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Sample records for prolonged exposure treatments

  1. Prolonged Exposure: a Rapid Treatment for Phobias

    Science.gov (United States)

    Watson, J. P.; Gaind, R.; Marks, I. M.

    1971-01-01

    Ten adult patients with long-standing specific phobias were treated by prolonged continuous exposure to their phobic objects in fantasy and reality without avoidance. All patients were greatly helped by four to five hours' treatment in two or three sessions, and all improved more after practice than after imaginal sessions. The treatment method is more economical and efficient than other methods described so far. PMID:5539135

  2. Virtual reality exposure versus prolonged exposure for PTSD: Which treatment for whom?

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    Norr, Aaron M; Smolenski, Derek J; Katz, Andrea C; Rizzo, Albert A; Rothbaum, Barbara O; Difede, JoAnn; Koenen-Woods, Patricia; Reger, Mark A; Reger, Greg M

    2018-06-01

    The majority of studies comparing active psychological treatments for posttraumatic stress disorder (PTSD) do not find significant differences at posttreatment. This was the case in a recent trial examining prolonged exposure (PE) and virtual reality exposure (VRE) among active-duty soldiers with combat-related PTSD. Matching individual patients to specific treatments provides a potential avenue to improve significantly the public health impact of effective treatments for PTSD. A composite moderator approach was used to identify profiles of patients who would see superior PTSD symptom reduction in VRE or PE to inform future treatment matching. Active duty U.S. army soldiers (N = 108) were enrolled in a randomized clinical trial comparing VRE and PE in the treatment of PTSD stemming from deployments to Iraq or Afghanistan. Eighteen baseline variables were examined to identify treatment response heterogeneity in two patient groups: those with a superior response to PE and those with a superior response to VRE. The final composite moderator comprised four of 18 baseline variables. Results revealed that patients who were predicted to see greater PTSD symptom reduction in VRE were likely to be younger, not taking antidepressant medication, had greater PTSD hyperarousal symptoms, and were more likely to have greater than minimal suicide risk. Results suggest that treatment matching based on patient profiles could meaningfully improve treatment efficacy for combat-related PTSD. Future research can build on these results to improve our understanding of how to improve treatment matching for PTSD. © 2018 Wiley Periodicals, Inc.

  3. Prolonged Exposure Treatment of Chronic PTSD in Juvenile Sex Offenders: Promising Results from Two Case Studies

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    Hunter, John A.

    2010-01-01

    Prolonged exposure (PE) was used to treat chronic PTSD secondary to severe developmental trauma in two adolescent male sex offenders referred for residential sex offender treatment. Both youth were treatment resistant prior to initiation of PE and showed evidence of long-standing irritability and depression/anxiety. Clinical observation and…

  4. Glycyrrhizin Treatment Facilitates Extinction of Conditioned Fear Responses After a Single Prolonged Stress Exposure in Rats.

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    Lai, Shuhua; Wu, Gangwei; Jiang, Zhixian

    2018-01-01

    Impaired fear memory extinction is widely considered a key mechanism of post-traumatic stress disorder (PTSD). Recent studies have suggested that neuroinflammation after a single prolonged stress (SPS) exposure may play a critical role in the impaired fear memory extinction. Studies have shown that high mobility group box chromosomal protein 1 (HMGB-1) is critically involved in neuroinflammation. However, the role of HMGB-1 underlying the development of impairment of fear memory extinction is still not known. Thus, we examined the levels of HMGB-1 in the basolateral amygdala (BLA) following SPS using Western blot and evaluated the levels of microglia and astrocytes activation in the BLA after SPS using immunohistochemical staining. We then examined the effects of pre-SPS intra-BLA administration of glycyrrhizin, an HMGB1 inhibitor, or LPS-RS, a competitive TLR4 antagonist, on subsequent post-SPS fear extinction. We found that SPS treatment prolonged the extinction of contextual fear memory after the SPS. The impairment of SPS-induced extinction of contextual fear memory was associated with increased HMGB1 and Toll-like receptor 4 (TLR4) levels in the BLA. Additionally, the impairment of SPS-induced extinction of contextual fear memory was associated with increased activation of microglia and astrocyte in the BLA. Intra-BLA administrations of glycyrrhizin (HMGB-1 inhibitor) or LPS-RS (TLR4 antagonist) can prevent the development of SPS-induced fear extinction impairment. Taken together, these results suggested that SPS treatment may not only produce short term effects on the HMGB1/TLR4-mediated pro-inflammation, but alter the response of microglia and astrocytes to the exposure to fear associated contextual stimuli. © 2018 The Author(s). Published by S. Karger AG, Basel.

  5. Glycyrrhizin Treatment Facilitates Extinction of Conditioned Fear Responses After a Single Prolonged Stress Exposure in Rats

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    Shuhua Lai

    2018-03-01

    Full Text Available Background/Aims: Impaired fear memory extinction is widely considered a key mechanism of post-traumatic stress disorder (PTSD. Recent studies have suggested that neuroinflammation after a single prolonged stress (SPS exposure may play a critical role in the impaired fear memory extinction. Studies have shown that high mobility group box chromosomal protein 1 (HMGB-1 is critically involved in neuroinflammation. However, the role of HMGB-1 underlying the development of impairment of fear memory extinction is still not known. Methods: Thus, we examined the levels of HMGB-1 in the basolateral amygdala (BLA following SPS using Western blot and evaluated the levels of microglia and astrocytes activation in the BLA after SPS using immunohistochemical staining. We then examined the effects of pre-SPS intra-BLA administration of glycyrrhizin, an HMGB1 inhibitor, or LPS-RS, a competitive TLR4 antagonist, on subsequent post-SPS fear extinction. Results: We found that SPS treatment prolonged the extinction of contextual fear memory after the SPS. The impairment of SPS-induced extinction of contextual fear memory was associated with increased HMGB1 and Toll-like receptor 4 (TLR4 levels in the BLA. Additionally, the impairment of SPS-induced extinction of contextual fear memory was associated with increased activation of microglia and astrocyte in the BLA. Intra-BLA administrations of glycyrrhizin (HMGB-1 inhibitor or LPS-RS (TLR4 antagonist can prevent the development of SPS-induced fear extinction impairment. Conclusion: Taken together, these results suggested that SPS treatment may not only produce short term effects on the HMGB1/TLR4-mediated pro-inflammation, but alter the response of microglia and astrocytes to the exposure to fear associated contextual stimuli.

  6. Neural changes in extinction recall following prolonged exposure treatment for PTSD: A longitudinal fMRI study

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    Liat Helpman, PhD

    2016-01-01

    Conclusions: Prolonged exposure treatment appears to alter neural activation in PTSD patients during recall of fear extinction, and change in extinction recall (measured by SCR is associated with symptom reduction. We discuss results in the context of neural systems involved in response to affective stimuli.

  7. The effect of shorter exposure versus prolonged exposure on treatment outcome in Tourette syndrome and chronic tic disorders - an open trial.

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    van de Griendt, Jolande M T M; van Dijk, Maarten K; Verdellen, Cara W J; Verbraak, Marc J P M

    2018-01-11

    Exposure and response prevention has shown to be an effective strategy and is considered a first-line intervention in the behavioural treatment of tic disorders. Prior research demonstrated significant tic reduction after 12 two hour sessions. In this open trial, the question is addressed whether, relative to these prolonged sessions, exposure sessions of shorter duration yield differential outcome for patients with tic disorders. A total of 29 patients diagnosed with Tourette syndrome (TS) or chronic tic disorder were treated with shorter exposure sessions (1 h), and these data were compared to the data from a study about prolonged exposure (2 h, n = 21). Outcome was measured by the Yale Global Tic Severity Scale (YGTSS). Results suggest that after taking the difference in illness duration between the two groups into account, the effectiveness of shorter exposure sessions is not inferior to that of prolonged exposure. Results suggest that treatment with shorter exposure might be more efficient and more patients can be reached. Future research is needed to gain more insight into the mechanisms underlying the efficacy of behavioural treatments for tics.

  8. Cultural Adaptations of Prolonged Exposure Therapy for Treatment and Prevention of Posttraumatic Stress Disorder in African Americans

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    Monnica T. Williams

    2014-05-01

    Full Text Available Posttraumatic stress disorder (PTSD is a highly disabling disorder, afflicting African Americans at disproportionately higher rates than the general population. When receiving treatment, African Americans may feel differently towards a European American clinician due to cultural mistrust. Furthermore, racism and discrimination experienced before or during the traumatic event may compound posttrauma reactions, impacting the severity of symptoms. Failure to adapt treatment approaches to encompass cultural differences and racism-related traumas may decrease treatment success for African American clients. Cognitive behavioral treatment approaches are highly effective, and Prolonged Exposure (PE in particular has the most empirical support for the treatment of PTSD. This article discusses culturally-informed adaptations of PE that incorporates race-related trauma themes specific to the Black experience. These include adding more sessions at the front end to better establish rapport, asking directly about race-related themes during the assessment process, and deliberately bringing to the forefront race-related experiences and discrimination during treatment when indicated. Guidelines for assessment and the development of appropriate exposures are provided. Case examples are presented demonstrating adaptation of PE for a survivor of race-related trauma and for a woman who developed internalized racism following a sexual assault. Both individuals experienced improvement in their posttrauma reactions using culturally-informed adaptations to PE.

  9. The Relationship between Posttraumatic and Depressive Symptoms during Prolonged Exposure with and without Cognitive Restructuring for the Treatment of Posttraumatic Stress Disorder

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    Aderka, Idan M.; Gillihan, Seth J.; McLean, Carmen P.; Foa, Edna B.

    2013-01-01

    Objective: In the present study, we examined the relationship between posttraumatic and depressive symptoms during prolonged exposure (PE) treatment with and without cognitive restructuring (CR) for the treatment of posttraumatic stress disorder (PTSD). Method: Female assault survivors (N = 153) with PTSD were randomized to either PE alone or PE…

  10. Pre-treatment Predictors of Dropout from Prolonged Exposure Therapy in Patients with Chronic Posttraumatic Stress Disorder and Comorbid Substance Use Disorders

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    Belleau, Emily L.; Chin, Eu Gene; Wanklyn, Sonya G.; Zambrano-Vazquez, Laura; Schumacher, Julie A.; Coffey, Scott F.

    2017-01-01

    Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) are commonly co-occurring disorders associated with more adverse consequences than PTSD alone. Prolonged exposure therapy (PE) is one of the most efficacious treatments for PTSD. However, among individuals with PTSD-SUD, 35–62% of individuals drop out of trauma-focused exposure treatments. Thus, it is important to identify predictors of PTSD treatment dropout among substance abusers with PTSD in order to gain information about adapting treatment strategies to enhance retention and outcomes. The current study explored pre-treatment predictors of early termination from PE treatment in a sample of 85 individuals receiving concurrent treatment for PTSD and a SUD in a residential treatment facility as part of a randomized controlled trial. The results indicated that less education and more anxiety sensitivity uniquely predicted PE treatment dropout. Demographic variables, PTSD severity, SUD severity, mental health comorbidities, and emotion regulation difficulties did not predict treatment dropout. These results suggest that adding pre-treatment interventions that address anxiety sensitivity, and promote social adjustment and cognitive flexibility, could possibly improve PE retention rates in clients with high anxiety or low education. PMID:28147254

  11. Prolonged Exposure Therapy For Post Traumatic Stress Disorder

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    Levent SÜTÇÝGÝL

    2012-08-01

    Full Text Available Post-traumatic Stress Disorder (PTSD is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related emotions common in posttraumatic stress disorder (PTSD and other anxiety disorders. During exposure, patients intentionally confront with feared objects, situations, thoughts and similar stimuli in order to reduce anxiety level. Exposure can be divided into two main techniques as in vivo exposure and imaginal exposure. Prolonged exposure therapy is a specialized treatment program configured for the treatment of posttraumatic stress disorder and it is based on emotional processing theory. Program is comprised of four main components: (a Psycho-education about trauma and posttraumatic disorders, (b Training for breathing exercises, (c repeated facing with objects, persons, situations and thoughts which causes re-experience about trauma, (d Patient are instructed for telling repeatedly and loudly about traumatic experiences . Prolonged exposure usually involves 9 to 12 sessions, each lasting about 60-90 minutes, administered once or twice a week. Prolonged exposure therapy was started to be implemented since the 1980s, during this period the effectiveness of the therapy has been shown in various empirical studies. [JCBPR 2012; 1(2.000: 98-104

  12. Prolonged Exposure Therapy For Post Traumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Levent SÜTÇİGİL

    2012-07-01

    Full Text Available Post-traumatic Stress Disorder (PTSD is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related emotions common in posttraumatic stress disorder (PTSD and other anxiety disorders. During exposure, patients intentionally confront with feared objects, situations, thoughts and similar stimuli in order to reduce anxiety level. Exposure can be divided into two main techniques as in vivo exposure and imaginal exposure. Prolonged exposure therapy is a specialized treatment program configured for the treatment of posttraumatic stress disorder and it is based on emotional processing theory. Program is comprised of four main components: (a Psycho-education about trauma and posttraumatic disorders, (b Training for breathing exercises, (c repeated facing with objects, persons, situations and thoughts which causes re-experience about trauma, (d Patient are instructed for telling repeatedly and loudly about traumatic experiences . Prolonged exposure usually involves 9 to 12 sessions, each lasting about 60-90 minutes, administered once or twice a week. Prolonged exposure therapy was started to be implemented since the 1980s, during this period the effectiveness of the therapy has been shown in various empirical studies.

  13. A Comparison of Cognitive-Processing Therapy With Prolonged Exposure and a Waiting Condition for the Treatment of Chronic Posttraumatic Stress Disorder in Female Rape Victims

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    Resick, Patricia A.; Nishith, Pallavi; Weaver, Terri L.; Astin, Millie C.; Feuer, Catherine A.

    2010-01-01

    The purpose of this study was to compare cognitive-processing therapy (CPT) with prolonged exposure and a minimal attention condition (MA) for the treatment of posttraumatic stress disorder (PTSD) and depression. One hundred seventy-one female rape victims were randomized into 1 of the 3 conditions, and 121 completed treatment. Participants were assessed with the Clinician-Administered PTSD Scale, the PTSD Symptom Scale, the Structured Clinical Interview for DSM–IV, the Beck Depression Inventory, and the Trauma-Related Guilt Inventory. Independent assessments were made at pretreatment, posttreatment, and 3 and 9 months posttreatment. Analyses indicated that both treatments were highly efficacious and superior to MA. The 2 therapies had similar results except that CPT produced better scores on 2 of 4 guilt subscales. PMID:12182270

  14. Prolonged exposure therapy for the treatment of patients diagnosed with psychogenic non-epileptic seizures (PNES) and post-traumatic stress disorder (PTSD).

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    Myers, Lorna; Vaidya-Mathur, Urmi; Lancman, Marcelo

    2017-01-01

    Although there is general consensus that psychogenic non-epileptic seizures (PNES) are treated with psychotherapy, the effectiveness of most psychotherapeutic modalities remains understudied. In this treatment series of 16 patients dually diagnosed with PNES and post-traumatic stress disorder (PTSD), we evaluated the effect of prolonged exposure therapy (PE) on reduction of PNES. Secondary measures included Beck Depression Inventory (BDI-II) and Post-Traumatic Disorder Diagnostic Scale (PDS). Subjects diagnosed with video EEG-confirmed PNES and PTSD confirmed through neuropsychological testing and clinical interview were treated with traditional PE psychotherapy with certain modifications for the PNES. Treatment was conducted over the course of 12-15 weekly sessions. Seizure frequency was noted in each session by examining the patients' seizure logs, and mood and PTSD symptomatology was assessed at baseline and on the final session. Eighteen subjects enrolled, and 16 (88.8%) completed the course of treatment. Thirteen of the 16 (81.25%) therapy completers reported no seizures by their final PE session, and the other three reported a decline in seizure frequency (Z=-3.233, p=0.001). Mean scores on scales of depression (M=-13.56, SD=12.27; t (15)=-4.420, pPTSD symptoms (M=-17.1875, SD=13.01; t (15)=-5.281, pPTSD reduced the number of PNES and improved mood and post traumatic symptomatology. Follow-up revealed that gains made in seizure control on the last day of treatment were maintained over time. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Glucocorticoid augmentation of prolonged exposure therapy: rationale and case report

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    Laura Pratchett

    2010-12-01

    Full Text Available Rationale: Prolonged exposure (PE therapy has been found to reduce symptoms of posttraumatic stress disorder (PTSD; however, it is difficult for many patients to engage fully in the obligatory retelling of their traumatic experiences. This problem is compounded by the fact that habituation and cognitive restructuring – the main mechanisms through which PE is hypothesized to work – are not instantaneous processes, and often require several weeks before the distress associated with imaginal exposure abates. Case reports: Two cases are described that respectively illustrate the use of hydrocortisone and placebo, in combination with PE, for the treatment of combat-related PTSD. Based on known effects of glucocorticoids on learning and memory performance, we hypothesized that augmentation with hydrocortisone would improve the therapeutic effects of PE by hastening “new” learning and facilitating decreases in the emotional impact of fear memories during the course of treatment. The veteran receiving hydrocortisone augmentation of PE displayed an accelerated and ultimately greater decline in PTSD symptoms than the veteran receiving placebo. Conclusions: While no general conclusion can be derived from comparison of two patients, the findings are consistent with the rationale for augmentation. These case reports support the potential for an appropriately designed and powered clinical trial to examine the efficacy of glucocorticoids in augmenting the effects of psychotherapy for PTSD.

  16. Response of Escherichia coli to Prolonged Berberine Exposure.

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    Budeyri Gokgoz, Nilay; Avci, Fatma Gizem; Yoneten, Kubra Karaosmanoglu; Alaybeyoglu, Begum; Ozkirimli, Elif; Sayar, Nihat Alpagu; Kazan, Dilek; Sariyar Akbulut, Berna

    2017-07-01

    Berberine is a plant-derived alkaloid possessing antimicrobial activity; unfortunately, its efflux through multidrug resistance pumps reduces its efficacy. Cellular life span of Escherichia coli is generally shorter with prolonged berberine exposure; nevertheless, about 30% of the cells still remain robust following this treatment. To elucidate its mechanism of action and to identify proteins that could be involved in development of antimicrobial resistance, protein profiles of E. coli cells treated with berberine for 4.5 and 8 hours were compared with control cells. A total of 42 proteins were differentially expressed in cells treated with berberine for 8 hours when compared to control cells. In both 4.5 and 8 hours of berberine-treated cells, carbohydrate and peptide uptake regimens remained unchanged, although amino acid maintenance regimen switched from transport to synthesis. Defect in cell division persisted and this condition was confirmed by images obtained from scanning electron microscopy. Universal stress proteins were not involved in stress response. The significant increase in the abundance of elongation factors could suggest the involvement of these proteins in protection by exhibiting chaperone activities. Furthermore, the involvement of the outer membrane protein OmpW could receive special attention as a protein involved in response to antimicrobial agents, since the expression of only this porin protein was upregulated after 8 hours of exposure.

  17. Prolonged Exposure Therapy for a Vietnam Veteran with PTSD and Early-Stage Dementia

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    Duax, Jeanne M.; Waldron-Perrine, Brigid; Rauch, Sheila A. M.; Adams, Kenneth M.

    2013-01-01

    Although prolonged exposure therapy (PE) is considered an evidence-based treatment for PTSD, there has been little published about the use of this treatment for older adults with comorbid early-stage dementia. As the number of older adults in the United States continues to grow, so will their unique mental health needs. The present article…

  18. Effectiveness of Cognitive Processing Therapy and Prolonged Exposure in the Department of Veterans Affairs.

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    Rutt, Benjamin T; Oehlert, Mary E; Krieshok, Thomas S; Lichtenberg, James W

    2018-04-01

    Objective This study evaluated the effectiveness of cognitive processing therapy and prolonged exposure in conditions reflective of current clinical practice within the Veterans Health Administration. Method This study involved a retrospective review of 2030 charts. A total of 750 veterans from 10 U.S. states who received cognitive processing therapy or prolonged exposure in individual psychotherapy were included in the study (participants in cognitive processing therapy, N = 376; participants in prolonged exposure, N = 374). The main dependent variable was self-reported posttraumatic stress disorder symptoms as measured by total scores on the Posttraumatic Stress Disorder Checklist. The study used multilevel modeling to evaluate the absolute and relative effectiveness of both treatments and determine the relationship between patient-level variables and total Posttraumatic Stress Disorder Checklist scores during treatment. Results Cognitive processing therapy and prolonged exposure were equally effective at reducing total Posttraumatic Stress Disorder Checklist scores. Veterans who completed therapy reported significantly larger reductions in the Posttraumatic Stress Disorder Checklist than patients who did not complete therapy. There were no significant differences in the improvement of posttraumatic stress disorder symptoms with respect to age and three racial/ethnic groups (Caucasian, African American, and Hispanic). Conclusions Cognitive processing therapy and prolonged exposure were shown to be effective in conditions highly reflective of clinical practice and with a highly diverse sample of veterans. Challenges related to dropout from trauma focused therapy should continue to be researched.

  19. Effect of prolonged exposure to low antigen concentration for sensitization

    International Nuclear Information System (INIS)

    Och, Francois M.M. van; Vandebriel, Rob J.; Jong, Wim H. de; Loveren, Henk van

    2003-01-01

    The local lymph node assay (LLNA) is an assay in mice to identify potential allergens. Compounds that do not induce a stimulation index (SI)≥3 are not considered sensitizers. Of the chemicals that do, the SI of 3 is used as a benchmark, and indicates the sensitizing potency of a chemical. Compared to the exposure duration of the LLNA (3 days), real life exposure often lasts for months or years. We therefore investigated whether prolonged exposure to sensitizers at concentrations that do not induce a SI≥3 in the LLNA, were able to surpass this threshold. Mice were treated for 2 months at 7-day intervals with a range of concentrations of the known allergens ethyl-p-aminobenzoate (benzocaine, BENZ), 2,4-dinitrochlorobenzene (DNCB), and tetramethyl thiuram disulfide (TMTD). Both proliferative activity and cytokine production were established at day 60. Neither BENZ nor TMTD showed a significant increase in the proliferation rate compared to vehicle controls. Only DNCB at concentrations originally above the EC 3 a significant increase in proliferation was seen after prolonged exposure. No significant effect on IFN-γ and IL-4 production was observed for all three compounds compared. These findings indicate that for classification of sensitizers the shorter exposure period employed in the standard LLNA is sufficient, and longer periods of exposure have no bearing on this classification

  20. Media Impacts on Women's Fertility Desires: A Prolonged Exposure Experiment.

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    Knobloch-Westerwick, Silvia; Willis, Laura E; Kennard, Ashley R

    2016-06-01

    Media exposure may have implications for family planning, a public health issue of key importance. Drawing on social comparison theory and social identity theory, a prolonged exposure experiment examined whether media portrayals of women's social roles affect fertility desires among 166 American, nonstudent, never married, childless women ages 21-35 years old. After sign-up and baseline sessions, participants viewed magazine pages five days in a row. Stimuli presented women in either mother/homemaker roles, beauty ideal roles, or professional roles. Three days later, participants again indicated their number of desired children and time planned until first birth. Exposure to mother/homemaker and beauty ideal portrayals increased the number of desired children across time. Exposure to professional portrayals increased the time planned until 1st birth compared to beauty ideal portrayals-this impact was partially mediated by a shift toward more progressive gender norms (per social identity theory) and assimilation (per social comparison theory).

  1. QT interval prolongation associated with sibutramine treatment

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    Harrison-Woolrych, Mira; Clark, David W J; Hill, Geraldine R; Rees, Mark I; Skinner, Jonathan R

    2006-01-01

    Aims To investigate a possible association of sibutramine with QT interval prolongation. Methods Post-marketing surveillance using prescription event monitoring in the New Zealand Intensive Medicines Monitoring Programme (IMMP) identified a case of QT prolongation and associated cardiac arrest in a patient taking sibutramine for 25 days. This patient was further investigated, including genotyping for long QT syndrome. Other IMMP case reports suggesting arrhythmias associated with sibutramine were assessed and further reports were obtained from the World Health Organisation (WHO) adverse drug reactions database. Results The index case displayed a novel mutation in a cardiac potassium channel subunit gene, KCNQ1, which is likely to prolong cardiac membrane depolarization and increase susceptibility to long QT intervals. Assessment of further IMMP reports identified five additional patients who experienced palpitations associated with syncope or presyncopal symptoms, one of whom had a QTc at the upper limit of normal. Assessment of reports from the WHO database identified three reports of QT prolongation and one fatal case of torsade de pointes in a patient also taking cisapride. Conclusions This case series suggests that sibutramine may be associated with QT prolongation and related dysrhythmias. Further studies are required, but in the meantime we would recommend that sibutramine should be avoided in patients with long QT syndrome and in patients taking other medicines that may prolong the QT interval. PMID:16542208

  2. Physiological Stress Responses to Prolonged Exposure to MS-222 and Surgical Implantation in Juvenile Chinook Salmon

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    Wagner, Katie A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Woodley, Christa M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Seaburg, Adam [Univ. of Washington, Seattle, WA (United States); Skalski, John R. [Univ. of Washington, Seattle, WA (United States); Eppard, Matthew B. [U.S. Army Corps of Engineers, Portland, OR (United States)

    2014-07-17

    While many studies have investigated the effects of transmitters on fish condition, behavior, and survival, to our knowledge, no studies have taken into account anesthetic exposure time in addition to tag and surgery effects. We investigated stress responses to prolonged MS-222 exposure after stage 4 induction in surgically implanted juvenile Chinook salmon (Oncorhynchus tshawytscha). Survival, tag loss, plasma cortisol concentration, and blood Na+, K+, Ca2+, and pH were measured immediately following anesthetic exposure and surgical implantation and 1, 7, and 14 days post-treatment. Despite the prolonged anesthetic exposure, 3-15 minutes post Stage 4 induction, there were no mortalities or tag loss in any treatment. MS-222 was effective at delaying immediate cortisol release during surgical implantation; however, osmotic disturbances resulted, which were more pronounced in longer anesthetic time exposures. From day 1 to day 14, Na+, Ca2+, and pH significantly decreased, while cortisol significantly increased. The cortisol increase was exacerbated by surgical implantation. There was a significant interaction between MS-222 time exposure and observation day for Na+, Ca2+, K+, and pH; variations were seen in the longer time exposures, although not consistently. In conclusion, stress response patterns suggest stress associated with surgical implantation is amplified with increased exposure to MS-222.

  3. Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.

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    Hui Qun Fu

    Full Text Available Inflammation is a hallmark of several disease states ranging from neurodegeneration to sepsis but is also implicated in physiological processes like ageing. Non-resolving inflammation and prolonged neuroinflammation are unclear processes implicated in several conditions, including ageing. In this study we studied the long-term effects of endotoxemia, as systemic lipopolysaccharide (LPS injection, focusing on the role of astrocyte activation and cytokine release in the brain of aged rats. A single dose of LPS (2 mg/kg or 0.9% saline was injected intraperitoneally in aged rats. Levels of pro-inflammatory cytokines (TNFα and IL-1β and NF-κB p65 activation were measured systemically and in hippocampal tissue. Astrocytes and cytokines release in the CNS were detected via double immunofluorescence staining at different time-points up to day 30. Serum levels of TNFα and IL-1β were significantly increased acutely after 30 minutes (p<0.001 and up to 6 hours (p<0.001 following LPS-injection. Centrally, LPS-treated rats showed up-regulated mRNA expression and protein levels of pro-inflammatory cytokines in the hippocampus. These changes associated with astrogliosis in the hippocampus dentate gyrus (DG, IL-1β immunoreactivity and elevated NF-κB p65 expression up to day 30 post LPS exposure. Overall, these data demonstrate that LPS induces prolonged neuroinflammation and astrocyte activation in the hippocampus of aged rats. Hippocampal NF-κB p65 and excessive astrocytes-derived IL-1β release may play a pivotal role in regulating long-lasting neuroinflammation.

  4. Deciding about treatments that prolong life

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    ... you are receiving or may need in the future. Learn about the treatments and how they would ... patients and their families. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: ...

  5. Prolonged Exposure Therapy For Post Traumatic Stress Disorder

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    Levent SÜTÇÝGÝL; Selçuk ASLAN

    2012-01-01

    Post-traumatic Stress Disorder (PTSD) is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related ...

  6. Effects of prolonged exposure to perchlorate on thyroid and reproductive function in zebrafish

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    Mukhi, S.; Patino, R.

    2007-01-01

    The objectives of this study were to determine the effects of prolonged exposure to perchlorate on (1) thyroid status and reproductive performance of adult zebrafish (Danio rerio) and (2) F1 embryo survival and early larval development. Using a static-renewal procedure, mixed sex populations of adult zebrafish were exposed to 0, 10, and 100 mg/l nominal concentrations of waterborne perchlorate for 10 weeks. Thyroid histology was qualitatively assessed, and females and males were separated and further exposed to their respective treatments for six additional weeks. Eight females in each tank replicate (n = 3) were paired weekly with four males from the same respective treatment, and packed-egg (spawn) volume (PEV) was measured each of the last five weeks. At least once during weeks 14-16 of exposure, other end points measured included fertilization rate, fertilized egg diameter, hatching rate, standard length, and craniofacial development of 4-day-postfertilization larvae and thyroid hormone content of 3.5-h embryos and of exposed mothers. At 10 weeks of exposure, perchlorate at both concentrations caused thyroidal hypertrophy and colloid depletion. A marked reduction in PEV was observed toward the end of the 6-week spawning period, but fertilization and embryo hatching rates were unaffected. Fertilized egg diameter and larval length were increased by parental exposure to perchlorate. Larval head depth was unaffected but the forward protrusion of the lower jaw-associated cartilage complexes, Meckel's and ceratohyal, was decreased. Exposure to both concentrations of perchlorate inhibited whole-body thyroxine content in mothers and embryos, but triiodothyronine content was unchanged. In conclusion, prolonged exposure of adult zebrafish to perchlorate not only disrupts their thyroid endocrine system but also impairs reproduction and influences early F1 development. ?? 2007 Oxford University Press.

  7. Streptococcus suis meningitis can require a prolonged treatment course

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    Jean Dejace

    2017-12-01

    Full Text Available We report a case of recrudescent Streptococcus suis meningitis requiring a prolonged treatment course. A few similar cases can be found in the burgeoning literature on what remains a relatively uncommon disease in humans, and these patients should be monitored carefully upon completion of therapy. Keywords: Meningitis, Relapse, Duration, Streptococcus suis

  8. Integrating Dialectical Behavior Therapy and Prolonged Exposure to Treat Co-Occurring Borderline Personality Disorder and PTSD: Two Case Studies

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    Harned, Melanie S.; Linehan, Marsha M.

    2008-01-01

    Despite the high rate of trauma and PTSD among individuals with borderline personality disorder (BPD), no studies have specifically evaluated the treatment of PTSD in a BPD population. These case studies illustrate the use of a protocol based on prolonged exposure therapy that can be integrated into standard dialectical behavior therapy to treat…

  9. Competing for Consciousness: Prolonged Mask Exposure Reduces Object Substitution Masking

    Science.gov (United States)

    Goodhew, Stephanie C.; Visser, Troy A. W.; Lipp, Ottmar V.; Dux, Paul E.

    2011-01-01

    In object substitution masking (OSM) a sparse, temporally trailing 4-dot mask impairs target identification, even though it has different contours from, and does not spatially overlap with the target. Here, we demonstrate a previously unknown characteristic of OSM: Observers show reduced masking at prolonged (e.g., 640 ms) relative to intermediate…

  10. Prolonged Remission in Neuromyelitis Optica Following Cessation of Rituximab Treatment.

    Science.gov (United States)

    Weinfurtner, Kelley; Graves, Jennifer; Ness, Jayne; Krupp, Lauren; Milazzo, Maria; Waubant, Emmanuelle

    2015-09-01

    Neuromyelitis optica is an autoimmune disease characterized by acute episodes of transverse myelitis and optic neuritis. Several small, open-label studies suggest rituximab, a monoclonal antibody against CD20, prevents relapses in neuromyelitis optica; however, there is little consensus on timing or duration of treatment. Here we report four patients with severe relapsing neuromyelitis optica who were stabilized on rituximab and, after discontinuing treatment, continued to experience prolonged remission of their disease. Remission ranged from 4.5 to 10.5 years total, including 3 to 9 years off all therapies. The patients had sustained clinical responses despite normal B-lymphocyte levels and, in at least 2 patients, continued seropositivity for aquaporin-4 antibodies. These cases suggest that rituximab may induce prolonged remission in certain neuromyelitis optica patients, and they highlight the need for further elucidation of rituximab's mechanism in neuromyelitis optica. © The Author(s) 2014.

  11. Feasibility and Efficacy of Prolonged Exposure for PTSD among Individuals with a Psychotic Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Anouk L. Grubaugh

    2017-06-01

    Full Text Available Objective: Few empirical studies have examined the feasibility of trauma-focused treatment among individuals with schizophrenia. This lack of research is important given the substantial overlap of trauma exposure and subsequent PTSD with psychotic spectrum disorders, and the potential for PTSD to complicate the course and prognosis of schizophrenia and other variants of severe mental illness.Method: As part of a larger study, 14 veterans with a psychotic spectrum disorder were enrolled to receive prolonged exposure (PE for PTSD within a single arm open trial study design. Patient reactions and responses to PE were examined using feasibility indices such as attrition, survey reactions, and treatment expectancy; pre and post-changes in PTSD severity and diagnostic status; and thematic interviews conducted post-intervention.Results: Quantitative and qualitative data indicate that implementation of PE is feasible, subjectively well-tolerated, and may result in clinically significant reductions in PTSD symptoms in patients with psychotic spectrum disorders.Conclusion: Consistent with treatment outcome data in clinical populations with a broader range of severe mental illnesses, the current results support the use of PTSD exposure-based interventions, such as PE, for individuals with psychotic spectrum disorders.

  12. Pankiller effect of prolonged exposure to menadione on glioma cells: potentiation by vitamin C.

    Science.gov (United States)

    Vita, Marina F; Nagachar, Nivedita; Avramidis, Dimitrios; Delwar, Zahid M; Cruz, Mabel H; Siden, Åke; Paulsson, Kajsa M; Yakisich, Juan Sebastian

    2011-12-01

    Menadione (Vitamin K3) has anti-tumoral effects against a wide range of cancer cells. Its potential toxicity to normal cells and narrow therapeutic range limit its use as single agent but in combination with radiation or other anti-neoplastic agents can be of therapeutic use. In this paper, we first evaluated the early (within 3 h) effect of menadione on ongoing DNA replication. In normal rat cerebral cortex mini-units menadione showed an age dependent anti-proliferative effect. In tissue mini-units prepared from newborn rats, menadione inhibited ongoing DNA replication with an IC (50) of approximately 10 μM but 50 μM had no effect on mini-units from prepared adult rat tissue. The effect of short (72 h) and prolonged exposure (1-2 weeks) to menadione alone in the DBTRG.05MG human glioma cells line and in combination with vitamin C was studied. After short period of exposure data show that menadione alone or in combination with vitamin C provided similar concentration-response curves (and IC(50) values). Prolonged exposure to these drugs was evaluated by their ability to kill 100% of glioma cells and prevent regrowth when cells are re-incubated in drug-free media. In this long-term assay, menadione:vitamin C at a ratio 1:100 showed higher anti-proliferative activity when compared to each drug alone and allowed to reduce each drug concentration between 2.5 to 5-fold. Similar anti-proliferative effect was demonstrated in 8 patient derived glioblastoma cell cultures. Our data should be able to encourage further advanced studies on animal models to evaluate the potential use of this combination therapy for glioma treatment.

  13. Dose formation and hematologic effects with prolonged internal exposure of rats by isotope 131I

    International Nuclear Information System (INIS)

    Sova, O.A.; Drozd, Yi.P.

    2013-01-01

    Processes in single dose formation and long-term domestic revenue 131 I in rats was investigated. Original method of estimating absorbed doses in hemacyte for macro-dosemeters indicators was proposed. Dose factors for hemacyte and the dynamics of the blood-forming organs doses for prolonged two cases of prolonged exposure was calculated. Hematologic effects were studied for two variants of entry of the isotope. Peculiarities of doses formation and identified hematological effects are discussed

  14. Risk Factors for Prolonged Treatment of Whiplash-Associated Disorders.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Oka

    Full Text Available Whiplash-associated disorders (WAD are the most common injuries that are associated with car collisions in Japan and many Western countries. However, there is no clear evidence regarding the potential risk factors for poor recovery from WAD. Therefore, we used an online survey of the Japanese population to examine the association between potential risk factors and the persistence of symptoms in individuals with WAD.An online survey was completed by 127,956 participants, including 4,164 participants who had been involved in a traffic collision. A random sample of the collision participants (n = 1,698 were provided with a secondary questionnaire. From among the 974 (57.4% respondents to the secondary questionnaire, we selected 183 cases (intractable neck pain that was treated over a period of 6 months and 333 controls (minor neck pain that was treated within 3 months. Multivariable logistic regression analysis was used to evaluate the potential risk factors for prolonged treatment of WAD.Female sex, the severity of the collision, poor expectations of recovery, victim mentality, dizziness, numbness or pain in the arms, and lower back pain were associated with a poor recovery from WAD.In the present study, the baseline symptoms (dizziness, numbness or pain in the arms, and lower back pain had the strongest associations with prolonged treatment for WAD, although the psychological and behavioral factors were also important. These risk factors should be considered when evaluating patients who may have the potential for poor outcomes.

  15. Prolonged Exposure Therapy Following Awareness under Anesthesia: A Case Study

    Science.gov (United States)

    Levinson, Cheri A.; Rodebaugh, Thomas L.; Bertelson, Amy D.

    2013-01-01

    Awareness during surgery is estimated to effect between 40,000 to 140,000 patients per year in the United States, and there is a growing literature suggesting that this event can lead to the development of posttraumatic stress disorder (PTSD). The current article describes treatment implemented from a manualized protocol of a woman diagnosed with…

  16. Implementation of Prolonged Exposure in the Army: Is Consultation Necessary for Effective Dissemination

    Science.gov (United States)

    2015-10-01

    to hiring websites and local advertisements , and several candidates were identified. An initial part-time offer was made to Loreli Leos, LPC in July...2015). Prolonged exposure vs eye movement desensitization and reprocessing vs waiting list for posttraumatic stress disorder in patients with a

  17. Neural Circuits via Which Single Prolonged Stress Exposure Leads to Fear Extinction Retention Deficits

    Science.gov (United States)

    Knox, Dayan; Stanfield, Briana R.; Staib, Jennifer M.; David, Nina P.; Keller, Samantha M.; DePietro, Thomas

    2016-01-01

    Single prolonged stress (SPS) has been used to examine mechanisms via which stress exposure leads to post-traumatic stress disorder symptoms. SPS induces fear extinction retention deficits, but neural circuits critical for mediating these deficits are unknown. To address this gap, we examined the effect of SPS on neural activity in brain regions…

  18. Prolonged Particulate Hexavalent Chromium Exposure Suppresses Homologous Recombination Repair in Human Lung Cells.

    Science.gov (United States)

    Browning, Cynthia L; Qin, Qin; Kelly, Deborah F; Prakash, Rohit; Vanoli, Fabio; Jasin, Maria; Wise, John Pierce

    2016-09-01

    Genomic instability is one of the primary models of carcinogenesis and a feature of almost all cancers. Homologous recombination (HR) repair protects against genomic instability by maintaining high genomic fidelity during the repair of DNA double strand breaks. The defining step of HR repair is the formation of the Rad51 nucleofilament, which facilitates the search for a homologous sequence and invasion of the template DNA strand. Particulate hexavalent chromium (Cr(VI)), a human lung carcinogen, induces DNA double strand breaks and chromosome instability. Since the loss of HR repair increases Cr(VI)-induced chromosome instability, we investigated the effect of extended Cr(VI) exposure on HR repair. We show acute (24 h) Cr(VI) exposure induces a normal HR repair response. In contrast, prolonged (120 h) exposure to particulate Cr(VI) inhibited HR repair and Rad51 nucleofilament formation. Prolonged Cr(VI) exposure had a profound effect on Rad51, evidenced by reduced protein levels and Rad51 mislocalization to the cytoplasm. The response of proteins involved in Rad51 nuclear import and nucleofilament formation displayed varying responses to prolonged Cr(VI) exposure. BRCA2 formed nuclear foci after prolonged Cr(VI) exposure, while Rad51C foci formation was suppressed. These results suggest that particulate Cr(VI), a major chemical carcinogen, inhibits HR repair by targeting Rad51, causing DNA double strand breaks to be repaired by a low fidelity, Rad51-independent repair pathway. These results further enhance our understanding of the underlying mechanism of Cr(VI)-induced chromosome instability and thus, carcinogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Effects of prolonged exposure to space flight factors for 175 days on lettuce seeds

    International Nuclear Information System (INIS)

    Nevzgodina, L.V.; Maximova, E.N.; Akatov, Yu.A.

    1981-01-01

    The effects of prolonged (up to 175 days) exposure of Lactuca sativa seeds to space flight factors, including primary cosmic radiation heavy ions have been studied. The data obtained evidence a significant fourfold increase of spontaneous mutagenesis in seeds both with regard to the total number of aberrant cells as well as the formation of single cells with multiple aberrations. Comparison of the present experiment with earlier works shows that the frequency of such aberrations increases with the duration of the flight

  20. The peculiarity of aerobic energy supply of rat tissues of different age upon prolonged ionizing and thermal exposure

    International Nuclear Information System (INIS)

    Tsyhun, G.F.

    1998-01-01

    Energy-producing functions of brain, myocardium, and hepatic mitochondria in mature and immature rats in remote period after prolonged ionizing X-ray at total dose 12,9 m C/kg and thermal exposure (4 hours, 37 degrees centigrade, 25 times) were studied. Dehydrogenase activities (pyruvate-, isocitrate-, 2-oxy glutarate-, succinate- and malate dehydrogenases) were reduced in mitochondria of different tissues of adult rats and it was especially considerable after combined influence. A higher resistance of young rats, as compared to adult ones, to combined radiation-thermal treatments was established

  1. Identifying Molecular Targets For PTSD Treatment Using Single Prolonged Stress

    Science.gov (United States)

    2014-10-01

    Post - traumatic stress disorder ( PTSD ) is a chronic, debilitating psychiatric disorder that can...SPS animals. Post - traumatic stress disorder ( PTSD ) is associated with neurocognitive impairments that have been attributed to functional deficits...and resilience. 2. KEYWORDS Post - traumatic stress disorder , Single Prolonged Stress , Neurobiological Mechanisms 5 3. ACCOMPLISHMENTS

  2. Prolonged exposure to particulate chromate inhibits RAD51 nuclear import mediator proteins.

    Science.gov (United States)

    Browning, Cynthia L; Wise, John Pierce

    2017-09-15

    Particulate hexavalent chromium (Cr(VI)) is a human lung carcinogen and a human health concern. The induction of structural chromosome instability is considered to be a driving mechanism of Cr(VI)-induced carcinogenesis. Homologous recombination repair protects against Cr(VI)-induced chromosome damage, due to its highly accurate repair of Cr(VI)-induced DNA double strand breaks. However, recent studies demonstrate Cr(VI) inhibits homologous recombination repair through the misregulation of RAD51. RAD51 is an essential protein in HR repair that facilitates the search for a homologous sequence. Recent studies show prolonged Cr(VI) exposure prevents proper RAD51 subcellular localization, causing it to accumulate in the cytoplasm. Since nuclear import of RAD51 is crucial to its function, this study investigated the effect of Cr(VI) on the RAD51 nuclear import mediators, RAD51C and BRCA2. We show acute (24h) Cr(VI) exposure induces the proper localization of RAD51C and BRCA2. In contrast, prolonged (120h) exposure increased the cytoplasmic localization of both proteins, although RAD51C localization was more severely impaired. These results correlate temporally with the previously reported Cr(VI)-induced RAD51 cytoplasmic accumulation. In addition, we found Cr(VI) does not inhibit interaction between RAD51 and its nuclear import mediators. Altogether, our results suggest prolonged Cr(VI) exposure inhibits the nuclear import of RAD51C, and to a lesser extent, BRCA2, which results in the cytoplasmic accumulation of RAD51. Cr(VI)-induced inhibition of nuclear import may play a key role in its carcinogenic mechanism since the nuclear import of many tumor suppressor proteins and DNA repair proteins is crucial to their function. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Diverse definitions of prolonged labour and its consequences with sometimes subsequent inappropriate treatment

    OpenAIRE

    Nystedt, Astrid; Hildingsson, Ingegerd

    2014-01-01

    Background: Prolonged labour very often causes suffering from difficulties that may have lifelong implications. This study aimed to explore the prevalence and treatment of prolonged labour and to compare birth outcome and women's experiences of prolonged and normal labour. Method: Women with spontaneous onset of labour, living in a Swedish county, were recruited two months after birth, to a cross-sectional study. Women (n = 829) completed a questionnaire that investigated socio-demographic an...

  4. Alantolactone Improves Prolonged Exposure of Interleukin-6-Induced Skeletal Muscle Inflammation Associated Glucose Intolerance and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Minjee Kim

    2017-06-01

    Full Text Available The pro-inflammatory cytokine, Interleukin-6 (IL-6, has been proposed to be one of the mediators that link chronic inflammation to glucose intolerance and insulin resistance. Many studies have demonstrated the effects of IL-6 on insulin action in the skeletal muscle. However, few studies have investigated the effect of long-term treatment of IL-6, leading to glucose intolerance and insulin resistance. In the present study, we observed protective effects of alantolactone, a sesquiterpene lactone isolated from Inula helenium against glucose intolerance and insulin resistance induced by prolonged exposure of IL-6. Alantolactone has been reported to have anti-inflammatory and anti-cancer effects through IL-6-induced signal transducer and activator of transcription 3 (STAT3 signaling pathway. The relationship between IL-6 exposure and expression of toll-like receptor 4 (TLR4, involved in inflammation in the skeletal muscle, and the underlying mechanisms were investigated. We observed maximum dysregulation of glucose uptake after 40 ng/ml IL-6 induction for 24 h in L6 myotubes. Prolonged IL-6 exposure suppressed glucose uptake regulating alpha serine/threonine-protein kinase (AKT phosphorylation; however, pretreatment with alantolactone activated AKT phosphorylation and improved glucose uptake. Alantolactone also attenuated IL-6-stimulated STAT3 phosphorylation, followed by an increase in expression of negative regulator suppressor of cytokine signaling 3 (SOCS3. Furthermore, IL-6-induced expression of pathogen recognition receptor, TLR4, was also suppressed by alantolactone pretreatment. Post-silencing of STAT3 using siRNA approach, IL-6-stimulated siRNA-STAT3 improved glucose uptake and suppressed TLR4 gene expression. Taken together, we propose that, as a STAT3 inhibitor, alantolactone, improves glucose regulation in the skeletal muscle by inhibiting IL-6-induced STAT3-SOCS3 signaling followed by inhibition of the TLR4 gene expression. Therefore

  5. Severe, multimodal stress exposure induces PTSD-like characteristics in a mouse model of single prolonged stress.

    Science.gov (United States)

    Perrine, Shane A; Eagle, Andrew L; George, Sophie A; Mulo, Kostika; Kohler, Robert J; Gerard, Justin; Harutyunyan, Arman; Hool, Steven M; Susick, Laura L; Schneider, Brandy L; Ghoddoussi, Farhad; Galloway, Matthew P; Liberzon, Israel; Conti, Alana C

    2016-04-15

    Appropriate animal models of posttraumatic stress disorder (PTSD) are needed because human studies remain limited in their ability to probe the underlying neurobiology of PTSD. Although the single prolonged stress (SPS) model is an established rat model of PTSD, the development of a similarly-validated mouse model emphasizes the benefits and cross-species utility of rodent PTSD models and offers unique methodological advantages to that of the rat. Therefore, the aims of this study were to develop and describe a SPS model for mice and to provide data that support current mechanisms relevant to PTSD. The mouse single prolonged stress (mSPS) paradigm, involves exposing C57Bl/6 mice to a series of severe, multimodal stressors, including 2h restraint, 10 min group forced swim, exposure to soiled rat bedding scent, and exposure to ether until unconsciousness. Following a 7-day undisturbed period, mice were tested for cue-induced fear behavior, effects of paroxetine on cue-induced fear behavior, extinction retention of a previously extinguished fear memory, dexamethasone suppression of corticosterone (CORT) response, dorsal hippocampal glucocorticoid receptor protein and mRNA expression, and prefrontal cortex glutamate levels. Exposure to mSPS enhanced cue-induced fear, which was attenuated by oral paroxetine treatment. mSPS also disrupted extinction retention, enhanced suppression of stress-induced CORT response, increased mRNA expression of dorsal hippocampal glucocorticoid receptors and decreased prefrontal cortex glutamate levels. These data suggest that the mSPS model is a translationally-relevant model for future PTSD research with strong face, construct, and predictive validity. In summary, mSPS models characteristics relevant to PTSD and this severe, multimodal stress modifies fear learning in mice that coincides with changes in the hypothalamo-pituitary-adrenal (HPA) axis, brain glucocorticoid systems, and glutamatergic signaling in the prefrontal cortex

  6. Elastic stockings effect on leg volume variability in healthy workers under prolonged gravitational gradient exposure

    Directory of Open Access Journals (Sweden)

    Mirko Tessari

    2015-06-01

    Full Text Available The aim of this study was to determine the elastic stockings effect on healthy workers (HW who are exposed to a prolonged hydrostatic pressure overload for professional reasons. The cohort was composed by 20 HW who voluntarily underwent a water plethysmography test before and after eight hour of standing up in an operating room, wearing elastic stockings. After 8 h of gravity exposure, we demonstrated the absence of leg volume increase in case of elastic stockings use. In the morning measurement we found that the lower limb volume was 1967.5 mL±224, while in the evening it was 1962.5 mL±227 (P<0.0828. The decreased volume is significantly correlated with the time that was spent under gravity forces for working purpose wearing elastic stockings (R2=0.99, P<0.0001. Our experiment demonstrates that elastic stockings may effectively counteract the increased leg volume over time in workers who are exposed to prolonged gravitational gradient. Further longitudinal studies are needed to determine if the above effect could correct one of the major risk factors for the development of chronic venous insufficiency.

  7. Previous Repeated Exposure to Food Limitation Enables Rats to Spare Lipid Stores during Prolonged Starvation.

    Science.gov (United States)

    McCue, Marshall D; Albach, Audrey; Salazar, Giovanni

    The risk of food limitation and, ultimately, starvation dates back to the dawn of heterotrophy in animals, yet starvation remains a major factor in the regulation of modern animal populations. Researchers studying starvation more than a century ago suggested that animals subjected to sublethal periods of food limitation are somehow more tolerant of subsequent starvation events. This possibility has received little attention over the past decades, yet it is highly relevant to modern science for two reasons. First, animals in natural populations are likely to be exposed to bouts of food limitation once or more before they face prolonged starvation, during which the risk of mortality becomes imminent. Second, our current approach to studying starvation physiology in the laboratory focuses on nourished animals with no previous exposure to nutritional stress. We examined the relationship between previous exposure to food limitation and potentially adaptive physiological responses to starvation in adult rats and found several significant differences. On two occasions, rats were fasted until they lost 20% of their body mass maintained lower body temperatures, and had presumably lower energy requirements when subjected to prolonged starvation than their naive cohort that never experienced food limitation. These rats that were trained in starvation also had lower plasma glucose set -points and reduced their reliance on endogenous lipid oxidation. These findings underscore (1) the need for biologists to revisit the classic hypothesis that animals can become habituated to starvation, using a modern set of research tools; and (2) the need to design controlled experiments of starvation physiology that more closely resemble the dynamic nature of food availability.

  8. Predictors of Prolonged TB Treatment in a Dutch Outpatient Setting.

    Directory of Open Access Journals (Sweden)

    Natasha Van't Boveneind-Vrubleuskaya

    Full Text Available Standard treatment duration for drug-susceptible tuberculosis (TB treatment is 6 months. Treatment duration is often extended-and for various different reasons. The aim of this study was to determine the prevalence and to assess risk factors associated with extended TB treatment.A cross-sectional study was conducted. Data including demographic, clinical, radiological and microbiological information from the Netherlands TB Register (NTR of 90 patients with smear and culture positive pulmonary TB of the region Haaglanden, The Netherlands, was eligible for analysis.Treatment was extended to ≥ 200 days by 46 (51% patients. Extended TB treatment was associated with a higher frequency of symptoms, presumed to be due to adverse drug reactions (ADR; OR 2.39 95% CI: 1.01-5.69, drug-induced liver injury (DILI (OR: 13.51; 95% CI: 1.66-109.82 and longer than 2 month smear and culture conversion rate (OR: 11.00; 95% CI: 1.24-97.96 and OR: 8.56; 95% CI: 1.53-47.96. In the multivariable logistic analysis, development of DILI emerged as the single statistically strong risk factor necessitating extension of TB treatment.This finding will need further confirmation in a prospective study, exploring the possible mutual role of pharmacokinetic and pharmacogenetic determinants of DILI among TB patients.

  9. Evidence of Complex Posttraumatic Stress Disorder (CPTSD) across populations with prolonged trauma of varying intensity and ages of exposure

    DEFF Research Database (Denmark)

    Palic, Sabina; Zerach, G; Shevlin, Mark

    2016-01-01

    , with a "Dissociative PTSD-subtype" class. ICD-11's CPTSD was not exclusively associated with childhood abuse, but also with exposure to adulthood trauma of severe interpersonal intensity. Furthermore, all types of prolonged trauma were equally associated with the "Anxiety symptoms" class. Finally, of all the classes......The ICD-11 proposes different types of prolonged trauma as risk factors for complex PTSD (CPTSD). However, CPTSD's construct validity has only been examined in childhood abuse, and single trauma exposure samples. Thus, the extent to which CPTSD applies to other repeatedly traumatized populations...... is unknown. This study examined ICD-11's PTSD and CPTSD across populations with prolonged trauma of varying interpersonal intensity and ages of exposure, including: 1) childhood sexual abuse, 2) adulthood trauma of severe interpersonal intensity (refugees and ex-prisoners of war), and 3) adulthood trauma...

  10. Unfavourable effect of prolonged treatment with antithyroid drugs on radioiodine therapy outcome in Graves' hyperthyroidism

    OpenAIRE

    Rajić, Milena; Vlajković, Marina; Ilić, Slobodan; Stević, Miloš; Sekulić, Vladan; Zečević, Mila

    2014-01-01

    Radioiodine therapy (RIT) of Graves' hyperthyroidism (GH) is usually recommended after failure of primary therapy with antithyroid drugs (ATDs), which are commonly prescribed for up to 18-24 months. However, in our region, the prolonged ATDs treatment of the disease is very common. Thus, we assessed the efficacy of RIT after prolonged continual pretreatment with ATDs in Graves' hyperthyroidism. Therapy outcome using a single dose of radioiodine was evaluated after one year in 91 patients (f/m...

  11. Chronic bronchiolitis in non-human primates after prolonged ozone exposure

    International Nuclear Information System (INIS)

    Eustis, S.L.

    1979-01-01

    Bonnet monkeys (Macaca radiata) were exposed to 0.0, 0.5, and 0.8 ppM ozone for 7, 28, or 90 consecutive d, eight h per d. Changes in the lung evoked by prolonged oxidant exposure were evaluated by light microscopy, scanning electron microscopy, transmission electron microscopy, autoradiography, and morphometry. Morphological changes were principally characterized as a low-grade chronic respiratory bronchiolitis. Proximal generations of respiratory bronchioles were the most consistently affected region of the pulmonary acinus. Major features of the bronchiolitis were intraluminal accumulations of macrophages and hypertrophy and hyperplasia of cuboidal bronchiolar epithelial cells. The degree of inflammation was greatest at the 0.8 ppM ozone concentration at each exposure period. The number of inflammatory cells observed at 90 d, however, was about one-half that observed at 7 d. Tritiated thymidine labeling and differential cell counts of respiratory bronchiolar epithelium demonstrated a proliferative response and an increase in the proportion of cubiodal bronchiolar cells which presumably function as the progenitor cell during cell renewal and repair of the epithelium. The labeling index remained elevated above control values through 90 d of ozone exposure despite a reduction below 7 d values at both 28 and 90 d. The epithelial hyperplasia persisted through 90 d at a level similar to but slightly above that present at 7 d. Since cell differentials remained shifted at 28 and 90 d, it appears that persistent ozone exposure delayed maturation and transformation of cubiodal bronchiolar cells to their mature phenotype

  12. Prolonged particulate chromate exposure does not inhibit homologous recombination repair in North Atlantic right whale (Eubalaena glacialis) lung cells.

    Science.gov (United States)

    Browning, Cynthia L; Wise, Catherine F; Wise, John Pierce

    2017-09-15

    Chromosome instability is a common feature of cancers that forms due to the misrepair of DNA double strand breaks. Homologous recombination (HR) repair is a high fidelity DNA repair pathway that utilizes a homologous DNA sequence to accurately repair such damage and protect the genome. Prolonged exposure (>72h) to the human lung carcinogen, particulate hexavalent chromium (Cr(VI)), inhibits HR repair, resulting in increased chromosome instability in human cells. Comparative studies have shown acute Cr(VI) exposure induces less chromosome damage in whale cells than human cells, suggesting investigating the effect of this carcinogen in other species may inform efforts to prevent Cr(VI)-induced chromosome instability. Thus, the goal of this study was to determine the effect of prolonged Cr(VI) exposure on HR repair and clastogenesis in North Atlantic right whale (Eubalaena glacialis) lung cells. We show particulate Cr(VI) induces HR repair activity after both acute (24h) and prolonged (120h) exposure in North Atlantic right whale cells. Although the RAD51 response was lower following prolonged Cr(VI) exposure compared to acute exposure, the response was sufficient for HR repair to occur. In accordance with active HR repair, no increase in Cr(VI)-induced clastogenesis was observed with increased exposure time. These results suggest prolonged Cr(VI) exposure affects HR repair and genomic stability differently in whale and human lung cells. Future investigation of the differences in how human and whale cells respond to chemical carcinogens may provide valuable insight into mechanisms of preventing chemical carcinogenesis. Copyright © 2017. Published by Elsevier Inc.

