like receptors (KIR) modulate NK cell functions in human immunity and reproduction. Although a minority of HLA-A and –B allotypes are KIR ligands, HLA-C allotypes dominate this regulation, because they all carry either the C1 epitope recognized by KIR2DL2/3 or the C2 epitope recognized by KIR2DL1. The C1 epitope and C1-specific KIR evolved first, followed several million years later by the C2 epitope and C2-specific KIR. Strong, varying selection pressure on NK cell functions drove the diversification and divergence of hominid KIR, with six positions in the HLA class I binding site of KIR being targets for positive selection. Introducing each naturally occurring residue at these positions into KIR2DL1 and KIR2DL3, produced 38 point mutants that were tested for binding to 95 HLA- A, -B and –C allotypes. Modulating specificity for HLA-C is position 44, whereas positions 71 and 131 control cross reactivity with HLA-A*11:02. Dominating avidity modulation is position 70, with lesser contributions from positions 68 and 182. KIR2DL3 has lower avidity and broader specificity than KIR2DL1. Mutation can increase the avidity and change the specificity of KIR2DL3, whereas KIR2DL1 specificity was resistant to mutation and its avidity could only be lowered. The contrasting inflexibility of KIR2DL1 and adaptability of KIR2DL3 fits with C2-specific KIR having evolved from C1-specific KIR, and not vice versa. Substitutions restricted to activating KIR all reduced the avidity of KIR2DL1 and KIR2DL3, further evidence that activating KIR function often becomes subject to selective attenuation.

Hilton, Hugo G.; Vago, Luca; Older Aguilar, Ana; Moesta, Achim K.; Graef, Thorsten; Abi Rached, Laurent; Norman, Paul J.; Guethlein, Lisbeth A.; Fleischhauer, Katharina; Parham, Peter

2012-01-01

139

Activity of the Novel Peptide Arminin against Multiresistant Human Pathogens Shows the Considerable Potential of Phylogenetically Ancient Organisms as Drug Sources?  

PubMed Central

The emergence of multidrug-resistant bacteria highlights the need for new antibacterial agents. Arminin 1a is a novel antimicrobial peptide discovered during investigations of the epithelial defense of the ancient metazoan Hydra. Following proteolytic processing, the 31-amino-acid-long positively charged C-terminal part of arminin 1a exhibits potent and broad-spectrum activity against bacteria, including multiresistant human pathogenic strains, such as methicillin-resistant Staphylococcus aureus (MRSA) strains (minimal bactericidal concentration, 0.4 ?M to 0.8 ?M). Ultrastructural observations indicate that bacteria are killed by disruption of the bacterial cell wall. Remarkably, the antibacterial activity of arminin 1a is not affected under the physiological salt conditions of human blood. In addition, arminin 1a is a selective antibacterial agent that does not affect human erythrocyte membranes. Arminin 1a shows no sequence homology to any known antimicrobial peptide. Because of its high level of activity against multiresistant bacterial strains pathogenic for humans, the peptide arminin 1a is a promising template for a new class of antibiotics. Our data suggest that ancient metazoan organisms such as Hydra hold promise for the detection of novel antimicrobial molecules and the treatment of infections caused by multiresistant bacteria.

Augustin, Rene; Anton-Erxleben, Friederike; Jungnickel, Stephanie; Hemmrich, Georg; Spudy, Bjorn; Podschun, Rainer; Bosch, Thomas C. G.

2009-01-01

140

Activity of the novel peptide arminin against multiresistant human pathogens shows the considerable potential of phylogenetically ancient organisms as drug sources.  

PubMed

The emergence of multidrug-resistant bacteria highlights the need for new antibacterial agents. Arminin 1a is a novel antimicrobial peptide discovered during investigations of the epithelial defense of the ancient metazoan Hydra. Following proteolytic processing, the 31-amino-acid-long positively charged C-terminal part of arminin 1a exhibits potent and broad-spectrum activity against bacteria, including multiresistant human pathogenic strains, such as methicillin-resistant Staphylococcus aureus (MRSA) strains (minimal bactericidal concentration, 0.4 microM to 0.8 microM). Ultrastructural observations indicate that bacteria are killed by disruption of the bacterial cell wall. Remarkably, the antibacterial activity of arminin 1a is not affected under the physiological salt conditions of human blood. In addition, arminin 1a is a selective antibacterial agent that does not affect human erythrocyte membranes. Arminin 1a shows no sequence homology to any known antimicrobial peptide. Because of its high level of activity against multiresistant bacterial strains pathogenic for humans, the peptide arminin 1a is a promising template for a new class of antibiotics. Our data suggest that ancient metazoan organisms such as Hydra hold promise for the detection of novel antimicrobial molecules and the treatment of infections caused by multiresistant bacteria. PMID:19770277

Augustin, René; Anton-Erxleben, Friederike; Jungnickel, Stephanie; Hemmrich, Georg; Spudy, Björn; Podschun, Rainer; Bosch, Thomas C G

2009-09-21

141

Recurrent major depressive disorder among human immunodeficiency virus (HIV)-positive and HIV-negative intravenous drug users: Findings of a 3-year longitudinal study  

Microsoft Academic Search

A longitudinal study was conducted to investigate the association between human immunodeficiency virus (HIV) infection, history of major depressive disorder (MDD), and persistent or recurrent MDD among intravenous drug users. Psychiatric disorders were assessed in a sample of HIV-positive (HIV+) and HIV-negative (HIV?) intravenous drug users every 6 months for 3 years. Results indicated that HIV status and baseline MDD

Jeffrey G Johnson; Judith G Rabkin; Joshua D Lipsitz; Janet B. W Williams; Robert H Remien

1999-01-01

142

Interaction Between Drugs and Biomedical Materials i: Binding Position of Bezafibrate to Human Serum Alubmin  

NASA Astrophysics Data System (ADS)

The interaction between bezafibrate (BZF) and human serum albumin (HSA) was investigated by equilibrium dialysis. Since the binding constant of BZF to HSA was independent of ionic strength and decreased with the addition of fatty acid, the interaction between BZF and HSA was considered to be due to hydrophobic mechanism. Chemical shifts in 1H-NMR spectra of BZF were independent of the concentration of BZF and addition of HSA. Spin-lattice relaxation time (T1) and spin-spin relaxation time (T2) of respective protons of BZF were independent of the concentration, but depended on the concentration of HSA added. The binding position of BZF to HSA was considered to involve the hydrophobic aromatic moiety of BZF from the ratio of spin-spin relaxation rates (1/T2) of BZF bound to HSA and free BZF.

Tanaka, Masami; Minagawa, Keiji; Berber, Mohamed R.; Hafez, Inas H.; Mori, Takeshi

143

Mathematical Modeling of Triphasic Viral Dynamics in Patients with HBeAg-Positive Chronic Hepatitis B Showing Response to 24-Week Clevudine Therapy  

PubMed Central

Background Modeling of short-term viral dynamics of hepatitis B with traditional biphasic model might be insufficient to explain long-term viral dynamics. The aim was to develop a novel method of mathematical modeling to shed light on the dissociation between early and long-term dynamics in previous studies. Methods We investigated the viral decay pattern in 50 patients from the phase III clinical trial of 24-week clevudine therapy, who showed virological response and HBsAg decline. Immune effectors were added as a new compartment in the model equations. We determined some parameter values in the model using the non-linear least square minimization method. Results Median baseline viral load was 8.526 Log10copies/mL, and on-treatment viral load decline was 5.683 Log10copies/mL. The median half-life of free virus was 24.89 hours. The median half-life of infected hepatocytes was 7.39 days. The viral decay patterns were visualized as triphasic curves with decreasing slopes over time: fastest decay in the first phase; slowest in the third phase; the second phase in between. Conclusions In the present study, mathematical modeling of hepatitis B in patients with virological response and HBsAg decline during 24-week antiviral therapy showed triphasic viral dynamics with direct introduction of immune effectors as a new compartment, which was thought to reflect the reduction of clearance rate of infected cells over time. This modeling method seems more appropriate to describe long-term viral dynamics compared to the biphasic model, and needs further validation.

Kim, Hwi Young; Kwon, Hee-Dae; Jang, Tae Soo; Lim, Jisun; Lee, Hyo-Suk

2012-01-01

144

Drugs  

Center for Biologics Evaluation and Research (CBER)

Quick Links: Skip to main page content Skip to Search Skip to Topics Menu Skip to Section Content Menu Skip to Common Links. ... More results from www.fda.gov/advisorycommittees/committeesmeetingmaterials/drugs

145

The Human Endometrium Expresses the Glycoprotein Mucin-1 and Shows Positive Correlation for Thomsen-Friedenreich Epitope Expression and Galectin-1 Binding  

PubMed Central

Mucin 1 (MUC1) is a glycoprotein in human endometrium and is abundant at the luminal epithelial surface in the receptive phase. It has a highly glycosylated ecto-domain that contains keratan sulfate chains, that disappears at the time of implantation. In addition, the glycoforms on MUC1 differ in fertile and infertile women. Therefore the aims of this study were investigations on glycosylation of MUC1 with the Thomsen-Friedenreich (TF) epitope on normal human endometrium throughout the menstrual cycle and binding of galectin-1 on the TF epitope in the endometrium and the expression of galectin-1 on the human oocyte. Human endometrial tissue was obtained from 54 premenopausal patients and was immunohistochemically analyzed with monoclonal antibodies against MUC1, TF epitope, galectin-1, and biotinylated galectin-1. In addition, human oocytes were analyzed for TF, galectin-1 expression, and galectin-1 binding. We identified a significant upregulation of MUC1 and TF epitope and, in addition, galectin-1 binding in glandular epithelium and epithelial apical surface tissue from proliferative to secretory phase. With double staining experiments, we identified a coexpression of TF and MUC1 in the early secretory phase and galectin-1 binding to TF during the same period of time. In addition we identified TF epitope and galectin-1 expression plus binding on the human oocyte and irregularly fertilized oocytes. Upregulation of TF epitope on the glandular epithelium and epithelial apical surface tissue in the secretory phase and binding of galectin-1 at the same time show the possibility of galectin-1–mediated trophectoderm binding to the endometrium within the window of implantation. (J Histochem Cytochem 57:871–881, 2009)

Jeschke, Udo; Walzel, Hermann; Mylonas, Ioannis; Papadopoulos, Panos; Shabani, Naim; Kuhn, Christina; Schulze, Sandra; Friese, Klaus; Karsten, Uwe; Anz, David; Kupka, Markus S.

2009-01-01

146

Surface Proteins of Gram-Positive Pathogens: Using Crystallography to Uncover Novel Features in Drug and Vaccine Candidates  

NASA Astrophysics Data System (ADS)

Proteins displayed on the cell surfaces of pathogenic organisms are the front-line troops of bacterial attack, playing critical roles in colonization, infection and virulence. Although such proteins can often be recognized from genome sequence data, through characteristic sequence motifs, their functions are often unknown. One such group of surface proteins is attached to the cell surface of Gram-positive pathogens through the action of sortase enzymes. Some of these proteins are now known to form pili: long filamentous structures that mediate attachment to human cells. Crystallographic analyses of these and other cell surface proteins have uncovered novel features in their structure, assembly and stability, including the presence of inter- and intramolecular isopeptide crosslinks. This improved understanding of structures on the bacterial cell surface offers opportunities for the development of some new drug targets and for novel approaches to vaccine design.

Baker, Edward N.; Proft, Thomas; Kang, Haejoo

147

Impact of Drug-Resistant Mycobacterium tuberculosis on Treatment Outcome of Culture-Positive Cases of Tuberculosis in the Archangel Oblast, Russia, in 1999  

Microsoft Academic Search

The objective of this study was to evaluate the outcome of treatment of culture-positive cases of tuberculosis registered in Archangel, Russia, in 1999, and to analyse the influence of Mycobacterium tuberculosis drug resistance on treatment outcome. The outcome of tuberculosis treatment was evaluated for 235 new and 61 previously treated culture-positive cases diagnosed in 1999. Of the 235 new cases,

O. S. Toungoussova; N. I. Nizovtseva; A. O. Mariandyshev; D. A. Caugant; P. Sandven; G. Bjune

2004-01-01

148

Discovery of 1,4-dihydroxy-2-naphthoate [corrected] prenyltransferase inhibitors: new drug leads for multidrug-resistant gram-positive pathogens.  

PubMed

Since utilization of menaquinone in the electron transport system is a characteristic of Gram-positive organisms, the 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) inhibitors 1a and 2a act as selective antibacterial agents against organisms such as methicillin-resistant Stapylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE), and Mycobacterium spp. Growth of drug-resistant Gram-positive organisms was sensitive to the MenA inhibitors, indicating that menaquinone synthesis is a valid new drug target in Gram-positive organisms. PMID:17658779

Kurosu, Michio; Narayanasamy, Prabagaran; Biswas, Kallolmay; Dhiman, Rakesh; Crick, Dean C

2007-07-21

149

Interventions for Seropositive Injectors???Research and Evaluation: An Integrated Behavioral Intervention With HIV-Positive Injection Drug Users to Address Medical Care, Adherence, and Risk Reduction  

Microsoft Academic Search

Background: Behavioral interventions to address the complex medical and HIV risk reduction needs of HIV-seropositive (HIV- positive) injection drug users (IDUs) are urgently needed. We de- scribe the development of Interventions for Seropositive Injectors— Research and Evaluation (INSPIRE), a randomized controlled trial of an integrated intervention for HIV-positive IDUs, and the character- istics of the baseline sample. Methods: HIV-positive IDUs

David W. Purcell; Lisa R. Metsch; Mary Latka; Scott Santibanez; Lois Eldred; Carl A. Latkin

2004-01-01

150

Structures of Substrate-And Inhibitor-Bound Adenosine Deaminase From a Human Malaria Parasite Show a Dramatic Conformational Change And Shed Light on Drug Selectivity  

SciTech Connect

Plasmodium and other apicomplexan parasites are deficient in purine biosynthesis, relying instead on the salvage of purines from their host environment. Therefore, interference with the purine salvage pathway is an attractive therapeutic target. The plasmodial enzyme adenosine deaminase (ADA) plays a central role in purine salvage and, unlike mammalian ADA homologs, has a further secondary role in methylthiopurine recycling. For this reason, plasmodial ADA accepts a wider range of substrates, as it is responsible for deamination of both adenosine and 5{prime}-methylthioadenosine. The latter substrate is not accepted by mammalian ADA homologs. The structural basis for this natural difference in specificity between plasmodial and mammalian ADA has not been well understood. We now report crystal structures of Plasmodium vivax ADA in complex with adenosine, guanosine, and the picomolar inhibitor 2{prime}-deoxycoformycin. These structures highlight a drastic conformational change in plasmodial ADA upon substrate binding that has not been observed for mammalian ADA enzymes. Further, these complexes illuminate the structural basis for the differential substrate specificity and potential drug selectivity between mammalian and parasite enzymes.

Larson, E.T.; Deng, W.; Krumm, B.E.; Napuli, A.; Mueller, N.; Voorhis, W.C.Van; Buckner, F.S.; Fan, E.; Lauricella, A.; DeTitta, G.; Luft, J.; Zucker, F.; Hol, W.G.J.; Verlinde, C.L.M.J.; Merritt, E.A.

2009-05-20

151

Drug assertiveness and sexual risk-taking behavior in a sample of HIV-positive, methamphetamine-using men who have sex with men.  

PubMed

Drug assertiveness skills have been demonstrated to be effective in reducing substance use behaviors among patients with alcohol or heroin use disorders. This study examined the association between drug assertiveness and methamphetamine use, psychological factors, and sexual risk behaviors in a sample of 250 HIV-positive men who have sex with men enrolled in a safer sex intervention in San Diego, CA. Less assertiveness in turning down drugs was associated with greater frequency and larger amounts of methamphetamine use, lower self-esteem, higher scores on a measure of sexual sensation seeking, and greater attendance at risky sexual venues. These data suggest that drug assertiveness training should be incorporated into drug abuse treatment programs and other risk reduction interventions for methamphetamine users. PMID:21550758

Semple, Shirley J; Strathdee, Steffanie A; Zians, Jim; McQuaid, John R; Patterson, Thomas L

2011-05-08

152

Drug assertiveness and sexual risk-taking behavior in a sample of HIV-positive, methamphetamine-using men who have sex with men  

PubMed Central

Drug assertiveness skills have been demonstrated effective in reducing substance use behaviors among patients with alcohol- or heroin-use disorders. This study examined the association between drug assertiveness and methamphetamine use, psychological factors, and sexual risk behaviors in a sample of 250 HIV-positive men who have sex with men (MSM) enrolled in a safer sex intervention in San Diego, CA. Less assertiveness in turning down drugs was associated with greater frequency and larger amounts of methamphetamine use, lower self-esteem, higher scores on a measure of sexual sensation-seeking, and greater attendance at risky sexual venues. These data suggest that drug assertiveness training should be incorporated into drug abuse treatment programs and other risk reduction interventions for methamphetamine users.

Semple, Shirley J.; Strathdee, Steffanie A.; Zians, Jim; McQuaid, John R.; Patterson, Thomas L.

2011-01-01

153

Cost-effectiveness of integrating methadone maintenance and antiretroviral treatment for HIV-positive drug users in Vietnam's injection-driven HIV epidemics.  

PubMed

Drug use negatively affects adherence to and outcomes of antiretroviral treatment (ART). This study evaluated the cost-effectiveness of integrating methadone maintenance treatment (MMT) with ART for HIV-positive drug users (DUs) in Vietnam. A decision analytical model was developed to compare the costs and consequences of 3 HIV/AIDS treatment strategies for DUs: (1) only ART, (2) providing ART and MMT in separated sites (ART-MMT), and (3) integrating ART and MMT with direct administration (DAART-MMT). The model was parameterized using empirical data of costs and outcomes extracted from the MMT and ART cohort studies in Vietnam, and international published sources. Probabilistic sensitivity analysis was conducted to examine the model's robustness. The base-case analysis showed that the cost-effectiveness ratio of ART, DAART-MMT, and ART-MMT strategies was USD 1358.9, 1118.0 and 1327.1 per 1 Quality-Adjusted Life Year (QALY), equivalent to 1.22, 1.00, and 1.19 times Gross Domestic Product per capita (GDPpc). The incremental cost-effectiveness ratio for DAART-MMT and ART-MMT versus ART strategy was 569.4 and 1227.8, approximately 0.51 and 1.10 times GDPpc/QALY. At the willingness to pay threshold of 3 times GDPpc, the probability of being cost-effective of DAART-MMT versus ART was 86.1%. These findings indicated that providing MMT along with ART for HIV-positive DUs is a cost-effective intervention in Vietnam. Integrating MMT and ART services could facilitate the use of directly observed therapy that supports treatment adherence and brings about clinically important improvements in health outcomes. This approach is also incrementally cost-effective in this large injection-driven HIV epidemic. PMID:22436971

Tran, Bach Xuan; Ohinmaa, Arto; Duong, Anh Thuy; Nguyen, Long Thanh; Vu, Phu Xuan; Mills, Steve; Houston, Stan; Jacobs, Philip

2012-03-20

154

Association between Rash and a Positive Drug Response Associated with Vinorelbine in a Patient with Primary Peritoneal Carcinoma  

PubMed Central

Vinorelbine (Navelbine, VRL) is commonly used for platinum-resistant ovarian cancer and has been shown to be effective in patients with recurrent primary peritoneal carcinoma. Of VRL's major side effects, skin rash is uncommon, and, if it does occur, it is usually localized to site of injection. In this case report, a 71-year-old Hispanic female with primary peritoneal carcinoma received single agent VRL as fourth-line regimen, which she tolerated very well except for a skin rash related to VRL. The rash continued to progress throughout 6 cycles of VRL, and follow-up CT/PET scan demonstrated complete metabolic and radiological responses. We, therefore, believe that this rash was linked to VRL administration and correlated with response to therapy. Rash has been recognized as a useful surrogate marker with targeted agents such as cetuximab and erlotinib; to the best of our knowledge, this case report describes the first patient with a possible drug rash and its association with a positive outcome. This case report incites interest in further investigation of similar cases to support this observation, since there is a lack of reports of skin rash with VRL therapy.

Mohammad, Mustafa M.; Syrigos, Kostas N.; Saif, M. Wasif

2013-01-01

155

Association between Rash and a Positive Drug Response Associated with Vinorelbine in a Patient with Primary Peritoneal Carcinoma.  

PubMed

Vinorelbine (Navelbine, VRL) is commonly used for platinum-resistant ovarian cancer and has been shown to be effective in patients with recurrent primary peritoneal carcinoma. Of VRL's major side effects, skin rash is uncommon, and, if it does occur, it is usually localized to site of injection. In this case report, a 71-year-old Hispanic female with primary peritoneal carcinoma received single agent VRL as fourth-line regimen, which she tolerated very well except for a skin rash related to VRL. The rash continued to progress throughout 6 cycles of VRL, and follow-up CT/PET scan demonstrated complete metabolic and radiological responses. We, therefore, believe that this rash was linked to VRL administration and correlated with response to therapy. Rash has been recognized as a useful surrogate marker with targeted agents such as cetuximab and erlotinib; to the best of our knowledge, this case report describes the first patient with a possible drug rash and its association with a positive outcome. This case report incites interest in further investigation of similar cases to support this observation, since there is a lack of reports of skin rash with VRL therapy. PMID:24073344

Mohammad, Mustafa M; Syrigos, Kostas N; Saif, M Wasif

2013-09-01

156

DIETARY INTAKE AND BODY MASS INDEX IN HIV-POSITIVE AND HIV-NEGATIVE DRUG ABUSERS OF HISPANIC ETHNICITY  

Technology Transfer Automated Retrieval System (TEKTRAN)

Malnutrition in drug abusers has been attributed to poor diet. However, previous studies are conflicting. Many studies have not considered possible concurrent HIV disease. The purpose of this study was to determine the relationship between drug abuse and dietary intake in Hispanic Americans with and...

157

Differences in treatment outcome between male alcohol dependent offenders of domestic violence with and without positive drug screens  

Microsoft Academic Search

Men who are violent toward their partners tend to have a dual problem with alcohol and drug use, yet little is known about differences between men with single rather than dual problems. This study was one of the first to evaluate differences between alcohol dependent men who were arrested for Intimate Partner Violence (IPV) with and without concurrent illicit drug

Caroline J. Easton; Dolores Mandel; Theresa Babuscio; Bruce J. Rounsaville; Kathleen M. Carroll

2007-01-01

158

Benzodiazepine whole blood concentrations in cases with positive oral fluid on-site screening test results using the DrugWipe(®) single for benzodiazepines.  

PubMed

Reliable on-site oral fluid screening devices are a useful and convenient means of policing traffic. In Finland, benzodiazepines represent a particular challenge to traffic safety. This study presents a retrospective examination of toxicological analysis results from whole blood in cases which gave a positive screening result for benzodiazepines in oral fluid using the DrugWipe Single device (Securetec). Use of oral fluid on-site screening tests and blood confirmation analyses reflects the real situation in many countries. The data were compiled from the databases of Alcohol and Drug Analytics Unit at the National Institute for Health and Welfare. Confirmation analysis results in whole blood were obtained using gas chromatography-mass spectrometry. Data were from 224 real cases in which the Finnish police had conducted a DrugWipe Single benzodiazepines test on drivers suspected of driving under the influence of drugs (DUID). The benzodiazepine concentrations encountered in positive oral fluid screening cases in this study indicate that the device is able to detect these substances even at relatively low levels. However, the DrugWipe device does not enable any distinction between therapeutic use and harmful use of benzodiazepines at higher doses. PMID:21740691

Blencowe, Tom; Vimpari, Kari; Lillsunde, Pirjo

2011-07-01

159

Failure to maintain adherence to haart in a cohort of French HIV-positive injecting drug users  

Microsoft Academic Search

The study, carriedoutintheFrench MANIF2000 cohortofHIVpositive patients contaminated through injecting drug use, assessed\\u000a the impact of patients’ sociodemographic and psychological characteristics, behaviors toward drug abuse, and antiretroviral\\u000a treatment characteristics on the maintenance of adherence to HAART (highly active antiretroviral therapies). A total of 96\\u000a patients (30 men and 66 women), who were initially adherent at their first visit after HAART prescription,

M. P. Carrieri; M. A. Chesney; B. Spire; A. Loundou; A. Sobel; G. Lepeu; J. P. Moatti

2003-01-01

160

Sexual Risk Behavior Associated with Co-administration of Methamphetamine and Other Drugs in a Sample of HIV-positive Men Who Have Sex with Men  

PubMed Central

This study examined the association between sexual risk behavior and co-administration of methamphetamine with other drugs in a sample of 341 HIV-positive MSM. Those who reported methamphetamine co-administration in the past two months (65%) reported significantly more unprotected anal and oral sex and a greater number of casual, anonymous, and paid sex partners in this timeframe compared to men who used methamphetamine alone. Two primary patterns of co-administration were identified: 1) drug combinations motivated by sexual performance and enhancement (e.g., methamphetamine, poppers, sildenafil) and 2) “party drug” combinations (e.g., methamphetamine, GHB, ketamine). Implications for further research and possible applications to risk-reduction interventions are discussed.

Semple, Shirley J.; Strathdee, Steffanie A.; Zians, Jim; Patterson, Thomas L.

2011-01-01

161

Elevated Phenotypic Switching and Drug Resistance of Candida albicans from Human Immunodeficiency Virus-Positive Individuals prior to First Thrush Episode  

PubMed Central

Strains of Candida albicans obtained from human immunodeficiency virus (HIV)-positive individuals prior to their first episode of oral thrush were already in a high-frequency mode of switching and were far more resistant to a number of antifungal drugs than commensal isolates from healthy individuals. Switching in these isolates also had profound effects both on susceptibility to antifungal drugs and on the levels of secreted proteinase activity. These results suggest that commensal strains colonizing HIV-positive individuals either undergo phenotypic alterations or are replaced prior to the first episode of oral thrush. They also support the suggestion that high-frequency phenotypic switching functions as a higher-order virulence trait, spontaneously generating in colonizing populations variants with alterations in a variety of specific virulence traits.

Vargas, Kaaren; Messer, Shawn A.; Pfaller, Michael; Lockhart, Shawn R.; Stapleton, Jack T.; Hellstein, John; Soll, David R.

2000-01-01

162

Hero or Hypocrite?United States and International Media Portrayals of Carl Lewis Amid Revelations of a Positive Drug Test  

Microsoft Academic Search

This article examines press coverage of track and field athlete Carl Lewis amid reports in April 2003 that he tested positive for three banned stimulants prior to United States Olympic Trials in 1988. Lewis, of course, won the 1988 100-meter gold medal after Canadian Ben Johnson tested positive for anabolic steroids, a development that brought disgrace to Johnson and adulation

Bryan E. Denham

2004-01-01

163

Psychosocial and Demographic Correlates of Drug Use in a Sample of HIV-Positive Adults Ages 50 and Older.  

PubMed

The prevalence of HIV among adults 50 and older in the USA is increasing as a result of improvements in treatment and detection of HIV infection. Substance use by this population has implications for physical and mental health outcomes. We examined patterns of demographics, mental health, and recent substance use in a diverse sample of heterosexual, bisexual, and gay adults 50 and older living with HIV/AIDS (PLWHA) in New York City. The most commonly used substances were cigarettes or alcohol; however, the majority of the sample did not report recent use of marijuana, poppers, or hard drugs (crystal methamphetamine, cocaine, crack, heroin, ecstasy, GHB, ketamine, and LSD or PCP). Statistically significant associations between substance use and psychological states (well-being and loneliness) were generally weak, and depression scores were not significantly related to use; instead, drug use was associated with gender/sexual orientation. The study observations support addressing substance use specific to subpopulations within PLWHA. PMID:23408281

Siconolfi, Daniel E; Halkitis, Perry N; Barton, Staci C; Kingdon, Molly J; Perez-Figueroa, Rafael E; Arias-Martinez, Vanessa; Karpiak, Stephen; Brennan-Ing, Mark

2013-12-01

164

Traceability of synthetic drugs by position-specific deuterium isotope ratio analysis: the case of Prozac and the fluoxetine generics.  

PubMed

Samples of fluoxetine of different origin were submitted to natural abundance 2H NMR spectroscopy. The deuterium content at the various sites of the molecule was found to depend on its synthetic history. Hints on the synthetic procedure can be obtained by comparison with standard compounds, whose synthesis is known. These preliminary results give an idea of the potential of site-specific isotope ratio analysis in the fight against patent infringement and drug counterfeiting. PMID:17920397

Brenna, Elisabetta; Fronza, Giovanni; Fuganti, Claudio

2007-09-02

165

Unprotected sex among HIV-positive injection drug-using women and their serodiscordant male partners: role of personal and partnership influences.  