  13. FEASIBILITY AND EFFECTIVENESS OF DYADIC PROLONGED EXPOSURE INTERVENTION FOR PREVENTING POSTTRAUMATIC GRIEF IN YOUNG CHILDREN: A CASE REPORT OF TWO SIBLINGS.

    Science.gov (United States)

    Rachamim, Lilach

    2017-09-01

    This article highlights the feasibility of a dyadic prolonged exposure (DPE) intervention (L. Rachamim, I. Mirochnik, L. Helpman, N. Nacasch, & E. Yadin, ) in a 3-year-old preschooler and in a 6-year-old kindergartener immediately following the traumatic death of their younger sibling. It presents a detailed case description of the DPE treatment addressing traumatic grief and includes transcribed treatment dialogue. At the time of treatment termination, both children and caregivers resumed normal functioning. The results suggest that DPE intervention may ameliorate posttraumatic grief symptoms in young children. Controlled studies of preventive interventions for this population are clearly warranted. © 2017 Michigan Association for Infant Mental Health.

  14. Low liver stiffness among cirrhotic patients with hepatitis B after prolonged treatment with nucleoside analogs

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Weiland, Ola; Leutscher, Peter

    2011-01-01

    Case reports and short-term clinical trials have suggested that treatment for chronic hepatitis B (CHB) may lead to improvement of cirrhosis. The aim of the present study was to measure liver stiffness in patients diagnosed with advanced fibrosis or cirrhosis prior to prolonged treatment...

  15. Changes in negative cognitions mediate PTSD symptom reductions during client-centered therapy and prolonged exposure for adolescents.

    Science.gov (United States)

    McLean, Carmen P; Yeh, Rebecca; Rosenfield, David; Foa, Edna B

    2015-05-01

    To assess whether changes in negative trauma-related cognitions play an important role in reducing symptoms of posttraumatic stress disorder (PTSD) and depression during prolonged exposure therapy for adolescents (PE-A). Secondary analysis of data from a randomized controlled trial comparing PE-A with client-centered therapy (CCT) for PTSD. Participants were 61 adolescent female sexual assault survivors ages 13-18 who received 8-14 weekly sessions of PE-A or CCT at a community rape crisis center. PTSD severity was assessed at baseline, mid-treatment, post-treatment, and 3-months post-treatment. Participants also completed self-report measures of negative posttraumatic cognitions and depressive symptoms at the same assessment points. Cross lag panel mediation analyses showed that change in negative trauma-related cognitions mediated change in PTSD symptoms and depressive symptoms whereas change in PTSD and depressive symptoms did not mediate change in negative cognitions. Our findings support EPT and suggest that change in negative trauma-related cognitions is a mechanism of both PE-A and CCT. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Diverse definitions of prolonged labour and its consequences with sometimes subsequent inappropriate treatment

    Science.gov (United States)

    2014-01-01

    Background Prolonged labour very often causes suffering from difficulties that may have lifelong implications. This study aimed to explore the prevalence and treatment of prolonged labour and to compare birth outcome and women’s experiences of prolonged and normal labour. Method Women with spontaneous onset of labour, living in a Swedish county, were recruited two months after birth, to a cross-sectional study. Women (n = 829) completed a questionnaire that investigated socio-demographic and obstetric background, birth outcome and women’s feelings and experiences of birth. The prevalence of prolonged labour, as defined by a documented ICD-code and inspection of partogram was calculated. Four groups were identified; women with prolonged labour as identified by documented ICD-codes or by partogram inspection but no ICD-code; women with normal labour augmented with oxytocin or not. Results Every fifth woman experienced a prolonged labour. The prevalence with the documented ICD-code was (13%) and without ICD-code but positive partogram was (8%). Seven percent of women with prolonged labour were not treated with oxytocin. Approximately one in three women (28%) received oxytocin augmentation despite having no evidence of prolonged labour. The length of labour differed between the four groups of women, from 7 to 23 hours. Women with a prolonged labour had a negative birth experience more often (13%) than did women who had a normal labour (3%) (P women with prolonged labour were emergency Caesarean section (OR 9.0, 95% CI 1.2-3.0) and to strongly agree with the following statement ‘My birth experience made me decide not to have any more children’ (OR 41.3, 95% CI 4.9-349.6). The factors that contributed most strongly to a negative birth experience in women with normal labour were less agreement with the statement ‘It was exiting to give birth’ (OR 0.13, 95% CI 0.34-0.5). Conclusions There is need for increased clinical skill in identification and classification

  17. The effect of interruptions and prolonged treatment time in radiotherapy for nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Kwong, Dora L.W.; Sham, Jonathan S.T.; Chua, Daniel T.T.; Choy, Damon T.K.; Au, Gordon K.H.; Wu, P.M.

    1997-01-01

    Purpose: The effect of interruptions and prolonged overall treatment time in radiotherapy for nasopharyngeal carcinoma and the significance of timing of interruption was investigated. Methods and Materials: Treatment records of 229 patients treated with continuous course (CC) and 567 patients treated with split course (SC) radiotherapy for nonmetastatic NPC were reviewed. Overall treatment time without inclusion of time for boost was calculated. Treatment that extended 1 week beyond scheduled time was considered prolonged. Outcome in patients who completed treatment 'per schedule' were compared with those who had 'prolonged' treatment. Because of known patient selection bias between CC and SC, patients on the two schedules were analyzed separately. Multivariate analysis was performed for patients on SC. Total number of days of interruption, age, sex, T and N stage, and the use of boost were tested for the whole SC group. Analysis on the effect of timing of interruption was performed in a subgroup of 223 patients on SC who had a single unplanned interruption. Timing of interruption, either before or after the fourth week for the unplanned interruption, was tested in addition to the other variables in multivariate analysis for this subgroup of SC. Results: Twenty-seven (11.8%) patients on CC and 96 (16.9%) patients on SC had prolonged treatment. Patients on SC who had prolonged treatment had significantly poorer loco-regional control rate and disease free survival when compared with those who completed radiotherapy per schedule (p = 0.0063 and 0.001, respectively, with adjustment for stage). For CC, the effect of prolonged treatment on outcome was not significant. The small number of events for patients on CC probably account for the insignificant finding. The number of days of interruption was confirmed as prognostic factor, independent of T and N stages, for loco-regional control and disease-free survival in multivariate analysis for SC. The hazard rate for loco

  18. Defining futile life-prolonging treatments through Neo-Socratic Dialogue.

    Science.gov (United States)

    Aizawa, Kuniko; Asai, Atsushi; Bito, Seiji

    2013-12-09

    In Japan, people are negative towards life-prolonging treatments. Laws that regulate withholding or discontinuing life-prolonging treatments and advance directives do not exist. Physicians, however, view discontinuing life-prolonging treatments negatively due to fears of police investigations. Although ministerial guidelines were announced regarding the decision process for end-of-life care in 2007, a consensus could not be reached on the definition of end-of-life and conditions for withholding treatment. We established a forum for extended discussions and consensus building on this topic. We used the Neo-Socratic Dialogue (NSD) method which promotes philosophical discussion based on a case-study to address a question and formulate a consensus and answer in a group. The question chosen for the dialogue was: "What is a life-prolonging treatment?" A series of dialogues took place over a period of one and a half days. It was carried out by three groups in 2010 and 2011. Seven participants with diverse backgrounds were recruited per group. We analyzed the content of the discussion. Based on three case studies concerning different opinions about treatment options for an older dementia patient, a patient demanding chemotherapy, and a severely ill neonate, conditions for futile life-prolonging treatment were elucidated through NSD. Such treatments are those carried out for the sole purpose of prolonging life and are detrimental to the patient, and should be decided based foremost on the patient's lack of desire for treatment, the consensus of those involved, and through social acceptance. These arguments are essentially consistent with ones on medical futility in the United States. By expressing the objective of healthcare and the requirement of social acceptance, participants were also able to elucidate issues related to the awareness of those involved and the medical environment. Compared to the end-of-life guidelines in Japan, the objective of treatment, its effects

  19. Dynamic adaptation of cardiac baroreflex sensitivity to prolonged exposure to microgravity: data from a 16-day spaceflight

    NARCIS (Netherlands)

    Di Rienzo, Marco; Castiglioni, Paolo; Iellamo, Ferdinando; Volterrani, Maurizio; Pagani, Massimo; Mancia, Giuseppe; Karemaker, John M.; Parati, Gianfranco

    2008-01-01

    Di Rienzo M, Castiglioni P, Iellamo F, Volterrani M, Pagani M, Mancia G, Karemaker JM, Parati G. Dynamic adaptation of cardiac baroreflex sensitivity to prolonged exposure to microgravity: data from a 16-day spaceflight. J Appl Physiol 105: 1569-1575, 2008. First published August 28, 2008;

  20. Evaluation of benzodiazepines and zolpidem in nails and their stability after prolonged exposure to chlorinated water.

    Science.gov (United States)

    Moretti, Matteo; Andrello, Luisa; Visonà, Silvia; Vignali, Claudia; Groppi, Angelo; Freni, Francesca; Osculati, Antonio; Tajana, Luca; Morini, Luca

    2018-04-15

    The study aims the development and validation of a LC-MS/MS method for the identification and quantification of benzodiazepines and zolpidem in nails as alternative keratinized matrix to hair in long-term monitoring of anxiolytic and hypnotic drugs. Both fingernail and toenail samples (1-2 mm) were collected by clipping the excess overhang of the nail from volunteers and from postmortem cases. They were washed twice with organic solvents, dried under nitrogen stream, pulverized, immersed in a methanol solution (internal standard: diazepam-D5) and sonicated up to two hours. The solution was then direct injected in the LC-MS/MS system. Mass spectrometry was set in MRM mode, selecting two transitions for each substance. 32 analytes among benzodiazepines, metabolites and hypnotics were included in the list. The method fulfilled the internationally required criteria for validation. Limits of detection ranged from 0.03 pg/mg (zolpidem) to 13.1 pg/mg (bromazepam). 9 subjects under therapy were positive at 7 different benzodiazepines and/or metabolites (lorazepam, desalkylflurazepam, bromazepam, diazepam, alprazolam, lormetazepam and prazepam), while 5 molecules were measured in 4 postmortem cases (diazepam, desmethyldiazepam, delorazepam, 7-aminoclonazepam and zolpidem). In vitro experiments on eight authentic samples suggested that benzodiazepines in nails are influenced by the prolonged exposure to chlorinated water. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Prolonged Corrosion Stability of a Microchip Sensor Implant during In Vivo Exposure

    Directory of Open Access Journals (Sweden)

    Paul Glogener

    2018-02-01

    Full Text Available A microelectronic biosensor was subjected to in vivo exposure by implanting it in the vicinity of m. trapezii (Trapezius muscle from cattle. The implant is intended for the continuous monitoring of glucose levels, and the study aimed at evaluating the biostability of exposed semiconductor surfaces. The sensor chip was a microelectromechanical system (MEMS prepared using 0.25 µm complementary metal–oxide–semiconductor CMOS/BiCMOS technology. Sensing is based on the principle of affinity viscometry with a sensoric assay, which is separated by a semipermeable membrane from the tissue. Outer dimensions of the otherwise hermetically sealed biosensor system were 39 × 49 × 16 mm. The test system was implanted into cattle in a subcutaneous position without running it. After 17 months, the device was explanted and analyzed by comparing it with unexposed chips and systems. Investigations focused on the MEMS chip using SEM, TEM, and elemental analysis by EDX mapping. The sensor chip turned out to be uncorroded and no diminishing of the topmost passivation layer could be determined, which contrasts remarkably with previous results on CMOS biosensors. The negligible corrosive attack is understood to be a side effect of the semipermeable membrane separating the assay from the tissue. It is concluded that the separation has enabled a prolonged biostability of the chip, which will be of relevance for biosensor implants in general.

  2. Treating posttraumatic stress disorder with MDMA-assisted psychotherapy: A preliminary meta-analysis and comparison to prolonged exposure therapy.

    Science.gov (United States)

    Amoroso, Timothy; Workman, Michael

    2016-07-01

    Since the wars in Iraq and Afghanistan, posttraumatic stress disorder (PTSD) has become a major area of research and development. The most widely accepted treatment for PTSD is prolonged exposure (PE) therapy, but for many patients it is intolerable or ineffective. ±3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy (MDMA-AP) has recently re-emerged as a new treatment option, with two clinical trials having been published and both producing promising results. However, these results have yet to be compared to existing treatments. The present paper seeks to bridge this gap in the literature. Often the statistical significance of clinical trials is overemphasized, while the magnitude of the treatment effects is overlooked. The current meta-analysis aims to provide a comparison of the cumulative effect size of the MDMA-AP studies with those of PE. Effect sizes were calculated for primary and secondary outcome measures in the MDMA-AP clinical trials and compared to those of a meta-analysis including several PE clinical trials. It was found that MDMA-AP had larger effect sizes in both clinician-observed outcomes than PE did (Hedges' g=1.17 vs. g=1.08, respectively) and patient self-report outcomes (Hedges' g=0.87 vs. g=0.77, respectively). The dropout rates of PE and MDMA-AP were also compared, revealing that MDMA-AP had a considerably lower percentage of patients dropping out than PE did. These results suggest that MDMA-AP offers a promising treatment for PTSD. © The Author(s) 2016.

  3. Treatment of prolonged convulsive seizures in children; a single centre, retrospective, observational study

    NARCIS (Netherlands)

    Vlaskamp, Danique R. M.; Brouwer, Oebele F.; Callenbach, Petra M. C.

    2014-01-01

    Objectives: To evaluate treatment of children with Prolonged Convulsive Seizures (PCS) at the University Medical Centre Groningen (UMCG). Material and methods: PCS were identified from an UMCG database of children with epilepsy aged = 10 mm and occurred between January 2000 and October 2012 in

  4. Prolonged continuous exposure to high fine particulate matter associated with cardiovascular and respiratory disease mortality in Beijing, China

    Science.gov (United States)

    Wang, Jinfeng; Yin, Qian; Tong, Shilu; Ren, Zhoupeng; Hu, Maogui; Zhang, Hongrui

    2017-11-01

    Although many studies examined the effects of fine particulate matter (PM2.5) on the deaths of cardiovascular disease (CVD) and respiratory disease (RD), few research has paid attention to the effects of prolonged continuous exposure to high PM2.5 pollution. This study estimated the excess risks (ER) of CVD and RD mortalities associated with prolonged continuous exposure to high PM2.5 pollution for the whole population and specific subsociodemographic groups in Beijing, which is the capital city of China with over 20 million residents and having severe PM2.5 pollution problems. Our results suggested that when high PM2.5 pollution occurred continuously, at various thresholds and durations, the adverse effects on CVD and RD mortalities varied significantly. The CVD mortality risks in association with prolonged continuous high PM2.5 pollution exposure were more serious for single individuals (including unmarried, divorced, and widowed), illiterate and outdoor workers than for other specific subsociodemographic groups. When the daily PM2.5 concentration higher than 105 μg/m3 consecutively occurs, at the ninth day, the ERs of CVD death for single individuals, illiterate and outdoor workers groups reached to 45% (95% CI: 22, 71), 51% (95% CI: 28, 79) and 53% (95% CI: 29, 82) respectively. On the other hand, prolonged continuous high PM2.5 pollution level appeared to contribute a higher proportion of RD deaths among illiterate and outdoor workers, but less significant for the other specific subsociodemographic groups. When the duration with daily PM2.5 pollution higher than 115 μg/m3 reached to six days, the ERs for outdoor workers and illiterate attributed to prolonged continuous PM2.5 pollution exposure increased 36% (95% CI: 5, 76) and 49% (95% CI: 16, 91) respectively.

  5. Nutritional considerations during prolonged exposure to a confined, hyperbaric, hyperoxic environment: recommendations for saturation divers.

    Science.gov (United States)

    Deb, S K; Swinton, P A; Dolan, E

    2016-01-01

    Saturation diving is an occupation that involves prolonged exposure to a confined, hyperoxic, hyperbaric environment. The unique and extreme environment is thought to result in disruption to physiological and metabolic homeostasis, which may impact human health and performance. Appropriate nutritional intake has the potential to alleviate and/or support many of these physiological and metabolic concerns, whilst enhancing health and performance in saturation divers. Therefore, the purpose of this review is to identify the physiological and practical challenges of saturation diving and consequently provide evidence-based nutritional recommendations for saturation divers to promote health and performance within this challenging environment. Saturation diving has a high-energy demand, with an energy intake of between 44 and 52 kcal/kg body mass per day recommended, dependent on intensity and duration of underwater activity. The macronutrient composition of dietary intake is in accordance with the current Institute of Medicine guidelines at 45-65 % and 20-35 % of total energy intake for carbohydrate and fat intake, respectively. A minimum daily protein intake of 1.3 g/kg body mass is recommended to facilitate body composition maintenance. Macronutrient intake between individuals should, however, be dictated by personal preference to support the attainment of an energy balance. A varied diet high in fruit and vegetables is highly recommended for the provision of sufficient micronutrients to support physiological processes, such as vitamin B12 and folate intake to facilitate red blood cell production. Antioxidants, such as vitamin C and E, are also recommended to reduce oxidised molecules, e.g. free radicals, whilst selenium and zinc intake may be beneficial to reinforce endogenous antioxidant reserves. In addition, tailored hydration and carbohydrate fueling strategies for underwater work are also advised.

  6. Synergistic interaction between prolonged increased glycemic exposure and mildly increased urinary albumin excretion on diabetic retinopathy.

    Science.gov (United States)

    Moon, Shinje; Yoo, Hyung-Joon; Ahn, You-Hern; Kim, Gheun-Ho; Yu, Jae Myung; Park, Joon-Sung

    2018-01-01

    The association of mild increase in urinary albumin excretion with diabetic retinopathy (DR) in clinical studies is controversial. The aim of this study is to clarify the interaction between increased glycemic exposure and mild increase in urinary albumin excretion on risk of DR.Data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2012. Overall, data from 953 participants without microalbuminuria (477 men and 476 women) were assessed. Logistic regression analysis was constructed to evaluate the association between DR and related clinical parameters, including urinary albumin-creatinine ratio (UACR, mg/g creatinine). The biological interaction of glycemic status and UACR on DR was evaluated by 3 indices: RERI, the relative excess risk due to the interaction; AP, the attributable proportion due to the interaction; and S, the additive interaction index of synergy.We found that UACR, glycated hemoglobin (HbA1c), and diabetic duration were deeply associated with increased risk of DR (UACR, odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.02-1.07; HbA1c, OR = 1.16, 95% CI = 1.04-1.30; diabetic duration, OR = 1.06, 95% CI = 1.04-1.07). Furthermore, our interaction analysis demonstrated that synergistic interaction between HbA1c and UACR on development of DR was prominent in participants with diabetic duration of ≥10 years (adjusted RERI = 0.92, 95% CI = 0.10-1.74; adjusted AP = 0.29, 95% CI = -0.82-1.41; adjusted S = 1.76, 95% CI = 1.27-2.25), but not subjects with shorter diabetic duration.These findings imply that there is the interaction between prolonged hyperglycemic exposure and increased urinary albumin excretion may exert additive synergistic effect on vascular endothelial dysfunction in the eye, even before the appearance of overt diabetic nephropathy. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  7. Effects of prolonged treatment with memantine in the MRL model of CNS lupus.

    Science.gov (United States)

    Marcinko, Katarina; Parsons, Tiffany; Lerch, Jason P; Sled, John G; Sakic, Boris

    2012-09-01

    Neuropsychiatric manifestations and brain atrophy of unknown etiology are common and severe complications of systemic lupus erythematosus (SLE). An autoantibody that binds to N-methyl-D-aspartate (NMDA) receptor NR2 has been proposed as a key factor in the etiology of central nervous system (CNS) SLE. This hypothesis was supported by evidence suggesting memantine (MEM), an uncompetitive NMDA receptor antagonist, prevents behavioral dysfunction and brain pathology in healthy mice immunized with a peptide similar to an epitope on the NR2 receptor. Given that SLE is a chronic condition, we presently examine the effects of MEM in MRL/lpr mice, which develop behavioral deficits alongside SLE-like disease. A broad behavioral battery and 7-Tesla MRI were used to examine whether prolonged treatment with MEM (~25 mg/kg b.w. in drinking water) prevents CNS involvement in this spontaneous model of SLE. Although MEM increased novel object exploration in MRL/lpr mice, it did not show other beneficial, substrain-specific effects. Conversely, MEM was detrimental to spontaneous activity in control MRL +/+ mice and had a negative effect on body mass gain. Similarly, MRI revealed comparable increases in the volume of periventricular structures in MEM-treated groups. Sustained exposure to MEM affects body growth, brain morphology, and behavior primarily by pharmacological, and not autoimmunity-dependant mechanisms. Substrain-specific improvement in exploratory behavior of MEM-treated MRL/lpr mice may indicate that the NMDA system is merely a constituent of a complex pathogenenic cascade. However, it was evident that chronic administration of MEM is unable to completely prevent the development of a CNS SLE-like syndrome.

  8. Prolonged exposure of colon cancer cells to 5-fluorouracil nanoparticles improves its anticancer activity

    Directory of Open Access Journals (Sweden)

    Essam Tawfik

    2017-02-01

    Full Text Available In this study, we aimed to improve the anticancer effect of 5-FU on human colon cancer cell lines by incorporating in poly(d,l lactic-co-glycolic acid (PLGA nanoparticles (NPs. The 5-FU-PLGA NPs were prepared by nanoprecipitation technique. Prepared NPs were moderately dispersed with an average diameter of 133 ± 25.19 nm. Scanning Electron Microscope (SEM images revealed spherical structures with subtle surface irregularity. Free 5-FU dose–response curves were constructed (12.5–2000 μM using MTT assay on HCT 116 and HT-29 cell lines for 1, 3, and 5 days. The calculated IC50 on HCT 116 were 185 μM after 1 day, 11.3 μM after 3 days, and 1.48 μM after 5 days. On HT-29, IC50 was only reached after 5 days of 5-FU treatment (11.25 μM. The HCT 116 viability following treatment with 100 μM 5-FU in free or NPs forms for 3 days was 38.8% and 18.6%, respectively. Similarly, when 250 μM was applied, HCT 116 viability was 17.03% and 14.6% after treatment with free and NPs forms of 5-FU, respectively. Moreover, HT-29 cell viability after 250 μM 5-FU treatment in free or NPs forms was 55.45% and 34.01%, respectively. We also noticed that HCT 116 cells were more sensitive to 5-FU-PLGA NPs as compared to HT-29 cells. Overall, our data indicate that 5-FU activity is time dependent and the prolonged effects created by PLGA NPs may contribute, at least in part, to the noticed enhancement of the anticancer activity of 5-FU drug.

  9. Effect of prolonged isothermal heat treatment on the mechanical behavior of advanced NANOBAIN steel

    Science.gov (United States)

    Avishan, Behzad

    2017-09-01

    The microstructural evolution and consequent changes in strength and ductility of advanced NANOBAIN steel during prolonged isothermal heat-treatment stages were investigated. The microstructure and mechanical properties of nanostructured bainite were not expected to be influenced by extending the heat-treatment time beyond the optimum value because of the autotempering phenomenon and high tempering resistance. However, experimental results indicated that the microstructure was thermodynamically unstable and that prolonged austempering resulted in carbon depletion from high-carbon retained austenite and carbide precipitations. Therefore, austenite became thermally less stable and partially transformed into martensite during cooling to room temperature. Prolonged austempering did not lead to the typical tempering sequence of bainite, and the sizes of the microstructural constituents were independent of the extended heat-treatment times. This independence, in turn, resulted in almost constant ultimate tensile strength values. However, microstructural variations enhanced the yield strength and the hardness of the material at extended isothermal heat-treatment stages. Finally, although microstructural changes decreased the total elongation and impact toughness, considerable combinations of mechanical properties could still be achieved.

  10. Homeostatic balance as an indicator of prolonged technogenic exposure in low dose range

    International Nuclear Information System (INIS)

    Karpov, A.B.; Voronova, I.A.; Takhauov, R.M.; Semyonova, Yu.V.; Sherstoboev, E.Yu.; Udut, V.V.

    2008-01-01

    Full text: Indication of changes induced by ionizing radiation starting up a wide range of pathologic reactions in the disease developments still poses a significant problem in radiation medicine. It mainly concerns exposure to low dose-rate ionizing radiation, since its effects are still open to question, and today any researcher acknowledges that radiation induced pathological changes can accumulate at both subclinical and prenosological stages and develop not only in exposed persons, but also in their offspring. The subject of this study was workers of reactor and radiochemical productions of Siberian Group of Chemical Enterprises (SGCE) exposed to external and combined (external and internal) radiation respectively. Two comparative groups were formed: reactor and radiochemical production workers. In the reactor production group of workers the cumulative dose of external γ-radiation was up to 300 mSv, in the radiochemical production group - up to 150 mSv. Age ranged from 40 to 50 years. The two groups were compared between each other. Above all, there were formed 'insider control' groups (workers of the same productions with zero doses) to assess the impact of radiation factor on central homeostatic mechanisms. These groups were created using pair technique in order to level somatic disorders influence on the parameters under study. Numbers of full and biochemical blood examinations, energy metabolism between cells, hormones of homeostasis by the adaptive hormone level - insulin and cortisol, lipid peroxidation and antioxidant protection systems, immune and vegetative systems were all analyzed. Analyses of the systems performed, it was found out that in persons having been exposed to long term occupational radiation there were significant changes indicating lipid peroxidation system activation, antioxidant protection system depression, as well as lowered energy metabolism. The higher external γ-doses the bigger these changes are. Results from the two groups of

  11. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage.

    Science.gov (United States)

    Liu, Fang; Rainosek, Shuo W; Frisch-Daiello, Jessica L; Patterson, Tucker A; Paule, Merle G; Slikker, William; Wang, Cheng; Han, Xianlin

    2015-10-01

    Sevoflurane is a volatile anesthetic that has been widely used in general anesthesia, yet its safety in pediatric use is a public concern. This study sought to evaluate whether prolonged exposure of infant monkeys to a clinically relevant concentration of sevoflurane is associated with any adverse effects on the developing brain. Infant monkeys were exposed to 2.5% sevoflurane for 9 h, and frontal cortical tissues were harvested for DNA microarray, lipidomics, Luminex protein, and histological assays. DNA microarray analysis showed that sevoflurane exposure resulted in a broad identification of differentially expressed genes (DEGs) in the monkey brain. In general, these genes were associated with nervous system development, function, and neural cell viability. Notably, a number of DEGs were closely related to lipid metabolism. Lipidomic analysis demonstrated that critical lipid components, (eg, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol) were significantly downregulated by prolonged exposure of sevoflurane. Luminex protein analysis indicated abnormal levels of cytokines in sevoflurane-exposed brains. Consistently, Fluoro-Jade C staining revealed more degenerating neurons after sevoflurane exposure. These data demonstrate that a clinically relevant concentration of sevoflurane (2.5%) is capable of inducing and maintaining an effective surgical plane of anesthesia in the developing nonhuman primate and that a prolonged exposure of 9 h resulted in profound changes in gene expression, cytokine levels, lipid metabolism, and subsequently, neuronal damage. Generally, sevoflurane-induced neuronal damage was also associated with changes in lipid content, composition, or both; and specific lipid changes could provide insights into the molecular mechanism(s) underlying anesthetic-induced neurotoxicity and may be sensitive biomarkers for the early detection of anesthetic-induced neuronal damage. Published by Oxford University Press on behalf of the

  12. The effect of duration of untreated psychosis and treatment delay on the outcomes of prolonged early intervention in psychotic disorders

    DEFF Research Database (Denmark)

    Albert, Nikolai; Melau, Marianne; Jensen, Heidi

    2017-01-01

    to the prolonged treatment with regards to disorganized and negative dimension. For participants with short duration from first symptom until start of SEI treatment there was a significant difference on the negative dimension favoring the prolonged OPUS treatment. The finding of an effect of prolonged treatment......The duration of untreated psychosis (DUP) has been shown to have an effect on outcome after first-episode psychosis. The premise of specialized early intervention (SEI) services is that intervention in the early years of illness can affect long-term outcomes. In this study, we investigate whether...... DUP affects treatment response after 5 years of SEI treatment compared to 2 years of SEI treatment. As part of a randomized controlled trial testing the effect of prolonged SEI treatment 400 participants diagnosed within the schizophrenia spectrum were recruited. For this specific study participants...

  13. QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

    Directory of Open Access Journals (Sweden)

    Piccinelli Marco

    2005-01-01

    Full Text Available Abstract Background Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. Method We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine or lithium. An Electrocardiogram (ECG was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Results Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms however this was not the case in Group 1 (-1 ± 30 ms (Repeated measures ANOVA p Conclusions No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a

  14. Low liver stiffness among cirrhotic patients with hepatitis B after prolonged treatment with nucleoside analogs

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Weiland, Ola; Leutscher, Peter

    2011-01-01

    Abstract Objective. Case reports and short-term clinical trials have suggested that treatment for chronic hepatitis B (CHB) may lead to improvement of cirrhosis. The aim of the present study was to measure liver stiffness in patients diagnosed with advanced fibrosis or cirrhosis prior to prolonged...... treatment with nucleoside or nucleotide analogs (NUCs) for CHB. Materials and methods. Patients with CHB and advanced fibrosis or cirrhosis prior to treatment with NUCs for at least 1 year were offered inclusion in the study. We measured liver stiffness using transient elastography (TE) at follow-up. TE cut...... duration was 50.5 months. Among patients with cirrhosis prior to treatment, 26 (49%) had liver stiffness below 11.0 kPa at follow-up, suggesting regression of cirrhosis. Among patients with advanced fibrosis (F3) prior to treatment, 10 (77%) had liver stiffness below 8.1 kPa after treatment, suggesting...

  15. Effect of prolonged and intermittent treatment on the clinical course of peptic ulcer.

    Science.gov (United States)

    Chornenka, Zhanetta A; Yasinska, Elvira Ts; Grytsiuk, Mariana I

    2018-01-01

    Introduction: The number of patients with peptic ulcer increases annually. According to published data, patients with peptic ulcer constitute about 15% of those hospitalized with gastrointestinal diseases. The aim: That is why we set the task to evaluate the methods of preventive treatment and to choose the most effective one. Materials and methods: For this purpose, we selected 103 patients with peptic ulcer without severe exacerbations and complications from one region (main group) and 101 patients from another region (control group) for observations. Making diagnosis was based on the study of complaints, anamnestic data, physical examination of the patient, evaluation of the functional state of the gastroduodenal system, as well as the X-ray and endoscopic examination. The sources of the study were medical records of outpatients, control cards for dispensary surveillance, registers of temporary disability records, sick leave records and others. Results: Most patients, from both the main and control groups, who were on prophylactic treatment, noticed that they had an increased working capacity, normalized sleep, better appetite and fewer dyspeptic disorders. Patients in the main group for two years were on prolonged prophylactic treatment according to the method that we had developed. by us. Patients in the control group received an intermittent preventive treatment twice a year (in spring and autumn). In the complex of therapeutic measures the following were used: dietary recommendations, antacids, cholinolytics, multivitamins, etc. Conclusions: Prolonged prophylactic treatment is an effective means to combat exacerbations and complications of peptic ulcer and can be recommended for implementation in practice.

  16. Hsp27, Hsp70, and metallothionein in MDCK and LLC-PK1 renal epithelial cells: effects of prolonged exposure to cadmium

    International Nuclear Information System (INIS)

    Bonham, Rita T.; Fine, Michael R.; Pollock, Fiona M.; Shelden, Eric A.

    2003-01-01

    Cadmium is a widely distributed industrial and environmental toxin. The principal target organ of chronic sublethal cadmium exposure is the kidney. In renal epithelial cells, acute high-dose cadmium exposure induces differential expression of proteins, including heat shock proteins. However, few studies have examined heat shock protein expression in cells after prolonged exposure to cadmium at sublethal concentrations. Here, we assayed total cell protein, neutral red uptake, cell death, and levels of metallothionein and heat shock proteins Hsp27 and inducible Hsp70 in cultures of MDCK and LLC-PK1 renal epithelial cells treated with cadmium for 3 days. Treatment with cadmium at concentrations equal to or greater than 10 μM (LLC-PK1) or 25 μM (MDCK) reduced measures of cell vitality and induced cell death. However, a concentration-dependent increase in Hsp27 was detected in both cell types treated with as little as 5 μM cadmium. Accumulation of Hsp70 was correlated only with cadmium treatment at concentrations also causing cell death. Metallothionein was maximally detected in cells treated with cadmium at concentrations that did not reduce cell vitality, and further increases were not detected at greater concentrations. These results reveal that heat shock proteins accumulate in renal epithelial cells during prolonged cadmium exposure, that cadmium induces differential expression of heat shock protein in epithelial cells, and that protein expression patterns in epithelial cells are specific to the cadmium concentration and degree of cellular injury. A potential role for Hsp27 in the cellular response to sublethal cadmium-induced injury is also implicated by our results

  17. Arsenic in an alkaline AMD treatment sludge: Characterization and stability under prolonged anoxic conditions

    International Nuclear Information System (INIS)

    Beauchemin, Suzanne; Fiset, Jean-Francois; Poirier, Glenn; Ablett, James

    2010-01-01

    Lime treatment of acid mine drainage (AMD) generates large volumes of neutralization sludge that are often stored under water covers. The sludge consists mainly of calcite, gypsum and a widespread ferrihydrite-like Fe phase with several associated species of metal(loid) contaminants. The long-term stability of metal(loid)s in this chemically ill-defined material remains unknown. In this study, the stability and speciation of As in AMD sludge subjected to prolonged anoxic conditions is determined. The total As concentration in the sludge is 300 mg kg -1 . In the laboratory, three distinct water cover treatments were imposed on the sludge to induce different redox conditions (100%N 2 , 100%N 2 + glucose, 95%N 2 :5%H 2 ). These treatments were compared against a control of oxidized, water-saturated sludge. Electron micro-probe (EMP) analysis and spatially resolved synchrotron X-ray fluorescence (SXRF) results indicate that As is dominantly associated with Fe in the sludge. In all treatments and throughout the experiment, measured concentrations of dissolved As were less than 5 μg L -1 . Dissolved Mn concentration in the N 2 + glucose treatment increased significantly compared to other treatments. Manganese and As K-edge X-ray absorption near edge structure spectroscopy (XANES) analyses showed that Mn was the redox-active element in the solid-phase, while As was stable. Arsenic(V) was still the dominant species in all water-covered sludges after 9 months of anoxic treatments. In contrast, Mn(IV) in the original sludge was partially reduced into Mn(II) in all water-covered sludges. The effect was most pronounced in the N 2 + glucose treatment, suggesting microbial reduction. Micro-scale SXRF and XANES analysis of the treated sludge showed that Mn(II) accumulated in areas already enriched in Fe and As. Overall, the study shows that AMD sludges remain stable under prolonged anoxic conditions. External sources of chemical reductants or soluble C were needed to induce

  18. Prolonged vertigo and ataxia after mandibular nerve block for treatment of trigeminal neuralgia

    Directory of Open Access Journals (Sweden)

    Arvind Chaturvedi

    2011-01-01

    Full Text Available Common complications of neurolytic mandibular nerve block are hypoesthesia, dysesthesia, and chemical neuritis. We report a rare complication, prolonged severe vertigo and ataxia, after neurolytic mandibular blockade in a patient suffering from trigeminal neuralgia. Coronoid approach was used for right sided mandibular block. After successful test injection with local anesthetic, absolute alcohol was given for neurolytic block. Immediately after alcohol injection, patient developed nausea and vomiting along with severe vertigo, ataxia and hypertension. Neurological evaluation was normal except for the presence of vertigo and ataxia. Computerised tomography scan brain was also normal. Patient was admitted for observation and symptomatic treatment was given. Vertigo and ataxia gradually improved over 24 hours.

  19. Prolonged vertigo and ataxia after mandibular nerve block for treatment of trigeminal neuralgia.

    Science.gov (United States)

    Chaturvedi, Arvind; Dash, Hh

    2011-07-01

    Common complications of neurolytic mandibular nerve block are hypoesthesia, dysesthesia, and chemical neuritis. We report a rare complication, prolonged severe vertigo and ataxia, after neurolytic mandibular blockade in a patient suffering from trigeminal neuralgia. Coronoid approach was used for right sided mandibular block. After successful test injection with local anesthetic, absolute alcohol was given for neurolytic block. Immediately after alcohol injection, patient developed nausea and vomiting along with severe vertigo, ataxia and hypertension. Neurological evaluation was normal except for the presence of vertigo and ataxia. Computerised tomography scan brain was also normal. Patient was admitted for observation and symptomatic treatment was given. Vertigo and ataxia gradually improved over 24 hours.

  20. Life-threatening asthma attack during prolonged fingolimod treatment: case report

    Directory of Open Access Journals (Sweden)

    Zecca C

    2014-07-01

    Full Text Available Chiara Zecca,1,* Matteo Caporro,1,* Sandor Györik,2 Claudio Gobbi11Neurocenter of Southern Switzerland, Department of Neurology, Ospedale Regionale di Lugano, Lugano, Switzerland; 2Department of Internal Medicine, Ospedale Regionale di Bellinzona, Bellinzona, Switzerland*These authors contributed equally to this workBackground: Fingolimod (FTY mediates bronchoconstriction by interacting with sphingosine-1-phosphate receptors. The majority of the reported adverse respiratory events occur during the first weeks of treatment.Case presentation: A 49-year-old woman developed a life-threatening asthma attack after 6 months of continuous FTY treatment. The adverse event required prolonged hospitalization, and the patient recovered without sequelae after FTY interruption. A history of previous airway hyperreactivity and a concurrent viral respiratory infection possibly acted as predisposing factors.Conclusion: This first description of a severe, life-threatening asthma attack during prolonged FTY treatment suggests the need for long-term clinical surveillance, especially in patients with known predisposing factors.Keywords: multiple sclerosis, bronchial hyper-reactivity

  1. Neural and behavioural changes in male periadolescent mice after prolonged nicotine-MDMA treatment.

    Science.gov (United States)

    Adeniyi, Philip A; Ishola, Azeez O; Laoye, Babafemi J; Olatunji, Babawale P; Bankole, Oluwamolakun O; Shallie, Philemon D; Ogundele, Olalekan M

    2016-02-01

    The interaction between MDMA and Nicotine affects multiple brain centres and neurotransmitter systems (serotonin, dopamine and glutamate) involved in motor coordination and cognition. In this study, we have elucidated the effect of prolonged (10 days) MDMA, Nicotine and a combined Nicotine-MDMA treatment on motor-cognitive neural functions. In addition, we have shown the correlation between the observed behavioural change and neural structural changes induced by these treatments in BALB/c mice. We observed that MDMA (2 mg/Kg body weight; subcutaneous) induced a decline in motor function, while Nicotine (2 mg/Kg body weight; subcutaneous) improved motor function in male periadolescent mice. In combined treatment, Nicotine reduced the motor function decline observed in MDMA treatment, thus no significant change in motor function for the combined treatment versus the control. Nicotine or MDMA treatment reduced memory function and altered hippocampal structure. Similarly, a combined Nicotine-MDMA treatment reduced memory function when compared with the control. Ultimately, the metabolic and structural changes in these neural systems were seen to vary for the various forms of treatment. It is noteworthy to mention that a combined treatment increased the rate of lipid peroxidation in brain tissue.

  2. Effects of Prolonged Silver Nanoparticle Exposure on the Contextual Cognition and Behavior of Mammals

    Directory of Open Access Journals (Sweden)

    Anna Antsiferova

    2018-04-01

    Full Text Available Silver nanoparticles have been widely used in the lighting and food industries, in medicine, and in pharmaceutics as an antiseptic agent. Recent research demonstrates that, after prolonged oral administration, silver nanoparticles may cross the blood-brain barrier and accumulate in the brain in rather high amounts. In ex vivo experiments, it has also been shown that silver nanoparticles demonstrate neurotoxicity. The objective of this work was to answer the questions whether silver nanoparticles change cognitive and behavioral functions of mammals after prolonged administration if silver nanoparticles have accumulated in the brain. C57Bl/6 male mice were orally exposed to PVP-coated silver nanoparticles daily for 30, 60, 120 and 180 days. Control mice were exposed to distilled water. After that they were tested in the Open Field, Elevated Plus Maze, Light-Dark Box and contextual fear conditioning task. The data have shown that the experimental mice went through three periods of switching in the behavior caused by adaptation to the toxic silver nanoparticles: anxiety, appearance of research instinct and impairment of long-term memory. This provides evidence of the hazardous effect of silver nanoparticles, which appears after long periods of silver nanoparticle oral administration.

  3. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

    DEFF Research Database (Denmark)

    van den Driesche, Sander; Macdonald, Joni; Anderson, Richard A

    2015-01-01

    Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons...

  4. Human ECG Changes During Prolonged Hyperbaric Exposures Breathing N2-O2 Mixtures

    National Research Council Canada - National Science Library

    Wilson, James M; Kligfield, Paul D; Adams, George M; Harvey, Claude; Schaefer, Karl E

    1976-01-01

    In an effort to determine whether hyperbaric exposures while breathing N2-O2 mixtures have an effect on cardiac depolarization and repolarization, electrocardiograms of 10 divers participating in four...

  5. Effects of prolonged agmatine treatment in aged male Sprague-Dawley rats.

    Science.gov (United States)

    Rushaidhi, M; Zhang, H; Liu, P

    2013-03-27

    Increasing evidence suggests that altered arginine metabolism contributes to cognitive decline during ageing. Agmatine, decarboxylated arginine, has a variety of pharmacological effects, including the modulation of behavioural function. A recent study demonstrated the beneficial effects of short-term agmatine treatment in aged rats. The present study investigated how intraperitoneal administration of agmatine (40mg/kg, once daily) over 4-6weeks affected behavioural function and neurochemistry in aged Sprague-Dawley rats. Aged rats treated with saline displayed significantly reduced exploratory activity in the open field, impaired spatial learning and memory in the water maze and object recognition memory relative to young rats. Prolonged agmatine treatment improved animals' performance in the reversal test of the water maze and object recognition memory test, and significantly suppressed age-related elevation in nitric oxide synthase activity in the dentate gyrus of the hippocampus and prefrontal cortex. However, this prolonged supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings further demonstrate that exogenous agmatine selectively improves behavioural function in aged rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Analysis of interaction of some systems of the organism in the prolonged time after radiation exposure

    International Nuclear Information System (INIS)

    Akoev, I.G.

    1978-01-01

    Prolonged observations have been carried out of the composition of the form elements of white and red blood and hemoglobin content in dogs irradiated with the 400 R dose as well as of the nine factors of the punctate of bone marrow characterizing the division and ripening of red and white sprouts. On the base of comparison of dynamics of these fourteen indices the following conclusions on the sequence of inclusion and exclusion of hemopoiesis reserves have been made. The primacy of hemopoiesis to the red side exists always when there is an insufficient quantity of erythrocytes and hemoglobin in them important for organism. The first reserve to be mobilized and mostly used is the expansion of hemopoiesis spring-board, the second-accelerated passage of cells of the dividingand dividing-ripening pools. Later and for a very short time the number of mitoses increases in erythroblasts which directly reflects the reduction of their generative cycle

  7. Influence of prolonged storage process, pasteurization, and heat treatment on biologically-active human milk proteins.

    Science.gov (United States)

    Chang, Jih-Chin; Chen, Chao-Huei; Fang, Li-Jung; Tsai, Chi-Ren; Chang, Yu-Chuan; Wang, Teh-Ming

    2013-12-01

    The bioactive proteins in human milk may be influenced by prolonged storage process, pasteurization, and heat treatment. This study was conducted to evaluate the effects of these procedures. Three forms of human milk - freshly expressed, frozen at -20°C for a prolonged duration, and pasteurized milk - were collected from 14 healthy lactating mothers and a milk bank. The concentrations of major bioactive proteins (secretory immunoglobulin A, lactoferrin, lysozyme, and leptin) were quantified using enzyme-linked immunosorbent assay kits. Changes in these proteins by heat treatment at 40°C or 60°C for 30 minutes were further evaluated. The mean concentrations of lactoferrin and secretory immunoglobulin A were significantly reduced by 66% and 25.9%, respectively, in pasteurized milk compared with those in freshly-expressed milk. Heat treatment at 40°C or 60°C did not cause significant changes in lactoferrin and secretory immunoglobulin A, but there was an apparent increase in lysozyme (p = 0.016). There were no significant differences in leptin level among these three forms of milk prior to (p = 0.153) or after heat treatment (p = 0.053). Various freezing/heating/pasteurization processes applied to human milk prior to delivery to neonates could affect the concentration of immunomodulatory proteins, especially lactoferrin, secretory immunoglobulin A, and lysozyme. Leptin was unaffected by the various handling processes tested. Fresh milk was found to be the best food for neonates. Further studies are warranted to evaluate the functional activity of these proteins and their effects on infants' immunological status. Copyright © 2013. Published by Elsevier B.V.

  8. [Exposure to addictogenic substances, conditioned response and treatment of the exposure with response prevention].

    Science.gov (United States)

    Khazaal, Y; Frésard, E; Zullino, D

    2007-01-01

    his/her natural environment. The difficulties encountered in the development of EPR treatments, despite the appealing reasoning behind them, could be explained by the tendency of conditional stimuli to re-occur spontaneously. However, it is clear from the studies reviewed that by selecting EPR conditions more rigorously, more efficient procedures might be developed at least for some patients. It seems that the place and the conditions of exposure are factors essential to the success of these therapeutic procedures. Exposure in vivo is better than exposure in imagination. Prolonged exposure over an hour is more effective than exposure lasting 10 minutes. Exposures in close succession are also associated with a better extinction of conditioned responses. The moment that the stimulus occurs, how appropriate it is and its proximity with potential reinforcement are also essential elements for the conditioning procedures. Improving the conditions in which EPR is applied could then enhance the therapeutic potential of this approach.

  9. Interferon alfa for chronic hepatitis B infection: increased efficacy of prolonged treatment. The European Concerted Action on Viral Hepatitis (EUROHEP)

    NARCIS (Netherlands)

    Janssen, H. L.; Gerken, G.; Carreño, V.; Marcellin, P.; Naoumov, N. V.; Craxi, A.; Ring-Larsen, H.; Kitis, G.; van Hattum, J.; de Vries, R. A.; Michielsen, P. P.; ten Kate, F. J.; Hop, W. C.; Heijtink, R. A.; Honkoop, P.; Schalm, S. W.

    1999-01-01

    Interferon alfa (IFN-alpha) is the primary treatment for chronic hepatitis B. The standard duration of IFN-alpha therapy is considered 16 weeks; however, the optimal treatment length is still poorly defined. We evaluated the efficacy and acceptability of prolonged IFN-alpha treatment in patients

  10. Evaluating a patient's request for life-prolonging treatment: an ethical framework.

    Science.gov (United States)

    Winkler, Eva C; Hiddemann, Wolfgang; Marckmann, Georg

    2012-11-01

    Contrary to the widespread concern about over-treatment at the end of life, today, patient preferences for palliative care at the end of life are frequently respected. However, ethically challenging situations in the current healthcare climate are, instead, situations in which a competent patient requests active treatment with the goal of life-prolongation while the physician suggests best supportive care only. The argument of futility has often been used to justify unilateral decisions made by physicians to withhold or withdraw life-sustaining treatment. However, we argue that neither the concept of futility nor that of patient autonomy alone is apt for resolving situations in which physicians are confronted with patients' requests for active treatment. Instead, we integrate the relevant arguments that have been put forward in the academic discussion about 'futile' treatment into an ethical algorithm with five guiding questions: (1) Is there a chance that medical intervention will be effective in achieving the patient's treatment goal? (2) How does the physician evaluate the expected benefit and the potential harm of the treatment? (3) Does the patient understand his or her medical situation? (4) Does the patient prefer receiving treatment after evaluating the benefit-harm ratio and the costs? (5) Does the treatment require many resources? This algorithm shall facilitate approaching patients' requests for treatments deemed futile by the physician in a systematic way, and responding to these requests in an ethically appropriate manner. It thereby adds substantive considerations to the current procedural approaches of conflict resolution in order to improve decision making among physicians, patients and families.

  11. Short vs prolonged dual antiplatelet treatment upon endovascular stenting of peripheral arteries

    Directory of Open Access Journals (Sweden)

    Kronlage M

    2017-10-01

    Full Text Available Mariya Kronlage,1 Maximilian Wassmann,1 Britta Vogel,1 Oliver J Müller,1 Erwin Blessing,2 Hugo Katus,1,3 Christian Erbel1 1Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, 2SRH Klinikum Karlsbad Langensteinbach, Karlsbad, 3DZHK German Center for Cardiovascular Research, Partner Site Heidelberg/Mannheim, Mannheim, Germany Introduction: Peripheral artery disease (PAD is a highly prevalent disorder with a substantial economical burden. Dual antiplatelet treatment (DAPT upon endovascular stenting to prevent acute thrombotic reocclusions is an universally accepted practice for postinterventional management of PAD patients. However, the optimal period of time for DAPT upon endovascular stenting is not known.Methods: In the current nonrandomized, retrospective monocentric study, we evaluated the duration of DAPT upon endovascular stenting. A total of 261 endovascular SFA and iliac stenting procedures were performed on 214 patients and these patients were subdivided into a short (4–6 weeks or a prolonged (8–12 weeks DAPT regime group. More than 65% of the patients included were male, approximately 35% were diabetic, and 61% had a history of smoking. Of all the patients, 90% exhibited a Rutherford stage 2–3, and approximately half of the patients had a moderate-to-severe calcified target lesion with a length of >13 cm. Major safety end points were defined as any bleeding, compartment syndrome, and ischemic events. In addition to this, patency, all-cause mortality, as well as amputation were followed up over a period of 12 months upon intervention.Results: Twelve months after endovascular stenting, primary patency in our cohort was comparable between the groups (83.94% short vs 79.8% long DAPT, P>0.05. Major bleeding occurred in 18 cases without any difference between the groups (P>0.05. In addition, during the 12-month follow-up, 6 (3.4% patients in the short and 3 (3.5% in the prolonged DAPT regime

  12. Prolonged ozone exposure in an allergic airway disease model: Adaptation of airway responsiveness and airway remodeling

    Directory of Open Access Journals (Sweden)

    Park Chang-Soo

    2006-02-01

    Full Text Available Abstract Background Short-term exposure to high concentrations of ozone has been shown to increase airway hyper-responsiveness (AHR. Because the changes in AHR and airway inflammation and structure after chronic ozone exposure need to be determined, the goal of this study was to investigate these effects in a murine model of allergic airway disease. Methods We exposed BALB/c mice to 2 ppm ozone for 4, 8, and 12 weeks. We measured the enhanced pause (Penh to methacholine and performed cell differentials in bronchoalveolar lavage fluid. We quantified the levels of IL-4 and IFN-γ in the supernatants of the bronchoalveolar lavage fluids using enzyme immunoassays, and examined the airway architecture under light and electron microscopy. Results The groups exposed to ozone for 4, 8, and 12 weeks demonstrated decreased Penh at methacholine concentrations of 12.5, 25, and 50 mg/ml, with a dose-response curve to the right of that for the filtered-air group. Neutrophils and eosinophils increased in the group exposed to ozone for 4 weeks compared to those in the filtered-air group. The ratio of IL-4 to INF-γ increased significantly after exposure to ozone for 8 and 12 weeks compared to the ratio for the filtered-air group. The numbers of goblet cells, myofibroblasts, and smooth muscle cells showed time-dependent increases in lung tissue sections from the groups exposed to ozone for 4, 8, and 12 weeks. Conclusion These findings demonstrate that the increase in AHR associated with the allergic airway does not persist during chronic ozone exposure, indicating that airway remodeling and adaptation following repeated exposure to air pollutants can provide protection against AHR.

  13. Music exposure induced prolongation of cardiac allograft survival and generated regulatory CD4⁺ cells in mice.

    Science.gov (United States)

    Uchiyama, M; Jin, X; Zhang, Q; Amano, A; Watanabe, T; Niimi, M

    2012-05-01

    In clinical practice, music has been used to decrease stress, heart rate, and blood pressure and to provide a distraction from disease symptoms. We investigated sound effects on alloimmune responses in murine heart transplantation. Naïve and eardrum-ruptured CBA/N (CBA, H2(K)) underwent transplantation of a C57BL/6 (B6, H2(b)) heart and were exposed to 1 of 3 types of music-opera (La Traviata), classical (Mozart), and New Age (Enya)-or 1 of 6 different single sound frequencies for 7 days. An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Cell-proliferation, cytokine, and flow cytometry assessments were also performed. CBA recipients of a B6 graft exposed to opera and classical music had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to 6 single sound frequencies and New Age did not (MSTs, 7, 8, 9, 8, 8, 8, and 11 days, respectively). Untreated and eardrum-ruptured CBA rejected B6 grafts acutely (MSTs, 7 and 8.5 days, respectively). Adoptive transfer of whole splenocytes, CD4(+) cells, and CD4(+)CD25(+) cells from opera-exposed primary recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and >50 days, respectively). Cell-proliferation, interleukin (IL)-2 and interferon-γ were suppressed in opera-exposed mice, whereas IL-4 and IL-10 from opera-exposed recipients were up-regulated. Flow cytometry studies showed an increased CD4(+)CD25(+)Foxp3(+) cell population in splenocytes from opera-exposed mice. In conclusion, exposure to some types of music may induce prolonged survival of fully allogeneic cardiac allografts and generate CD4(+)CD25(+)Foxp3(+) regulatory cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. [Prolonged exposure to atmospheric air pollution and mortality from respiratory causes].

    Science.gov (United States)

    Eilstein, D

    2009-12-01

    Different designs can be used to analyze the relationships between respiratory mortality and long term exposure to atmospheric pollution: epidemiological studies (cohort, prevalence study) demonstrate the reality of the relationship and toxicological studies explain it. Cohort studies have the advantage of being able to take into account many confounding factors and thus avoid biases (which is not the case with prevalence studies), but require significant human and financial resources. They were first adopted in the US, but are now more often applied in Europe. The results are relatively consistent, as they all show a statistically significant association between an increase in particulate pollution and cardiopulmonary mortality. Mortality from lung cancer is also associated with long term exposition to particles and sometimes to ozone or nitrogen oxides. Cerebrovascular diseases and sudden death of young children have also been associated with particulate pollution. The relationships are more powerful for long term than short term exposure but are also linear and without threshold. In order to explain these effects (today the causality of the relationship is certain) there are many possible factors, particularly regarding particulate exposures: an increase in cardiovascular risk biomarkers (fibrinogen, white blood cells, and platelets), atherosclerosis, chronic inflammation of lung tissues increased by acute exposure, etc. More and more studies address the interaction between gene and environment and even epigenetic phenomena which could be responsible of these effects. Public Health impact could be quantified. The European E&H surveillance program Apheis, for example, estimated that if PM2.5 levels remained below 15 microg/m(3), a 30 year old person could see his life expectancy increased by 1 month to 2 years, depending on the studied city. Finally, mortality is not the only relevant indicator for health effects of air pollution. ISAAC studies address asthma

  15. Circulation, metabolism, and ventilation during prolonged exposure to carbon monoxide and to high altitude

    Energy Technology Data Exchange (ETDEWEB)

    Klausen, K.; Rasmussen, B; Gjellerod, H.; Madsen, H.; Petersen, E.

    1968-01-01

    Eight volunteers were exposed to CO (13% COHb) or high altitude (3454 m). There was no change in circulation, metabolism, or ventilation during CO exposure. With similar arterial O/sub 2/ concentration from high-altitude, V/sub e/ (BTPS) increased, Pa/sub CO/sub 2// decreased. Regulating mechanisms respond to a decrease in Pa/sub CO/sub 2// rather than a gereral lack in tissue O/sub 2/ per se.

  16. QTc Prolongation in Veterans With Heroin Dependence on Methadone Maintenance Treatment.

    Science.gov (United States)

    Hassamal, Sameer; Fernandez, Antony; Moradi Rekabdarkolaee, Hossein; Pandurangi, Ananda

    2015-06-01

    QTc prolongation and Torsade de Ppointes have been reported in patients on methadone maintenance. In this study, QTc was compared before and after the veteran (n = 49) was on a stable dosage of methadone for 8.72 ± 4.50 years to treat heroin dependence. Risk factors were correlated with the QTc once the veteran was on a stable dose of methadone. Differences in the clinical risk factors in subgroups of veterans with below and above mean QTc change was compared. ECG data was obtained from a 12-lead electrocardiogram (pre-methadone and on methadone) on 49 veterans. Data and risk factors were retrospectively collected from the medical records. The mean QTc at baseline (pre-methadone) was 426 ± 34 msec and after being on methadone for an average of 8.72 ± 4.50 years was significantly higher at 450 ± 35 msec. No significant relationships were found between QTc prolongation and risk factors except for calcium. The methadone dosage was significantly higher in veterans with a QTc change above the mean change of ≥ 24 msec (88.48 ± 27.20 mg v.s 68.96 ± 19.84 mg). None of the veterans experienced cardiac arrhythmias. The low complexity of medical co-morbidities may explain the lack of a significant correlation between any risk factor with the QTc except calcium and methadone dosage. The absence of TdP may be explained by the low prevalence of QTc values > 500 msec as well as the retrospective design of the study. During long-term methadone treatment, there was a slight increase in the QTc interval but we did not find evidence of increased cardiac toxicity as a reason for treatment termination.

  17. Treating PTSD in suicidal and self-injuring women with borderline personality disorder: development and preliminary evaluation of a Dialectical Behavior Therapy Prolonged Exposure Protocol.