PubMed

We investigated the characteristics of human immunodeficiency virus (HIV)-positive injection drug-using women who reported unprotected vaginal and/or anal sex with HIV-negative or unknown serostatus (serodiscordant) male partners. Of 426 female study participants, 370 were sexually active. Of these women, 39% (144/370) and 40% (148/370) reported vaginal and/or anal sex with serodiscordant main and casual partners, respectively. Sixty percent of women inconsistently used condoms with their serodiscordant main partners, whereas 53% did so with casual partners. In multivariate analysis, during sex with main partners, inconsistent condom users were less likely to feel confident about achieving safe sex (self-efficacy), personal responsibility for limiting HIV transmission, and that their partner supported safe sex. Inconsistent condom use was also more likely among women who held negative beliefs about condoms and in couplings without mutual disclosure of HIV status. Regarding sex with casual partners, inconsistent condom users were more likely to experience psychologic distress, engage in sex trading, but they were less likely to feel confident about achieving safe sex. These findings suggest that there are widespread opportunities for the sexual transmission of HIV from drug-using women to HIV-uninfected men, and that reasons vary by type of partnership. Multifaceted interventions that address personal, dyadic, and addiction problems are needed for HIV-positive injection drug-using women. PMID:16760799

Latka, Mary H; Metsch, Lisa R; Mizuno, Yulo; Tobin, Karin; Mackenzie, Sonia; Arnsten, Julia H; Gourevitch, Marc N

2006-06-01

166

Perceptions of community- and family-level injection drug user (IDU)- and HIV-related stigma, disclosure decisions and experiences with layered stigma among HIV-positive IDUs in Vietnam  

Microsoft Academic Search

This paper explores how perceived stigma and layered stigma related to injection drug use and being HIV-positive influence the decision to disclose one's HIV status to family and community and experiences with stigma following disclosure among a population of HIV-positive male injection drug users (IDUs) in Thai Nguyen, Vietnam. In qualitative interviews conducted between 2007 and 2008, 25 HIV-positive male

A. E. Rudolph; W. W. Davis; V. M. Quan; T. V. Ha; N. L. Minh; A. Gregowski; M. Salter; D. D. Celentano; V. Go

2012-01-01

167

Perceptions of community- and family-level injection drug user (IDU)- and HIV-related stigma, disclosure decisions and experiences with layered stigma among HIV-positive IDUs in Vietnam  

Microsoft Academic Search

This paper explores how perceived stigma and layered stigma related to injection drug use and being HIV-positive influence the decision to disclose one's HIV status to family and community and experiences with stigma following disclosure among a population of HIV-positive male injection drug users (IDUs) in Thai Nguyen, Vietnam. In qualitative interviews conducted between 2007 and 2008, 25 HIV-positive male

A. E. Rudolph; W. W. Davis; V. M. Quan; T. V. Ha; N. L. Minh; A. Gregowski; M. Salter; D. D. Celentano; V. Go

2011-01-01

168

Antiepileptic carbamazepine drug treatment induces alteration of membrane in red blood cells: possible positive effects on metabolism and oxidative stress.  

PubMed

Carbamazepine (CBZ) is an iminostilbene derivative commonly used for treatment of neuralgic pain and bipolar affective disorders. CBZ blood levels of treated patients are within the range of micromolar concentrations and therefore, significant interactions of this drug with erythrocytes are very likely. Moreover, the lipid domains of the cell membrane are believed to be one of the sites where iminostilbene derivatives exert their effects. The present study aimed to deeply characterize CBZ effects on erythrocytes, in order to identify extra and/or cytosolic cell targets. Our results indicate that erythrocyte morphological changes promoted by the drug, may be triggered by an alteration in band 3 functionality i.e. at the level of anionic flux. In addition, from a metabolic point of view this perturbation could be considered, at least in part, as a beneficial event because it could favour the CO2 elimination. Since lipid peroxidation, superoxide and free radical scavenging activities, caspase 3 activity and hemoglobin (Hb) functionality were not modified within the CBZ treated red blood cell (RBC), band 3 protein (B3) may well be a specific membrane target for CBZ and responsible for CBZ-induced toxic effects in erythrocytes. However some beneficial effects of this drug have been evidenced; among them an increased release of ATP and nitric oxide (NO) derived metabolites from erythrocytes to lumen, leading to an increased NO pool in the vasculature. In conclusion, these results indicate that CBZ, though considered responsible for toxic effects on erythrocytes, can also exhibit effects that at least in some conditions may be seen as beneficial. PMID:23246915

Ficarra, Silvana; Misiti, Francesco; Russo, Annamaria; Carelli-Alinovi, Cristiana; Bellocco, Ersilia; Barreca, Davide; Laganŕ, Giuseppina; Leuzzi, Ugo; Toscano, Giovanni; Giardina, Bruno; Galtieri, Antonio; Tellone, Ester

2012-12-12

169

Ovarian involvement by desmoplastic small round cell tumor with leydig cell hyperplasia showing an unusual immunophenotype (cytokeratin negative, calretinin and inhibin positive) mimicking poorly differentiated sertoli leydig cell tumor.  

PubMed

Desmoplastic small round cell tumor (DSRCT) is a rare aggressive tumor primarily involving serosal surfaces in adolescents and young men. Diagnosis is based on specific clinicomorphologic, immunohistochemical, and genetic features. We report here a variant of DSRCT involving the ovaries that mimics the Sertoli-Leydig cell tumor in a 21-year-old woman complaining of abdominal pain. Abdominal ultrasonography and computed tomography showed a right adnexal mass. She had a slightly raised serum CA-125 level. Frozen section examination identified the right ovarian mass as a poorly differentiated Sertoli-Leydig cell tumor. The surgically resected tumor and left ovary and omentum implants found during laparoscopy were diagnosed as DSRCT with Leydig cell hyperplasia. Immunohistochemically, the tumor cells were negative for epithelial markers but were positive for calretinin and inhibin. The patient is still undergoing chemotherapy at 8 months after initial presentation with partial response. This case showed that DSRCT with unusual immunohistochemical profiles and Leydig cells hyperplasia pose a diagnostic challenge. Molecular genetic techniques may help in these cases. PMID:19851210

Engohan-Aloghe, Corinne; Aubain Sommerhausen, Nicolas de Saint; Noël, Jean-Christophe

2009-11-01

170

Social-structural contexts of needle and syringe sharing behaviours of HIV-positive injecting drug users in Manipur, India: a mixed methods investigation  

PubMed Central

Background Few investigations have assessed risk behaviours and social-structural contexts of risk among injecting drug users (IDUs) in Northeast India, where injecting drug use is the major route of HIV transmission. Investigations of risk environments are needed to inform development of effective risk reduction interventions. Methods This mixed methods study of HIV-positive IDUs in Manipur included a structured survey (n = 75), two focus groups (n = 17), seven in-depth interviews, and two key informant interviews. Results One-third of survey participants reported having shared a needle/syringe in the past 30 days; among these, all the men and about one-third of the women did so with persons of unknown HIV serostatus. A variety of social-structural contextual factors influenced individual risk behaviours: barriers to carrying sterile needles/syringes due to fear of harassment by police and "anti-drug" organizations; lack of sterile needles/syringes in drug dealers' locales; limited access to pharmacy-sold needles/syringes; inadequate coverage by needle and syringe programmes (NSPs); non-availability of sterile needles/syringes in prisons; and withdrawal symptoms superseding concern for health. Some HIV-positive IDUs who shared needles/syringes reported adopting risk reduction strategies: being the 'last receiver' of needles/syringes and not a 'giver;' sharing only with other IDUs they knew to be HIV-positive; and, when a 'giver,' asking other IDUs to wash used needles/syringes with bleach before using. Conclusions Effective HIV prevention and care programmes for IDUs in Northeast India may hinge on several enabling contexts: supportive government policy on harm reduction programmes, including in prisons; an end to harassment by the police, army, and anti-drug groups, with education of these entities regarding harm reduction, creation of partnerships with the public health sector, and accountability to government policies that protect IDUs' human rights; adequate and sustained funding for NSPs to cover all IDU populations, including prisoners; and non-discriminatory access by IDUs to affordable needles/syringes in pharmacies.

2011-01-01

171

CALM/AF10-positive leukemias show upregulation of genes involved in chromatin assembly and DNA repair processes and of genes adjacent to the breakpoint at 10p12.  

PubMed

The t(10;11)(p12;q14) is a recurring chromosomal translocation that gives rise to the CALM/AF10 fusion gene, which is found in acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma. We analyzed the fusion transcripts in 20 new cases of CALM/AF10-positive leukemias, and compared the gene expression profile of 10 of these to 125 patients with other types of leukemia and 10 normal bone marrow samples. Based on gene set enrichment analyses, the CALM/AF10-positive samples showed significant upregulation of genes involved in chromatin assembly and maintenance and DNA repair process, and downregulation of angiogenesis and cell communication genes. Interestingly, we observed a striking upregulation of four genes located immediately centromeric to the break point of the t(10;11)(p12;q14) on 10p12 (COMMD3 (COMM domain containing 3), BMI1 (B lymphoma Mo-MLV insertion region 1 homolog), DNAJC1 (DnaJ (Hsp40) homolog subfamily C member 1) and SPAG6 (sperm associated antigen 6)). We also conducted semiquantitative reverse transcriptase-PCR analysis on leukemic blasts from a murine CALM/AF10 transplantation model that does not have the translocation. Commd3, Bmi1 and Dnajc1, but not Spag6 were upregulated in these samples. These results strongly indicate that the differential regulation of these three genes is not due to the break point effect but as a consequence of the CALM/AF10 fusion gene expression, though the mechanism of regulation is not well understood. PMID:22064352

Mulaw, M A; Krause, A; Krause, A J; Deshpande, A J; Krause, L F; Rouhi, A; La Starza, R; Borkhardt, A; Buske, C; Mecucci, C; Ludwig, W-D; Lottaz, C; Bohlander, S K

2011-11-08

172

Are feelings of responsibility to limit the sexual transmission of HIV associated with safer sex among HIV-positive injection drug users?  

PubMed

We developed a scale among HIV-positive injection drug users (IDUs) to measure self-perceived responsibility to limit HIV transmission during sex. We describe the characteristics of HIV-positive IDUs (n=1114, 62% male, HIV-positive for 9 years on average) who felt responsible for protecting their sexual partners from HIV and evaluated whether such feelings were associated with safer sexual practices. Using this scale (Cronbach alpha=0.83) and audio computer-assisted self-interviewing technology, 75% of this sample felt responsible for protecting their sexual partners from HIV. In cross-sectional multivariate analysis, HIV-positive IDUs who felt responsible were those with greater HIV knowledge (adjusted odds ratio [95% confidence interval]: 1.74 [1.26 to 2.40]), perceived social support (1.77 [1.28 to 2.44]), self-efficacy for safely injecting (1.41 [1.02 to 1.94]), and self-efficacy for using condoms (1.92 [1.38 to 2.68]). Feeling responsible was associated with having relatively fewer sex partners (<10 vs. >or=10, 0.57 [0.34 to 0.96]) and a lower odds of unprotected sex (0.63 [0.45 to 0.89]) but was not associated with safer injection practices. Feelings of responsibility did not vary by demographic characteristics, suggesting that prevention messages that encourage HIV-positive people to play a role in curbing HIV transmission may be acceptable to many HIV-positive IDUs. Working with HIV-positive IDUs to increase or reinforce feelings of responsibility may reduce the sexual transmission of HIV. PMID:18089989

Latka, Mary H; Mizuno, Yuko; Wu, YingFeng; Tobin, Karin E; Metsch, Lisa R; Frye, Victoria; Gómez, Cynthia A; Arnsten, Julia H

2007-11-01

173

[Effect of GABA-positive drugs on the background and superior sagittalis sinus-electrostimulated activity of neurons in the nucleus trigeminalis caudalis of rats].  

PubMed

There is extensive clinical evidence for the high efficacy of GABA-ergic drugs in prophylactic and abortive treatment of migraine and cluster headache, while the mechanisms of anticephalgic drugs action are not clear, in particular, because of insufficient number of investigations on experimental headache models. In this study, the influence of baclofen (i.v.) in doses 2.5, 5, 10, and 15 mg/kg and valproate (i.v.) in doses 25, 50, 100, and 200 mg/kg on the background activity of the trigeminal nucleus caudalis neurons and that evoked by electrical stimulation of the superior sagittalis sinus was investigated in series of acute experiments on rats. It is established, that baclofen and valproate reduce both the background and evoked activity of trigeminal complex neurons in dose-dependent manner, thus determining the role of GABA-A and GABA-B receptors in realization of this effect. These results provide experimental basis for explanation of the clinical efficacy of the GABA-positive drugs in vascular headaches. PMID:19093363

Sokolov, A Iu; Amelin, A V; Ignatov, Iu D; Panteleev, S S

174

Differential Predictors of Medication Adherence in HIV: Findings from a Sample of African American and Caucasian HIV-Positive Drug-Using Adults  

PubMed Central

Abstract Modest or even occasional nonadherence to combined antiretroviral therapy (cART) can result in adverse clinical outcomes. African Americans demonstrate lower rates of adherence than Caucasians or Latinos. Identifying factors that influence medication adherence among African Americans is a critical step toward reducing HIV/AIDS disease progression and mortality. In a sample of 181 African American (n=144) and Caucasian (n=37) HIV-positive drug-using individuals [age (M=42.31; SD=6.6) education (M=13.41; SD=2.1)], we examined the influence of baseline drug use, literacy, neurocognition, depression, treatment-specific social support, and patient satisfaction with health care provider on medication adherence averaged over the course of 6 months (study dates 2002–2006). Our findings suggest differential baseline predictors of medication adherence for African Americans and Caucasians, such that patient satisfaction with provider was the strongest predictor of follow-up medication adherence for African Americans whereas for Caucasians depressive symptoms and treatment-specific social support were predictive of medication adherence (after controlling for duration of drug use).

Moizel, Jennifer; Panos, Stella E.; Patel, Sapna M.; Byrd, Desiree A.; Myers, Hector F.; Wyatt, Gail E.; Hinkin, Charles H.

2012-01-01

175

Differential predictors of medication adherence in HIV: findings from a sample of African American and Caucasian HIV-positive drug-using adults.  

PubMed

Modest or even occasional nonadherence to combined antiretroviral therapy (cART) can result in adverse clinical outcomes. African Americans demonstrate lower rates of adherence than Caucasians or Latinos. Identifying factors that influence medication adherence among African Americans is a critical step toward reducing HIV/AIDS disease progression and mortality. In a sample of 181 African American (n=144) and Caucasian (n=37) HIV-positive drug-using individuals [age (M=42.31; SD=6.6) education (M=13.41; SD=2.1)], we examined the influence of baseline drug use, literacy, neurocognition, depression, treatment-specific social support, and patient satisfaction with health care provider on medication adherence averaged over the course of 6 months (study dates 2002-2006). Our findings suggest differential baseline predictors of medication adherence for African Americans and Caucasians, such that patient satisfaction with provider was the strongest predictor of follow-up medication adherence for African Americans whereas for Caucasians depressive symptoms and treatment-specific social support were predictive of medication adherence (after controlling for duration of drug use). PMID:22889235

Thames, April D; Moizel, Jennifer; Panos, Stella E; Patel, Sapna M; Byrd, Desiree A; Myers, Hector F; Wyatt, Gail E; Hinkin, Charles H

2012-08-13

176

Using Electronic Drug Monitor Feedback to Improve Adherence to Antiretroviral Therapy Among HIV-Positive Patients in China  

Microsoft Academic Search

Effective antiretroviral therapy (ART) requires excellent adherence. Little is known about how to improve ART adherence in\\u000a many HIV\\/AIDS-affected countries, including China. We therefore assessed an adherence intervention among HIV-positive patients\\u000a in southwestern China. Eighty subjects were enrolled and monitored for 6 months. Sixty-eight remaining subjects were randomized\\u000a to intervention\\/control arms. In months 7–12, intervention subjects were counseled using EDM feedback;

Lora L. Sabin; Mary Bachman DeSilva; Davidson H. Hamer; Keyi Xu; Jianbo Zhang; Tao Li; Ira B. Wilson; Christopher J. Gill

2010-01-01

177

Association between heroin use, needle sharing and tattoos received in prison with hepatitis B and C positivity among street-recruited injecting drug users in New Mexico, USA.  

PubMed

This study aimed to assess the seroprevalence and risk factors for hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV-1 infections among injecting drug users (IDU) in New Mexico. Serological and behavioural surveys were conducted in conjunction with street-based outreach, education and HIV counselling and testing. High rates of antibody positivity for HCV (82.2%) and HBV (61.1%), and a low rate for HIV (0.5%) were found. In multivariate analyses, both HBV and HCV infection were positively associated with increasing age, increasing years of injection and heroin use. Receipt of a tattoo in prison/jail was associated with HBV (odds ratio = 2.3, 95% confidence interval 1.4, 3.8) and HCV (OR = 3.4, 95% CI = 1.6, 7.5) infections. Prevention of bloodborne pathogens among IDUs should focus on young users, early in their drug use experience. Studies examining the relationship between tattooing and HBV and HCV infection are needed as are efforts to promote sterile tattooing, in prisons and elsewhere. PMID:11811881

Samuel, M C; Doherty, P M; Bulterys, M; Jenison, S A

2001-12-01

178

SLC6A14 (ATB0,+) Protein, a Highly Concentrative and Broad Specific Amino Acid Transporter, Is a Novel and Effective Drug Target for Treatment of Estrogen Receptor-positive Breast Cancer*  

PubMed Central

SLC6A14, also known as ATB0,+, is an amino acid transporter with unique characteristics. It transports 18 of the 20 proteinogenic amino acids. However, this transporter is expressed only at low levels in normal tissues. Here, we show that the transporter is up-regulated specifically in estrogen receptor (ER)-positive breast cancer, demonstrable with primary human breast cancer tissues and human breast cancer cell lines. SLC6A14 is an estrogen/ER target. The transport features of SLC6A14 include concentrative transport of leucine (an activator of mTOR), glutamine (an essential amino acid for nucleotide biosynthesis and substrate for glutaminolysis), and arginine (an essential amino acid for tumor cells), suggesting that ER-positive breast cancer cells up-regulate SLC6A14 to meet their increased demand for these amino acids. Consequently, treatment of ER-positive breast cancer cells in vitro with ?-methyl-dl-tryptophan (?-MT), a selective blocker of SLC6A14, induces amino acid deprivation, inhibits mTOR, and activates autophagy. Prolongation of the treatment with ?-MT causes apoptosis. Addition of an autophagy inhibitor (3-methyladenine) during ?-MT treatment also induces apoptosis. These effects of ?-MT are specific to ER-positive breast cancer cells, which express the transporter. The ability of ?-MT to cause amino acid deprivation is significantly attenuated in MCF-7 cells, an ER-positive breast cancer cell line, when SLC6A14 is silenced with shRNA. In mouse xenograft studies, ?-MT by itself is able to reduce the growth of the ER-positive ZR-75-1 breast cancer cells. These studies identify SLC6A14 as a novel and effective drug target for the treatment of ER-positive breast cancer.

Karunakaran, Senthil; Ramachandran, Sabarish; Coothankandaswamy, Veena; Elangovan, Selvakumar; Babu, Ellappan; Periyasamy-Thandavan, Sudharsan; Gurav, Ashish; Gnanaprakasam, Jaya P.; Singh, Nagendra; Schoenlein, Patricia V.; Prasad, Puttur D.; Thangaraju, Muthusamy; Ganapathy, Vadivel

2011-01-01

179

Perceptions of community- and family-level injection drug user (IDU)- and HIV-related stigma, disclosure decisions and experiences with layered stigma among HIV-positive IDUs in Vietnam.  

PubMed

This paper explores how perceived stigma and layered stigma related to injection drug use and being HIV-positive influence the decision to disclose one's HIV status to family and community and experiences with stigma following disclosure among a population of HIV-positive male injection drug users (IDUs) in Thai Nguyen, Vietnam. In qualitative interviews conducted between 2007 and 2008, 25 HIV-positive male IDUs described layered stigma in their community but an absence of layered stigma within their families. These findings suggest the importance of community-level HIV prevention interventions that counter stigma and support families caring for HIV-positive relatives. PMID:21777075

Rudolph, A E; Davis, W W; Quan, V M; Ha, T V; Minh, N L; Gregowski, A; Salter, M; Celentano, D D; Go, V

2011-07-21

180

Pharmacodynamic Modeling of Clarithromycin against Macrolide-Resistant [PCR-Positive mef(A) or erm(B)] Streptococcus pneumoniae Simulating Clinically Achievable Serum and Epithelial Lining Fluid Free-Drug Concentrations  

Microsoft Academic Search

The association between macrolide resistance mechanisms and clinical outcomes remains understudied. The present study, using an in vitro pharmacodynamic model, assessed clarithromycin (CLR) activity against mef(A)-positive and erm(B)-negative Streptococcus pneumoniae isolates by simulating free-drug concentrations in serum and both total (protein-bound and free) and free drug in epithelial lining fluid (ELF). Five mef(A)- positive and erm(B)-negative strains, one mef(A)-negative and

Ayman M. Noreddin; Danielle Roberts; Kim Nichol; Aleksandra Wierzbowski; Daryl J. Hoban; George G. Zhanel

2002-01-01

181

New Drug Approval: FDA Needs to Enhance Its Oversight of Drugs Approved on the Basis of Surrogate Endpoints.  

National Technical Information Service (NTIS)

Before approving a drug, the Food and Drug Administration (FDA) assesses a drug's effectiveness. This assessment may be based on evidence showing that a drug has a positive impact on a surrogate endpoint--a laboratory measure, such as blood pressure--inst...

2009-01-01

182

Anal human papillomavirus infection in a street-based sample of drug using HIV-positive men.  

PubMed

HIV facilitates an increase in human papillomavirus (HPV)-associated conditions. HIV-positive men living in a substance use context in Los Angeles, USA, were recruited using respondent-driven sampling, completed a questionnaire and had biological samples including an anal HPV swab taken. A total of 316 evaluable men were enrolled in the study. The prevalence of any HPV, high-risk (HR) infection and multiple-type infection was highest for men who have sex with men (MSM) (93.9%, 64.6% and 29.7%, respectively). When any HPV and HR-HPV prevalence in all men was stratified by age, the youngest group had 100% and 68.2% prevalence, respectively, with similarly high rates maintained up to age 49 years. The individual's use of alcohol, marijuana, cocaine, methamphetamine or heroin was not significantly associated with anal HPV detection. In this marginalized population, high prevalence rates of anal HPV and HR-HPV occurring over a wide age range may increase the individual's risk for anal dysplasia and anal cancer. PMID:22581874

Cranston, R D; Murphy, R; Weiss, R E; Da Costa, M; Palefsky, J; Shoptaw, S; Gorbach, P M

2012-03-01

183

Using Electronic Drug Monitor Feedback to Improve Adherence to Antiretroviral Therapy Among HIV-Positive Patients in China  

PubMed Central

Effective antiretroviral therapy (ART) requires excellent adherence. Little is known about how to improve ART adherence in many HIV/AIDS-affected countries, including China. We therefore assessed an adherence intervention among HIV-positive patients in southwestern China. Eighty subjects were enrolled and monitored for 6 months. Sixty-eight remaining subjects were randomized to intervention/control arms. In months 7–12, intervention subjects were counseled using EDM feedback; controls continued with standard of care. Among randomized subjects, mean adherence and CD4 count were 86.8 vs. 83.8% and 297 vs. 357 cells/?l in intervention vs. control subjects, respectively. At month 12, among 64 subjects who completed the trial, mean adherence had risen significantly among intervention subjects to 96.5% but remained unchanged in controls. Mean CD4 count rose by 90 cells/?l and declined by 9 cells/?l among intervention and control subjects, respectively. EDM feedback as a counseling tool appears promising for management of HIV and other chronic diseases.

DeSilva, Mary Bachman; Hamer, Davidson H.; Xu, Keyi; Zhang, Jianbo; Li, Tao; Wilson, Ira B.; Gill, Christopher J.

2009-01-01

184

Weakening of negative relative to positive associations with cocaine-paired cues contributes to cue-induced responding after drug removal  

PubMed Central

Cocaine has been shown to have initial positive (euphoric) and delayed negative (anxiogenic) effects in both humans and animals. Cocaine-paired cues are consequently imbued with mixed positive and negative associations. The current study examines the relative roles of these dual associations in the enhanced drug-seeking observed upon presentation of cocaine-paired cues. Rats ran a straight alley once/day for a single i.v. injection of cocaine (1.0 mg/kg/inj) in the presence of a distinctive olfactory cue (scented cotton swabs placed under the apparatus). An alternate scent was presented in a separate cage 2-hr prior to runway testing. After 15 trials/days, the scents and cocaine reinforcer were removed and a series of extinction trials (lasting for one or three weeks) was initiated. Immediately following extinction, runway responding was tested during a single trial in the presence of the cocaine-paired or non-paired cue. As previously reported, while subjects initiated responding faster over trials (reduced latencies to leave the start box), they exhibited a progressive increase in approach-avoidance conflict behavior (“retreats”) regarding goal-box entry, reflecting cocaine’s dual positive + negative effects. Once established, retreat behaviors persisted over the course of 6 and 20 days of extinction. However, both run times and retreats decreased in response to presentation of the cocaine-paired but not the non-paired scent. These data suggest that, after reinforcer removal, cue-induced cocaine-seeking stems in part from a reduction in approach-avoidance conflict; i.e., a greater weakening of the negative relative to the positive associations that animals form with cocaine-paired stimuli.

Su, Zu-In; Kichaev, Gleb; Wenzel, Jennifer; Ben-Shahar, Osnat; Ettenberg, Aaron

2011-01-01

185

Endogenous and Transplanted Small Hepatocytes in Retrorsine-treated/Partially Hepatectomized Rat Liver Show Differences in Growth, Phenotype, and Proximity to Clusters of ?-Glutamyl Transpeptidase-positive Host Hepatocytes  

PubMed Central

In the present report, we have compared the phenotype and growth of small hepatocyte progenitors (SHPs) induced by retrorsine/partial hepatectomy (R/PH) and small hepatocytes (SHs) isolated from normal adult liver. SHs were isolated by a combination of differential centrifugation and Percoll isodensity fractionation from a liver cell suspension prepared by collagenase perfusion of a dipeptidyl peptidase IV (DPPIV)–positive Fischer F344 rat liver. Following further purification by flow cytometry, the SH-R3 fraction was transplanted via the portal vein into R/PH–treated, DPPIV-negative Fischer F344 rats. Frozen sections from tissue harvested at 5, 7, and 21 days after transplantation were analyzed by indirect immunofluorescence to compare the phenotypic characteristics of colonies formed by exogenous SH-R3s and endogenous SHPs. Colonies of transplanted SHs and endogenous SHPs displayed similar histologies and phenotypes but were distinguished from surrounding hepatocytes by their elevated expression of transferrin receptor. SH-R3 colonies were frequently located within clusters of ?-glutamyl transpeptidase–positive host hepatocytes. Although significantly smaller at 5 and 7 days after PH, by day 21, SH-R3 colonies were similar in size to those formed by SHPs. The present results suggest that endogenous SHPs are derived, at least in part, from SHPs. (J Histochem Cytochem 58:61–72, 2010)

Tateno, Chise; Carreiro, Marie P.; Hixson, Douglas C.

2010-01-01

186

Towards estimation of HIV-1 date of infection: a time-continuous IgG-model shows that seroconversion does not occur at the midpoint between negative and positive tests.  

PubMed

Estimating date of infection for HIV-1-infected patients is vital for disease tracking and informed public health decisions, but is difficult to obtain because most patients have an established infection of unknown duration at diagnosis. Previous studies have used HIV-1-specific immunoglobulin G (IgG) levels as measured by the IgG capture BED enzyme immunoassay (BED assay) to indicate if a patient was infected recently, but a time-continuous model has not been available. Therefore, we developed a logistic model of IgG production over time. We used previously published metadata from 792 patients for whom the HIV-1-specific IgG levels had been longitudinally measured using the BED assay. To account for patient variability, we used mixed effects modeling to estimate general population parameters. The typical patient IgG production rate was estimated at r?=?6.72[approximate 95% CI 6.17,7.33]×10(-3) OD-n units day(-1), and the carrying capacity at K?=?1.84[1.75,1.95] OD-n units, predicting how recently patients seroconverted in the interval (?) t?=?(31,711) days. Final model selection and validation was performed on new BED data from a population of 819 Swedish HIV-1 patients diagnosed in 2002-2010. On an appropriate subset of 350 patients, the best model parameterization had an accuracy of 94% finding a realistic seroconversion date. We found that seroconversion on average is at the midpoint between last negative and first positive HIV-1 test for patients diagnosed in prospective/cohort studies such as those included in the training dataset. In contrast, seroconversion is strongly skewed towards the first positive sample for patients identified by regular public health diagnostic testing as illustrated in the validation dataset. Our model opens the door to more accurate estimates of date of infection for HIV-1 patients, which may facilitate a better understanding of HIV-1 epidemiology on a population level and individualized prevention, such as guidance during contact tracing. PMID:23613753

Skar, Helena; Albert, Jan; Leitner, Thomas

2013-04-16

187

Towards Estimation of HIV-1 Date of Infection: A Time-Continuous IgG-Model Shows That Seroconversion Does Not Occur at the Midpoint between Negative and Positive Tests  

PubMed Central

Estimating date of infection for HIV-1-infected patients is vital for disease tracking and informed public health decisions, but is difficult to obtain because most patients have an established infection of unknown duration at diagnosis. Previous studies have used HIV-1-specific immunoglobulin G (IgG) levels as measured by the IgG capture BED enzyme immunoassay (BED assay) to indicate if a patient was infected recently, but a time-continuous model has not been available. Therefore, we developed a logistic model of IgG production over time. We used previously published metadata from 792 patients for whom the HIV-1-specific IgG levels had been longitudinally measured using the BED assay. To account for patient variability, we used mixed effects modeling to estimate general population parameters. The typical patient IgG production rate was estimated at r?=?6.72[approximate 95% CI 6.17,7.33]×10?3 OD-n units day?1, and the carrying capacity at K?=?1.84[1.75,1.95] OD-n units, predicting how recently patients seroconverted in the interval ?t?=?(31,711) days. Final model selection and validation was performed on new BED data from a population of 819 Swedish HIV-1 patients diagnosed in 2002–2010. On an appropriate subset of 350 patients, the best model parameterization had an accuracy of 94% finding a realistic seroconversion date. We found that seroconversion on average is at the midpoint between last negative and first positive HIV-1 test for patients diagnosed in prospective/cohort studies such as those included in the training dataset. In contrast, seroconversion is strongly skewed towards the first positive sample for patients identified by regular public health diagnostic testing as illustrated in the validation dataset. Our model opens the door to more accurate estimates of date of infection for HIV-1 patients, which may facilitate a better understanding of HIV-1 epidemiology on a population level and individualized prevention, such as guidance during contact tracing.

Skar, Helena; Albert, Jan; Leitner, Thomas

2013-01-01

188

Frequency of positive XmnIGgamma polymorphism and coinheritance of common alpha thalassemia mutations do not show statistically significant difference between thalassemia major and intermedia cases with homozygous IVSII-1 mutation.  

PubMed

From 362 thalassemia cases referred to adult thalassemia clinic of the Iranian blood transfusion organization (IBTO) for genotyping, 103 cases (28.5%) had a common primary disease factor, IVSII-1 mutation in homozygous state. 61 (59.2%) of these individuals represented thalassemia major and 42 (40.8%) thalassemia intermedia clinical phenotype. To re-evaluate our current diagnostic criteria, XmnI(G)gamma polymorphism and coexistence of alpha thalassemia mutations, frequently recalled as important factors modifying the clinical phenotype of homozygous beta zero thalassemia cases in our country, were examined in both groups. No statistically significant difference in the frequency of positive XmnI(G)gamma polymorphism was observed between thalassemia intermedia and thalassemia major patients. Double gene deletion --(Med) was observed in only one thalassemia major case, while -a(3.7) in heterozygous state (-a(3.7)/aa) was identified in 6 (9.8%) of thalassemia major and 8 (19%) of thalassemia intermedia patients. -a(4.2) was observed in only one thalassemia major case. No statistically significant difference in the frequency of coinheritance of alpha thalassemia was observed between the two groups. These results imply that other interacting mechanisms which modify the phenotype of thalassemia patients is still in the dark in our current diagnostic criteria of thalassemia. PMID:19892574

Neishabury, Maryam; Azarkeivan, Azita; Najmabadi, Hossein

2009-11-04

189

Prevalence of drug resistance and culture-positive rate among microorganisms isolated from patients with ocular infections over a 4-year period  

PubMed Central

Purpose To investigate the microbial isolates from patients with ocular infections and the trend in the emergence of levofloxacin-resistant strains over the past four years from 2006 to 2009 retrospectively. Patients and methods The subjects were 242 patients with ocular infections or traumas treated in our hospital including outpatients, inpatients, and emergency room patients. Most of them needed urgent care presenting with eye complaints, traumas, or decreased vision. Clinical samples were obtained from discharges, corneal, conjunctival tissues or vitreous fluid or aqueous humor, and cultured. Items for assessment included the patient’s age, the diagnosis, the prevalence of isolated bacteria, and the results of susceptibility tests for levofloxacin (LVFX) cefamezin (CEZ), gentamicin (GM) and vancomycin. This information was obtained from the patients’ medical records. Results There were 156 male patients and 86 female patients who were aged from 2 months old to 94 years old and mean age was 56.8 ± 24.2 years. Of the 242 patients, 78 (32.2%) had positive cultures. The culture-positive rate was significantly higher in male patients than female in total (P = 0.002) and in patients with corneal perforation (P = 0.005). Corneal perforation was the highest culture-positive rate (60.0%), followed by orbital cellulitis (56.5%), blepharitis (50.0%), dacryoadenitis (45.5%), conjunctivitis (38.2%), infectious corneal ulcer (28.5%) and endophthalmitis (24.7%). LVFX-resistant strains accounted for 40 out of a total of 122 strains (32.8%), and the minimum inhibitory concentration (MIC) was significantly higher in LVFX and GM compared with the other antibiotics. There were no vancomycin-resistant strains. Conclusion Attention should be paid to a possible future increase of strains with resistance to LVFX, as commonly prescribed ocular antibiotics bring emergence of resistant bacteria. Although no vancomycin-resistant strains were isolated this drug should be reserved as the last resort, in order to prevent the emergence of vancomycin resistance.

Shimizu, Yusuke; Toshida, Hiroshi; Honda, Rio; Matsui, Asaki; Ohta, Toshihiko; Asada, Yousuke; Murakami, Akira

2013-01-01

190

Television Quiz Show Simulation  

ERIC Educational Resources Information Center

|This article explores the simulation of four television quiz shows for students in China studying English as a foreign language (EFL). It discusses the adaptation and implementation of television quiz shows and how the students reacted to them.|

Hill, Jonnie Lynn

2007-01-01

191

Positive and negative electrospray LC-MS-MS methods for quantitation of the antiparasitic endectocide drugs, abamectin, doramectin, emamectin, eprinomectin, ivermectin, moxidectin and selamectin in milk.  

PubMed

Avermectin endectocides are used for the treatment of cattle against a variety of nematode and arthropod parasites, and consequently may appear in milk after normal or off-label use. The compounds abamectin, doramectin, and ivermectin, contain only C, H and O and may be expected to be detected by LC-MS in negative ion mode. The others contain nitrogen in addition and would be expected to be preferentially ionized in positive mode. The use of positive ion and negative ion methods with electrospray LC-MS-MS were compared. Using negative ion the compounds abamectin, doramectin, ivermectin, emamectin, eprinomectin, and moxidectin gave a curvilinear response and were quantified in raw milk by LC-MS-MS with a triethylamine-acetonitrile buffer over the concentration range 1-60 ppb (microg/kg) using selamectin as the internal standard. The limits of detection (LOD) were between 0.19 ppb (doramectin) and 0.38 ppb (emamectin). The compounds gave maximum sensitivity with positive ionisation from a formic acid-ammonium formate-acetonitrile buffer and were detected in milk (LC-MS-MS) also with a curvilinear response over the range 0.5-60 ppb. Although the positive ion signals were larger, with somewhat lower limits of detection (LOD between 0.06 ppb (doramectin) and 0.32 ppb (moxidectin) the negative ion procedure gave a more linear response and more consistent results. Comparison of spiked samples in the range 2-50 ppb showed a high degree of correlation between the two methods. PMID:17129769

Durden, David A

2006-11-28

192

A Holographic Road Show.  

ERIC Educational Resources Information Center

|Describes the viewing sessions and the holograms of a holographic road show. The traveling exhibits, believed to stimulate interest in physics, include a wide variety of holograms and demonstrate several physical principles. (GA)|

Kirkpatrick, Larry D.; Rugheimer, Mac

1979-01-01

193

The Diane Rehm Show  

NSDL National Science Digital Library

The Diane Rehm Show has its origins in a mid-day program at WAMU in Washington, D.C. Diane Rehm came on to host the program in 1979, and in 1984 it was renamed "The Diane Rehm Show". Over the past several decades, Rehm has played host to hundreds of guests, include Archbishop Desmond Tutu, Julie Andrews, and President Bill Clinton. This website contains an archive of her past programs, and visitors can use the interactive calendar to look through past shows. Those visitors looking for specific topics can use the "Topics" list on the left-hand side of the page, or also take advantage of the search engine. The show has a number of social networking links, including a Facebook page and a Twitter feed.

194

Positive Proof.  

ERIC Educational Resources Information Center

Presents experiments which show that in electrostatics there are logical reasons for describing charged materials as positive or negative. Indicates that static and current electricity are not separate areas of physics. Diagrams of experiments and circuits are included. (RT)

Auty, Geoffrey

1988-01-01

195

Exceptional Leadership: Allow Positive Psychology to Show you the Way  

Microsoft Academic Search

The recent events of the Atlanta Falcon's star quarterback Michael Vick are a strong reminder of just how essential character is to leadership. Vick is allegedly guilty of promoting\\/sponsoring dog fighting, along with general cruelty to animals. He has been indicted by the federal government. Anyone who knows football would not question Vick's talent as a quarterback. Some consider him

Johnny Parker

196

Do Elephants Show Empathy?  

Microsoft Academic Search

Elephants show a rich social organization and display a number of unusual traits. In this paper, we analyse reports collected over a thirty-five year period, describing behaviour that has the potential to reveal signs of empathic understanding. These include coalition formation, the offering of protection and comfort to others, retrieving and 'babysitting' calves, aiding individuals that would otherwise have difficulty

Lucy A. Bates; Phyllis C. Lee; Norah Njiraini; Joyce H. Poole; Katito Sayialel; Soila Sayialel; Cynthia J. Moss; Richard W. Byrne

2008-01-01

197

What Do Maps Show?  

ERIC Educational Resources Information Center

|This curriculum packet, appropriate for grades 4-8, features a teaching poster which shows different types of maps (different views of Salt Lake City, Utah), as well as three reproducible maps and reproducible activity sheets which complement the maps. The poster provides teacher background, including step-by-step lesson plans for four geography…

Geological Survey (Dept. of Interior), Reston, VA.

198

Shakespearean Slide Shows.  

ERIC Educational Resources Information Center

|Presents a condensed method for involving students in the kind of theatrical problem-solving that transforms a script to a play. Describes how to incorporate a "human slide show" into the class. Notes that students must read plays not just to understand events, but to make artistic choices about how to stage the action so that an audience…

Flynn, Rosalind M.

2002-01-01

199

Btu accounting: Showing results  

Microsoft Academic Search

In the preceding article in this series last month, the author showed how to calculate the energy consumed to make a pound of product. To realize a payoff, however, the results must be presented in graphs or tables that clearly display what has happened. They must call attention to plant performance and ultimately lead to more efficient use of energy.

1994-01-01

200

Stage a Water Show  

ERIC Educational Resources Information Center

In the author's book titled "The Incredible Water Show," the characters from "Miss Alaineus: A Vocabulary Disaster" used an ocean of information to stage an inventive performance about the water cycle. In this article, the author relates how she turned the story into hands-on science teaching for real-life fifth-grade students. The author also…

Frasier, Debra

2008-01-01

201

ISU Demonstration Road Show  

NSDL National Science Digital Library

The Idaho State University Department of Physics conducts science demonstration shows at SE Idaho schools. Four different presentations are currently available; "Forces and Motion", "States of Matter", "Electricity and Magnetism", and "Sound and Waves". Student activities and descriptions of the demonstrated material are also provided.

Shropshire, Steven

2004-04-06

202

Viewing television talk shows  

Microsoft Academic Search

We examined how motivation, audience activity, and attitudes influenced the likelihood of watching societal?issue and relational topics on television talk programs. Path analysis supported differences in ritualized and instrumental motives for watching talk shows. Information and exciting?entertainment motivation predicted greater’ realism of, affinity with, involvement with, and intent to watch talk television. Pass?time motivation predicted reduced affinity with and intent

Alan M. Rubin; Mary M. Step

1997-01-01

203

The Truman Show  

Microsoft Academic Search

The Truman Show is hardly a film you would automatically speak about as a game. At first glance, it is tempting to interpret the story of\\u000a Truman Burbank — his perpetual subjection to the artificial (televisual) world of Seahaven and its gargantuan reality TV project,\\u000a his eventual escape from the “OmniCam Ecosphere” building and the paternalistic surveillance of director Christof

Rolf F. Nohr

204

21 CFR 1314.150 - Order To show cause.  

Code of Federal Regulations, 2013 CFR

...cause. 1314.150 Section 1314.150 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE RETAIL SALE OF SCHEDULED LISTED CHEMICAL PRODUCTS Order to Show Cause § 1314.150 Order To show cause....

2013-04-01

205

NPR: The Picture Show  

NSDL National Science Digital Library

National Public Radio's "The Picture Show" photo blog is a great way to avoid culling through the thousands of less interesting and engaging photographs on the web. With a dedicated team of professionals, this blog brings together different posts that profile various sets of photographs that cover 19th century war in Afghanistan, visual memories of WWII, unpublished photographs of JFK's presidential campaign, and abandoned buildings on the islands in Boston Harbor. Visitors can search through previous posts, use social media features to share the photo features with friends, and also sign up to receive new materials via their RSS feed. There's quite a nice mix of material here, and visitors can also comment on the photos and recommend the collection to friends and others.

206

Egg: the Arts Show  

NSDL National Science Digital Library

"Egg is a new TV show about people making art across America" from PBS. This accompanying Website presents excerpts from sixteen episodes of the series, with three more "hatching soon," such as Close to Home, profiling three photographers: Jeanine Pohlhaus, whose pictures document her father's struggle with mental illness; Gregory Crewdson's photos of Lee, Massachusetts; and Joseph Rodriguez's photos of Hispanics in New York City. Excerpts include video clips, gallery listings where the artists' work can be seen, and short interviews with artists. Some episodes also offer "peeps," glimpses of material not shown on TV, such as the Space episode's peep, Shooting Stars, that provides directions for astrophotography, taking photographs of star trails. Other sections of the site are airdates, for local listings; see and do usa, where vacationers can search for art events at their destinations; and egg on the arts, a discussion forum.

207

American History Picture Show  

NSDL National Science Digital Library

In class we read Katie's Picture Show, a book about a girl who discovers art first-hand one day at an art museum in London. She realizes she can climb into the paintings, explore her surroundings, and even solve problems for the subjects of the paintings. As part of our unit on American history, we are going to use art to further learn about some of the important events we have been discussing. Each of these works of art depicts an important event in American History. When you click on a picture, you will be able to see the name of the event as well as the artist who created it. You will be using all three pictures for this assignment.Use the websites ...

Bennion, Ms.

2009-11-23

208

Rat colorectal tumours treated with a range of non-steroidal anti-inflammatory drugs show altered cyclooxygenase-2 and cyclooxygenase-1 splice variant mRNA expression levels.  

PubMed

Non-steroidal anti-inflammatory drugs (NSAIDs) reduce tumour mass by increasing the rate of tumour cell apoptosis and decreasing cell proliferation. The classically recognized target for NSAID action are the two isoforms of the cyclooxygenase (COX) gene, which is responsible for prostaglandin production. In the rat, the COX-1 gene expresses an alternatively spliced mRNA COX-1 splice variant (SV) which may, at best, code for a truncated COX-1 protein. Previously, we reported that COX-1SV mRNA is differentially expressed in the ageing stomach. In this study, carcinogen treated rats were treated for 23 weeks with celecoxib, sulindac or sulindac sulfone, while untreated rats received vehicle alone. For each animal, the number and volume of tumour per animal was recorded and histology was performed. Using competitive polymerase chain reaction, we determined whether COX gene expression was altered in colorectal tumours and in regions of adjacent and distant macroscopically normal intestine, from vehicle or NSAID treated rats. In addition, we immunolocalized COX-1 and COX-2 in the same tumour and normal colonic tissue. Tumours from animals treated with vehicle or celecoxib expressed significantly elevated levels of COX-2 mRNA in comparison with the adjacent normal mucosa. In contrast, tumours from sulindac and sulindac sulfone treated rats expressed significantly less COX-2 mRNA than tumours from vehicle treated rats. The expression of COX-1 mRNA remained unchanged in all tissues examined. However, COX-1SV mRNA levels were elevated in colorectal tumours and reduced after NSAID treatment to the levels observed in normal colonic mucosa. Our results indicate that the anti-neoplastic actions of NSAIDs may be attributed to COX dependent and/or COX independent mechanisms of action. We also demonstrate the presence and differential expression of COX-1SV mRNA in colon tumours. COX-1SV mRNA represents 2% of the total COX-1 mRNA expressed and its role in colon cancer remains to be established. PMID:11375891

Vogiagis, D; Brown, W; Glare, E M; O'Brien, P E

2001-06-01

209

Drugs’ pleasures  

Microsoft Academic Search

Discourses on drug use and public health show a relative neglect of the study of pleasure. We argue that work on the social, cultural and historical specificity of bodies and the emotions can be usefully drawn upon to study the pleasures of drug use. This article reflects upon the nature of pleasure and its under-representation in public health approaches to

Robin Bunton; John Coveney

2011-01-01

210

The Great Cometary Show  

NASA Astrophysics Data System (ADS)

The ESO Very Large Telescope Interferometer, which allows astronomers to scrutinise objects with a precision equivalent to that of a 130-m telescope, is proving itself an unequalled success every day. One of the latest instruments installed, AMBER, has led to a flurry of scientific results, an anthology of which is being published this week as special features in the research journal Astronomy & Astrophysics. ESO PR Photo 06a/07 ESO PR Photo 06a/07 The AMBER Instrument "With its unique capabilities, the VLT Interferometer (VLTI) has created itself a niche in which it provide answers to many astronomical questions, from the shape of stars, to discs around stars, to the surroundings of the supermassive black holes in active galaxies," says Jorge Melnick (ESO), the VLT Project Scientist. The VLTI has led to 55 scientific papers already and is in fact producing more than half of the interferometric results worldwide. "With the capability of AMBER to combine up to three of the 8.2-m VLT Unit Telescopes, we can really achieve what nobody else can do," added Fabien Malbet, from the LAOG (France) and the AMBER Project Scientist. Eleven articles will appear this week in Astronomy & Astrophysics' special AMBER section. Three of them describe the unique instrument, while the other eight reveal completely new results about the early and late stages in the life of stars. ESO PR Photo 06b/07 ESO PR Photo 06b/07 The Inner Winds of Eta Carinae The first results presented in this issue cover various fields of stellar and circumstellar physics. Two papers deal with very young solar-like stars, offering new information about the geometry of the surrounding discs and associated outflowing winds. Other articles are devoted to the study of hot active stars of particular interest: Alpha Arae, Kappa Canis Majoris, and CPD -57o2874. They provide new, precise information about their rotating gas envelopes. An important new result concerns the enigmatic object Eta Carinae. Using AMBER with its high spatial and spectral resolution, it was possible to zoom into the very heart of this very massive star. In this innermost region, the observations are dominated by the extremely dense stellar wind that totally obscures the underlying central star. The AMBER observations show that this dense stellar wind is not spherically symmetric, but exhibits a clearly elongated structure. Overall, the AMBER observations confirm that the extremely high mass loss of Eta Carinae's massive central star is non-spherical and much stronger along the poles than in the equatorial plane. This is in agreement with theoretical models that predict such an enhanced polar mass-loss in the case of rapidly rotating stars. ESO PR Photo 06c/07 ESO PR Photo 06c/07 RS Ophiuchi in Outburst Several papers from this special feature focus on the later stages in a star's life. One looks at the binary system Gamma 2 Velorum, which contains the closest example of a star known as a Wolf-Rayet. A single AMBER observation allowed the astronomers to separate the spectra of the two components, offering new insights in the modeling of Wolf-Rayet stars, but made it also possible to measure the separation between the two stars. This led to a new determination of the distance of the system, showing that previous estimates were incorrect. The observations also revealed information on the region where the winds from the two stars collide. The famous binary system RS Ophiuchi, an example of a recurrent nova, was observed just 5 days after it was discovered to be in outburst on 12 February 2006, an event that has been expected for 21 years. AMBER was able to detect the extension of the expanding nova emission. These observations show a complex geometry and kinematics, far from the simple interpretation of a spherical fireball in extension. AMBER has detected a high velocity jet probably perpendicular to the orbital plane of the binary system, and allowed a precise and careful study of the wind and the shockwave coming from the nova. The stream of results from the VLTI and AMBER

2007-01-01

211

"Show me" bioethics and politics.  

PubMed

Missouri, the "Show Me State," has become the epicenter of several important national public policy debates, including abortion rights, the right to choose and refuse medical treatment, and, most recently, early stem cell research. In this environment, the Center for Practical Bioethics (formerly, Midwest Bioethics Center) emerged and grew. The Center's role in these "cultural wars" is not to advocate for a particular position but to provide well researched and objective information, perspective, and advocacy for the ethical justification of policy positions; and to serve as a neutral convener and provider of a public forum for discussion. In this article, the Center's work on early stem cell research is a case study through which to argue that not only the Center, but also the field of bioethics has a critical role in the politics of public health policy. PMID:17926217

Christopher, Myra J

2007-10-01

212

Predicting the Onset of Sexual and Drug Risk Behaviors in HIV-Negative Youths with HIV-Positive Mothers: The Role of Contextual, Self-Regulation, and Social-Interaction Factors  

Microsoft Academic Search

HIV-negative, inner-city adolescents with HIV-infected parents are considered to be at high risk for acquiring HIV themselves.\\u000a Using a modified theory of health behavior, this study examined the effects of maternal HIV infection and psychosocial variables\\u000a on the onset of sexual and drug risk behavior in 144 HIV-negative adolescents with and without HIV-positive mothers. Adolescents\\u000a and their mothers were interviewed

Claude A. Mellins; Curtis Dolezal; Elizabeth Brackis-Cott; Ouzama Nicholson; Patricia Warne; Heino F. L. Meyer-Bahlburg

2007-01-01

213

Detection of drug binding to DNA by hydroxyl radical footprinting. Relationship of distamycin binding sites to DNA structure and positioned nucleosomes on 5S RNA genes of Xenopus  

Microsoft Academic Search

We report the use of hydroxyl radical footprinting to analyze the interaction of distamycin and actinomycin with the 5s ribosomal RNA genes of Xenopus. There is a qualitative difference in the hydroxyl radical footprints of the two drugs. Distamycin gives a conventional (albeit high-resolution) footprint, while actinomycin does not protect DNA from hydroxyl radical attack, but instead induces discrete sites

Mair E. A. Churchill; Jeffrey J. Hayes; Thomas D. Tullius

1990-01-01

214

Oral Fluid Testing for Drugs of Abuse: Positive Prevalence Rates by Intercept™ Immunoassay Screening and GC-MS-MS Confirmation and Suggested Cutoff Concentrations  

Microsoft Academic Search

Draft guidelines for the use of oral fluid for workplace drug testing are under development by the Substance Abuse and Mental Health Services Administration (SAMHSA) in cooperation with industry and researchers. Comparison studies of the effectiveness of oral fluid testing versus urine testing are needed to establish scientifically reliable cutoff concentrations for oral fluid testing. We present the results of

Edward J. Cone; Lance Presley; Michael Lehrer; William Seiter; Melissa Smith; Keith W. Kardos; Dean Fritch; Sal Salamone; R. Sam Niedbala

215

Detection of drug binding to DNA by hydroxyl radical footprinting. Relationship of distamycin binding sites to DNA structure and positioned nucleosomes on 5S RNA genes of Xenopus.  

PubMed

We report the use of hydroxyl radical footprinting to analyze the interaction of distamycin and actinomycin with the 5S ribosomal RNA genes of Xenopus. There is a qualitative difference in the hydroxyl radical footprints of the two drugs. Distamycin gives a conventional (albeit high-resolution) footprint, while actinomycin does not protect DNA from hydroxyl radical attack, but instead induces discrete sites of hyperreactivity. We find concentration-dependent changes in the locations of distamycin binding sites on the somatic 5S gene of Xenopus borealis. A high-affinity site, containing a G.C base pair, is replaced at higher levels of bound drug by a periodic array of different lower affinity sites that coincide with the places where the minor groove of the DNA would face in toward a nucleosome core that is known to bind to the same sequence. These results suggest that distamycin recognizes potential binding sites more by the shape of the DNA than by the specific sequence that is contained in the site and that structures of many sequences are deformable to a shape that allows drug binding. We discuss the utility of hydroxyl radical footprinting of distamycin for investigating the underlying structure of DNA. PMID:1696501

Churchill, M E; Hayes, J J; Tullius, T D

1990-06-26

216

Experimental Drug Shows Promise for Rare Genetic Disorder  

MedlinePLUS

... published in the Aug. 29 issue of the New England Journal of Medicine . Amyloidosis is a very rare ... Laboratory, Tufts Medical Center, Boston; Aug. 29, 2013, New England Journal of Medicine HealthDay Copyright (c) 2013 HealthDay . ...

217

Nuclear Mapping of Nano-Drug Delivery Systems in Dynamic Cellular Environments  

PubMed Central

Nanoformulations have shown great promise for delivering chemotherapeutics and hold tremendous clinical relevance. However nuclear mapping of the chemo drugs is important to predict the success of the nanoformulation. Herein in this study fluorescence microscopy and a subcellular tracking algorithm were used to map the diffusion of chemotherapeutic drugs in cancer cells. Positively charged nanoparticles efficiently carried the chemo drug across the cell membrane. The algorithm helped map free drug and drug loaded nanoparticles, revealing varying nuclear diffusion pattern of the chemotherapeutics in drug-sensitive and resistant cells in a live dynamic cellular environment. While the drug-sensitive cells showed an exponential uptake of the drug with time, resistant cells showed random and asymmetric drug distribution. Moreover nanoparticles carrying the drug remained in the perinuclear region while the drug got accumulated in the cell nuclei. The tracking approach has enabled us to predict the therapeutic success of different nanoscale formulations of doxorubicin.

Bhirde, Ashwinkumar A.; Kapoor, Ankur; Liu, Gang; Iglesias-Bartolome, Ramiro; Jin, Albert; Zhang, Guofeng; Xing, Ruijun; Lee, Seulki; Leapman, Richard D.; Gutkind, J Silvio; Chen, Xiaoyuan

2012-01-01

218

Positive Lives  

NSDL National Science Digital Library

The Positive Lives project is "a unique international project that photographs and documents the social and emotional impact of the global HIV/AIDS epidemic, illuminating positive human responses to this world crisis." Sponsored by the Levi Strauss Foundation and the Terrence Higgins Trust, the project has sponsored photographers from across the world to photograph various persons living with HIV/AIDS in a host of very different settings. While the project has sponsored a number of various photographic exhibits, this online collection represents a small portion of the work thus far. Using an interactive map of the world, users can click on different geographic areas to view photographic exhibits documenting the lived experience of this condition. In South Africa, visitors can learn about the work and the residents of Nazareth House, which is a children's home in Cape Town taking care of abandoned children with HIV or AIDS. In Edinburgh, visitors are taken through the lives of young drug abusers at the Muirhouse Estate who are also living with either HIV or AIDS. In the words of photographer John Sturrock, "In Muirhouse I witnessed the emotional struggle of people enduring a tragedy..." However, hope is present in these photographic essays as well, as they represent a broad range of emotions.

219

The great American medicine show revisited.  

PubMed

Since the late 1800s, changes in the advertising and marketing of medicinal drugs have produced heated debates in the United States. With the emergence of the modern prescription drug between 1938 and 1951, concerns that once focused primarily on patients' use of over-the-counter drugs were broadened to include physicians and their "doctors' drugs" as well. The medical profession's growing control over their patients' drug choices inevitably heightened the scrutiny of their own performance as consumers. Although deeply divided over issues of the patient's role in medical decision making, consumer activists and physician reformers expressed similar concerns about the impact of aggressive pharmaceutical marketing and advertising on the doctor-patient relationship, and starting in the late 1950s they employed strikingly similar strategies to counter the new corporate "medicine show." Yet their efforts to promote a more rational use of prescription drugs have usually been too little and too late to offset the effectiveness of pharmaceutical advertising and mar-keting activities. PMID:16327082

Tomes, Nancy

2005-01-01

220

[Comparison of four drug interaction screening programs].  

PubMed

Adverse drug events (ADE) are a major public health issue, with drug-drug interactions (DDI) being one of well-recognized causes of ADE that could be preventable by the use of DDI screening software. We compared the ability of four programs to detect clinically important DDI. We tested 62 drug pairs with and 12 drug pairs without clinically important DDI. Lexi-Interact and Epocrates were the most sensitive (95%) compared to the Compendium and Theriaque (80 and 73%, respectively). The Compendium and Theriaque also showed the lowest negative predictive value. All programs showed high specificity and positive predictive value. The qualitative assessment showed the best performances for Compendium and Lexi-Interact. The last one seems to be the best screening program, but the Compendium is in French and is freely available. PMID:23198652

Ing Lorenzini, K; Reutemann, B; Samer, C F; Guignard, B; Bonnabry, P; Dayer, P; Perrier, A; Desmeules, J

2012-10-17

221

The Role of Cavitation in Acoustically Activated Drug Delivery  

PubMed Central

Pluronic P105 micelles are potential candidates as chemotherapy drug delivery vehicles using ultrasonic stimulation as a release trigger. Acoustic power has been previously shown to release two anthracycline agents from these polymeric carriers. In this study, an ultrasonic exposure chamber with fluorescence detection was used to examine the mechanism of doxorubicin release from P105 micelles. Acoustic spectra were collected and analyzed, at the same spatial position as fluorescence data, to probe the role of cavitation in drug release. Our study showed a strong correlation between percent drug release and subharmonic acoustic emissions, and we attribute the drug release to collapse cavitation that perturbs the structure of the micelle and releases drug.

Husseini, Ghaleb A.; Diaz de la Rosa, Mario A.; Richardson, Eric S.; Christensen, Douglas A.; Pitt, William G.

2006-01-01

222

CD30+ lymphomatoid drug reactions.  

PubMed

We report 5 cases of cutaneous CD30+ lymphomatoid drug reactions that occurred shortly after the onset of drug exposure and resolved promptly upon withdrawal of the offending agents. The cases showed protean dermatologic manifestations ranging from diffuse erythema with desquamation to macules, papules, and annular plaques. The suspect drugs were amlodipine (a calcium channel blocker) for 2 cases, sertraline (a selective serotonin reuptake inhibitor) for 1 case, gabapentin for 1 case, and levofloxacin (a fluoroquinolone) versus cefepime (a fourth generation cephalosporin), and metoprolol (a beta blocker), in the fifth case. The histopathologic findings included varying combinations of spongiotic dermatitis, lichenoid infiltrates, and interface dermatitis with a dermal infiltrate of large atypical lymphocytes. Three of the 5 cases contained as much as 30% CD30+ staining of all lymphocytes, whereas the remaining 2 showed 5%-15% positivity. Three patients had a history of allergy or immune dysregulation. Increased knowledge of CD30 positivity in lymphomatoid drug reactions may be relevant in an era of targeted drug therapies. Recognition of these findings may help clinicians to tailor appropriate clinical evaluation and treatment including a review of medications and the removal of possible offending agents. PMID:23328787

Pulitzer, Melissa P; Nolan, Katherine A; Oshman, Robin G; Phelps, Robert G

2013-05-01

223

[Antihypertensive drugs and malignant neoplasia].  

PubMed

Analysis of epidemiological, cohort and randomized studies of antihypertensive drugs containing reports of development of malignant neoplasms shows that long term use of some antihypertensive drugs while preventing cardiovascular complications has been associated with increased risk of malignancies. Most convincing evidence exists for association between the use of diuretics and renal cancer. Association between the use of reserpine and breast cancer in women, between atenolol and some types of cancer in elderly men also can not be ruled out. There is no proof of existence of either negative or positive correlation between malignant neoplasia and long-term use of calcium antagonists, angiotensin converting enzyme inhibitors or angiotensin receptor blockers. PMID:12494152

Preobrazhenski?, D V; Sidorenko, B A; Stetsenko, T M; Kiktev, V G

2002-01-01

224

Secondary analyses of data from four studies with fourth-grade children show that sex, race, amounts eaten of standardized portions, and energy content given in trades explain the positive relationship between BMI and energy intake at school-provided meals  

PubMed Central

Results from a 2012 article showed a positive relationship between children’s body mass index (BMI) and energy intake at school-provided meals. To help explain that positive relationship, secondary analyses investigated 1) whether the relationship differed by sex and race, and 2) the relationship between BMI and six aspects of school-provided meals—amounts eaten of standardized portions, energy content given in trades, energy intake received in trades, energy intake from flavored milk, energy intake from a la carte ice cream, and breakfast type. Data were from four studies conducted one per school year (1999–2000 to 2002–2003). Fourth-grade children (n=328; 50% female; 54% Black) from 13 schools total were observed eating school-provided breakfast and lunch on one to three days per child for 1,178 total meals (50% breakfast). Children were weighed and measured. Marginal regression models were fit using BMI as the dependent variable. For Purpose One, independent variables were energy intake at school-provided meals, sex, race, age, and study; additional models included interaction terms involving energy intake and sex/race. For Purpose Two, independent variables were the six aspects of school-provided meals, sex, race, age, and study. The relationship between BMI and energy intake at school-provided meals differed by sex (p<0.0001; stronger for females) and race (p=0.0063; stronger for Black children). BMI was positively related to amounts eaten of standardized portions (p<0.0001) and negatively related to energy content given in trades (p=0.0052). Explaining the positive relationship between BMI and energy intake at school-provided meals may contribute to school-based obesity prevention efforts.