    Science.gov (United States)

    Harned, Melanie S; Korslund, Kathryn E; Foa, Edna B; Linehan, Marsha M

    2012-06-01

    This study focused on the development and pilot testing of a protocol based on Prolonged Exposure (PE) that can be added to Dialectical Behavior Therapy (DBT) to treat PTSD in suicidal and self-injuring individuals with borderline personality disorder (BPD). Women with BPD, PTSD, and recent and/or imminent serious intentional self-injury (n = 13) received one year of DBT with the DBT PE Protocol, plus three months of follow-up assessment. The treatment was associated with significant reductions in PTSD, with the majority of patients no longer meeting criteria for PTSD at post-treatment (71.4% of DBT PE Protocol completers, 60.0% of the intent-to-treat sample). A minority of patients (27.3%) engaged in intentional self-injury during the study. Improvements were also found for suicidal ideation, dissociation, trauma-related guilt cognitions, shame, anxiety, depression, and social adjustment. There was no evidence that the DBT PE Protocol led to exacerbations of intentional self-injury urges or behaviors, PTSD, treatment dropout, or crisis service use. Overall, the results indicate that this integrated BPD and PTSD treatment is feasible to implement within one year of treatment, highly acceptable to patients and therapists, safe to administer, and shows promise as an effective intervention for PTSD in this complex and high-risk patient population. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Comparing Virtual Reality Exposure Therapy to Prolonged Exposure in the Treatment of Soldiers with PTSD

    Science.gov (United States)

    2014-06-01

    Rev. 8-98) Prescribed by ANSI Std. Z39.18 Table of Contents Page 1. Introduction………………………………………………………………4 2. Keywords...different audio (i.e., incoming mortars, weapons fire, voices, wind, etc.) and audiovisual stimuli (e.g., helicopter flyovers) to further approximate the

  19. Beta-lactam antibiotic-induced platelet dysfunction: Evidence for irreversible inhibition of platelet activation in vitro and in vivo after prolonged exposure to penicillin

    International Nuclear Information System (INIS)

    Burroughs, S.F.; Johnson, G.J.

    1990-01-01

    beta-Lactam antibiotics cause platelet dysfunction with bleeding complications. Previous in vitro studies documented reversible inhibition of agonist-receptor interaction. This mechanism is inadequate to explain the effect of beta-lactam antibiotics in vivo. Platelet function does not return to normal immediately after drug treatment, implying irreversible inhibition of platelet function. We report here evidence of irreversible platelet functional and biochemical abnormalities after in vitro and in vivo exposure to beta-lactam antibiotics. Irreversible binding of [14C]-penicillin (Pen) occurred in vitro. After 24 hours' in vitro incubation with 10 to 20 mmol/L Pen, or ex vivo after antibiotic treatment, irreversible functional impairment occurred; but no irreversible inhibition of alpha 2 adrenergic receptors, measured with [3H]-yohimbine, or high-affinity thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors, measured with agonist [3H]-U46619 and antagonist [3H]-SQ29548, occurred. However, low-affinity platelet TXA2/PGH2 receptors were decreased 40% after Pen exposure in vitro or in vivo, indicating irreversible membrane alteration. Two postreceptor biochemical events were irreversibly inhibited in platelets incubated with Pen for 24 hours in vitro or ex vivo after antibiotic treatment. Thromboxane synthesis was inhibited 28.3% to 81.7%. Agonist-induced rises in cytosolic calcium ([Ca2+]i) were inhibited 40.1% to 67.5% in vitro and 26.6% to 52.2% ex vivo. Therefore, Pen binds to platelets after prolonged exposure, resulting in irreversible dysfunction attributable to inhibition of TXA2 synthesis and impairment of the rise in [Ca2+]i. The loss of low-affinity TXA2/PGH2 receptors suggests that the primary site of action of these drugs is on the platelet membrane

  20. Maintenance of thyroidal radiological protection with stable iodine in adults in case of prolonged exposure

    International Nuclear Information System (INIS)

    Verger, P.; Piechowski, J.

    2000-01-01

    Ingestion of stable iodine (potassium iodide) offers an efficient protection against the irradiation of the thyroid when an accidental exposure to radioiodine occurs. This prophylaxis aims at obtaining a rapid and maximum thyroid protection without anti thyroid effects. The recommended posology is 100 mg of iodine in one time ( that is to say a tablet of 130 mg potassium iodide). After this single dose of iodine, the percentage of avoided radiation dose after 48 hours is near 75%, then decreases until 50% at 72 hours. It is possible to keep an efficient thyroid protection by taking a stable tablet of iodine on the first day, then a fourth of tablet the following days. This approach is an optimization allowing an efficient protection while reducing the eventual side effects linked to an excess of iodine. This protocol can be applied to adults, fifteen years or more adolescents, young adults and pregnant women. For children and babies there are not data to confirm the thyroid protection. The children constitute the most sensitize age group and this question should deserve to be thoroughly discussed. (N.C.)

  1. Glucose Homeostasis During Short-term and Prolonged Exposure to High Altitudes

    Science.gov (United States)

    Ader, Marilyn; Bergman, Richard N.

    2015-01-01

    Most of the literature related to high altitude medicine is devoted to the short-term effects of high-altitude exposure on human physiology. However, long-term effects of living at high altitudes may be more important in relation to human disease because more than 400 million people worldwide reside above 1500 m. Interestingly, individuals living at higher altitudes have a lower fasting glycemia and better glucose tolerance compared with those who live near sea level. There is also emerging evidence of the lower prevalence of both obesity and diabetes at higher altitudes. The mechanisms underlying improved glucose control at higher altitudes remain unclear. In this review, we present the most current evidence about glucose homeostasis in residents living above 1500 m and discuss possible mechanisms that could explain the lower fasting glycemia and lower prevalence of obesity and diabetes in this population. Understanding the mechanisms that regulate and maintain the lower fasting glycemia in individuals who live at higher altitudes could lead to new therapeutics for impaired glucose homeostasis. PMID:25675133

  2. Antibiotic-eluting hydrophilized PMMA bone cement with prolonged bactericidal effect for the treatment of osteomyelitis.

    Science.gov (United States)

    Oh, Eun Jo; Oh, Se Heang; Lee, In Soo; Kwon, Oh Soo; Lee, Jin Ho

    2016-05-01

    Osteomyelitis is still considered to be one of the major challenges for orthopedic surgeons despite advanced antiseptic surgical procedures and pharmaceutical therapeutics. In this study, hydrophilized poly(methyl methacrylate) (PMMA) bone cements containing Pluronic F68 (EG79PG28EG79) as a hydrophilic additive and vancomycin (F68-VAcements) were prepared to allow the sustained release of the antibiotic for adequate periods of time without any significant loss of mechanical properties. The compressive strengths of the bone cements with Pluronic F68 compositions less than 7 wt% were not significantly different compared with the control vancomycin-loaded bone cement (VAcement). TheF68 (7 wt%)-VAcement showed sustained release of the antibiotic for up to 11 weeks and almost 100% release from the bone cement. It also prohibited the growth ofS. aureus(zone of inhibition) over six weeks (the required period to treat osteomyelitis), and it did not show any notable cytotoxicity. From an animal study using a femoral osteomyelitis rat model, it was observed that theF68 (7 wt%)-VAcement was effective for the treatment of osteomyelitis, probably as a result of the prolonged release of antibiotic from the PMMA bone cement. On the basis of these findings, it can be suggested that the use of Pluronic F68 as a hydrophilic additive for antibiotic-eluting PMMA bone cement can be a promising strategy for the treatment of osteomyelitis. © The Author(s) 2016.

  3. One-Year Outcome of Geriatric Hip-Fracture Patients following Prolonged ICU Treatment

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    Daphne Eschbach

    2016-01-01

    Full Text Available Purpose. Incidence of geriatric fractures is increasing. Knowledge of outcome data for hip-fracture patients undergoing intensive-care unit (ICU treatment, including invasive ventilatory management (IVM and hemodiafiltration (CVVHDF, is sparse. Methods. Single-center prospective observational study including 402 geriatric hip-fracture patients. Age, gender, the American Society of Anesthesiologists (ASA classification, and the Barthel index (BI were documented. Underlying reasons for prolonged ICU stay were registered, as well as assessed procedures like IVM and CVVHDF. Outcome parameters were in-hospital, 6-month, and 1-year mortality and need for nursing care. Results. 15% were treated > 3 days and 68% 3d cohort were significantly increased (p=0.001. Most frequent indications were cardiocirculatory pathology followed by respiratory failure, renal impairment, and infection. 18% of patients needed CVVHDF and 41% IVM. In these cohorts, 6-month mortality ranged > 80% and 12-month mortality > 90%. 100% needed nursing care after 6 and 12 months. Conclusions. ICU treatment > 3 days showed considerable difference in mortality and nursing care needed after 6 and 12 months. Particularly, patients requiring CVVHDF or IVM had disastrous long-term results. Our study may add one further element in complex decision making serving this vulnerable patient cohort.

  4. Plasticity of photoreceptor-generating retinal progenitors revealed by prolonged retinoic acid exposure

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    Cameron David A

    2011-08-01

    Full Text Available Abstract Background Retinoic acid (RA is important for vertebrate eye morphogenesis and is a regulator of photoreceptor development in the retina. In the zebrafish, RA treatment of postmitotic photoreceptor precursors has been shown to promote the differentiation of rods and red-sensitive cones while inhibiting the differentiation of blue- and UV-sensitive cones. The roles played by RA and its receptors in modifying photoreceptor fate remain to be determined. Results Treatment of zebrafish embryos with RA, beginning at the time of retinal progenitor cell proliferation and prior to photoreceptor terminal mitosis, resulted in a significant alteration of rod and cone mosaic patterns, suggesting an increase in the production of rods at the expense of red cones. Quantitative pattern analyses documented increased density of rod photoreceptors and reduced local spacing between rod cells, suggesting rods were appearing in locations normally occupied by cone photoreceptors. Cone densities were correspondingly reduced and cone photoreceptor mosaics displayed expanded and less regular spacing. These results were consistent with replacement of approximately 25% of positions normally occupied by red-sensitive cones, with additional rods. Analysis of embryos from a RA-signaling reporter line determined that multiple retinal cell types, including mitotic cells and differentiating rods and cones, are capable of directly responding to RA. The RA receptors RXRγ and RARαb are expressed in patterns consistent with mediating the effects of RA on photoreceptors. Selective knockdown of RARαb expression resulted in a reduction in endogenous RA signaling in the retina. Knockdown of RARαb also caused a reduced production of rods that was not restored by simultaneous treatments with RA. Conclusions These data suggest that developing retinal cells have a dynamic sensitivity to RA during retinal neurogenesis. In zebrafish RA may influence the rod vs. cone cell fate

  5. Experimental therapy of epilepsy with transcranial magnetic stimulation: lack of additional benefit with prolonged treatment

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    Brasil-Neto Joaquim P.

    2004-01-01

    Full Text Available OBJECTIVE: To investigate the effect of three months of low-frequency repetitive transcranial magnetic stimulation (rTMS treatment in intractable epilepsy. METHODS: Five patients (four males, one female; ages 6 to 50 years, were enrolled in the study; their epilepsy could not be controlled by medical treatment and surgery was not indicated. rTMS was performed twice a week for three months; patients kept records of seizure frequency for an equal period of time before, during, and after rTMS sessions. rTMS was delivered to the vertex with a round coil, at an intensity 5 % below motor threshold. During rTMS sessions, 100 stimuli (five series of 20 stimuli, with one-minute intervals between series were delivered at a frequency of 0.3 Hz. RESULTS: Mean daily number of seizures (MDNS decreased in three patients and increased in two during rTMS- one of these was treated for only one month; the best result was achieved in a patient with focal cortical dysplasia (reduction of 43.09 % in MDNS. In the whole patient group, there was a significant (p<0.01 decrease in MDNS of 22.8 %. CONCLUSION: Although prolonged rTMS treatment is safe and moderately decreases MDNS in a group of patients with intractable epilepsy, individual patient responses were mostly subtle and clinical relevance of this method is probably low. Our data suggest, however, that patients with focal cortical lesions may indeed benefit from this novel treatment. Further studies should concentrate on that patient subgroup.

  6. Efficacy and Safety of Prolonged Rituximab Treatment in Patients with Systemic Juvenile Idiopathic Arthritis

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    E. I. Alexeeva

    2013-01-01

    Full Text Available Aim: to assess efficacy and safety of rituximab treatment in children with systemic juvenile idiopathic arthritis under prolonged follow-up. Patients and methods: results of treatment of 60 children (33 girls and 27 boys with systemic variant of juvenile idiopathic arthritis being followed-up in rheumatology department of the Federal State Institution «Scientific Centre of Children Health» of RAMS (FSI «SCCH» RAMS were analyzed. The mean age of children was 8,7 years. The mean duration of disease course at the moment of first rituximab administration was 5,3 years. At the beginning of rituximab therapy all children had active articular syndrome, severe systemic manifestations and significantly increased laboratory markers of activity. As the signs of improvement the authors used pediatric criteria of the American College of Rheumatology. The treatment was approved by the local ethic committee of the FSI «SCCH» RAMS; the patients’ representatives and patients older than 14 years old had signed informed agreement. Results: remission was induced in 26 of 60 (43% patients: in 9 of them after the 1st course of treatment, in 8 — after the 2nd, in 6 — after the 3d and in 3 — after the 4th. The maximal duration of remission was 5 years 4 months, minimal — 6 months. Other genetically engineered drugs were administered to 34 (57% of the patients: due to the primary inefficiency in 15, secondary inefficiency — in 10; due to partial inefficiency — in 9 children. The drug was well-tolerated in most of the patients. Undesirable effects were represented by transfusional reactions to the rituximab infusion, infections with different severity and granulocytopenia. Conclusions: rituximab has high efficiency in patients with severe systemic variant of juvenile idiopathic arthritis. The drug induced remission in patients who had been considered almost incurable, with low status of physical and social adaptation.

  7. Serum proteomic changes after randomized prolonged erythropoietin treatment and/or endurance training: detection of novel biomarkers.

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    Britt Christensen

    Full Text Available Despite implementation of the biological passport to detect erythropoietin abuse, a need for additional biomarkers remains. We used a proteomic approach to identify novel serum biomarkers of prolonged erythropoiesis-stimulating agent (ESA exposure (Darbepoietin-α and/or aerobic training.Thirty-six healthy young males were randomly assigned to the following groups: Sedentary-placebo (n = 9, Sedentary-ESA (n = 9, Training-placebo (n = 10, or Training-ESA (n = 8. They were treated with placebo/Darbepoietin-α subcutaneously once/week for 10 weeks followed by a 3-week washout period. Training consisted of supervised biking 3/week for 13 weeks at the highest possible intensity. Serum was collected at baseline, week 3 (high dose Darbepoietin-α, week 10 (reduced dose Darbepoietin-α, and after a 3-week washout period.Serum proteins were separated according to charge and molecular mass (2D-gel electrophoresis. The identity of proteins from spots exhibiting altered intensity was determined by mass spectrometry.Six protein spots changed in response to Darbepoietin-α treatment. Comparing all 4 experimental groups, two protein spots (serotransferrin and haptoglobin/haptoglobin related protein showed a significant response to Darbepoietin-α treatment. The haptoglobin/haptoglobin related protein spot showed a significantly lower intensity in all subjects in the training-ESA group during the treatment period and increased during the washout period.An isoform of haptoglobin/haptoglobin related protein could be a new anti-doping marker and merits further research.ClinicalTrials.gov NCT01320449.

  8. Prolonged methylprednisolone therapy after the pulse treatment for patients with moderate-to-severe paraquat poisoning: A retrospective analysis.

    Science.gov (United States)

    Gao, Jie; Feng, ShunYi; Wang, Jian; Yang, SiYuan; Li, Yong

    2017-06-01

    This retrospective study aims to evaluate the effect of prolonged methylprednisolone (MP) therapy on the mortality of patients with moderate-to-severe paraquat (PQ) poisoning after the pulse treatment.We performed a retrospective analysis of patients with acute moderate-to-severe PQ poisoning that were admitted to the emergency department from May 2012 to August 2016. Out of 138 patients, 60 were treated with pulse treatment (15 mg kg day MP for 3 days) and 78 were treated with prolonged MP therapy after pulse treatment (15 mg kg day MP for 3 days; afterward, the dosage was reduced in half every 2 days, and the MP therapy was terminated until 0.47 mg kg day). Kaplan-Meier method was used to compare the mortality between the 2 groups. Cox proportional hazard models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI).The mortality of the prolonged MP therapy after pulse treatment group was lower than that of the pulse group (47.4% vs 63.3%; log-rank tests, P  =  .003). According to the multivariate Cox analysis, the prolonged MP therapy after pulse treatment was significantly associated with a lower mortality risk (HR: 0.31, 95% CI: 0.19-0.52, P treatment caused more incidences of leucopenia than the pulse treatment alone (25.6% vs 11.7%, P  =  .04).The prolonged MP therapy after pulse treatment can reduce the mortality of moderate-to-severe PQ poisoning patients.

  9. Effect of Prolonged Exposure Therapy Delivered Over 2 Weeks vs 8 Weeks vs Present-Centered Therapy on PTSD Symptom Severity in Military Personnel: A Randomized Clinical Trial.

    Science.gov (United States)

    Foa, Edna B; McLean, Carmen P; Zang, Yinyin; Rosenfield, David; Yadin, Elna; Yarvis, Jeffrey S; Mintz, Jim; Young-McCaughan, Stacey; Borah, Elisa V; Dondanville, Katherine A; Fina, Brooke A; Hall-Clark, Brittany N; Lichner, Tracey; Litz, Brett T; Roache, John; Wright, Edward C; Peterson, Alan L

    2018-01-23

    Effective and efficient treatment is needed for posttraumatic stress disorder (PTSD) in active duty military personnel. To examine the effects of massed prolonged exposure therapy (massed therapy), spaced prolonged exposure therapy (spaced therapy), present-centered therapy (PCT), and a minimal-contact control (MCC) on PTSD severity. Randomized clinical trial conducted at Fort Hood, Texas, from January 2011 through July 2016 and enrolling 370 military personnel with PTSD who had returned from Iraq, Afghanistan, or both. Final follow-up was July 11, 2016. Prolonged exposure therapy, cognitive behavioral therapy involving exposure to trauma memories/reminders, administered as massed therapy (n = 110; 10 sessions over 2 weeks) or spaced therapy (n = 109; 10 sessions over 8 weeks); PCT, a non-trauma-focused therapy involving identifying/discussing daily stressors (n = 107; 10 sessions over 8 weeks); or MCC, telephone calls from therapists (n = 40; once weekly for 4 weeks). Outcomes were assessed before and after treatment and at 2-week, 12-week, and 6-month follow-up. Primary outcome was interviewer-assessed PTSD symptom severity, measured by the PTSD Symptom Scale-Interview (PSS-I; range, 0-51; higher scores indicate greater PTSD severity; MCID, 3.18), used to assess efficacy of massed therapy at 2 weeks posttreatment vs MCC at week 4; noninferiority of massed therapy vs spaced therapy at 2 weeks and 12 weeks posttreatment (noninferiority margin, 50% [2.3 points on PSS-I, with 1-sided α = .05]); and efficacy of spaced therapy vs PCT at posttreatment. Among 370 randomized participants, data were analyzed for 366 (mean age, 32.7 [SD, 7.3] years; 44 women [12.0%]; mean baseline PSS-I score, 25.49 [6.36]), and 216 (59.0%) completed the study. At 2 weeks posttreatment, mean PSS-I score was 17.62 (mean decrease from baseline, 7.13) for massed therapy and 21.41 (mean decrease, 3.43) for MCC (difference in decrease, 3.70 [95% CI,0.72 to 6.68]; P = .02

  10. Prolonged Minocycline Treatment Impairs Motor Neuronal Survival and Glial Function in Organotypic Rat Spinal Cord Cultures

    Science.gov (United States)

    Pinkernelle, Josephine; Fansa, Hisham; Ebmeyer, Uwe; Keilhoff, Gerburg

    2013-01-01

    Background Minocycline, a second-generation tetracycline antibiotic, exhibits anti-inflammatory and neuroprotective effects in various experimental models of neurological diseases, such as stroke, Alzheimer’s disease, amyotrophic lateral sclerosis and spinal cord injury. However, conflicting results have prompted a debate regarding the beneficial effects of minocycline. Methods In this study, we analyzed minocycline treatment in organotypic spinal cord cultures of neonatal rats as a model of motor neuron survival and regeneration after injury. Minocycline was administered in 2 different concentrations (10 and 100 µM) at various time points in culture and fixed after 1 week. Results Prolonged minocycline administration decreased the survival of motor neurons in the organotypic cultures. This effect was strongly enhanced with higher concentrations of minocycline. High concentrations of minocycline reduced the number of DAPI-positive cell nuclei in organotypic cultures and simultaneously inhibited microglial activation. Astrocytes, which covered the surface of the control organotypic cultures, revealed a peripheral distribution after early minocycline treatment. Thus, we further analyzed the effects of 100 µM minocycline on the viability and migration ability of dispersed primary glial cell cultures. We found that minocycline reduced cell viability, delayed wound closure in a scratch migration assay and increased connexin 43 protein levels in these cultures. Conclusions The administration of high doses of minocycline was deleterious for motor neuron survival. In addition, it inhibited microglial activation and impaired glial viability and migration. These data suggest that especially high doses of minocycline might have undesired affects in treatment of spinal cord injury. Further experiments are required to determine the conditions for the safe clinical administration of minocycline in spinal cord injured patients. PMID:23967343

  11. The effect of duration of untreated psychosis and treatment delay on the outcomes of prolonged early intervention in psychotic disorders.

    Science.gov (United States)

    Albert, Nikolai; Melau, Marianne; Jensen, Heidi; Hastrup, Lene Halling; Hjorthøj, Carsten; Nordentoft, Merete

    2017-09-26

    The duration of untreated psychosis (DUP) has been shown to have an effect on outcome after first-episode psychosis. The premise of specialized early intervention (SEI) services is that intervention in the early years of illness can affect long-term outcomes. In this study, we investigate whether DUP affects treatment response after 5 years of SEI treatment compared to 2 years of SEI treatment. As part of a randomized controlled trial testing the effect of prolonged SEI treatment 400 participants diagnosed within the schizophrenia spectrum were recruited. For this specific study participants were dichotomized based on DUP, treatment delay, and time from first symptom until start of SEI treatment. The groups were analyzed with regard to treatment response on psychopathology, level of functioning, and cognitive functioning. The participants with a short DUP had a tendency to respond better to the prolonged treatment with regards to disorganized and negative dimension. For participants with short duration from first symptom until start of SEI treatment there was a significant difference on the negative dimension favoring the prolonged OPUS treatment. The finding of an effect of prolonged treatment for participants with a short total treatment delay could mean that prolonged SEI treatment is more beneficial than treatment as usual (TAU) so long as it is provided in the early years of illness and not just in the early years after diagnosis. THE EARLIER THE BETTER: The duration of untreated psychosis influences the long-term outcomes of treatment. Nikolai Albert, at the Copenhagen Mental Health Centre, and a team of Danish researchers have investigated the effects of a specialized early intervention program (OPUS) in 400 patients diagnosed with schizophrenia spectrum disorders and compared the effects of OPUS after two and five years. Their findings suggest that five years of specialized early intervention was most beneficial when the total duration from symptom start to

  12. Prolonged exposure of resveratrol induces reactive superoxide species-independent apoptosis in murine prostate cells.

    Science.gov (United States)

    Kumar, Sanjay; Stokes, James; Singh, Udai P; Scissum-Gunn, Karyn; Singh, Rajesh; Manne, Upender; Mishra, Manoj K

    2017-10-01

    Nitric oxide, a signaling molecule, inhibits mitochondrial respiration by binding with cytochrome c oxidase, resulting in elevated production of reactive superoxide species (reactive oxygen and nitrogen) in the mitochondria and increased susceptibility to cell death. Generation of mitochondrial superoxide species can be suppressed by natural compounds such as resveratrol, a dietary polyphenol found in the skin of red fruits. In various cancer cells, resveratrol shows anti-oxidant and cancer preventive properties. Since, the effect of resveratrol on reactive superoxide species-independent apoptosis in prostate cancer cells is not well illustrated; therefore, we investigated this phenomenon in TRAMP murine prostate cancer cells. To accomplish this, TRAMP cells were incubated with resveratrol, resveratrol + DETA-NONOate, DETA-NONOate (nitric oxide donor), resveratrol + L-NMMA, or L-NMMA (nitric oxide inhibitor) for 48 h, and reactive superoxide species in the mitochondria and culture supernatant were measured. In addition, the mitochondrial membrane potential, cell viability, expression of apoptotic markers (Bax and Bcl2), γ-H2A.x, p53, and caspase-3 was determined. We found that resveratrol suppressed reactive superoxide species such as reactive oxygen species in the mitochondria and nitric oxide in culture supernatant when compared to the DETA-NONOate treatment and disrupted the mitochondrial membrane potential. Resveratrol also reduced cell viability, altered the expression of apoptotic markers (Bax and Bcl2), and increased expression of γ-H2A.x (indicative marker of DNA fragmentation) and p53 (a critical DNA damage response protein). However, there was no appreciable modulation of the caspase-3. Therefore, our data suggest that resveratrol induces superoxide species-independent apoptosis and may act as a therapeutic agent against prostate cancer.

  13. Antenatal exposure to Ureaplasma species exacerbates bronchopulmonary dysplasia synergistically with subsequent prolonged mechanical ventilation in preterm infants.

    Science.gov (United States)

    Inatomi, Tadashi; Oue, Shinya; Ogihara, Tohru; Hira, Seigo; Hasegawa, Masashi; Yamaoka, Shigeo; Yasui, Masako; Tamai, Hiroshi

    2012-03-01

    The presence of microorganisms in gastric fluid in neonates at birth is postulated to reflect antenatal infection and also to be associated with the development of bronchopulmonary dysplasia (BPD). A logistic regression analysis, after controlling for other risk factors, indicated that Ureaplasma-positive infants were not at increased risk for moderate/severe BPD (adjusted odds ratio (OR): 2.58, 95% confidence interval (CI): 0.57-6.89, P = 0.12). However, the association between the presence of Ureaplasma species and the risk for moderate/severe BPD increased significantly in infants on mechanical ventilation (MV) ≥2 wk (adjusted OR: 4.17, 95% CI: 1.62-44.1, P = 0.009). An analysis using a lung injury marker indicated that Ureaplasma-positive infants with MV ≥2 wk, but not other infants, showed higher serum KL-6 levels in samples taken from cord blood, and that KL-6 levels increased time-dependently up to 4 wk of age. Antenatal exposure to Ureaplasma species induces lung injury prior to birth and synergistically contributes to the development of BPD in infants requiring prolonged MV (≥2 wk). We recovered gastric fluid specimens from 122 infants with gestational age (GA) Ureaplasma-positive or Ureaplasma-negative infants.

  14. Different regional gray matter loss in recent onset PTSD and non PTSD after a single prolonged trauma exposure.

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    Yunchun Chen

    Full Text Available OBJECTIVE: Gray matter loss in the limbic structures was found in recent onset post traumatic stress disorder (PTSD patients. In the present study, we measured regional gray matter volume in trauma survivors to verify the hypothesis that stress may cause different regional gray matter loss in trauma survivors with and without recent onset PTSD. METHOD: High resolution T1-weighted magnetic resonance imaging (MRI were obtained from coal mine flood disaster survivors with (n = 10 and without (n = 10 recent onset PTSD and 20 no trauma exposed normal controls. The voxel-based morphometry (VBM method was used to measure the regional gray matter volume in three groups, the correlations of PTSD symptom severities with the gray matter volume in trauma survivors were also analyzed by multiple regression. RESULTS: Compared with normal controls, recent onset PTSD patients had smaller gray matter volume in left dorsal anterior cingulate cortex (ACC, and non PTSD subjects had smaller gray matter volume in the right pulvinar and left pallidum. The gray matter volume of the trauma survivors correlated negatively with CAPS scores in the right frontal lobe, left anterior and middle cingulate cortex, bilateral cuneus cortex, right middle occipital lobe, while in the recent onset PTSD, the gray matter volume correlated negatively with CAPS scores in bilateral superior medial frontal lobe and right ACC. CONCLUSION: The present study identified gray matter loss in different regions in recent onset PTSD and non PTSD after a single prolonged trauma exposure. The gray matter volume of left dorsal ACC associated with the development of PTSD, while the gray matter volume of right pulvinar and left pallidum associated with the response to the severe stress. The atrophy of the frontal and limbic cortices predicts the symptom severities of the PTSD.

  15. Protection of the public in situations of prolonged radiation exposure. The application of the Commission's system of radiological protection to controllable radiation exposure due to natural sources and long-lived radioactive residues.

    Science.gov (United States)

    1999-01-01

    This report provides guidance on the application of the ICRP system of radiological protection to prolonged exposure situations affecting members of the public. It addresses the general application of the Commission's system to the control of prolonged exposures resulting from practices and to the undertaking of interventions in prolonged exposure situations. Additionally, it provides recommendations on generic reference levels for such interventions. The report also considers some specific situations and discusses a number of issues that have been of concern, namely: natural radiation sources that may give rise to high doses; the restoration and rehabilitation of sites where human activities involving radioactive substances have been carried out; the return to 'normality' following an accident that has released radioactive substances to the environment; and the global marketing of commodities for public consumption that contain radioactive substances. Annexes provide some examples of prolonged exposure situations and discuss the radiological protection quantities, radiation-induced health effects and aspects of the Commission's system of radiological protection relevant to prolonged exposure. Quantitative recommendations for prolonged exposures are provided in the report. They must be interpreted with extreme caution; Chapters 4 and 5 stress the upper bound nature of the following values: Generic reference levels for intervention, in terms of existing total annual doses, are given as < approximately 100 mSv, above which intervention is almost always justifiable (situations for which the annual dose threshold for deterministic effects in relevant organs is exceeded will almost always require intervention), and < approximately 10 mSv, below which intervention is not likely to be justifiable (and above which it may be necessary). Intervention exemption levels for commodities, especially building materials, are expressed as an additional annual dose of approximately 1

  16. Single Intravenous Dose of Novel Flurbiprofen-Loaded Proniosome Formulations Provides Prolonged Systemic Exposure and Anti-inflammatory Effect.

    Science.gov (United States)

    Verma, Preeti; Prajapati, Sunil K; Yadav, Rajbharan; Senyschyn, Danielle; Shea, Peter R; Trevaskis, Natalie L

    2016-11-07

    hydrated proniosomes can prolong systemic drug exposure over 3 days and provide a sustained therapeutic effect. The developed proniosomes represent a novel approach to treat acute pain and inflammation with the potential to be administered as a single intravenous dose by a clinician at the time of injury or surgery that provides adequate relief for several days and reduces fluctuations in therapy. Similar systems loaded with different drugs have potential for broader application in anesthesia, anti-infective, antiemetic, and cancer therapy.

  17. [Secondary traumatization/trauma among employees in palliative care units--the products of prolonged repeated exposure to suffering and death].

    Science.gov (United States)

    Samson, Tali; Shvartzman, Pesach

    2012-11-01

    The palliative care philosophy accepts the dying process as a natural phase in the life cycle and provides quality end of life care for terminal patients and their family members. Prolonged exposure to the physical symptoms and pain, as well as the psychological, spiritual, and existential suffering of the dying patient, may be fertile ground for the development of post-traumatic stress symptoms among palliative care teams. Work-related positive outcomes (such as compassion, satisfaction and meaning) and work-related negative outcomes (such as compassion fatigue, secondary traumatization and burnout) can exist side by side, and the unique balance between them will determine the quality of life of the worker. This review presents the current knowledge about the prevalence and causes of work-related stress outcomes among palliative care teams and measurement tools that are available. The literature review discusses secondary traumatization in palliative care teams and relevant messages for the development of treatment options, burnout prevention programs and support interventions for professionals who lead the care for terminal patients in Israel.

  18. New developments in the treatment of primary insomnia in elderly patients: focus on prolonged-release melatonin

    Directory of Open Access Journals (Sweden)

    Vigo DE

    2012-10-01

    Full Text Available Daniel P Cardinali, María F Vidal, Daniel E VigoDepartment of Teaching and Research, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, Buenos Aires, ArgentinaAbstract: A temporal relationship between the nocturnal rise in melatonin secretion and the increase in sleep propensity at the beginning of the night, coupled with the sleep-promoting effects of exogenous melatonin, indicate that melatonin is involved in the regulation of sleep. This action is attributed to the MT1 and MT2 melatonin receptors present in the hypothalamic suprachiasmatic nucleus and other brain areas. The sleep-promoting actions of melatonin, which are demonstrable in healthy humans, have been found to be useful in subjects suffering from circadian rhythm sleep disorders and in elderly patients, who had low nocturnal melatonin production and secretion. The effectiveness of melatonin in treating sleep disturbances in these patients is relevant because the sleep-promoting compounds that are usually prescribed, such as benzodiazepines and related drugs, have many adverse effects, such as next-day hangover, dependence, and impairment of memory. Melatonin has been used for improving sleep in patients with insomnia mainly because it does not cause any hangover or show any addictive potential. However, there is a lack of consistency concerning its therapeutic value (partly because of its short half-life and the small quantities of melatonin used. Thus, attention has been focused either on the development of more potent melatonin analogs with prolonged effects or on the design of slow-release melatonin preparations. A prolonged-release preparation of melatonin 2 mg (Circadin® has been approved for the treatment of primary insomnia in patients aged ≥55 years in the European Union. This prolonged-release preparation of melatonin had no effect on psychomotor functions, memory recall, or driving skills during the night or the next morning relative to placebo

  19. Work-related limitations and return-to-work experiences in prolonged fatigue: workers' perspectives before and after vocational treatment.

    Science.gov (United States)

    Joosen, Margot C W; Frings-Dresen, Monique H W; Sluiter, Judith K

    2011-01-01

    To gain insight into fatigued workers' perspectives regarding work experience before and after receiving vocational rehabilitation (VR) treatments. A qualitative survey was conducted using semi-structured interviews with 21 fatigued workers who attended an outpatient multi-component VR treatment. Six months after treatment, work-related limitations and employed VR strategies at work before treatment were explored. Next, VR treatment experiences regarding return-to-work (RTW) were explored. Two researchers performed partially independent, qualitative analyses that revealed topics, discussed by the project team, and organised into domains, categories and sub-categories. Work-related limitations were: symptoms of prolonged fatigue, personal limitations (e.g. lack of self-reflection on individual capacity and limitations), interpersonal factors, activities and conditions at work and life/work imbalance. Before the treatment, VR strategies such as work adaptations, well-intentioned advice and support, and/or referral to psychological or physical care were employed. VR treatment experiences on RTW were: personal challenges (e.g. gained awareness and coping skills), improved activities during work, work adaptations and unresolved problems (e.g. remaining fatigue symptoms and sickness absence). New information about work experiences before and after multi-component VR treatments in workers with prolonged fatigue may help employers, occupational physicians and other caregivers to develop VR strategies that better meet individuals' needs.

  20. Dynamics of immediate early gene and neuropeptide gene response to prolonged immobilization stress: evidence against a critical role of the termination of exposure to the stressor.

    Science.gov (United States)

    Trnecková, Lenka; Rotllant, David; Klenerová, Vera; Hynie, Sixtus; Armario, Antonio

    2007-02-01

    Stress-induced expression of immediate early genes (IEGs) appears to be transient even if the exposure to the stressor persists. However, there are some exceptions which suggest that particular characteristics of stressors can affect the dynamics of IEG expression. We studied in selected telencephalic, diencephalic and brainstem regions the mRNA levels of two clearly distinct IEGs (c-fos and arc) during prolonged exposure to a severe stressor such as immobilization (IMO) and after releasing the rats from the situation. Although regional differences were observed with the two IEGs, overall, c-fos mRNA levels progressively declined over the course of 4 h of continuous exposure to IMO, whereas arc mRNA levels were maintained at high levels in the brain regions that express this gene under stress (telencephalon). Levels of CRF hnRNA in the hypothalamus paraventricular nucleus only slightly declined during prolonged exposure to IMO. Surprisingly, termination of exposure to IMO did not modify CRF gene expression in the paraventricular nucleus or the pattern of IEGs expression, with the exception of c-fos in the lateral septum. Thus, putative signals associated to the termination of exposure to IMO were unable to modify either IEG expression in most brain areas or CRF gene expression in the paraventricular nucleus.

  1. Evaluation of Serum for Pathophysiological Effects of Prolonged Low Salinity Water Exposure in Displaced Bottlenose Dolphins (Tursiops truncatus

    Directory of Open Access Journals (Sweden)

    Ruth Y. Ewing

    2017-06-01

    Full Text Available We conducted a retrospective study of serum biochemistry and hematologic findings from displaced, out-of-habitat bottlenose dolphins (Tursiops truncatus exposed to various low salinity environments in waters along the southern United States including southeastern Atlantic and northern Gulf of Mexico. Serum sodium, chloride, and calculated osmolality were significantly lower and below reference ranges in displaced animals compared to free-ranging case control animals. This suggests clinical hyponatremia, hypochloremia, and hypo-osmolality due to an uptake of low saline water from the environment. In addition, significant differences were found in other serum chemistry variables, although none were outside of normal reference ranges for non-controlled free-ranging animals. Multiple linear regressions demonstrated the degree of salinity had a greater pathophysiologic response than the duration of fresh water exposure. The Na/Cl ratio and bicarbonate were the only variables that were significantly modulated by exposure duration. These findings suggest that the degree of salinity is a critical factor when assessing and managing care for dolphins chronically exposed to low salinity water. Results from this study indicate that changes in various biochemical parameters can be used to determine fresh water exposure and aid in determining the treatment for animals recovered from low salinity waters.

  2. Increased albumin excretion in industrial workers due to shift work rather than to prolonged exposure to low concentrations of chlorinated hydrocarbons.

    OpenAIRE

    Boogaard, P J; Caubo, M E

    1994-01-01

    OBJECTIVES--It has been reported that groups of workers in petrochemical industries who have been exposed to low concentrations of chemicals for prolonged periods have an increased urinary albumin excretion compared with unexposed controls. This increase, however, seemed to be unrelated to the extent, duration, and type of exposure. The aim of the present study was to investigate the suggestion that the small increase in albumin excretion might be due to differences in physical workload betwe...

  3. Prolonged vertigo and ataxia after mandibular nerve block for treatment of trigeminal neuralgia

    OpenAIRE

    Arvind Chaturvedi; H H Dash

    2011-01-01

    Common complications of neurolytic mandibular nerve block are hypoesthesia, dysesthesia, and chemical neuritis. We report a rare complication, prolonged severe vertigo and ataxia, after neurolytic mandibular blockade in a patient suffering from trigeminal neuralgia. Coronoid approach was used for right sided mandibular block. After successful test injection with local anesthetic, absolute alcohol was given for neurolytic block. Immediately after alcohol injection, patient developed nausea and...

  4. Endoscopic stent suture fixation for prevention of esophageal stent migration during prolonged dilatation for achalasia treatment.

    Science.gov (United States)

    Rieder, E; Asari, R; Paireder, M; Lenglinger, J; Schoppmann, S F

    2017-04-01

    The aim of this study is to compare endoscopic stent suture fixation with endoscopic clip attachment or the use of partially covered stents (PCS) regarding their capability to prevent stent migration during prolonged dilatation in achalasia. Large-diameter self-expanding metal stents (30 mm × 80 mm) were placed across the gastroesophageal junction in 11 patients with achalasia. Stent removal was scheduled after 4 to 7 days. To prevent stent dislocation, endoscopic clip attachment, endoscopic stent suture fixation, or PCS were used. The Eckardt score was evaluated before and 6 months after prolonged dilatation. After endoscopic stent suture fixation, no (0/4) sutured stent migrated. When endoscopic clips were used, 80% (4/5) clipped stents migrated (p = 0.02). Of two PCS (n = 2), one migrated and one became embedded leading to difficult stent removal. Technical adverse events were not seen in endoscopic stent suture fixation but were significantly correlated with the use of clips or PCS (r = 0.828, p = 0.02). Overall, 72% of patients were in remission regarding their achalasia symptoms 6 months after prolonged dilatation. Endoscopic suture fixation of esophageal stents but not clip attachment appears to be the best method of preventing early migration of esophageal stents placed at difficult locations such as at the naive gastroesophageal junction. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. [Prolonged blockade of nervus ischiadicus in a system of complex treatment of patients, suffering complicated diabetic foot syndrome].

    Science.gov (United States)

    Shapoval, S D; Savon, I L; Sofilkanych, M M

    2015-03-01

    General principles of treatment in patients, suffering diabetic foot syndrome, are adduced. There was proved, that reconvalescence of the patients depends not only on quality of complex treatment, but from optimal choice of anesthesia method, its impact on postoperative period course. Application of prolonged blockade of n. ischiadicus gives possibility to perform operative intervention on the lower extremity in full volume, guarantees sufficient motor and sensory block, permits patients to reject from application of narcotic analgetics, to reduce the dose of strong nonnarcotic analgetics, the terms of transition of the wound process phase I into phase II, promotes early activization of patients postoperatively, constitutes alternative for other methods of anesthesiological support.

  6. Changes in CR-39 proton sensitivity due to prolonged exposure to high vacuums relevant to the National Ignition Facility and OMEGA.

    Science.gov (United States)

    Manuel, M J-E; Rosenberg, M J; Sinenian, N; Rinderknecht, H; Zylstra, A B; Séguin, F H; Frenje, J; Li, C K; Petrasso, R D

    2011-09-01

    When used at facilities like OMEGA and the NIF, CR-39 is exposed to high vacuum environments before and after irradiation by charged particles and neutrons. Using an electrostatic linear accelerator at MIT, studies have been conducted to investigate the effects of high vacuum exposure on the sensitivity of CR-39 to fusion protons in the ~1-9 MeV energy range. High vacuum conditions, of order 10(-5) Torr, experienced by CR-39 samples at these facilities were emulated. It is shown that vacuum exposure times longer than ~16 h before proton irradiation result in a decrease in proton sensitivity, whereas no effect was observed for up to 67 h of vacuum exposure after proton irradiation. CR-39 sensitivity curves are presented for samples with prolonged exposure to high vacuum before and after proton irradiation. © 2011 American Institute of Physics

  7. Room-temperature X-ray diffraction studies of cisplatin and carboplatin binding to His15 of HEWL after prolonged chemical exposure

    International Nuclear Information System (INIS)

    Tanley, Simon W. M.; Schreurs, Antoine M. M.; Kroon-Batenburg, Loes M. J.; Helliwell, John R.

    2012-01-01

    Binding of cisplatin to His15 in hen egg-white lysozyme in aqueous media is observed after prolonged chemical exposure for 15 months, in contrast to the lack of binding that was observed after 4 d in a previous study. Binding of carboplatin is seen in greater detail in the case of room-temperature data collection compared with cryo data collection. The anticancer complexes cisplatin and carboplatin are known to bind to both the N δ and the N ∊ atoms of His15 of hen egg-white lysozyme (HEWL) in the presence of dimethyl sulfoxide (DMSO). However, neither binds in aqueous media after 4 d of crystallization and crystal growth, suggesting that DMSO facilitates cisplatin/carboplatin binding to the N atoms of His15 by an unknown mechanism. Crystals of HEWL cocrystallized with cisplatin in both aqueous and DMSO media, of HEWL cocrystallized with carboplatin in DMSO medium and of HEWL cocrystallized with cisplatin and N-acetylglucosamine (NAG) in DMSO medium were stored for between seven and 15 months. X-ray diffraction studies of these crystals were carried out on a Bruker APEX II home-source diffractometer at room temperature. Room-temperature X-ray diffraction data collection removed the need for cryoprotectants to be used, ruling out any effect that the cryoprotectants might have had on binding to the protein. Both cisplatin and carboplatin still bind to both the N δ and N ∊ atoms of His15 in DMSO media as expected, but more detail for the cyclobutanedicarboxylate (CBDC) moiety of carboplatin was observed at the N ∊ binding site. However, two molecules of cisplatin were now observed to be bound to His15 in aqueous conditions. The platinum peak positions were identified using anomalous difference electron-density maps as a cross-check with F o − F c OMIT electron-density maps. The occupancies of each binding site were calculated using SHELXTL. These results show that over time cisplatin binds to both N atoms of His15 of HEWL in aqueous media, whereas this

  8. Stress-altered synaptic plasticity and DAMP signaling in the hippocampus-PFC axis; elucidating the significance of IGF-1/IGF-1R/CaMKIIα expression in neural changes associated with a prolonged exposure therapy.

    Science.gov (United States)

    Ogundele, Olalekan M; Ebenezer, Philip J; Lee, Charles C; Francis, Joseph

    2017-06-14

    Traumatic stress patients showed significant improvement in behavior after a prolonged exposure to an unrelated stimulus. This treatment method attempts to promote extinction of the fear memory associated with the initial traumatic experience. However, the subsequent prolonged exposure to such stimulus creates an additional layer of neural stress. Although the mechanism remains unclear, prolonged exposure therapy (PET) likely involves changes in synaptic plasticity, neurotransmitter function and inflammation; especially in parts of the brain concerned with the formation and retrieval of fear memory (Hippocampus and Prefrontal Cortex: PFC). Since certain synaptic proteins are also involved in danger-associated molecular pattern signaling (DAMP), we identified the significance of IGF-1/IGF-1R/CaMKIIα expression as a potential link between the concurrent progression of synaptic and inflammatory changes in stress. Thus, a comparison between IGF-1/IGF-1R/CaMKIIα, synaptic and DAMP proteins in stress and PET may highlight the significance of PET on synaptic morphology and neuronal inflammatory response. In behaviorally characterized Sprague-Dawley rats, there was a significant decline in neural IGF-1 (pIGF-1R expression. These animals showed a significant loss of presynaptic markers (synaptophysin; pIGF-1 (pIGF-1R was recorded in the Stress-PET group (pIGF-1/IGF-1R, an increase in activated hippocampal and cortical microglia was seen in stress (pIGF1/IGF-1R/CaMKIIα. Firstly, we showed a direct relationship between IGF-1/IGF-1R expression, presynaptic function (synaptophysin) and neurotransmitter activity in stress and PET. Secondly, we identified the possible role of CaMKIIα in post-synaptic function and regulation of small ion conductance channels. Lastly, we highlighted some of the possible links between IGF1/IGF-1R/CaMKIIα, the expression of DAMP proteins, Microglia activation, and its implication on synaptic plasticity during stress and PET. Copyright © 2017

  9. Inulin Supplementation Lowered the Metabolic Defects of Prolonged Exposure to Chlorpyrifos from Gestation to Young Adult Stage in Offspring Rats.

    Science.gov (United States)

    Reygner, Julie; Lichtenberger, Lydia; Elmhiri, Ghada; Dou, Samir; Bahi-Jaber, Narges; Rhazi, Larbi; Depeint, Flore; Bach, Veronique; Khorsi-Cauet, Hafida; Abdennebi-Najar, Latifa

    2016-01-01

    Increasing evidence indicates that chlorpyrifos (CPF), an organophosphorus insecticide, is involved in metabolic disorders. We assess the hypothesis whether supplementation with prebiotics from gestation to adulthood, through a modulation of microbiota composition and fermentative activity, alleviates CPF induced metabolic disorders of 60 days old offspring. 5 groups of Wistar rats, from gestation until weaning, received two doses of CPF pesticide: 1 mg/kg/day (CPF1) or 3.5 mg/kg/day (CPF3.5) with free access to inulin (10g/L in drinking water). Then male pups received the same treatment as dams. Metabolic profile, leptin sensitivity, insulin receptor (IR) expression in liver, gut microbiota composition and short chain fatty acid composition (SCFAs) in the colon, were analyzed at postnatal day 60 in the offspring (PND 60). CPF3.5 increased offspring's birth body weight (BW) but decreased BW at PND60. Inulin supplementation restored the BW at PND 60 to control levels. Hyperinsulinemia and decrease in insulin receptor β in liver were seen in CPF1 exposed rats. In contrast, hyperglycemia and decrease in insulin level were found in CPF3.5 rats. Inulin restored the levels of some metabolic parameters in CPF groups to ranges comparable with the controls. The total bacterial population, short chain fatty acid (SCFA) production and butyrate levels were enhanced in CPF groups receiving inulin. Our data indicate that developmental exposure to CPF interferes with metabolism with dose related effects evident at adulthood. By modulating microbiota population and fermentative activity, inulin corrected adult metabolic disorders of rats exposed to CPF during development. Prebiotics supply may be thus considered as a novel nutritional strategy to counteract insulin resistance and diabetes induced by a continuous pesticide exposure.

  10. Inulin Supplementation Lowered the Metabolic Defects of Prolonged Exposure to Chlorpyrifos from Gestation to Young Adult Stage in Offspring Rats.

    Directory of Open Access Journals (Sweden)

    Julie Reygner

    Full Text Available Increasing evidence indicates that chlorpyrifos (CPF, an organophosphorus insecticide, is involved in metabolic disorders. We assess the hypothesis whether supplementation with prebiotics from gestation to adulthood, through a modulation of microbiota composition and fermentative activity, alleviates CPF induced metabolic disorders of 60 days old offspring. 5 groups of Wistar rats, from gestation until weaning, received two doses of CPF pesticide: 1 mg/kg/day (CPF1 or 3.5 mg/kg/day (CPF3.5 with free access to inulin (10g/L in drinking water. Then male pups received the same treatment as dams. Metabolic profile, leptin sensitivity, insulin receptor (IR expression in liver, gut microbiota composition and short chain fatty acid composition (SCFAs in the colon, were analyzed at postnatal day 60 in the offspring (PND 60. CPF3.5 increased offspring's birth body weight (BW but decreased BW at PND60. Inulin supplementation restored the BW at PND 60 to control levels. Hyperinsulinemia and decrease in insulin receptor β in liver were seen in CPF1 exposed rats. In contrast, hyperglycemia and decrease in insulin level were found in CPF3.5 rats. Inulin restored the levels of some metabolic parameters in CPF groups to ranges comparable with the controls. The total bacterial population, short chain fatty acid (SCFA production and butyrate levels were enhanced in CPF groups receiving inulin. Our data indicate that developmental exposure to CPF interferes with metabolism with dose related effects evident at adulthood. By modulating microbiota population and fermentative activity, inulin corrected adult metabolic disorders of rats exposed to CPF during development. Prebiotics supply may be thus considered as a novel nutritional strategy to counteract insulin resistance and diabetes induced by a continuous pesticide exposure.

  11. Exposure Plus Response-Prevention Treatment of Bulimia Nervosa.

    Science.gov (United States)

    Leitenberg, Harold; And Others

    1988-01-01

    Evaluated exposure plus response-prevention treatment of bulimia nervosa among 47 women. Subjects were assigned to either exposure plus response-prevention in one setting, exposure plus response-prevention in multiple settings, cognitive-behavioral therapy, or waiting-list control conditions. Found three treatment groups improved significantly on…

  12. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: involvement of the adaptive antioxidant response.

    Science.gov (United States)

    Xue, Peng; Hou, Yongyong; Zhang, Qiang; Woods, Courtney G; Yarborough, Kathy; Liu, Huiyu; Sun, Guifan; Andersen, Melvin E; Pi, Jingbo

    2011-04-08

    There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 μM) inorganic arsenite (iAs³(+)) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs³(+) exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs³(+) exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4 expression may also be involved in arsenic-induced insulin resistance in adipocytes. Taken together our studies suggest that prolonged low-level iAs³(+) exposure activates the cellular adaptive oxidative stress response, which impairs insulin-stimulated ROS signaling that is involved in ISGU, and thus causes insulin resistance in adipocytes. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Lactate and pH evaluation in exhausted humans with prolonged TASER X26 exposure or continued exertion.

    Science.gov (United States)

    Ho, Jeffrey D; Dawes, Donald M; Cole, Jon B; Hottinger, Julie C; Overton, Kenneth G; Miner, James R

    2009-09-10

    Safety concerns about TASER Conducted Electrical Weapon (CEW) use and media reports of deaths after exposure have been expressed. CEWs are sometimes used on exhausted subjects to end resistance. The alternative is often a continued struggle. It is unclear if CEW use is metabolically different than allowing a continued struggle. We sought to determine if CEW exposure on exhausted humans caused worsening acidosis when compared with continued exertion. This was a prospective study of human volunteers recruited during a CEW training course. Volunteers were from several different occupations and represented a wide range of ages and body mass index characteristics. Medical histories, baseline pH and lactate values were obtained. Patients were assigned to one of four groups: 2 control groups consisting of Exertion only and CEW Exposure only, and the 2 experimental groups that were Exertion plus CEW Exposure and Exertion plus additional Exertion. Blood sampling occurred after Exertion and after any CEW exposure. This was repeated every 2-min until 20 min after protocol completion. Descriptive statistics were used to compare the four groups. The experimental groups and the control groups were compared individually at each time point using Wilcoxon rank sum tests. Lactate and pH association was assessed using multiple linear regression. Forty subjects were enrolled. There were no median pH or lactate differences between CEW Exposure groups at baseline, or between Exertion protocol groups immediately after completion. The CEW Exposure only group had higher pH and lower lactate values at all time points after exposure than the Exertion only group. After completing the Exertion protocol, there was no difference in the pH or lactate values between the continued Exertion group and the CEW Exposure group at any time points. Subjects who had CEW Exposure only had higher pH and lower lactate values than subjects who completed the Exertion protocol only. CEW exposure does not appear

  14. Comparison of phototoxic effects of pregnant rats exposure in Chernobyl NPP site and external prolonged exposure in the dose of 0.5 Gy

    International Nuclear Information System (INIS)

    Grigor'eva, E.E.; Rogov, Yu.I.

    2007-01-01

    The morphometric study showed that within the 10-kilometre zone of the Chernobyl NPP delay of the rat fetus cerebral cortex maturation occurred, whereas used in the experiment prolonged low-dose irradiation did not cause essential disorders of cortical ontogenesis.(authors)

  15. Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain

    OpenAIRE

    Wang Kate; Schins Roel PF; Cassee Flemming R; van Berlo Damien; Gerlofs-Nijland Miriam E; Campbell Arezoo

    2010-01-01

    Abstract Background The etiology and progression of neurodegenerative disorders depends on the interactions between a variety of factors including: aging, environmental exposures, and genetic susceptibility factors. Enhancement of proinflammatory events appears to be a common link in different neurological impairments, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Studies have shown a link between exposure to particulate matter (PM)...

  16. Therapeutic evaluation of prolonged infusions of β-lactam antibiotics in the treatment and management of critically ill patients

    Directory of Open Access Journals (Sweden)

    Jorge S. Amador

    2017-04-01

    Full Text Available Context: Critically ill patients has a large number of pathophysiological changes product of commitment and organ systems. Therefore, knowledge of the pharmacological properties of antimicrobials is essential to choose the best treatment. In order to optimize the response of antibiotic therapy and these drugs, new strategies have been proposed dosage, the most used drug application of the model, called: Pharmacokinetics/Pharmacodynamics (PK/PD. In the case of β-lactam antibiotics, the PK/PD model is known as time-dependent on the Minimum Inhibitory Concentration (Time > MIC. For optimal concentrations in β-lactam antibiotics, prolonged or continuous infusions, thus exposing the drug on the pathogen is achieved in a longer optimal concentrations through are used. Aims: To evaluate the therapeutic response of β-lactam antibiotics in critically ill patients with prolonged infusions by applying the model PK/ PD. Methods: Prospective observational study (concurrent cohort, taking as a control non-concurrent historic cohort, conducted for a period of seven months in the intensive care unit of the Hospital Clínico San Borja Arriarán (HCSBA, Santiago, Chile. Results: It was found a significant difference in number of days of hospitalization in ICU for the group bolus versus infusion group (12.5 ± 5.4 vs. 18 ± 9.7 days, IC: 1.5-9.5; p = 0.009. Conclusions: This study suggests that there would be a therapeutic advantage in the use of prolonged infusion in ICU stay duration.

  17. Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain.

    Science.gov (United States)

    Gerlofs-Nijland, Miriam E; van Berlo, Damien; Cassee, Flemming R; Schins, Roel P F; Wang, Kate; Campbell, Arezoo

    2010-05-17

    The etiology and progression of neurodegenerative disorders depends on the interactions between a variety of factors including: aging, environmental exposures, and genetic susceptibility factors. Enhancement of proinflammatory events appears to be a common link in different neurological impairments, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Studies have shown a link between exposure to particulate matter (PM), present in air pollution, and enhancement of central nervous system proinflammatory markers. In the present study, the association between exposure to air pollution (AP), derived from a specific source (diesel engine), and neuroinflammation was investigated. To elucidate whether specific regions of the brain are more susceptible to exposure to diesel-derived AP, various loci of the brain were separately analyzed. Rats were exposed for 6 hrs a day, 5 days a week, for 4 weeks to diesel engine exhaust (DEE) using a nose-only exposure chamber. The day after the final exposure, the brain was dissected into the following regions: cerebellum, frontal cortex, hippocampus, olfactory bulb and tubercles, and the striatum. Baseline levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 alpha (IL-1alpha) were dependent on the region analyzed and increased in the striatum after exposure to DEE. In addition, baseline level of activation of the transcription factors (NF-kappaB) and (AP-1) was also region dependent but the levels were not significantly altered after exposure to DEE. A similar, though not significant, trend was seen with the mRNA expression levels of TNF-alpha and TNF Receptor-subtype I (TNF-RI). Our results indicate that different brain regions may be uniquely responsive to changes induced by exposure to DEE. This study once more underscores the role of neuroinflammation in response to ambient air pollution, however, it is valuable to assess if and to

  18. Beyond Extinction: Prolonged Conditioning and Repeated Threat Exposure Abolish Contextual Renewal of Fear-Potentiated Startle Discrimination but Leave Expectancy Ratings Intact.