Baxter, Suzanne Domel; Paxton-Aiken, Amy E.; Tebbs, Joshua M.; Royer, Julie A.; Guinn, Caroline H.; Finney, Christopher J.

2012-01-01

225

View of hospital district, showing cannon in foreground, showing building ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View of hospital district, showing cannon in foreground, showing building H1 at left, showing building H72 in background; camera facing north. - Mare Island Naval Shipyard, East of Nave Drive, Vallejo, Solano County, CA

226

Drug Tolerance, Drug Addiction, and Drug Anticipation  

Microsoft Academic Search

Environmental cues associated with drugs often elicit withdrawal symptoms and relapse to drug use. Such cues also modulate drug tolerance. The contribution of drug-associated stimuli to withdrawal and tolerance is emphasized in a Pavlovian-conditioning analysis of drug administration. Conditional responses occur in the presence of cues that have been associated with the drug in the past, such as the setting

Shepard Siegel

2005-01-01

227

Attitudes towards drug legalization among drug users.  

PubMed

Research shows that support for legalization of drugs varies significantly among different sociodemographic and political groups. Yet there is little research examining the degree of support for legalization of drugs among drug users. This paper examines how frequency and type of drug use affect the support for legalization of drugs after adjusting for the effects of political affiliation and sociodemographic characteristics. A sample of 188 drug users and non-drug users were asked whether they would support the legalization of marijuana, cocaine, and heroin. Respondents reported their use of marijuana, crack, cocaine, heroin, speedball, and/or methamphetamines during the previous 30 days. Support for legalization of drugs was analyzed by estimating three separate logistic regressions. The results showed that the support for the legalization of drugs depended on the definition of "drug user" and the type of drug. In general, however, the results showed that marijuana users were more likely to support legalizing marijuana, but they were less likely to support the legalization of cocaine and heroin. On the other hand, users of crack, cocaine, heroin, speedball, and/or methamphetamines were more likely to support legalizing all drugs including cocaine and heroin. PMID:11853137

Trevino, Roberto A; Richard, Alan J

2002-01-01

228

TRAIL shows potential cardioprotective activity  

Microsoft Academic Search

Summary  Recent clinical trials carried out in patients with advanced cancer have shown that recombinant TRAIL administration is usually\\u000a safe and well tolerated when used either alone or in association with chemotherapeutic drugs. Notably, anticancer chemotherapy\\u000a can be associated to cardiomiopathy. We have here demonstrated that TRAIL (administrated as either recombinant soluble TRAIL\\u000a or as AAV-TRAIL expression viral vector) reduced the

Barbara Toffoli; Stella Bernardi; Riccardo Candido; Serena Zacchigna; Bruno Fabris; Paola Secchiero

229

Scaring Kids' Shows Off TV.  

ERIC Educational Resources Information Center

|Presents the view that activist groups whose attitude is that television advertising is bad for children are scaring off the advertisers and making it difficult for positive children's programs to obtain funding. (SS)|

Raspberry, William

1980-01-01

230

Drug Usage and Attitude Toward Drugs Among College Students  

ERIC Educational Resources Information Center

Results of the data presented suggest that there is considerable experimentation among college students with illegal drugs, especially marijuana. Their attitudes toward other drugs still seems cautious. Marijuana, however, seems-to be accepted and generally positively evaluated. (Author)

Cross, Herbert J.; Keir, Richard G.

1971-01-01

231

Positive Position Interlock Concealment Shutter.  

National Technical Information Service (NTIS)

The patent relates to a positive position interlock concealment shutter for preventing the accidential or intentional actuation of a concealed interlock switch in a microwave oven when its door is in the open position. It comprises a moveable metal plate ...

E. W. Robinson A. V. D. Griek R. W. Kisielewski

1975-01-01

232

Positive Psychology  

ERIC Educational Resources Information Center

|Positive psychology is a deliberate correction to the focus of psychology on problems. Positive psychology does not deny the difficulties that people may experience but does suggest that sole attention to disorder leads to an incomplete view of the human condition. Positive psychologists concern themselves with four major topics: (1) positive

Peterson, Christopher

2009-01-01

233

Positive Psychology \\  

Microsoft Academic Search

Positive psychology is the study of human strength, resilience, and optimal human functioning. The goal of positive psychology is to make people happier by understanding and building positive emotion, gratification and meaning. The constructs of happiness, hope, optimism, well-being, resilience and flow are examined in how they relate to positive psychology. The \\

Andrew W Fleming

2006-01-01

234

Avoiding Drug-Drug Interactions  

Microsoft Academic Search

Background: Drugs may be prescribed in combinations causing drug-drug interactions (DDI) and adverse drug reactions (ADR), resulting in hospital care. Methods: To provide prescribers of drug therapy with a better knowledge of individuals’ current drug therapy, governments have started to collect prescribing data. Results: The data on individuals’ dispensed drugs is available for prescribers, pharmacists, and the registered individuals in

Bengt Ĺstrand

2009-01-01

235

Asia: Showing the Changing Seasons  

NSDL National Science Digital Library

SeaWiFS false color data showing seasonal change in the oceans and on land for Asia. The data is seasonally averaged, and shows the sequence: fall, winter, spring, summer, fall, winter, spring (for the Northern Hemisphere).

Allen, Jesse; Newcombe, Marte; Feldman, Gene

1998-09-09

236

Drugs of abuse, driving and traffic safety.  

PubMed

Roadside studies indicate that 1-15% of drivers drive under the influence of one or more drugs of abuse. After drug use, drivers are more often culpable for an accident than non-users. Information on drugs and traffic safety comes from roadside studies, epidemiological research, experimental studies on driving-related skills, and on-the-road driving tests. Road-side studies show that drivers most frequently test positive for the use of alcohol and/or cannabis. These two drugs affect driving ability in a dose-dependent matter and result in poor vehicle control, especially when used in combination. Drivers on cocaine, ecstasy and amphetamine show no impairment on basic driving skills, but often overestimate their driving skills. In combination with impaired decision making, this increases risk taking during driving. Only few studies looked at the effects on driving of other drugs of abuse, such as ketamine, inhalants and anabolic steroids, but suggest a negative effect on driving performance. In conclusion, most drugs of abuse negatively affect driving ability, especially when used in combination with alcohol or another drug. It is of concern that a substantial number of drug users are not aware that their driving is impaired. PMID:20088818

Penning, Renske; Veldstra, Janet L; Daamen, Anne P; Olivier, Berend; Verster, Joris C

2010-03-01

237

28. MAP SHOWING LOCATION OF ARVFS FACILITY AS BUILT. SHOWS ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

28. MAP SHOWING LOCATION OF ARVFS FACILITY AS BUILT. SHOWS LINCOLN BOULEVARD, BIG LOST RIVER, AND NAVAL REACTORS FACILITY. F.C. TORKELSON DRAWING NUMBER 842-ARVFS-101-2. DATED OCTOBER 12, 1965. INEL INDEX CODE NUMBER: 075 0101 851 151969. - Idaho National Engineering Laboratory, Advanced Reentry Vehicle Fusing System, Scoville, Butte County, ID

238

Immobilized liposome chromatography to study drug-membrane interactions. Correlation with drug absorption in humans.  

PubMed

For rapid screening of drug-membrane interactions and predicting drug absorption in vivo, unilamellar liposomes were stably immobilized in the pores of gel beads by avidin-biotin binding. Interactions of a diverse set of well-described drugs with the immobilized liposomal membranes were reflected by their elution profiles. The membrane partitioning coefficients (KLM) of the drugs were determined from the retention volumes. The drug retentions on egg phosphatidylcholine (EPC)-phosphatidylserine (PS)-cholesterol (chol) and EPC-PS-phosphatidylethanolamine (PE)-chol columns intended to mimic small intestine membranes were similar, although the positively-charged drugs were more strongly retarded on the negatively-charged liposomes than the negatively-charged drugs. The relationship between log KLM with the drug fraction absorbed in humans showed that the log KLM values obtained with unilamellar liposomes can be used to predict drug passive transcellular absorption, similarly to that previously shown for entrapped multilamellar liposomes. The immobilized liposome chromatography method should be useful for screening compounds at an early stage of the drug discovery process. The avidin-biotin immobilization of the liposomes prolongs the lifetime of the columns. PMID:12186381

Liu, Xue-Ying; Nakamura, Chikashi; Yang, Qing; Kamo, Naoki; Miyake, Jun

2002-06-28

239

Primary drug resistance to anti-tuberculosis drugs in major towns of Amhara region, Ethiopia.  

PubMed

Drug resistance is a major obstacle to effective TB control program performance. In this study, we assessed the prevalence of primary drug resistance in Mycobacterium tuberculosis (Mtb) isolates in Amhara Region, Ethiopia. A total of 112 Mtb isolates from cases with newly diagnosed pulmonary TB were subjected to drug susceptibility testing (DST) in a cross-sectional study. Isolates were tested for sensitivity to isoniazid, rifampicin, ethambutol, and streptomycin using the MGIT 960 protocol. A total of 93 Mtb isolates yielded valid DST results and 28 (30.1%) were resistant to one or more of first line anti-TB drugs. One isolate (1.0%) was multi-drug resistant (MDR), five (5.4%) were classified as poly-resistant and 22 showed single drug resistance to either streptomycin (n = 19) or isoniazid (n = 3). Isolates from HIV-positive patients were more likely to be resistant to at least one of the four anti-TB drugs compared with HIV-negative individuals (odds ratio 2.76, 95% confidence interval 1.06-7.22; p = 0.03). The study showed a high prevalence of primary drug resistance. Even though the prevalence of MDR was low, conditions that can contribute to the development of MDR are increasing. Therefore, regular monitoring of drug resistance and enhanced implementation of TB/HIV collaborative activities in the study region are imperative. PMID:22583363

Yimer, Solomon Abebe; Agonafir, Mulualem; Derese, Yohannes; Sani, Yusuf; Bjune, Gunnar A; Holm-Hansen, Carol

2012-01-12

240

ADHD Drugs  

MedlinePLUS

... Insurance Plan Rankings Heart Surgeon Ratings Hospital Ratings ADHD Allergies Back Pain Depression Diabetes Heart Health Insomnia ... Hospitals Insurance Home > Consumer Reports Best Buy Drugs > ADHD Drugs ADHD Drugs How we rate drugs Our ...

241

Drug Reactions  

MedlinePLUS

... version Drug Reactions Drug Reactions What is an adverse drug reaction? Medicines can treat or prevent illness ... medicines can cause problems. These problems are called adverse drug reactions. You should know what to do ...

242

Show Them You Really Want the Job  

ERIC Educational Resources Information Center

Showing that one really "wants" the job entails more than just really wanting the job. An interview is part Broadway casting call, part intellectual dating game, part personality test, and part, well, job interview. When there are 300 applicants for a position, many of them will "fit" the required (and even the preferred) skills listed in the job…

Perlmutter, David D.

2012-01-01

243

Show Them You Really Want the Job  

ERIC Educational Resources Information Center

|Showing that one really "wants" the job entails more than just really wanting the job. An interview is part Broadway casting call, part intellectual dating game, part personality test, and part, well, job interview. When there are 300 applicants for a position, many of them will "fit" the required (and even the preferred) skills listed in the job…

Perlmutter, David D.

2012-01-01

244

PET Drug Inspection  

Center for Drug Evaluation (CDER)

Text Version... manufacturing operation • Storage of the bulk product vial in non-sterile bag • Out of limit personnel monitoring results • EM positive for mold ... More results from www.fda.gov/downloads/drugs/scienceresearch

245

Nonprescription drug abuse.  

PubMed

Nonprescription drug, also referred to as over-the-counter (OTC) abuse, is a serious and growing global health challenge. Drugs from many different therapeutic classes and numerous dosage forms and drug delivery systems are implicated in nonprescription drug abuse. Individuals who commonly abuse certain nonprescription medications are likewise diverse, varying in age, demographics, and overall health status. The clinician is in a unique position to assist in identifying those patients at risk for nonprescription drug abuse and those who are abusers, and may play an important role in intervention, patient care, and in the treatment of nonprescription drug abuse. A concise review of nonprescription drug abuse may be of use to the clinician in this regard. PMID:22215648

Conca, Addison J; Worthen, David R

2012-01-03

246

Drug Design: Designer Drugs  

Microsoft Academic Search

\\u000a This article interrogates the contemporary comprehension of rational drug design in the development of pharmaceutical products\\u000a with therapeutic and enhancing properties and its extensions to designer drugs on the grey and black market. The latter not\\u000a only evidently leads to ethical and hence societal questions of standardizing the state of well-being of body and mind, but\\u000a also virtually sets the

Gerd Folkers; Elvan Kut; Martin Boyer

247

National Orange Show Photovoltaic Demonstration  

SciTech Connect

National Orange Show Photovoltaic Demonstration created a 400KW Photovoltaic self-generation plant at the National Orange Show Events Center (NOS). The NOS owns a 120-acre state fairground where it operates an events center and produces an annual citrus fair known as the Orange Show. The NOS governing board wanted to employ cost-saving programs for annual energy expenses. It is hoped the Photovoltaic program will result in overall savings for the NOS, help reduce the State's energy demands as relating to electrical power consumption, improve quality of life within the affected grid area as well as increase the energy efficiency of buildings at our venue. In addition, the potential to reduce operational expenses would have a tremendous effect on the ability of the NOS to service its community.

Dan Jimenez (NOS)Sheri Raborn, CPA (National Orange Show); Tom Baker (California Construction Authority)

2008-03-31

248

Drugs in oral fluid in randomly selected drivers.  

PubMed

There were 13,176 roadside drug tests performed in the first year of the random drug-testing program conducted in the state of Victoria. Drugs targeted in the testing were methamphetamines and Delta(9)-tetrahydrocannabinol (THC). On-site screening was conducted by the police using DrugWipe, while the driver was still in the vehicle and if positive, a second test on collected oral fluid, using the Rapiscan, was performed in a specially outfitted "drug bus" located adjacent to the testing area. Oral fluid on presumptive positive cases was sent to the laboratory for confirmation with limits of quantification of 5, 5, and 2 ng/mL for methamphetamine (MA), methylenedioxy-methamphetamine (MDMA), and THC, respectively. Recovery experiments conducted in the laboratory showed quantitative recovery of analytes from the collector. When oral fluid could not be collected, blood was taken from the driver and sent to the laboratory for confirmation. These roadside tests gave 313 positive cases following GC-MS confirmation. These comprised 269, 118, and 87 cases positive to MA, MDMA, and THC, respectively. The median oral concentrations (undiluted) of MA, MDMA, and THC was 1136, 2724, and 81 ng/mL. The overall drug positive rate was 2.4% of the screened population. This rate was highest in drivers of cars (2.8%). The average age of drivers detected with a positive drug reading was 28 years. Large vehicle (trucks over 4.5 t) drivers were older; on average at 38 years. Females accounted for 19% of all positives, although none of the positive truck drivers were female. There was one false positive to cannabis when the results of both on-site devices were considered and four to methamphetamines. PMID:17658711

Drummer, Olaf H; Gerostamoulos, Dimitri; Chu, Mark; Swann, Philip; Boorman, Martin; Cairns, Ian

2007-07-20

249

The OOPSLA trivia show (TOOTS)  

Microsoft Academic Search

OOPSLA has a longstanding tradition of being a forum for discussing the cutting edge of technology in a fun and participatory environment. The type of events sponsored by OOPSLA sometimes border on the unconventional. This event represents an atypical panel that conforms to the concept of a game show that is focused on questions and answers related to OOPSLA themes.

Jeff Gray; Douglas C. Schmidt

2009-01-01

250

Position Effects  

Microsoft Academic Search

Position effects describe the observed alteration in protein-coding gene expression that may accompany a change in genomic\\u000a position of a given gene. A position effect may result from chromosomal translocation or other genomic rearrangements. Recent\\u000a advances in chromatin studies in several different species including yeast, Drosophila, and mouse have contributed significantly\\u000a to better understanding of human diseases resulting from abnormal

Pawel Stankiewicz

251

The drug cocktail network  

PubMed Central

Background Combination of different agents is widely used in clinic to combat complex diseases with improved therapy and reduced side effects. However, the identification of effective drug combinations remains a challenging task due to the huge number of possible combinations among candidate drugs that makes it impractical to screen putative combinations. Results In this work, we construct a 'drug cocktail network' using all the known effective drug combinations extracted from the Drug Combination Database (DCDB), and propose a network-based approach to investigate drug combinations. Our results show that the agents in an effective combination tend to have more similar therapeutic effects and share more interaction partners. Based on our observations, we further develop a statistical approach termed as DCPred (Drug Combination Predictor) to predict possible drug combinations by exploiting the topological features of the drug cocktail network. Validating on the known drug combinations, DCPred achieves the overall AUC (Area Under the receiver operating characteristic Curve) score of 0.92, indicating the predictive power of our proposed approach. Conclusions The drug cocktail network constructed in this work provides useful insights into the underlying rules of effective drug combinations and offer important clues to accelerate the future discovery of new drug combinations.

2012-01-01

252

Reading the traveling exhibition show: \\  

Microsoft Academic Search

This dissertation utilizes the motif of the traveling exhibition show in order to analyze how the Massachusetts Magazine (1789–96) participated in the cultural discussion regarding the construction of the American woman in the new nation. Although others have focused on the role of women in America (i.e., “Republican Motherhood”), I assert that whatever situation a woman found herself in—single, married,

Beverly Jean Reed

2000-01-01

253

Do Trade Shows Pay Off?  

Microsoft Academic Search

rade show expenditures are the second largest item in the business marketing communications budget after advertising, and they account for nearly one-fifth of the total budget for U.S. firms and approximately one-fourth of the budget for European firms (Jacobson 1990; Schafer 1987). The level of these expenditures, including direct costs and allocation of exhibitor staff time, though exclud- ing planning

Srinath Gopalakrishna; Gary L. Lilien; Jerome D. Williams; Ian K. Sequeira

254

Serum antioxidant micromineral (Cu, Zn, Fe) status of drug dependent subjects: Influence of illicit drugs and lifestyle  

PubMed Central

Background Use of illicit drugs induces multiple nutrient deficiencies. Drug habit, sexual practice and socioeconomic factors influence the nutrient profile of drug dependent subjects. The literature on this issue is still insufficient. This study has tested the hypothesis that illicit drug use and lifestyle impair mineral status. To test this hypothesis, 253 men multiple drug users of age 18–45 years were recruited to investigate their serum copper, zinc and iron levels. Influence of illicit drugs and their lifestyle on the mineral levels was also examined. The study subjects were drug dependent who had shared needles and had sexual activity with multiple partners. Serum concentrations of the minerals were estimated by atomic absorption flame spectrometry. Results Results showed a significant increase in serum copper and zinc concentrations, and decrease in iron level in drug dependent subjects. The increase of copper level was found to be much higher than that of zinc. Period of drug abuse had made a significant positive influence on the copper and iron levels, but it was apparently reversed for zinc concentration. Multiple sexual partnerships had significant influence on zinc status. There also were significant relationships observed between body mass index (BMI) as well as certain socioeconomic factors, and mineral status of drug dependent subjects and non-drug dependent controls. A series of multiple linear regression analysis predicted mineral values for education, age and BMI. The group (drug dependent subject = 1, non-drug dependent control = 2) had a significant influence on these parameters. However, after controlling these factors, it was shown that illicit drug use significantly contributed to influence the serum mineral levels. Conclusion Illicit drug use impairs serum mineral value causing an increase in copper and zinc and a decrease in iron. Lifestyle and nutritional status of drug dependent subjects influence serum mineral concentrations.

Hossain, Kazi Jahangir; Kamal, Md Mustafa; Ahsan, Monira; Islam, SK Nazrul

2007-01-01

255

Positive Psychotherapy  

ERIC Educational Resources Information Center

Positive psychotherapy (PPT) contrasts with standard interventions for depression by increasing positive emotion, engagement, and meaning rather than directly targeting depressive symptoms. The authors have tested the effects of these interventions in a variety of settings. In informal student and clinical settings, people not uncommonly reported…

Seligman, Martin E. P.; Rashid, Tayyab; Parks, Acacia C.

2006-01-01

256

Positive Psychotherapy  

ERIC Educational Resources Information Center

|Positive psychotherapy (PPT) contrasts with standard interventions for depression by increasing positive emotion, engagement, and meaning rather than directly targeting depressive symptoms. The authors have tested the effects of these interventions in a variety of settings. In informal student and clinical settings, people not uncommonly reported…

Seligman, Martin E. P.; Rashid, Tayyab; Parks, Acacia C.

2006-01-01

257

DRUG DISTRIBUTION AND STENT RETENTION OF DRUG ELUTING STENTS  

Microsoft Academic Search

In this paper the examinations of drug eluting coronary stents are shown, such as the morphology of the coatings before expansion, drug distribution, the methodology and the value of stent retention. Surface qualities of drug coatings were examined with stereo- microscope, metallographic microscope and scanning electron microscope. Examinations with confocal microscope show drug distribution in the coatings. Stent retention is

E. Bognár; T. Balázs

258

Rocks and Minerals Slide Show  

NSDL National Science Digital Library

This interactive slide show of common rocks and minerals allows students to choose from two sets of minerals and click on a thumbnail to see a larger photograph with a full description of the mineral including color, streak, hardness, cleavage/fracture, and chemical composition. Also included are its use and where it is found. The rocks are divided into igneous, sedimentary, and metamorphic and can be accessed in the same manner. They are described on the basis of crystal size and mineral composition as well as use.

259

21 CFR 868.6820 - Patient position support.  

Code of Federal Regulations, 2013 CFR

...Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Miscellaneous § 868.6820 Patient position support. (a) Identification. A patient position...

2013-04-01

260

Effects of Drugs and Alcohol on Behavior, Job Performance, and Workplace Safety  

ERIC Educational Resources Information Center

|A study of records for 1 large U.S. company revealed that employees with positive drug screens were fired, whereas workers who self-disclosed drug/alcohol problems remained employed. Both groups were offered substance abuse intervention, and some previously fired workers were rehired after they received treatment. Accident results showed that…

Elliott, Karen; Shelley, Kyna

2006-01-01

261

Overview of Selected Drug Trends.  

ERIC Educational Resources Information Center

This document begins with a brief overview of findings from national surveys conducted by the National Institute on Drug Abuse which show increasing drug use throughout the 1970s and a decreasing trend in drug use during the 1980s. In spite of this decline, drug use in the U.S. is described as still constituting a major public health problem that…

Adams, Edgar H.; And Others

262

Overview of Selected Drug Trends.  

ERIC Educational Resources Information Center

|This document begins with a brief overview of findings from national surveys conducted by the National Institute on Drug Abuse which show increasing drug use throughout the 1970s and a decreasing trend in drug use during the 1980s. In spite of this decline, drug use in the U.S. is described as still constituting a major public health problem that…

Adams, Edgar H.; And Others

263

Review: Drugs and Traffic Collisions  

Microsoft Academic Search

Three categories of drugs, and specific commonly used drug subcategories are examined in this paper: depressants (benzodiazepines, methadone), stimulants (cocaine), and hallucinogens (cannabis). Descriptive, epidemiological studies on the incidence of drugs in driving populations show that cannabis or benzodiazepines are the most common drugs detected in most industrialized countries. The large number of experimental studies on the impact of various

Evelyn Vingilis; Scott Macdonald

2002-01-01

264

Legalization of drugs of abuse and the pediatrician.  

PubMed

Growing numbers of individuals are proposing that drugs be legalized in the United States, with claims that federal, state, and local efforts to prohibit the use of illicit drugs are irrational and unenforceable. "Drug reform" advocates include persons of all political persuasions. Ironically, the call for drug reform comes at a time when trends in drug abuse, as reflected in national and state surveys, show a promising decline. It also is contradictory to at least one recent public opinion poll, in which respondents opposed the legalization of marijuana by a five-to-one margin. While their position is by no means unanimous, proponents of drug reform generally base their arguments on several key premises, such as elimination of or reductions in drug trafficking, enforcement, and interdiction expenditures; increased tax revenues from the legal sale of drugs; and reductions in health-care expenses associated with drug treatment. Reform advocates further claim that legalization would not be followed by an increase in drug use. The validity of each of these arguments is highly questionable. Legalization is a simplistic, short-sighted solution to a complex issue with public health, economic, criminal justice, and societal ramifications. Legalization would, moreover, abrogate the position taken in 1961 by the United States and 114 other nations in ratifying the United Nations Single Convention on Narcotic Drugs. The impact of drug reform merits an unbiased study by an independent agency. Until that time, pediatricians should inform themselves of the arguments for and against drug reform and be prepared to educate patients and their families about the issue. PMID:1928008

Schwartz, R H

1991-10-01

265

When Oprah Intervenes: Political Correlates of Daytime Talk Show Viewing  

Microsoft Academic Search

This study examined the influence of daytime talk shows on opinion formation. Using agenda-setting and cultivation perspectives, it was hypothesized that both exposure to daytime talk shows and the apparent reality of these shows would be positively related to support for government involvement in social issues. In addition to exposure and apparent reality being positively related to levels of support,

Carroll J. Glynn; Michael Huge; Jason B. Reineke; Bruce W. Hardy; James Shanahan

2007-01-01

266

Drug-target network.  

PubMed

The global set of relationships between protein targets of all drugs and all disease-gene products in the human protein-protein interaction or 'interactome' network remains uncharacterized. We built a bipartite graph composed of US Food and Drug Administration-approved drugs and proteins linked by drug-target binary associations. The resulting network connects most drugs into a highly interlinked giant component, with strong local clustering of drugs of similar types according to Anatomical Therapeutic Chemical classification. Topological analyses of this network quantitatively showed an overabundance of 'follow-on' drugs, that is, drugs that target already targeted proteins. By including drugs currently under investigation, we identified a trend toward more functionally diverse targets improving polypharmacology. To analyze the relationships between drug targets and disease-gene products, we measured the shortest distance between both sets of proteins in current models of the human interactome network. Significant differences in distance were found between etiological and palliative drugs. A recent trend toward more rational drug design was observed. PMID:17921997

Yildirim, Muhammed A; Goh, Kwang-Il; Cusick, Michael E; Barabási, Albert-László; Vidal, Marc

2007-10-01

267

Casimir experiments showing saturation effects  

SciTech Connect

We address several different Casimir experiments where theory and experiment disagree. First out is the classical Casimir force measurement between two metal half spaces; here both in the form of the torsion pendulum experiment by Lamoreaux and in the form of the Casimir pressure measurement between a gold sphere and a gold plate as performed by Decca et al.; theory predicts a large negative thermal correction, absent in the high precision experiments. The third experiment is the measurement of the Casimir force between a metal plate and a laser irradiated semiconductor membrane as performed by Chen et al.; the change in force with laser intensity is larger than predicted by theory. The fourth experiment is the measurement of the Casimir force between an atom and a wall in the form of the measurement by Obrecht et al. of the change in oscillation frequency of a {sup 87}Rb Bose-Einstein condensate trapped to a fused silica wall; the change is smaller than predicted by theory. We show that saturation effects can explain the discrepancies between theory and experiment observed in all these cases.

Sernelius, Bo E. [Division of Theory and Modeling, Department of Physics, Chemistry and Biology, Linkoeping University, SE-581 83 Linkoeping (Sweden)

2009-10-15

268

Instrument Development for SHOW project  

NASA Astrophysics Data System (ADS)

Water is a critically important constituent throughout the stratosphere and mesosphere The SHOW project will develop a new instrument to measure water vapour from 15km to 85km height on a global scale using the unique capabilities provided by Spatial Heterodyne Spectroscopy SHS This work builds on Canadian expertise in fabricating solid Michelson interferometers to fill a significant niche in our current capability The SHS setup the FTS with the mirrors replaced by diffraction gratings at Littrow configuration wavelength depended Fizeau fringes are recorded by a 320 256 InGaAs near infrared camera without any scanning elements the high resolution spectral information along one detector dimension can be obtain from Fourier analysis and the other dimension will provide the spatial information At a limb view point a field-widened SHS with half-angle of 6 degrees for water observations at 1364nm is desired the resolution is 0 02nm within full bandwidth of 2nm and the resolving power is about 68 000 The laboratory work for the instrument development and the designing building and testing of the pre-prototype are presented

Lin, Y. L.; Shepherd, M. G.; Shepherd, G. G.; Solheim, B. H.; Brown, S.

269

Positive Prevention: Successful Approaches To Preventing Youthful Drug and Alcohol Use [and] La Prevencion Positiva: Metodos que han tenido exito en la prevencion del uso de drogas y alcohol entre la juventud.  

ERIC Educational Resources Information Center

The United States has the highest rate of youthful drug abuse of any industrialized country in the world. There is a growing awareness that drug and alcohol use are closely connected to other problems such as teenage suicide, adolescent pregnancy, traffic fatalities, juvenile delinquency, poor school performance, runaways, and dropouts. Youthful…

American Association of School Administrators, Arlington, VA.

270

Prescription Drugs  

MedlinePLUS

... drugs—addiction is a real possibility. How Many Teens Abuse Prescription Drugs? Every day in the United States, an average ... fairly or very easy to get. Why Do Teens Abuse Prescription Drugs? Teens abuse prescription drugs for a number of ...

271

Generic Drugs  

MedlinePLUS

... the drug. Drug companies spend billions of dollars advertising brand-name drugs, like Lipitor and Celebrex. But oft en you can get a generic drug that works just as well— and costs much less! Are generics as good as brand-names? By law, all generics must have the same active ingredients ...

272

Drug Views  

Microsoft Academic Search

Substance abuse is a significant social problem and political issue. Students at a Midwestern university were surveyed on their drug views. The findings suggest that race is a statistically significant factor on students' views toward drugs. White students were more likely than non-Whites to view drugs as a pressing social issue, to consider drug use as a character weakness, and

Eric G. Lambert; Lois A. Ventura; David N. Baker; Morris Jenkins

2006-01-01

273

Drug Addiction  

Microsoft Academic Search

Drug addiction causes an enormous burden to patients, families, and societies. This chapter summarizes current concepts of\\u000a drug addiction, epidemiology, etiology, pathogenesis, pathology, clinical course, laboratory findings, assessment, and treatment\\u000a of drug addiction. Pathologic consequences from drugs of abuse (e.g., opioids, sedatives, amphetamines, cocaine, cannabis,\\u000a nicotine, phencyclidine [PCP], hallucinogens) are explained as well. The understanding of drug addiction has improved

Joseph Westermeyer; Gihyun Yoon

274

Glioma-associated endothelial cells show evidence of replicative senescence  

SciTech Connect

The innately programmed process of replicative senescence has been studied extensively with respect to cancer, but primarily from the perspective of tumor cells overcoming this stringent innate barrier and acquiring the capacity for unlimited proliferation. In this study, we focus on the potential role of replicative senescence affecting the non-transformed endothelial cells of the blood vessels within the tumor microenvironment. Based on the well-documented aberrant structural and functional features of blood vessels within solid tumors, we hypothesized that tumor-derived factors may lead to premature replicative senescence in tumor-associated brain endothelial cells (TuBEC). We show here that glioma tissue, but not normal brain tissue, contains cells that express the signature of replicative senescence, senescence-associated {beta}-galactosidase (SA-{beta}-gal), on CD31-positive endothelial cells. Primary cultures of human TuBEC stain for SA-{beta}-gal and exhibit characteristics of replicative senescence, including increased levels of the cell cycle inhibitors p21 and p27, increased resistance to cytotoxic drugs, increased growth factor production, and inability to proliferate. These data provide the first demonstration that tumor-derived brain endothelial cells may have reached an end-stage of differentiation known as replicative senescence and underscore the need for anti-angiogenic therapies to target this unique tumor-associated endothelial cell population.

Charalambous, Christiana [Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Virrey, Jenilyn [Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Kardosh, Adel [Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Jabbour, Mark N. [Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Qazi-Abdullah, Lubna [Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Pen, Ligaya [Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Zidovetzki, Raphael [Department of Cell Biology and Neuroscience, University of California, Riverside, CA (United States); Schoenthal, Axel H. [Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Chen, Thomas C. [Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Department of Neurosurgery, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Hofman, Florence M. [Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States) and Department of Neurosurgery, University of Southern California Keck School of Medicine, Los Angeles, CA (United States)]. E-mail: hofman@usc.edu

2007-04-01

275

Positively Adolescent!  

ERIC Educational Resources Information Center

|Believes that music teachers should reassess their views toward adolescent behavior in the music classroom by learning to see their behavior in a positive light. Describes teaching strategies that build on four adolescent behaviors: (1) desire for peer acceptance; (2) abundant energy; (3) love of fun; and (4) limited time-managing skills. (CMK)|

Williamson, Sue

2000-01-01

276

Club drug use among college students  

Microsoft Academic Search

This study examined prevalence and frequency of “club” drug use among college students (N=831) and associations with marijuana and alcohol use, sensation seeking, and positive and negative affectivity. Eighteen percent (n=146) of the sample had used club drugs at least once in their lifetime. Results of a logistic regression indicated that club drug use was positively associated with marijuana use,

Jeffrey S. Simons; Raluca M. Gaher; Christopher J. Correia; Jacqueline A. Bush

2005-01-01

277

Ordering for Positive Dependence.  

National Technical Information Service (NTIS)

A partial ordering for positive dependent bivariate distributions is introduced. The main result shows that tests of independence based on rank statistics such as Spearman's rho, Kendall's tau, Fisher-Yates' normal score statistic, vander Waerden's statis...

B. F. Schriever

1986-01-01

278

A Computational Approach to Finding Novel Targets for Existing Drugs  

Microsoft Academic Search

Repositioning existing drugs for new therapeutic uses is an efficient approach to drug discovery. We have developed a computational drug repositioning pipeline to perform large-scale molecular docking of small molecule drugs against protein drug targets, in order to map the drug-target interaction space and find novel interactions. Our method emphasizes removing false positive interaction predictions using criteria from known interaction

Yvonne Y. Li; Jianghong An; Steven J. M. Jones

2011-01-01

279

Relation of the pre-employment drug testing result to employment status: a one-year follow-up.  

PubMed

All employees hired over a six-month period at a large hospital underwent pre-employment urinary toxicology screening. Results of the screening were kept confidential. After a year of employment, the personnel folders of all employees studied were reviewed. Twenty-two of 180 employees (12%) had tested positive for drug use. Employees in clerical/aide positions were significantly more likely to test positive than were employees in professional positions (17% vs. 6%). Drug-positive employees were also more likely to be young and male. Comparison of job performance variables, job retention, supervisor evaluations, and reasons for termination showed no difference between drug-positive and drug-negative employees. Eleven drug-negative employees were fired during the study; no drug-positive employee was fired. There was a strongly significant difference between clerical and professional employees on each of these variables. This study did not find a relation between drug use and job performance. The widespread use of drug screening prior to employment makes further studies of this issue important. PMID:2915272

Parish, D C

280

Positive Psychologists on Positive Constructs  

ERIC Educational Resources Information Center

|Comments on the original article by McNulty and Fincham (see record 2011-15476-001). In their article, the authors offered compelling evidence that constructs such as forgiveness and optimism can have both beneficial and adverse consequences, depending on the context. Their caution about labeling particular psychological processes as "positive"…

Lyubomirsky, Sonja

2012-01-01

281

Political Influence and Regulatory Policy: The 1984 Drug Legislation  

Microsoft Academic Search

This paper applies a positive theory of legislation to explain the development of the 1984 Drug Price Competition Act and the Patent Term Restoration Act. Specifically, it examines why regulatory reforms prior to 1984 were stalemated and why the 1984 legislation was enacted. Results show that, prior to 1984, members of the key congressional committees had preferences in which the

Mary K. Olson

1994-01-01

282

Cancer Drugs  

Center for Drug Evaluation (CDER)

... drug approval. Endpoints were examined for the most common cancers, such as lung cancer, colon cancer, etc. For each ... More results from www.fda.gov/drugs/developmentapprovalprocess/developmentresources

283

Generic Drugs  

Center for Drug Evaluation (CDER)

Text Version... Post-Marketing • Same policies & systems as new/brand drugs • Product quality surveys – a recent review of ... Post-approval product surveys CDER ... More results from www.fda.gov/downloads/drugs/developmentapprovalprocess

284

Drug Shortages  

Center for Drug Evaluation (CDER)

... The article "FDA's Role in Responding to Drug Shortages” published in the American Journal of Health Systems Pharmacists (2002 Aug 1;59(15 ... More results from www.fda.gov/drugs/resourcesforyou/healthprofessionals

285

Drug Promotion  

Center for Drug Evaluation (CDER)

... Watch Video. Transcript. FDA reviews advertising and promotional materials for prescription drugs to ensure the content isn't false or misleading. ... More results from www.fda.gov/drugs/resourcesforyou/healthprofessionals

286

Approved Drugs  

Center for Drug Evaluation (CDER)

... The majority of patient information, labels, approval letters, reviews, and other ... drug products approved on the basis of safety and effectiveness by ... More results from www.fda.gov/drugs/informationondrugs/approveddrugs

287

Prescription Drugs  

MedlinePLUS

... Marijuana) LSD (Acid) Marijuana MDMA (Ecstasy/Molly) Methamphetamine PCP/Phencyclidine Prescription Drugs Salvia Steroids (Anabolic) Tobacco Addiction ... Marijuana) LSD (Acid) Marijuana MDMA (Ecstasy/Molly) Methamphetamine PCP/Phencyclidine Prescription Drugs Fentanyl Salvia Steroids (Anabolic) Tobacco ...

288

Drugged Driving  

MedlinePLUS

... Marijuana) LSD (Acid) Marijuana MDMA (Ecstasy/Molly) Methamphetamine PCP/Phencyclidine Prescription Drugs Salvia Steroids (Anabolic) Tobacco Addiction ... Marijuana) LSD (Acid) Marijuana MDMA (Ecstasy/Molly) Methamphetamine PCP/Phencyclidine Prescription Drugs Fentanyl Salvia Steroids (Anabolic) Tobacco ...

289

Club Drugs  

MedlinePLUS

... Marijuana) LSD (Acid) Marijuana MDMA (Ecstasy/Molly) Methamphetamine PCP/Phencyclidine Prescription Drugs Salvia Steroids (Anabolic) Tobacco Addiction ... Marijuana) LSD (Acid) Marijuana MDMA (Ecstasy/Molly) Methamphetamine PCP/Phencyclidine Prescription Drugs Fentanyl Salvia Steroids (Anabolic) Tobacco ...

290

Drug abuse  

MedlinePLUS

... marijuana that is laced with a drug called PCP) Regular users may have withdrawal effects when they ... nausea caused by chemotherapy in cancer patients PHENCYCLIDINE (PCP, "angel dust") PCP is an illegal drug that ...

291

Perceived Positions Determine Crowding  

PubMed Central

Crowding is a fundamental bottleneck in object recognition. In crowding, an object in the periphery becomes unrecognizable when surrounded by clutter or distractor objects. Crowding depends on the positions of target and distractors, both their eccentricity and their relative spacing. In all previous studies, position has been expressed in terms of retinal position. However, in a number of situations retinal and perceived positions can be dissociated. Does retinal or perceived position determine the magnitude of crowding? Here observers performed an orientation judgment on a target Gabor patch surrounded by distractors that drifted toward or away from the target, causing an illusory motion-induced position shift. Distractors in identical physical positions led to worse performance when they drifted towards the target (appearing closer) versus away from the target (appearing further). This difference in crowding corresponded to the difference in perceived positions. Further, the perceptual mislocalization was necessary for the change in crowding, and both the mislocalization and crowding scaled with drift speed. The results show that crowding occurs after perceived positions have been assigned by the visual system. Crowding does not operate in a purely retinal coordinate system; perceived positions need to be taken into account.

Maus, Gerrit W.; Fischer, Jason; Whitney, David

2011-01-01

292

Ligand-exchangeability of 2-coordinate phosphinegold(I) complexes with AuSP and AuNP cores showing selective antimicrobial activities against Gram-positive bacteria. Crystal structures of [Au(2-Hmpa)(PPh 3)] and [Au(6-Hmna)(PPh 3)] (2-H 2mpa=2-mercaptopropionic acid, 6-H 2mna=6-mercaptonicotinic acid)  

Microsoft Academic Search

Selective and effective antimicrobial activities against Gram-positive bacteria (B. subtilis and\\/or S. aureus) were found in 2-coordinate gold(I)–PPh3 complexes with AuSP and AuNP cores, i.e. [Au(L)(PPh3)] (HL=2-H2mna [H2mna=mercaptonicotinic acid] 3, d-H2pen [H2pen=penicillamine] 4, d,l-H2pen 5, 4-H2mba [H2mba=mercaptobenzoic acid] 8, Hpz [Hpz=pyrazole] 9, Him [Him=imidazole] 10, 1,2,3-Htriz [Htriz=triazole] 11, 1,2,4-Htriz 12, Htetz [Htetz=tetrazole] 13), whereas no activity was observed in 2-coordinate

Kenji Nomiya; Satoshi Yamamoto; Ryusuke Noguchi; Hironari Yokoyama; Noriko Chikaraishi Kasuga; Kei Ohyama; Chieko Kato

2003-01-01

293

Behavioral Treatments for Drug Abuse and Dependence.  

National Technical Information Service (NTIS)

Contents: Behavior Treatments for Drug Abuse and Dependence: Progress, Potential, and Promise; Advancing the Application of Behavioral Treatment Approaches for Drug Dependence; Contingency Management in Methadone Treatment: The Case for Positive Incentive...

J. D. Blaine J. J. Boren L. S. Onken

1993-01-01

294

Influenza (Flu) Antiviral Drugs and Related Information  

Center for Drug Evaluation (CDER)

... However, a negative test does not rule out the ... of an influenza infection, and positive tests do not ... check the FDA Drug Shortages web page for ... More results from www.fda.gov/drugs/drugsafety/informationbydrugclass

295

Positioning apparatus  

DOEpatents

An apparatus is provided for precisely adjusting the position of an article relative to a beam emerging from a neutron source disposed in a housing. The apparatus includes a support pivotably mounted on a movable base plate and freely suspended therefrom. The support is gravity biased toward the housing and carries an article holder movable in a first direction longitudinally of the axis of said beam and normally urged into engagement against said housing. Means are provided for moving the base plate in two directions to effect movement of the suspended holder in two mutually perpendicular directions, respectively, normal to the axis of the beam.

Vogel, M.A.; Alter, P.

1983-07-07

296

Educational Outreach: The Space Science Road Show  

NASA Astrophysics Data System (ADS)

The poster presented will give an overview of a study towards a "Space Road Show". The topic of this show is space science. The target group is adolescents, aged 12 to 15, at Dutch high schools. The show and its accompanying experiments would be supported with suitable educational material. Science teachers at schools can decide for themselves if they want to use this material in advance, afterwards or not at all. The aims of this outreach effort are: to motivate students for space science and engineering, to help them understand the importance of (space) research, to give them a positive feeling about the possibilities offered by space and in the process give them useful knowledge on space basics. The show revolves around three main themes: applications, science and society. First the students will get some historical background on the importance of space/astronomy to civilization. Secondly they will learn more about novel uses of space. On the one hand they will learn of "Views on Earth" involving technologies like Remote Sensing (or Spying), Communication, Broadcasting, GPS and Telemedicine. On the other hand they will experience "Views on Space" illustrated by past, present and future space research missions, like the space exploration missions (Cassini/Huygens, Mars Express and Rosetta) and the astronomy missions (Soho and XMM). Meanwhile, the students will learn more about the technology of launchers and satellites needed to accomplish these space missions. Throughout the show and especially towards the end attention will be paid to the third theme "Why go to space"? Other reasons for people to get into space will be explored. An important question in this is the commercial (manned) exploration of space. Thus, the questions of benefit of space to society are integrated in the entire show. It raises some fundamental questions about the effects of space travel on our environment, poverty and other moral issues. The show attempts to connect scientific with community thought. The difficulty with a show this elaborate and intricate is communicating on a level understandable for teenagers, whilst not treating them like children. Professional space scientists know how easy it is to lose oneself in technical specifics. This would, of course, only confuse young people. The author would like to discuss the ideas for this show with a knowledgeable audience and hopefully get some (constructive) feedback.

Cox, N. L. J.

2002-01-01

297

Satellite positioning  

NASA Astrophysics Data System (ADS)

Geodetic positioning programs with the U.S. Navy Transit and GPS satellite systems and satellite laser ranging programs are described. As of 1982 the number of Doppler receivers had increased to over 16,000 units, 1000 with two-frequency geodetic apparatus. The Nova 1 satellite, launched in 1981, was a drag-free satellite, incorporating a single-axis disturbance compensation system (DISCOS) to continuously correct track aberrations due to perturbing forces acting on the satellite. One of the Transit system units, Nova 1 lowered the broadcast ephemeris prediction errors to 5-15 m rms, compared to the 5-70 m rms error for the Oscar satellite. The Navstar GPS system is in full engineering development and will lead to an 18 satellite configuration, with four in view from any point on earth. Global positioning accuracies of 10 m have been found in tests. The Lageos, Starlette, beacon Explorer-C, and Geos-3 satellites have been used in laser ranging experiments to measure polar motions by reflecting laser light from the ground off reflectors on the satellite surfaces. NASA is currently moving a transportable laser station to Easter Island to obtain an accuracy of 10 cm.

Hill, R. W.

1983-04-01

298

Better position  

NASA Astrophysics Data System (ADS)

The U.S. Global Positioning System (GPS) will soon become more accurate for civilian users, improving the quality of navigation and of some types of scientific research. The Clinton Administration announced March 29 that within a decade, the federal government will stop degrading the civilian GPS signal and will allow nonmilitary users access to the same clear signals that U.S. troops rely upon.Designed as dual-use system with primary use by the American military, the GPS is a constellation of 24 satellites that allows soldiers to determine their exact positions (in latitude and longitude) anywhere in the world. While the GPS is operated by the Department of Defense (DoD), scientists and adventurous civilians have been able to purchase small, portable GPS devices. However, the U.S. military has kept to itself a capability known as “selective availability” that provides a much more precise signal than is available to the public. According to the White House, that selected signal will be available to all users within 4-10 years.

Carlowicz, Michael

299

The Economics of Preemployment Drug Testing  

Microsoft Academic Search

A labor market matching model shows that preemployment drug testing leads to a net improvement in social welfare, but the overall level of drug testing will exceed the social optimum. These results hold for wide ranges of parameter values. Drug testing results in fewer and shorter episodes of unemployment for drug-free workers while producing the opposite effect for drug users.

Jason Zimmerman

2002-01-01

300

Patents associated with high-cost drugs in Australia.  

PubMed

Australia, like most countries, faces high and rapidly-rising drug costs. There are longstanding concerns about pharmaceutical companies inappropriately extending their monopoly position by "evergreening" blockbuster drugs, through misuse of the patent system. There is, however, very little empirical information about this behaviour. We fill the gap by analysing all of the patents associated with 15 of the costliest drugs in Australia over the last 20 years. Specifically, we search the patent register to identify all the granted patents that cover the active pharmaceutical ingredient of the high-cost drugs. Then, we classify the patents by type, and identify their owners. We find a mean of 49 patents associated with each drug. Three-quarters of these patents are owned by companies other than the drug's originator. Surprisingly, the majority of all patents are owned by companies that do not have a record of developing top-selling drugs. Our findings show that a multitude of players seek monopoly control over innovations to blockbuster drugs. Consequently, attempts to control drug costs by mitigating misuse of the patent system are likely to miss the mark if they focus only on the patenting activities of originators. PMID:23577165

Christie, Andrew F; Dent, Chris; McIntyre, Peter; Wilson, Lachlan; Studdert, David M

2013-04-05

301

Drug metabolism and drug toxicity  

Microsoft Academic Search

Adverse drug reactions are a major problem for both health care providers and the pharmaceutical industry. They are a common and significant cause of morbidity and mortality and occasionally result in the withdrawal of an otherwise valuable therapeutic agent. There is now overwhelming evidence that adverse drug reactions are often caused by a metabolite of the drug rather than the

B. Kevin Park; Neil R. Kitteringham; Jane R. Kenny; Munir Pirmohamed

2001-01-01

302

Competitive positioning  

SciTech Connect

Changes in the utility industry are making established utility-customer relationships more vulnerable to competitors. Recent competitive forays into electric wholesale markets illustrate what's in store for utilities as customers gain more freedom of choice. For 40 years, the Borough of Butler's 19-megawatt load had been served by Jersey Central Power Light (a General Public Utilities [GPU] subsidiary). Following passage of the Energy Policy Act of 1992, the New Jersey Borough asked neighboring utility Public Service Electric Gas Co. (PSE G) to bid on its business. Just as Butler tentatively decided to sign a new contract with PSE G, other utilities joined the fray and began bidding the price down. When the dust settled, Jersey Central was given one year's cancellation notice and Butler signed a new contract with Pennsylvania Electric (another GPU subsidiary) for a 40-percent cost savings. Jersey Central's problems didn't stop there. The utility's four other municipal customers were also approached by neighboring utilities; in each case, Jersey Central lost their business (although it ultimately remained within the GPU system). The basis for success within the utility industry is shifting from operations reliability to competitive positioning. The new success model requires utilities to be market-driven, produce customer value, provide competitive versus justifiable pricing, focus more on cost productivity than on costs in rate base, and increasingly look toward forging partnerships with others. Those utilities able to successfully implement the new success model first will secure defensive and offensive competitive positions that will enable them to capitalize on changes in regulation.

Murray, W.R.

1994-07-01

303

Characteristics of injection drug users who participate in drug dealing: implications for drug policy.  

PubMed

So-called "balanced" drug policy couples enforcement initiatives targeting drug dealers with health-focused interventions serving addicted individuals. There are few evaluations of this approach, and little is known about how these two populations may overlap. We evaluated factors associated with drug dealing among injection drug users (IDUs) in Vancouver, Canada, and examined self-reported drug-dealing roles and reasons for dealing. Among 412 IDUs seen from March through December 2005, 68 (17%) had dealt drugs during the previous six months. Variables independently associated with drug dealing included: recent incarceration (adjusted odds ratio [AOR] = 2.9; 95%CI: 1.4-6.0); frequent heroin injection (AOR = 2.5; 95%CI: 1.4-4.6); frequent cocaine injection (AOR = 2.0; 95%CI: 1.1-3.8); and recent overdose (AOR = 2.7; 95%CI: 1.0-7.3). The most common drug-dealing roles were direct selling (82%), middling (35%), and steering (19%), while the most common reasons for dealing included obtaining drugs (49%) and money (36%). Drug dealing among IDUs was predicted by several markers of higher intensity addiction, and drug-dealing IDUs tended to occupy the most dangerous positions in the drug-dealing hierarchy. These findings suggest that elements of "balanced" drug policies may undermine each other and indicate the need for alternative interventions. PMID:18720663

Kerr, Thomas; Small, William; Johnston, Caitlin; Li, Kathy; Montaner, Julio S G; Wood, Evan

2008-06-01

304

1. Historic American Buildings Survey, August, 1971 STREETSCAPE SHOWING SOUTH ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. Historic American Buildings Survey, August, 1971 STREETSCAPE SHOWING SOUTH (FRONT) ELEVATIONS OF LOVE AND BILGER TIN SHOP (FAR LEFT), SACHS BROTHERS STORE, NEUBER'S JEWELRY STORE, KAHLER'S DRUG STORE, BEEKMAN BANK, UNITED STATES HOTEL. - Neuber's Jewelry Store, 130 West California Street, Jacksonville, Jackson County, OR

305

DRUG-INDUCED LIVER DISEASE  

Center for Drug Evaluation (CDER)

Text Version... can we minimize missing this (study design)? - historical validation? (also false positive and negative “signals”) - when to pull the plug? ... More results from www.fda.gov/downloads/drugs/scienceresearch

306

Media coverage of drug approvals  

Microsoft Academic Search

This research examines how newly approved drugs are presented in newspapers, Food and Drug Administration (FDA) press releases, and websites. It finds that the print media coverage is more positive than FDA press releases and lacks basic information that would be important to consumers. The shortcomings of traditional media appear to be mitigated by the varied sources of information about

Robert J. Klotz; Stephen J. Ceccoli

2005-01-01

307

Fixed drug eruption to tartrazine.  

PubMed

An 11-year-old girl with a recurrent fixed drug eruption to tartrazine on the dorsum of the left hand is presented. Oral provocation tests to both the suspected food, an artificially coloured cheese crisp, and to tartrazine were positive. This case highlights fire need to consider artificial flavours, colours and preservatives as potential culprits in classic drug eruptions. PMID:9431719

Orchard, D C; Varigos, G A

1997-11-01

308

Sex, drugs and moral goals: reproductive strategies and views about recreational drugs.  

PubMed

Humans, unlike most other species, show intense interest in the activities of conspecifics, even when the activities in question pose no obvious fitness threat or opportunity. Here, we investigate one content domain in which people show substantial interest, the use of drugs for non-medical purposes. Drawing from two subject populations--one undergraduate and one Internet-based--we look at the relationships among (i) abstract political commitments; (ii) attitudes about sexuality; and (iii) views surrounding recreational drugs. Whereas some theories suggest that drug views are best understood as the result of abstract political ideology, we suggest that these views can be better understood in the context of reproductive strategy. We show that, as predicted by a strategic construal, drug attitudes are best predicted by sexual items rather than abstract political commitments and, further, that the relationship between factors such as political ideology and drugs, while positive, are reduced to zero or nearly zero when items assessing sexuality are controlled for. We conclude that considering morality from the standpoint of strategic interests is a potentially useful way to understand why humans care about third party behaviour. PMID:20554547

Kurzban, Robert; Dukes, Amber; Weeden, Jason

2010-06-16

309

Sex, drugs and moral goals: reproductive strategies and views about recreational drugs  

PubMed Central

Humans, unlike most other species, show intense interest in the activities of conspecifics, even when the activities in question pose no obvious fitness threat or opportunity. Here, we investigate one content domain in which people show substantial interest, the use of drugs for non-medical purposes. Drawing from two subject populations—one undergraduate and one Internet-based—we look at the relationships among (i) abstract political commitments; (ii) attitudes about sexuality; and (iii) views surrounding recreational drugs. Whereas some theories suggest that drug views are best understood as the result of abstract political ideology, we suggest that these views can be better understood in the context of reproductive strategy. We show that, as predicted by a strategic construal, drug attitudes are best predicted by sexual items rather than abstract political commitments and, further, that the relationship between factors such as political ideology and drugs, while positive, are reduced to zero or nearly zero when items assessing sexuality are controlled for. We conclude that considering morality from the standpoint of strategic interests is a potentially useful way to understand why humans care about third party behaviour.

Kurzban, Robert; Dukes, Amber; Weeden, Jason

2010-01-01

310

P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic myelogenous leukemia cells to treatment with imatinib mesylate  

Microsoft Academic Search

Imatinib (Glivec®, STI571) is an intracellular acting drug that demonstrates high activity against BCR-ABL-positive chronic myelogenous leukemia (CML) or acute lymphoblastic leukemia (ALL). However, many patients, especially with advanced disease, develop drug resistance. Here, we show by a novel high-performance liquid chromatography-based method that intracellular levels of imatinib decrease in P-glycoprotein (Pgp)-positive leukemic cells. In a model of K562 cells

T Illmer; M Schaich; U Platzbecker; J Freiberg-Richter; U Oelschlägel; M von Bonin; S Pursche; T Bergemann; G Ehninger; E Schleyer

2004-01-01

311

Drug use  

Microsoft Academic Search

In “Drug Use,” Peter Reuter, a professor at the University of Maryland School of Public Affairs and Department of Criminology,\\u000a examines substance abuse and addiction among welfare and low-income mothers. He describes the changing patterns of drug use\\u000a in the general population. Reuter explains that drug use increased rapidly in the late 1970s, declined in the 1980s, and remained\\u000a relatively

Peter Reuter

2006-01-01

312

36. INTERIOR VIEW, BERK SWITCH TOWER, SOUTH NORWALK, SHOWING SWITCHING ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

36. INTERIOR VIEW, BERK SWITCH TOWER, SOUTH NORWALK, SHOWING SWITCHING LEVERS FROM OPERATOR'S POSITION - New York, New Haven & Hartford Railroad, Automatic Signalization System, Long Island Sound shoreline between Stamford & New Haven, Stamford, Fairfield County, CT

313

2. VIEW OF ELEVATOR AT SECOND FLOOR BEDROOM, SHOWING ELEVATOR ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. VIEW OF ELEVATOR AT SECOND FLOOR BEDROOM, SHOWING ELEVATOR CAR IN THE 'STUCK' POSITION, WHERE IT REMAINED FROM 1942 UNTIL REMOVAL IN 1985, LOOKING NORTHEAST - 72 Marlborough Street, Residential Hydraulic Elevator, Boston, Suffolk County, MA

314

37. HANGAR FROM RAILROAD DECK TELESCOPED IN COLUMN & SHOWING ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

37. HANGAR FROM RAILROAD DECK TELESCOPED IN COLUMN & SHOWING PIN WHICH TRANSFERS LOAD FROM RAILROAD DECK TO TRUSS WHEN IN DOWN POSITION - Armour, Swift, Burlington Bridge, Kansas City, Jackson County, MO

315

4. VIEW, LOOKING SOUTHWEST, SHOWING TIMBER PILL APPROACH SPAN AND ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. VIEW, LOOKING SOUTHWEST, SHOWING TIMBER PILL APPROACH SPAN AND BRIDGE IN OPEN POSITION - New York, New Haven & Hartford Railroad, Shaw's Cove Bridge, Spanning Shaw's Cove, New London, New London County, CT

316

RIVER AND ROAD VIEW SHOWING METAL CRIB RETAINING WALLS AT ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

RIVER AND ROAD VIEW SHOWING METAL CRIB RETAINING WALLS AT RIGHT, FACING SOUTHWEST. PHOTO IS TAKEN FROM SAME POSITION AS PHOTO NO. 84, BUT WITH LONG LENS - Generals Highway, Three Rivers, Tulare County, CA

317

Design and Feasibility of a Randomized Behavioral Intervention to Reduce Distributive Injection Risk and Improve HealthCare Access Among hepatitisC virus Positive Injection Drug Users: The Study to Reduce Intravenous Exposures (STRIVE)  

Microsoft Academic Search

Hepatitis C virus (HCV) is hyperendemic among injection drug users (IDUs). However, few scientifically proven interventions\\u000a to prevent secondary transmission of HCV from infected IDUs to others exist. This report describes the design, feasibility,\\u000a and baseline characteristics of participants enrolled in the Study to Reduce Intravenous Exposure (STRIVE). STRIVE was a multisite,\\u000a randomized-control trial to test a behavioral intervention developed

Farzana Kapadia; Mary H. Latka; Holly Hagan; Elizabeth T. Golub; Jennifer V. Campbell; Micaela H. Coady; Richard S. Garfein; David L. Thomas; Sebastian Bonner; Thelma Thiel; Steffanie A. Strathdee

2007-01-01

318

In vitro validation of drug-induced phospholipidosis.  