    Science.gov (United States)

    Leer, Arne; Haesen, Kim; Vervliet, Bram

    2018-01-01

    Extinction treatments decrease fear via repeated exposures to the conditioned stimulus (CS) and are associated with a return of fear. Alternatively, fear can be reduced via reductions in the perceived intensity of the unconditioned stimulus (US), e.g., through repeated exposures to the US. Promisingly, the few available studies show that repeated US exposures outperform standard extinction. US exposure treatments can decrease fear via two routes: (1) by weakening the CS-US association (extinction-like mechanism), and/or (2) by weakening the subjective US aversiveness (habituation-like mechanism). The current study further investigated the conditions under which US exposure treatment may reduce renewal, by adding a group in which CS-US pairings continued following fear acquisition. During acquisition, participants learned that one of two visual stimuli (CS+/CS-) predicted the occurrence of an aversive electrocutaneous stimulus (US). Next, the background context changed and participants received one of three interventions: repeated CS exposures, (2) repeated US exposures, or (3) continued CS-US pairings. Following repeated CS exposures, test presentations of the CSs in the original conditioning context revealed intact CS+/CS- differentiation in the fear-potentiated startle reflex, while the differentiation was abolished in the other two groups. Differential US expectancy ratings, on the other hand, were intact in all groups. Skin conductance data were inconclusive because standard context renewal following CS exposures did not occur. Unexpectedly, there was no evidence for a habituation-like process having taken place during US exposures or continued CS-US pairings. The results provide further evidence that US exposures outperform the standard extinction treatment and show that effects are similar when US exposures are part of CS-US pairings.

  19. Exposure and non-fear emotions: A randomized controlled study of exposure-based and rescripting-based imagery in PTSD treatment.

    Science.gov (United States)

    Langkaas, Tomas Formo; Hoffart, Asle; Øktedalen, Tuva; Ulvenes, Pål G; Hembree, Elizabeth A; Smucker, Mervin

    2017-10-01

    Interventions involving rescripting-based imagery have been proposed as a better approach than exposure-based imagery when posttraumatic stress disorder (PTSD) is associated with emotions other than fear. Prior research led to the study's hypotheses that (a) higher pretreatment non-fear emotions would predict relatively better response to rescripting as compared to exposure, (b) rescripting would be associated with greater reduction in non-fear emotions, and (c) pretreatment non-fear emotions would predict poor response to exposure. A clinically representative sample of 65 patients presenting a wide range of traumas was recruited from patients seeking and being offered PTSD treatment in an inpatient setting. Subjects were randomly assigned to 10 weeks of treatment involving either rescripting-based imagery (Imagery Rescripting; IR) or exposure-based imagery (Prolonged Exposure; PE). Patients were assessed on outcome and emotion measures at pretreatment, posttreatment and 12 months follow-up. Comparison to control benchmarks indicated that both treatments were effective, but no outcome differences between them appeared. None of the initial hypotheses were supported. The results from this study challenge previous observations and hypotheses about exposure mainly being effective for fear-based PTSD and strengthen the notion that exposure-based treatment is a generally effective treatment for all types of PTSD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Donor dopamine treatment limits pulmonary oedema and inflammation in lung allografts subjected to prolonged hypothermia

    NARCIS (Netherlands)

    Hanusch, Christine; Nowak, Kai; Toerlitz, Patrizia; Gill, Ishar S.; Song, Hui; Rafat, Neysan; Brinkkoetter, Paul T.; Leuvenink, Henri G.; Van Ackern, Klaus C.; Yard, Benito A.; Beck, Grietje C.

    2008-01-01

    Background. Endothelial barrier dysfunction severely compromises organ function after reperfusion. Because dopamine pretreatment improves hypothermia mediated barrier dysfunction, we tested the hypothesis that dopamine treatment of lung allografts positively affects tissue damage associated with

  1. Prior Trauma Exposure for Youth in Treatment Foster Care

    Science.gov (United States)

    Dorsey, Shannon; Burns, Barbara J.; Southerland, Dannia G.; Cox, Julia Revillion; Wagner, H. Ryan; Farmer, Elizabeth M. Z.

    2012-01-01

    Very little research has focused on rates of trauma exposure for youth in treatment foster care (TFC). Available research has utilized record review for assessing exposure, which presents limitations for the range of trauma types examined, as records are predominantly focused on abuse and neglect. The current study examines exposure rates and…

  2. University Counseling Center Use of Prolonged Exposure Therapy: In-Clinic Treatment for Students with PTSD

    Science.gov (United States)

    Bonar, Ted C.

    2015-01-01

    Students utilize university counseling center services to address distress related to post-traumatic stress disorder (PTSD). Since counseling centers services such as group work or general psychotherapy may not address specific PTSD-symptom reduction, centers often give community referrals in such cases. Evidence-based therapies (EBTs), including…

  3. Prolonged decrease of adipocyte size after rosiglitazone treatment in high- and low-fat-fed rats.

    Science.gov (United States)

    Johnson, Julia A; Trasino, Steven E; Ferrante, Anthony W; Vasselli, Joseph R

    2007-11-01

    The anti-diabetic thiazolidinediones (TZDs) stimulate adipocyte differentiation and decrease mean adipocyte size. However, whether these smaller, more insulin-sensitive adipocytes maintain their size after TZD therapy is discontinued has not been studied. Adult female Sprague-Dawley rats were fed a low-fat (10% fat) diet or, to elevate body weight (BW), a high-fat (HF) diet (45% fat) for 6 weeks. Rats were initially randomized to groups (n = 12) fed either low-fat or HF diets, with or without the TZD rosiglitazone (ROSI; 5 mg/kg per day), for 6 weeks. ROSI was then discontinued, and all animals were fed HF for another 6 weeks before sacrifice. Retroperitoneal (RP) adipose tissue morphology was determined from tissue collected by serial biopsies before and after 6 weeks of ROSI treatment and at sacrifice. Measures of BW and adiposity did not differ among groups 6 weeks after stopping ROSI treatment. However, during treatment, ROSI in both diets significantly decreased RP adipocyte size and increased RP DNA content, and these effects continued to be observed after discontinuing treatment. ROSI administration also decreased circulating insulin, leptin, and triglycerides and increased circulating adiponectin levels; however, these effects were reversed on stopping treatment. These results demonstrated that TZD-induced effects on adipocyte size and number were maintained after discontinuing treatment, even with consumption of an obesigenic diet. However, additional studies are needed to determine whether TZD-treated animals eventually achieve an adipocyte size similar to that of untreated animals at the expense of a higher BW.

  4. Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain

    Directory of Open Access Journals (Sweden)

    Wang Kate

    2010-05-01

    Full Text Available Abstract Background The etiology and progression of neurodegenerative disorders depends on the interactions between a variety of factors including: aging, environmental exposures, and genetic susceptibility factors. Enhancement of proinflammatory events appears to be a common link in different neurological impairments, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Studies have shown a link between exposure to particulate matter (PM, present in air pollution, and enhancement of central nervous system proinflammatory markers. In the present study, the association between exposure to air pollution (AP, derived from a specific source (diesel engine, and neuroinflammation was investigated. To elucidate whether specific regions of the brain are more susceptible to exposure to diesel-derived AP, various loci of the brain were separately analyzed. Rats were exposed for 6 hrs a day, 5 days a week, for 4 weeks to diesel engine exhaust (DEE using a nose-only exposure chamber. The day after the final exposure, the brain was dissected into the following regions: cerebellum, frontal cortex, hippocampus, olfactory bulb and tubercles, and the striatum. Results Baseline levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α and interleukin-1 alpha (IL-1α were dependent on the region analyzed and increased in the striatum after exposure to DEE. In addition, baseline level of activation of the transcription factors (NF-κB and (AP-1 was also region dependent but the levels were not significantly altered after exposure to DEE. A similar, though not significant, trend was seen with the mRNA expression levels of TNF-α and TNF Receptor-subtype I (TNF-RI. Conclusions Our results indicate that different brain regions may be uniquely responsive to changes induced by exposure to DEE. This study once more underscores the role of neuroinflammation in response to ambient air pollution

  5. Changes in the radiation sensitivity of mouse skin during fractionated and prolonged treatments

    International Nuclear Information System (INIS)

    Ruifrok, A.C.C.; Mason, K.A.; Hunter, N.; Thames, H.D.

    1994-01-01

    Reactions of the skin of the right thigh of mice were used as an experimental model to test possible changes in the radiosensitivity of mouse skin, as represented by changes in the linear-quadratic (LQ) model parameters α and β, as a function of fractionation interval and overall treatment time. In the first series of experiments, variable numbers of 3-Gy fractions with intervals of 6, 24 or 48 h were applied, followed by top-up doses to increase the skin damage to a level that could be scored. The results showed that mouse skin is more sensitive to 3-Gy fractions applied with 48-h intervals than to 3-Gy fractions applied with 6- or 24-h intervals. In the second series of experiments we used single-dose or fractonated test treatments for previously unirradiated mice and mice treated with priming doses of 10, 20 or 30 Gy given 1-18 days before the test treatment. The sensitivity appeared to be higher after intervals of 14-18 days than after 1-10 days after priming treatments of 20 and 30 Gy. The increased sensitivity 18 days after 20 Gy was mainly the result of an increase in the β component of the LQ model; higher values of α were also determined. We conclude that the radiosensitivity of mouse skin is higher during a radiation-induced proliferative response. 28 refs., 3 figs., 7 tabs

  6. A pilot randomized controlled trial of Dialectical Behavior Therapy with and without the Dialectical Behavior Therapy Prolonged Exposure protocol for suicidal and self-injuring women with borderline personality disorder and PTSD.

    Science.gov (United States)

    Harned, Melanie S; Korslund, Kathryn E; Linehan, Marsha M

    2014-04-01

    This study evaluates the efficacy of integrating PTSD treatment into Dialectical Behavior Therapy (DBT) for women with borderline personality disorder, PTSD, and intentional self-injury. Participants were randomized to DBT (n=9) or DBT with the DBT Prolonged Exposure (DBT PE) protocol (n=17) and assessed at 4-month intervals during the treatment year and 3-months post-treatment. Treatment expectancies, satisfaction, and completion did not differ by condition. In DBT+DBT PE, the DBT PE protocol was feasible to implement for a majority of treatment completers. Compared to DBT, DBT+DBT PE led to larger and more stable improvements in PTSD and doubled the remission rate among treatment completers (80% vs. 40%). Patients who completed the DBT PE protocol were 2.4 times less likely to attempt suicide and 1.5 times less likely to self-injure than those in DBT. Among treatment completers, moderate to large effect sizes favored DBT+DBT PE for dissociation, trauma-related guilt cognitions, shame, anxiety, depression, and global functioning. DBT with the DBT PE protocol is feasible, acceptable, and safe to administer, and may lead to larger improvements in PTSD, intentional self-injury, and other outcomes than DBT alone. The findings require replication in a larger sample. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Prolonged treatment with N-acetylcysteine and L-arginine restores gonadal function in patients with polycystic ovary syndrome.

    Science.gov (United States)

    Masha, A; Manieri, C; Dinatale, S; Bruno, G A; Ghigo, E; Martina, V

    2009-12-01

    Nitric oxide (NO) plays a wide spectrum of biological actions including a positive role in oocyte maturation and ovulation. Free radicals levels have been shown elevated in polycystic ovary syndrome (PCOS) and therefore would be responsible for quenching NO that, in turn, would play a role in determining oligo- or amenorrhea connoting PCOS. Eight patients with PCOS displaying oligo-amenorrhea from at least 1 yr underwent a combined treatment with N-acetylcysteine (NAC) (1200 mg/die) plus L-arginine (ARG) (1600 mg/die) for 6 months. Menstrual function, glucose and insulin levels, and, in turn, homeostasis model assessment (HOMA) index were monitored. Menstrual function was at some extent restored as indicated by the number of uterine bleedings under treatment (3.00, 0.18-5.83 vs 0.00, 0.00-0.83; p<0.02). Also, a well-defined biphasic pattern in the basal body temperature suggested ovulatory cycles. The HOMA index decreased under treatment (2.12, 1.46-4.42 vs 3.48, 1.62-5.95; p<0.05). In conclusion, this preliminary, open study suggests that prolonged treatment with NAC+ARG might restore gonadal function in PCOS. This effect seems associated to an improvement in insulin sensitivity.

  8. Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells.

    Science.gov (United States)

    Pavlikova, Nela; Smetana, Pavel; Halada, Petr; Kovar, Jan

    2015-10-01

    Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cell line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Prolonged utilization of proton pump inhibitors in patients with ischemic and valvular heart disease is associated with surgical treatments, weight loss and aggravates anemia.

    Science.gov (United States)

    Boban, Marko; Zulj, Marinko; Persic, Viktor; Medved, Igor; Zekanovic, Drazen; Vcev, Aleksandar

    2016-09-15

    Proton pump inhibitors (PPIs) are among the commonest drugs used nowadays. The aim of our study was to analyze prolonged utilization of proton pump inhibitors in medical therapy of patients with ischemic and valvular heart disease. Secondly, profile of utilization was scrutinized to patient characteristics and type of cardiovascular treatments. The study included consecutive patients scheduled for cardiovascular rehabilitation 2-6months after index cardiovascular treatment. Two hundred ninety-four patients (n=294/604; 48.7%) have been using proton pump inhibitor in their therapy after index cardiovascular treatment. Cardiovascular treatments were powerfully connected with utilization of PPIs; surgery 5.77 (95%-confidence intervals [CI]: 4.05-8.22; pvalvular heart disease utilized proton pump inhibitor in prolonged courses. Prolonged courses of PPIs were connected with existence and worsening of red blood count indexes, older age, lesser weight of patients and underutilization of cardioprotective drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Effect of leucine supplementation on fat free mass with prolonged hypoxic exposure during a 13-day trek to Everest Base Camp: a double-blind randomized study.

    Science.gov (United States)

    Wing-Gaia, Stacie L; Gershenoff, Dana C; Drummond, Micah J; Askew, E Wayne

    2014-03-01

    Loss of body weight and fat-free mass (FFM) are commonly noted with prolonged exposure to hypobaric hypoxia. Recent evidence suggests protein supplementation, specifically leucine, may potentially attenuate loss of FFM in subcaloric conditions during normoxia. The purpose of this study was to determine if leucine supplementation would prevent the loss of FFM in subcaloric conditions during prolonged hypoxia. Eighteen physically active male (n = 10) and female (n = 8) trekkers completed a 13-day trek in Nepal to Everest Base Camp with a mean altitude of 4140 m (range 2810-5364 m). In this double-blind study, participants were randomized to ingest either leucine (LEU) (7 g leucine, 93 kcal, 14.5 g whey-based protein) or an isocaloric isonitrogenous control (CON) (0.3 g LEU, 93 kcal, 11.3 g collagen protein) twice daily prior to meals. Body weight, body composition, and circumferences of bicep, thigh, and calf were measured pre- and post-trek. There was a significant time effect for body weight (-2.2% ± 1.7%), FFM (-1.7% ± 1.5%), fat mass (-4.0% ± 6.9%), and circumferences (p FFM (CON -2.1 ± 1.5%; LEU -1.2 ± 1.6%), fat mass (CON -2.9% ± 5.9%; LEU -5.4% ± 8.1%), or circumferences. Although a significant loss of body weight, FFM, and fat mass was noted in 13 days of high altitude exposure, FFM loss was not attenuated by leucine. Future studies are needed to determine if leucine attenuates loss of FFM with longer duration high altitude exposure.

  11. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    International Nuclear Information System (INIS)

    Xue, Peng; Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu; Sun, Guifan; Andersen, Melvin E.; Pi, Jingbo

    2011-01-01

    Highlights: → In 3T3-L1 adipocytes iAs 3+ decreases insulin-stimulated glucose uptake. → iAs 3+ attenuates insulin-induced phosphorylation of AKT S473. → iAs 3+ activates the cellular adaptive oxidative stress response. → iAs 3+ impairs insulin-stimulated ROS signaling. → iAs 3+ decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 μM) inorganic arsenite (iAs 3+ ) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs 3+ exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs 3+ exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4 expression may also be involved in arsenic-induced insulin resistance in

  12. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Peng [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); School of Public Health, China Medical University, Shenyang 110001 (China); Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Sun, Guifan [School of Public Health, China Medical University, Shenyang 110001 (China); Andersen, Melvin E. [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States)

    2011-04-08

    Highlights: {yields} In 3T3-L1 adipocytes iAs{sup 3+} decreases insulin-stimulated glucose uptake. {yields} iAs{sup 3+} attenuates insulin-induced phosphorylation of AKT S473. {yields} iAs{sup 3+} activates the cellular adaptive oxidative stress response. {yields} iAs{sup 3+} impairs insulin-stimulated ROS signaling. {yields} iAs{sup 3+} decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 {mu}M) inorganic arsenite (iAs{sup 3+}) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs{sup 3+} exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs{sup 3+} exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4

  13. Colorectal Transit and Volume During Treatment With Prolonged-release Oxycodone/Naloxone Versus Oxycodone Plus Macrogol 3350.

    Science.gov (United States)

    Poulsen, Jakob L; Mark, Esben B; Brock, Christina; Frøkjær, Jens B; Krogh, Klaus; Drewes, Asbjørn M

    2018-01-30

    Opioid-induced constipation (OIC) is the most common gastrointestinal (GI) side effect to opioid treatment. Opioid receptor antagonists against OIC have been introduced, but their efficacy has not been directly compared to conventional laxatives. Our aim was to compare symptoms and objective parameters of gut function in an experimental model of OIC during treatment with the opioid antagonist naloxone and oxycodone in prolonged-release (PR) formulation versus oxycodone plus macrogol 3350. In this randomized, double-blind, crossover trial 20 healthy men received a 5-day treatment of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Regional GI transit times and segmental colorectal transit were assessed with the Motilis 3D-Transit electromagnetic capsule system. Colorectal volumes were determined by MRI. OIC symptoms were assessed with validated questionnaires, along with stool frequency and consistency. Total colorectal volume did not change after 5 days' treatment with PR oxycodone/naloxone (941 vs 1036 mL; P = 0.091), but increased significantly after PR oxycodone plus macrogol treatment (912 vs 1123 mL; P transit times nor segmental colorectal transit differed between the treatments (all P > 0.05). The Patient Assessment of Constipation Symptom Questionnaire abdominal symptoms score was lower during PR oxycodone/naloxone compared to PR oxycodone plus macrogol (0.2 vs 3.2; P = 0.002). Stool frequency was lower during PR oxycodone/naloxone compared to PR oxycodone plus macrogol (4.2 vs 5.4; P = 0.035). PR oxycodone plus macrogol increases colorectal volume, but does not improve GI transit compared to PR oxycodone/naloxone. However, PR oxycodone/naloxone results in a lower abdominal symptom burden, despite higher stool frequency during macrogol treatment.

  14. High-dose radiation therapy alone for inoperable non-small cell lung cancer. Experience with prolonged overall treatment times

    International Nuclear Information System (INIS)

    Willers, H.; Wuerschmidt, F.; Buenemann, H.; Heilmann, H.P.

    1998-01-01

    The purpose of this study was to determine the impact of overall treatment time on long-term survival after high-dose radiation therapy alone for inoperable non-small cell lung cancer (NSCLC). Between 1978 and 1990, 229 patients with stage I-III disease and Karnofsky Performance Scores of 80-100 received a conventionally fractionated total dose of 70 Gy through a split-course technique. After a first treatment course of 40 or 50 Gy, a rest aging was performed and only patients without any contraindications, such as newly diagnosed distant metastases or serious deterioration of performance status, were given a second course. In 83% of patients this break lasted for 4-6 weeks. Overall treatment time ranged between 7 and 24 weeks (median 12 weeks). Median follow-up time was 6.6 years (range 4.0-9.3 years). Actuarial overall survival rates at 2 and 5 years were 28% and 7% respectively. Complete radiological tumor response was observed in 31% of patients, and was found to be the strongest positive predictor of survival with 2- and 5-year rates of 50% and 12% respectively compared with 17% and 4% for patients without complete response. Treatment duration was not found to be a significant prognostic factor in univariate or multivariate analysis. For overall treatment times of 7-11 weeks (n=50), 12 weeks (n=79) and >12 weeks (n=100), 5-year survival was 4%, 6%, and 8%, respectively (p=0.6). To conclude, in our experience and in contrast to other studies, prolonged overall treatment times in radiation therapy alone for inoperable NSCLC had no negative impact on long-term survival. It is hypothesized that accelerated tumor cell repopulation is absent in a significant number of these patients with the time-factor playing no apparent role for outcome of treatment. (orig.)

  15. Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells

    Energy Technology Data Exchange (ETDEWEB)

    Pavlikova, Nela, E-mail: nela.pavlikova@lf3.cuni.cz [Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic); Smetana, Pavel [Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic); Halada, Petr [Laboratory of Molecular Structure Characterization, Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague (Czech Republic); Kovar, Jan [Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic)

    2015-10-15

    Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cell line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. - Highlights: • Epidemiologic studies connect pollution with incidence of diabetes mellitus. • We explored the effect of DDT and DDE on protein expression in the NES2Y pancreatic beta cell line. • One month exposure to three sublethal concentrations of DDT and DDE was employed. • Expression of alpha-enolase, actin

  16. Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells

    International Nuclear Information System (INIS)

    Pavlikova, Nela; Smetana, Pavel; Halada, Petr; Kovar, Jan

    2015-01-01

    Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cell line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. - Highlights: • Epidemiologic studies connect pollution with incidence of diabetes mellitus. • We explored the effect of DDT and DDE on protein expression in the NES2Y pancreatic beta cell line. • One month exposure to three sublethal concentrations of DDT and DDE was employed. • Expression of alpha-enolase, actin

  17. Successful treatment of massive pulmonary embolism with prolonged catheter-directed thrombolysis.

    LENUS (Irish Health Repository)

    Kelly, Peter

    2012-02-03

    This is a case report of a young woman who presented with an extensive pulmonary embolism and echocardiographic evidence of right ventricular dysfunction. Although hemodynamically stable, the patient\\'s clinical condition failed to improve with standard heparin anticoagulation. Successful local catheter-directed thrombolysis was performed over an extended period of 48 h with regular monitoring of response to therapy by computed tomography-pulmonary angiography and echocardiography. To our knowledge, treatment of a pulmonary embolism by catheter-directed thrombolytic infusion over an extended period of 48 h has not previously been described.

  18. New approach for treatment of prolonged postoperative pain: APS Out-Patient Clinic.

    Science.gov (United States)

    Tiippana, Elina; Hamunen, Katri; Heiskanen, Tarja; Nieminen, Teija; Kalso, Eija; Kontinen, Vesa K

    2016-07-01

    Persistent postoperative pain (PPP) is a significant clinical problem. Several patient-related risk factors for PPP have been identified, including a previous chronic pain problem, young age, female gender and psychological vulnerability. Intra- and postoperative risk factors include surgical complications such as infections, haematoma, nerve damage and repeated surgery. As the length of hospital stay has been shortened, some patients may be discharged despite ongoing pain and insufficient analgesic medication. The challenge is to identify patients at high risk of developing PPP and to create a targeted care pathway to ensure effective and safe pain treatment especially in the subacute postoperative phase at home. This observational study describes the first two years of the Acute Pain Service Out-Patient Clinic (APS-OPC) at the Helsinki University Hospital. Patient characteristics, known risk factors, and details of treatment of PPP for the first 200 patients referred to our APS-OPC were retrospectively collected from the medical records. The APS-OPC clinic functions in close collaboration with the Multidisciplinary Pain Clinic (MPC), and the number of patients in need of physiotherapist, psychologist or psychiatrist counselling was recorded, as well as the number of patients referred to the MPC for further PPP management. Patients were referred to the APS-OPC from different surgical specialities, the two most common being thoracic and orthopaedic surgery. Seventy per cent of the patients (139/200) presented symptoms indicating neuropathic postsurgical pain. The patients had, on average, five risk factors for PPP. The median time from surgery to the first contact to the APS-OPC was two months, and the median duration of follow-up was 2.8 months (0-16 months). The median number of contacts with APS-OPC was 3 (range 1-14). Every fourth patient needed only one contact to the APS-OPC. Nineteen per cent of the patients had an appointment with the physiotherapist and 20

  19. Restless legs syndrome: a new entity of neuropathic pain? Treatment with prolonged release oxycodone/naloxone combination

    Directory of Open Access Journals (Sweden)

    Gemignani F

    2016-04-01

    Full Text Available Franco Gemignani,1 Andrea Melpignano,1,2 Giulia Milioli,1,2 Silvia Riccardi,1,2 Liborio Parrino1,2 1Neurology Unit, Department of Neurosciences, University of Parma, Parma, Italy; 2Sleep Disorders Center, Department of Neurosciences, University of Parma, Parma, Italy Abstract: Restless legs syndrome (RLS is a disorder of sensorimotor integration characterized by an urge to move the legs when at rest, especially at night or in the evening, which is relieved by movement. Sensory symptoms may be prominent, often exhibiting features consistent with neuropathic pain. Iron deficiency and genetic factors are implicated in RLS causation in most patients. The pathogenetic model of impaired circadian dopaminergic modulation of sensorimotor integration circuitry at the spinal level is fitting with the co-occurrence of movement disorders, sensory symptoms, and sleep disruption in RLS. Accordingly, levodopa and dopamine agonists are effective for RLS symptoms, which compensate for the impaired descending control by diencephalo-spinal dopa(minergic pathway. Dopamine agonists are usually indicated as the first-line therapy, but their use in long-term treatment is often complicated by augmentation and impulse control disorder, thus alpha-2-delta ligands also are now considered the first line of treatment. It has been recognized that endogenous opioid system is also involved in the mechanisms generating RLS, possibly through an impaired modulation of pain pathways. Opioids can be considered as an alternative therapy, particularly in patients with augmentation and/or refractory to other treatments. Recently introduced prolonged-release oxycodone–naloxone was efficacious for short-term treatment of patients with severe RLS inadequately controlled with previous treatment. It will be important to assess whether opioids, as well as other drugs, are especially effective in definite RLS subtypes such as the painful phenotype. Keywords: small fiber neuropathy

  20. Cardiomyocyte apoptosis vs autophagy with prolonged doxorubicin treatment: comparison with osteosarcoma cells.

    Science.gov (United States)

    Tacar, Oktay; Indumathy, Sivanjah; Tan, Mei Lin; Baindur-Hudson, Swati; Friedhuber, Anna M; Dass, Crispin R

    2015-02-01

    Doxorubicin (Dox) is a frontline chemotherapeutic against osteosarcoma (OS) that is plagued by side effects, particularly in the heart. The specific objective of this article is to investigate whether low-dose Dox treatment had pro-autophagic effects in cardiomyocytes as well as osteosarcoma cells. This study characterises apoptotic (Bax) and autophagic (Beclin-1) biomarker levels in human OS and cardiomyocyte cell lines as well as in various tissues when mice are exposed to low (1 mg/kg, thrice weekly) and high (3 mg/kg thrice weekly) dose Dox for a month. There was a decrease in Bax and increase in Beclin-1 in cardiac tissue in the high-dose group. Dox decreased Beclin-1 in the skin and liver, with no clear indication in the stomach, small intestine and testis. At low Dox doses of 10 and 100 nm in cardiomyocytes and OS cells, there is a pro-apoptotic effect, with a quicker response in the 100-nm condition, and a slower but steady increase of a pro-apoptotic response at the lower 10-nm dose. However, electron microscopy images revealed changes to human OS cells that resembled autophagy. Human prostate, breast and colorectal cells treated with 10-nm Dox showed ∼ 40% reduction in cell viability after 24 h. In culture, cells of both cardiomyocytes and OS revealed a predominant pro-apoptotic response at the expense of autophagy, although both seemed to be occurring in vivo. © 2014 Royal Pharmaceutical Society.

  1. An exploratory study: prolonged periods of binocular stimulation can provide an effective treatment for childhood amblyopia.

    Science.gov (United States)

    Knox, Pamela J; Simmers, Anita J; Gray, Lyle S; Cleary, Marie

    2012-02-21

    The purpose of the present study was to explore the potential for treating childhood amblyopia with a binocular stimulus designed to correlate the visual input from both eyes. Eight strabismic, two anisometropic, and four strabismic and anisometropic amblyopes (mean age, 8.5 ± 2.6 years) undertook a dichoptic perceptual learning task for five sessions (each lasting 1 hour) over the course of a week. The training paradigm involved a simple computer game, which required the subject to use both eyes to perform the task. A statistically significant improvement (t(₁₃) = 5.46; P = 0.0001) in the mean visual acuity (VA) of the amblyopic eye (AE) was demonstrated, from 0.51 ± 0.27 logMAR before training to 0.42 ± 0.28 logMAR after training with six subjects gaining 0.1 logMAR or more of improvement. Measurable stereofunction was established for the first time in three subjects with an overall significant mean improvement in stereoacuity after training (t(₁₃) =2.64; P = 0.02). The dichoptic-based perceptual learning therapy employed in the present study improved both the monocular VA of the AE and stereofunction, verifying the feasibility of a binocular approach in the treatment of childhood amblyopia.

  2. The treatment of exposure for VNEM calculations

    International Nuclear Information System (INIS)

    Beere, William

    2004-01-01

    The VNEM approach to solving multi assembly neutron calculations has been shown to accurately reproduce pin power distributions [1]. However, this high accuracy is only possible when the contents of a node are accurately known. This is generally the case for fresh fuel, but once fuel has been exposed its composition changes. Often these changes are described by only a few parameters per node, such as exposure and spectral history. This ignores any tilt or boundary effects for the node. This can have significant effect on the accuracy of any neutron calculation. So if accurate neutron flux and power distributions are required it is also necessary to accurately describe the effects of exposure in a reactor situation. Thus, it is desired to study possible methods to generate VNEM coefficients for a node in a reactor situation. In this report we will suggest a possible method for modelling exposure and spectral history effects. Other effects as void fraction or boron concentration will not be considered here. Special attention has been placed on the ability to accommodate differences in power and spectral spatial distributions. The spatial distributions of exposure and spectral history are modelled as a set of expansion functions based on a set of given functions and the results of infinite lattice calculations. This method is shown to be adequate in reproducing multi assembly cross section distributions. Thus, further testing is required to check its ability to generate VNEM coefficients and ultimately flux distributions for multi assembly calculations. (Author)

  3. Bronchopulmonary C-fibers' IL1RI contributes to the prolonged apneic response to intra-atrial injection of capsaicin by prenatal nicotinic exposure in rat pups

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Lei; Zhuang, Jianguo; Xu, Fadi, E-mail: fxu@lrri.org

    2016-07-15

    Prenatal nicotinic exposure (PNE) as a SIDS model reportedly sensitizes bronchopulmonary C-fibers (PCFs), contributing to the prolonged PCF-mediated apnea in rat pups, but the relevant mechanisms are not fully understood. Pulmonary IL-1β upregulated by cigarette smoke is known to stimulate or sensitize PCFs acting via IL-1 type I receptor (IL1RI) and inhibit inspiration frequency. Because of its upregulation observed in SIDS victims, we hypothesized that PNE increased pulmonary IL-1β release and IL1RI expression in pulmonary C-neurons via action on α7 nicotinic acetylcholine receptors (α7nAChR) to induce the prolonged PCF-mediated apnea. IL-1β in BALF and IL1RI in the nodose/jugular (N/J) ganglion and vagal pulmonary C-neurons retrogradely-traced were compared between Ctrl (saline) and PNE pups and among the vehicle-treated Ctrl and PNE and methyllycaconitine (a selective α7nAChR antagonist)-treated PNE pups. The effect of IL-1RI blockade (IL-1Ra) on the PCF-mediated apnea was also compared between Ctrl and PNE pups. PNE significantly elevated IL-1β in BALF and upregulated IL1RI gene and protein expression in N/J ganglia and gene in vagal pulmonary C-neurons. All of these responses were eliminated by pretreatment with blockade of α7nAChR. In addition, the prolonged PCF-mediated apnea in PNE pups was significantly shortened by right atrial bolus injection of IL-1Ra. We conclude that PNE enhances pulmonary IL-1β release and PCF IL1RI expression acting via α7nAChR in contributing to sensitization of PCFs and prolongation of the PCF-mediated apneic response. - Highlights: • PNE increased pulmonary IL-1β release and IL1R1 expression in the N/J ganglia. • PNE elevated IL1R1 mRNA in vagal pulmonary C-neurons. • Blockage of peripheral IL1R1 reduced the PNE-induced PCF sensitization. • PNE induced the changes in IL-1β and IL1R1 dependent on action of α7nAChR.

  4. Lack of mucosal immune reconstitution during prolonged treatment of acute and early HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Saurabh Mehandru

    2006-12-01

    Full Text Available During acute and early HIV-1 infection (AEI, up to 60% of CD4(+ T cells in the lamina propria of the lower gastrointestinal (GI tract are lost as early as 2-4 wk after infection. Reconstitution in the peripheral blood during therapy with highly active antiretroviral therapy (HAART is well established. However, the extent of immune reconstitution in the GI tract is unknown.Fifty-four AEI patients and 18 uninfected control participants underwent colonic biopsy. Forty of the 54 AEI patients were followed after initiation of antiretroviral therapy (18 were studied longitudinally with sequential biopsies over a 3-y period after beginning HAART, and 22 were studied cross sectionally after 1-7 y of uninterrupted therapy. Lymphocyte subsets, markers of immune activation and memory in the peripheral blood and GI tract were determined by flow cytometry and immunohistochemistry. In situ hybridization was performed in order to identify persistent HIV-1 RNA expression. Of the patients studied, 70% maintained, on average, a 50%-60% depletion of lamina propria lymphocytes despite 1-7 y of HAART. Lymphocytes expressing CCR5 and both CCR5 and CXCR4 were persistently and preferentially depleted. Levels of immune activation in the memory cell population, CD45RO+ HLA-DR+, returned to levels seen in the uninfected control participants in the peripheral blood, but were elevated in the GI tract of patients with persistent CD4+ T cell depletion despite therapy. Rare HIV-1 RNA-expressing cells were detected by in situ hybridization.Apparently suppressive treatment with HAART during acute and early infection does not lead to complete immune reconstitution in the GI mucosa in the majority of patients studied, despite immune reconstitution in the peripheral blood. Though the mechanism remains obscure, the data suggest that there is either viral or immune-mediated accelerated T cell destruction or, possibly, alterations in T cell homing to the GI tract. Although clinically

  5. Current health and preferences for life-prolonging treatments: an application of prospect theory to end-of-life decision making.

    Science.gov (United States)

    Winter, Laraine; Parker, Barbara

    2007-10-01

    As a substantial body of research attests, the acceptability of life-prolonging treatment (e.g., tube feeding) tends to be greater among people in worse health than among healthier ones. Because a decision for or against a life-prolonging treatment represents a choice between two prospects-life (usually in poor health) and death-we propose a decision model, Prospect Theory, as a theoretical account of this phenomenon. Prospect Theory postulates that pairs of distant prospects are less distinguishable than pairs of closer ones. Thus, to healthy individuals, the prospects of death and life in poor health would both be remote, and therefore, the distinction between them, small. To less healthy individuals, however, the difference between the same pairs of prospects would appear greater, and therefore, life-prolonging treatment may be more acceptable. In a cross-sectional study of 304 community-dwelling people, aged 60 years and over in the Philadelphia area, USA, preferences for 4 life-prolonging treatments in 9 health scenarios were examined in relation to participants' current health, operationalized as number of deficits in physical functioning. As predicted, less healthy people expressed stronger preferences for all life-prolonging treatments compared with healthier ones, with differences greatest in the worse-health scenarios. Preferences also varied by health scenario, with any treatment preferred in the better health scenarios. Treatment preferences did not differ by type of treatment, depressed mood or any demographic characteristic except race, with African-Americans expressing stronger treatment preferences. Implications for advance care planning are discussed.

  6. Acceleration of spontaneous intimal-subintimal changes in rabbit aorta by a prolonged moderate carbon monoxide exposure

    Energy Technology Data Exchange (ETDEWEB)

    Wanstrup, J; Kjeldsen, K; Astrup, P

    1969-01-01

    Rabbits were exposed to 90 ppM CO by volume (11% COHb) for 3 months. More exposed animals had areas in the heart with hyperemia and/or hemorrhages, a greater degree of fibrous plaque formation on the aorta, and definitely more intimal-subintimal changes, including focal subintimal edema, endothelial cellular proliferation and breakdown, splitting up of subintimal fibrils, and collagen formation. There were no macroscopic differences, except abnomal amounts of fluid in serous cavity in experimental animals indicating increased endothelial membrane permeability. Tissue hypoxia (carbon monoxide exposure) seems to play a basic role in the development of focal vascular changes of the atherosclerotic type.

  7. The Use of Dialectical Behavior Therapy and Prolonged Exposure to Treat Comorbid Dissociation and Self-Harm: The Case of a Client With Borderline Personality Disorder and Posttraumatic Stress Disorder.

    Science.gov (United States)

    Granato, Hollie F; Wilks, Chelsey R; Miga, Erin M; Korslund, Kathryn E; Linehan, Marsha M

    2015-08-01

    There is a high rate of comorbidity between borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD; Pagura et al., 2010). Preliminary studies have evaluated the treatment of PTSD in a BPD population and found positive outcomes for the integration of dialectical behavior therapy (DBT) and prolonged exposure (PE). This case study illustrates the implementation of a PE protocol into standard DBT treatment, specifically focusing on the management of self-harm and severe dissociation for a client with co-occurring PTSD and BPD. The client entered into treatment with severe and persistent dissociation and a recent history of self-harm, and the case includes consideration of two separate pauses in PTSD treatment related to elevated dissociation and self-harm behaviors. The client successfully completed the DBT PE protocol and results indicate significant improvements in PTSD symptoms as well as outcomes related to self-harm and dissociation. These findings demonstrate the efficacy of combining DBT with PE for clients with comorbid BPD and PTSD and exemplify how complex clients with BPD who present with severe dissociation and self-harm behavior can safely and successfully receive treatment for PTSD. © 2015 Wiley Periodicals, Inc.

  8. Agitation during prolonged mechanical ventilation at a long-term acute care hospital: risk factors, treatments, and outcomes.

    Science.gov (United States)

    O'Connor, Heidi; Al-Qadheeb, Nada S; White, Alexander C; Thaker, Vishal; Devlin, John W

    2014-01-01

    The prevalence, risk factors, treatment practices, and outcomes of agitation in patients undergoing prolonged mechanical ventilation (PMV) in the long-term acute care hospital (LTACH) setting are not well understood. We compared agitation risk factors, management strategies, and outcomes between patients who developed agitation and those who did not, in LTACH patients undergoing PMV. Patients admitted to an LTACH for PMV over a 1-year period were categorized into agitated and nonagitated groups. The presence of agitation risk factors, management strategies, and relevant outcomes were extracted and compared between the 2 groups. A total of 80 patients were included, 41% (33) with agitation and 59% (47) without. Compared to the nonagitated group, the agitated group had a lower Sequential Organ Failure Assessment score (P agitated group, use of benzodiazepines (P = .16), opioids (P = .11), or psychiatric evaluation (P = .90) was not. Weaning success, duration of LTACH stay, and daily costs were similar. Agitation among the LTACH patients undergoing PMV is associated with greater delirium and use of antipsychotics and restraints but does not influence weaning success or LTACH stay. Strategies focused on agitation prevention and treatment in this population need to be developed and formally evaluated. © The Author(s) 2013.

  9. Presymptomatic Treatment with Acetylcholinesterase Antisense Oligonucleotides Prolongs Survival in ALS (G93A-SOD1 Mice

    Directory of Open Access Journals (Sweden)

    Gotkine Marc

    2013-01-01

    Full Text Available Objective. Previous research suggests that acetylcholinesterase (AChE may be involved in ALS pathogenesis. AChE enzyme inhibitors can upregulate AChE transcription which in certain contexts can have deleterious (noncatalytic effects, making them theoretically harmful in ALS, whilst AChE antisense-oligonucleotides (mEN101, which downregulate AChE may be beneficial. Our aim was to investigate whether downregulation of AChE using mEN101 is beneficial in an ALS mouse model. Methods. ALS (G93A-SOD1 mice received saline, mEN101, inverse-EN101, or neostigmine. Treatments were administered from 5 weeks. Disease-onset and survival were recorded. Additional mice were sacrificed for pathological analysis at 15 weeks of age. In a follow-up experiment treatment was started at the symptomatic stage at a higher dose. Results. mEN101 given at the presymptomatic (but not symptomatic stage prolonged survival and attenuated motor-neuron loss in ALS mice. In contrast, neostigmine exacerbated the clinical parameters. Conclusions. These results suggest that AChE may be involved in ALS pathogenesis. The accelerated disease course with neostigmine suggests that any beneficial effects of mEN101 occur through a non-catalytic rather than cholinergic mechanism.

  10. Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice

    International Nuclear Information System (INIS)

    Hillerdal, Victoria; Ramachandran, Mohanraj; Leja, Justyna; Essand, Magnus

    2014-01-01

    Adoptive transfer of T cells genetically engineered with a chimeric antigen receptor (CAR) has successfully been used to treat both chronic and acute lymphocytic leukemia as well as other hematological cancers. Experimental therapy with CAR-engineered T cells has also shown promising results on solid tumors. The prostate stem cell antigen (PSCA) is a protein expressed on the surface of prostate epithelial cells as well as in primary and metastatic prostate cancer cells and therefore a promising target for immunotherapy of prostate cancer. We developed a third-generation CAR against PSCA including the CD28, OX-40 and CD3 ζ signaling domains. T cells were transduced with a lentivirus encoding the PSCA-CAR and evaluated for cytokine production (paired Student’s t-test), proliferation (paired Student’s t-test), CD107a expression (paired Student’s t-test) and target cell killing in vitro and tumor growth and survival in vivo (Log-rank test comparing Kaplan-Meier survival curves). PSCA-CAR T cells exhibit specific interferon (IFN)-γ and interleukin (IL)-2 secretion and specific proliferation in response to PSCA-expressing target cells. Furthermore, the PSCA-CAR-engineered T cells efficiently kill PSCA-expressing tumor cells in vitro and systemic treatment with PSCA-CAR-engineered T cells significantly delays subcutaneous tumor growth and prolongs survival of mice. Our data confirms that PSCA-CAR T cells may be developed for treatment of prostate cancer

  11. Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2016-05-01

    Full Text Available Background/Aims: Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Methods: Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks, which is known to involve inflammation and oxidative stress. DEP (0.5m/kg was intratracheally (i.t. instilled every 4th day for 4 weeks (7 i.t. instillation. Four days following the last exposure to either DEP or saline (control, various renal endpoints were measured. Results: While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Conclusion: Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic

  12. Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure.

    Science.gov (United States)

    Nemmar, Abderrahim; Karaca, Turan; Beegam, Sumaya; Yuvaraju, Priya; Yasin, Javed; Hamadi, Naserddine Kamel; Ali, Badreldin H

    2016-01-01

    Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP) on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks), which is known to involve inflammation and oxidative stress. DEP (0.5m/kg) was intratracheally (i.t.) instilled every 4th day for 4 weeks (7 i.t. instillation). Four days following the last exposure to either DEP or saline (control), various renal endpoints were measured. While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic renal failure. Our data provide biological plausibility that air

  13. Lung volumes identify an at-risk group in persons with prolonged secondhand tobacco smoke exposure but without overt airflow obstruction.

    Science.gov (United States)

    Arjomandi, Mehrdad; Zeng, Siyang; Geerts, Jeroen; Stiner, Rachel K; Bos, Bruce; van Koeverden, Ian; Keene, Jason; Elicker, Brett; Blanc, Paul D; Gold, Warren M

    2018-01-01

    Exposure to secondhand smoke (SHS) is associated with occult obstructive lung disease as evident by abnormal airflow indices representing small airway disease despite having preserved spirometry (normal forced expiratory volume in 1 s-to-forced vital capacity ratio, FEV 1 /FVC). The significance of lung volumes that reflect air trapping in the presence of preserved spirometry is unclear. To investigate whether lung volumes representing air trapping could determine susceptibility to respiratory morbidity in people with SHS exposure but without spirometric chronic obstructive pulmonary disease, we examined a cohort of 256 subjects with prolonged occupational SHS exposure and preserved spirometry. We elicited symptom prevalence by structured questionnaires, examined functional capacity (maximum oxygen uptake, VO 2max ) by exercise testing, and estimated associations of those outcomes with air trapping (plethysmography-measured residual volume-to-total lung capacity ratio, RV/TLC), and progressive air trapping with exertion (increase in fraction of tidal breathing that is flow limited on expiration during exercise (per cent of expiratory flow limitation, %EFL)). RV/TLC was within the predicted normal limits, but was highly variable spanning 22%±13% and 16%±8% across the increments of FEV 1 /FVC and FEV 1 , respectively. Respiratory complaints were prevalent (50.4%) with the most common symptom being ≥2 episodes of cough per year (44.5%). Higher RV/TLC was associated with higher OR of reporting respiratory symptoms (n=256; r 2 =0.03; p=0.011) and lower VO 2max (n=179; r 2 =0.47; p=0.013), and %EFL was negatively associated with VO 2max (n=32; r 2 =0.40; p=0.017). In those at risk for obstruction due to SHS exposure but with preserved spirometry, higher RV/TLC identifies a subgroup with increased respiratory symptoms and lower exercise capacity.

  14. Increase in hypothalamic AMPK phosphorylation induced by prolonged exposure to LPS involves ghrelin and CB1R signaling.

    Science.gov (United States)

    Rivas, Priscila M S; Vechiato, Fernanda M V; Borges, Beatriz C; Rorato, Rodrigo; Antunes-Rodrigues, Jose; Elias, Lucila L K

    2017-07-01

    Acute administration of lipopolysaccharide (LPS) from Gram-negative bacteria induces hypophagia. However, the repeated administration of LPS leads to desensitization of hypophagia, which is associated with increased hypothalamic p-AMPK expression. Because ghrelin and endocannabinoids modulate AMPK activity in the hypothalamus, we hypothesized that these neuromodulators play a role in the reversal of tolerance to hypophagia in rats under long-term exposure to LPS. Male Wistar rats were treated with single (1 LPS, 100μg/kg body weight, ip) or repeated injections of LPS over 6days (6 LPS). Food intake was reduced in the 1 LPS, but not in the 6 LPS group. 6 LPS rats showed an increased serum concentration of acylated ghrelin and reduced ghrelin receptor mRNA expression in the hypothalamus. Ghrelin injection (40μg/kg body weight, ip) increased food intake, body weight gain, p-AMPK hypothalamic expression, neuropeptide Y (NPY) and Agouti related peptide (AgRP) mRNA expression in control animals (Saline). However, in 6 LPS rats, ghrelin did not alter these parameters. Central administration of a CB1R antagonist (AM251, 200ng/μl in 5μl/rat) induced hypophagia in 6 LPS animals, suggesting that the endocannabinoid system contributes to preserved food intake during LPS tolerance. In the presence of AM251, the ability of ghrelin to phosphorylate AMPK in the hypothalamus of 6 LPS group was restored, but not its orexigenic effect. Our data highlight that the orexigenic effects of ghrelin require CB1R signaling downstream of AMPK activation. Moreover, CB1R-mediated pathways contribute to the absence of hypophagia during repeated exposure to endotoxin. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Changes in quality and biochemical parameters in 'Idared' apples during prolonged shelf life and 1-MCP treatment.

    Science.gov (United States)

    Bizjak, Jan; Slatnar, Ana; Stampar, Franci; Veberic, Robert

    2012-12-01

    In this study, changes in quality and various biochemical parameters of 'Idared' apples during prolonged shelf life period after ultra-low oxygen (ULO) storage were investigated. Additionally, the impact of the postharvest application of 1-methylcyclopropene (1-MCP) on different parameters was evaluated. After the harvest, apples were stored in the ULO storage for 6 months and then exposed to room temperature. Fruit firmness, peel color, and changes in sugars, organic acids and phenolics were monitored during the 3 weeks of shelf life. Malic acid, sugars and firmness decreased at room temperature. However, the color of the apples remained unchanged. The level of citric and ascorbic acid remained constant. Levels of phenolics in the peel increased significantly, whereas remained constant in the pulp of apples. 1-MCP treatment resulted in higher amounts of fructose and glucose, malic acid and greater firmness of apples. However, 1-MCP did not influence the phenolic content, ascorbic acid or color. The results obtained indicate that the content of different health-promoting compounds of apples does not change dramatically at room temperature. At the same time these results suggest that 1-MCP could be useful for maintaining certain quality and biochemical parameters and might extend the shelf life of apples.

  16. The parents' ability to take care of their baby as a factor in decisions to withhold or withdraw life-prolonging treatment in two Dutch NICUs

    NARCIS (Netherlands)

    Moratti, Sofia

    In The Netherlands, it is openly acknowledged that the parents' ability to take care of their child plays a role in the decision-making process over administration of life-prolonging treatment to severely defective newborn babies. Unlike other aspects of such decision-making process up until the

  17. Dynamic regulation of six histone H3 lysine (K) methyltransferases in response to prolonged anoxia exposure in a freshwater turtle.

    Science.gov (United States)

    Wijenayake, Sanoji; Hawkins, Liam J; Storey, Kenneth B

    2018-04-05

    The importance of histone lysine methylation is well established in health, disease, early development, aging, and cancer. However, the potential role of histone H3 methylation in regulating gene expression in response to extended periods of oxygen deprivation (anoxia) in a natural, anoxia-tolerant model system is underexplored. Red-eared sliders (Trachemys scripta elegans) can tolerate and survive three months of absolute anoxia and recover without incurring detrimental cellular damage, mainly by reducing the overall metabolic rate by 90% when compared to normoxia. Stringent regulation of gene expression is a vital aspect of metabolic rate depression in red-eared sliders, and as such we examined the anoxia-responsive regulation of histone lysine methylation in the liver during 5 h and 20 h anoxia exposure. Interestingly, this is the first study to illustrate the existence of histone lysine methyltransferases (HKMTs) and corresponding histone H3 lysine methylation levels in the liver of anoxia-tolerant red-eared sliders. In brief, H3K4me1, a histone mark associated with active transcription, and two corresponding histone lysine methyltransferases that modify H3K4me1 site, significantly increased in response to anoxia. On the contrary, H3K27me1, another transcriptionally active histone mark, significantly decreased during 20 h anoxia, and a transcriptionally repressive histone mark, H3K9me3, and the corresponding KMTs, similarly increased during 20 h anoxia. Overall, the results suggest a dynamic regulation of histone H3 lysine methylation in the liver of red-eared sliders that could theoretically aid in the selective upregulation of genes that are necessary for anoxia survival, while globally suppressing others to conserve energy. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Contribution of Hippocampal 5-HT3 Receptors in Hippocampal Autophagy and Extinction of Conditioned Fear Responses after a Single Prolonged Stress Exposure in Rats.

    Science.gov (United States)

    Wu, Zhong-Min; Yang, Li-Hua; Cui, Rong; Ni, Gui-Lian; Wu, Feng-Tian; Liang, Yong

    2017-05-01

    One of the hypotheses about the pathogenesis of posttraumatic stress disorder (PTSD) is the dysfunction of serotonin (5-HT) neurotransmission. While certain 5-HT receptor subtypes are likely critical for the symptoms of PTSD, few studies have examined the role of 5-HT 3 receptor in the development of PTSD, even though 5-HT 3 receptor is critical for contextual fear extinction and anxiety-like behavior. Therefore, we hypothesized that stimulation of 5-HT 3 receptor in the dorsal hippocampus (DH) could prevent hippocampal autophagy and the development of PTSD-like behavior in animals. To this end, we infused SR57227, selective 5-HT 3 agonist, into the DH after a single prolonged stress (SPS) treatment in rats. Three weeks later, we evaluated the effects of this pharmacological treatment on anxiety-related behaviors and extinction of contextual fear memory. We also accessed hippocampal autophagy and the expression of 5-HT 3A subunit, Beclin-1, LC3-I, and LC3-II in the DH. We found that SPS treatment did not alter anxiety-related behaviors but prolonged the extinction of contextual fear memory, and such a behavioral phenomenon was correlated with increased hippocampal autophagy, decreased 5-HT 3A expression, and increased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. Furthermore, intraDH infusions of SR57227 dose-dependently promoted the extinction of contextual fear memory, prevented hippocampal autophagy, and decreased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. These results indicated that 5-HT 3 receptor in the hippocampus may play a critical role in the pathogenesis of hippocampal autophagy, and is likely involved in the pathophysiology of PTSD.

  19. Prenatal nicotinic exposure upregulates pulmonary C-fiber NK1R expression to prolong pulmonary C-fiber-mediated apneic response

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Lei; Zhuang, Jianguo; Zang, Na; Lin, Yong [Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, NM (United States); Lee, Lu-Yuan [Department of Physiology, University of Kentucky, Lexington, KY (United States); Xu, Fadi, E-mail: fxu@lrri.org [Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, NM (United States); Department of Physiology, University of Kentucky, Lexington, KY (United States)

    2016-01-01

    Prenatal nicotinic exposure (PNE) prolongs bronchopulmonary C-fiber (PCF)-mediated apneic response to intra-atrial bolus injection of capsaicin in rat pups. The relevant mechanisms remain unclear. Pulmonary substance P and adenosine and their receptors (neurokinin-A receptor, NK1R and ADA{sub 1} receptor, ADA{sub 1}R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) expressed on PCFs are critical for PCF sensitization and/or activation. Here, we compared substance P and adenosine in BALF and NK1R, ADA{sub 1}R, and TRPV1 expression in the nodose/jugular (N/J) ganglia (vagal pulmonary C-neurons retrogradely labeled) between Ctrl and PNE pups. We found that PNE failed to change BALF substance P and adenosine content, but significantly upregulated both mRNA and protein TRPV1 and NK1R in the N/J ganglia and only NK1R mRNA in pulmonary C-neurons. To define the role of NK1R in the PNE-induced PCF sensitization, the apneic response to capsaicin (i.v.) without or with pretreatment of SR140333 (a peripheral and selective NK1R antagonist) was compared and the prolonged apnea by PNE significantly shortened by SR140333. To clarify if the PNE-evoked responses depended on action of nicotinic acetylcholine receptors (nAChRs), particularly α7nAChR, mecamylamine or methyllycaconitine (a general nAChR or a selective α7nAChR antagonist) was administrated via another mini-pump over the PNE period. Mecamylamine or methyllycaconitine eliminated the PNE-evoked mRNA and protein responses. Our data suggest that PNE is able to elevate PCF NK1R expression via activation of nAChRs, especially α7nAChR, which likely contributes to sensitize PCFs and prolong the PCF-mediated apneic response to capsaicin. - Highlights: • PNE upregulated NK1R and TRPV1 gene and protein expression in the N/J ganglia. • PNE only elevated NK1R mRNA in vagal pulmonary C-neurons. • Blockage of peripheral NK1R reduced the PNE-induced PCF sensitization. • PNE induced gene and protein

  20. Prenatal nicotinic exposure upregulates pulmonary C-fiber NK1R expression to prolong pulmonary C-fiber-mediated apneic response

    International Nuclear Information System (INIS)

    Zhao, Lei; Zhuang, Jianguo; Zang, Na; Lin, Yong; Lee, Lu-Yuan; Xu, Fadi

    2016-01-01

    Prenatal nicotinic exposure (PNE) prolongs bronchopulmonary C-fiber (PCF)-mediated apneic response to intra-atrial bolus injection of capsaicin in rat pups. The relevant mechanisms remain unclear. Pulmonary substance P and adenosine and their receptors (neurokinin-A receptor, NK1R and ADA 1 receptor, ADA 1 R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) expressed on PCFs are critical for PCF sensitization and/or activation. Here, we compared substance P and adenosine in BALF and NK1R, ADA 1 R, and TRPV1 expression in the nodose/jugular (N/J) ganglia (vagal pulmonary C-neurons retrogradely labeled) between Ctrl and PNE pups. We found that PNE failed to change BALF substance P and adenosine content, but significantly upregulated both mRNA and protein TRPV1 and NK1R in the N/J ganglia and only NK1R mRNA in pulmonary C-neurons. To define the role of NK1R in the PNE-induced PCF sensitization, the apneic response to capsaicin (i.v.) without or with pretreatment of SR140333 (a peripheral and selective NK1R antagonist) was compared and the prolonged apnea by PNE significantly shortened by SR140333. To clarify if the PNE-evoked responses depended on action of nicotinic acetylcholine receptors (nAChRs), particularly α7nAChR, mecamylamine or methyllycaconitine (a general nAChR or a selective α7nAChR antagonist) was administrated via another mini-pump over the PNE period. Mecamylamine or methyllycaconitine eliminated the PNE-evoked mRNA and protein responses. Our data suggest that PNE is able to elevate PCF NK1R expression via activation of nAChRs, especially α7nAChR, which likely contributes to sensitize PCFs and prolong the PCF-mediated apneic response to capsaicin. - Highlights: • PNE upregulated NK1R and TRPV1 gene and protein expression in the N/J ganglia. • PNE only elevated NK1R mRNA in vagal pulmonary C-neurons. • Blockage of peripheral NK1R reduced the PNE-induced PCF sensitization. • PNE induced gene and protein changes in

  1. Study On Irradiated Vietnam Java Rambutan Fruit Which Was Postharvested Treatment To Prolong The Shelflife For Export Purposes

    International Nuclear Information System (INIS)

    Nguyen Thuy Khanh; Nguyen Thi Ly; Doan Thi The; Cao Van Chung; Nguyen Van Phong

    2014-01-01

    The research - Study on irradiated Vietnam Java rambutan fruit which was postharvested treatment to prolong the shelflife for export purposes - was conducted at Research and Development Center for Radiation Technology and Southern Horticultural Research Institute for 12 months. On the one hand, the theme was to study the effects of low-dose radiation in the range (200-500 Gy) combined with two types of packaging: carton boxes and carton boxes + PE perforated cover 0.5% of the area bags. After 13 days monitoring in 13 o C, RH= 85-90% the results showed that Java rambutan fruit which was packed in carton boxes combined PE bags then irradiated at 300 Gy dose could limit the browning pericarp, dehydration through the rate of browning, browning level and the percentage of weight loss. Irradiated ramtuban also remains their pulp quality when testing the soluble solids, the titratable acidity and the ascorbic acid content. Irradiation did not affect the cell structure of pericarp and pulp by investigating the total ion leakage. On the other hand, the topics also examined the influence of some postharvest handling and low-dose radiation on Java rambutan. The results showed that pre-irradiation processing: hot water treatment at 43 o C in 6 minute, dipping in cloruacalxi 0.4% + citric acid 0.5% solution in 3 minutes, packed in carton boxes + PE bags and irradiated at 300 Gy dose capable of maintaining the quality which extends the shelflife of Java rambutan more 4 days when kept under conditions of 13 o C, RH= 85-90%. (author)

  2. The treatment progress of radiation dermatitis from external exposure

    International Nuclear Information System (INIS)

    Pu Wangyang; Liu Yulong

    2009-01-01

    Radiation dermatitis is often seen and is often a complication of radiation therapy of tumors. It is characterized by poor healing, stubborn relapse, and carcinogenesis.. The treatment include drug, physical therapy and surgery. This article describes the treatment progress of radiation dermatitis from external exposure. (authors)

  3. Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival.

    Science.gov (United States)

    Kadera, Brian E; Sunjaya, Dharma B; Isacoff, William H; Li, Luyi; Hines, O Joe; Tomlinson, James S; Dawson, David W; Rochefort, Matthew M; Donald, Graham W; Clerkin, Barbara M; Reber, Howard A; Donahue, Timothy R

    2014-02-01

    ), also correlated with OS. On multivariate Cox proportional hazard modeling of HP and prognostic biomarkers, only SMAD4 protein loss was significant (hazard ratio, 9.3; P=.004). Our approach to patients with LA/BR PDAC, which includes prolonged preoperative chemotherapy, is associated with a high incidence of LN-negative disease and excellent OS. After surgical resection, HP treatment response, perineural invasion, and SMAD4 status should help determine who should receive adjuvant therapy in this select subset of patients.

  4. Prolonged Treatment Duration is Required for Successful Helicobacter pylori Eradication with Proton Pump Inhibitor Triple Therapy in Canada

    Directory of Open Access Journals (Sweden)

    Carlo A Fallone

    2013-01-01

    Full Text Available BACKGROUND: Traditional seven-day proton pump inhibitor triple therapy for Helicobacter pylori eradication has recently shown disappointing results outside of Canada. Prolonging therapy may be associated with poorer compliance and, hence, may not have a better outcome in a real-world setting.

  5. Virtual reality exposure therapy in the treatment of driving phobia

    Directory of Open Access Journals (Sweden)

    Rafael Thomaz da Costa

    Full Text Available A growing number of researches has appeared on virtual reality exposure therapy (VRET to treat anxiety disorders. The purpose of this article was to review some evidences that support the VRET efficacy to treat driving phobia. The studies were identified through computerized search (PubMed/Medline, Web of Science, and Scielo databases from 1984 to 2007. Some findings are promising. Anxiety/avoidance ratings declined from pre to post-treatment. VRET may be used as a first step in the treatment of driving phobia, as long as it may facilitate the in vivo exposure, thus reducing risks and high costs of such exposure. Notwithstanding, more randomized/controlled clinical trials are required to prove its efficacy.

  6. Prolonged Exposures to Intermittent Hypoxia Promote Visceral White Adipose Tissue Inflammation in a Murine Model of Severe Sleep Apnea: Effect of Normoxic Recovery.

    Science.gov (United States)

    Gileles-Hillel, Alex; Almendros, Isaac; Khalyfa, Abdelnaby; Nigdelioglu, Recep; Qiao, Zhuanhong; Hamanaka, Robert B; Mutlu, Gökhan M; Akbarpour, Mahzad; Gozal, David

    2017-03-01

    Increased visceral white adipose tissue (vWAT) mass results in infiltration of inflammatory macrophages that drive inflammation and insulin resistance. Patients with obstructive sleep apnea (OSA) suffer from increased prevalence of obesity, insulin resistance, and metabolic syndrome. Murine models of intermittent hypoxia (IH) mimicking moderate-severe OSA manifest insulin resistance following short-term IH. We examined in mice the effect of long-term IH on the inflammatory cellular changes within vWAT and the potential effect of normoxic recovery (IH-R). Male C57BL/6J mice were subjected to IH for 20 weeks, and a subset was allowed to recover in room air (RA) for 6 or 12 weeks (IH-R). Stromal vascular fraction was isolated from epididymal vWAT and mesenteric vWAT depots, and single-cell suspensions were prepared for flow cytometry analyses, reactive oxygen species (ROS), and metabolic assays. IH reduced body weight and vWAT mass and IH-R resulted in catch-up weight and vWAT mass. IH-exposed vWAT exhibited increased macrophage counts (ATMs) that were only partially improved in IH-R. IH also caused a proinflammatory shift in ATMs (increased Ly6c(hi)(+) and CD36(+) ATMs). These changes were accompanied by increased vWAT insulin resistance with only partial improvements in IH-R. In addition, ATMs exhibited increased ROS production, altered metabolism, and changes in electron transport chain, which were only partially improved in IH-R. Prolonged exposures to IH during the sleep period induce pronounced vWAT inflammation and insulin resistance despite concomitant vWAT mass reductions. These changes are only partially reversible after 3 months of normoxic recovery. Thus, long-lasting OSA may preclude complete reversibility of metabolic changes. © Sleep Research Society (SRS) 2016. All rights reserved. For permissions, please email: journals.permissions@oup.com

  7. Prolonged infusion versus intermittent boluses of β-lactam antibiotics for treatment of acute infections: a meta-analysis.

    Science.gov (United States)

    Teo, Jocelyn; Liew, Yixin; Lee, Winnie; Kwa, Andrea Lay-Hoon

    2014-05-01

    The clinical advantages of prolonged (extended/continuous) infusion remain controversial. Previous studies and reviews have failed to show consistent clinical benefits of extending the infusion time. This meta-analysis sought to determine whether prolonged β-lactam infusions were associated with a reduction in mortality and improvement in clinical success. A search of PubMed, EMBASE and The Cochrane Library for randomised controlled trials (RCTs) and observational studies comparing prolonged infusion with intermittent bolus administration of the same antibiotic in hospitalised adult patients was conducted. Primary outcomes evaluated were mortality and clinical success. A total of 29 studies with 2206 patients (18 RCTs and 11 observational studies) were included in the meta-analysis. Compared with intermittent boluses, use of prolonged infusion appeared to be associated with a significant reduction in mortality [pooled relative risk (RR) = 0.66, 95% confidence interval (CI) 0.53-0.83] and improvement in clinical success (RR = 1.12, 95% CI 1.03-1.21). Statistically significant benefit was supported by non-randomised studies (mortality, RR = 0.57, 95% CI 0.43-0.76; clinical success, RR = 1.34, 95% CI 1.02-1.76) but not by RCTs (mortality, RR = 0.83, 95% CI 0.57-1.21; clinical success, RR = 1.05, 95% CI 0.99-1.12). The positive results from observational studies, especially in the face of increasing antibiotic resistance, serve to justify the imperative need to conduct a large-scale, well-designed, multicentre RCT involving critically ill patients infected with high minimum inhibitory concentration pathogens to clearly substantiate this benefit. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  8. A multi-level modeling approach examining PTSD symptom reduction during prolonged exposure therapy: moderating effects of number of trauma types experienced, having an HIV-related index trauma, and years since HIV diagnosis among HIV-positive adults.

    Science.gov (United States)

    Junglen, Angela G; Smith, Brian C; Coleman, Jennifer A; Pacella, Maria L; Boarts, Jessica M; Jones, Tracy; Feeny, Norah C; Ciesla, Jeffrey A; Delahanty, Douglas L

    2017-11-01

    People living with HIV (PLWH) have extensive interpersonal trauma histories and higher rates of posttraumatic stress disorder (PTSD) than the general population. Prolonged exposure (PE) therapy is efficacious in reducing PTSD across a variety of trauma samples; however, research has not examined factors that influence how PTSD symptoms change during PE for PLWH. Using multi-level modeling, we examined the potential moderating effect of number of previous trauma types experienced, whether the index trauma was HIV-related or not, and years since HIV diagnosis on PTSD symptom reduction during a 10-session PE protocol in a sample of 51 PLWH. In general, PTSD symptoms decreased linearly throughout the PE sessions. Experiencing more previous types of traumatic events was associated with a slower rate of PTSD symptom change. In addition, LOCF analyses found that participants with a non-HIV-related versus HIV-related index trauma had a slower rate of change for PTSD symptoms over the course of PE. However, analyses of raw data decreased this finding to marginal. Years since HIV diagnosis did not impact PTSD symptom change. These results provide a better understanding of how to tailor PE to individual clients and aid clinicians in approximating the rate of symptom alleviation. Specifically, these findings underscore the importance of accounting for trauma history and index trauma type when implementing a treatment plan for PTSD in PLWH.

  9. Virtual reality exposure in the treatment of social phobia.

    Science.gov (United States)

    Klinger, Evelyne; Légeron, Patrick; Roy, Stéphane; Chemin, Isabelle; Lauer, Françoise; Nugues, Pierre

    2004-01-01

    Social phobia is one of the most frequent psychiatric disorders and is accessible to two forms of scientifically validated treatments: anti-depressant drugs and cognitive-behavioral therapies. Graded exposure to feared social situations (either in vivo or by imagining the situations) is fundamental to obtain an improvement of the anxious symptoms. Virtual reality (VR) may be an alternative to these standard exposure techniques and seems to bring significant advantages by allowing exposures to numerous and varied situations. Moreover studies have shown that human subjects are appropriately sensitive to virtual environments. This chapter reports the definition of a VR-based clinical protocol and a study to treat social phobia using virtual reality techniques. The virtual environments used in the treatment reproduce four situations that social phobics feel the most threatening: performance, intimacy, scrutiny and assertiveness. With the help of the therapist, the patient learns adapted cognitions and behaviors when coping with social situations, with the aim of reducing her or his anxiety in the corresponding real life situations. Some studies have been carried out using virtual reality in the treatment of fear of public speaking, which is only a small part of the symptomatology of most of social phobic patients. The novelty of our work is to address a larger group of situations that the phobic patients experience with high anxiety. In our protocol, the efficacy of the virtual reality treatment is compared to well established and well validated group cognitive-behavioral treatment.

  10. Virtual Reality Exposure Therapy for Treatment of Dental Phobia.

    Science.gov (United States)

    Gujjar, Kumar Raghav; Sharma, Ratika; Jongh, Ad De

    2017-05-01

    popularity as an effective treatment for anxiety disorders. The purpose of this article is to determine the applicability of VRET in the treatment of dental phobia of two patients. Two case examples of female dental patients, aged 56 and 24 years, who met the criteria for dental phobia according to the Phobia Checklist, illustrate the use of VRET in the dental setting. VRET that is used as a psychological treatment for dental fear and dental phobia can potentially be given by a non-specialist (for example dental assistant), thereby making it a cost-effective therapy for the treatment of dental phobia. Clinical relevance: This article is the first of its kind to demonstrate Virtual Reality Exposure Therapy (VRET) in the treatment of dental anxiety.

  11. Active-imaginal exposure: examination of a new behavioral treatment for cynophobia (dog phobia)

    NARCIS (Netherlands)

    Rentz, T.O.; Powers, M.B.; Smits, J.A.J.; Cougle, J.R.; Telch, M.J.

    2003-01-01

    The aims of this study were to investigate exposure-based treatments for cynophobia (dog phobia) and to test a newly developed hybrid imaginal exposure treatment that we have named active imaginal exposure. The treatment introduces an in vivo coping component to imaginal exposure whereby the patient

  12. [The prevention and treatment of suppurative-inflammatory complications in the bronchopulmonary system during prolonged artificial ventilation].

    Science.gov (United States)

    Mozhaev, G A; Tikhonovskiĭ, I Iu

    1992-01-01

    The use of physical methods, namely low frequency magnetic field in critically ill patients under respiratory therapy made it possible to prevent and in case of their development to effectively treat pyoinflammatory bronchopulmonary complications that accompany prolonged controlled lung ventilation. The results obtained were due to the elimination of an unfavourable effect of controlled lung ventilation on natural resistance and immune response of the respiratory tract because of normalization of physicochemical properties of the tracheobronchial tree secretion, enhanced functional capacities of phagocytes, repaired bonds between cellular and humoral local immunity in the lungs.

  13. In utero exposure to heat stress during late gestation has prolonged effects on the activity patterns and growth of dairy calves.

    Science.gov (United States)

    Laporta, J; Fabris, T F; Skibiel, A L; Powell, J L; Hayen, M J; Horvath, K; Miller-Cushon, E K; Dahl, G E

    2017-04-01

    Exposure to heat stress during late gestation exerts negative carryover effects on the postnatal performance of the calf. In this study, we evaluated the health, growth, and activity patterns of calves born to cows exposed to heat stress (HT, provided only shade, n = 31) or cooling (CL, fans, soakers, and shade, n = 29) during late gestation (∼46 d, maternal dry period). Calves' body weight, rectal temperature, suckling reflex, and movement scores were recorded at birth, and calves were fed 6.6 L of maternal colostrum in 2 meals. Blood samples were collected at birth (before feeding), 24 h after birth, and at d 10 and 28 of age. Calves were housed in individual pens, fed pasteurized milk (6 L/d), and had ad libitum access to grain and water until weaning (49 d). Activity was assessed during the first week of life (wk 1), at weaning (wk 7), and in the first week postweaning (wk 8) using electronic data loggers. Health and body weight were monitored weekly. At birth, calves born to CL cows were heavier (41.9 vs. 39.1 ± 0.8 kg), their temperature was lower (38.9 vs. 39.3 ± 0.08°C), and they were more efficient at absorbing IgG than HT calves. Suckling reflex and movement score at birth were not different between groups, but calves born to CL cows spent more time (50 min/d) standing in the first week of life as a result of longer standing bouts. In wk 7 and 8, calves born to CL cows had less frequent standing bouts than HT heifers, but CL heifers maintained greater total daily standing time (36 min/d) due to longer (7 min/bout) standing bouts. All calves were healthy, but HT heifers tended to have higher (looser) fecal scores on d 10. Heifers born from CL cows gained 0.2 kg/d more from birth to weaning, weighed 4 kg more at weaning, and had greater concentrations of IGF-1 than HT calves, particularly on d 28. In utero heat stress during late gestation had immediate and prolonged effects on passive immunity, growth, and activity patterns in dairy calves. Copyright

  14. Prolonging the duration of masseter muscle reduction by adjusting the masticatory movements after the treatment of masseter muscle hypertrophy with botulinum toxin type a injection.

    Science.gov (United States)

    Wei, Jiao; Xu, Hua; Dong, Jiasheng; Li, Qingfeng; Dai, Chuanchang

    2015-01-01

    Botulinum toxin type A (BTX-A) is widely used for the clinical treatment of masseteric hypertrophy. Until now, few reports have discussed how to prolong the duration of its effectiveness. This study evaluated that purposely adjusting the masticatory movements is possible of postponing the masseter muscle rehypertrophy. Ninety-eight patients were randomly and equally divided into 2 groups, and 35 U BTX-A per side was injected into the masseters. The thickness and volume of the masticatory muscles were measured by ultrasound and computerized tomography, respectively. Patients in Group 1 were instructed to strengthen their masticatory effort during the denervated atrophic stage of the masseter (the interval was evaluated by real-time ultrasound monitoring), whereas patients in Group 2 were not given this instruction. When the masseter muscle began to recover, patients in both groups were instructed to reduce their chewing. The duration of the masseter muscle rehypertrophy was significantly prolonged in Group 1 patients. The thickness and the volume of the other masticatory muscles were significantly increased in Group 1 but were either slightly decreased or insignificantly different in Group 2. Purposely strengthening masticatory muscle movement during the denervated atrophic stage of the masseter can prolong the duration of masseter rehypertrophy.

  15. Prolonged conservative treatment or 'early' surgery in sciatica caused by a lumbar disc herniation: rationale and design of a randomized trial [ISRCT 26872154

    Science.gov (United States)

    Peul, Wilco C; van Houwelingen, Hans C; van der Hout, Wilbert B; Brand, Ronald; Eekhof, Just AH; Tans, Joseph ThJ; Thomeer, Ralph TWM; Koes, Bart W

    2005-01-01

    Background The design of a randomized multicenter trial is presented on the effectiveness of a prolonged conservative treatment strategy compared with surgery in patients with persisting intense sciatica (lumbosacral radicular syndrome). Methods/design Patients presenting themselves to their general practitioner with disabling sciatica lasting less than twelve weeks are referred to the neurology outpatient department of one of the participating hospitals. After confirmation of the diagnosis and surgical indication MRI scanning is performed. If a distinct disc herniation is discerned which in addition covers the clinically expected site the patient is eligible for randomization. Depending on the outcome of the randomization scheme the patient will either be submitted to prolonged conservative care or surgery. Surgery will be carried out according to the guidelines and between six and twelve weeks after onset of complaints. The experimental therapy consists of a prolonged conservative treatment under supervision of the general practitioner, which may be followed by surgical intervention in case of persisting or progressive disability. The main primary outcome measure is the disease specific disability of daily functioning. Other primary outcome measures are perceived recovery and intensity of legpain. Secondary outcome measures encompass severity of complaints, quality of life, medical consumption, absenteeism, costs and preference. The main research question will be answered at 12 months after randomization. The total follow-up period covers two years. Discussion Evidence is lacking concerning the optimal treatment of lumbar disc induced sciatica. This pragmatic randomized trial, focusses on the 'timing' of intervention, and will contribute to the decision of the general practictioner and neurologist, regarding referral of patients for surgery. PMID:15707491

  16. Prolonged first-line PEG-asparaginase treatment in pediatric acute lymphoblastic leukemia in the NOPHO ALL2008 protocol-Pharmacokinetics and antibody formation

    DEFF Research Database (Denmark)

    Tram Henriksen, Louise; Gottschalk Højfeldt, Sofie; Schmiegelow, Kjeld

    2017-01-01

    BACKGROUND: As pegylated asparaginase is becoming the preferred first-line asparaginase preparation in the chemotherapy regimens of childhood acute lymphoblastic leukemia (ALL), there is a need to evaluate this treatment. METHODS: The aim of this study was to evaluate the pharmacokinetics...... of prolonged upfront biweekly PEG-asparaginase (where PEG is polyethylene glycol) treatment by measuring serum l-asparaginase activity and formation of anti-PEG-asparaginase antibodies. A total of 97 evaluable patients (1-17 years), diagnosed with ALL, and treated according to the NOPHO ALL2008 protocol (where...... NOPHO is Nordic Society of Paediatric Haematology and Oncology) were included. In the NOPHO ALL2008 protocol, patients are randomized to 8 or 15 doses of intramuscular PEG-asparaginase (Oncaspar(®) ) 1,000 IU/m²/dose, at 2-week or 6-week intervals with a total of 30-week treatment (Clinical trials...

  17. Clinical Outcome with Oral Linezolid and Rifampin Following Recurrent Methicillin-Resistant Staphylococcus aureus Bacteremia Despite Prolonged Vancomycin Treatment

    Directory of Open Access Journals (Sweden)

    Jon-David Schwalm

    2004-01-01

    Full Text Available Drug-resistant Gram-positive bacteria, especially Staphylococcus aureus, are emerging as the predominant organisms involved in both nosocomial and community-acquired infections. Since the 1980s, vancomycin has been the first-line antibiotic used to treat methicillin-resistant S aureus. However, allergy and intolerance to vancomycin, the increasing number of vancomycin clinical failures and the existence of vancomycin intermediate-susceptible isolates of S aureus suggest that new antibiotics are needed. This paper reports the only known case of a successful clinical outcome with long term oral linezolid and rifampin therapy in the management of recurrent and persistent methicillin-resistant S aureus bacteremia with metastatic infections despite prolonged vancomycin use. More than two years since the initiation of linezolid and rifampin, the study patient has been clinically well with no evidence of adverse drug reactions including cytopenia and hepatic toxicities. Physicians must be aware of the novel developments in antibiotic therapy to treat drug-resistant bacterial infections.

  18. Complete Response after Treatment with Neoadjuvant Chemoradiation with Prolonged Chemotherapy for Locally Advanced, Unresectable Adenocarcinoma of the Pancreas

    Directory of Open Access Journals (Sweden)

    Tiffany A. Pompa

    2017-01-01

    Full Text Available Surgery is the only chance for cure in pancreatic ductal adenocarcinoma. In unresectable, locally advanced pancreatic cancer (LAPC, the National Comprehensive Cancer Network (NCCN suggests chemotherapy and consideration for radiation in cases of unresectable LAPC. Here we present a rare case of unresectable LAPC with a complete histopathological response after chemoradiation followed by surgical resection. A 54-year-old female presented to our clinic in December 2013 with complaints of abdominal pain and 30-pound weight loss. An MRI demonstrated a mass in the pancreatic body measuring 6.2×3.2 cm; biopsy revealed proven ductal adenocarcinoma. Due to splenic vein/artery and contiguous celiac artery encasement, she was deemed surgically unresectable. She was started on FOLFIRINOX therapy (three cycles, intensity modulated radiation to a dose of 54 Gy in 30 fractions concurrent with capecitabine, followed by FOLFIRI, and finally XELIRI. After 8 cycles of ongoing XELIRI completed in March 2015, restaging showed a remarkable decrease in tumor size, along with PET-CT revealing no FDG-avid uptake. She was reevaluated by surgery and taken for definitive resection. Histopathological evaluation demonstrated a complete R0 resection and no residual tumor. Based on this patient and literature review, this strategy demonstrates potential efficacy of neoadjuvant chemoradiation with prolonged chemotherapy, followed by surgery, which may improve outcomes in patients deemed previously unresectable.

  19. Work-related limitations and return-to-work experiences in prolonged fatigue: workers' perspectives before and after vocational treatment

    NARCIS (Netherlands)

    Joosen, Margot C. W.; Frings-Dresen, Monique H. W.; Sluiter, Judith K.

    2011-01-01

    To gain insight into fatigued workers' perspectives regarding work experience before and after receiving vocational rehabilitation (VR) treatments. A qualitative survey was conducted using semi-structured interviews with 21 fatigued workers who attended an outpatient multi-component VR treatment.

  20. Increasing the efficacy of cue exposure treatment in preventing relapse of addictive behavior.

    Science.gov (United States)

    Havermans, Remco C; Jansen, Anita T M

    2003-07-01

    Theoretically, cue exposure treatment should be able to prevent relapse by extinguishing conditioned drug responding (e.g. cue-elicited craving). According to contemporary learning theory, though, extinction does not eliminate conditioned responding. Analogous cue exposure with response prevention (CERP) as a treatment of addictive behavior might not eliminate the learned relation between drug-related cues and drug use. This does not necessarily mean that cue exposure cannot successfully prevent relapse. Various suggestions for increasing the efficacy of cue exposure treatment are being discussed from a contemporary learning theory perspective. It is suggested that cue exposure treatment incorporating retrieval cues can be a beneficial treatment in preventing relapse of addictive behavior.

  1. Exposure assessment of residents living near a wood treatment plant

    International Nuclear Information System (INIS)

    Dahlgren, James; Warshaw, Raphael; Horsak, Randy D.; Parker, Frank M. III; Takhar, Harpreet

    2003-01-01

    We report the results of environmental sampling and modeling in a neighborhood adjacent to a wood processing plant. This plant used creosote and pentachlorophenol (PCP) to treat wood for over 70 years. Between 1999 and 2001, environmental samples were obtained to quantify the level of environmental contamination from the wood processing plant. Blood from 10 residents was measured for chlorinated dioxins and dibenzofurans. Soil sediment samples from drainage ditches and attic/dust samples from nearby residents' homes were tested for polychlorinated dioxins, furans, and polycyclic aromatic hydrocarbons (PAH). The dioxin congeners analysis of the 10 residents revealed elevated valued for octachlorodibenzo-p-dioxin and heptachlorodibenzo-p-dioxin compatible with PCP as the source. The levels of carcinogenic PAHs were higher than background levels and were similar to soil contamination on wood preserving sites. Wipe sampling in the kitchens of 11 homes revealed that 20 of the 33 samples were positive for octachlorinated dioxins with a mean value of 10.27 ng/m 2 . The soil, ditch samples, and positive wipe samples from the homes indicate a possible ongoing route of exposure to the contaminants in the homes of these residents. Modeled air exposure estimated for the wood processing waste chemicals indicate some air exposure to combustion products. The estimated air levels for benzo(a)pyrene and tetrachlorodibenzodiozin in this neighborhood exceeded the recommended levels for these compounds in some states. The quantitative data presented suggest a significant contamination of a neighborhood by wood processing waste chemicals. These findings suggest the need for more stringent regulations on waste discharges from wood treatment plants

  2. Enzyme pretreatment of fats, oil and grease from restaurant waste to prolong septic soil treatment system effectiveness.

    Science.gov (United States)

    Dong, Younsuk; Safferman, Steven I; Ostahowski, Jeff; Herold, Tom; Panter, Ronald

    2017-01-02

    When a fast-food restaurant's wastewater containing fats, oil and grease (FOG) is discharged into a collection system, it builds up over time and clogs pipes. Similarly, when such wastewater flows into a septic soil treatment system, it adheres to the surface of inlet pipes, gravel/distribution media and soil, restricting the flow and eventually clogging the septic soil treatment system. In this study, an enzymatic pretreatment system was tested on wastewater from a fast-food restaurant to determine its effectiveness in preventing septic soil treatment system clogging. This system used aeration equipment, baffles and a one-time inoculum that excretes enzymes to reduce the molecular weight and number of double bonds associated with FOG. FOG containing triglycerides having lower molecular weights and fewer double bonds are less sticky. The enzymatic pretreatment system was found to cause these changes as verified by measuring the types of triglycerides (compounds in FOG) using liquid chromatography/mass spectrometry. A unique bench-scale septic soil treatment system (soil trench) was also used. Each contained six soil moisture sensors to enable the determination of moisture saturation trends among the five tested conditions: sanitary wastewater only, a combination of sanitary and kitchen wastewater, enzymatically pretreated sanitary and kitchen wastewater, kitchen wastewater, and enzymatically pretreated kitchen wastewater. For all influent types, a significant amount of FOG and other pollutants were removed, regardless of the initial concentrations. Moisture sensor readings showed differences among the tested conditions, indicating that septic soil treatment system clogging was delayed. Inspection of the influent pipe and gravel at the end of testing verified these differences as did the measurements of volatile solids.

  3. Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy.

    Science.gov (United States)

    Norrholm, Seth Davin; Jovanovic, Tanja; Gerardi, Maryrose; Breazeale, Kathryn G; Price, Matthew; Davis, Michael; Duncan, Erica; Ressler, Kerry J; Bradley, Bekh; Rizzo, Albert; Tuerk, Peter W; Rothbaum, Barbara O

    2016-07-01

    Baseline cue-dependent physiological reactivity may serve as an objective measure of posttraumatic stress disorder (PTSD) symptoms. Additionally, prior animal model and psychological studies would suggest that subjects with greatest symptoms at baseline may have the greatest violation of expectancy to danger when undergoing exposure based psychotherapy; thus treatment approaches which enhanced the learning under these conditions would be optimal for those with maximal baseline cue-dependent reactivity. However methods to study this hypothesis objectively are lacking. Virtual reality (VR) methodologies have been successfully employed as an enhanced form of imaginal prolonged exposure therapy for the treatment of PTSD. Our goal was to examine the predictive nature of initial psychophysiological (e.g., startle, skin conductance, heart rate) and stress hormone responses (e.g., cortisol) during presentation of VR-based combat-related stimuli on PTSD treatment outcome. Combat veterans with PTSD underwent 6 weeks of VR exposure therapy combined with either d-cycloserine (DCS), alprazolam (ALP), or placebo (PBO). In the DCS group, startle response to VR scenes prior to initiation of treatment accounted for 76% of the variance in CAPS change scores, p < 0.001, in that higher responses predicted greater changes in symptom severity over time. Additionally, baseline cortisol reactivity was inversely associated with treatment response in the ALP group, p = 0.04. We propose that baseline cue-activated physiological measures will be sensitive to predicting patients' level of response to exposure therapy, in particular in the presence of enhancement (e.g., DCS). Published by Elsevier Ltd.

  4. Impacted maxillary central incisor: surgical exposure and orthodontic treatment.

    Science.gov (United States)

    Pinho, Teresa; Neves, Manuel; Alves, Célia

    2011-08-01

    This case report describes the treatment of a patient with a horizontally impacted maxillary central incisor, a canine in the same quadrant, and an inclusion tendency. Due to severe crowing in the maxilla and the Class II molar relationship on the impaction side, a 2-stage treatment plan was developed. In the first stage, the right first premolar and deciduous canine were extracted; this allowed enough space for the eruption of the maxillary right permanent canine. The second stage included surgical exposure and traction of the impacted central incisor with a fixed orthodontic appliance. An excisional uncovering technique was needed to expose the impacted incisor. After it erupted, an apically positioned partial-thickness flap was used to add keratinized attached gingiva in the area surrounding the crown, initially located in an area of unattached gingiva. The patient finished treatment with a normal and stable occlusion between the maxillary and mandibular arches and an adequate width of attached gingiva. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  5. Demonstrating the Efficacy of Group Prolonged Exposure Treatment of PTSD in OEF/OIF/OND Male Veterans

    Science.gov (United States)

    2015-12-01

    anxiety reactions to trauma memories , so that memories or situations no longer result in anxious arousal to trauma followed by escape or avoidance...Group (PEG) or Present-Centered Therapy (PCT) group. The goal of the PEG therapy is to promote emotional processing of the trauma memory and desensitize...symptoms compared to the Present-Centered Therapy control group. Hypothesis 2. While subjects in both groups will improve in self-reported overall PTSD

  6. Limitation of life-sustaining treatment in patients with prolonged admission to the ICU. Current situation in Spain as seen from the EPIPUSE Study.

    Science.gov (United States)

    Hernández-Tejedor, A; Martín Delgado, M C; Cabré Pericas, L; Algora Weber, A

    2015-10-01

    Limitation of life-sustaining treatment (LLST) is a recommended practice in certain circumstances. Limitation practices are varied, and their application differs from one center to another. The present study evaluates the current situation of LLST practices in patients with prolonged admission to the ICU who suffer worsening of their condition. A prospective, observational cohort study was carried out. Seventy-five Spanish ICUs. A total of 589 patients suffering 777 complications or adverse events with organ function impairment after day 7 of admission, during a three-month recruitment period. The timing of limitation, the subject proposing LLST, the degree of agreement within the team, the influence of LLST upon the doctor-patient-family relationship, and the way in which LLST is implemented. LLST was proposed in 34.3% of the patients presenting prolonged admission to the ICU with severe complications. The incidence was higher in patients with moderate to severe lung disease, cancer, immunosuppressive treatment or dependence for basic activities of daily living. LLST was finally implemented in 97% of the cases in which it was proposed. The decision within the medical team was unanimous in 87.9% of the cases. The doctor-patient-family relationship usually does not change or even improves in this situation. LLST in ICUs is usually carried out under unanimous decision of the medical team, is performed more frequently in patients with severe comorbidity, and usually does not have a negative impact upon the relationship with the patients and their families. Copyright © 2013 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  7. ActRII blockade protects mice from cancer cachexia and prolongs survival in the presence of anti-cancer treatments.

    Science.gov (United States)

    Hatakeyama, Shinji; Summermatter, Serge; Jourdain, Marie; Melly, Stefan; Minetti, Giulia C; Lach-Trifilieff, Estelle

    2016-01-01

    Cachexia affects the majority of patients with advanced cancer and is associated with reduced treatment tolerance, response to therapy, quality of life, and life expectancy. Cachectic patients with advanced cancer often receive anti-cancer therapies against their specific cancer type as a standard of care, and whether specific ActRII inhibition is efficacious when combined with anti-cancer agents has not been elucidated yet. In this study, we evaluated interactions between ActRII blockade and anti-cancer agents in CT-26 mouse colon cancer-induced cachexia model. CDD866 (murinized version of bimagrumab) is a neutralizing antibody against the activin receptor type II (ActRII) preventing binding of ligands such as myostatin and activin A, which are involved in cancer cachexia. CDD866 was evaluated in association with cisplatin as a standard cytotoxic agent or with everolimus, a molecular-targeted agent against mammalian target of rapamycin (mTOR). In the early studies, the treatment effect on cachexia was investigated, and in the additional studies, the treatment effect on progression of cancer and the associated cachexia was evaluated using body weight loss or tumor volume as interruption criteria. Cisplatin accelerated body weight loss and tended to exacerbate skeletal muscle loss in cachectic animals, likely due to some toxicity of this anti-cancer agent. Administration of CDD866 alone or in combination with cisplatin protected from skeletal muscle weight loss compared to animals receiving only cisplatin, corroborating that ActRII inhibition remains fully efficacious under cisplatin treatment. In contrast, everolimus treatment alone significantly protected the tumor-bearing mice against skeletal muscle weight loss caused by CT-26 tumor. CDD866 not only remains efficacious in the presence of everolimus but also showed a non-significant trend for an additive effect on reversing skeletal muscle weight loss. Importantly, both combination therapies slowed down time

  8. Soil microbial community responses to acid exposure and neutralization treatment.

    Science.gov (United States)

    Shin, Doyun; Lee, Yunho; Park, Jeonghyun; Moon, Hee Sun; Hyun, Sung Pil

    2017-12-15

    Changes in microbial community induced by acid shock were studied in the context of potential release of acids to the environment due to chemical accidents. The responses of microbial communities in three different soils to the exposure to sulfuric or hydrofluoric acid and to the subsequent neutralization treatment were investigated as functions of acid concentration and exposure time by using 16S-rRNA gene based pyrosequencing and DGGE (Denaturing Gradient Gel Electrophoresis). Measurements of soil pH and dissolved ion concentrations revealed that the added acids were neutralized to different degrees, depending on the mineral composition and soil texture. Hydrofluoric acid was more effectively neutralized by the soils, compared with sulfuric acid at the same normality. Gram-negative ß-Proteobacteria were shown to be the most acid-sensitive bacterial strains, while spore-forming Gram-positive Bacilli were the most acid-tolerant. The results of this study suggest that the Gram-positive to Gram-negative bacterial ratio may serve as an effective bio-indicator in assessing the impact of the acid shock on the microbial community. Neutralization treatments helped recover the ratio closer to their original values. The findings of this study show that microbial community changes as well as geochemical changes such as pH and dissolved ion concentrations need to be considered in estimating the impact of an acid spill, in selecting an optimal remediation strategy, and in deciding when to end remedial actions at the acid spill impacted site. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Limited prolonged effects of rifaximin treatment on irritable bowel syndrome-related differences in the fecal microbiome and metabolome.

    Science.gov (United States)

    Zeber-Lubecka, Natalia; Kulecka, Maria; Ambrozkiewicz, Filip; Paziewska, Agnieszka; Goryca, Krzysztof; Karczmarski, Jakub; Rubel, Tymon; Wojtowicz, Wojciech; Mlynarz, Piotr; Marczak, Lukasz; Tomecki, Roman; Mikula, Michal; Ostrowski, Jerzy

    2016-09-02

    Irritable bowel syndrome (IBS) is a chronic functional disorder and its development may be linked, directly and indirectly, to intestinal dysbiosis. Here we investigated the interactions between IBS symptoms and the gut microbiome, including the relation to rifaximin (1200 mg daily; 11.2 g per a treatment). We recruited 72 patients, including 31 with IBS-D (diarrhea), 11 with IBS-C (constipation), and 30 with IBS-M (mixed constipation and diarrhea) and 30 healthy controls (HCs). Of them, 68%, 64%, and 53% patients with IBS-D, IBS-C, and IBS-M, respectively, achieved 10-12 week-term improvement after the rifaximin treatment. Stool samples were collected before and after the treatment, and fecal microbiotic profiles were analyzed by deep sequencing of 16S rRNA, while stool metabolic profiles were studied by hydrogen 1-nuclear magnetic resonance ((1)H-NMR) and gas chromatography-mass spectrometry (GC-MS). Of 26 identified phyla, only Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria were consistently found in all samples. Bacteroidetes was predominant in fecal samples from HCs and IBS-D and IBS-M subjects, whereas Firmicutes was predominant in samples from IBS-C subjects. Species richness, but not community diversity, differentiated all IBS patients from HCs. Metabolic fingerprinting, using NMR spectra, distinguished HCs from all IBS patients. Thirteen metabolites identified by GC-MS differed HCs and IBS patients. However, neither metagenomics nor metabolomics analyses identified significant differences between patients with and without improvement after treatment.

  10. The Cruelest Cure? Ethical Issues in the Implementation of Exposure-Based Treatments

    Science.gov (United States)

    Olatunji, Bunmi O.; Deacon, Brett J.; Abramowitz, Jonathan S.

    2009-01-01

    Numerous studies have provided supportive evidence for the efficacy of exposure-based treatments for many psychological disorders. However, surprisingly few therapists use exposure therapy in the clinical setting. Although the limited use of exposure-based treatments may be partially attributable to a shortage of suitably trained therapists,…

  11. Synchrotron macro ATR-FTIR microspectroscopic analysis of silica nanoparticle-embedded polyester coated steel surfaces subjected to prolonged UV and humidity exposure.

    Directory of Open Access Journals (Sweden)

    Jitraporn Vongsvivut

    Full Text Available Surface modification of polymers and paints is a popular and effective way to enhance the properties of these materials. This can be achieved by introducing a thin coating that preserves the bulk properties of the material, while protecting it from environmental exposure. Suitable materials for such coating technologies are inorganic oxides, such as alumina, titania and silica; however, the fate of these materials during long-term environmental exposure is an open question. In this study, polymer coatings that had been enhanced with the addition of silica nanoparticles (SiO2NPs and subsequently subjected to environmental exposure, were characterized both before and after the exposure to determine any structural changes resulting from the exposure. High-resolution synchrotron macro ATR-FTIR microspectroscopy and surface topographic techniques, including optical profilometry and atomic force microscopy (AFM, were used to determine the long-term effect of the environment on these dual protection layers after 3 years of exposure to tropical and sub-tropical climates in Singapore and Queensland (Australia. Principal component analysis (PCA based on the synchrotron macro ATR-FTIR spectral data revealed that, for the 9% (w/w SiO2NP/polymer coating, a clear discrimination was observed between the control group (no environmental exposure and those samples subjected to three years of environmental exposure in both Singapore and Queensland. The PCA loading plots indicated that, over the three year exposure period, a major change occurred in the triazine ring vibration in the melamine resins. This can be attributed to the triazine ring being very sensitive to hydrolysis under the high humidity conditions in tropical/sub-tropical environments. This work provides the first direct molecular evidence, acquired using a high-resolution mapping technique, of the climate-induced chemical evolution of a polyester coating. The observed changes in the surface

  12. Synchrotron macro ATR-FTIR microspectroscopic analysis of silica nanoparticle-embedded polyester coated steel surfaces subjected to prolonged UV and humidity exposure.

    Science.gov (United States)

    Vongsvivut, Jitraporn; Truong, Vi Khanh; Al Kobaisi, Mohammad; Maclaughlin, Shane; Tobin, Mark J; Crawford, Russell J; Ivanova, Elena P

    2017-01-01

    Surface modification of polymers and paints is a popular and effective way to enhance the properties of these materials. This can be achieved by introducing a thin coating that preserves the bulk properties of the material, while protecting it from environmental exposure. Suitable materials for such coating technologies are inorganic oxides, such as alumina, titania and silica; however, the fate of these materials during long-term environmental exposure is an open question. In this study, polymer coatings that had been enhanced with the addition of silica nanoparticles (SiO2NPs) and subsequently subjected to environmental exposure, were characterized both before and after the exposure to determine any structural changes resulting from the exposure. High-resolution synchrotron macro ATR-FTIR microspectroscopy and surface topographic techniques, including optical profilometry and atomic force microscopy (AFM), were used to determine the long-term effect of the environment on these dual protection layers after 3 years of exposure to tropical and sub-tropical climates in Singapore and Queensland (Australia). Principal component analysis (PCA) based on the synchrotron macro ATR-FTIR spectral data revealed that, for the 9% (w/w) SiO2NP/polymer coating, a clear discrimination was observed between the control group (no environmental exposure) and those samples subjected to three years of environmental exposure in both Singapore and Queensland. The PCA loading plots indicated that, over the three year exposure period, a major change occurred in the triazine ring vibration in the melamine resins. This can be attributed to the triazine ring being very sensitive to hydrolysis under the high humidity conditions in tropical/sub-tropical environments. This work provides the first direct molecular evidence, acquired using a high-resolution mapping technique, of the climate-induced chemical evolution of a polyester coating. The observed changes in the surface topography of the

  13. Arginase treatment prevents the recovery of canine lymphoma and osteosarcoma cells resistant to the toxic effects of prolonged arginine deprivation.

    Science.gov (United States)

    Wells, James W; Evans, Christopher H; Scott, Milcah C; Rütgen, Barbara C; O'Brien, Timothy D; Modiano, Jaime F; Cvetkovic, Goran; Tepic, Slobodan

    2013-01-01

    Rapidly growing tumor cells require a nutrient-rich environment in order to thrive, therefore, restricting access to certain key amino acids, such as arginine, often results in the death of malignant cells, which frequently display defective cell cycle check-point control. Healthy cells, by contrast, become quiescent and remain viable under arginine restriction, displaying full recovery upon return to arginine-rich conditions. The use of arginase therapy to restrict available arginine for selectively targeting malignant cells is currently under investigation in human clinical trials. However, the suitability of this approach for veterinary uses is unexplored. As a prelude to in vivo studies in canine malignancies, we examined the in vitro effects of arginine-deprivation on canine lymphoid and osteosarcoma cell lines. Two lymphoid and 2 osteosarcoma cell lines were unable to recover following 6 days of arginine deprivation, but all remaining cell lines displayed full recovery upon return to arginine-rich culture conditions. These remaining cell lines all proved susceptible to cell death following the addition of arginase to the cultures. The lymphoid lines were particularly sensitive to arginase, becoming unrecoverable after just 3 days of treatment. Two of the osteosarcoma lines were also susceptible over this time-frame; however the other 3 lines required 6-8 days of arginase treatment to prevent recovery. In contrast, adult progenitor cells from the bone marrow of a healthy dog were able to recover fully following 9 days of culture in arginase. Over 3 days in culture, arginase was more effective than asparaginase in inducing the death of lymphoid lines. These results strongly suggest that short-term arginase treatment warrants further investigation as a therapy for lymphoid malignancies and osteosarcomas in dogs.

  14. Arginase treatment prevents the recovery of canine lymphoma and osteosarcoma cells resistant to the toxic effects of prolonged arginine deprivation.

    Directory of Open Access Journals (Sweden)

    James W Wells

    Full Text Available Rapidly growing tumor cells require a nutrient-rich environment in order to thrive, therefore, restricting access to certain key amino acids, such as arginine, often results in the death of malignant cells, which frequently display defective cell cycle check-point control. Healthy cells, by contrast, become quiescent and remain viable under arginine restriction, displaying full recovery upon return to arginine-rich conditions. The use of arginase therapy to restrict available arginine for selectively targeting malignant cells is currently under investigation in human clinical trials. However, the suitability of this approach for veterinary uses is unexplored. As a prelude to in vivo studies in canine malignancies, we examined the in vitro effects of arginine-deprivation on canine lymphoid and osteosarcoma cell lines. Two lymphoid and 2 osteosarcoma cell lines were unable to recover following 6 days of arginine deprivation, but all remaining cell lines displayed full recovery upon return to arginine-rich culture conditions. These remaining cell lines all proved susceptible to cell death following the addition of arginase to the cultures. The lymphoid lines were particularly sensitive to arginase, becoming unrecoverable after just 3 days of treatment. Two of the osteosarcoma lines were also susceptible over this time-frame; however the other 3 lines required 6-8 days of arginase treatment to prevent recovery. In contrast, adult progenitor cells from the bone marrow of a healthy dog were able to recover fully following 9 days of culture in arginase. Over 3 days in culture, arginase was more effective than asparaginase in inducing the death of lymphoid lines. These results strongly suggest that short-term arginase treatment warrants further investigation as a therapy for lymphoid malignancies and osteosarcomas in dogs.

  15. Prolonged survival of patients with non-small-cell lung cancer with leptomeningeal carcinomatosis in the modern treatment era.

    Science.gov (United States)

    Riess, Jonathan W; Nagpal, Seema; Iv, Michael; Zeineh, Michael; Gubens, Matthew A; Ramchandran, Kavitha; Neal, Joel W; Wakelee, Heather A

    2014-05-01

    Leptomeningeal carcinomatosis (LM) is a severe complication of non-small-cell lung cancer (NSCLC) historically associated with poor prognosis. New chemotherapeutic and targeted treatments could potentially affect the natural history of LM. Patients with a pathologic diagnosis of NSCLC with LM treated at Stanford between 2003 and 2011 were identified via institutional databases and medical records. LM was defined by cerebrospinal fluid (CSF) that was positive for malignant cells or by LM enhancement on magnetic resonance imaging with gadolinium contrast. Retrospective, landmark analyses were performed to estimate survival. Statistical analyses were performed using SAS Enterprise Guide, version 4.3. LM was identified in 30 patients. All cases were adenocarcinoma; 60% of patients had a known or suspected driver mutation. The mean age was 58 years. Of the 30 patients, 67% were women; 70% were nonsmokers; 27% initially presented with LM; 84% received systemic treatment at or after development of LM; and 53% of these patients received modern systemic therapy for their LM, defined as a regimen containing pemetrexed, bevacizumab, or a tyrosine kinase inhibitor. Mean overall survival after LM diagnosis was 6 months (95% CI, 3-12). Patients who received modern systemic therapy for LM had decreased hazard of death (hazard ratio [HR], 0.24; P = .007). In this retrospective, single-institution analysis, median survival with LM was higher compared with historical experience. Patients who received modern systemic therapy for their LM had particularly good outcomes. These data provide evidence for improving survival outcomes in the modern treatment era for this difficult-to-treat complication. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Combined treatment with immunoadsorption and rituximab leads to fast and prolonged clinical remission in difficult-to-treat pemphigus vulgaris.

    Science.gov (United States)

    Behzad, M; Möbs, C; Kneisel, A; Möller, M; Hoyer, J; Hertl, M; Eming, R

    2012-04-01

    Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune bullous disorder which is characterized by blisters and erosions of the skin and mucous membranes. A frequently applied first-line therapy for PV consists of systemic corticosteroids (CS) combined with immunosuppressive agents. In refractory cases, novel therapeutic strategies such as immunoadsorption (IA) and the anti-CD20 antibody rituximab (Rtx) aim at directly interfering with pathogenic autoantibodies (auto-Abs). To investigate the long-term efficacy of IA in combination with Rtx in patients with difficult-to-treat PV, we assessed the clinical response to treatment by monitoring the Autoimmune Bullous Skin Disorder Intensity Score, IgG auto-Abs against desmoglein 1 and 3 (Dsg1 and Dsg3) and the dose of systemic CS. We retrospectively analysed clinical and serological parameters of 10 patients with difficult-to-treat PV who received IA at 4-week intervals, followed by Rtx either twice at 1000 mg or four times at 375mg m(-2) . During a 12-month follow-up period, CS were tapered according to the individual clinical status. Six months after the first IA treatment eight of 10 patients were in complete remission on therapy while one patient showed a partial response and one patient was unresponsive to the treatment. At 12 months, six of eight patients were in complete remission on therapy, one patient showed stable disease and one patient had relapsed. Overall, anti-Dsg3 IgG and anti-Dsg1 IgG auto-Abs correlated well with the clinical activity and systemic CS were tapered gradually. The present findings show that the combination of IA and Rtx induces rapid clinical remission and long-term control in difficult-to-treat pemphigus. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

  17. Homologous Recombination Repair Signaling in Chemical Carcinogenesis: Prolonged Particulate Hexavalent Chromium Exposure Suppresses the Rad51 Response in Human Lung Cells

    Science.gov (United States)

    Qin, Qin; Xie, Hong; Wise, Sandra S.; Browning, Cynthia L.; Thompson, Kelsey N.; Holmes, Amie L.; Wise, John Pierce

    2014-01-01

    The aim of this study was to focus on hexavalent chromium, [Cr(VI)], a chemical carcinogen and major public health concern, and consider its ability to impact DNA double strand break repair. We further focused on particulate Cr(VI), because it is the more potent carcinogenic form of Cr(VI). DNA double strand break repair serves to protect cells against the detrimental effects of DNA double strand breaks. For particulate Cr(VI), data show DNA double strand break repair must be overcome for neoplastic transformation to occur. Acute Cr(VI) exposures reveal a robust DNA double strand break repair response, however, longer exposures have not been considered. Using the comet assay, we found longer exposures to particulate zinc chromate induced concentration-dependent increases in DNA double strand breaks indicating breaks were occurring throughout the exposure time. Acute (24 h) exposure induced DNA double strand break repair signaling by inducing Mre11 foci formation, ATM phosphorylation and phosphorylated ATM foci formation, Rad51 protein levels and Rad51 foci formation. However, longer exposures reduced the Rad51 response. These data indicate a major chemical carcinogen can simultaneously induce DNA double strand breaks and alter their repair and describe a new and important aspect of the carcinogenic mechanism for Cr(VI). PMID:25173789

  18. Post-exposure treatment with nasal atropine methyl bromide protects against microinstillation inhalation exposure to sarin in guinea pigs

    International Nuclear Information System (INIS)

    Che, Magnus M.; Conti, Michele; Chanda, Soma; Boylan, Megan; Sabnekar, Praveena; Rezk, Peter; Amari, Ethery; Sciuto, Alfred M.; Gordon, Richard K.; Doctor, Bhupendra P.; Nambiar, Madhusoodana P.

    2009-01-01

    We evaluated the protective efficacy of nasal atropine methyl bromide (AMB) which does not cross the blood-brain barrier against sarin inhalation exposure. Age and weight matched male guinea pigs were exposed to 846.5 mg/m 3 sarin using a microinstillation inhalation exposure technique for 4 min. The survival rate at this dose was 20%. Post-exposure treatment with nasal AMB (2.5 mg/kg, 1 min) completely protected against sarin induced toxicity (100% survival). Development of muscular tremors was decreased in animals treated with nasal AMB. Post-exposure treatment with nasal AMB also normalized acute decrease in blood oxygen saturation and heart rate following sarin exposure. Inhibition of blood AChE and BChE activities following sarin exposure was reduced in animals treated with nasal AMB, indicating that survival increases the metabolism of sarin or expression of AChE. The body weight loss of animals exposed to sarin and treated with nasal AMB was similar to saline controls. No differences were observed in lung accessory lobe or tracheal edema following exposure to sarin and subsequent treatment with nasal AMB. Total bronchoalveolar lavage fluid (BALF) protein, a biomarker of lung injury, showed trends similar to saline controls. Surfactant levels post-exposure treatment with nasal AMB returned to normal, similar to saline controls. Alkaline phosphatase levels post-exposure treatment with nasal AMB were decreased. Taken together, these data suggest that nasal AMB blocks the copious airway secretion and peripheral cholinergic effects and protects against lethal inhalation exposure to sarin thus increasing survival.

  19. Sleep disturbances in treatment-seeking OCD-patients: Changes after concentrated exposure treatment.

    Science.gov (United States)

    Nordahl, Håkon; Havnen, Audun; Hansen, Bjarne; Öst, Lars-Göran; Kvale, Gerd

    2018-04-01

    Research indicates that patients with Obsessive Compulsive Disorder (OCD) frequently suffer from comorbid sleep difficulties, and that these difficulties often are not clinically recognized and diagnosed. There has been limited research investigating if comorbid sleep difficulties impair treatment outcome for OCD and if the sleep difficulties change following OCD-treatment. Thirty-six patients with obsessive compulsive disorder underwent concentrated exposure treatment delivered in a group over four consecutive days and were assessed with measures of OCD, depressive symptoms and sleep disturbance at three different time points (pre, post and 6 months follow-up). The sample was characterized by a high degree of comorbidity with other psychiatric disorders. At pre-treatment nearly 70% of the patients reported sleep difficulties indicative of primary insomnia. The results showed that patients had large reductions of OCD-symptoms as well as significant improvements in sleep disturbance assessed after treatment, and that these improvements were maintained at follow-up. Sleep disturbance did not impair treatment outcome, on the contrary patients with higher degree of sleep disturbance at pre-treatment had better outcome on OCD-symptoms after treatment. The results indicated that the majority of the OCD sample suffered from sleep disturbances and that these sleep disturbances were significantly reduced following adequate treatment of OCD without specific sleep interventions. However, a proportion of the patients suffered from residual symptoms of insomnia after treatment. © 2017 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  20. IL-7 treatment augments and prolongs sepsis-induced expansion of IL-10-producing B lymphocytes and myeloid-derived suppressor cells.

    Science.gov (United States)

    Kulkarni, Upasana; Herrmenau, Christoph; Win, Stephanie J; Bauer, Michael; Kamradt, Thomas

    2018-01-01

    Immunological dysregulation in sepsis is associated with often lethal secondary infections. Loss of effector cells and an expansion of immunoregulatory cell populations both contribute to sepsis-induced immunosuppression. The extent and duration of this immunosuppression are unknown. Interleukin 7 (IL-7) is important for the maintenance of lymphocytes and can accelerate the reconstitution of effector lymphocytes in sepsis. How IL-7 influences immunosuppressive cell populations is unknown. We have used the mouse model of peritoneal contamination and infection (PCI) to investigate the expansion of immunoregulatory cells as long-term sequelae of sepsis with or without IL-7 treatment. We analysed the frequencies and numbers of regulatory T cells (Tregs), double negative T cells, IL-10 producing B cells and myeloid-derived suppressor cells (MDSCs) for 3.5 months after sepsis induction. Sepsis induced an increase in IL-10+ B cells, which was enhanced and prolonged by IL-7 treatment. An increased frequency of MDSCs in the spleen was still detectable 3.5 months after sepsis induction and this was more pronounced in IL-7-treated mice. MDSCs from septic mice were more potent at suppressing T cell proliferation than MDSCs from control mice. Our data reveal that sepsis induces a long lasting increase in IL-10+ B cells and MDSCs. Late-onset IL-7 treatment augments this increase, which should be relevant for clinical interventions.

  1. Treatment of hemodialysis vascular access rupture irresponsive to prolonged balloon tamponade: Retrospective evaluation of the effectiveness of N-butyl cyanoacrylate seal-off technique

    Energy Technology Data Exchange (ETDEWEB)

    Weng, Mei Jul; Liang, Huei Lung; Pan, Huay Ben [Dept. of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung (China); Chen, Matt Chiung Yu [Dept. of Radiology, Yuan' s General Hospital, Kaohsiung (China)

    2013-01-15

    The current study retrospectively evaluated whether the percutaneous N-butyl cyanoacrylate (NBCA) seal-off technique is an effective treatment for controlling the angioplasty-related ruptures, which are irresponsive to prolonged balloon tamponade, during interventions for failed or failing hemodialysis vascular accesses. We reviewed 1588 interventions performed during a 2-year period for dysfunction and/or failed hemodialysis vascular access sites in 1569 patients. For the angioplasty-related ruptures, which could not be controlled with repeated prolonged balloon tamponade, the rupture sites were sealed off with an injection of a glue mixture (NBCA and lipiodol), via a needle/needle sheath to the rupture site, under a sonographic guidance. Technical success rate, complications and clinical success rate were reported. The post-seal-off primary and secondary functional patency rates were calculated by a survival analysis with the Kaplan-Meier method. Twenty ruptures irresponsive to prolonged balloon tamponade occurred in 1588 interventions (1.3%). Two technical failures were noted; one was salvaged with a bailout stent-graft insertion and the other was lost after access embolization. Eighteen accesses (90.0%) were salvaged with the seal-off technique; of them, 16 ruptures were completely sealed off, and two lesions were controlled as acute pseudoaneurysms. Acute pseudoaneurysms were corrected with stentgraft insertion in one patient, and access ligation in the other. The most significant complication during the follow-up was delayed pseudoaneurysm, which occurred in 43.8% (7 of 16) of the completely sealed off accesses. Delayed pseudoaneurysms were treated with surgical revision (n = 2), access ligation (n = 2) and observation (n = 3). During the follow-up, despite the presence of pseudoaneurysms (acute = 1, delayed = 7), a high clinical success rate of 94.4% (17 of 18) was achieved, and they were utilized for hemodialysis at the mean of 411.0 days. The post

  2. Young, low-birth-weight men are not more susceptible to the diabetogenic effects of a prolonged free fatty acid exposure than matched controls

    DEFF Research Database (Denmark)

    Jensen, Christine B; Storgaard, Heidi; Holst, Jens Juul

    2005-01-01

    a prolonged physiological lipid load could unmask or augment existing metabolic defects in otherwise healthy young LBW subjects. Forty 19-year-old men (LBW [n = 20], controls [normal birth weight, NBW] [n = 20]) without a family history of diabetes underwent an intravenous glucose tolerance test (0.3 g kg(-1......Low birth weight (LBW) is associated with increased risk of developing type 2 diabetes later in life. Progression from normal to impaired glucose tolerance and overt diabetes may depend, to some extent, on elevation of plasma free fatty acids (FFAs). We undertook this study to elucidate whether...... with normal glucose tolerance and in NBW controls. We reproduced our previous finding of lower insulin-stimulated glycolysis in this population....

  3. Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts.

    Science.gov (United States)

    Stracina, Tibor; Slaninova, Iva; Polanska, Hana; Axmanova, Martina; Olejnickova, Veronika; Konecny, Petr; Masarik, Michal; Krizanova, Olga; Novakova, Marie

    2015-07-01

    Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.