PubMed

Intracellular accumulation of phospholipids with lamellar bodies is a hallmark of drug-induced phospholipidosis (PLD) which is caused by impaired phospholipid metabolism of the lysosome. Although it remains uncertain whether PLD is associated with the adverse effects, sponsors generally terminate the development of a candidate drug when PLD is observed in an organ. For drugs that are used without serious adverse events, there should be labels indicating that the drug can induce PLD. We conducted LipidTox and NBD-PE assays for detecting PLD to compare and validate the methods. In the case of contrary results in both assays, electron microscopy was performed to confirm the data. We selected 12 chemicals and divided them into 4 categories: P+S+, PLD and steatosis positive; P+/S-, PLD positive and steatosis negative; P-S+, PLD negative and steatosis positive; P-/S-, PLD and steatosis negative. In general, results showed very good agreement with the known information with some minor discrepancies. LipidTox assay is proven to be a very sensitive method. Considering the contrary results of acetaminophen and menadione in LipidTox and the NBD-PE assay, the combination of two methods using different phospholipids is advantageous to reduce false positives. The finding that acetaminophen was positive in LipidTos assay and increased the frequency of lamellar body implies that acetaminophen is a weak inducer of PLD. PMID:22467016

Park, Sora; Choi, You-Jin; Lee, Byung-Hoon

2012-01-01

319

Drug Rash (Unclassified Drug Eruption) in Adults  

MedlinePLUS

newsletter | contact Share | Drug Eruption, Unclassified Information for adults A A A Acute drug eruption with numerous red, raised lesions. Overview A drug rash (drug eruption), also known as a drug ...

320

[Antidepressant drugs].  

PubMed

Depression is a disorder of mood that causes strong impact on the patient and his family's quality of life. The increasing number of cases and its social consequences have made depression a great public health problem. Some depressant patients develop suicide thoughts and may try suicide later. The disease occurs in all ages and its prevalence is of 7.4%. Women aged 15 to 29 are more likely to be affected, whereas people aged 50 or older are less affected. The presence of depression worsens the prognostic of other clinical conditions when compared to not depressant patients. This paper describes the main drugs used in the treatment of depression and correlates the drug with the neurobiology of the disease. Aiming the study of the pharmacologic and therapeutic characteristics of antidepressant drugs, a literature review was performed using electronic databases (Pubmed and Lilacs), papers and books related to the theme. The main antidepressant drugs are classified according to their chemical structure or their action on neurotransmitters. An important point in the therapy is the understanding of the pharmacokinetics of the drugs. The choice of the drug must consider the symptoms, the patient's age, other drugs in use, the history of pharmacological treatments and so forth. No drug is significantly better than the other in the treatment of depression. The important thing in choosing a drug is to have the best therapeutic response, the reduction of symptoms, a good adherence to therapy, few side effects and secure drug interaction. By understanding the use of these drugs, it will be possible to give the patient and his family a better quality of life. PMID:21672446

Aguiar, C Clayton; Castro, Thiago R; Carvalho, André F; Vale, Otoni C; Sousa, F Cléa; Vasconcelos, Silvânia M

2011-02-28

321

[Drug dependence and psychotropic drugs].  

PubMed

Although the utility of psychotropic drugs has been well demonstrated, caution must still be exercised in their use. Among their potential risks, drug dependency must be kept in mind. This risk is well accepted with regard to benzodiazepines, and it appeared useful to study the potential risk for antidepressants, neuroleptics and thymoregulatory agents. Whatever the drug, the predominant factor appears to be psychological dependency. Prevention of drug dependency is most often achieved by informing the patient, limiting the length of use of the drug, making regular reevaluation of symptoms and of drug indication, and frequently be establishing a "treatment contract". The importance of the patient-physician relationship in the prescription of such treatment must be underlined. PMID:7984941

Giraud, M J; Lemonnier, E; Bigot, T

1994-11-01

322

Drug Testing.  

ERIC Educational Resources Information Center

|A number of legal issues are involved in conducting a drug testing program to determine whether students--and occasionally teachers--are using illegal drugs. Two legal issues have been raised concerning the accuracy of the urinalysis test: whether it is chemically accurate and whether appropriate procedures have been followed to make certain that…

Legal Memorandum, 1987

1987-01-01

323

Drug Testing.  

ERIC Educational Resources Information Center

A number of legal issues are involved in conducting a drug testing program to determine whether students--and occasionally teachers--are using illegal drugs. Two legal issues have been raised concerning the accuracy of the urinalysis test: whether it is chemically accurate and whether appropriate procedures have been followed to make certain that…

Legal Memorandum, 1987

1987-01-01

324

Antineoplastic Drugs  

NASA Astrophysics Data System (ADS)

The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

Sadée, Wolfgang; El Sayed, Yousry Mahmoud

325

Contribution of Saccadic Motion to Intravitreal Drug Transport: Theoretical Analysis  

PubMed Central

Purpose The vitreous humor liquefies with age and readily sloshes during eye motion. The objective was to develop a computational model to determine the effect of sloshing on intravitreal drug transport for transscleral and intra-vitreal drug sources at various locations Methods A finite element model based on a telescopic implicit envelope tracking scheme was developed to model drug dispersion. Flow velocities due to saccadic oscillations were solved for and were used to simulate drug dispersion. Results Saccades induced a three-dimensional flow field that indicates intense drug dispersion in the vitreous. Model results showed that the time scale for transport decreased for the sloshing vitreous when compared to static vitreous. Macular concentrations for the sloshing vitreous were found be much higher than that for the static vitreous. For low viscosities the position of the intravitreal source did not have a big impact on drug distribution. Conclusion Model results show that care should be taken when extrapolating animal data, which are mostly done on intact vitreous, to old patients whose vitreous might be a liquid. The decrease in drug transport time scales and changes in localized concentrations should be considered when deciding on treatment modalities and dosing strategies.

Balachandran, Ram K.

2011-01-01

326

Neural effects of positive and negative incentives during marijuana withdrawal.  

PubMed

In spite of evidence suggesting two possible mechanisms related to drug-seeking behavior, namely reward-seeking and harm avoidance, much of the addiction literature has focused largely on positive incentivization mechanisms associated with addiction. In this study, we examined the contributing neural mechanisms of avoidance of an aversive state to drug-seeking behavior during marijuana withdrawal. To that end, marijuana users were scanned while performing the monetary incentive delay task in order to assess positive and negative incentive processes. The results showed a group x incentive interaction, such that marijuana users had greater response in areas that underlie reward processes during positive incentives while controls showed greater response in the same areas, but to negative incentives. Furthermore, a negative correlation between withdrawal symptoms and response in the amygdala during negative incentives was found in the marijuana users. These findings suggest that although marijuana users have greater reward sensitivity and less harm avoidance than controls, that attenuated amygdala response, an area that underlies fear and avoidance, was present in marijuana users with greater marijuana withdrawal symptoms. This is concordant with models of drug addiction that involve multiple sources of reinforcement in substance use disorders, and suggests the importance of strategies that focus on respective mechanisms. PMID:23690923

Filbey, Francesca M; Dunlop, Joseph; Myers, Ursula S

2013-05-15

327

Magic, Monsters, and Movies: Americas Midnight Ghost Shows  

Microsoft Academic Search

This essay examines midnight ghost shows (alternately known as “spook shows,” or “spookers”) and seeks to reinsert them into theatre history and to posit them as a cultural barometer of the time in which they were popular. Ghost shows were magic shows presented on the stages of America’s movie theatres throughout the first half of the twentieth century. A ghost

Beth A. Kattelman

2010-01-01

328

Utilising Discursive Positioning in Counselling  

ERIC Educational Resources Information Center

|Foucault's concern with the production of subjectivity has led to the development of positioning theory, as it has been called by Bronwyn Davies, Rom Harr and Luk van Langenhve. The concept of discursive positioning has particular value for counselling because it shows how people are positioned in discourse in particular moments by their own and…

Winslade, John M.

2005-01-01

329

Tunable drug loading and release from polypeptide multilayer nanofilms  

PubMed Central

Polypeptide multilayer nanofilms were prepared using electrostatic layer-by-layer self-assembly nanotechnology. Small charged drug molecules (eg, cefazolin, gentamicin, and methylene blue) were loaded in polypeptide multilayer nanofilms. Their loading and release were found to be pH-dependent and could also be controlled by changing the number of film layers and drug incubation time, and applying heat-treatment after film formation. Antibioticloaded polypeptide multilayer nanofilms showed controllable antibacterial properties against Staphylococcus aureus. The developed biodegradable polypeptide multilayer nanofilms are capable of loading both positively- and negatively-charged drug molecules and promise to serve as drug delivery systems on biomedical devices for preventing biomedical device-associated infection, which is a significant clinical complication for both civilian and military patients.

Jiang, Bingbing; Li, Bingyun

2009-01-01

330

Prison rights: mandatory drugs tests and performance indicators for prisons.  

PubMed

Mandatory drugs testing of prisoners applies throughout England and Wales. Data from the 1995 pilot study in eight prisons show that the proportion testing positive for opiates or benzodiazepines rose from 4.1% to 7.4% between the first and second phase of random testing and that there was a 20% increase over 1993-4 in the provisional total of assaults for 1995. Interpretation of these data is difficult, but this is no excuse for prevarication over the danger that this policy may induce inmates to switch from cannabis (which has a negligible public health risk) to injectable class A drugs (a serious public health risk) in prison. The performance indicators for misuse of drugs that are based on the random mandatory drugs testing programme lack relevant covariate information about the individuals tested and are not reliable or timely for individual prisons. PMID:8646103

Gore, S M; Bird, A G; Ross, A J

1996-06-01

331

Sun Position (Polar Coordinates)  

NSDL National Science Digital Library

This applet shows the current (realtime) Sun position as seen from a polar view above the North pole. The elevation and azimuth of the Sun are given, and a brief description of celestial coordinates and celestial spheres is covered as well. A demonstration of this applet is available to download.

Giesen, Juergen

332

[Club drugs].  

PubMed

Club drugs are the following substances: Methylenedioxymethamphetamine (MDMA); Methamphetamine; Lysergic Acid Diethylamide (LSD); Ketamine; Gamma-hydroxybutyrate (GHB) and Flunitrazepam. These substances are mainly used by adolescents and young adults, mostly in recreational settings like dance clubs and rave parties. These drugs have diverse psychotropic effects, are associated with several degrees of toxicity, dependence and long term adverse effects. Some have been used for several decades, while others are relatively recent substances of abuse. They have distinct pharmacodynamic and pharmacokinetic properties, are not easy to detect and, many times, the use of club drugs is under diagnosed. Although the use of these drugs is increasingly common, few health professionals feel comfortable with the diagnosis and treatment. The authors performed a systematic literature review, with the goal of synthesising the existing knowledge about club drugs, namely epidemiology, mechanism of action, detection, adverse reactions and treatment. The purpose of this article is creating in Portuguese language a knowledge data base on club drugs, that health professionals of various specialties can use as a reference when dealing with individual with this kind of drug abuse. PMID:22525626

Guerreiro, Diogo Frasquilho; Carmo, Ana Lisa; da Silva, Joaquim Alves; Navarro, Rita; Góis, Carlos

2011-12-29

333

A Randomized Pilot Study of the Engaging Moms Program for Family Drug Court  

PubMed Central

In response to the need for effective drug court interventions, the effectiveness of the Engaging Moms Program (EMP) versus intensive case management services (ICMS) on multiple outcomes for mothers enrolled in family drug court was investigated. In this intent-to-treat study, mothers (N = 62) were randomly assigned to either usual drug court care or the Engaging Moms drug court program. Mothers were assessed at intake, and 3, 6, 12, and 18 months following intake. Results indicated that at 18 months post drug court enrollment, 77% of mothers assigned to EMP versus 55% of mothers assigned to ICMS had positive child welfare dispositions. There were statistically significant time effects for both intervention groups on multiple outcomes including substance use, mental health, parenting practices, and family functioning. EMP showed equal or better improvement than ICMS on all outcomes. The results suggest that EMP in family drug court is a viable and promising intervention approach to reduce maternal addiction and child maltreatment.

Dakof, Gayle A.; Cohen, Jeri B.; Henderson, Craig E.; Duarte, Eliette; Boustani, Maya; Blackburn, Audra; Venzer, Ellen; Hawes, Sam

2010-01-01

334

Discontinued drugs in 2012: cardiovascular drugs.  

PubMed

The continued high rate of cardiovascular morbidity and mortality has attracted wide concern and great attention of pharmaceutical industry. In order to reduce the attrition of cardiovascular drug R&D, it might be helpful recapitulating previous failures and identifying the potential factors to success. This perspective mainly analyses the 30 cardiovascular drugs dropped from clinical development in 2012. Reasons causing the termination of the cardiovascular drugs in the past 5 years are also tabulated and analysed. The analysis shows that the attrition is highest in Phase II trials and financial and strategic factors and lack of clinical efficacy are the principal reasons for these disappointments. To solve the four problems (The 'better than the Beatles' problem, the 'cautious regulator' problem, the 'throw money at it' tendency and the 'basic researchbrute force' bias) is recommended as the main measure to increase the number and quality of approvable products. PMID:23992034

Zhao, Hong-Ping; Jiang, Hong-Min; Xiang, Bing-Ren

2013-08-30

335

Prescription Drug Data Summary.  

National Technical Information Service (NTIS)

Data on prescription drugs are provided in regard to personal health expenditures and outpatient prescription drug insurance coverage, government expenditures for drugs and drug services, drug industry and product information, and drug vendors and prices ...

T. R. Fulda

1974-01-01

336

Drug Paraphernalia  

MedlinePLUS

DEA - Get Smart About Drugs - A Resource for Parents from the DEA Email Page Print Page Font Size Contact Us Home ... small paper bags Cigarette packages Small glass vials Pill bottles Candy or gum wrappers Baseball cap/ski ...

337

Drug Rashes  

MedlinePLUS

... Skin Infections Fungal Skin Infections Viral Skin Infections Sunlight and Skin Damage Noncancerous Skin Growths Skin Cancers ... the skin particularly sensitive to the effects of sunlight (photosensitivity). These drugs include certain antipsychotics, tetracycline Some ...

338

Drug Facts  

Center for Drug Evaluation (CDER)

Text Version... have 3 or more alcoholic drinks every day while using ... It is especially important not to use ibuprofen during ... effective dose should be used ? do not ... More results from www.fda.gov/downloads/drugs/drugsafety

339

Drug Interactions  

MedlinePLUS

... You and your health care provider should carefully review the information that comes with each medication (the “ ... taking. Also, be sure that your care providers review ALL medications, drugs, and supplements or herbs you ...

340

Hazardous Drugs  

MedlinePLUS

... requires the reporting of employee exposure to hazardous medications, and allows access to these records by employees. 1910.1200 , Hazard communication. Includes the coverage of drugs and pharmaceuticals in ...

341

Generic Drugs  

Center for Drug Evaluation (CDER)

... Page Last Updated: 09/09/2010 Note: If you need help accessing information in different file formats, see Instructions for Downloading Viewers and ... More results from www.fda.gov/drugs/resourcesforyou

342

Drug Addiction  

MedlinePLUS

... rate and blood pressure Drowsiness and loss of consciousness (with GHB and Rohypnol) GHB and Rohypnol are ... drugs are taken with alcohol. Because they worsen consciousness and memory and they're easy to give ...

343

Antipsychotic Drugs  

MedlinePLUS

... and risperidone— come as generics. Our advice: For schizophrenia: In general, almost everyone who is diagnosed with ... Should Know Antipsychotic drugs can help people with schizophrenia lead more stable lives and spend less time ...

344

Drug dependence  

MedlinePLUS

... Hallucinogens include LSD, mescaline, psilocybin ("mushrooms"), and phencyclidine (PCP or "angel dust"). They can cause people to ... NIDA . NIDA InfoFacts: Hallucinogens - LSD, Peyote, Psilocybin, and PCP . National Institute on Drug Abuse. NIDA. Revised 6/ ...

345

Drug Name  

Center for Drug Evaluation (CDER)

Text Version... in Americans ages 60 and older. Erwinaze asparaginase Erwinia chrysanthemi 11/18 To treat acute lymphoblastic leukemia ... More results from www.fda.gov/downloads/drugs/developmentapprovalprocess

346

Drug Recalls  

Center for Drug Evaluation (CDER)

... See Definitions of Market Withdrawals and Class I, II, and III recalls. All recalls (Class I, II, and III) can be found in the FDA Enforcement Report. ... More results from www.fda.gov/drugs/drugsafety/drugrecalls

347

Why drugs?  

Microsoft Academic Search

Drug therapy for obesity has had a difficult past history. A number of drugs have had addictive or toxic properties that have\\u000a required discontinuation. Pharmacotherapy for obesity has an important role in those persons who have failed behavioral weight\\u000a loss attempts or as an adjunct to those attempts. The interest in pharmacotherapy for obesity is an outgrowth of the now

F. Xavier Pi-Sunyer

348

Teens and Prescription Drugs: An Analysis of Recent Trends on the Emerging Drug Threat  

ERIC Educational Resources Information Center

|This report synthesizes a number of national studies that show the intentional abuse of prescription drugs to get high is a growing concern, particularly among teens. The analysis shows that teens are turning away from street drugs and using prescription drugs to get high. New users of prescription drugs have caught up with new users of…

Office of National Drug Control Policy, 2007

2007-01-01

349

Pharmacologic and Behavioral Withdrawal From Addictive Drugs  

Microsoft Academic Search

Recent theories suggest that drug withdrawal does not motivate drug use and relapse. However, data now show that withdrawal produces complex changes over time in at least two symptoms (i.e., negative affect and urges) that are highly predictive of relapse. Evidence suggests that falling levels of the drug in the blood and interruption of the drug self-administration ritual both affect

Timothy B. Baker; Sandra J. Japuntich; Joanne M. Hogle; Danielle E. McCarthy; John J. Curtin

2006-01-01

350

Drug allergy  

PubMed Central

Allergic drug reactions occur when a drug, usually a low molecular weight molecule, has the ability to stimulate an immune response. This can be done in one of two ways. The first is by binding covalently to a self-protein, to produce a haptenated molecule that can be processed and presented to the adaptive immune system to induce an immune response. Sometimes the drug itself cannot do this but a reactive breakdown product of the drug is able to bind covalently to the requisite self-protein or peptide. The second way in which drugs can stimulate an immune response is by binding non-covalently to antigen presenting or antigen recognition molecules such as the major histocompatibility complex (MHC) or the T cell receptor. This is known as the p-I or pharmacological interaction hypothesis. The drug binding in this situation is reversible and stimulation of the response may occur on first exposure, not requiring previous sensitization. There is probably a dependence on the presence of certain MHC alleles and T cell receptor structures for this type of reaction to occur.

Warrington, Richard

2012-01-01

351

Drug Development and Drug Interactions  

Center for Drug Evaluation (CDER)

... organizes and participates in various conferences and workshops and regularly publishes new considerations and findings in the scientific literature ... More results from www.fda.gov/drugs/developmentapprovalprocess/developmentresources

352

In silico modeling to predict drug-induced phospholipidosis.  

PubMed

Drug-induced phospholipidosis (DIPL) is a preclinical finding during pharmaceutical drug development that has implications on the course of drug development and regulatory safety review. A principal characteristic of drugs inducing DIPL is known to be a cationic amphiphilic structure. This provides evidence for a structure-based explanation and opportunity to analyze properties and structures of drugs with the histopathologic findings for DIPL. In previous work from the FDA, in silico quantitative structure-activity relationship (QSAR) modeling using machine learning approaches has shown promise with a large dataset of drugs but included unconfirmed data as well. In this study, we report the construction and validation of a battery of complementary in silico QSAR models using the FDA's updated database on phospholipidosis, new algorithms and predictive technologies, and in particular, we address high performance with a high-confidence dataset. The results of our modeling for DIPL include rigorous external validation tests showing 80-81% concordance. Furthermore, the predictive performance characteristics include models with high sensitivity and specificity, in most cases above ?80% leading to desired high negative and positive predictivity. These models are intended to be utilized for regulatory toxicology applied science needs in screening new drugs for DIPL. PMID:23541745

Choi, Sydney S; Kim, Jae S; Valerio, Luis G; Sadrieh, Nakissa

2013-03-27

353

Enhancement of anticancer efficacy using modified lipophilic nanoparticle drug encapsulation  

PubMed Central

Background Development of anticancer drugs is challenging. Indeed, much research effort has been spent in the development of new drugs to improve clinical outcomes with minimal toxicity. We have previously reported that a formulation of lipid gold porphyrin nanoparticles reduced systemic drug toxicity when compared with free gold porphyrin. In this study, we investigated the delivery and treatment efficiency of PEG surface-modified lipid nanoparticles as a carrier platform. Methods We encapsulated antitumor drugs into PEG-modified lipid nanoparticles and these were characterized by size, zeta potential, and encapsulation efficiency. The delivery efficiency into tumor tissue was evaluated using a biodistribution study. To evaluate antitumor efficacy, gold porphyrin or camptothecin (a DNA topoisomerase I inhibitor) were encapsulated and compared using an in vivo neuroblastoma (N2A) model. Results We showed that drug encapsulation into PEG-modified lipid nanoparticles enhanced the preferential uptake in tumor tissue. Furthermore, higher tumor killing efficiency was observed in response to treatment with PEG-modified lipid nanoparticles encapsulating gold porphyrin or camptothecin when compared with free gold porphyrin or free camptothecin. The in vivo antitumor effect was further confirmed by study of tumor inhibition and positive apoptosis activity. Surface modification of lipophilic nanoparticles with PEG increased the efficiency of drug delivery into tumor tissue and subsequently more effective antitumor activity. Conclusion This specific design of a chemotherapeutic agent using nanotechnology is important in the development of a safe and effective drug in cancer therapy.

Lee, Puiyan; Zhang, Ruizhong; Li, Vincent; Liu, Xuelai; Sun, Raymond WY; Che, Chi-Ming; Wong, Kenneth KY

2012-01-01

354

Pharmaceutical Policy Change and the Safety of New Drugs  

Microsoft Academic Search

Policy reforms in the Food and Drug Administration (FDA) have led to substantial increases in the speed of new-drug review. While data show that FDA review times for new drugs have fallen as much as 50 percent, other data show that several new drugs have been withdrawn from the market for safety reasons. This flurry of new- drug withdrawals raises

2002-01-01

355

Acacetin and Chrysin, Two Polyphenolic Compounds, Alleviate Telomeric Position Effect in Human Cells  

PubMed Central

We took advantage of the ability of human telomeres to silence neighboring genes (telomere position effect or TPE) to design a high-throughput screening assay for drugs altering telomeres. We identified, for the first time, that two dietary flavones, acacetin and chrysin, are able to specifically alleviate TPE in human cells. We further investigated their influence on telomere integrity and showed that both drugs drastically deprotect telomeres against DNA damage response. However, telomere deprotection triggered by shelterin dysfunction does not affect TPE, indicating that acacetin and chrysin target several functions of telomeres. These results show that TPE-based screening assays represent valuable methods to discover new compounds targeting telomeres.

Boussouar, Amina; Barette, Caroline; Nadon, Robert; Saint-Leger, Adelaide; Broucqsault, Natacha; Ottaviani, Alexandre; Firozhoussen, Arva; Lu, Yiming; Lafanechere, Laurence; Gilson, Eric; Magdinier, Frederique; Ye, Jing

2013-01-01

356

Prevalence of drug use in French seamen.  

PubMed

The main objective of the present study is to determine the prevalence of lifetime use and use in the past 30 days of narcotics in French seamen and to assess factors correlated with positive urine test in seamen as a whole. A stratified survey conducted in 19 French ports collected 1,928 self-administered questionnaires on cigarette, alcohol and narcotics consumption. Seafarers were randomly selected and interviewed during their annual seafaring aptitude consultation. Only the 1847 male respondents were included in analysis. Nearly half of the seamen had tried cannabis at some point in their life, and 16% were users in the past 30 days. Lifetime use of certain other illegal drugs (cocaine, heroin, hallucinogenic mushrooms, poppers and ecstasy) was non-negligible, but cocaine and heroin were the only ones showing exceptional prevalence of consumption over the previous 30 days. Lifetime use of drugs was non-negligible among seamen. Prevalence of recent cannabis use was elevated. Recent consumption as indicated by positive urine test correlated with age group, family situation, occupational category, geographical area, young age of first alcohol consumption and experimentation with other drugs. PMID:22130516

Fort, Emmanuel; Massardier-Pilonchéry, Amélie; Facy, Françoise; Bergeret, Alain

2011-11-15

357

Cationic amphiphilic drugs self-assemble to the core-shell interface of PEGylated phospholipid micelles and stabilize micellar structure.  

PubMed

Since polymeric micelles are promising and have potential in drug delivery systems, people have become more interested in studying the compatibility of polymeric carriers and drugs, which might help them to simplify the preparation method and increase the micellar stability. In this article, we report that cationic amphiphilic drugs can be easily encapsulated into PEGylated phospholipid (PEG-PE) micelles by self-assembly method and that they show high encapsulation efficiency, controllable drug release and better micellar stability than empty micelles. The representative drugs are doxorubicin and vinorelbine. However, gemcitabine and topotecan are not suitable for PEG-PE micelles due to lack of positive charge or hydrophobicity. Using a series of experiments and molecular modelling, we figured out the assembly mechanism, structure and stability of drug-loaded micelles, and the location of drugs in micelles. Integrating the above information, we explain the effect of the predominant force between drugs and polymers on the assembly mechanism and drug release behaviour. Furthermore, we discuss the importance of pKa and to evaluate the compatibility of drugs with PEG-PE in self-assembly preparation method. In summary, this work provides a scientific understanding for the reasonable designing of PEG-PE micelle-based drug encapsulation and might enlighten the future study on drug-polymer compatibility for other polymeric micelles. PMID:24000361

Wang, Jing; Xing, Xueqing; Fang, Xiaocui; Zhou, Chang; Huang, Feng; Wu, Zhonghua; Lou, Jizhong; Liang, Wei

2013-09-02

358

Positive predictive value of a case definition for diabetes mellitus using automated administrative health data in children and youth exposed to antipsychotic drugs or control medications: a Tennessee Medicaid study  

PubMed Central

Background We developed and validated an automated database case definition for diabetes in children and youth to facilitate pharmacoepidemiologic investigations of medications and the risk of diabetes. Methods The present study was part of an in-progress retrospective cohort study of antipsychotics and diabetes in Tennessee Medicaid enrollees aged 6–24 years. Diabetes was identified from diabetes-related medical care encounters: hospitalizations, outpatient visits, and filled prescriptions. The definition required either a primary inpatient diagnosis or at least two other encounters of different types, most commonly an outpatient diagnosis with a prescription. Type 1 diabetes was defined by insulin prescriptions with at most one oral hypoglycemic prescription; other cases were considered type 2 diabetes. The definition was validated for cohort members in the 15 county region geographically proximate to the investigators. Medical records were reviewed and adjudicated for cases that met the automated database definition as well as for a sample of persons with other diabetes-related medical care encounters. Results The study included 64 cases that met the automated database definition. Records were adjudicated for 46 (71.9%), of which 41 (89.1%) met clinical criteria for newly diagnosed diabetes. The positive predictive value for type 1 diabetes was 80.0%. For type 2 and unspecified diabetes combined, the positive predictive value was 83.9%. The estimated sensitivity of the definition, based on adjudication for a sample of 30 cases not meeting the automated database definition, was 64.8%. Conclusion These results suggest that the automated database case definition for diabetes may be useful for pharmacoepidemiologic studies of medications and diabetes.

2012-01-01

359

Transcript: Drug Safety Communications  

Center for Drug Evaluation (CDER)

... Drugs. ... Division of Drug Information tweets every single Drug Safety Communication. ... you have questions about Drug Safety Communications, call ... More results from www.fda.gov/drugs/resourcesforyou/healthprofessionals

360

FDA Drug Safety Newsletter  

Center for Drug Evaluation (CDER)

... Section Contents Menu. Drug Safety and Availability. FDA Drug Safety Newsletter. ... FDA Drug Safety Newsletter. The FDA Drug Safety ... More results from www.fda.gov/drugs/drugsafety/drugsafetynewsletter

361

Drug Safety Information  

Center for Drug Evaluation (CDER)

... Postmarket Drug Safety Information for Patients and Providers; Index to Drug-Specific Information Drug safety and side effects; includes drugs with ... More results from www.fda.gov/drugs/resourcesforyou/healthprofessionals

362

Flat Globe: Showing the Changing Seasons  

NSDL National Science Digital Library

SeaWiFS false color data showing seasonal change in the oceans and on land for the entire globe. The data is seasonally averaged, and shows the sequence: fall, winter, spring, summer, fall, winter, spring (for the Northern Hemisphere).

Allen, Jesse; Newcombe, Marte; Feldman, Gene

1998-09-09

363

The Franklin Institute's Traveling Science Shows  

NSDL National Science Digital Library

The Franklin Institute's team of science educators are available for shows on a variety of science topics. Traveling Science shows are aligned with National Science Education Standards, and focus on Physics, Biology and Chemistry.

Shows, Traveling S.

2004-04-05

364

Remote Controlled Drug Release Induced by a Rotating Magnetic Field  

Microsoft Academic Search

A novel type of a medical capsule is described which is suitable to perform remote controlled drug release at predetermined\\u000a positions in the gastrointestinal tract without the use of ionizing radiation. This capsule is based on magnetically generated\\u000a heating effects and completely consists of biocompatible parts. Theoretical estimations show that the maximum depth of the\\u000a capsule below the abdominal wall

W. Andrä; T. Gesener; A. Raabgrund; M. E. Bellemann

365

Urine drug testing of chronic pain patients: licit and illicit drug patterns.  