  4. Virtual reality exposure-based therapy for the treatment of post-traumatic stress disorder: a review of its efficacy, the adequacy of the treatment protocol, and its acceptability

    Directory of Open Access Journals (Sweden)

    Botella C

    2015-10-01

    Full Text Available Cristina Botella,1 Berenice Serrano,1 Rosa M Baños,2 Azucena Garcia-Palacios1 1Universitat Jaume I, Castellón de la Plana, Spain; 2Universitat de Valencia, Valencia, Spain Introduction: The essential feature of post-traumatic stress disorder (PTSD is the development of characteristic symptoms following exposure to one or more traumatic events. According to evidence-based intervention guidelines and empirical evidence, one of the most extensively researched and validated treatments for PTSD is prolonged exposure to traumatic events; however, exposure therapy can present some limitations. Virtual reality (VR can help to improve prolonged exposure because it creates fictitious, safe, and controllable situations that can enhance emotional engagement and acceptance. Objective: In addition to carrying out a review to evaluate the efficacy of VR exposure-based therapy (VR-EBT for the treatment of PTSD, the aim of this study was to contribute to analyzing the use of VR-EBT by: first, evaluating the adequacy of psychological treatment protocols that use VR-EBT to treat PTSD; and second, analyzing the acceptability of VR-EBT. Method: We performed a replica search with descriptors and databases used in two previous reviews and updated to April 2015. Next, we carried out an evaluation of the efficacy, adequacy, and acceptability of VR-EBT protocols. Results: Results showed that VR-EBT was effective in the treatment of PTSD. The findings related to adequacy showed that not all studies using VR-EBT reported having followed the clinical guidelines for evidence-based interventions in the treatment of PTSD. Regarding acceptability, few studies evaluated this subject. However, the findings are very promising, and patients reported high acceptability and satisfaction with the inclusion of VR in the treatment of PTSD. Conclusion: The main weaknesses identified in this review focus on the need for more controlled studies, the need to standardize treatment

  5. The parents' ability to take care of their baby as a factor in decisions to withhold or withdraw life-prolonging treatment in two Dutch NICUs.

    Science.gov (United States)

    Moratti, Sofia

    2010-06-01

    In The Netherlands, it is openly acknowledged that the parents' ability to take care of their child plays a role in the decision-making process over administration of life-prolonging treatment to severely defective newborn babies. Unlike other aspects of such decision-making process up until the present time, the 'ability to take care' has not received specific attention in regulation or in empirical research. The present study is based on interviews with neonatologists in two Dutch NICUs concerning their definition of the ability to take care and its relevance in non-treatment decisions. All of the respondents think that the ability to take care consists of more than one factor. Most doctors mention the parents' emotional state, social network and cognitive abilities. Some doctors mention the presence of psychological conditions in the parents, their financial situation and physical condition. A few refer to the parents' experience and age, their chances to have another baby and their cultural background. Most doctors think the ability to take care has a secondary relevance in the decision-making process, while the primary concern is assessing the condition of the child. A substantial minority thinks the ability to take care does not play any role, while one doctor thinks it is a factor of primary importance. The study constitutes an important stepping-stone for future research in The Netherlands and elsewhere.

  6. Complete Restoration of Refractory Mandibular Osteoradionecrosis by Prolonged Treatment with a Pentoxifylline-Tocopherol-Clodronate Combination (PENTOCLO): A Phase II Trial

    International Nuclear Information System (INIS)

    Delanian, Sylvie; Chatel, Cecile; Porcher, Raphael; Depondt, Joel; Lefaix, Jean-Louis

    2011-01-01

    Purpose: Osteoradionecrosis (ORN) is a nonhealing wound of the bone that is difficult to manage. Combined treatment with pentoxifylline and vitamin E reduces radiation-induced fibrosis and ORN with a good prognosis. We previously showed that the combination of pentoxifylline and vitamin E with clodronate (PENTOCLO) is useful in healing sternocostal and some mandibular ORN. Is PENTOCLO effective in ORN of poor prognosis? Methods: 54 eligible patients previously irradiated for head and neck cancer (among 72 treated) a mean 5 years previously received exteriorized refractory mandibular ORN for 1.4 ± 1.8 years, mainly after local surgery and hyperbaric oxygen had been ineffective. The mean length of exposed bone (D) was 17 ± 8 mm as primary endpoint, and the mean Subjective, Objective, Management, and Analytic evaluation of injury (SOMA) score was 16 ± 4. Between August 2000 and August 2008, all patients were given daily oral PENTOCLO: 800 mg pentoxifylline, 1,000 IU vitamin E, and 1,600 mg clodronate 5 days per week alternating with 20 mg prednisone and 1,000 mg ciprofloxacin 2 days per week. The duration of treatment was related to consolidated healing. Results: Prolonged treatment (16 ± 9 months) was safe and well tolerated. All patients improved, with an exponential progressive-(f[t] = a.exp(-b.t)-and significant (p 2 -42%, D 4 -62%, D 6 -77%, D 12 -92%, and D 18 -96%, combined with iterative spontaneous sequestrectomies in 36 patients. All patients experienced complete recovery in a median of 9 months. Clinical improvement was measured in terms of discontinuation of analgesics, new fracture, closed skin fistulae, and delayed radiologic improvement: SOMA 6 -64%, SOMA 12 -89%, and SOMA 30 -96%. Conclusion: Long-term PENTOCLO treatment is effective, safe, and curative for refractory ORN and induces mucosal and bone healing with significant symptom improvement. These findings will need to be confirmed in a randomized trial.

  7. Prolonged survival and improved glycemia in BioBreeding diabetic rats after early sustained exposure to glucagon-like peptide 1.

    Science.gov (United States)

    Yanay, Ofer; Moralejo, Daniel; Kernan, Kelly; Brzezinski, Margaret; Fuller, Jessica M; Barton, Randall W; Lernmark, Ake; Osborne, William R

    2010-06-01

    Type 1 diabetes (T1D) in both humans and BioBreeding (BB) rats is an autoimmune disease that results in complete destruction of islets and insulin dependency for life. Glucagon-like peptide 1 (GLP-1) promotes beta cell proliferation and neogenesis and has a potent insulinotropic effect. We hypothesized that the expression of GLP-1 before disease onset would increase islet mass, delay diabetes and prolong survival of BB rats. Vascular smooth muscle cells retrovirally transduced to secrete GLP-1 were seeded into TheraCyte encapsulation devices, implanted subcutaneously, and rats were monitored for diabetes. In untreated control rats, plasma GLP-1 levels were 34.5-39.5 pmol/l, whereas, in treated rats, plasma levels were elevated, in the range 90-250.4 pmol/l. Hypoglycemia was not detected and this was anticipated from the glucose-regulated action of GLP-1. Diabetes onset (mean + or - SEM) in untreated rats occurred at 56.5 + or - 0.6 days (n = 6) and, in GLP-1-treated rats, was delayed until 76.4 + or - 3.3 days (n = 5) (p 650 mg/dl) and did not survive beyond 11 days. At 5 days after diabetes onset, insulin-secreting islets were absent in untreated rats. By contrast, treated rats maintained weight for up to 143 days of age and showed insulin-secreting beta cells. Sustained GLP-1 expression delivered by encapsulated cells before diabetes onset in BB rats showed an improved clinical outcome, suggesting the potential for treating patients using long lasting GLP-1 analogs.

  8. Prolonged Exposure of Cortical Neurons to Oligomeric Amyloid-β Impairs NMDA Receptor Function Via NADPH Oxidase-Mediated ROS Production: Protective Effect of Green Tea (--Epigallocatechin-3-Gallate

    Directory of Open Access Journals (Sweden)

    Yan He

    2011-01-01

    Full Text Available Excessive production of Aβ (amyloid β-peptide has been shown to play an important role in the pathogenesis of AD (Alzheimer's disease. Although not yet well understood, aggregation of Aβ is known to cause toxicity to neurons. Our recent study demonstrated the ability for oligomeric Aβ to stimulate the production of ROS (reactive oxygen species in neurons through an NMDA (N-methyl-D-aspartate-dependent pathway. However, whether prolonged exposure of neurons to aggregated Aβ is associated with impairment of NMDA receptor function has not been extensively investigated. In the present study, we show that prolonged exposure of primary cortical neurons to Aβ oligomers caused mitochondrial dysfunction, an attenuation of NMDA receptor-mediated Ca2+ influx and inhibition of NMDA-induced AA (arachidonic acid release. Mitochondrial dysfunction and the decrease in NMDA receptor activity due to oligomeric Aβ are associated with an increase in ROS production. Gp91ds-tat, a specific peptide inhibitor of NADPH oxidase, and Mn(III-tetrakis(4-benzoic acid-porphyrin chloride, an ROS scavenger, effectively abrogated Aβ-induced ROS production. Furthermore, Aβ-induced mitochondrial dysfunction, impairment of NMDA Ca2+ influx and ROS production were prevented by pretreatment of neurons with EGCG [(–-epigallocatechin-3-gallate], a major polyphenolic component of green tea. Taken together, these results support a role for NADPH oxidase-mediated ROS production in the cytotoxic effects of Aβ, and demonstrate the therapeutic potential of EGCG and other dietary polyphenols in delaying onset or retarding the progression of AD.

  9. Extended ankle and foot fasciotomy as an enhancement to the surgical treatment of patients with prolonged ischemia of the lower extremities

    Directory of Open Access Journals (Sweden)

    Mišović Sidor

    2005-01-01

    Full Text Available Aim. To present the technique and efficacy of extended ankle and foot fasciotomy, as a surgical limb-salvage procedure associated with the successful revascularization after the gold interval. Method. A retrospective review of six patients at the age of 16−79 years (mean 39 in the period from 1996 to 2003, treated with the extended ankle and foot fasciotomy. There were four males undergoing the delayed treatment of war injuries to the lower extremity, and two females with atherosclerotic occlusive disease (a. illiacae dex and a. poplitealis dex.. The average ishemic time in the wounded patients was 22 hours (range, 14−30 hours, and ischemic time in occlusive disease (range, 48−72 hours. Clinical signs, indications, surgical access and the technique of extended ankle and foot fasciotomy was reported. Results. The obtained results were classified as early and late. There was no cases with lethal outcome. Incisional wounds closed 15 days after the intervention, using secondary suture or skin transplant sec. Thiersch. The satisfactory functional results were achieved in 4 of the patients, 1 had a small edema, while amputation was performed in 1 patient. Conclusion. In cases of prolonged foot ischemia with edema and paresthesia in the toes, extended ankle and foot fasciotomy should be performed as a surgical limb-salvage procedure.

  10. Prolonged Response and Restoration of Functional Independence with Bevacizumab plus Vinorelbine as Third-Line Treatment for Breast Cancer-Related Leptomeningeal Metastases

    Directory of Open Access Journals (Sweden)

    Emilie Le Rhun

    2015-02-01

    Full Text Available Background: Survival of patients with leptomeningeal metastases (LM and impaired functional status is limited to several months, and rarely does neurological function improve with treatment. Case Report: A 34-year-old female with hormone-negative and HER2-positive metastatic breast cancer was diagnosed with bulky radiographic LM 45 months after initial diagnosis. She was treated with intra-CSF trastuzumab followed by intra-CSF liposomal cytarabine; however, the cancer progressed 8 months after the diagnosis of LM. At the time of the third LM progression, the patient presented with a cauda equina syndrome and cerebellar impairment resulting in an inability to walk. She was treated with CNS-directed radiotherapy (lumbosacral and cerebellar and bevacizumab plus vinorelbine. Rapid functional improvement occurred, and the patient regained the ability to walk and independently manage her daily activities. Twelve months later, she presented with rapid progression of the LM resulting in death within several weeks. Conclusion: In radiographically defined bulky LM, the combination of systemic therapy and CNS-directed radiotherapy likely is more active than intra-CSF therapy only. In lieu of the rapid and significant improvement in neurological function combined with the prolonged response, bevacizumab alone or in combination with chemotherapy and CNS-directed radiotherapy may be considered in select patients with radiographically bulky breast cancer-related LM.

  11. Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

    Science.gov (United States)

    Terryn, Sanne; Francart, Aurélie; Rommelaere, Heidi; Stortelers, Catelijne; Van Gucht, Steven

    2016-01-01

    Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP. PMID:27483431

  12. Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection.

    Directory of Open Access Journals (Sweden)

    Sanne Terryn

    2016-08-01

    Full Text Available Post-exposure prophylaxis (PEP against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days and decreased mortality (60% versus 19% survival rate, when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP.

  13. Longitudinal changes of nerve conduction velocity, distal motor latency, compound motor action potential duration, and skin temperature during prolonged exposure to cold in a climate chamber.

    Science.gov (United States)

    Maetzler, Walter; Klenk, Jochen; Becker, Clemens; Zscheile, Julia; Gabor, Kai-Steffen; Lindemann, Ulrich

    2012-09-01

    Changes of nerve conduction velocity (NCV), distal motor latency (DML), compound motor action potential (CMAP) duration, and skin temperature with regard to cold have been investigated by use of ice packs or cold water baths, but not after cooling of environmental temperature which has higher ecological validity. The aim of this study was to investigate these parameters during cooled room temperature. NCV, DML, and CMAP duration of the common fibular nerve, and skin temperature were measured in 20 healthy young females during exposure to 15°C room temperature, coming from 25°C room. We found that NCV decreased and DML increased linearly during 45 min observation time, in contrast to CMAP duration and skin temperature which changes followed an exponential curve. To the best of our knowledge, this is the first study investigating changes of these parameters during exposure to environmental cold. The results may pilot some new hypotheses and studies on physiological and pathological changes of the peripheral nervous system and skin to environmental cold, e.g., in elderly with peripheral neuropathies.

  14. Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment.

    Science.gov (United States)

    Nelson, Antoinette G; Zhang, Xiaoping; Ganapathi, Usha; Szekely, Zoltan; Flexner, Charles W; Owen, Andrew; Sinko, Patrick J

    2015-12-10

    The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel

  15. Prolonged-release fampridine treatment improved subject-reported impact of multiple sclerosis: Item-level analysis of the MSIS-29.

    Science.gov (United States)

    Gasperini, Claudio; Hupperts, Raymond; Lycke, Jan; Short, Christine; McNeill, Manjit; Zhong, John; Mehta, Lahar R

    2016-11-15

    Prolonged-release (PR) fampridine is approved to treat walking impairment in persons with multiple sclerosis (MS); however, treatment benefits may extend beyond walking. MOBILE was a phase 2, 24-week, double-blind, placebo-controlled exploratory study to assess the impact of 10mg PR-fampridine twice daily versus placebo on several subject-assessed measures. This analysis evaluated the physical and psychological health outcomes of subjects with progressing or relapsing MS from individual items of the Multiple Sclerosis Impact Scale (MSIS-29). PR-fampridine treatment (n=68) resulted in greater improvements from baseline in the MSIS-29 physical (PHYS) and psychological (PSYCH) impact subscales, with differences of 89% and 148% in mean score reduction from baseline (n=64) at week 24 versus placebo, respectively. MSIS-29 item analysis showed that a higher percentage of PR-fampridine subjects had mean improvements in 16/20 PHYS and 6/9 PSYCH items versus placebo after 24weeks. Post hoc analysis of the 12-item Multiple Sclerosis Walking Scale (MSWS-12) improver population (≥8-point mean improvement) demonstrated differences in mean reductions from baseline of 97% and 111% in PR-fampridine MSIS-29 PHYS and PSYCH subscales versus the overall placebo group over 24weeks. A higher percentage of MSWS-12 improvers treated with PR-fampridine showed mean improvements in 20/20 PHYS and 8/9 PSYCH items versus placebo at 24weeks. In conclusion, PR-fampridine resulted in physical and psychological benefits versus placebo, sustained over 24weeks. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Dosimetric effect of images of double field exposure and positioning in radiotherapy of breast treatment

    International Nuclear Information System (INIS)

    Bermudez Luna, R.; Rodriguez Rodriguez, C.; Martin Martin, G.; Lopez Fernandez, A.; Caballero Perea, B.; Ludena Martinez, B.; Prados Losa, R.

    2013-01-01

    The objectives of this study are to quantify the increased dose in white volume and the organ at risk in breast radiotherapy treatment, derived from portals of double-exposure images scheduled for treatment, evaluate dose reduction by passing images of single exposure and consider whether it would be wise to consider this doses in the planning process. (Author)

  17. Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review

    OpenAIRE

    de Kleine, Rianne A.; Rothbaum, Barbara O.; van Minnen, Agnes

    2013-01-01

    There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD). Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. Th...

  18. Prolonged exposure of methicillin-resistant Staphylococcus aureus (MRSA) COL strain to increasing concentrations of oxacillin results in a multidrug-resistant phenotype

    DEFF Research Database (Denmark)

    Martins, Ana; Couto, Isabel; Aagaard, Lone

    2007-01-01

    Our previous studies demonstrated that exposure of a bacterium to increasing concentrations of an antibiotic would increase resistance to that antibiotic as a consequence of activating efflux pumps. This study utilises the same approach; however, it employs the methicillin-resistant Staphylococcus...... aureus (MRSA) COL strain, which is highly resistant to oxacillin (OXA). MRSA COL was adapted to 3200 mg/L of OXA. Changes in resistance to other antibiotics were evaluated and efflux pump activity during the adaptation process was determined. MRSA COL was exposed to stepwise two-fold increases of OXA....... At the end of each step, minimum inhibitory concentration determination for erythromycin (ERY) and other antibiotics was conducted. Reserpine (RES) was employed to evaluate whether resistance to ERY was dependent on efflux pump activity. Efflux pump activity was also evaluated using the ethidium bromide (EB...

  19. Prolonged treatment with transcutaneous electrical nerve stimulation (TENS) modulates neuro-gastric motility and plasma levels of vasoactive intestinal peptide (VIP), motilin and interleukin-6 (IL-6) in systemic sclerosis.

    Science.gov (United States)

    McNearney, Terry A; Sallam, Hanaa S; Hunnicutt, Sonya E; Doshi, Dipti; Chen, Jiande D Z

    2013-01-01

    We assessed the effects of transcutaneous electrical nerve stimulation (TENS) on neurogastric functioning in scleroderma patients. Seventeen SSc patients underwent 30 min TENS treatment >10Hz at GI acupuncture points PC6 and ST36, once (acute TENS) and then after two weeks of TENS sessions for 30 min twice daily (prolonged TENS). Data collected at Visits 1 and 2 included gastric myoelectrical activity (GMA) by surface electrogastrography (EGG), heart rate variability (HRV) by surface electrocardiography (EKG), GI specific symptoms and health related SF-36 questionnaires. Plasma VIP, motilin and IL-6 levels were determined. Statistical analyses were performed by Student's t-test, Spearman Rank and p-values TENS, the percentages of normal slow waves and average slow wave coupling (especially channels 1, 2 reflecting gastric pacemaker and corpus regions) were significantly increased; 2. the percentage of normal slow waves was significantly correlated to sympathovagal balance; 3. Mean plasma VIP and motilin levels were significantly decreased after acute TENS, (vs. baseline), generally maintained in the prolonged TENS intervals. Compared to baseline, mean plasma IL-6 levels were significantly increased after acute TENS, but significantly decreased after prolonged TENS. 4. After prolonged TENS, the frequency of awakening due to abdominal pain and abdominal bloating were significantly and modestly decreased, respectively. In SSc patients, two weeks of daily TENS improved patient GMA scores, lowered plasma VIP, motilin and IL-6 levels and improved association between GMA and sympathovagal balance. This supports the therapeutic potential of prolonged TENS to enhance gastric myoelectrical functioning in SSc.

  20. Excess relative risk for solid cancer mortality during prolonged exposure to high-background natural radiation in Yangjiang area of China

    International Nuclear Information System (INIS)

    Sun Quanfu; Tao Zufan; Yuan Yongling; Zou Jianming; Cha Yongru; Jian Yuannu; Wei Luxin; Akiba, S.

    2002-01-01

    Objective: To estimate the excess relative risk for solid cancer associated with chronically exposure to high-background natural radiation in Yangjiang area of China. Methods: Based on hamlet-specific environmental doses and sex-and age-specific occupancy factors, the authors calculated cumulative doses for each cohort member. Assuming a linear dose response relationship and using cancer mortality data for the period 1979-1995 and Poisson model, the authors estimated the excess relative risk (ERR) for solid cancer. Results: The ERR per Sv of all solid cancer is estimated to be -0.11 (95% CI, -0.67, 0.69 to 95%). The corresponding figures for cancers of liver, nasopharynx, lungs and stomach are -0.99 (-1.60, 0.10), 0.10 (-1.21, 3.28), -0.68 (-1.58, 1.66) and -0.27 (-1.37, 2.69) respectively. Conclusion: The association between ERR of solid cancer and dose can not be found

  1. Applying extinction research and theory to cue-exposure addiction treatments.

    Science.gov (United States)

    Conklin, Cynthia A; Tiffany, Stephen T

    2002-02-01

    To evaluate the efficacy of cue-exposure addiction treatment and review modern animal learning research to generate recommendations for substantially enhancing the effectiveness of this treatment. Meta-analysis of cue-exposure addiction treatment outcome studies (N=9), review of animal extinction research and theory, and evaluation of whether major principles from this literature are addressed adequately in cue-exposure treatments. The meta-analytical review showed that there is no consistent evidence for the efficacy of cue-exposure treatment as currently implemented. Moreover, procedures derived from the animal learning literature that should maximize the potential of extinction training are rarely used in cue-exposure treatments. Given what is known from animal extinction theory and research about extinguishing learned behavior, it is not surprising that cue-exposure treatments so often fail. This paper reviews current animal research regarding the most salient threats to the development and maintenance of extinction, and suggests several major procedures for increasing the efficacy of cue-exposure addiction treatment.

  2. Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial

    Directory of Open Access Journals (Sweden)

    Francine Foss

    2016-03-01

    Full Text Available Abstract Background Achievement of durable responses in patients with relapsed/refractory peripheral T cell lymphoma (PTCL is challenging with current therapies, and there are few data regarding the potential benefits of continuing treatment in patients with the best response of stable disease (SD. Histone deacetylase inhibitors are a novel class of drugs with activity in T cell malignancies. Romidepsin was approved by the US Food and Drug Administration for the treatment of relapsed/refractory PTCL based on a pivotal trial demonstrating an objective response rate of 25 % (33/130, including 15 % with confirmed/unconfirmed complete response and a median duration of response of 28 months. Our objective was to further study the clinical benefits of romidepsin in patients that had the best response of SD. Methods Patients with PTCL relapsed/refractory to ≥1 prior therapy were treated with the approved dose of 14 mg/m2 romidepsin on days 1, 8, and 15 of six 28-day cycles; patients with SD or response after cycle 6 were allowed to continue on study until progression. By protocol amendment, patients treated for ≥12 cycles could receive maintenance dosing twice per cycle; after cycle 24, dosing could be further reduced to once per cycle in those who had received maintenance dosing for ≥6 months. Results Of the 32 patients (25 % with the best response of SD, 22 had SD for ≥90 days (SD90; cycle 4 response assessment. The longest SD was >3 years in a patient who received maintenance dosing of 14 mg/m2 on days 1 and 15 beginning in cycle 13. Patients with the best response of SD90 or partial response achieved similar overall and progression-free survival. Prolonged dosing of romidepsin was well tolerated. Conclusions We concluded that patients who achieve SD may consider continuing treatment because the clinical benefits of romidepsin may extend beyond objective responses. Trial registration NCT00426764

  3. The decreased influence of overall treatment time on the response of human breast tumor xenografts following prolongation of the potential doubling time (T{sub pot})

    Energy Technology Data Exchange (ETDEWEB)

    Sarkaria, Jann N; Fowler, John F; Lindstrom, Mary J; Jordan, V Craig; Mulcahy, R Timothy

    1995-02-15

    Purpose: Repopulation during fractionated radiotherapy has been postulated to result in a significant loss in local control in rapidly proliferating tumors. Clinical data suggest that accelerated fractionation schedules can overcome the influence of repopulation by limiting the overall treatment time. Unfortunately, accelerated therapy frequently leads to increased acute reactions, which may become dose limiting. An alternative to accelerated fractionation would be to decrease the rate of repopulation during therapy. To test the potential efficacy of this alternative, we examined the effect of reducing tumor proliferation rate on the response of MCF-7 human breast carcinoma xenografts treated with a short vs. a long course of fractionated therapy. To reduce the proliferation rate, we deprived nude mice transplanted with MCF-7 xenografts of the growth-stimulating hormone estradiol (E{sub 2}). We have previously reported that E{sub 2} deprivation increases the potential doubling time (T{sub pot}) for MCF-7 xenografts from a mean of 2.6 days to 5.3 days (p < 0.001). Methods and Materials: E{sub 2}-stimulated and E{sub 2}-deprived MCF-7 breast carcinoma xenografts were clamped hypoxically and irradiated with four fractions of 5 Gy each, using either a short (3-day) or long (9-day) treatment course. E{sub 2} stimulation was restored in all animals at the completion of irradiation. Radiation response was determined by regrowth time and regrowth delay of the irradiated tumors as compared to unirradiated controls. Results: Prolongation of therapy in rapidly proliferating, E{sub 2}-stimulated tumors (T{sub pot} {approx} 2.6 days) resulted in a significant decrease in regrowth time in two identical experiments. With results pooled for analysis, the regrowth times for the short and long treatments were 62 and 32 days, respectively (combined p < 0.001). The shorter regrowth times suggest that there was less overall tumor damage with the longer fractionated radiotherapy course

  4. Effect of spirulina on the levels of zinc, vitamin E and linoleic acid in the palm skin extracts of people with prolonged exposure to arsenic

    Directory of Open Access Journals (Sweden)

    Mir Misbahuddin

    2013-03-01

    Full Text Available Spirulina, a dietary supplement, improves the symptoms of arsenical palmer keratosis. To understand its mechanism of action, palm skin extracts of moderate palmer arsenical keratosis (n=10, arsenic exposed controls (n=10 and healthy volunteers (n=10 were collected before and after treatment with spirulina powder 10 g/day orally for 12 weeks. The mean (±SD amount of zinc in the palm skin of healthy volunteers was 13.1 ± 5.7 ng/cm2, which was not changed significantly in patients (11.3 ± 5.3 ng/cm2. The amount of vitamin E in healthy volunteers was 6.0 ± 0.3 ng/cm2 which was severely reduced in patients (3.5 ± 0.6 ng/cm2. The amount of linoleic acid was lowered in patient (26.7 ± 17.1 ng/cm2 which was statistically significant in comparison to healthy volunteers (p=0.029. After supplementation of spirulina, zinc level in the palm skin of arsenic exposed controls was increased but it was not statistically significant (p=0.068. The vitamin E and linoleic acid levels were not changed significantly in the skin of palm. In conclusion, arsenical keratosis showed significantly low levels of vitamin E and linoleic acid without any significant change in zinc level. After supplementation of spirulina, low levels of these three compounds were not returned towards the normal levels.

  5. Subtleties in practical application of prolonged infusion of β-lactam antibiotics.

    Science.gov (United States)

    De Waele, Jan J; Lipman, Jeffrey; Carlier, Mieke; Roberts, Jason A

    2015-05-01

    Prolonged infusion (PI) of β-lactam antibiotics is increasingly used in order to optimise antibiotic exposure in critically ill patients. Physicians are often not aware of a number of subtleties that may jeopardise the treatment. In this clinically based paper, we stress pragmatic issues, such as the importance of a loading dose before PI, and discuss a number of important practicalities that are mandatory to benefit from the pharmacokinetic advantages of prolonged β-lactam antibiotic administration. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  6. Is Exposure Necessary? A Randomized Clinical Trial of Interpersonal Psychotherapy for PTSD

    Science.gov (United States)

    Markowitz, John C.; Petkova, Eva; Neria, Yuval; Van Meter, Page E.; Zhao, Yihong; Hembree, Elizabeth; Lovell, Karina; Biyanova, Tatyana; Marshall, Randall D.

    2015-01-01

    Background Exposure to trauma reminders has been considered imperative in psychotherapy for posttraumatic stress disorder (PTSD). No treatment benefits all patients, however. We tested Interpersonal Psychotherapy, which has demonstrated antidepressant efficacy and showed promise in pilot PTSD research, as a non-exposure-based, non-cognitive behavioral PTSD treatment. Methods A randomized, fourteen-week trial compared Interpersonal Psychotherapy; Prolonged Exposure, an exposure-based exemplar; and Relaxation Therapy, an active control psychotherapy. Subjects were 110 unmedicated patients having DSM-IV chronic PTSD and Clinician-Administered PTSD Scale (CAPS) score >50. Randomization stratified for comorbid major depression. We hypothesized Interpersonal Psychotherapy would be no more than minimally inferior (CAPS difference 30% CAPS improvement) were: Interpersonal Psychotherapy 63%, Prolonged Exposure 47%, Relaxation Therapy 38% (n.s.). Interpersonal psychotherapy and Prolonged Exposure CAPS outcome differed by 5.5 points (n.s.); the null hypothesis of more than minimal Interpersonal Psychotherapy inferiority was rejected (p=0.035). Patients with comorbid major depression dropped out from Prolonged Exposure nine times more than non-depressed Prolonged Exposure patients. Interpersonal Psychotherapy and Prolonged Exposure improved quality of life and social functioning more than Relaxation Therapy. Conclusions This first controlled study of individual Interpersonal Psychotherapy for PTSD demonstrated non-inferiority to the “gold standard” PTSD treatment. Interpersonal Psychotherapy had (non-significantly) lower attrition and higher response rates than Prolonged Exposure. Contradicting a widespread clinical belief, PTSD treatment may not require cognitive behavioral exposure to trauma reminders. Moreover, as differential therapeutics, patients with comorbid major depression may fare better in Interpersonal Psychotherapy than Prolonged Exposure. PMID:25677355

  7. 9 CFR 72.12 - Cattle; exposure to tick infestation after treatment or inspection prohibited.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Cattle; exposure to tick infestation... (INCLUDING POULTRY) AND ANIMAL PRODUCTS TEXAS (SPLENETIC) FEVER IN CATTLE § 72.12 Cattle; exposure to tick infestation after treatment or inspection prohibited. The cattle shall not be exposed to tick infestation...

  8. Occupational Exposures to Ebola Virus in Ebola Treatment Center, Conakry, Guinea.

    Science.gov (United States)

    Savini, Hélène; Janvier, Frédéric; Karkowski, Ludovic; Billhot, Magali; Aletti, Marc; Bordes, Julien; Koulibaly, Fassou; Cordier, Pierre-Yves; Cournac, Jean-Marie; Maugey, Nancy; Gagnon, Nicolas; Cotte, Jean; Cambon, Audrey; Mac Nab, Christine; Moroge, Sophie; Rousseau, Claire; Foissaud, Vincent; De Greslan, Thierry; Granier, Hervé; Cellarier, Gilles; Valade, Eric; Kraemer, Philippe; Alla, Philippe; Mérens, Audrey; Sagui, Emmanuel; Carmoi, Thierry; Rapp, Christophe

    2017-08-01

    We report 77 cases of occupational exposures for 57 healthcare workers at the Ebola Treatment Center in Conakry, Guinea, during the Ebola virus disease outbreak in 2014-2015. Despite the high incidence of 3.5 occupational exposures/healthcare worker/year, only 18% of workers were at high risk for transmission, and no infections occurred.

  9. Virtual Reality versus Computer-Aided Exposure Treatments for Fear of Flying

    Science.gov (United States)

    Tortella-Feliu, Miquel; Botella, Cristina; Llabres, Jordi; Breton-Lopez, Juana Maria; del Amo, Antonio Riera; Banos, Rosa M.; Gelabert, Joan M.

    2011-01-01

    Evidence is growing that two modalities of computer-based exposure therapies--virtual reality and computer-aided psychotherapy--are effective in treating anxiety disorders, including fear of flying. However, they have not yet been directly compared. The aim of this study was to analyze the efficacy of three computer-based exposure treatments for…

  10. Daptomycin in the treatment of prosthetic joint infection by Enterococcus faecalis: safety and efficacy of high-dose and prolonged therapy

    OpenAIRE

    José Ramón Yuste; Milena Quesada; Pablo Díaz-Rada; José Luis Del Pozo

    2014-01-01

    Enterococci are implicated in less than 2.3% of prosthetic joint infections. These infections can be difficult to treat and therapeutic failures are not uncommon. In these situations, daptomycin is a safe and effective alternative. We present a clinical case with a successful response to the prolonged use of high-dose daptomycin.

  11. Daptomycin in the treatment of prosthetic joint infection by Enterococcus faecalis: safety and efficacy of high-dose and prolonged therapy

    Directory of Open Access Journals (Sweden)

    José Ramón Yuste

    2014-10-01

    Full Text Available Enterococci are implicated in less than 2.3% of prosthetic joint infections. These infections can be difficult to treat and therapeutic failures are not uncommon. In these situations, daptomycin is a safe and effective alternative. We present a clinical case with a successful response to the prolonged use of high-dose daptomycin.

  12. Treatment of phobophobia by exposure to CO2-induced anxiety symptoms.

    Science.gov (United States)

    Griez, E; van den Hout, M A

    1983-08-01

    It is argued that fear of fear, or phobophobia, can be an important maintaining factor in cases of seemingly free-floating anxiety with periodic panic attacks and that effective treatment consists of exposure to the feared neurovegetative sensations. The case history presented suggests that inhalation of CO2-O2 mixtures induces the phobic interoceptive sensations and that it can be used in the exposure treatment of phobophobia.

  13. Prolonged ketamine exposure induces increased activity of the GluN2B-containing N-methyl-d-aspartate receptor in the anterior cingulate cortex of neonatal rats.

    Science.gov (United States)

    Kokane, Saurabh S; Gong, Kerui; Jin, Jianhui; Lin, Qing

    2017-09-01

    Ketamine is a commonly used anesthetic among pediatric patients due to its high efficacy. However, it has been demonstrated by several preclinical studies that, widespread accelerated programmed death of neurons (neuroapoptosis) occurs due to prolonged or repeated exposure to ketamine specifically in the neonatal brain. Therefore, an emphasis on understanding the molecular mechanisms underlying this selective vulnerability of the neonatal brain to ketamine-induced neuroapoptosis becomes important in order to identify potential therapeutic targets, which would help prevent or at least ameliorate this neuroapoptosis. In this study, we demonstrated that repeated ketamine administration (6 injections of 20mg/kg dose given over 12h time period) in neonatal (postnatal day 7; PND 7) Sprague-Dawley rats induced a progressive increase in N-methyl-d-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents (EPSCs) in the neurons of the anterior cingulate cortex (ACC) for up to 6h after the last ketamine dose. Specifically, we observed that the increased EPSCs were largely mediated by GluN2B-containing NMDARs in the neurons of the ACC. Along with increased synaptic transmission, there was also a significant increase in the expression of the GluN2B-containing NMDARs as well. Taken together, these results showed that after repeated exposure to ketamine, the synaptic transmission mediated by GluN2B-containing NMDARs was significantly increased in the neonatal brain. This was significant as it showed for the first time that ketamine had subunit-specific effects on GluN2B-containing NMDARs, potentially implicating the involvement of these subunits in the increased vulnerability of immature neurons of the neonatal brain to ketamine-induced neuroapoptosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. 1976 Hanford americium-exposure incident: decontamination and treatment facility

    International Nuclear Information System (INIS)

    Berry, J.R.; McMurray, B.J.; Jech, J.J.; Breitenstein, B.D.; Quigley, E.J.

    1982-01-01

    An injured worker, contaminated with over 6 mCi of americium-241, required special treatment and housing for 4 months. This paper is a description of the design and management of the facility in which most of the treatment and housing occurred. The problems associated with contamination control, waste handling, supplies, and radiological concerns during the two-stage transfer of the patient from a controlled situation to his normal living environment are discussed in detail

  15. Exposure dose in recent treatment of nuclear medicine and countermeasures

    International Nuclear Information System (INIS)

    Iio, Masahiro

    1974-01-01

    Radioactive pharmaceuticals widely used for the diagnosis in nuclear medicine utilize radiation as tracer for dynamic behavior measurement and locality diagnosis, and the exposure due to their use has very little chance to attain the maximum permissible dose of ICRP. The MIRD (Medical Internal Radiation Dose) method tends to be adopted for the measurement of internally absorbed dose due to radio-pharmaceuticals in future. The feature of the MIRD method is that the targeted object is not a critical organ but the region of interest, and the source organ and target organ are fully taken into consideration. Recently, the exposure of patients has been significantly lowered by applying sup(99m)Tc and the like. Though the contribution to national dose is small, it is required to perform immediate conversion from the older nuclear medicine typified with conventional 131 I, 198 Au and 203 Hg to modern one centering around sup(99m)Tc. The problems in calculating the absorbed dose due to nuclear medicine diagnosis are very low accuracy of biological data though the high accuracy of data in physics has been achieved, and the difficulty to obtain data for calculating patients' absorbed dose in routine inspection. (Wakatsuki, Y.)

  16. Efficacy of virtual reality exposure therapy in the treatment of PTSD: a systematic review.

    Directory of Open Access Journals (Sweden)

    Raquel Gonçalves

    Full Text Available The use of Information and Communication Technologies, such as virtual reality, has been employed in the treatment of anxiety disorders with the goal of augmenting exposure treatment, which is already considered to be the first-line treatment for Post-traumatic Stress Disorder (PTSD. To evaluate the efficacy of virtual reality exposure therapy (VRET in the treatment of PTSD, we performed a systematic review of published articles using the following electronic databases: Web of Science, PubMed, PsycINFO, and PILOTS. Eligibility criteria included the use of patients diagnosed with PTSD according to DSM-IV, the use of cognitive behavioral therapy (CBT and the use of virtual reality for performing exposure. 10 articles were selected, seven of which showed that VRET produced statistically significant results in comparison to the waiting list. However, no difference was found between VRET and exposure treatment. Of these 10, four were randomized, two were controlled but not randomized and four were non-controlled. The majority of the articles used head-mounted display virtual reality (VR equipment and VR systems specific for the population that was being treated. Dropout rates do not seem to be lower than in traditional exposure treatment. However, there are a few limitations. Because this is a new field of research, there are few studies in the literature. There is also a need to standardize the number of sessions used. The randomized studies were analyzed to assess the quality of the methodology, and important deficiencies were noted, such as the non-use of intent-to- treat-analysis and the absence of description of possible concomitant treatments and comorbidities. Preliminary data suggest that VRET is as efficacious as traditional exposure treatment and can be especially useful in the treatment of patients who are resistant to traditional exposure.

  17. The combined use of virtual reality exposure in the treatment of agoraphobia.

    Science.gov (United States)

    Pitti, Carmen T; Peñate, Wenceslao; de la Fuente, Juan; Bethencourt, Juan M; Roca-Sánchez, María J; Acosta, Leopoldo; Villaverde, María L; Gracia, Ramón

    2015-01-01

    This study compares the differential efficacy of three groups of treatments for agoraphobia: paroxetine combined with cognitive-behavioral therapy, paroxetine combined with cognitive-behavioral therapy and virtual reality exposure, and a group with only paroxetine. 99 patients with agoraphobia were finally selected. Both combined treatment groups received 11 sessions of cognitive-behavioral therapy, and one of the groups was also exposed to 4 sessions of virtual reality treatment. Treatments were applied in individual sessions once a week for 3 months. The three treatment groups showed statistically significant improvements. In some measures, combined treatment groups showed greater improvements. The virtual reality exposure group showed greater improvement confronting phobic stimuli. Treatments combining psychopharmacological and psychological therapy showed greater efficacy. Although the use of new technologies led to greater improvement, treatment adherence problems still remain.

  18. Variables influencing radiation exposure during extracorporeal shock wave lithotripsy. Review of 298 treatments

    International Nuclear Information System (INIS)

    Carter, H.B.; Naeslund, E.B.R.; Riehle, R.A. Jr.

    1987-01-01

    Retrospective review of 298 extracorporeal shock wave lithotripsy (ESWL) treatments was undertaken to determine the factors which influence radiation exposure during ESWL. Fluoroscopy time averaged 160 seconds (3-509), and the average number of spot films taken per patient was 26 (5-68). The average stone burden was 19.3 mm (3-64). Average calculated skin surface radiation exposure was 17.8 R per treatment. Radiation exposure increased with increasing stone burden and patient weight. Stones treated in the ureter resulted in a higher average patient radiation exposure than for renal stones (19 R vs 16 R), even though the average size of these ureteral stones (11.3 mm) was significantly less than the mean. However, type of anesthetic (general or regional) used was not a significant factor. Operator training, experience, and familiarity with radiation physics should significantly decrease the amount of imaging time and consequent patient radiation exposure during ESWL

  19. Variables influencing radiation exposure during extracorporeal shock wave lithotripsy. Review of 298 treatments

    Energy Technology Data Exchange (ETDEWEB)

    Carter, H.B.; Naeslund, E.B.R.; Riehle, R.A. Jr.

    1987-12-01

    Retrospective review of 298 extracorporeal shock wave lithotripsy (ESWL) treatments was undertaken to determine the factors which influence radiation exposure during ESWL. Fluoroscopy time averaged 160 seconds (3-509), and the average number of spot films taken per patient was 26 (5-68). The average stone burden was 19.3 mm (3-64). Average calculated skin surface radiation exposure was 17.8 R per treatment. Radiation exposure increased with increasing stone burden and patient weight. Stones treated in the ureter resulted in a higher average patient radiation exposure than for renal stones (19 R vs 16 R), even though the average size of these ureteral stones (11.3 mm) was significantly less than the mean. However, type of anesthetic (general or regional) used was not a significant factor. Operator training, experience, and familiarity with radiation physics should significantly decrease the amount of imaging time and consequent patient radiation exposure during ESWL.

  20. Exhaustion from prolonged gambling

    Directory of Open Access Journals (Sweden)

    Fatimah Lateef

    2013-01-01

    Full Text Available Complaints of fatigue and physical exhaustion are frequently seen in the acute medical setting, especially amongst athletes, army recruits and persons involved in strenuous and exertional physical activities. Stress-induced exhaustion, on the other hand, is less often seen, but can present with very similar symptoms to physical exhaustion. Recently, three patients were seen at the Department of Emergency Medicine, presenting with exhaustion from prolonged involvement in gambling activities. The cases serve to highlight some of the physical consequences of prolonged gambling.

  1. Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review

    Directory of Open Access Journals (Sweden)

    Rianne A. de Kleine

    2013-10-01

    Full Text Available There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD. Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: D-cycloserine, MDMA, hydrocortisone, and propranolol.

  2. Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review.

    Science.gov (United States)

    de Kleine, Rianne A; Rothbaum, Barbara O; van Minnen, Agnes

    2013-10-17

    There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD). Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: d-cycloserine, MDMA, hydrocortisone, and propranolol.

  3. [Pathophysiology of prolonged hypokinesia].

    Science.gov (United States)

    Kovalenko, E A

    1976-01-01

    Hypokinesia is an important problem in modern medicine. In the pathogenetic effect of prolonged hypokinesia the main etiological factor is diminished motor activity; of major importance are disorders in the energy and plastic metabolism which affect the muscle system; the contributing factors are cardiovascular deconditioning and orthostatic intolerance. This is attributed to a decreased oxygen supply and eliminated hydrostatic influences during a prolonged recumbency. Blood redistribution in the vascular bed is related to the Gauer-Henry reflex and subsequent changes in the fluid-electrolyte balance. Decreased load on the bone system induces changes in the protein-phosphate-calcium metabolism, diminished bone density and increased calcium content in the blood and urine. Changes in the calcium metabolism are systemic. The activity of the higher nervous system and reflex functions is lowered. Changes in the function of the autonomic nervous system which include a noticeable decline of its adaptive-trophic role as a result of the decrease of afferent and efferent impulsation are of great importance. Changes in the hormonal function involve a peculiar stress-reaction which develops at an early stage of hypokinesia as a response to an unusual situation. Prolonged hypokinesia may result in a disturbed function of the pituitary-adrenal system. It is assumed that prolonged hypokinesia may induce a specific disease of hypokinesia during which man cannot lead a normal mode of life and work.

  4. Exposure to Airborne Noroviruses and Other Bioaerosol Components at a Wastewater Treatment Plant in Denmark

    DEFF Research Database (Denmark)

    Uhrbrand, Katrine; Schultz, Anna Charlotte; Madsen, Anne Mette

    2011-01-01

    Exposure to bioaerosols associated with wastewater treatment processes may represent an occupational health risk for workers at wastewater treatment plants (WWTPs). A high frequency of acute symptoms in the gastrointestinal tract among the wastewater workers at a Danish WWTP has been reported. Th...

  5. Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review

    NARCIS (Netherlands)

    Kleine, R.A. de; Rothbaum, B.O.; Minnen, A. van

    2013-01-01

    There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD). Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in

  6. Virtual reality exposure using three-dimensional images for the treatment of social phobia

    Directory of Open Access Journals (Sweden)

    Cristiane M. Gebara

    2015-01-01

    Full Text Available Objective:To test a potential treatment for social phobia, which provides exposure to phobia-inducing situations via computer-generated, three-dimensional images, using an open clinical trial design.Methods:Twenty-one patients with a DSM-IV diagnosis of social phobia took part in the trial. Treatment consisted of up to 12 sessions of exposure to relevant images, each session lasting 50 minutes.Results:Improvements in social anxiety were seen in all scales and instruments used, including at follow-up 6 months after the end of treatment. The average number of sessions was seven, as the participants habituated rapidly to the process. Only one participant dropped out.Conclusion:This study provides evidence that exposure to computer-generated three-dimensional images is relatively inexpensive, leads to greater treatment adherence, and can reduce social anxiety. Further studies are needed to corroborate these findings.

  7. Fluoxetine treatment ameliorates depression induced by perinatal arsenic exposure via a neurogenic mechanism

    Science.gov (United States)

    Tyler, Christina R.; Solomon, Benjamin R.; Ulibarri, Adam L.; Allan, Andrea M.

    2014-01-01

    Several epidemiological studies have reported an association between arsenic exposure and increased rates of psychiatric disorders, including depression, in exposed populations. We have previously demonstrated that developmental exposure to low amounts of arsenic induces depression in adulthood along with several morphological and molecular aberrations, particularly associated with the hippocampus and the hypothalamic–pituitary–adrenal (HPA) axis. The extent and potential reversibility of this toxin-induced damage has not been characterized to date. In this study, we assessed the effects of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on adult animals exposed to arsenic during development. Perinatal arsenic exposure (PAE) induced depressive-like symptoms in a mild learned helplessness task and in the forced swim task after acute exposure to a predator odor (2,4,5-trimethylthiazoline, TMT). Chronic fluoxetine treatment prevented these behaviors in both tasks in arsenic-exposed animals and ameliorated arsenic-induced blunted stress responses, as measured by corticosterone (CORT) levels before and after TMT exposure. Morphologically, chronic fluoxetine treatment reversed deficits in adult hippocampal neurogenesis (AHN) after PAE, specifically differentiation and survival of neural progenitor cells. Protein expression of BDNF, CREB, the glucocorticoid receptor (GR), and HDAC2 was significantly increased in the dentate gyrus of arsenic animals after fluoxetine treatment. This study demonstrates that damage induced by perinatal arsenic exposure is reversible with chronic fluoxetine treatment resulting in restored resiliency to depression via a neurogenic mechanism. PMID:24952232

  8. Studies on Relationship between Serum Nitric Oxide and Plasma Cyclic Guanosine Monophosphate and Prolonged Bleeding after Medical Abortion as well as Prophylaxis and Treatment of Bleeding with Traditional Chinese Medicine

    Institute of Scientific and Technical Information of China (English)

    廖玎玲; 谭布珍; 辛华; 贺晓菊

    1999-01-01

    Objectives To study the relationship between serum nitric oxide(NO and plasma cyclic guanosine monophosphate(cGMP)and prolonged bleeding after medical abortion.Methods A total of 120women having received medical abortions at random were recruited and divided into two groups:the one(Group A,n=60) taking “Gong-Fu Mixture(Uterus-Recovering Mixture)”and the other(Group B,n=60)not taking it after abortion.On d 10,20 and 30 after medical abortion,serum NO and plasma cGMP were tested before and after mifepristone administration and 10 d later by Gresis reac-tion method and radioimmunoassay respectively.Results NO concentration in serum and cGMP concentration in plasma decreased signifi-cantly after taking mifeprlstone given(P<0. 05).Ten days later,the number of thos ewith bleeding discontinuation in the group A was significantly greater than that in the group B(P<0.05).Serum NO level and plasma cGMP level in the group A de-creased more significantly than those in the group B(P<0. 05).Conclusion The slow decrease of serum NO and plasma cGMP is closely related to prolonged bleeding after medical abortion.“Gong-Fu Mixture(uterus-recovering mixture)”is effective in prevention and treatment of prolonged bleeding.

  9. A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation

    International Nuclear Information System (INIS)

    Mason, Jay W; Moon, Thomas E; O’Boyle, Erin; Dietz, Albert

    2014-01-01

    Regulatory concern about potential QT-interval prolongation by serotonin-receptor antagonist antiemetics prompted product-label changes. The first-generation serotonin-receptor antagonist granisetron is available in oral (PO), intravenous (IV), and transdermal formulations. APF530 is a formulation that provides sustained release of granisetron when administered as a single subcutaneous (SC) injection. The Phase I study reported here evaluated effects of APF530 on electrocardiographic intervals. This single-site, double-blind, placebo-controlled, four-period crossover trial randomized healthy men and women to receive varying sequences of APF530 1 g SC, granisetron 50 μg/kg IV, moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after each treatment. The primary objective was to evaluate differences between baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia rate correction (dQTcF) for APF530 1 g SC and placebo. Electrocardiograms were performed at various times throughout the assessment period. Pharmacokinetics and safety were evaluated. The upper one-sided 95% confidence interval (CI) for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI, 0.94 to 7.36) at Hour 3. No clinically significant changes in other electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median time to maximum plasma concentration 11.1 hours) and slow elimination (mean half-life 18.6 hours; systemic clearance 20.2 L/hour) of granisetron versus the expected early peak concentration and elimination of granisetron IV. APF530 SC was well tolerated. Adverse events, most commonly constipation and SC injection-site reactions, were generally mild and quickly resolved. APF530 1 g SC did

  10. A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation

    Directory of Open Access Journals (Sweden)

    Mason JW

    2014-03-01

    Full Text Available Jay W Mason,1 Thomas E Moon,2 Erin O’Boyle,3 Albert Dietz41Department of Medicine, University of Utah, Salt Lake City, UT, 2Tarizona eHealth Services, Inc., San Carlos, CA, 3AP Pharma, Redwood City, CA, 4Spaulding Clinical Research, West Bend, WI, USABackground: Regulatory concern about potential QT-interval prolongation by serotonin-receptor antagonist antiemetics prompted product-label changes. The first-generation serotonin-receptor antagonist granisetron is available in oral (PO, intravenous (IV, and transdermal formulations. APF530 is a formulation that provides sustained release of granisetron when administered as a single subcutaneous (SC injection. The Phase I study reported here evaluated effects of APF530 on electrocardiographic intervals.Methods: This single-site, double-blind, placebo-controlled, four-period crossover trial randomized healthy men and women to receive varying sequences of APF530 1 g SC, granisetron 50 μg/kg IV, moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after each treatment. The primary objective was to evaluate differences between baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia rate correction (dQTcF for APF530 1 g SC and placebo. Electrocardiograms were performed at various times throughout the assessment period. Pharmacokinetics and safety were evaluated.Results: The upper one-sided 95% confidence interval (CI for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI, 0.94 to 7.36 at Hour 3. No clinically significant changes in other electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median time to maximum plasma concentration 11.1 hours and slow elimination (mean half-life 18.6 hours

  11. Effect of variations in treatment regimen and liver cirrhosis on exposure to benzodiazepines during treatment of alcohol withdrawal syndrome

    Directory of Open Access Journals (Sweden)

    Pavel Gershokovich

    2015-08-01

    Full Text Available Purpose: Benzodiazepines (BDZs are the drugs of choice to prevent the symptoms of alcohol withdrawal syndrome (AWS. Various treatment protocols are published and have been shown to be effective in both office-managed and facility-managed treatment of AWS. The aim of this scientific commentary is to demonstrate the differences in the expected exposure to BDZs during AWS treatment using different treatment regimens available in the literature, in patients with or without alcoholic liver cirrhosis. Methods: Diazepam and lorazepam AWS protocols were examined and reviewed in the literature, and blood plasma levels were examined and compared, respectively. Results: Considerable variation in the blood levels with the different dosing schedules was found. Because the drugs are metabolized differently, we have also shown that liver disease affects the blood levels of diazepam, but not of lorazepam. Conclusions: Differences in treatment regimens, the choice of BDZ, as well as the presence of liver cirrhosis can substantially alter the exposure of patients to drugs used for AWS treatment. Outpatient treatment of AWS has been shown to be relatively safe and effective for the treatment of AWS but patients should be carefully monitored.

  12. In Vivo versus Augmented Reality Exposure in the Treatment of Small Animal Phobia: A Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Cristina Botella

    Full Text Available Although in vivo exposure is the treatment of choice for specific phobias, some acceptability problems have been associated with it. Virtual Reality exposure has been shown to be as effective as in vivo exposure, and it is widely accepted for the treatment of specific phobias, but only preliminary data are available in the literature about the efficacy of Augmented Reality. The purpose of the present study was to examine the efficacy and acceptance of two treatment conditions for specific phobias in which the exposure component was applied in different ways: In vivo exposure (N = 31 versus an Augmented Reality system (N = 32 in a randomized controlled trial. "One-session treatment" guidelines were followed. Participants in the Augmented Reality condition significantly improved on all the outcome measures at post-treatment and follow-ups. When the two treatment conditions were compared, some differences were found at post-treatment, favoring the participants who received in vivo exposure. However, these differences disappeared at the 3- and 6-month follow-ups. Regarding participants' expectations and satisfaction with the treatment, very positive ratings were reported in both conditions. In addition, participants from in vivo exposure condition considered the treatment more useful for their problem whereas participants from Augmented Reality exposure considered the treatment less aversive. Results obtained in this study indicate that Augmented Reality exposure is an effective treatment for specific phobias and well accepted by the participants.

  13. In Vivo versus Augmented Reality Exposure in the Treatment of Small Animal Phobia: A Randomized Controlled Trial.

    Science.gov (United States)

    Botella, Cristina; Pérez-Ara, M Ángeles; Bretón-López, Juana; Quero, Soledad; García-Palacios, Azucena; Baños, Rosa María

    2016-01-01

    Although in vivo exposure is the treatment of choice for specific phobias, some acceptability problems have been associated with it. Virtual Reality exposure has been shown to be as effective as in vivo exposure, and it is widely accepted for the treatment of specific phobias, but only preliminary data are available in the literature about the efficacy of Augmented Reality. The purpose of the present study was to examine the efficacy and acceptance of two treatment conditions for specific phobias in which the exposure component was applied in different ways: In vivo exposure (N = 31) versus an Augmented Reality system (N = 32) in a randomized controlled trial. "One-session treatment" guidelines were followed. Participants in the Augmented Reality condition significantly improved on all the outcome measures at post-treatment and follow-ups. When the two treatment conditions were compared, some differences were found at post-treatment, favoring the participants who received in vivo exposure. However, these differences disappeared at the 3- and 6-month follow-ups. Regarding participants' expectations and satisfaction with the treatment, very positive ratings were reported in both conditions. In addition, participants from in vivo exposure condition considered the treatment more useful for their problem whereas participants from Augmented Reality exposure considered the treatment less aversive. Results obtained in this study indicate that Augmented Reality exposure is an effective treatment for specific phobias and well accepted by the participants.

  14. Management of prolonged pregnancy

    International Nuclear Information System (INIS)

    Iqbal, S.

    2004-01-01

    Objective: To compare two strategies for management of prolonged pregnancy (= or >294 days) i.e. induction (intervention) versus expectant management (non-intervention) and evaluate the associated feto-maternal risks. Subjects and Methods: One hundred cases of uncomplicated prolonged gestation were selected. The gestational age was confirmed by ultrasound in first trimester. One group (50 patients) was managed by intervention i.e. induction of labour (group A) and other group (50 patients) by non-intervention i.e. expectant management (group B). In group A intervention was done at 42 weeks. In expectant group, the methods of monitoring were fetal kick charting recorded daily by the patient, and ultrasound for amniotic fluid index. The biophysical profile score and NST (non stress test) were performed once a week till 42 weeks and then twice weekly. Results: The frequency of prolonged pregnancy was found to be 10.9%. There was no significant difference in the number of spontaneous vaginal deliveries between the two groups. The rate of LSCS (lower segment caesarean section) was higher in intervention group ( 30% versus 18% ). The neonatal depression at birth was more in group B ( 10% versus 4%) and at 5 minutes almost same between two groups (4% versus 2%). There were 11 cases of meconium aspiration syndrome, leading to one neonatal death. Among nine perinatal deaths two were neonatal deaths. Seven cases of intrauterine deaths in which antepartum deaths occurred because of non compliance of patients. No cause could be detected for the other three fetuses. Conclusion: There was increased LSCS rate in group A. However in expectant group B perinatal mortality was about twice more as compared to intervention group. Active early intervention at 42 weeks is warranted to reduce perinatal morbidity and mortality. (author)

  15. External beam radiotherapy (EBRT) techniques used in breast cancer treatment to reduce cardiac exposure

    International Nuclear Information System (INIS)

    Fung, Esther; Hendry, Julie

    2013-01-01

    Radiotherapy in breast cancer treatment has been shown to reduce local recurrence and improve survival rates. However, there is a concern that breast radiotherapy can cause an increase in cardiac mortality, particularly in patients being treated for left-sided breast cancer. This review aims to investigate how cardiac exposure is minimised in breast radiotherapy and determine an optimal method for reducing cardiac dose, using literature from ScienceDirect, Medline and CINAHL. IMRT and breathing-adapted radiotherapy both reduce cardiac exposure but IMRT also increases the irradiated volume at low dose. Several issues were reported with regards to the clinical implementation of these techniques. It is suggested that inspiration breath-hold radiotherapy, is the preferred solution to minimising cardiac exposure but more research is warranted to confirm this. Long-term follow-up is required to determine dose–response relationships. Research needs to focus on breast cancer treatment as a whole in order to effectively reduce cardiac mortality.

  16. Symptom Dimensions in Obsessive-Compulsive Disorder: Phenomenology and Treatment Outcomes with Exposure and Ritual Prevention

    OpenAIRE

    Williams, Monnica T.; Mugno, Beth; Franklin, Martin; Faber, Sonya

    2013-01-01

    Obsessive-compulsive disorder (OCD) is a severe condition with varied symptom presentations. The cognitive-behavioral treatment with the most empirical support is currently exposure and ritual prevention (EX/RP); however, clinical impression and some empirical data suggest that certain OCD symptoms are more responsive to treatment than others. Prior work identifying symptom dimensions within OCD is discussed, including epidemiological findings, factor analytic studies, and biological findings...

  17. Habituation of Premonitory Sensations during Exposure and Response Prevention Treatment in Tourette's Syndrome

    Science.gov (United States)

    Verdellen, Cara W. J.; Hoogduin, Cees A. L.; Kato, Bernet S.; Keijsers, Ger P. J.; Cath, Danielle C.; Hoijtink, Herbert B.

    2008-01-01

    Exposure to premonitory sensations and response prevention of tics (ER) has been shown to be a promising new treatment for Tourette's syndrome (TS). The present study tested the hypothesis that habituation to unpleasant premonitory sensations associated with the tic is an underlying mechanism of change in ER. Patients rated the severity of…

  18. In-Session Exposure Tasks and Therapeutic Alliance across the Treatment of Childhood Anxiety Disorders

    Science.gov (United States)

    Kendall, Philip C.; Comer, Jonathan S.; Marker, Craig D.; Creed, Torrey A.; Puliafico, Anthony C.; Hughes, Alicia A.; Martin, Erin D.; Suveg, Cynthia; Hudson, Jennifer

    2009-01-01

    The study examined the shape of therapeutic alliance using latent growth curve modeling and data from multiple informants (therapist, child, mother, father). Children (n = 86) with anxiety disorders were randomized to family-based cognitive-behavioral treatment (FCBT; N = 47) with exposure tasks or to family education, support, and attention…

  19. Inhibition of spontaneous recovery of fear by mGluR5 after prolonged extinction training.

    Directory of Open Access Journals (Sweden)

    Sheng-Chun Mao

    Full Text Available Fear behavior is vital for survival and involves learning contingent associations of non-threatening cues with aversive stimuli. In contrast, excessive levels of fear can be maladaptive and lead to anxiety disorders. Generally, extensive sessions of extinction training correlates with reduced spontaneous recovery. The molecular mechanisms underlying the long-term inhibition of fear recovery following repeated extinction training are not fully understood. Here we show that in rats, prolonged extinction training causes greater reduction in both fear-potentiated startle and spontaneous recovery. This effect was specifically blocked by metabotropic glutamate receptor 5 (mGluR5, but not by mGluR1 antagonists and by a protein synthesis inhibitor. Similar inhibition of memory recovery following prolonged extinction training was also observed in mice. In agreement with the instrumental role of mGluR5 in the prolonged inhibition of fear recovery, we found that FMR1-/- mice which exhibit enhanced mGluR5-mediated signaling exhibit lower spontaneous recovery of fear after extinction training than wild-type littermates. At the molecular level, we discovered that prolonged extinction training reversed the fear conditioning-induced increase in surface expression of GluR1, AMPA/NMDA ratio, postsynaptic density-95 (PSD-95 and synapse-associated protein-97 (SAP97. Accordingly, delivery of Tat-GluR2(3Y, a synthetic peptide that blocks AMPA receptor endocytosis, inhibited prolonged extinction training-induced inhibition of fear recovery. Together, our results demonstrate that prolonged extinction training results in the mGluR5-dependent long-term inhibition of fear recovery. This effect may involve the degradation of original memory and may explain the beneficial effects of prolonged exposure therapy for the treatment of phobias.

  20. Inhibition of spontaneous recovery of fear by mGluR5 after prolonged extinction training.

    Science.gov (United States)

    Mao, Sheng-Chun; Chang, Chih-Hua; Wu, Chia-Chen; Orejarena, M Juliana; Orejanera, Maria Juliana; Manzoni, Olivier J; Gean, Po-Wu

    2013-01-01

    Fear behavior is vital for survival and involves learning contingent associations of non-threatening cues with aversive stimuli. In contrast, excessive levels of fear can be maladaptive and lead to anxiety disorders. Generally, extensive sessions of extinction training correlates with reduced spontaneous recovery. The molecular mechanisms underlying the long-term inhibition of fear recovery following repeated extinction training are not fully understood. Here we show that in rats, prolonged extinction training causes greater reduction in both fear-potentiated startle and spontaneous recovery. This effect was specifically blocked by metabotropic glutamate receptor 5 (mGluR5), but not by mGluR1 antagonists and by a protein synthesis inhibitor. Similar inhibition of memory recovery following prolonged extinction training was also observed in mice. In agreement with the instrumental role of mGluR5 in the prolonged inhibition of fear recovery, we found that FMR1-/- mice which exhibit enhanced mGluR5-mediated signaling exhibit lower spontaneous recovery of fear after extinction training than wild-type littermates. At the molecular level, we discovered that prolonged extinction training reversed the fear conditioning-induced increase in surface expression of GluR1, AMPA/NMDA ratio, postsynaptic density-95 (PSD-95) and synapse-associated protein-97 (SAP97). Accordingly, delivery of Tat-GluR2(3Y), a synthetic peptide that blocks AMPA receptor endocytosis, inhibited prolonged extinction training-induced inhibition of fear recovery. Together, our results demonstrate that prolonged extinction training results in the mGluR5-dependent long-term inhibition of fear recovery. This effect may involve the degradation of original memory and may explain the beneficial effects of prolonged exposure therapy for the treatment of phobias.

  1. The Exposure Hierarchy as a Measure of Progress and Efficacy in the Treatment of Social Anxiety Disorder

    Science.gov (United States)

    Katerelos, Marina; Hawley, Lance L.; Antony, Martin M.; McCabe, Randi E.

    2008-01-01

    This study explored the psychometric properties and utility of the exposure hierarchy as a measure of treatment outcome for social anxiety disorder (SAD). An exposure hierarchy was created for each of 103 individuals with a diagnosis of SAD who completed a course of cognitive behavioral group therapy. Exposure hierarchy ratings were collected on a…

  2. Direct pulp capping after a carious exposure versus root canal treatment: a cost-effectiveness analysis.

    Science.gov (United States)

    Schwendicke, Falk; Stolpe, Michael

    2014-11-01

    Excavation of deep caries often leads to pulpal exposure even in teeth with sensible, nonsymptomatic pulps. Although direct pulp capping (DPC) aims to maintain pulpal health, it frequently requires follow-up treatments like root canal treatment (RCT), which could have been performed immediately after the exposure, with possibly improved outcomes. We quantified and compared the long-term cost-effectiveness of both strategies. A Markov model was constructed following a molar with an occlusally located exposure of a sensible, nonsymptomatic pulp in a 20-year-old male patient over his lifetime. Transition probabilities or hazard functions were estimated based on systematically and nonsystematically assessed literature. Costs were estimated based on German health care, and cost-effectiveness was analyzed using Monte Carlo microsimulations. Despite requiring follow-up treatments significantly earlier, teeth treated by DPC were retained for long periods of time (52 years) at significantly reduced lifetime costs (545 vs 701 Euro) compared with teeth treated by RCT. For teeth with proximal instead of occlusal exposures or teeth in patients >50 years of age, this cost-effectiveness ranking was reversed. Although sensitivity analyses found substantial uncertainty regarding the effectiveness of both strategies, DPC was usually found to be less costly than RCT. We found both DPC and RCT suitable to treat exposed vital, nonsymptomatic pulps. DPC was more cost-effective in younger patients and for occlusal exposure sites, whereas RCT was more effective in older patients or teeth with proximal exposures. These findings might change depending on the health care system and underlying literature-based probabilities. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  3. Treatment of avoidance behavior as an adjunct to exposure therapy: Insights from modern learning theory.

    Science.gov (United States)

    Treanor, Michael; Barry, Tom J

    2017-09-01

    Pathological avoidance of benign stimuli is a hallmark of anxiety and related disorders, and exposure-based treatments have often encouraged the removal of avoidance, or safety behaviors, due to their negative effects on extinction learning. Unfortunately, empirical evidence suggests that avoidance behaviors can persist following treatment, and the mere availability of avoidance behavior can be sufficient to renew fear following successful extinction learning. The present paper critically examines the function of avoidance behavior through the lens of modern learning theory, and speculates on novel behavioral and pharmacological strategies for targeting avoidance as an adjunct to current evidence-based treatments. Copyright © 2017. Published by Elsevier Ltd.

  4. Cue-exposure software for the treatment of bulimia nervosa and binge eating disorder.

    Science.gov (United States)

    Gutiérrez-Maldonado, José; Pla-Sanjuanelo, Joana; Ferrer-García, Marta

    2016-11-01

    Cue-exposure therapy (CET) has proven its efficacy in treating patients with bulimia nervosa and binge eating disorder who are resistant to standard treatment. Furthermore, incorporating virtual reality (VR) technology is increasingly considered a valid exposure method that may help to increase the efficacy of standard treatments in a variety of eating disorders. Although immersive displays improve the beneficial effects, expensive technology is not always necessary. We aimed to assess whether exposure to food related virtual environments could decrease food craving in a non-clinical sample. In addition, we specifically compared the effects of two VR systems (one non-immersive and one immersive) during CET. We therefore applied a one-session CET to 113 undergraduate students. Decreased food craving was found during exposure to both VR environments compared with pre-treatment levels, supporting the efficacy of VR-CET in reducing food craving. We found no significant differences in craving between immersive and non-immersive systems. Low-cost non-immersive systems applied through 3D laptops can improve the accessibility of this technique. By reducing the costs and improving the usability, VR-CET on 3D laptops may become a viable option that can be readily applied in a greater range of clinical contexts.

  5. Integrated, exposure-based treatment for PTSD and comorbid substance use disorders: Predictors of treatment dropout.

    Science.gov (United States)

    Szafranski, Derek D; Snead, Alexandra; Allan, Nicholas P; Gros, Daniel F; Killeen, Therese; Flanagan, Julianne; Pericot-Valverde, Irene; Back, Sudie E

    2017-10-01

    High rates of comorbid posttraumatic stress disorder (PTSD) and substance use disorders (SUD) have been noted in veteran populations. Fortunately, there are a number of evidence-based psychotherapies designed to address comorbid PTSD and SUD. However, treatments targeting PTSD and SUD simultaneously often report high dropout rates. To date, only one study has examined predictors of dropout from PTSD/SUD treatment. To address this gap in the literature, this study aimed to 1) examine when in the course of treatment dropout occurred, and 2) identify predictors of dropout from a concurrent treatment for PTSD and SUD. Participants were 51 male and female veterans diagnosed with current PTSD and SUD. All participants completed at least one session of a cognitive-behavioral treatment (COPE) designed to simultaneously address PTSD and SUD symptoms. Of the 51 participants, 22 (43.1%) dropped out of treatment prior to completing the full 12 session COPE protocol. Results indicated that the majority of dropout (55%) occurred after session 6, with the largest amount of dropout occurring between sessions 9 and 10. Results also indicated a marginally significant relationship between greater baseline PTSD symptom severity and premature dropout. These findings highlight inconsistencies related to timing and predictors of dropout, as well as the dearth of information noted about treatment dropout within PTSD and SUD literature. Suggestions for procedural changes, such as implementing continual symptom assessments during treatment and increasing dialog between provider and patient about dropout were made with the hopes of increasing consistency of findings and eventually reducing treatment dropout. Published by Elsevier Ltd.

  6. Does fear extinction in the laboratory predict outcomes of exposure therapy? A treatment analog study.

    Science.gov (United States)

    Forcadell, Eduard; Torrents-Rodas, David; Vervliet, Bram; Leiva, David; Tortella-Feliu, Miquel; Fullana, Miquel A

    2017-11-01

    Fear extinction models have a key role in our understanding of anxiety disorders and their treatment with exposure therapy. Here, we tested whether individual differences in fear extinction learning and fear extinction recall in the laboratory were associated with the outcomes of an exposure therapy analog (ETA). Fifty adults with fear of spiders participated in a two-day fear-learning paradigm assessing fear extinction learning and fear extinction recall, and then underwent a brief ETA. Correlational analyses indicated that enhanced extinction learning was associated with better ETA outcome. Our results partially support the idea that individual differences in fear extinction learning may be associated with exposure therapy outcome, but suggest that further research in this area is needed. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Prolonged sulforaphane treatment activates survival signaling in nontumorigenic NCM460 colon cells but apoptotic signaling in tumorigenic HCT116 colon cells.

    Science.gov (United States)

    Zeng, Huawei; Trujillo, Olivia N; Moyer, Mary P; Botnen, James H

    2011-01-01

    Sulforaphane (SFN) is a naturally occurring chemopreventive agent; the induction of cell cycle arrest and apoptosis is a key mechanism by which SFN exerts its colon cancer prevention. However, little is known about the differential effects of SFN on colon cancer and normal cells. In this study, we demonstrated that SFN (15 μmol/L) exposure (72 h) inhibited cell proliferation by up to 95% in colon cancer cells (HCT116) and by 52% in normal colon mucosa-derived (NCM460) cells. Our data also showed that SFN exposure (5 and 10 μmol/L) led to the reduction of G1 phase cell distribution and an induction of apoptosis in HCT116 cells, but to a much lesser extent in NCM460 cells. Furthermore, the examination of mitogen-activated protein kinase (MAPK) signaling status revealed that SFN upregulated the phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) in NCM460 cells but not in HCT116 cells. In contrast, SFN enhanced the phosphorylation of stress-activated protein kinase (SAPK) and decreased cellular myelocytomatosis oncogene (c-Myc) expression in HCT116 cells but not NCM460 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic signaling in HCT116 cells may play a critical role in SFN's stronger potential of inhibiting cell proliferation in colon cancer cells than in normal colon cells. Copyright © 2011, Taylor & Francis Group, LLC

  8. Dextromethorphan as a phenotyping test to predict endoxifen exposure in patients on tamoxifen treatment.

    Science.gov (United States)

    de Graan, Anne-Joy M; Teunissen, Sebastiaan F; de Vos, Filip Y F L; Loos, Walter J; van Schaik, Ron H N; de Jongh, Felix E; de Vos, Aad I; van Alphen, Robbert J; van der Holt, Bronno; Verweij, Jaap; Seynaeve, Caroline; Beijnen, Jos H; Mathijssen, Ron H J

    2011-08-20

    Tamoxifen, a widely used agent for the prevention and treatment of breast cancer, is mainly metabolized by CYP2D6 and CYP3A to form its most abundant active metabolite, endoxifen. Interpatient variability in toxicity and efficacy of tamoxifen is substantial. Contradictory results on the value of CYP2D6 genotyping to reduce the variable efficacy have been reported. In this pharmacokinetic study, we investigated the value of dextromethorphan, a known probe drug for both CYP2D6 and CYP3A enzymatic activity, as a potential phenotyping probe for tamoxifen pharmacokinetics. In this prospective study, 40 women using tamoxifen for invasive breast cancer received a single dose of dextromethorphan 2 hours after tamoxifen intake. Dextromethorphan, tamoxifen, and their respective metabolites were quantified. Exposure parameters of all compounds were estimated, log transformed, and subsequently correlated. A strong and highly significant correlation (r = -0.72; P dextromethorphan (0 to 6 hours) and endoxifen (0 to 24 hours). Also, the area under the plasma concentration-time curve of dextromethorphan (0 to 6 hours) and daily trough endoxifen concentration was strongly correlated (r = -0.70; P dextromethorphan exposure. Dextromethorphan exposure after a single administration adequately predicted endoxifen exposure in individual patients with breast cancer taking tamoxifen. This test could contribute to the personalization and optimization of tamoxifen treatment, but it needs additional validation and simplification before being applicable in future dosing strategies.

  9. Seed Treatment Combined with a Spot Application of Clothianidin Granules Prolongs the Efficacy of Controlling Piercing-Sucking Insect Pests in Cotton Fields.

    Science.gov (United States)

    Zhang, Zhengqun; Zhao, Yunhe; Wang, Yao; Li, Beixing; Lin, Jin; Zhang, Xuefeng; Mu, Wei

    2017-09-13

    Seed treatments can directly protect cotton from early season piercing-sucking insect Aphis gossypii Glover but hardly provide long-term protection against Apolygus lucorum (Meyer-Dür). Therefore, the efficacy of clothianidin seed treatments combined with spot applications of clothianidin granules at the bud stage of cotton was evaluated to control piercing-sucking pests during the entire cotton growing season. Clothianidin seed treatments (at the rate of 4 g ai/kg seed) combined with a clothianidin granular treatment (even at low rate of 0.9 kg ai/ha) at the bud stage can effectively suppress A. gossypii and A. lucorum infestations throughout the seedling and blooming stages after planting and can improve cotton yield. The spot application of clothianidin granules also reduced the population densities of Bemisia tabaci (Gennadius). The dynamic changes of clothianidin residues demonstrated that the control efficacy of clothianidin against A. gossypii and A. lucorum might be related to the residues of this neonicotinoid in cotton leaves. This pest management practice provided long-term protection against cotton piercing-sucking pests for the entire growing season of cotton plants and could supplement the short-term control efficiency of clothianidin used as a seed treatment.

  10. Treatment experiences among LGBT veterans with discrimination-based trauma exposure: A pilot study.

    Science.gov (United States)

    Shipherd, Jillian C; Ruben, Mollie A; Livingston, Nicholas A; Curreri, Andrew; Skolnik, Avy A

    2018-01-01

    Past research suggests that rates of trauma exposure and Posttraumatic Stress Disorder (PTSD) are elevated among lesbian, gay, bisexual, and transgender (LGBT) veterans compared to heterosexual and cisgender veterans. Given higher rates of trauma exposure and PTSD, and the culture associated with the Department of Defense's history of policies excluding LGBT people, it is important to understand if LGBT veterans are seeking PTSD treatment following discrimination-based traumatic events, where they seek care, and if they are satisfied with treatment. This study aimed to describe the experiences of discrimination-based trauma-exposed LGBT veterans' (n = 47) experiences with PTSD treatment, including location of treatment (Veterans Health Administration [VHA] versus non-VHA) and satisfaction with care. The majority of veterans had received a PTSD diagnosis from a health-care provider in their lifetimes (78.72%, n = 37), and over half reported currently experiencing PTSD symptoms. Approximately 47% of LGBT veterans with discrimination-based trauma histories preferred to seek PTSD treatment exclusively at VHA (46.81%) or with a combination of VHA and non-VHA services (38.30%). Veterans who received PTSD treatment exclusively from VHA reported higher satisfaction ratings (7.44 on 0-9 scale) than veterans who received PTSD treatment exclusively from outside VHA (5.25 on 0-9 scale). For veterans who sought PTSD treatment at both VHA and non-VHA facilities, there were no significant differences regarding satisfaction ratings for their PTSD treatment in the two settings. Results are discussed in terms of VHA's continued efforts to establish equitable, patient-centered health care for all veterans and the importance of non-VHA facilities to recognize veteran identities.

  11. Evaluation of an external exposure of a worker during manipulation with waste packages stored in Bohunice radioactive waste treatment centre

    International Nuclear Information System (INIS)

    Slimak, A.; Hrncir, T.; Necas, V.

    2012-01-01

    The paper briefly describes current state of radioactive waste management as well as radioactive waste treatment and conditioning technologies used in Bohunice Radioactive Waste Treatment Centre. Radioactive Waste management includes pretreatment, treatment, conditioning, storage, transport and disposal of radioactive waste. Presented paper deals with the evaluation of an external exposure of a worker during manipulation with fibre-reinforced concrete container stored under shelter object. The external exposure of a worker was evaluated using VISIPLAN 3D ALARA code. (Authors)

  12. Intrapartum antibiotic exposure for group B Streptococcus treatment did not increase penicillin allergy in children.

    Science.gov (United States)

    May, Sara M; Hartz, Martha F; Joshi, Avni Y; Park, Miguel A

    2016-02-01

    Group B Streptococcus (GBS) is the leading infectious cause of neonatal morbidity and mortality in the United States. Intrapartum administration of antibiotics to mothers with positivity to GBS is performed for prevention, with penicillin being the drug of choice. Previous studies have noted an increase in atopic diseases other than drug allergy associated with intrapartum antibiotic exposure. To determine whether intrapartum exposure to penicillin for GBS increases the likelihood of penicillin allergy in children. Retrospective chart review was performed for patients from a birth cohort. The birth cohort included children born in 2007 at a tertiary care hospital and had local addresses. Information on GBS status of the mother, intrapartum antibiotic exposure, delivery mode, and birth order was collected and analyzed. Of 927 children identified, 804 were included in the cohort. Eighty children (10%) had a reported penicillin allergy; most were white (79%) and boys (61%). Intrapartum exposure to penicillin (odds ratio 0.84, 95% confidence interval 0.45-1.57, P = .59) or to amoxicillin or ampicillin (odds ratio 0.22, 95% confidence interval 0.01-3.71, P = .29) did not increase the risk of penicillin allergy in children. In addition, all other factors evaluated did not affect the risk of penicillin allergy in children. To the authors' knowledge, this is the first study to evaluate intrapartum exposure to penicillin for GBS treatment and subsequent development of penicillin allergy in the child. In contrast to other atopic diseases, intrapartum antibiotic exposure does not alter the risk of penicillin allergy. Parents and obstetricians should be reassured when using penicillin for prevention of neonatal GBS. Published by Elsevier Inc.

  13. Integrated MRSA-Management (IMM with prolonged decolonization treatment after hospital discharge is effective: a single centre, non-randomised open-label trial

    Directory of Open Access Journals (Sweden)

    Bernhard Jahn

    2016-06-01

    Full Text Available Abstract Background Guidelines for the control of hospital-acquired MRSA include decolonization measures to end MRSA carrier status in colonized and infected patients. Successful decolonization typically requires up to 22 days of treatment, which is longer than the average hospital length of stay (LOS. Incomplete decolonization is therefore common, with long-term MRSA carriage as a consequence. To overcome this, we developed an integrated MRSA Management (IMM by extending MRSA decolonization to the outpatient and domestic setting. The protocol makes use of polyhexanide-based products, in view of reported qac-mediated resistance to chlorhexidine in S. aureus and MRSA. Methods This is a prospective, single centre, controlled, non-randomized, open-label study to evaluate the efficiency of the IMM concept. The outcome of guideline-approved decolonization during hospital stay only (control group; n = 201 was compared to the outcome following IMM treatment whereby decolonization was continued after discharge in the domestic setting or in a long-term care facility (study group; n = 99. As a secondary outcome, the effect of MRSA-status of skin alterations was assessed. Results The overall decolonization rate was 47 % in the IMM patient group compared to 12 % in the control group (p  0.05. For patients with skin alterations (e.g. wounds and entry sites, decolonization success was 50 % if the skin alterations were MRSA-negative at baseline, compared to 22 % success for patients entering the study with MRSA-positive skin alterations (p < 0.01. Conclusions The IMM strategy offers an MRSA decolonization protocol that is feasible in the domestic setting and is equally effective compared with inpatient decolonization treatment when hospital LOS is long enough to complete the treatment. Moreover, for patients with average LOS, decolonization rates obtained with IMM are significantly higher than for in-hospital treatment. IMM is a promising

  14. Basal exposure therapy: A new approach for treatment resistant patients with severe and comorbid mental disorders

    Directory of Open Access Journals (Sweden)

    Didrik Heggdal

    2016-12-01

    Full Text Available New treatment approaches are needed for patients with severe and composite mental disorders who appear resistant to conventional treatments. Such treatment resistant patients often have diagnoses of psychotic or bipolar disorders or severe personality disorders and comorbid conditions. Here we evaluate Basal Exposure Therapy (BET, a novel ward-integrated psychotherapeutic approach for these patients. Central to BET is the conceptualization of undifferentiated existential fear as basic to the patients’ problem, exposure to this fear, and the therapeutic platform Complementary External Regulation (CER which integrates and governs the totality of interventions throughout the treatment process. BET is administered at a locked-door ward with six patient beds and 13.5 full time employees, including a psychiatrist and two psychologists. Thirty-eight patients who had completed BET were included, all but two being female, mean age 29.9 years. Fourteen patients had a diagnosis of schizophrenia or schizoaffective disorder (F20/25, eight had bipolar disorder or recurrent depressive disorder (F31/33, eight had diagnoses in the F40-49 domain (anxiety, stress, dissociation, five were diagnosed with emotionally unstable personality disorder (F60.3, and three patients had other diagnoses. Twenty of the patients (53% had more than one ICD-10 diagnosis. Average treatment time in BET was 13 months, ranging from 2 to 72 months. Time-series data show significant improvements in symptoms and functioning from enrolment to discharge, with effect sizes at 0.76 for the Dissociation Experience Scale, 0.93 for the Brief Symptom Inventory, 1.47 for the Avoidance and Action Questionnaire, and 1.42 and 1.56, respectively for the functioning and symptom subscales of the Global Assessment of Functioning Scale. In addition, the patients used significantly less antiepileptic, antipsychotic, anxiolytic and antidepressant medications at discharge than at treatment enrolment

  15. Exposure to Mobile Phone Radiation Opens New Horizons in Alzheimer’s Disease Treatment

    Science.gov (United States)

    Mortazavi, SAR; Shojaei-Fard, MB; Haghani, M; Shokrpour, N; Mortazavi, SMJ

    2013-01-01

    Alzheimer’s disease, the most common type of dementia and a progressive neurodegenerative disease, occurs when the nerve cells in the brain die. Although there are medications that can help delay the development of Alzheimer’s disease, there is currently no cure for this disease. Exposure to ionizing and non-ionizing radiation may cause adverse health effects such as cancer.  Looking at the other side of the coin, there are reports indicating stimulatory or beneficial effects after exposure to cell phone radiofrequency radiation. Mortazavi et al. have previously reported some beneficial cognitive effects such as decreased reaction time after human short-term exposure to cell phone radiation or occupational exposure to radar microwave radiation. On the other hand, some recent reports have indicated that RF radiation may have a role in protecting against cognitive impairment in Alzheimer’s disease. Although the majority of these data come from animal studies that cannot be easily extrapolated to humans, it can be concluded that this memory enhancing approach may open new horizons in treatment of cognitive impairment in Alzheimer disease. PMID:25505755

  16. Exposure to Mobile Phone Radiation Opens New Horizons in Alzheimer’s Disease Treatment

    Directory of Open Access Journals (Sweden)

    Mortazavi SAR

    2013-09-01

    Full Text Available Alzheimer’s disease, the most common type of dementia and a progressive neurodegenerative disease, occurs when the nerve cells in the brain die. Although there are medications that can help delay the development of Alzheimer’s disease, there is currently no cure for this disease. Exposure to ionizing and non-ionizing radiation may cause adverse health effects such as cancer. Looking at the other side of the coin, there are reports indicating stimulatory or benefcial effects after exposure to cell phone radiofrequency radiation. Mortazavi et al. have previously reported some benefcial cognitive effects such as decreased reaction time after human short-term exposure to cell phone radiation or occupational exposure to radar microwave radiation. On the other hand, some recent reports have indicated that RF radiation may have a role in protecting against cognitive impairment in Alzheimer’s disease. Although the majority of these data come from animal studies that cannot be easily extrapolated to humans, it can be concluded that this memory enhancing approach may open new horizons in treatment of cognitive impairment in Alzheimer disease.

  17. Exposure to mobile phone radiation opens new horizons in Alzheimer's disease treatment.

    Science.gov (United States)

    Mortazavi, Sar; Shojaei-Fard, Mb; Haghani, M; Shokrpour, N; Mortazavi, Smj

    2013-09-01

    Alzheimer's disease, the most common type of dementia and a progressive neurodegenerative disease, occurs when the nerve cells in the brain die. Although there are medications that can help delay the development of Alzheimer's disease, there is currently no cure for this disease. Exposure to ionizing and non-ionizing radiation may cause adverse health effects such as cancer.  Looking at the other side of the coin, there are reports indicating stimulatory or beneficial effects after exposure to cell phone radiofrequency radiation. Mortazavi et al. have previously reported some beneficial cognitive effects such as decreased reaction time after human short-term exposure to cell phone radiation or occupational exposure to radar microwave radiation. On the other hand, some recent reports have indicated that RF radiation may have a role in protecting against cognitive impairment in Alzheimer's disease. Although the majority of these data come from animal studies that cannot be easily extrapolated to humans, it can be concluded that this memory enhancing approach may open new horizons in treatment of cognitive impairment in Alzheimer disease.

  18. [The effect of prolonged treatment of hypertensive rats with antihypertensive drugs of various actions on the arterial tension and noradrenaline level in the myocardium, brain and aortal].

    Science.gov (United States)

    Kiriakov, A; Khlebarova, M; Staneva-stoicheva, D; Panova, I

    1975-01-01

    The authors examined the changes in arterial blood pressure and the content of Noradrenaline in the myocardium, brain and aorta of rats with hypertension due to nephrectomy and treatment with desoxycorticosterone and NaCl, and after a chronic 6-month treatment of hypertension with various antihypertensive means. The most significant reduction of noradrenaline in the three of the examined tissues was found in rats, which received dic. sulfyram (100 mg/kg per os). Clondine (10 mkg/kg, per os) manifested the strongest hypotensive effect and lowered the level of noradrenaline in the myocardium, while it was raised in the aorta. Reserpine (10 mkg/kg, s. c) induced a clear reduction of Noradrenaline content in the brain, but an increase in the other two tissues. Insignificant hypotensive effect was observed in animals, treated with guanetidine (0.5 mg/kg, per os), which did not affect substantially noradrenaline in the examined organs. The increase of noradrenaline level was established in the three of the organs of animals, treated with alpha-methyl-DOFA (25 mg/kg, per os). Furosemide (1 mg/kg, s.c.) induced a statistically significant elevation of noradrenaline in the aorta, but was noneffective to noradrenaline in the myocardium and brain.

  19. [Androgens and prolonged complete remissions in acute non lymphoblastic leukemias. Results of a systematic treatment with stanozolol associated with chemotherapy (author's transl)].

    Science.gov (United States)

    Sotto, J J; Hollard, D; Schaerer, R; Bensa, J C; Seigneurin, D

    1975-01-01

    An androgen (stanozolol: 0,15 mg/kg/d) was systematically associated to the treatment of acute non lymphoblastic leukemias, since the beginning of induction therapy (vincristin, daunorubicin, prednisone) and throughout the maintenance period (6-mercaptopurine and methotrexate). Thirty-six patients less than 60 years old (median age: 44 years) presenting with acute non-lymphoblastic leukemia were entered to the study. Sixteen achieved complete remission (C.R.), i.e. 44% of the whole and 53% of treated patients. Out of 16 patients with complete remission, 4 relapsed during the observation period which lasted 4-1/2 years. The stability of the hematologic equilibrium in patients in C.R. is the main finding of the present study. The actuarial curve of the duration of the first complete remission reaches a "plateau"; after the 8th month only one relapse was observed in 9 patients. The rate of C.R. at 2 years is 76 +/- 23%. As compared to the results from other schedules of treatment, this rate appears significantly better, specially in the case of immunotherapy (p less than 0,001). A prospective randomized study is now suggested as to confirm this result; its therapeutic and theoretical basis and perspectives are discussed.

  20. Dream recall and dream content in obsessive-compulsive patients: is there a change during exposure treatment?

    Science.gov (United States)

    Kuelz, Anne K; Stotz, Ulrike; Riemann, Dieter; Schredl, Michael; Voderholzer, Ulrich

    2010-08-01

    Very little is known about dreams in patients with obsessive compulsive disorder, especially regarding changes over the course of treatment with stimulus exposure and response prevention. By use of dream content analysis, 40 dreams of 9 obsessive compulsive (OC) inpatients were compared with 84 dreams of 10 matched OC outpatients and 63 dreams of 11 healthy control participants. Dream protocols of inpatients were collected at the beginning of treatment and after the first exposure exercises. Controls filled in dream protocols in respective intervals. Before treatment, dreams of patients showed significantly less positive contents than dreams of healthy controls. Under treatment with exposure, a significant reduction of OC themes was observed. The findings support the continuity hypothesis of dreaming by showing a link between day-time symptoms and OC symptoms in dreams. Contrary to expectations, however, exposure treatment does not intensify dreams.

  1. Factors associated with prolonged time to treatment failure with fulvestrant 500 mg in patients with post-menopausal estrogen receptor-positive advanced breast cancer: a sub-group analysis of the JBCRG-C06 Safari study.

    Science.gov (United States)

    Kawaguchi, Hidetoshi; Masuda, Norikazu; Nakayama, Takahiro; Aogi, Kenjiro; Anan, Keisei; Ito, Yoshinori; Ohtani, Shoichiro; Sato, Nobuaki; Saji, Shigehira; Takano, Toshimi; Tokunaga, Eriko; Nakamura, Seigo; Hasegawa, Yoshie; Hattori, Masaya; Fujisawa, Tomomi; Morita, Satoshi; Yamaguchi, Miki; Yamashita, Hiroko; Yamashita, Toshinari; Yamamoto, Yutaka; Yotsumoto, Daisuke; Toi, Masakazu; Ohno, Shinji

    2018-01-01

    The JBCRG-C06 Safari study showed that earlier fulvestrant 500 mg (F500) use, a longer time from diagnosis to F500 use, and no prior palliative chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with estrogen receptor-positive (ER+) advanced breast cancer (ABC). The objective of this sub-group analysis was to further examine data from the Safari study, focusing on ER + and human epidermal growth factor receptor-negative (HER2-) cases. The Safari study (UMIN000015168) was a retrospective, multi-center cohort study, conducted in 1,072 patients in Japan taking F500 for ER + ABC. The sub-analysis included only patients administered F500 as second-line or later therapy (n = 960). Of these, 828 patients were HER2-. Results Multivariate analysis showed that advanced age (≥65 years; p = .035), longer time (≥3 years) from ABC diagnosis to F500 use (p < .001), no prior chemotherapy (p < .001), and F500 treatment line (p < .001) were correlated with prolonged TTF (median = 5.39 months). In ER+/HER2- patients receiving F500 as a second-line or later therapy, treatment line, advanced age, no prior palliative chemotherapy use, and a longer period from ABC diagnosis to F500 use were associated with longer TTF.

  2. Down-regulation of dopamine D-2, 5-HT2 receptors and β-adrenoceptors in rat brain after prolonged treatment with a new potential antidepressant, Lu 19-005

    International Nuclear Information System (INIS)

    Nowak, G.; Arnt, J.; Hyttel, J.; Svendsen, O.

    1985-01-01

    Lu 19-005 is a new phenylindan derivative with strong and equipotent inhibitory effect on dopamine (DA), noradrenaline (NA) and serotonin (5-HT) uptake. The adaptive effects of 2 weeks treatment with Lu 19-005, on receptor binding in vitro and on d-amphetamine responsiveness in vivo have been investigated in rats. One or 3 days after the final dose the number of β-adrenoceptors and of 5-HT 2 and DA D-2 receptors was decreased by 20-30%, whereas αsub1-adrenoceptor number was slightly decreased only 1 day after withdrawal. The DA D-2 receptor number remained decreased at 7 days withdrawal, but returned to normal after another 3 days. The brain levels of DA, NA and 5-HT were not changed by 2 weeks' Lu 19-005 treatment. The down-regulation of DA D-2 receptors was accompanied by tolerance to d-amphetamine-induced hypermotility (after low doses) and stereotyped licking or biting (after a high dose). The tolerance to d-amphetamine-induced hypermotility was maximal 3-5 days withdrawal time, and remained significant also 15 days after the last dose. The results are discussed in relation to the effect of prolonged treatment with other antidepressant drugs. (Author)

  3. Prolonged efficacy of the 300IR 5-grass pollen tablet up to 2 years after treatment cessation, as measured by a recommended daily combined score

    DEFF Research Database (Denmark)

    Didier, Alain; Malling, Hans-Jørgen; Worm, Margitta

    2015-01-01

    BACKGROUND: The 300IR (index of reactivity) 5-grass pollen tablet has favorable short-term and sustained clinical efficacy in patients with grass pollen-induced allergic rhinoconjunctivitis (ARC). Here, we report maintenance of efficacy and safety over 2 years following treatment discontinuation....... METHODS: Randomized, double-blind, placebo-controlled, parallel-group, multicenter Phase 3 trial in patients aged 18-50 years with ARC. During study years 1-3, patients received a daily sublingual tablet containing either 300IR 5-grass pollen extract or placebo, according to a discontinuous pre...... medication score (DRMS). RESULTS: 633 patients with ARC were randomized to placebo (n = 219) or 300IR 5-grass pollen tablet, beginning 4 months (4 M, n = 207) or 2 months (2 M, n = 207) prior to the estimated start of the grass pollen season and continuing until season's end. During the first post...

  4. Prolonged treatment with imatinib mesylate in patients with advanced chronic myeloid leukemia causes a reduction of bcr/abl mRNA levels independent of cytogenetic response.

    Science.gov (United States)

    Cariani, E; Capucci, M; Micheletti, M; Spalenza, F; Zanella, I; Albertini, A; Rossi, G

    2003-06-01

    Bcr/abl mRNA levels were monitored in 13 patients with chronic myeloid leukemia receiving imatinib mesylate over a period of 78 weeks. During treatment median bcr/abl mRNA levels progressively declined from 77.2 normalized dose (nD) at baseline to 11.28 nD after 13 weeks ( P<0.05) and to 1.28 nD after 78 weeks ( P<0.05). After 13 weeks, bcr/abl mRNA levels were significantly lower in cytogenetic responders compared to nonresponders ( P<0.05), but subsequent decrease in the transcript levels caused the loss of any correlation to the cytogenetic status. These results suggest that bcr/abl mRNA levels may reflect cytogenetic response only during the early phases of imatinib therapy.

  5. The long-term effects of a life-prolonging heat treatment on the Drosophila melanogaster transcriptome suggest that heat shock proteins extend lifespan

    DEFF Research Database (Denmark)

    Sarup, Pernille Merete; Sørensen, Peter; Loeschcke, Volker

    2014-01-01

    Heat-induced hormesis, i.e. the beneficial effect of mild heat-induced stress, increases the average lifespan of many organisms. This effect, which depends on the heat shock factor, decreases the log mortality rate weeks after the stress has ceased. To identify candidate genes that mediate......-treated flies. Several hsp70 probe sets were up-regulated 1.7–2-fold in the mildly stressed flies weeks after the last heat treatment (P shock protein, Hsp70, is reported to return to normal levels of expression shortly after heat stress. We...... conclude that the heat shock response, and Hsp70 in particular, may be central to the heat-induced increase in the average lifespan in flies that are exposed to mild heat stress early in life....

  6. Evaluation of the Methods of portective Treatment against microbiological damages and prolonged antimicrobic protection of the interior and the equipment of space objects

    Science.gov (United States)

    Deshevaya, E.; Novikova, N.; Polycarpov, N.; Poddubko, S.; Shumilina, G.; Bragina, M.; Zarubina, K.; Tverskoy, V.; Akova, M. D.

    The researches which have been carried out onboard the orbital complex (? C) MIR, testify that environment of the manned space object may be considered as peculiar ecological niche for development of the microbial community generated by microorganisms of various physiological and taxonomic groups. As a result of vital activity of fungi during OC MIR operation zones of fungi growth on various elements of interior and equipment, cases of destruction of the materials and attributes of corrosion of metals were noted. Existing methods of development of microorganisms on a surface of constructional materials using sanitary treatment of the accessible surfaces with disinfectants, represent the big labour input for the crew. More radical solution of the problem is the development and use of methods of superficial modification of constructional materials and use of methods of superficial modification of constructional materials and treatment of their surface of varnish or paint, resistant to biocontamination and growth of the microorganisms. As a result of the conducted research, the following methods of protection of constructional materials against development of microorganisms were chosen: - fluorination, sylilition, radiating graft polymerization etc., resulting in formation of the functional groups having biocide action; For varnish and paint coverings - coverings on a basis stoichiometrical interpolymeric polyelectrolytic complexes, organosilicone coverings, etc. For testing of the biological effects of samples of the materials subjected to the different methods of surface modification, researches were carried out and experimental models of typical biodestructive processes of the constructional materials are developed considering microclimatic parameters of local zones (the increased temperature and humidity), resistance of the materials to the influence of fungi and increased radiating background influence. Biological testing testifying the efficiency of developed

  7. Effects of cue-exposure treatment on neural cue reactivity in alcohol dependence: a randomized trial.

    Science.gov (United States)

    Vollstädt-Klein, Sabine; Loeber, Sabine; Kirsch, Martina; Bach, Patrick; Richter, Anne; Bühler, Mira; von der Goltz, Christoph; Hermann, Derik; Mann, Karl; Kiefer, Falk

    2011-06-01

    In alcohol-dependent patients, alcohol-associated cues elicit brain activation in mesocorticolimbic networks involved in relapse mechanisms. Cue-exposure based extinction training (CET) has been shown to be efficacious in the treatment of alcoholism; however, it has remained unexplored whether CET mediates its therapeutic effects via changes of activity in mesolimbic networks in response to alcohol cues. In this study, we assessed CET treatment effects on cue-induced responses using functional magnetic resonance imaging (fMRI). In a randomized controlled trial, abstinent alcohol-dependent patients were randomly assigned to a CET group (n = 15) or a control group (n = 15). All patients underwent an extended detoxification treatment comprising medically supervised detoxification, health education, and supportive therapy. The CET patients additionally received nine CET sessions over 3 weeks, exposing the patient to his/her preferred alcoholic beverage. Cue-induced fMRI activation to alcohol cues was measured at pretreatment and posttreatment. Compared with pretreatment, fMRI cue-reactivity reduction was greater in the CET relative to the control group, especially in the anterior cingulate gyrus and the insula, as well as limbic and frontal regions. Before treatment, increased cue-induced fMRI activation was found in limbic and reward-related brain regions and in visual areas. After treatment, the CET group showed less activation than the control group in the left ventral striatum. The study provides first evidence that an exposure-based psychotherapeutic intervention in the treatment of alcoholism impacts on brain areas relevant for addiction memory and attentional focus to alcohol-associated cues and affects mesocorticolimbic reward pathways suggested to be pathophysiologically involved in addiction. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  8. H2O2 homeostasis in wild-type and ethylene-insensitive Never ripe tomato in response to salicylic acid treatment in normal photoperiod and in prolonged darkness.

    Science.gov (United States)

    Takács, Zoltán; Poór, Péter; Borbély, Péter; Czékus, Zalán; Szalai, Gabriella; Tari, Irma

    2018-05-01

    Ethylene proved to be an important modulator of salicylic acid (SA) signalling pathway. Since SA may regulate both the production and scavenging of hydrogen peroxide (H 2 O 2 ), which show light-dependency, the aim of this study was to compare H 2 O 2 metabolism in the leaves of SA-treated wild-type (WT) tomato (Solanum lycopersicum L. cv. Ailsa Craig) and in ethylene receptor Never-ripe (Nr) mutants grown in normal photoperiod or in prolonged darkness. H 2 O 2 accumulation was higher in the WT than in the mutants in normal photoperiod after 1 mM SA treatment, while Nr leaves contained more H 2 O 2 after light deprivation. The expression of certain superoxide dismutase (SOD) genes and activity of the enzyme followed the same tendency as H 2 O 2 , which was scavenged by different enzymes in the two genotypes. Catalase (CAT, EC 1.11.1.6) activity was inhibited by SA in WT, while the mutants maintained enhanced enzyme activity in the dark. Thus, in WT, CAT inhibition was the major component of the H 2 O 2 accumulation elicited by 1 mM SA in a normal photoperiod, since the expression and/or activity of ascorbate (APX, EC 1.11.1.11) and guaiacol peroxidases (POD, EC 1.11.1.7) were induced in the leaves. The absence of APX and POD activation in mutant plants suggests that the regulation of these enzymes by SA needs functional ethylene signalling. While the block of ethylene perception in Nr mutants was overwritten in the transcription and activity of certain SOD and CAT isoenzymes during prolonged darkness, the low APX and POD activities led to H 2 O 2 accumulation in these tissues. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  9. Low socioeconomic status is associated with prolonged times to assessment and treatment, sepsis and infectious death in pediatric fever in El Salvador.

    Directory of Open Access Journals (Sweden)

    Ronald Gavidia

    Full Text Available BACKGROUND: Infection remains the most common cause of death from toxicity in children with cancer in low- and middle-income countries. Rapid administration of antibiotics when fever develops can prevent progression to sepsis and shock, and serves as an important indicator of the quality of care in children with acute lymphoblastic leukemia and acute myeloid leukemia. We analyzed factors associated with (1 Longer times from fever onset to hospital presentation/antibiotic treatment and (2 Sepsis and infection-related mortality. METHOD: This prospective cohort study included children aged 0-16 years with newly diagnosed acute leukemia treated at Benjamin Bloom Hospital, San Salvador. We interviewed parents/caregivers within one month of diagnosis and at the onset of each new febrile episode. Times from initial fever to first antibiotic administration and occurrence of sepsis and infection-related mortality were documented. FINDINGS: Of 251 children enrolled, 215 had acute lymphoblastic leukemia (85.7%. Among 269 outpatient febrile episodes, median times from fever to deciding to seek medical care was 10.0 hours (interquartile range [IQR] 5.0-20.0, and from decision to seek care to first hospital visit was 1.8 hours (IQR 1.0-3.0. Forty-seven (17.5% patients developed sepsis and 7 (2.6% died of infection. Maternal illiteracy was associated with longer time from fever to decision to seek care (P = 0.029 and sepsis (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.09-8.63; P = 0.034. More infectious deaths occurred in those with longer travel time to hospital (OR 1.36, 95% CI 1.03-1.81; P = 0.031 and in families with an annual household income treatment of fever and with sepsis and infectious mortality in pediatric leukemia. Providing additional education to high-risk families

  10. Ways to Optimize Therapy of Prolonged Conjugation Jaundice in Infants

    Directory of Open Access Journals (Sweden)

    O.G. Shadrin

    2015-09-01

    Full Text Available The article is devoted to the optimization of the treatment of prolonged conjugation jaundice. Inclusion of ursodeoxycholic acid in the treatment of neonatal prolonged conjugation jaundice in a dose of 15–20 mg/kg of body mass per day increases the terms of regression of clinical and paraclinical signs of jaundice as much as 2 times and leads to cytolysis normalization. The preparation has a sufficient level of safety, there were not revealed side effects whilst its application.

  11. Exposure to professional pest control treatments and the risk of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Bailey, Helen D; Armstrong, Bruce K; de Klerk, Nicholas H; Fritschi, Lin; Attia, John; Scott, Rodney J; Smibert, Elizabeth; Milne, Elizabeth

    2011-10-01

    Previous studies suggest that exposure to pesticides increases the risk of childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to investigate whether professional pest treatments in or around the home before birth or during childhood increased the risk of childhood ALL. Data from 388 cases and 870 frequency-matched controls were analyzed using unconditional logistic regression, adjusting for study matching variables and potential confounders, to calculate odds ratios (ORs). A meta-analysis of our findings with the published findings of previous studies was also conducted. The ORs for any professional pest control treatments were 1.19 (95% CI 0.83, 1.69) in the year before pregnancy, 1.30 (95% CI 0.86, 1.97) during pregnancy and 1.24 (95% CI 0.93, 1.65) for those done after the child's birth. The ORs for exposure after birth were highest when it occurred between the ages of two and three years. ORs were elevated for termite treatments before birth. ORs were higher for pre-B than T cell ALL and for t(12;21) (ETV6-Runx-1) than other cytogenetic sub-types. The pooled OR from a meta-analysis of our study with three previous studies of professional pest control treatments during pregnancy was 1.37 (95% CI 1.00, 1.88). Our results, and those of our meta-analysis, provide some evidence of a modestly increased risk of ALL for professional pest control treatments done during the index pregnancy and possibly in the child's early years. The analysis of pooled data from international collaborations may provide more certainty regarding these potentially important associations. Copyright © 2011 UICC.

  12. Lifetime prevalence of mental disorders in Lebanon: first onset, treatment, and exposure to war.

    Directory of Open Access Journals (Sweden)

    Elie G Karam

    2008-04-01

    Full Text Available There are no published data on national lifetime prevalence and treatment of mental disorders in the Arab region. Furthermore, the effect of war on first onset of disorders has not been addressed previously on a national level, especially in the Arab region. Thus, the current study aims at investigating the lifetime prevalence, treatment, age of onset of mental disorders, and their relationship to war in Lebanon.The Lebanese Evaluation of the Burden of Ailments and Needs Of the Nation study was carried out on a nationally representative sample of the Lebanese population (n = 2,857 adults. Respondents were interviewed using the fully structured WHO Composite International Diagnostic Interview 3.0. Lifetime prevalence of any Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV disorder was 25.8%. Anxiety (16.7% and mood (12.6% were more common than impulse control (4.4% and substance (2.2% disorders. Only a minority of people with any mental disorder ever received professional treatment, with substantial delays (6 to 28 y between the onset of disorders and onset of treatment. War exposure increased the risk of first onset of anxiety (odds ratio [OR] 5.92, 95% confidence interval [CI] 2.5-14.1, mood (OR 3.32, 95% CI 2.0-5.6, and impulse control disorders (OR 12.72, 95% CI 4.5-35.7.About one-fourth of the sample (25.8% met criteria for at least one of the DSM-IV disorders at some point in their lives. There is a substantial unmet need for early identification and treatment. Exposure to war events increases the odds of first onset of mental disorders.

  13. Diagnosis and emergency treatment of human exposures to ionizing radiations: practical aspects

    International Nuclear Information System (INIS)

    Martin, A.

    1980-01-01

    In case of accidental exposure, occupational physicians in nuclear power plants are faced with problems of diagnosis and early treatment. External irradiation, external and internal contamination will be considered successively. The experience is large as the first unit of the nuclear plant, the second in the world for the capacity, was started up 8 years ago. Of course, problems of radiation protection are different from those encountered in a research center or a hospital and cannot be solved in the same manner. The information gathered should be useful to all those that are faced with such problems [fr

  14. Prolonged QRS Widening After Aripiprazole Overdose.

    Science.gov (United States)

    Mazer-Amirshahi, Maryann; Porter, Robert; Dewey, Kayla

    2018-05-05

    Aripiprazole is an atypical antipsychotic with a long half-life. Overdose can result in protracted somnolence and cardiac disturbances, particularly QT interval prolongation. This is a single case report of a 14-year-old boy who took an overdose of aripiprazole and developed QRS widening. A 14-year-old boy intentionally ingested 20 tablets of aripiprazole (5 mg). He was brought to the emergency department when his ingestion was discovered. The patient's vital signs were as follows: temperature, 37.7°C; heart rate, 108 beats/min; blood pressure, 138/98 mm Hg; and respirations, 16 breaths/min. Activated charcoal was administered within 90 minutes of ingestion. Initial electrocardiogram (EKG) showed sinus tachycardia, with a QRS of 138 ms and QT interval of 444 ms. QRS duration was 90 ms on an EKG performed 3 months earlier. A bolus of sodium bicarbonate was administered, and the patient was transferred to the pediatric intensive care unit. Repeat EKG demonstrated a QRS of 156 ms, and a sodium bicarbonate infusion was initiated. The patient continued to have QRS prolongation for the next 8 days, reaching a peak of 172 ms 3 days postingestion. Despite aggressive treatment with sodium bicarbonate, there was persistent QRS prolongation; however, the patient did not have any dysrhythmias and remained hemodynamically stable. The patient was discharged 9 days postingestion when the QRS duration normalized to 82 ms. Genetic testing revealed that the patient was a CYP2D6 poor metabolizer. This case suggests that aripiprazole toxicity may possibly be associated with QRS prolongation without associated dysrhythmias or cardiovascular compromise. In addition, toxicity may be prolonged in patients who are CYP2D6 poor metabolizers.

  15. Prolongation of islet allograft survival

    International Nuclear Information System (INIS)

    Lacy, P.E.; Davie, J.M.; Finke, E.H.; Scharp, D.W.

    1979-01-01

    Pretreatment of donor rats with irradiation and silica followed by in vitro culture of the islets for 1 to 2 days prolonged survival of allografts across a minor histocompatibility barrier if hand-picked, clean islets were used for transplantation. Pretreatment of donor rats with irradiation and silica in conjunction with a single injection of antilymphocyte serum (ALS) into the recipient produced a prolongation of survival of hand-picked islets transplanted across a major histocompatibility barrier

  16. Genetic influence on prolonged gestation

    DEFF Research Database (Denmark)

    Laursen, Maja; Bille, Camilla; Olesen, Annette Wind

    2004-01-01

    OBJECTIVE: The purpose of this study was to test a possible genetic component to prolonged gestation. STUDY DESIGN: The gestational duration of single, first pregnancies by both female and male twins was obtained by linking the Danish Twin Registry, The Danish Civil Registration System, and the D...... factors. CONCLUSION: Maternal genes influence prolonged gestation. However, a substantial paternal genetic influence through the fetus was not found....

  17. Treatment of radiation exposure and regeneration medicine. Regeneration treatment of blood vessels by transplantation of autologous marrow monocytes

    International Nuclear Information System (INIS)

    Nagai, Kazuhiro; Kamihira, Shimeru; Matsumaru, Ichiro; Fukushima, Takuya; Yamaguchi, Hakuichiro; Miyazaki, Yasushi; Yamachika, Shiro; Eishi, Kiyoyuki; Tomonaga, Masao

    2007-01-01

    Described are usefulness and future view of regenerative medicine in the treatment of radiation exposure as exemplified by the vascular regeneration by autologous marrow cell transplantation. Vascular endothelial cells (VEC), possessing a high ability to divide, are known sensitive to radiation, which gives damage of blood vessel to alter its permeability leading to apoptosis of VEC, organ/tissue injuries and final damages in the cerebral blood vessels, central nervous system and skin, the acute radiation syndrome (ARS). Authors present successful cases of patients with chronic limb ischemia in the Therapeutic Angiogenesis using Cell Transplantation Trial (TACT), to whom the treatment is conducted with transplantation of autologous marrow monocyte fraction containing endothelial progenitor cells that differentiate to VEC. As well, they touch on a case of the patient encountered in a nuclear accident, mentioning that VEC are found partly derived from the donor after heamatopoietic stem cell transplantation (HSCT). Efficacy of HSCT in a literature is reviewed and commented to be an only limited one in 31 patients of various radiation accidents. However, treatment of ARS where stem cells are target, with regenerative medicine will become more useful in future, as basic and clinical researches will provide requisite findings. (T.I.)

  18. Exposure to virtual social interactions in the treatment of social anxiety disorder: A randomized controlled trial.

    Science.gov (United States)

    Kampmann, Isabel L; Emmelkamp, Paul M G; Hartanto, Dwi; Brinkman, Willem-Paul; Zijlstra, Bonne J H; Morina, Nexhmedin

    2016-02-01

    This randomized controlled trial investigated the efficacy of a stand-alone virtual reality exposure intervention comprising verbal interaction with virtual humans to target heterogeneous social fears in participants with social anxiety disorder. Sixty participants (Mage = 36.9 years; 63.3% women) diagnosed with social anxiety disorder were randomly assigned to individual virtual reality exposure therapy (VRET), individual in vivo exposure therapy (iVET), or waiting-list. Multilevel regression analyses revealed that both treatment groups improved from pre-to postassessment on social anxiety symptoms, speech duration, perceived stress, and avoidant personality disorder related beliefs when compared to the waiting-list. Participants receiving iVET, but not VRET, improved on fear of negative evaluation, speech performance, general anxiety, depression, and quality of life relative to those on waiting-list. The iVET condition was further superior to the VRET condition regarding decreases in social anxiety symptoms at post- and follow-up assessments, and avoidant personality disorder related beliefs at follow-up. At follow-up, all improvements were significant for iVET. For VRET, only the effect for perceived stress was significant. VRET containing extensive verbal interaction without any cognitive components can effectively reduce complaints of generalized social anxiety disorder. Future technological and psychological improvements of virtual social interactions might further enhance the efficacy of VRET for social anxiety disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. PMO Delivery System Using Bubble Liposomes and Ultrasound Exposure for Duchenne Muscular Dystrophy Treatment.

    Science.gov (United States)

    Negishi, Yoichi; Ishii, Yuko; Nirasawa, Kei; Sasaki, Eri; Endo-Takahashi, Yoko; Suzuki, Ryo; Maruyama, Kazuo

    2018-01-01

    Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration, caused by nonsense or frameshift mutations in the dystrophin (DMD) gene. Antisense oligonucleotides can be used to induce specific exon skipping; recently, a phosphorodiamidate morpholino oligomer (PMO) has been approved for clinical use in DMD. However, an efficient PMO delivery strategy is required to improve the therapeutic efficacy in DMD patients. We previously developed polyethylene glycol (PEG)-modified liposomes containing ultrasound contrast gas, "Bubble liposomes" (BLs), and found that the combination of BLs with ultrasound exposure is a useful gene delivery tool. Here, we describe an efficient PMO delivery strategy using the combination of BLs and ultrasound exposure to treat muscles in a DMD mouse model (mdx). This ultrasound-mediated BL technique can increase the PMO-mediated exon-skipping efficiency, leading to significantly increased dystrophin expression. Thus, the combination of BLs and ultrasound exposure may be a feasible PMO delivery method to improve therapeutic efficacy and reduce the PMO dosage for DMD treatment.

  20. Behavioural treatment of tics: habit reversal and exposure with response prevention.

    Science.gov (United States)

    van de Griendt, J M T M; Verdellen, C W J; van Dijk, M K; Verbraak, M J P M

    2013-07-01

    Behaviour therapy has been shown to be an effective strategy in treating tics; both habit reversal (HR) and exposure and response prevention (ER) are recommended as first-line interventions. This review provides an overview of the history, theoretical concepts and evidence at present for HR and ER. In addition, treatment manuals for HR and ER are described. Despite the evidence and availability of treatment manuals, many patients do not receive a first-line psychological intervention for tics. Barriers to the acceptance and dissemination of behaviour therapy are discussed as are ways to overcome these barriers, such as the use of E-health and E-learning. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Cholinesterase reactivators and bioscavengers for pre- and post-exposure treatments of organophosphorus poisoning.