PubMed

Chronic pain patients are frequently maintained on one or more powerful opioid medications in combination with other psychoactive medications. Urine tests provide objective information regarding patient compliance status. Little information is available on testing this unique population. The goal of this study was to characterize drug disposition patterns in urine specimens collected from a large population of pain patients. Confirmation data for 10,922 positive specimens were collated into 11 drug Classes. The number of drug/metabolites tested (#) and number of confirmed positive specimens were as follows: amphetamines (7), 160; barbiturates (5), 308; benzodiazepines (6), 2397; cannabinoids (1), 967; carisoprodol (2), 611; cocaine (1), 310; fentanyl (1), 458; meperidine (2), 58; methadone (2), 1209; opiates (7), 8996; and propoxyphene (2), 385. Subdivision into 19 distinct drug Groups allowed characterization of drug use patterns. Of the 10,922 positive specimens, 15,859 results were reported as positive in various drug Classes, and 27,197 drug/metabolites were measured by gas chromatography-mass spectrometry. The frequency of illicit drug use (cannabis, cocaine, ecstasy) was 10.8%. Being the first study of this type, these data present a large array of information on licit and illicit drug use, drug detection frequencies, drug/metabolite patterns, and multi-drug use combinations in pain patients. PMID:19007501

Cone, Edward J; Caplan, Yale H; Black, David L; Robert, Timothy; Moser, Frank

2008-10-01

366

Silicon nanowire detectors showing phototransistive gain  

Microsoft Academic Search

Nanowire photodetectors are shown to function as phototransistors with high sensitivity. Due to small lateral dimensions, a nanowire detector can have low dark current while showing large phototransistive gain. Planar and vertical silicon nanowire photodetectors fabricated in a top-down approach using an etching process show a phototransistive gain above 35 000 at low light intensities. Simulations show that incident light

Arthur Zhang; Cesare Soci; Yisi Liu; Deli Wang; Yu-Hwa Lo

2008-01-01

367

Watching The Daily Show in Kenya  

Microsoft Academic Search

Global distribution of a popular American television programme – Jon Stewart's Daily Show – offers a rare opportunity to examine transnational contingencies of meaning in political satire. Drawing on focus group discussions in Kenya, this analysis shows how some East Africans appropriated and reinterpreted – indeed unexpectedly subverted – The Daily Show's political content, deriving from it insights that Stewart

Angelique Haugerud; Dillon Mahoney; Meghan Ference

2012-01-01

368

Short communication Club drug use among college students  

Microsoft Academic Search

This study examined prevalence and frequency of bclubQ drug use among college students (N=831) and associations with marijuana and alcohol use, sensation seeking, and positive and negative affectivity. Eighteen percent (n=146) of the sample had used club drugs at least once in their lifetime. Results of a logistic regression indicated that club drug use was positively associated with marijuana use,

Jeffrey S. Simons; Raluca M. Gaher; Christopher J. Correia; Jacqueline A. Bush

369

Drug Filtering  

NSDL National Science Digital Library

In this math meets health science activity, learners observe a model of exponential decay, and how kidneys filter blood. Learners will calculate the amount of a drug in the body over a period of time. Then, they will make and analyze the graphical representation of this exponential function. This lesson guide includes questions for learners, assessment options, extensions, and reflection questions.

Iles, Lawrence F.

2010-01-01

370

Antineoplastic Drugs.  

ERIC Educational Resources Information Center

|This module on antineoplastic drugs is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are…

Morris, Sara; Michael, Nancy, Ed.

371

Drug Rescue Distinguishes between Different Structural Models of Human P-Glycoprotein.  

PubMed

There is no high-resolution crystal structure of the human P-glycoprotein (P-gp) drug pump. Homology models of human P-gp based on the crystal structures of mouse or Caenorhabditis elegans P-gps show large differences in the orientation of transmembrane segment 5 (TM5). TM5 is one of the most important transmembrane segments involved in drug-substrate interactions. Drug rescue of P-gp processing mutants containing an arginine at each position in TM5 was used to identify positions facing the lipid or internal aqueous chamber. Only the model based on the C. elegans P-gp structure was compatible with the drug rescue results. PMID:24083983

Loo, Tip W; Clarke, David M

2013-10-02

372

Drug Rescue Distinguishes between Different Structural Models of Human P-Glycoprotein  

PubMed Central

There is no high-resolution crystal structure of the human P-glycoprotein (P-gp) drug pump. Homology models of human P-gp based on the crystal structures of mouse or Caenorhabditis elegans P-gps show large differences in the orientation of transmembrane segment 5 (TM5). TM5 is one of the most important transmembrane segments involved in drug–substrate interactions. Drug rescue of P-gp processing mutants containing an arginine at each position in TM5 was used to identify positions facing the lipid or internal aqueous chamber. Only the model based on the C. elegans P-gp structure was compatible with the drug rescue results.

2013-01-01

373

Drug users’ perceptions of ‘controlled’ and ‘uncontrolled’ use  

Microsoft Academic Search

How do certain users lose control over the drug or drugs they are using and others manage to achieve and maintain control? The control of drugs is largely established by (sub)culturally based social controls (rituals and rules) which pattern the way a drug is used. Controlled users have a multiplicity of meaningful roles, which give them a positive identity and

Tom Decorte

2001-01-01

374

Patterns of drug use and expectations in methadone patients  

Microsoft Academic Search

Expectations about future behavior have been shown to have a positive relationship with subsequent behavior. For patients in drug treatment, recovery should manifest changes in drug use and in cognitive perceptions of being able to refrain from use. The present study identified latent patterns of the longitudinal relationship between drug use expectation and illegal drug use during treatment. Latent variable

George W. Joe; Patrick M. Flynn; Kirk M. Broome; D. Dwayne Simpson

2007-01-01

375

Study Shows Potential for Antarctic Climate Change  

NSDL National Science Digital Library

This article reports on a study, conducted at the National Aeronautics and Space Administration's (NASA's) Goddard Institute of Space Studies (GISS), in which researchers found depleted ozone levels and greenhouse gases are currently contributing to cooler South Pole temperatures. However, this trend is likely to reverse in the next 50 years. Low ozone levels in the stratosphere and increasing greenhouse gases promote a positive phase of a shifting atmospheric climate pattern in the Southern Hemisphere, called the Southern Annular Mode (SAM). A positive SAM isolates colder air in the Antarctic interior. In the coming decades, ozone levels are expected to recover due to international treaties that banned ozone-depleting chemicals. Higher ozone in the stratosphere protects Earth's surface from harmful ultraviolet radiation. The study found higher ozone levels might have a reverse impact on the SAM, promoting a warming, negative phase.

376

Why We Should be Vigilant: Drug Cytotoxicity Observed with In Vitro Transporter Inhibition Studies  

PubMed Central

From routine in vitro drug-transporter inhibition assays, observed inhibition is typically assumed from direct interaction with the transporter. Other mechanisms that possibly reduce substrate uptake are not frequently fully examined. The objective of this study was to investigate the association of transporter inhibition with drug cytotoxicity. From a pool of drugs that were identified as known ASBT or OCTN2 inhibitors, twenty one drugs were selected to screen inhibitory potency of their prototypical substrate and cytotoxicity against three human sodium-dependent solute carrier (SLC) transporters: apical sodium-dependent bile acid transporter (ASBT), organic cation/carnitine transporter (OCTN2), and the excitatory amino acid transporter 4 (EAAT4) in stable cell lines. Twenty drugs showed apparent inhibition in OCTN2-MDCK and ASBT-MDCK. Four dihydropyridine calcium channel blockers were cytotoxic to MDCK cells, and the observed cytotoxicity of three of them accounted for their apparent OCTN2 inhibition, and consequently were classified as non-OCTN2 inhibitors. Meanwhile, since their cytotoxicity only moderately contributed to ASBT inhibition, these three were still considered ASBT inhibitors. Four other drugs showed apparent inhibition in EAAT4-HEK cells, and cytotoxicity of three drugs corresponded with their inhibition of this transporter. Therefore, cytotoxicity significantly affected EAAT4 observations. Results showed the potential of cytotoxicity as a mechanism that can account for apparent in vitro transporter inhibition. Drug cytotoxicity varied in different cell lines, which could increase false positives for pharmacophore development.

Zheng, Xiaowan; Diao, Lei; Ekins, Sean; Polli, James E.

2010-01-01

377

[Visceral leishmaniasis in an HIV positive patient].  

PubMed

Background: visceral leishmaniasis is the most serious clinical picture of leishmaniasis or kala azar. In Mexico it is a rare disease, which is a reason why it is diagnosed late concluding with patient's death most of the time. We present a clinical case of an HIV-positive male patient who developed visceral leishmaniasis, with the objective of showing the pathophysiological characteristics as well as the diagnostic approach and treatment. Clinical case: a 45-year-old male, a water utility company worker, presented to the hospital as having chronic bloody diarrhea, abdominal distension, cramping pain, weight loss and fever. On physical examination, he was febrile, with pain localized to the right lower quadrant and hepatosplenomegaly. The ELISA test for HIV was positive and the ultrasound showed a cecal tumor. A tumor biopsy was performed and the pathology report described leishmaniasis. Conclusions: in patients with leishmaniasis and HIV the response to treatment is poor and the mortality rate is high due to lower immune response from the host. Current studies suggest treating these patients with HIV and leishmaniasis with pertinent drugs in combination with miltefosine and liposomal amphotericin B. PMID:23693114

Rossiere-Echazarreta, Natalia Lorena; Rodríguez-Campos, Esther Alicia; Morales-Esponda, Mario; Domínguez-Moreno, Rogelio; Cruz-Ortiz, Margarita; Rodríguez-Guzmán, Leoncio Miguel

378

A reconnaissance survey of radon in show caves in Ireland  

Microsoft Academic Search

A reconnaissance survey of radon gas concentrations and radon decay product concentrations in three Irish show caves was undertaken in Spring 1993. The caves, which are open to the public, are located in carboniferous limestone regions in western and southern Ireland. Area monitoring of underground radon concentrations was conducted using passive CR-39 alpha track detectors positioned at sampling locations spatially

P. A. Colgan

1996-01-01

379

5. FLOOR 3; SHOWS BRAKE LEVER, BLOCK FORMERLY USED TO ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. FLOOR 3; SHOWS BRAKE LEVER, BLOCK FORMERLY USED TO RAISE IT AND HOOK WHICH KEPT IT IN THE 'OFF' POSITION; ALSO SEEN ARE THE LARGE BLOCKS SUSPENDED FROM THE CAP FRAME WHICH HOLD THE TRUCK WHEELS TO CENTER THE CAP - Hayground Windmill, Windmill Lane, East Hampton, Suffolk County, NY

380

11. CALIFORNIATYPE DEPRESSION BEAM: Photocopy of photograph showing a Californiatype ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

11. CALIFORNIA-TYPE DEPRESSION BEAM: Photocopy of photograph showing a California-type depression beam positioned in its yokes. A car would approach the beam moving towards the camera. Note the open access cover, pulleys, counterweight hatchcover, and the wooden construction of the beam. - San Francisco Cable Railway, Washington & Mason Streets, San Francisco, San Francisco County, CA

381

Psychophysiological prediction of choice: relevance to insight and drug addiction  

PubMed Central

An important goal of addiction research and treatment is to predict behavioural responses to drug-related stimuli. This goal is especially important for patients with impaired insight, which can interfere with therapeutic interventions and potentially invalidate self-report questionnaires. This research tested (i) whether event-related potentials, specifically the late positive potential, predict choice to view cocaine images in cocaine addiction; and (ii) whether such behaviour prediction differs by insight (operationalized in this study as self-awareness of image choice). Fifty-nine cocaine abusers and 32 healthy controls provided data for the following laboratory components that were completed in a fixed-sequence (to establish prediction): (i) event-related potential recordings while passively viewing pleasant, unpleasant, neutral and cocaine images, during which early (400–1000 ms) and late (1000–2000 ms) window late positive potentials were collected; (ii) self-reported arousal ratings for each picture; and (iii) two previously validated tasks: one to assess choice for viewing these same images, and the other to group cocaine abusers by insight. Results showed that pleasant-related late positive potentials and arousal ratings predicted pleasant choice (the choice to view pleasant pictures) in all subjects, validating the method. In the cocaine abusers, the predictive ability of the late positive potentials and arousal ratings depended on insight. Cocaine-related late positive potentials better predicted cocaine image choice in cocaine abusers with impaired insight. Another emotion-relevant event-related potential component (the early posterior negativity) did not show these results, indicating specificity of the late positive potential. In contrast, arousal ratings better predicted respective cocaine image choice (and actual cocaine use severity) in cocaine abusers with intact insight. Taken together, the late positive potential could serve as a biomarker to help predict drug-related choice—and possibly associated behaviours (e.g. drug seeking in natural settings, relapse after treatment)—when insight (and self-report) is compromised.

Moeller, Scott J.; Hajcak, Greg; Parvaz, Muhammad A.; Dunning, Jonathan P.; Volkow, Nora D.

2012-01-01

382

Sickle Cell Crisis Associated with Drugs.  

National Technical Information Service (NTIS)

Drug overdose precipitated sickle cell crisis leading to death in four cases. Toxicologic studies in life and postmortem examinations showed the deaths to be caused by a combination of the ingested drugs and associated sickle cell crisis. Both the homozyg...

C. Delage F. G. Mullick N. S. Irey

1972-01-01

383

Downfall: Sports and Drugs (Closed Captioned).  

National Technical Information Service (NTIS)

This show profiles athletes whose careers were disrupted by drugs, especially steroids. Scene of the athletes performing are mixed with present day. Sobering interviews, the video examines the consequences of drugs on all aspects of an athlete's life-care...

1994-01-01

384

Utility of alkylaminoquinolinyl methanols as new antimalarial drugs.  

PubMed

Mefloquine has been one of the more valuable antimalarial drugs but has never reached its full clinical potential due to concerns about its neurologic side effects, its greater expense than that of other antimalarials, and the emergence of resistance. The commercial development of mefloquine superseded that of another quinolinyl methanol, WR030090, which was used as an experimental antimalarial drug by the U.S. Army in the 1970s. We evaluated a series of related 2-phenyl-substituted alkylaminoquinolinyl methanols (AAQMs) for their potential as mefloquine replacement drugs based on a series of appropriate in vitro and in vivo efficacy and toxicology screens and the theoretical cost of goods. Generally, the AAQMs were less neurotoxic and exhibited greater antimalarial potency, and they are potentially cheaper than mefloquine, but they showed poorer metabolic stability and pharmacokinetics and the potential for phototoxicity. These differences in physiochemical and biological properties are attributable to the "opening" of the piperidine ring of the 4-position side chain. Modification of the most promising compound, WR069878, by substitution of an appropriate N functionality at the 4 position, optimization of quinoline ring substituents at the 6 and 7 positions, and deconjugation of quinoline and phenyl ring systems is anticipated to yield a valuable new antimalarial drug. PMID:16966402

Dow, G S; Heady, T N; Bhattacharjee, A K; Caridha, D; Gerena, L; Gettayacamin, M; Lanteri, C A; Obaldia, N; Roncal, N; Shearer, T; Smith, P L; Tungtaeng, A; Wolf, L; Cabezas, M; Yourick, D; Smith, K S

2006-09-11

385

Co-lethality studied as an asset against viral drug escape: the HIV protease case  

PubMed Central

Background Co-lethality, or synthetic lethality is the documented genetic situation where two, separately non-lethal mutations, become lethal when combined in one genome. Each mutation is called a "synthetic lethal" (SL) or a co-lethal. Like invariant positions, SL sets (SL linked couples) are choice targets for drug design against fast-escaping RNA viruses: mutational viral escape by loss of affinity to the drug may induce (synthetic) lethality. Results From an amino acid sequence alignment of the HIV protease, we detected the potential SL couples, potential SL sets, and invariant positions. From the 3D structure of the same protein we focused on the ones that were close to each other and accessible on the protein surface, to possibly bind putative drugs. We aligned 24,155 HIV protease amino acid sequences and identified 290 potential SL couples and 25 invariant positions. After applying the distance and accessibility filter, three candidate drug design targets of respectively 7 (under the flap), 4 (in the cantilever) and 5 (in the fulcrum) amino acid positions were found. Conclusions These three replication-critical targets, located outside of the active site, are key to our anti-escape strategy. Indeed, biological evidence shows that 2/3 of those target positions perform essential biological functions. Their mutational variations to escape antiviral medication could be lethal, thus limiting the apparition of drug-resistant strains. Reviewers This article was reviewed by Arcady Mushegian, Shamil Sunyaev and Claus Wilke.

2010-01-01

386

The War on Illegal Drugs  

Microsoft Academic Search

This paper develops a simple model of the war against illegal drugs in producer and consumer countries. The analysis shows how the equilibrium quantity of illegal drugs, as well as their price, depend on key parametres of the model such as the price elasticity of demand and the effectiveness of the resources allocated to enforcement and prevention and treatment policies.

Daniel Mejía

387

Isolated pelvic perfusion: plasma pharmacokinetics depend primarily on drug dosage and not the type of drug  

Microsoft Academic Search

Purpose Comparison of the pharmacokinetics of four drugs with the isolated pelvic perfusion protocol showed linear relationships between drug dosage and two isolated pelvic plasma parameters, mean AUC (pelvic exposure, ? M min) and the mean maximum pelvic drug level (? M). It appears that the pharmacokinetics are sufficiently defined as to predict plasma distribution curves for an additional drug with

James F. Belliveau; Elisabeth Arevalo; Hank Griffin; Harold J. Wanebo

2005-01-01

388

Chronotherapeutic drug delivery.  

PubMed

Living organisms follow a circadian rhythm in which physiological processes such as hormonal secretion, metabolism, heart rate, and renal output are affected by the time of day. Chronotherapy coordinates drug delivery with the circadian rhythm to enhance effectiveness and mitigate adverse effects and is achieved by delivering a drug when the system is most susceptible. Cancer is a chronotherapeutic disorder. Cancer treatment requires high doses of intravenous medication to kill cancerous cells; however, normal cells are also killed, creating intolerable side effects. This review shows that chronotherapy can play a vital role in the quality of life and survival rate for oncology patients. PMID:22955155

Librodo, Paul; Buckley, Mitchell; Luk, Marilyn; Bisso, Andrea

389

Drug use, drug abuse and heterogeneity  

Microsoft Academic Search

Concepts and criteria for drug abuse have significant impacts on research and the development of interventions. The empirically supported differentiation of drug use and drug abuse has led to important gains in understanding the aetiology (etio- logy) of drug abuse. The need for further distinctions that reflect the heterogeneity of drug abuse is explored. The need for more sophisticated models

M. D. GLANTZ; J. D. COLLIVER

2002-01-01

390

Talk shows’ representations of interpersonal conflicts  

Microsoft Academic Search

In the past ten years, daytime talk shows became very popular among television programmers and viewers alike. Given the large audiences to whom talk shows communicate, it is important to analyze the messages contained in the programs. Remarkably little academic attention has been paid to this phenomenon, however. The present study focuses on the presentation of interpersonal conflicts, particularly regarding

Susan L. Brinson; J. Emmett Winn

1997-01-01

391

International Plowing Match & Farm Machinery Show  

NSDL National Science Digital Library

The 1995 International Plowing Match & Farm Machinery Show in Ontario, Canada has a site of the Web. The IPM is a non-profit organization of volunteers which annually organizes Canada's largest farm machinery show. The event is commercial and educational. Thousands of school children and educators attend and participate in organized educational activities.

1995-01-01

392

The Language of Show Biz: A Dictionary.  

ERIC Educational Resources Information Center

This dictionary of the language of show biz provides the layman with definitions and essays on terms and expressions often used in show business. The overall pattern of selection was intended to be more rather than less inclusive, though radio, television, and film terms were deliberately omitted. Lengthy explanations are sometimes used to express…

Sergel, Sherman Louis, Ed.

393

Show Me: Automatic Presentation for Visual Analysis  

Microsoft Academic Search

This paper describes Show Me, an integrated set of user interface commands and defaults that incorporate automatic presentation into a commercial visual analysis system called Tableau. A key aspect of Tableau is VizQL, a language for specifying views, which is used by Show Me to extend automatic presentation to the generation of tables of views (commonly called small multiple displays).

Jock D. Mackinlay; Pat Hanrahan; Chris Stolte

2007-01-01

394

Acculturation, Cultivation, and Daytime TV Talk Shows.  

ERIC Educational Resources Information Center

|Explores the cultivation phenomenon among international college students in the United States by examining the connection between levels of acculturation, daytime TV talk show viewing, and beliefs about social reality. Finds that students who scored low on acculturation and watched a great deal of daytime talk shows had a more negative perception…

Woo, Hyung-Jin; Dominick, Joseph R.

2003-01-01

395

The Language of Show Biz: A Dictionary.  

ERIC Educational Resources Information Center

|This dictionary of the language of show biz provides the layman with definitions and essays on terms and expressions often used in show business. The overall pattern of selection was intended to be more rather than less inclusive, though radio, television, and film terms were deliberately omitted. Lengthy explanations are sometimes used to…

Sergel, Sherman Louis, Ed.

396

Absolute Positioning Using the Global Positioning System.  

National Technical Information Service (NTIS)

The Global Positioning System (GPS) has become a useful tool in providing relative survey control. The relative positioning accuracies of the GPS are commonly on the order of 1-10 parts per million (ppm). The drawback with relative positioning is the user...

B. A. Fosburgh T. M. Cox

1994-01-01

397

Obese women show greater delay discounting than healthy-weight women  

Microsoft Academic Search

Delay discounting (DD) is a measure of the degree to which an individual is driven by immediate gratification vs. the prospect of larger, but delayed, rewards. Because of hypothesized parallels between drug addiction and obesity, and reports of increased delay discounting in drug-dependent individuals, we hypothesized that obese individuals would show higher rates of discounting than controls. Obese and healthy-weight

Rosalyn E. Weller; Edwin W. Cook; Kathy B. Avsar; James E. Cox

2008-01-01

398

Ulcerogenic drugs  

Microsoft Academic Search

>:CREaS~(~ ~U~B~:RS of new therapeutic agents make it extremely difficult for the individual physician to keep informed of the many side effects that might be anticipated in their use. Fortunately, most of these effects are mild and not serious, and usually the possibly grave side effects are well identified before the drugs are marketed. Unfortunately, some of the undesirable reactions

John R. Kelsey

1959-01-01

399

[Management of drug addiction in France (a short history)].  

PubMed

A brief history of drug addiction in France can be garnered from a combination of the fragmented testimonies of physicians, social scientists, drug users, and of the OFDT reports edited since the middle of the nineties. It shows a tremendous evolution in the nature of drugs abused and the number of addicts, taking place in less than fifty years, from a small number of opiate addicts restricted to the major French ports to two separate drug scenes (urban and festive) accounting for several hundred thousand people. Those two scenes have shown a tendency to merge following the unification of drug trafficking. The failure of the repression policy initialized in 1970 was responsible of the AIDS and hepatitis epidemic which resulted in the introduction of large scale substitution treatments in 1996. Initiated to reduce contamination risks, later on, they were recognized as an effective treatment of heroin addiction. Beside the positive effects of this "French revolution", emergence of buprenorphine as a new urban drug must be accounted and dealt with. PMID:17965635

Chossegros, Philippe

400

Drug delivery and nanoparticles: Applications and hazards  

PubMed Central

The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed.

De Jong, Wim H; Borm, Paul JA

2008-01-01

401

Photomechanical drug delivery  

NASA Astrophysics Data System (ADS)

Photomechanical waves (PW) are generated by Q-switched or mode-locked lasers. Ablation is a reliable method for generating PWs with consistent characteristics. Depending on the laser wavelength and target material, PWs with different parameters can be generated which allows the investigation of PWs with cells and tissue. PWs have been shown to permeabilize the stratum corneum (SC) in vivo and facilitate the transport of drugs into the skin. Once a drug has diffused into the dermis it can enter the vasculature, thus producing a systemic effect. Fluorescence microscopy of biopsies show that 40-kDa molecules can be delivered to a depth of > 300 micrometers into the viable skin of rats. Many important drugs such as insulin, and erythropoietin are smaller or comparable in size, making the PWs attractive for transdermal drug delivery. There are three possible pathways through the SC: Transappendageal via hair follicles or other appendages, transcellular through the corneocytes, and intercellular via the extracellular matrix. The intracellular route appears to be the most likely pathway of drug delivery through the SC.

Doukas, Apostolos G.; Lee, Shun

2000-05-01

402

Frequently Asked Questions about Drug Testing in Schools  

MedlinePLUS

... it should be a component of broader prevention, intervention and treatment programs, with the common goal of reducing students' drug use. If a student tests positive for drugs, should that student face disciplinary consequences? The ...

403

FDA Drug Podcast: Valproate Anti-seizure Products ...  

Center for Drug Evaluation (CDER)

... Pregnancy Category X means that studies in animals or humans have shown positive evidence of fetal risk, and the risk of the use of the drug in ... More results from www.fda.gov/drugs/drugsafety/drugsafetypodcasts

404

Silicon nanowire detectors showing phototransistive gain  

NASA Astrophysics Data System (ADS)

Nanowire photodetectors are shown to function as phototransistors with high sensitivity. Due to small lateral dimensions, a nanowire detector can have low dark current while showing large phototransistive gain. Planar and vertical silicon nanowire photodetectors fabricated in a top-down approach using an etching process show a phototransistive gain above 35 000 at low light intensities. Simulations show that incident light can be waveguided into vertical nanowires resulting in up to 40 times greater external quantum efficiency above their physical fill factor. Vertical silicon nanowire phototransistors formed by etching are attractive for low light level detection and for integration with silicon electronics.

Zhang, Arthur; You, Sifang; Soci, Cesare; Liu, Yisi; Wang, Deli; Lo, Yu-Hwa

2008-09-01

405

Non-isotopic immunoassay drug tests in racing horses: a review of their application to pre- and post-race testing, drug quantitation, and human drug testing.  

PubMed

We have introduced large scale non-isotopic immunoassay testing into pre- and post-race drug testing in racehorses. The technologies utilized are Particle Concentration Fluorescence Immuno Assay (PCFIA) and the one-step Enzyme Linked Immuno Sorbent Assay (ELISA). These technologies are rapid, inexpensive, and highly effective. On introduction into post-race testing in the Western United States, these ELISA tests exposed several previously undetected patterns of drug abuse. The drugs detected were buprenorphine, oxymorphone, mazindol, sufentanil and cocaine. This led to the suspension of a large number of trainers and exposed the high false negative rate of thin layer chromatography (TLC) based testing. More recently, we have introduced both PCFIA and ELISA assays into pre- and post-race testing in Illinois. Within days, our pre-race PCFIA tests detected signs of acepromazine abuse. Directed searches of post-race urines from these horses showed evidence for acepromazine metabolites in the urine of these horses. Examination of frozen samples from associated horses yielded about 70 ELISA "positives" for acepromazine. To date, about 25 of these ELISA "positives" have been confirmed by mass spectrometry. We have also raised antibodies to phenylbutazone and furosemide to enable rapid and inexpensive quantitation of these permitted medications. Furosemide is a particular problem since its use requires a pre-race detention barn. For furosemide, we have developed a regulatory schedule based on our immunoassay test that allows elimination of the detention barn. For phenylbutazone, we have developed a similar immunoassay that allows rapid and inexpensive quantitation of this drug in blood. To enable racing authorities to test jockeys and other racetrack personnel, we have adapted PCFIA technology to human drug testing, and a full range of very sensitive tests for human drugs of abuse is available. These immunoassays are sufficiently sensitive to control abuse of the most potent drugs available to horsemen. In principle, an immunoassay can be raised to any drug within about six months, and made available worldwide at competitive rates. It appears clear that these non-isotopic immunoassays provide racing with the only technological basis that is sufficiently sensitive to detect the most potent abused drugs pre- and post-race, and has the flexibility to be readily adaptable to different drugs. Because of the high false negative rate generated by TLC, credible pre- and post-race testing programs cannot be based on TLC alone.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3065859

Tobin, T; Watt, D S; Kwiatkowski, S; Tai, H H; Blake, J W; McDonald, J; Prange, C A; Wie, S

1988-12-01

406

Cost-Benefit Analysis of Endocrine Therapy in the Adjuvant Setting for Postmenopausal Patients with Hormone Receptor-Positive Breast Cancer, Based on Survival Data and Future Prices for Generic Drugs in the Context of the German Health Care System.  

PubMed

BACKGROUND: Cost-effectiveness analyses have focused on aromatase inhibitors (AIs), but the results are inconsistent and disease-free survival has often been extrapolated to overall survival. The present study calculates the cost-effectiveness of 5 years of letrozole versus tamoxifen versus anastrozole in the context of the German health care system, using survival data from the Breast International Group (BIG) 1-98 study and the Arimidex, Tamoxifen, Alone or in Combination (ATAC) study and generic prices. MATERIALS AND METHODS: A hybrid model was developed that incorporates recurrence rates, overall survival, treatment costs and treatment-associated adverse events and the resulting costs. The basic assumption was that generic anastrozole would lead to a price reduction to 75% of the original price. Further analyses were carried out with 50% and 25% of the original prices for anastrozole and letrozole. RESULTS: The cost-benefit model showed a gain of 0.3124 or 0.0659 quality-adjusted life years (QALYs) for letrozole or anastrozole. Incremental costs of € 29,375.15/QALY for letrozole (100% of original price) were calculated and € 94,648.03/QALY for anastrozole (75% of original price). Marked increases in cost-effectiveness are observed with further decreases in price (anastrozole: 50% price € 54,715.17/QALY, 25% price € 14,779.57/QALY; letrozole 75% price € 20,988.59/QALY, 50% price € 12,602.03/QALY, 25% price € 4,215.46/QALY). CONCLUSION: The present model including the inverse probability of censoring weighted analysis (IPCW) for letrozole and generic prices for both AIs shows that letrozole is cost effective. PMID:22619649

Lux, Michael P; Reichelt, Claudia; Karnon, Jon; Tänzer, Thorsten D; Radosavac, Dragan; Fasching, Peter A; Beckmann, Matthias W; Thiel, Falk C

2011-10-13

407

Homelessness and HIV risk behaviors among injection drug users.  

PubMed

This article uses data from an 8-year study of injection drug users to examine whether homelessness independently influenced the likelihood of engaging in human immunodeficiency virus (HIV) risk behaviors. Fixed effects regression analyses are used to estimate the associations between four different housing contexts and four different behaviors related to transmitting HIV infections. Results showed that 16% of the study group experienced homelessness at some point during the study, and that homelessness was significantly associated with a higher likelihood of frequenting shooting galleries (odds ratio = 2.05), but did not have a significant effect on sharing syringes, sharing other injection drug paraphernalia, or participating in paid sex. These results provide limited support for positing homelessness as independently associated with increased levels of HIV-related risk behavior among injection drug users and highlights the need for more research that examines the housing dynamics among this population. PMID:15466843

Metraux, Stephen; Metzger, David S; Culhane, Dennis P

2004-12-01

408

Recent development of molecular-targeted drugs in lung cancer.  

PubMed

Numerous molecular target drugs have been introduced for the treatment of advanced malignancies. In the treatment of lung cancer, epidermoid growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) demonstrate striking antitumor activity in selected EGFR mutation positive patients. Patient selection by biomarker is extremely important to obtain successful results. The anti-vascular endothelial growth factor (VEGF) antibody, bevacizumab, shows a markedly increased response rate, progression free survival of advanced non-squamous cell lung cancer when combined with cytotoxic drugs. The classification of lung cancer is rapidly changing based on the advances in molecular biology. Here, the recent development of new molecular target drugs against lung cancer is thoroughly reviewed in addition to EGFR-TKIs and bevacizumab with special emphasis on the clinical application. PMID:20847494

Saijo, Nagahiro; Kenmotsu, Hirotsugu

2010-09-15

409

Bioterrorism and Drug Preparedness  

Center for Drug Evaluation (CDER)

... Bioterrorism and Drug Preparedness. Anthrax; Plague; Radiation Emergencies; Chemical Agents; Regulatory Information for Counter-Terrorism Drug ... More results from www.fda.gov/drugs/emergencypreparedness/bioterrorismanddrugpreparedness

410

Drug Interaction: Contact Information  

Center for Drug Evaluation (CDER)

... Development Resources. Section Contents Menu. Development & Approval Process (Drugs). ... Drug Interaction: Contact Information. ... More results from www.fda.gov/drugs/developmentapprovalprocess/developmentresources

411

Fluoroquinolone Antimicrobial Drugs Information  

Center for Drug Evaluation (CDER)

... Information by Drug Class. ? -. Resources for You. Antibiotics and Antibiotic Resistance. -. Fluoroquinolone Antimicrobial Drugs Information. ... More results from www.fda.gov/drugs/drugsafety/informationbydrugclass

412

FOOD AND DRUG ADMINISTRATION Center for Drug ...  

Center for Biologics Evaluation and Research (CBER)

Text VersionPage 1. FOOD AND DRUG ADMINISTRATION Center for Drug Evaluation and Research Page 1 of 2 Anti-Infective Drugs ... More results from www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials

413

FOOD AND DRUG ADMINISTRATION Center for Drug ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... II (ODE-II) Office of New Drugs (OND), CDER ... DRUG ADMINISTRATION Center for Drug Evaluation and ... Health, Exercise, and Sport Sciences The ... More results from www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials

414

FOOD AND DRUG ADMINISTRATION Center for Drug ...  

Center for Drug Evaluation (CDER)

Text VersionPage 1. FOOD AND DRUG ADMINISTRATION Center ... interim period, working to implement Section 503(a) of the Food, Drug ... More results from www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation

415

47 CFR 90.505 - Showing required.  

Code of Federal Regulations, 2011 CFR

...PRIVATE LAND MOBILE RADIO SERVICES Developmental Operation § 90.505 Showing required...this section, each application for developmental operation shall be accompanied by a...apply when an application is made for developmental operation solely for the reason...

2011-10-01

416

47 CFR 90.505 - Showing required.  

Code of Federal Regulations, 2012 CFR

...PRIVATE LAND MOBILE RADIO SERVICES Developmental Operation § 90.505 Showing required...this section, each application for developmental operation shall be accompanied by a...apply when an application is made for developmental operation solely for the reason...

2012-10-01

417

map showing predicted habitat potentional for tortoise  

USGS Multimedia Gallery

This map shows the spatial representation of the predicted habitat potential index values for desert tortoise in the Mojave and parts of the Sonoran Deserts of California, Nevada, Utah, and Arizona. Map: USGS. ...

2009-05-21

418

NFL Veterans Show 'Abnormalities' in Brain Activity  

MedlinePLUS

... please enable JavaScript. NFL Veterans Show 'Abnormalities' in Brain Activity: Study Ex-players who had been sent ... researchers say they see unusual activity in the brains of former National Football League players. These traits ...

419

Stutterers Show Different Brain Development, Study Says  

MedlinePLUS

... this page, please enable JavaScript. Stutterers Show Different Brain Development, Study Says Less gray matter seen in ... have less gray matter in regions of the brain responsible for speech than those who don't ...

420

FDA Broadcast Shows Food Industry Personnel and ...  

Center for Food Safety and Applied Nutrition (CFSAN)

... FDA Broadcast Shows Food Industry Personnel and Consumers How Proper Health and Hygiene Helps to Prevent Foodborne Illness Outbreaks. ... More results from www.fda.gov/food/newsevents/constituentupdates

421

Do dogs (Canis familiaris) show contagious yawning?  

PubMed

We report an experimental investigation into whether domesticated dogs display contagious yawning. Fifteen dogs were shown video clips of (1) humans and (2) dogs displaying yawns and open-mouth expressions (not yawns) to investigate whether dogs showed contagious yawning to either of these social stimuli. Only one dog performed significantly more yawns during or shortly after viewing yawning videos than to the open-mouth videos, and most of these yawns occurred to the human videos. No dogs showed significantly more yawning to the open-mouth videos (human or dog). The percentage of dogs showing contagious yawning was less than chimpanzees and humans showing this behavior, and considerably less than a recently published report investigating this behavior in dogs (Joly-Mascheroni et al. in Biol Lett 4:446-448, 2008). PMID:19452178

Harr, Aimee L; Gilbert, Valerie R; Phillips, Kimberley A

2009-05-19

422

Novel Antibiotics Targeting Respiratory ATP Synthesis in Gram-Positive Pathogenic Bacteria  

PubMed Central

Emergence of drug-resistant bacteria represents a high, unmet medical need, and discovery of new antibacterials acting on new bacterial targets is strongly needed. ATP synthase has been validated as an antibacterial target in Mycobacterium tuberculosis, where its activity can be specifically blocked by the diarylquinoline TMC207. However, potency of TMC207 is restricted to mycobacteria with little or no effect on the growth of other Gram-positive or Gram-negative bacteria. Here, we identify diarylquinolines with activity against key Gram-positive pathogens, significantly extending the antibacterial spectrum of the diarylquinoline class of drugs. These compounds inhibited growth of Staphylococcus aureus in planktonic state as well as in metabolically resting bacteria grown in a biofilm culture. Furthermore, time-kill experiments showed that the selected hits are rapidly bactericidal. Drug-resistant mutations were mapped to the ATP synthase enzyme, and biochemical analysis as well as drug-target interaction studies reveal ATP synthase as a target for these compounds. Moreover, knockdown of the ATP synthase expression strongly suppressed growth of S. aureus, revealing a crucial role of this target in bacterial growth and metabolism. Our data represent a proof of principle for using the diarylquinoline class of antibacterials in key Gram-positive pathogens. Our results suggest that broadening the antibacterial spectrum for this chemical class is possible without drifting off from the target. Development of the diarylquinolines class may represent a promising strategy for combating Gram-positive pathogens.

Balemans, Wendy; Vranckx, Luc; Lounis, Nacer; Pop, Ovidiu; Guillemont, Jerome; Vergauwen, Karen; Mol, Selena; Gilissen, Ron; Motte, Magali; Lancois, David; De Bolle, Miguel; Bonroy, Kristien; Lill, Holger; Andries, Koen

2012-01-01

423

Study Shows Drug Is Effective for Cancer Patients with Peripheral Neuropathy  

MedlinePLUS

... while the average scores of those in the placebo group fell about 3 percent. The difference is similar to that seen in other studies of duloxetine for chronic pain. The most commonly reported side effect was fatigue, which was higher in patients taking ...

424

Terpanes from oil shows of Lake Baikal  

Microsoft Academic Search

The composition and distribution of terpanes in oil shows that emerge from the bottom of Lake Baikal were studied. The oil\\u000a samples from three sites of Baikal showed different extents of their bacterial degradation, from practically unaltered to\\u000a heavily degraded oils. In the unaltered samples of oils and moderately degraded differences, a unique variety of biomarkers\\u000a (sesquiterpanes, secohopanes, new regular

V. A. Kashirtsev; A. E. Kontorovich; V. I. Moskvin; V. P. Danilova; V. N. Melenevskii

2006-01-01

425

The heart of Daphnia magna: effects of four cardioactive drugs.  

PubMed

We used Daphnia magna bioassays to determine the LC(50) and the effects on the heart of the cardioactive drugs ouabain, verapamil, metaproterenol and metoprolol. Distinctions were made between the pharmacological and toxicological effects of these drugs and the adequacy of physicochemical characteristics of its habitat (reconstituted water). Video microscopy and digital image processing were used to study the pharmacological effects on the heart. D. magna exhibited the expected sensitivity to the reference toxicant sodium dodecyl sulfate with a LC(50) of 15.6+/-4.5 mg/l. All drugs were toxic with 48 h-LC(50) of 2.03 mg/l ouabain, 7.04 mg/l verapamil, 32.45 mg/l metaproterenol and 76.21 mg/l metoprolol. Ouabain was the most toxic and caused a positive concentration-dependent inotropic effect. Verapamil caused positive chronotropic and inotropic effects, while metaproterenol showed positive concentration-dependent chronotropic effects at high concentrations (10(-3) and 10(-4) M). Metoprolol induced a positive chronotropic effect at low concentrations (10(-8), 10(-7), 10(-6) M) and a negative chronotropic effect at high concentration (10(-4) M). Ouabain, metaproterenol and metoprolol in D. magna caused similar effects to those produced in mammals. In contrast, verapamil caused opposite effects. The results suggest the presence of Na(+), K(+)-ATPase receptors to verapamil and of non-specific adrenergic receptors in heart of D. magna. PMID:14559294

Villegas-Navarro, Arturo; Rosas-L, Esperanza; Reyes, José L

2003-10-01

426

Transmucosal macromolecular drug delivery.  

PubMed

Mucosal surfaces are the most common and convenient routes for delivering drugs to the body. However, macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and/or are degraded before reaching the blood stream. Among the approaches explored so far in order to optimize the transport of these macromolecules across mucosal barriers, the use of nanoparticulate carriers represents a challenging but promising strategy. The present paper aims to compare the characteristics and potential of nanostructures based on the mucoadhesive polysaccharide chitosan (CS). These are CS nanoparticles, CS-coated oil nanodroplets (nanocapsules) and CS-coated lipid nanoparticles. The characteristics and behavior of CS nanoparticles and CS-coated lipid nanoparticles already reported [A. Vila, A. Sanchez, M. Tobio, P. Calvo, M.J. Alonso, Design of biodegradable particles for protein delivery, J. Control. Rel. 78 (2002) 15-24; R. Fernandez-Urrusuno, P. Calvo, C. Remunan-Lopez, J.L. Vila-Jato, M.J. Alonso, Enhancement of nasal absorption of insulin using chitosan nanoparticles, Pharm. Res. 16 (1999) 1576-1581; M. Garcia-Fuentes, D. Torres, M.J. Alonso, New surface-modified lipid nanoparticles as delivery vehicles for salmon calcitonin (submitted for publication).] are compared with those of CS nanocapsules originally reported here. The three types of systems have a size in the nanometer range and a positive zeta potential that was attributed to the presence of CS on their surface. They showed an important capacity for the association of peptides such as insulin, salmon calcitonin and proteins, such as tetanus toxoid. Their mechanism of interaction with epithelia was investigated using the Caco-2 model cell line. The results showed that CS-coated systems caused a concentration-dependent reduction in the transepithelial resistance of the cell monolayer. Moreover, within the range of concentrations investigated, these systems were internalized in the monolayer in a concentration-dependent manner. This uptake was slightly enhanced by the presence of the CS coating but, as compared with previously published results [M. Garcia-Fuentes, C. Prego, D. Torres, M.J. Alonso, Triglyceride-chitosan nanostructures for oral calcitonin delivery: evaluation in the Caco-2 cell model and in vivo (submitted for publication)], highly dependent on the nature of the lipid core. Nevertheless, these differences in the uptake of the CS-coated systems (solid lipid core or oily core) by the Caco-2 cells did not have a consequence in the in vivo behaviour. Indeed, both CS-coated systems (nanocapsules and CS-coated nanoparticles) showed an important capacity to enhance the intestinal absorption of the model peptide, salmon calcitonin, as shown by the important and long-lasting decrease in the calcemia levels observed in rats. PMID:15588901

Prego, C; García, M; Torres, D; Alonso, M J

2005-01-01

427

Effect of route of administration and distribution on drug action  

Microsoft Academic Search

The extent and time course of drug action can be markedly affected by the route of drug administration into the patient as well as the pattern of drug distribution within the patient. Drugs which are rapidly cleared by hepatic processes will show a decreased extent of availability following oral administration due to metabolism of drug on its first pass through

Leslie Z. Benet

1978-01-01

428

Neurologic drug-psychotropic drug update  

Microsoft Academic Search

It is essential that both the neurologist and the psychiatrist be aware of the neurology drug-psychotropic drug interactions because neurologists prescribe many psychotropic medications and psychiatric consultants often recommend the use of psychotropic drugs for neurology patients. Six methods of examining drug-drug interactions were employed: 1) PubMed (MEDLINE); 2) Hanston’s Drug Interaction Analysis and Management Text (July 2001 quarterly updated

James J Strain; Anwarul Karim; Gina Caliendo; Matthew Brodsky; R. Sandlin Lowe; Carol Himelein

2002-01-01

429

Neurologic drug-psychotropic drug update  

Microsoft Academic Search

It is essential that both the neurologist and the psychiatrist be aware of the neurology drug-psychotropic drug interactions because neurologists prescribe many psychotropic medications and psychiatric consultants often recommend the use of psychotropic drugs for neurology patients. Six methods of examining drug-drug interactions were employed: 1) PubMed (MEDLINE); 2) Hanston's Drug Interaction Analysis and Management Text (July 2001 quarterly updated

James J. Strain; Anwarul Karim; Gina Caliendo; Matthew Brodsky; R. Sandlin Lowe; Carol Himelein

2003-01-01

430

Global Positioning Systems (GPS)  

NSDL National Science Digital Library

View an animated Flash slide show explaining how GPS works. GPS operates because of three interconnected segments: the satellite, ground control, and user segments. This animation focuses on the satellite and user segments, briefly touching upon how the satellite signal is processed to produce positional values in hand-held GPS units. Note that the accuracy claimed for handheld GPS units 100 m is now routinely exceeded. With the turning off of selective availability, today's GPS handheld units usually get accuracies of better than 10 meters. Note that the video loads slowly.

Wiley

431

Drug Use and Medication Adherence among HIV1 Infected Individuals  

Microsoft Academic Search

This longitudinal study examined the impact of drug use and abuse on medication adherence among 150 HIV-infected individuals,\\u000a 102 who tested urinalysis positive for recent illicit drug use. Medication adherence was tracked over a 6-month period using\\u000a an electronic monitoring device (MEMS caps). Over the 6-month study drug-positive participants demonstrated significantly\\u000a worse medication adherence than did drug-negative participants (63 vs.

Charles H. Hinkin; Terry R. Barclay; Steven A. Castellon; Andrew J. Levine; Ramani S. Durvasula; Sarah D. Marion; Hector F. Myers; Douglas Longshore

2007-01-01

432

Expansion of Bcr-Abl-positive leukemic stem cells is dependent on Hedgehog pathway activation.  

PubMed

Resistance of Bcr-Abl-positive leukemic stem cells (LSCs) to imatinib treatment in patients with chronic myeloid leukemia (CML) can cause relapse of disease and might be the origin for emerging drug-resistant clones. In this study, we identified Smo as a drug target in Bcr-Abl-positive LSCs. We show that Hedgehog signaling is activated in LSCs through upregulation of Smo. While Smo(-/-) does not impact long-term reconstitution of regular hematopoiesis, the development of retransplantable Bcr-Abl-positive leukemias was abolished in the absence of Smo expression. Pharmacological Smo inhibition reduced LSCs in vivo and enhanced time to relapse after end of treatment. Our results indicate that Smo inhibition might be an effective treatment strategy to reduce the LSC pool in CML. PMID:18772113

Dierks, Christine; Beigi, Ronak; Guo, Gui-Rong; Zirlik, Katja; Stegert, Mario R; Manley, Paul; Trussell, Christopher; Schmitt-Graeff, Annette; Landwerlin, Klemens; Veelken, Hendrik; Warmuth, Markus

2008-09-01

433

On a national drug policy for Bangladesh.  

PubMed

On April 27, 1982 the Ministry of Health of the government of Bangladesh, set up an 8-man expert committee to evaluate all the registered pharmaceutical products presently available, and to formulate a draft National Drug Policy. Objectives are: 1) to provide support for ensuring quality and availability of drugs; 2) to reduce drug prices; 3) to eliminate useless, nonessential, and harmful drugs from the market; 4) to promote local production of finished drugs; 5) to ensure coordination among government branches; 6) to develop a drug monitoring and information system; 7) to promote the scientific development and application of unani, ayurvedic, and homeopathic medicines; 8) to improve the standard of hospital and retail pharmacies; and 9) to insure good manufacturing practices. 16 criteria were agreed on as guidelines for evaluating the drugs on the country's market. Drugs in Bangladesh have been classified into 3 categories. The 1st is drugs that are positively harmful. They should be banned immediately and withdrawn from the market. There are 265 locally manufactured drugs and 40 imported drugs in this category. The 2nd, drugs to be slightly reformulated by eliminating some of their requirements. There are 134 drugs in this category. The 3rd is drugs that do not conform to 1 or more of the 16 criteria/guidelines. There are over 500 drugs in this category. The new drug policy will produce a saving of 800 million taka (US $32.4 million). Drug supply in Bangladesh is a problem. The public sector distributes 20% of the total. In the private sector, drugs are supplied through import and local production. Investment for research by the pharmaceutical companies is essential. The principles laid down by the International Federation of Pharmaceutical Manufacturers Associations for the supply of good medicine needs to be put into practice. PMID:6729960

Islam, N

1984-01-01

434

Drug Development and Drug Interactions: Regulatory ...  

Center for Drug Evaluation (CDER)

... Clinical Pharmacology and Biopharmaceutics Review Template (PDF - 332KB), April 2004. Concept Papers. ... Issues drug interaction concept paper. ... More results from www.fda.gov/drugs/developmentapprovalprocess/developmentresources

435

Positional information, in bits  

PubMed Central

Cells in a developing embryo have no direct way of “measuring” their physical position. Through a variety of processes, however, the expression levels of multiple genes come to be correlated with position, and these expression levels thus form a code for “positional information.” We show how to measure this information, in bits, using the gap genes in the Drosophila embryo as an example. Individual genes carry nearly two bits of information, twice as much as would be expected if the expression patterns consisted only of on/off domains separated by sharp boundaries. Taken together, four gap genes carry enough information to define a cell’s location with an error bar of along the anterior/posterior axis of the embryo. This precision is nearly enough for each cell to have a unique identity, which is the maximum information the system can use, and is nearly constant along the length of the embryo. We argue that this constancy is a signature of optimality in the transmission of information from primary morphogen inputs to the output of the gap gene network.

Dubuis, Julien O.; Tkacik, Gasper; Wieschaus, Eric F.; Gregor, Thomas; Bialek, William

2013-01-01

436

Positional information, in bits.  

PubMed

Cells in a developing embryo have no direct way of "measuring" their physical position. Through a variety of processes, however, the expression levels of multiple genes come to be correlated with position, and these expression levels thus form a code for "positional information." We show how to measure this information, in bits, using the gap genes in the Drosophila embryo as an example. Individual genes carry nearly two bits of information, twice as much as would be expected if the expression patterns consisted only of on/off domains separated by sharp boundaries. Taken together, four gap genes carry enough information to define a cell's location with an error bar of along the anterior/posterior axis of the embryo. This precision is nearly enough for each cell to have a unique identity, which is the maximum information the system can use, and is nearly constant along the length of the embryo. We argue that this constancy is a signature of optimality in the transmission of information from primary morphogen inputs to the output of the gap gene network. PMID:24089448

Dubuis, Julien O; Tkacik, Gasper; Wieschaus, Eric F; Gregor, Thomas; Bialek, William

2013-10-02

437

Positive clinical neuroscience: explorations in positive neurology.  

PubMed

Disorders of the brain and its sensory organs have traditionally been associated with deficits in movement, perception, cognition, emotion, and behavior. It is increasingly evident, however, that positive phenomena may also occur in such conditions, with implications for the individual, science, medicine, and for society. This article provides a selective review of such positive phenomena--enhanced function after brain lesions, better-than-normal performance in people with sensory loss, creativity associated with neurological disease, and enhanced performance associated with aging. We propose that, akin to the well-established field of positive psychology and the emerging field of positive clinical psychology, the nascent fields of positive neurology and positive neuropsychology offer new avenues to understand brain-behavior relationships, with both theoretical and therapeutic implications. PMID:23286954

Kapur, Narinder; Cole, Jonathan; Manly, Tom; Viskontas, Indre; Ninteman, Aafke; Hasher, Lynn; Pascual-Leone, Alvaro

2013-01-03

438

Prevalence of Potential Drug Interactions in an Iranian General Hospital  

PubMed Central

The hazards of prescribing many drugs, including side-effects, drug-drug interactions and difficulties of compliance have long been recognized as particular problems when prescribing. This study estimates the rate and factors associated with potential drug-drug interactions in prescriptions from wards of An Iranian General Hospital. Data were retrieved from the pharmacy of a general hospital (200 beds) during one year period 2010. Potential drug-drug interaction were identified using a computerized drug-drug interaction database system (Prescription Analyzer 2000, Sara Rayane Co., Iran). Patients of both genders and 15 years-old or more were included in this study. Prescriptions with two or more drugs prescribed were selected during one year period 2010. Gender number of drugs and therapeutic drug classes on prescriptions were explored as associated factors to drug-drug interaction. The overall prevalence of potential drug-drug interaction was 20.3%. The risks of severe potential drug interactions were relatively high and the rate of potential drug-drug interaction was significantly higher in women (60.6%) and the patients aged over 60 years old (57.1%). The frequency of the potentially severe drug-drug interaction was 10.8% with digoxin-furosemide as the most common interacting pair (5.91%). A positive correlation was found between drug-drug interaction, patient's age, number of drugs and drugs acting on cardiovascular system. So cardiology women inpatients, age more then 60 years old, and patients prescribed digoxin and angiotensin-converting enzyme inhibitors should be closely monitored for adverse outcomes from drug-drug interaction.

Sepehri, G.; Khazaelli, P.; Dahooie, F. Arabpour; Sepehri, E.; Dehghani, M. R.

2012-01-01

439

Facts About Generic Drugs  

Center for Drug Evaluation (CDER)

... drugs? Yes. The FDA says that all drugs must work well and be safe. ... Do generic drugs take longer to work in the body? No. Generic ... More results from www.fda.gov/drugs/emergencypreparedness/bioterrorismanddrugpreparedness

440

Compliance Activities (Drugs)  

Center for Drug Evaluation (CDER)

... New Drug Application (NDA) Field Alert Reports; Drug Recalls; Importing and Exporting of Human Drugs and Biologics. Training Courses. ... More results from www.fda.gov/drugs/developmentapprovalprocess/smallbusinessassistance

441

Unapproved Drugs Initiative  

Center for Drug Evaluation (CDER)

... Drugs with potential safety risks; Drugs that lack evidence of effectiveness; Health fraud drugs; ... once the risk-based assessment has been ... More results from www.fda.gov/drugs/guidancecomplianceregulatoryinformation/enforcementactivitiesbyfda

442

Investigational New Drug Applications  

Center for Biologics Evaluation and Research (CBER)

... New Drug Applications, Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well ... More results from www.fda.gov/drugs/guidancecomplianceregulatoryinformation/guidances

443

Drugs and Young People  

MedlinePLUS

... susceptible to drug abuse and addiction than adult brains. Abused drugs include Amphetamines Anabolic steroids Club drugs Cocaine Heroin Inhalants Marijuana Prescription drugs There are different types of treatment ...

444

Generic Drug Review Process  

Center for Drug Evaluation (CDER)

... Generic Drug Review Process. ... Office of Generic Drugs Home Page. The FDA Process for Approving Generic Drugs (free online training course). -. -. ... More results from www.fda.gov/drugs/developmentapprovalprocess/smallbusinessassistance

445

Facts About Generic Drugs  

Center for Drug Evaluation (CDER)

... In the United States, trademark laws do not allow generic drugs to look exactly like the brand ... Does every brand-name drug have a generic drug? ... More results from www.fda.gov/drugs/resourcesforyou

446

Drugs and their effects  

NSDL National Science Digital Library

There are many illegal drugs in existence. These drugs are often dangerous to create and extremely harmful to the human body. Drugs are addictive and can ultimately cause death if drug abuse or over-dosages occur.

Olivia Worland (Purdue University;Biological Sciences)

2008-07-07

447

Facts About Generic Drugs  

Center for Drug Evaluation (CDER)

Text Version... Yes. FDA requires generic drugs must be as: • high quality • strong • pure, and • stable as brand-name drugs ARE BRAND-NAME DRUGS MADE IN ... More results from www.fda.gov/downloads/drugs/emergencypreparedness

448

The Morning Show at WLES-TV.  

ERIC Educational Resources Information Center

|Describes the production and programing of daily quarter-hour television shows by different groups of students at Laurel (Maryland) Elementary School, guided by the library media specialist who started them five years ago. The video experience has improved students' reading, writing, and math skills, as well as behavior. (MF)|

Blondell, Beverley

1979-01-01

449

Showing Enantiomorphous Crystals of Tartaric Acid  

ERIC Educational Resources Information Center

|Most of the articles and textbooks that show drawings of enantiomorphous crystals use an inadequate view to appreciate the fact that they are non-superimposable mirror images of one another. If a graphical presentation of crystal chirality is not evident, the main attribute of crystal enantiomorphism can not be recognized by students. The classic…

Andrade-Gamboa, Julio

2007-01-01

450

Olaparib shows promise in multiple tumor types.  

PubMed

A phase II study of the PARP inhibitor olaparib (AstraZeneca) for cancer patients with inherited BRCA1 and BRCA2 gene mutations confirmed earlier results showing clinical benefit for advanced breast and ovarian cancers, and demonstrated evidence of effectiveness against pancreatic and prostate cancers. PMID:23847380

2013-06-06

451

The Last Great American Picture Show  

Microsoft Academic Search

The Last Great American Picture Show brings together essays by scholars and writers who chart the changing evaluations of the American cinema of the 1970s, sometimes referred to as the decade of the lost generation, but now more and more recognized as the first New Hollywood, without which the cinema of Francis Coppola, Steven Spielberg, Robert Zemeckis, Tim Burton or

Thomas Elsaesser; Noel King; Alexander Horwath

2004-01-01

452

The object-oriented trivia show (TOOTS)  

Microsoft Academic Search

OOPSLA has a longstanding tradition of being a forum for discussing the cutting edge of technology in a fun and participatory environment. The type of events sponsored by OOPSLA sometimes border on the unconventional. This event represents an atypical panel that conforms to the concept of a game show that is focused on questions and answers related to SPLASH, OOPSLA,

Jeff Gray; Jules White

2010-01-01

453

A Talk Show from the Past.  

ERIC Educational Resources Information Center

|Describes a two-day activity in which elementary students examine voting rights, the right to assemble, and women's suffrage. Explains the game, "Assemble, Reassemble," and a student-produced talk show with five students playing the roles of leaders of the women's suffrage movement. Profiles Elizabeth Cady Stanton, Lucretia Mott, Susan B.…

Gallagher, Arlene F.

1991-01-01

454

A Talk Show from the Past.  

ERIC Educational Resources Information Center

Describes a two-day activity in which elementary students examine voting rights, the right to assemble, and women's suffrage. Explains the game, "Assemble, Reassemble," and a student-produced talk show with five students playing the roles of leaders of the women's suffrage movement. Profiles Elizabeth Cady Stanton, Lucretia Mott, Susan B. Anthony,…

Gallagher, Arlene F.

1991-01-01

455

Children's Art Show: An Educational Family Experience  

ERIC Educational Resources Information Center

|In a time of seemingly rampant budget cuts in the arts in school systems throughout the country, a children's art show reaps many rewards. It can strengthen family-school relationships and community ties and stimulate questions and comments about the benefits of art and its significance in the development of young children. In this photo essay of…

Bakerlis, Julienne

2007-01-01

456

Effects of mindset on positive illusions  

Microsoft Academic Search

S. E. Taylor and J. D. Brown's (1988) position that mentally healthy people exhibit positive illusions raises a dilemma: How do people function effectively if their perceptions are positively biased? Using Gollwitzer's deliberative-implemental mindset distinction, we assessed whether people in a deliber- ative mindset show less evidence of positive illusions than people in an implemental mindset. Partic- ipants completed a

Shelley E. Taylor; Peter M. Gollwitzer

1995-01-01

457

Recovery position - series (image)  

MedlinePLUS

... CPR, the victim should be placed in the recovery position. The recovery position helps keep the victim's airway open. To put the victim in the recovery position grab the victim's leg and shoulder and ...

458

Benign Paroxysmal Positional Vertigo  

MedlinePLUS

MENU Return to Web version Benign Paroxysmal Positional Vertigo Overview What is benign paroxysmal positional vertigo? Benign paroxysmal positional vertigo (BPPV) is a problem with the nerves and structure of ...

459

Behavioral Intervention Techniques in Drug Abuse Treatment.  

National Technical Information Service (NTIS)

The monograph applies the perspective of behavioral pharmacology to issues of drug abuse treatment. Behavioral interventions are based on the premise that behavior is controlled by its positive and negative consequences and can be modified by making chang...

J. Grabowski M. L. Stitzer J. E. Henningfield

1984-01-01

460

The Novel New Drugs of 2011  

Center for Drug Evaluation (CDER)

Text Version... positive impact on quality care and public health. Page 5. 47% 10% 50% ... and the important new roles they are serving to advance medical care. ... More results from www.fda.gov/downloads/drugs/developmentapprovalprocess