    Science.gov (United States)

    Masson, Patrick; Nachon, Florian

    2017-08-01

    Organophosphorus agents (OPs) irreversibly inhibit acetylcholinesterase (AChE) causing a major cholinergic syndrome. The medical counter-measures of OP poisoning have not evolved for the last 30 years with carbamates for pretreatment, pyridinium oximes-based AChE reactivators, antimuscarinic drugs and neuroprotective benzodiazepines for post-exposure treatment. These drugs ensure protection of peripheral nervous system and mitigate acute effects of OP lethal doses. However, they have significant limitations. Pyridostigmine and oximes do not protect/reactivate central AChE. Oximes poorly reactivate AChE inhibited by phosphoramidates. In addition, current neuroprotectants do not protect the central nervous system shortly after the onset of seizures when brain damage becomes irreversible. New therapeutic approaches for pre- and post-exposure treatments involve detoxification of OP molecules before they reach their molecular targets by administrating catalytic bioscavengers, among them phosphotriesterases are the most promising. Novel generation of broad spectrum reactivators are designed for crossing the blood-brain barrier and reactivate central AChE. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

  2. Vaginal mucosal flap as a sling preservation for the treatment of vaginal exposure of mesh.

    Science.gov (United States)

    Kim, Sea Young; Park, Jong Yeon; Kim, Han Kwon; Park, Chang Hoo; Kim, Sung Jin; Sung, Gi Teck; Park, Chang Myon

    2010-06-01

    Tension-free vaginal tape (TVT) procedures are used for the treatment of stress urinary incontinence in women. The procedures with synthetic materials can have a risk of vaginal erosion. We experienced transobturator suburethral sling (TOT) tape-induced vaginal erosion and report the efficacy of a vaginal mucosal covering technique. A total of 560 female patients diagnosed with stress urinary incontinence underwent TOT procedures at our hospital between January 2005 and August 2009. All patients succeeded in follow-ups, among which 8 patients (mean age: 50.5 years) presented with vaginal exposure of the mesh. A vaginal mucosal covering technique was performed under local anesthesia after administration of antibiotics and vaginal wound dressings for 3-4 days. Seven of the 8 patients complained of persistent vaginal discharge postoperatively. Two of the 8 patients complained of dyspareunia of their male partners. The one remaining patient was otherwise asymptomatic, but mesh erosion was discovered at the routine follow-up visit. Six of the 8 patients showed complete mucosal covering of the mesh after the operation (mean follow-up period: 16 moths). Vaginal mucosal erosion recurred in 2 patients, and the mesh was then partially removed. One patient had recurrent stress urinary incontinence. Vaginal mucosal covering as a sling preservation with continued patient continence may be a feasible and effective option for the treatment of vaginal exposure of mesh after TOT tape procedures.

  3. Protein Characterization of Javan Cobra (Naja sputatrix) Venom Following Sun Exposure and Photo-Oxidation Treatment

    Science.gov (United States)

    Sulistiyani; Biki, R. S.; Andrianto, D.

    2017-03-01

    Snake venom has always been known for its toxicity that can cause fatality, however, it is also one of the important biological resources to be used for disease treatment. In Indonesia, snake venom previously expose under the sun has been used for alternative treatment of some diseases such as dengue fever, atherosclerosis, cancer, and diabetes. There has been very little scientific evidence on the use of snake venom of Indonesia origin as well as its protein characteristic. Thus, the objective of this research is to characterize the protein content and the specific activity of the venom of Javan Cobra (N.sputatrix) when treated with sun exposure in comparison with photo-oxidation by ultraviolet. Qualitative analysis of protein contents was determined using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE). The L-amino acid oxidase activity (LAAO) and the phospholipase A2 (PLA2) activities were determined using spectrophotometry. The venom’s protein was separated into 5 main protein bands with molecular weight ranging from 14 to 108 kDa. A time course study showed that the venom lost 91% of its LAAO activity and 96% of PLA2 activity after 6 hours of sun exposure. UV photo-oxidation carried out for 3 hours decreased 91% of LAAO activity, and almost diminished all of PLA2 activity (99.8%). These findings suggest that the exposure of N. sputatrix venom under the sun and UV photo-oxidation decreased its toxicity as shown by the significant reduction of the enzymes activity, but did not affect the protein’s integrity. Therefore, these approaches produced N.sputatrix venom with less toxicity but still withheld other characters of intact proteins.

  4. Severe bradycardia and prolonged hypotension in ciguatera.

    Science.gov (United States)

    Chan, Thomas Yan Keung

    2013-06-01

    Ciguatera results when ciguatoxin-contaminated coral reef fish from tropical or subtropical waters are consumed. The clinical features that present in affected persons are mainly gastrointestinal, neurological, general, and much less commonly, cardiovascular. We report the case of a 50-year-old man who developed the characteristic combination of acute gastrointestinal and neurological symptoms after the consumption of an unidentified coral reef fish head. In addition to those symptoms, he developed dizziness, severe bradycardia (46 bpm) and prolonged hypotension, which required the administration of intravenous atropine and over three days of intravenous fluid replacement with dopamine infusion. Patients with ciguatera can develop severe bradycardia and prolonged hypotension. Physicians should recognise the possible cardiovascular complications of ciguatera and promptly initiate treatment with intravenous atropine, intravenous fluid replacement and inotropic therapy if such complications are observed.

  5. "Dwelling in the Past": The Role of Rumination in the Treatment of Posttraumatic Stress Disorder

    Science.gov (United States)

    Echiverri, Aileen M.; Jaeger, Jeff J.; Chen, Jessica A.; Moore, Sally A.; Zoellner, Lori A.

    2011-01-01

    Prolonged exposure, a cognitive behavioral therapy including both in vivo and imaginal exposure to the traumatic memory, is one of several empirically supported treatments for chronic posttraumatic stress disorder (PTSD). In this article, we provide a case illustration in which this well-validated treatment did not yield expected clinical gains…

  6. Does engagement with exposure yield better outcomes? Components of presence as a predictor of treatment response for virtual reality exposure therapy for social phobia.

    Science.gov (United States)

    Price, Matthew; Mehta, Natasha; Tone, Erin B; Anderson, Page L

    2011-08-01

    Virtual reality exposure (VRE) has been shown to be effective for treating a variety of anxiety disorders, including social phobia. Presence, or the level of connection an individual feels with the virtual environment, is widely discussed as a critical construct both for the experience of anxiety within a virtual environment and for a successful response to VRE. Two published studies show that whereas generalized presence relates to fear ratings during VRE, it does not relate to treatment response. However, presence has been conceptualized as multidimensional, with three primary factors (spatial presence, involvement, and realness). These factors can be linked to other research on the facilitation of fear during exposure, inhibitors of treatment response (e.g., distraction), and more recent theoretical discussions of the mechanisms of exposure therapy, such as Bouton's description of expectancy violation. As such, one or more of these components of presence may be more strongly associated with the experience of fear during VRE and treatment response than the overarching construct. The current study (N=41) evaluated relations between three theorized components of presence, fear ratings during VRE, and treatment response for VRE for social phobia. Results suggest that total presence and realness subscale scores were related to in-session peak fear ratings. However, only scores on the involvement subscale significantly predicted treatment response. Implications of these findings are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Symptom dimensions in obsessive-compulsive disorder: phenomenology and treatment outcomes with exposure and ritual prevention.

    Science.gov (United States)

    Williams, Monnica T; Mugno, Beth; Franklin, Martin; Faber, Sonya

    2013-01-01

    Obsessive-compulsive disorder (OCD) is a severe condition with varied symptom presentations. Currently, the cognitive-behavioral treatment with the most empirical support is exposure and ritual prevention (EX/RP); however, clinical impression and some empirical data suggest that certain OCD symptoms are more responsive to treatment than others. Prior work identifying symptom dimensions within OCD is discussed, including epidemiological findings, factor analytic studies, and biological findings. Symptom dimensions most reliably identified include contamination/cleaning, doubt about harm/checking, symmetry/ordering, and unacceptable thoughts/mental rituals. The phenomenology of each of these subtypes is described and research literature is summarized, emphasizing the differential effects of EX/RP and its variants on each of these primary symptom dimensions. To date it appears that EX/RP is an effective treatment for the various OCD dimensions, although not all dimensions have been adequately studied (i.e. symmetry and ordering). Modifications to treatment may be warranted for some types of symptoms. Clinical implications and directions for future research are discussed. Copyright © 2013 S. Karger AG, Basel.

  8. Effect of previous exposure to hbv on liver histology and treatment response in chc patients

    International Nuclear Information System (INIS)

    Khan, H.A.

    2015-01-01

    Objective: To analyze the influence of previous exposure to HBV on liver histology and treatment outcomes in chronic hepatitis C (CHC) patients. Study Design: Case control study. Place and Duration of Study: Rawalian Liver Clinic, Department of Medicine, Holy Family Hospital, Rawalpindi, from January 2011 to December 2012. Methodology: Medical records of CHC patients attending the Rawalian Liver Clinic were retrospectively analyzed. Virological and treatment responses along with histological changes were compared between cases (anti-HBc positive) and controls (anti-HBc negative). Significance was determined through chi-square test at p < 0.05. Results: Among the 592 CHC patients, 254 (42.9%) had serological evidence of a positive anti-HBc (cases) and 338 (57.1%), patients had negative anti-HBc (controls). No significant difference was found between ETR, SVR and treatment responses (n=220) between the two groups. Out of 65 patients whose liver biopsy data was available, cases were more likely to respond in the absence of fibrosis (63.2%, (n=24) vs. 36.8%, (n=14), p=0.001). The controls responded more in the presence of fibrosis (100% (n=9) vs. 0, p=0.001). There was no significant effect of anti-HBc positivity on grades of inflammation and consequent treatment response (p=0.14). Conclusion: There are a significant number of CHC patients with markers of previous HBV infection in Pakistani population. Previous HBV (anti-HBc positive) does not seem to have an adverse effect on liver histology and treatment responses in HBV infection. (author)

  9. Virtual Reality Treatment in Acrophobia : A Comparison with Exposure in Vivo

    NARCIS (Netherlands)

    Emmelkamp, P.M.G.; Bruynzeel, M.; Drost, L.; Van der Mast, C.A.P.G.

    2001-01-01

    The aim of the present study was to evaluate the effectiveness of low-budget virtual reality exposure versus exposure in vivo in a within-group design in 10 individuals suffering from acrophobia. Virtual reality exposure was found to be at least as effective as exposure in vivo on anxiety and

  10. Moving forward in treatment of posttraumatic stress disorder: innovations to exposure-based therapy.

    Science.gov (United States)

    Nijdam, Mirjam J; Vermetten, Eric

    2018-01-01

    The field of treatment of posttraumatic stress disorder (PTSD) has been a pacesetter for the changing face of psychotherapy, as is illustrated in the introduction of Virtual Reality Exposure Therapy. This paper outlines a novel approach that builds on a cognitive-motor interaction in a virtual interactive environment. It is based on the theory of memory reconsolidation and the embodiment of cognition. The framework we envision allows the patient to 'step into the past' by using forward motion as an essential ingredient to augment the impact of exposure to traumatic events. The behavioural response of approaching that is the exact opposite from the avoidance usually applied by patients and the enhancement of divergent thinking are the most prominent hypothesized mechanisms of action. This can contribute to strengthening of personal efficacy and self-reflection that is generated by high emotional engagement, as well as a sense of accomplishment and enhanced recovery as illustrated by a clinical case example. We argue that innovations with personalized virtual reality and motion need to be further investigated and implemented in current therapy settings.

  11. Virtual reality exposure therapy for the treatment of anxiety disorders: an evaluation of research quality.

    Science.gov (United States)

    McCann, Russell A; Armstrong, Christina M; Skopp, Nancy A; Edwards-Stewart, Amanda; Smolenski, Derek J; June, Jennifer D; Metzger-Abamukong, Melinda; Reger, Greg M

    2014-08-01

    Randomized controlled trials (RCTs) support the effectiveness of virtual reality exposure therapy (VRET) for anxiety disorders; however, the overall quality of the VRET RCT literature base has yet to be evaluated. This study reviewed 27 VRET RCTs and the degree of adherence to 8 RCT research design criteria derived from existing standards. Adherence to the study quality criteria was generally low as the articles met an average 2.85 criteria (SD=1.56). None of the studies met more than six quality criteria. Study quality did not predict effect size; however, a reduction in effect size magnitude was observed for studies with larger sample sizes when comparing VRET to non-active control groups. VRET may be an effective method of treatment but caution should be exercised in interpreting the existing body of literature supporting VRET relative to existing standards of care. The need for well-designed VRET research is discussed. Copyright © 2014. Published by Elsevier Ltd.

  12. Prolonged acid rain facilitates soil organic carbon accumulation in a mature forest in Southern China.

    Science.gov (United States)

    Wu, Jianping; Liang, Guohua; Hui, Dafeng; Deng, Qi; Xiong, Xin; Qiu, Qingyan; Liu, Juxiu; Chu, Guowei; Zhou, Guoyi; Zhang, Deqiang

    2016-02-15

    With the continuing increase in anthropogenic activities, acid rain remains a serious environmental threat, especially in the fast developing areas such as southern China. To detect how prolonged deposition of acid rain would influence soil organic carbon accumulation in mature subtropical forests, we conducted a field experiment with simulated acid rain (SAR) treatments in a monsoon evergreen broadleaf forest at Dinghushan National Nature Reserve in southern China. Four levels of SAR treatments were set by irrigating plants with water of different pH values: CK (the control, local lake water, pH ≈ 4.5), T1 (water pH=4.0), T2 (water pH=3.5), and T3 (water pH=3.0). Results showed reduced pH measurements in the topsoil exposed to simulated acid rains due to soil acidification. Soil respiration, soil microbial biomass and litter decomposition rates were significantly decreased by the SAR treatments. As a result, T3 treatment significantly increased the total organic carbon by 24.5% in the topsoil compared to the control. Furthermore, surface soil became more stable as more recalcitrant organic matter was generated under the SAR treatments. Our results suggest that prolonged acid rain exposure may have the potential to facilitate soil organic carbon accumulation in the subtropical forest in southern China. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Therapist-Aided Exposure for Women with Lifelong Vaginismus: Mediators of Treatment Outcome: A Randomized Waiting List Control Trial.

    Science.gov (United States)

    Ter Kuile, Moniek M; Melles, Reinhilde J; Tuijnman-Raasveld, Charlotte C; de Groot, Helen E; van Lankveld, Jacques J D M

    2015-08-01

    Therapist-aided exposure seems an effective treatment for lifelong vaginismus, but mechanisms of action have not yet been established. The purpose of the present study was to investigate whether treatment outcome of a therapist-aided exposure treatment was mediated by changes in positive and negative penetration beliefs or feelings of sexual disgust. Participants with lifelong vaginismus were allocated at random to a 3-month exposure (n = 35) or a waiting list control condition (n = 35). Full intercourse was assessed daily during 12 weeks. Secondary outcome measures (complaints about vaginismus and coital pain) were assessed at baseline and after 12 weeks. Possible mediators: penetration beliefs (catastrophic pain beliefs, genital incompatibility beliefs, perceived control beliefs) and feelings of sexual disgust were assessed at baseline and 6 weeks. Treatment outcome (coital frequency, symptoms of vaginismus, and coital pain) at 12 weeks was mediated by changes in negative and positive penetration beliefs at 6 weeks, in particular by more pronounced reduction of catastrophic pain penetration beliefs. No evidence was found that changes in feelings of sexual disgust mediated treatment outcome. The results strongly suggest that therapist-aided exposure affects negative penetration beliefs and that these changes in negative penetration beliefs mediate treatment outcome in women with lifelong vaginismus. Implications for treatment are discussed. © 2015 International Society for Sexual Medicine.

  14. Efficacy of virtual reality exposure therapy for treatment of dental phobia: a randomized control trial.

    Science.gov (United States)

    Raghav, Kumar; Van Wijk, A J; Abdullah, Fawzia; Islam, Md Nurul; Bernatchez, Marc; De Jongh, Ad

    2016-02-27

    Virtual Reality Exposure Therapy (VRET) is found to be a promising and a viable alternative for in vivo exposure in the treatment of specific phobias. However, its usefulness for treating dental phobia is unexplored. The aims of the present study are to determine: (a) the efficacy of VRET versus informational pamphlet (IP) control group in terms of dental trait and state anxiety reductions at 1 week, 3 months and 6 months follow-up (b) the real-time physiological arousal [heart rate (HR)] of VRET group participants during and following therapy (c) the relation between subjective (presence) and objective (HR) measures during VRET. This study is a single blind, randomized controlled trial with two parallel arms in which participants will be allocated to VRET or IP with a ratio of 1:1. Thirty participants (18-50 years) meeting the Phobia Checklist criteria of dental phobia will undergo block randomization with allocation concealment. The primary outcome measures include participants' dental trait anxiety (Modified Dental Anxiety Scale and Dental Fear Survey) and state anxiety (Visual Analogue Scale) measured at baseline (T0), at intervention (T1), 1-week (T2), 3 months (T3) and 6 months (T4) follow-up. A behavior test will be conducted before and after the intervention. The secondary outcome measures are real-time evaluation of HR and VR (Virtual Reality) experience (presence, realism, nausea) during and following the VRET intervention respectively. The data will be analyzed using intention-to-treat and per-protocol analysis. This study uses novel non-invasive VRET, which may provide a possible alternative treatment for dental anxiety and phobia. ISRCTN25824611 , Date of registration: 26 October 2015.

  15. Perfluoroalkyl substances (PFASs) in wastewater treatment plants and drinking water treatment plants: Removal efficiency and exposure risk.

    Science.gov (United States)

    Pan, Chang-Gui; Liu, You-Sheng; Ying, Guang-Guo

    2016-12-01

    Perfluoroalkyl substances (PFASs) are a group of chemicals with wide industrial and commercial applications, and have been received great attentions due to their persistence in the environment. The information about their presence in urban water cycle is still limited. This study aimed to investigate the occurrence and removal efficiency of eighteen PFASs in wastewater treatment plants (WWTPs) and drinking water plants (DWTPs) with different treatment processes. The results showed that both perfluorobutane sulfonic acid (PFBS) and perfluorooctane sulfonic acid (PFOS) were the predominant compounds in the water phase of WWTPs and DWTPs, while PFOS was dominant in dewatered sludge of WWTPs. The average total PFASs concentrations in the three selected WWTPs were 19.6-232 ng/L in influents, 15.5-234 ng/L in effluents, and 31.5-49.1 ng/g dry weight in sludge. The distribution pattern of PFASs differed between the wastewater and sludge samples, indicating strong partition of PFASs with long carbon chains to sludge. In the WWTPs, most PFASs were not eliminated efficiently in conventional activated sludge treatment, while the membrane bio-reactor (MBR) and Unitank removed approximately 50% of long chain (C ≥ 8) perfluorocarboxylic acids (PFCAs). The daily mass loads of total PFASs in WWTPs were in the range of 1956-24773 mg in influent and 1548-25085 mg in effluent. PFASs were found at higher concentrations in the wastewater from plant A with some industrial wastewater input than from the other two plants (plant B and plant C) with mainly domestic wastewater sources. Meanwhile, the average total PFASs concentrations in the two selected DWTPs were detected at 4.74-14.3 ng/L in the influent and 3.34-13.9 ng/L in the effluent. In DWTPs, only granular activated carbon (GAC) and powder activated carbon (PAC) showed significant removal of PFASs. The PFASs detected in the tap water would not pose immediate health risks in the short term exposure. The findings from this

  16. Lethal exposure times of anoxic treatment in eight species of museum pests (fam. Dermestidae, Ptinidae and Tineidae)

    DEFF Research Database (Denmark)

    Bergh, Jan-Erik; Hansen, Lise Stengaard; Nielsen, Per Væggemose

    1999-01-01

    Based on surveys of species of museum pest insects commonly found in Fennoscandia, a number of important species were selected for a study of mortality caused by exposure to modified atmosphere (>99.7 % nitrogen). In most of the species 100 % mortality was obtained within 72 hours of exposure....... Preliminary analysis of the results revealed that the larval and pupal stages were most tolerant to the anoxic treatment....

  17. Narrative exposure therapy: an evidence-based treatment for multiple and complex trauma

    Directory of Open Access Journals (Sweden)

    Ruud A. Jongedijk

    2014-12-01

    Full Text Available Narrative exposure therapy (NET is a recently developed, short-term treatment for patients with a posttraumatic stress disorder (PTSD as a result of multiple trauma. NET can be applied very successfully in patients with complex trauma complaints (Jongedijk, 2014; Schauer, Neuner, & Elbert, 2011.An important feature of NET is that trauma processing is never an isolated event but is always embedded in the context of a traumatic event and in the life history as a whole. At the start, the lifeline is laid. The lifeline is made up of a rope, with flowers (happy events, stones (traumatic events, sometimes candles (grief, or recently also sticks for aggressive acts (NET for offenders; see Stenmark, Cuneyt Guzey, Elbert, & Holen, 2014. These symbols are laid down along the rope, in chronological order. Subsequently, in the subsequent therapy sessions the lifeline is processed in chronological order, giving attention to all the important events a person has experienced in his or her life, both the adverse as well as the pleasurable ones. The narration ends with a written testimony.To date, there is good evidence NET is effective in the treatment of PTSD patients, with support from 18 RCTs (N=950. For culturally diverse populations, NET is recommended as the most evidence-based trauma treatment, besides culturally adapted CBT. NET has been investigated in different populations in Africa, Europe, and Asia. In Asia, research has been carried out in Sri Lanka as well as in China. In China, NET was conducted and investigated with survivors of the Sichuan earthquake (Zang, Hunt, & Cox, 2013, 2014. NET is understandable, even appealing and also supportive for patients with multiple trauma. In this presentation, the treatment principles and the practice of NET will be explained.

  18. Prolonged unexplained fatigue in paediatrics

    NARCIS (Netherlands)

    Bakker, R.J.

    2010-01-01

    Prolonged Unexplained Fatigue in Paediatrics. Fatigue, as the result of mental or physical exertion, will disappear after rest, drinks and food. Fatigue as a symptom of illness will recover with the recovering of the illness. But when fatigue is ongoing for a long time, and not the result of

  19. Physiology Of Prolonged Bed Rest

    Science.gov (United States)

    Greenleaf, John E.

    1991-01-01

    Report describes physiological effects of prolonged bed rest. Rest for periods of 24 hours or longer deconditions body to some extent; healing proceeds simultaneously with deconditioning. Report provides details on shifts in fluid electrolytes and loss of lean body mass, which comprises everything in body besides fat - that is, water, muscle, and bone. Based on published research.

  20. Extended UVB Exposures Alter Tumorigenesis and Treatment Efficacy in a Murine Model of Cutaneous Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Burns, E. M.; Tober, K. L.; Riggenbach, J. A.; Oberyszyn, T. M.; Kusewitt, D. F.; Young, G. S.

    2013-01-01

    Epidemiological studies support a link between cumulative sun exposure and cutaneous squamous cell carcinoma (SCC) development. However, the presumed effects of extended ultraviolet light B (UVB) exposure on tumorigenesis in the sexes have not been formally investigated. We examined differences in ultimate tumorigenesis at 25 weeks in mice exposed to UVB for either 10 or 25 weeks. Additionally, we investigated the effect of continued UVB exposure on the efficacy of topical treatment with anti-inflammatory (diclofenac) or antioxidant (C E Ferulic or vitamin E) compounds on modulating tumorigenesis. Vehicle-treated mice in the 25-week UVB exposure model exhibited an increased tumor burden and a higher percentage of malignant tumors compared to mice in the 10-week exposure model, which correlated with increases in total and mutant p53-positive epidermal cells. Only topical diclofenac decreased tumor number and burden in both sexes regardless of UVB exposure length. These data support the commonly assumed but not previously demonstrated fact that increased cumulative UVB exposure increases the risk of UVB-induced SCC development and can also affect therapeutic efficacies. Our study suggests that cessation of UVB exposure by at-risk patients may decrease tumor development and that topical NSAIDs such as diclofenac may be chemo preventive.

  1. Extended UVB Exposures Alter Tumorigenesis and Treatment Efficacy in a Murine Model of Cutaneous Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Erin M. Burns

    2013-01-01

    Full Text Available Epidemiological studies support a link between cumulative sun exposure and cutaneous squamous cell carcinoma (SCC development. However, the presumed effects of extended ultraviolet light B (UVB exposure on tumorigenesis in the sexes have not been formally investigated. We examined differences in ultimate tumorigenesis at 25 weeks in mice exposed to UVB for either 10 or 25 weeks. Additionally, we investigated the effect of continued UVB exposure on the efficacy of topical treatment with anti-inflammatory (diclofenac or antioxidant (C E Ferulic or vitamin E compounds on modulating tumorigenesis. Vehicle-treated mice in the 25-week UVB exposure model exhibited an increased tumor burden and a higher percentage of malignant tumors compared to mice in the 10-week exposure model, which correlated with increases in total and mutant p53-positive epidermal cells. Only topical diclofenac decreased tumor number and burden in both sexes regardless of UVB exposure length. These data support the commonly assumed but not previously demonstrated fact that increased cumulative UVB exposure increases the risk of UVB-induced SCC development and can also affect therapeutic efficacies. Our study suggests that cessation of UVB exposure by at-risk patients may decrease tumor development and that topical NSAIDs such as diclofenac may be chemopreventive.

  2. Are ECG monitoring recommendations before prescription of QT-prolonging drugs applied in daily practice?

    DEFF Research Database (Denmark)

    Warnier, Miriam Jacoba; Rutten, Frans Hendrik; Souverein, Patrick Cyriel

    2015-01-01

    PURPOSE: Monitoring of the QT duration by electrocardiography (ECG) prior to treatment is frequently recommended in the label of QT-prolonging drugs. It is, however, unknown how often general practitioners in daily clinical practice are adhering to these risk-minimization measures. We assessed...... the frequency of ECG measurements in patients where haloperidol was initiated in primary care. METHODS: Patients (≥18 years) with a first prescription of haloperidol in the UK Clinical Practice Research Datalink (2009-2013) were included. The proportion of ECGs made was determined in two blocks of 4 weeks......: during the exposure period when haloperidol was initiated, and during the control period, 1 year before. Conditional logistic regression analysis was applied to calculate the relative risk of having an ECG in the exposure period compared with the control period. Subgroup analyses were performed to assess...

  3. Virtual reality exposure therapy for the treatment of posttraumatic stress disorder: a methodological review using CONSORT guidelines.

    Science.gov (United States)

    Motraghi, Terri E; Seim, Richard W; Meyer, Eric C; Morissette, Sandra B

    2014-03-01

    Virtual reality exposure therapy (VRET) is an extension of traditional exposure therapy and has been used to treat a variety of anxiety disorders. VRET utilizes a computer-generated virtual environment to present fear-relevant stimuli. Recent studies have evaluated the use of VRET for treatment of PTSD; however, a systematic evaluation of the methodological quality of these studies has yet to be conducted. This review aims to (a) identify treatment outcome studies examining the use of VRET for the treatment of PTSD and (b) appraise the methodological quality of each study using the 2010 Consolidating Standards of Reporting Trials (CONSORT) Statement and its 2008 extension for nonpharmacologic interventions. Two independent assessors conducted a database search (PsycINFO, Medline, CINAHL, Google Scholar) of studies published between January 1990 and June 2013 that reported outcome data comparing VRET with another type of treatment or a control condition. Next, a CONSORT quality appraisal of each study was completed. The search yielded nine unique studies. The CONSORT appraisal revealed that the methodological quality of studies examining VRET as a treatment for PTSD was variable. Although preliminary findings suggest some positive results for VRET as a form of exposure treatment for PTSD, additional research using well-specified randomization procedures, assessor blinding, and monitoring of treatment adherence is warranted. Movement toward greater standardization of treatment manuals, virtual environments, and equipment would further facilitate interpretation and consolidation of this literature. © 2013 Wiley Periodicals, Inc.

  4. RD50 Prolongation Request 2018

    CERN Document Server

    Casse, Gianluigi

    2018-01-01

    With this document, we request the prolongation of the CERN RD50 research program for 5 years. A very brief historical review of the RD50 research program since the RD50 project approval by the Research Board in the year 2002 is presented and the biggest RD50 achievements are highlighted. The present composition of the collaboration, its organizational structure, and the research methodology are described. The role of RD50 in the present various upgrade and research programs of the LHC Experiments community is given and the overall work plan explained. Finally, a detailed 5-years work program with precise milestones and deliverables for the various research activities is presented. We conclude with our prolongation request towards the LHCC.

  5. Evaluation of eleven years of area monitoring in ore treatment unit: I external exposure

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, W.S.; Py Junior, D.A.; Oliveira, S.Q. de; Dantas, M.V.A., E-mail: pereiraws@gmail.com [Industrias Nucleares do Brasil (INB), Pocos de Caldas, MG (Brazil). Unidade de Tratamento de Minerio. Grupo Multidisciplinar de Radioprotecao; Kelecom, A., E-mail: akelecom@id.uff.br [Universidade Federal Fluminense (LARARA-PLS/GETA/UFF), Niteroi, RJ (Brazil). Laboratorio de Radiobiologia e Radiometria Pedro Lopes dos Santos. Grupo de Estudos em Temas Ambientais; Pereira, J.R.S., E-mail: pereirarsj@gmail.com [Universidade Federal de Alfenas (UNIFAL), Pocos de Caldas, MG (Brazil)

    2013-07-01

    The Ore Treatment Unit (OTU) is an uranium mining and milling complex deactivated in 1995 that operated monazite during the years 2004 and 2005 in a plant used especially for that purpose called Chemical Treatment of Monazite (CTM). This study aims to analyze the monitoring of area to exposure rate from 2002 to 2012, comparing periods of suspended operation of OTU and identifying the influences of CTM and of the radioactive waste deposit, from other facilities of OTU. A total of 22,294 samples were analyzed for area dose rates; average values were obtained of 6.74 μSv h{sup -1} with an amplitude from 0 to 420 μSv h{sup -1}. 92% of the monitoring were below the derivative limit for workers, and 1,702 monitoring samples showed values above this limit. Ignoring the monitoring that was realized at CTM and at the deposit of radioactive waste, the number of monitoring samples were reduced to 1,341. In this case, the average reduces to 0.96 μSv h{sup -1}, going from 0 to 25 μSv h{sup -1}, only 15 samples remained above the threshold for workers and 675 samples were below the limit for individual public. It can be concluded that the OTU is an installation with nearly 99% of monitoring area safe for workers and 50% for individual public. The inclusion of new practices (CTM) and the deposit of radioactive waste coming from other facilities alter this picture dramatically, increased the dose rates. (author)

  6. Virtual Reality Exposure Therapy for the Treatment of Dental Phobia: A Controlled Feasibility Study.

    Science.gov (United States)

    Gujjar, Kumar Raghav; van Wijk, Arjen; Sharma, Ratika; de Jongh, Ad

    2018-05-01

    Virtual reality exposure therapy (VRET) has been used to treat a variety of fears and phobias. To determine the feasibility (i.e. safety and efficacy) of using VRET to treat dental phobia. Safety was evaluated by determining any adverse events or symptom exacerbation. Efficacy of VRET was evaluated by comparing the reduction in dental anxiety scores (measured 16 times within a 14-week study period, and at 6-month follow-up), and its behavioural effects with that of an informational pamphlet (IP) on ten randomized patients with dental phobia using a controlled multiple baseline design. Participants' heart rate response during VRET, and their experience post-VRET, were indexed. No personal adverse events or symptom exacerbation occurred. Visual analysis and post-hoc intention-to-treat analysis showed a significantly greater decrease in dental anxiety scores [higher PND (percentage of non-overlap data) scores of 100% and lower POD (percentage of overlap data) of 0%, Modified Dental Anxiety Scale, F (1,8) = 8.61, p = 0.019, and Dental Fear Scale, F (1,8) = 10.53, p = 0.012], and behavioural avoidance in the VRET compared with the IP group [d = 4.2 and -1.4, respectively). There was no increase in average heart rate during VRET. Of the nine treatment completers, six (four from the VRET group and two from the IP group) no longer had dental phobia at 6-month follow-up. Four of the five VRET participants, but none of the IP participants, scheduled a dental treatment appointment following the intervention. VRET is a feasible alternative for patients with dental phobia.

  7. An Evaluation of Multi-Component Exposure Treatment of Needle Phobia in an Adult with Autism and Intellectual Disability

    Science.gov (United States)

    Wolff, Jason J.; Symons, Frank J.

    2013-01-01

    Background: Fear of medical procedures in general and needles in particular can be a difficult clinical challenge to providing effective health care for individuals with intellectual and developmental disabilities. Methods: A changing criterion design was used to examine graduated exposure treatment for blood-injury-injection phobia in an adult…

  8. Internet-delivered multi-patient virtual reality exposure therapy system for the treatment of anxiety disorders

    NARCIS (Netherlands)

    Kang, N.; Brinkman, W.P.; Riemsdijk, M.B. van; Neerincx, M.A.

    2011-01-01

    Motivation - The project is to reduce the therapist's workload in virtual reality exposure therapy (VRET) for anxiety disorders and explore cognitive ergonomic factors in the design of an internet-delivered multi-patient treatment system. Research questions - The aim can be achieved by system

  9. Cue exposure therapy for the treatment of opiate addiction: results of a randomized controlled clinical trial.

    Science.gov (United States)

    Marissen, Marlies A E; Franken, Ingmar H A; Blanken, Peter; van den Brink, Wim; Hendriks, Vincent M

    2007-01-01

    Persistent cue reactivity to drug-related stimuli is a well-known phenomenon among abstinent drug users and has been found to be a predictor of relapse. Cue exposure therapy (CET) aims to reduce this cue reactivity by exposing abstinent drug users to conditioned drug-related stimuli while preventing their habitual response, i.e. drug use. 127 abstinent heroin-dependent Dutch inpatients were randomized to CET (n = 65; 55 completers) and placebo psychotherapy treatment (PPT) (n = 62; 59 completers). It was examined whether CET would lead to a decrease in drug-related cue reactivity (using mixed-design ANOVA) and subsequently to lower dropout and relapse rates (using logistic regression) compared to PPT. Both groups responded with a similar decrease in self-reported cue reactivity (craving, mood). The CET group did show a significant decrease in physiological reactivity (skin conductance) compared to PPT. However, dropout and relapse rates were, contrary to our expectations, significantly higher in the CET group. This is the first randomized controlled trial showing that CET, compared to a non-specific psychotherapy, might increase dropout and relapse rates among abstinent heroin-dependent clients in a drug-free setting. Caution is warranted when applying CET in this specific context. Copyright 2007 S. Karger AG, Basel.

  10. Virtual reality exposure versus cognitive restructuring for treatment of public speaking anxiety: a pilot study.

    Science.gov (United States)

    Wallach, Helene S; Safir, Marilyn P; Bar-Zvi, Margalit

    2011-01-01

    To determine the utility of Virtual Reality Exposure Therapy (VRE) in comparison with Cognitive Therapy (CT ) and with Cognitive-Behavior Therapy (CBT). Subjects suffering from public speaking anxiety (PSA) were randomly allocated to VRE and CT , and received 12 therapy sessions, employing standardized treatment manuals. Outcome (questionnaires, observer and self ratings of a behavioral task) was compared to results of subjects in a previous study CBT and Wait List Controls who were not significantly different on demographic data. CT was not superior to VRE on cognitive measures, but was superior to VRE on one behavioral measure (LSAS fear). VRE was superior to CT on one behavioral measure (fear reduction on a behavioral task). No differences were found between either CT , or VRE, and CBT and all were superior to WL. Subject group was small and homogeneous. It appeared advisable to increase number of therapy sessions. VRE and CT proved to be equally effective to CBT in reducing PSA relative to a control group, with minimal differential effects between them. Therefore, employing either one may be satisfactory and sufficient.

  11. Prolonged response without prolonged chemotherapy: a lesson from PCV chemotherapy in low-grade gliomas

    Science.gov (United States)

    Peyre, Matthieu; Cartalat-Carel, Stéphanie; Meyronet, David; Ricard, Damien; Jouvet, Anne; Pallud, Johan; Mokhtari, Karima; Guyotat, Jacques; Jouanneau, Emmanuel; Sunyach, Marie-Pierre; Frappaz, Didier; Honnorat, Jérôme; Ducray, François

    2010-01-01

    Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). PCV (procarbazine, CCNU, vincristine) chemotherapy has demonstrated efficacy in treating LGGs, but this therapy cannot be used for a prolonged period because of the cumulative toxicity. The aim of the present study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth kinetics. The mean tumor diameter (MTD) of 21 LGGs was measured on serial magnetic resonance images before (n=13), during, and after PCV onset (n=21). During PCV treatment, a decrease in the MTD was observed in all patients. After PCV discontinuation, an ongoing decrease in MTD was observed in 20 of the 21 patients. Median duration of the MTD decrease was 3.4 years (range, 0.8–7.7) after PCV onset and 2.7 years (range, 0–7) after the end of PCV treatment with 60% of LGGs, demonstrating an ongoing and prolonged (>2 years) response despite chemotherapy no longer being administered. According to McDonald's criteria, the rates of partial and minor responses were 5% and 38% at the end of PCV but 38% and 42% at the time of maximal MTD decrease, which occurred after a median period of 3.4 years after PCV onset. These results challenge the idea that a prolonged duration of chemotherapy is necessary for treating LGGs and raise the issue of understanding the mechanisms involved in the persistent tumor volume decrease once chemotherapy is terminated. PMID:20488959

  12. The key role of extinction learning in anxiety disorders: behavioral strategies to enhance exposure-based treatments.

    Science.gov (United States)

    Pittig, Andre; van den Berg, Linda; Vervliet, Bram

    2016-01-01

    Extinction learning is a major mechanism for fear reduction by means of exposure. Current research targets innovative strategies to enhance fear extinction and thereby optimize exposure-based treatments for anxiety disorders. This selective review updates novel behavioral strategies that may provide cutting-edge clinical implications. Recent studies provide further support for two types of enhancement strategies. Procedural enhancement strategies implemented during extinction training translate to how exposure exercises may be conducted to optimize fear extinction. These strategies mostly focus on a maximized violation of dysfunctional threat expectancies and on reducing context and stimulus specificity of extinction learning. Flanking enhancement strategies target periods before and after extinction training and inform optimal preparation and post-processing of exposure exercises. These flanking strategies focus on the enhancement of learning in general, memory (re-)consolidation, and memory retrieval. Behavioral strategies to enhance fear extinction may provide powerful clinical applications to further maximize the efficacy of exposure-based interventions. However, future replications, mechanistic examinations, and translational studies are warranted to verify long-term effects and naturalistic utility. Future directions also comprise the interplay of optimized fear extinction with (avoidance) behavior and motivational antecedents of exposure.

  13. Radon exposure during treatment in some thermal spa centers in Greece

    International Nuclear Information System (INIS)

    Nikolopoulos, D.; Louizi, A.; Serefoglou, A.; Georgiou, E.; Vogiannis, E.; Halvadakis, C.

    2004-01-01

    Radon ( 222 Rn) present in the spa facilities has been identified as an agent of additional radiation burden both for bathers and the working personnel. Although some researchers have been concentrated on the health impact of radon activity transient increases due to water flow of domestically used water, limited work has been reported on this effect in spa facilities. The aim of this work was to study the exposure both of bathers and working personnel due to water flow under working conditions in some thermal spas in Greece. The spas studied were built at two locations in Greece; Lesvos Island and the city of Loutra- Edipsou. The study was performed between 1999 and 2003. Measurements involved determination of radon concentration in the waters of the thermal spas, monitoring of radon and short-lived decay product activity (both in attached and unattached form) and coarse particles (> 500 nm). Water radon concentration was measured by Alpha Guard PQ2000Pro of Genitron GmbH equipped with an appropriate unit (Aquakit). Indoor radon activity was monitored by Alpha Guard PQ2000Pro and EQF3023 of Sarad GmbH which was also used for monitoring of radon short-lived decay product activity. Coarse particle concentration measurements were performed by a GRIMM 1.104 Portable Dust Monitor. Measurements indoors were performed in the treatment room and in the reception room, if existing, under working conditions. Several procedures for bath filling and pouring out of the treatment room, during the measurements, were studied. Radon concentrations of thermal waters were found to lie in the range 1 Bq.L -1 and 304 Bq.L -1 . Some of these concentrations may be considered as elevated. Elevated (about 2-6 kBq.m -3 ) indoor radon concentrations were measured in the treatment rooms of the spas of Polichnitos, Eftalou and Loutra Edipsou. This found to be in accordance to the high radon potential of these spas, as detected out of the measurements of their thermal waters. Concentration

  14. Neuraminidase inhibitors in the treatment and post exposure prevention of influenza

    Directory of Open Access Journals (Sweden)

    von der Schulenburg, Johann-Matthias

    2006-01-01

    and spread of the virus begin. Objective: The effectiveness of NI during treatment and post exposure prophylaxis (PEP of an influenza infection are analyzed from a medical and an economical perspective. The effectiveness of NI in seasonal prophylaxis is not investigated in this report. Safety aspects of the drugs are also discussed. Methods: The relevant literature was identified by a systematic, structured bibliographic data base review. In addition, a manual search of relevant journals was conducted. The structured electronic data base analysis was supported by DIMDI and comprised the bibliographic data bases MEDLINE, HealthStar, Current Contents/Clinical Medicine, EMBASE, DA-RA, Cochrane Library, CancerLit, as well as Dissertation Abstracts for the period between 1999 and September 2004. Pre-defined key words were linked by AND/OR operators. A manual search of the Cochrane register was conducted for the time period before September 1999. Relevant medical journals were also hand-searched from January to November 2004. Quantitative reviews, randomized, double-blind clinical trials (RCT, and cost-benefit-analyses were considered as relevant if they fulfilled predefined inclusion criteria. Results: As compared to placebo, NI shortened the median duration of symptoms by approximately one day in meta-analyses, when the drug was taken within 48 hours after the onset of symptoms. The symptom reduction for other subgroups (such as patients who are at-risk for complicated influenza courses was even greater. For children under twelve, however, this was not the case. However, the incidence of severe influenza courses which led to hospitalization or death was low in the controlled studies. Pooled analyses nevertheless showed a tendency of a possible benefit of NI with respect to the hospitalization rate. Regarding PEP in homes with one infected household member, the reviewed studies showed a prophylactic effect of inhaled Zanamivir and Oseltamivir if a person started

  15. The acceptability of an Internet-based exposure treatment for flying phobia with and without therapist guidance: patients’ expectations, satisfaction, treatment preferences, and usability

    Science.gov (United States)

    Campos, Daniel; Mira, Adriana; Bretón-López, Juana; Castilla, Diana; Botella, Cristina; Baños, Rosa Maria; Quero, Soledad

    2018-01-01

    Purpose Internet-based treatments have been tested for several psychological disorders. However, few studies have directly assessed the acceptability of these self-applied interventions in terms of expectations, satisfaction, treatment preferences, and usability. Moreover, no studies provide this type of data on Internet-based treatment for flying phobia (FP), with or without therapist guidance. The aim of this study was to analyze the acceptability of an Internet-based treatment for FP (NO-FEAR Airlines) that includes exposure scenarios composed of images and real sounds. A secondary aim was to compare patients’ acceptance of two ways of delivering this treatment (with or without therapist guidance). Patients and methods The sample included 46 participants from a randomized controlled trial who had received the self-applied intervention with (n = 23) or without (n = 23) therapist guidance. All participants completed an assessment protocol conducted online and by telephone at both pre- and posttreatment. Results Results showed good expectations, satisfaction, opinion, and usability, regardless of the presence of therapist guidance, including low aversiveness levels from before to after the intervention. However, participants generally preferred the therapist-supported condition. Conclusion NO-FEAR Airlines is a well-accepted Internet-based treatment that can help enhance the application of the exposure technique, improving patient acceptance and access to FP treatment. PMID:29636613

  16. Acceptability of Virtual Reality Interoceptive Exposure for the Treatment of Panic Disorder with Agoraphobia

    Science.gov (United States)

    Quero, Soledad; Pérez-Ara, M. Ángeles; Bretón-López, Juana; García-Palacios, Azucena; Baños, Rosa M.; Botella, Cristina

    2014-01-01

    Interoceptive exposure (IE) is a standard component of cognitive-behavioural therapy (CBT) for panic disorder and agoraphobia. The virtual reality (VR) program "Panic-Agoraphobia" has several virtual scenarios designed for applying exposure to agoraphobic situations; it can also simulate physical sensations. This work examines patients'…

  17. Plutonium-aerosol emission rates and potential inhalation exposure during cleanup and treatment test at Area 11, Nevada Test Site

    International Nuclear Information System (INIS)

    Shinn, J.H.; Homan, D.N.

    1985-01-01

    A Cleanup and Treatment (CAT) test was conducted in 1981 at Area 11, Nevada Test Site. Its purpose was to evaluate the effectiveness of using a large truck-mounted vacuum cleaner similar to those used to clean paved streets for cleaning radiological contamination from the surface of desert soils. We found that four passes with the vehicle removed 97% of the alpha contamination and reduced resuspension by 99.3 to 99.7%. Potential exposure to cleanup workers was slight when compared to natural background exposure. 7 refs., 1 fig., 2 tabs

  18. Radiation exposure of owners and veterinary staff members after treatment of hyperthyroid cats with 131I

    International Nuclear Information System (INIS)

    Vandermeulen, E.; Dobbeleir, A.; Peremans, K.; Bacher, K.; Monsieurs, M.

    2015-01-01

    Full text of publication follows. Aim: the present study aims to evaluate radiation exposure of owners and veterinary staff members after 131 I treatment of hyperthyroid cats. Additionally, radiation dose rates from the treated cats were measured at different time points to analyze the effective half-life of 131 I within the cat. Materials and methods: 28 cats received a mean activity of (173 ± 84) MBq of 131 I. During the 5 day hospitalization period, the veterinary staff (3 persons) involved in the care for these cats wore waterproof bracelets and rings (at left and right hand) containing calibrated (LiF:Mg,Cu,P) thermoluminescent dosimeters (TLDs). TLDs were read out after 5 days and readings were converted in a dose value using an in-house measured calibration factor. Further, equivalent dose rates (μSv/h) were registered at 1 m distance from the cat at 4 h, 24 h, 48 h and 72 h after injection. The dose rates were plotted against time and fitted to an exponential function. From the fitting results, the effective half-life (T 1/2eff ) could be calculated. Owners were also given waterproof bracelets containing TLDs at the moment their cat was released from the Veterinary Nuclear Medicine Division. They were given strict instructions concerning the management of the cat at home (emphasizing limited time, keeping distance and waste management). The bracelets were returned by mail after 1 week together with the owners' estimation of the time spent with the cat. TLDs doses were analyzed using the aforementioned procedure. Results: 4 hours after injection, mean equivalent dose rate at 1 m was (9 ± 4) μSv/h. This value further decreased to (4 ± 3) μSv/h. Based on the dose rate measurements a mean T 1/2eff of (3.0 ± 1.6) days was found. Over 7 days, the average accumulated wrist dose of the owners was 504 μSv (range 26-2682 μSv). Concerning staff members, mean accumulated wrist doses over 5 days were 101 μGy and 120 μGy for left and right wrists

  19. Do drug treatment facilities increase clients' exposure to potential neighborhood-level triggers for relapse? A small-area assessment of a large, public treatment system.

    Science.gov (United States)

    Jacobson, Jerry O

    2006-03-01

    Research on drug treatment facility locations has focused narrowly on the issue of geographic proximity to clients. We argue that neighborhood conditions should also enter into the facility location decision and illustrate a formal assessment of neighborhood conditions at facilities in a large, metropolitan area, taking into account conditions clients already face at home. We discuss choice and construction of small-area measures relevant to the drug treatment context, including drug activity, disadvantage, and violence as well as statistical comparisons of clients' home and treatment locations with respect to these measures. Analysis of 22,707 clients discharged from 494 community-based outpatient and residential treatment facilities that received public funds during 1998-2000 in Los Angeles County revealed no significant mean differences between home and treatment neighborhoods. However, up to 20% of clients are exposed to markedly higher levels of disadvantage, violence, or drug activity where they attend treatment than where they live, suggesting that it is not uncommon for treatment locations to increase clients' exposure to potential environmental triggers for relapse. Whereas on average both home and treatment locations exhibit higher levels of these measures than the household locations of the general population, substantial variability in public treatment clients' home neighborhoods calls into question the notion that they hail exclusively from poor, high drug activity areas. Shortcomings of measures available for neighborhood assessment of treatment locations and implications of the findings for other areas of treatment research are also discussed.

  20. Dynamic, morphotype-specific Candida albicans beta-glucan exposure during infection and drug treatment.

    Directory of Open Access Journals (Sweden)

    Robert T Wheeler

    2008-12-01

    Full Text Available Candida albicans, a clinically important dimorphic fungal pathogen that can evade immune attack by masking its cell wall beta-glucan from immune recognition, mutes protective host responses mediated by the Dectin-1 beta-glucan receptor on innate immune cells. Although the ability of C. albicans to switch between a yeast- or hyphal-form is a key virulence determinant, the role of each morphotype in beta-glucan masking during infection and treatment has not been addressed. Here, we show that during infection of mice, the C. albicans beta-glucan is masked initially but becomes exposed later in several organs. At all measured stages of infection, there is no difference in beta-glucan exposure between yeast-form and hyphal cells. We have previously shown that sub-inhibitory doses of the anti-fungal drug caspofungin can expose beta-glucan in vitro, suggesting that the drug may enhance immune activity during therapy. This report shows that caspofungin also mediates beta-glucan unmasking in vivo. Surprisingly, caspofungin preferentially unmasks filamentous cells, as opposed to yeast form cells, both in vivo and in vitro. The fungicidal activity of caspofungin in vitro is also filament-biased, as corroborated using yeast-locked and hyphal-locked mutants. The uncloaking of filaments is not a general effect of anti-fungal drugs, as another anti-fungal agent does not have this effect. These results highlight the advantage of studying host-pathogen interaction in vivo and suggest new avenues for drug development.

  1. Potential Dermal Exposure to Flonicamid and Risk Assessment of Applicators During Treatment in Apple Orchards.

    Science.gov (United States)

    Zhao, Mei-Ai; Yu, Aili; Zhu, Yong-Zhe; Kim, Jeong-Han

    2015-01-01

    Exposure and risk assessments of flonicamid for applicators were performed in apple orchards in Korea. Fifteen experiments were done with two experienced applicators under typical field conditions using a speed sprayer. In this study, cotton gloves, socks, masks, and dermal patches were used to monitor potential dermal exposure to flonicamid, and personal air samplers with XAD-2 resin and glass fiber filter were used to monitor potential inhalation exposure. The analytical methods were validated for the limit of detection, limit of quantitation, reproducibility, linearity of the calibration curve, and recovery of flonicamid from various exposure matrices. The results were encouraging and acceptable for an exposure study. The applicability of XAD-2 resin was evaluated via a trapping efficiency and breakthrough test. During the mixing/loading, the average total dermal exposure was 22.6 μg of flonicamid, corresponding to 4.5×10(-5)% of the prepared amount. For the spraying, the potential dermal exposure was 9.32 mg, and the ratio to applied amount was 1.9 × 10(-2%). The primary exposed body parts were the thigh (2.90 mg), upper arm (1.75 mg), and lower leg (1.66 mg). By comparison, absorbable quantity of exposure was small, only 1.62 μg (3.2×10(-6)%). The margin of safety (MOS) were calculated for risk assessment, in all sets of trials, MOS > 1, indicating the exposure level of flonicamid was considered to be safe in apple orchards. Although this was a limited study, it provided a good estimate of flonicamid exposure for orchard applicators.

  2. Arsenic exposure and outcomes of antimonial treatment in visceral leishmaniasis patients in Bihar, India: a retrospective cohort study.

    Directory of Open Access Journals (Sweden)

    Meghan R Perry

    2015-03-01

    Full Text Available In the late twentieth century, emergence of high rates of treatment failure with antimonial compounds (SSG for visceral leishmaniasis (VL caused a public health crisis in Bihar, India. We hypothesize that exposure to arsenic through drinking contaminated groundwater may be associated with SSG treatment failure due to the development of antimony-resistant parasites.A retrospective cohort design was employed, as antimony treatment is no longer in routine use. The study was performed on patients treated with SSG between 2006 and 2010. Outcomes of treatment were assessed through a field questionnaire and treatment failure used as a proxy for parasite resistance. Arsenic exposure was quantified through analysis of 5 water samples from within and surrounding the patient's home. A logistic regression model was used to evaluate the association between arsenic exposure and treatment failure. In a secondary analysis survival curves and Cox regression models were applied to assess the risk of mortality in VL patients exposed to arsenic.One hundred and ten VL patients treated with SSG were analysed. The failure rate with SSG was 59%. Patients with high mean local arsenic level had a non-statistically significant higher risk of treatment failure (OR = 1.78, 95% CI: 0.7-4.6, p = 0.23 than patients using wells with arsenic concentration <10 μg/L. Twenty one patients died in our cohort, 16 directly as a result of VL. Arsenic levels ≥ 10 μg/L increased the risk of all-cause (HR 3.27; 95% CI: 1.4-8.1 and VL related (HR 2.65; 95% CI: 0.96-7.65 deaths. This was time dependent: 3 months post VL symptom development, elevated risks of all-cause mortality (HR 8.56; 95% CI: 2.5-29.1 and of VL related mortality (HR 9.27; 95% CI: 1.8-49.0 were detected.This study indicates a trend towards increased treatment failure in arsenic exposed patients. The limitations of the retrospective study design may have masked a strong association between arsenic exposure and selection

  3. Examination of occupational exposure to medical staff (primarily nurses) during 131I medical treatments

    International Nuclear Information System (INIS)

    Watanabe, Masayoshi; Ishikawa, Naofumi; Ito, Kunihiko; Ito, Koichi

    2004-01-01

    Recently, a new amendment to protect against radiation damage to humans has been enacted based on a 1990 recommendation by the International Commission on Radiological Protection (ICRP). Consequently, the dose limits of occupational exposure to medical staff were cut down sharply compared with conventional readjustments. This amended bill, however, may be triggering a reduction in the number of applicants, which hope to engage in radiotherapy. This being the case, we measured the dose levels of the occupational exposure to medical staff (doctor's group, nuclear medicine technologist's group, nurse's group and pharmacist's group) from 1999 to 2002. Moreover, we investigated what the main factor is in nurse's occupational exposure to 131 I. The highest doses of occupational exposure were 3.640 mSv to doctors, 7.060 mSv to nuclear medicine technologists, 1.486 mSv to nurses and 0.552 mSv to pharmacists. According to our results, it was clear that the highest doses in each group were far below the legally mandated upper limits of exposure doses. Although we investigated the correlations between the factors of nurse's occupational exposure to 131 I with the number of inpatients, the amount of 131 I and the number of servicing times for patients, there were no correlations found. Furthermore, to analyzing the factors in detail, it became clear that the main factor in the nurse's occupational exposure was due to the existence of patients who needed many more servicing times for their care than ordinary patients. (author)

  4. Integrating Antiretroviral Strategies for Human Immunodeficiency Virus Prevention: Post- and Pre-Exposure Prophylaxis and Early Treatment.

    Science.gov (United States)

    Grant, Robert M; Smith, Dawn K

    2015-12-01

    Best practices for integrating human immunodeficiency virus (HIV) testing and antiretroviral interventions for prevention and treatment are suggested based on research evidence and existing normative guidance. The goal is to provide high-impact prevention services during periods of substantial risk. Antiretroviral medications are recommended for postexposure prophylaxis (PEP), pre-exposure prophylaxis (PrEP), and treatment of HIV infection. We reviewed research evidence and current normative guidelines to identify best practices for integrating these high-impact prevention strategies. More sensitive HIV tests used for screening enable earlier diagnosis and treatment of HIV infection, more appropriate counseling, and help limit drug resistance. A fully suppressive PEP regimen should be initiated based on exposure history or physical findings when sensitive diagnostic testing is delayed or not available and antibody tests are negative. Transitions from PEP to PrEP are often warranted because HIV exposure events may continue to occur. This algorithmic approach to integrating PEP, PrEP, and early treatment decisions may increase the uptake of these interventions by a greater number and diversity of knowledgeable healthcare providers.

  5. Physiological response of rabbit bucks to prolonged feeding of ...

    African Journals Online (AJOL)

    Sixty-four (64) weanling rabbit bucks, 5 to 6 weeks old, were involved in a 2 x 4 factorial experiment to evaluate the effects of prolonged feeding of cottonseed cake (CSC) – based diets with or without vitamin E supplementation on the physiological response of the bucks. There were eight treatment combinations comprising ...

  6. Multifactorial QT Interval Prolongation and Takotsubo Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Michael Gysel

    2014-01-01

    Full Text Available A 71-year-old woman collapsed while working as a grocery store cashier. CPR was performed and an AED revealed torsades de pointes (TdP. She was subsequently defibrillated resulting in restoration of sinus rhythm with a QTc interval of 544 msec. Further evaluation revealed a diagnosis of Takotsubo Cardiomyopathy (TCM contributing to the development of a multifactorial acquired long QT syndrome (LQTS. The case highlights the role of TCM as a cause of LQTS in the setting of multiple risk factors including old age, female gender, hypokalemia, and treatment with QT prolonging medications. It also highlights the multifactorial nature of acquired LQTS and lends support to growing evidence of an association with TCM.

  7. Mediators of exposure therapy for youth obsessive-compulsive disorder: specificity and temporal sequence of client and treatment factors.

    Science.gov (United States)

    Chu, Brian C; Colognori, Daniela B; Yang, Guang; Xie, Min-ge; Lindsey Bergman, R; Piacentini, John

    2015-05-01

    Behavioral engagement and cognitive coping have been hypothesized to mediate effectiveness of exposure-based therapies. Identifying which specific child factors mediate successful therapy and which therapist factors facilitate change can help make our evidence-based treatments more efficient and robust. The current study examines the specificity and temporal sequence of relations among hypothesized client and therapist mediators in exposure therapy for pediatric Obsessive Compulsive Disorder (OCD). Youth coping (cognitive, behavioral), youth safety behaviors (avoidance, escape, compulsive behaviors), therapist interventions (cognitive, exposure extensiveness), and youth anxiety were rated via observational ratings of therapy sessions of OCD youth (N=43; ages=8 - 17; 62.8% male) who had received Exposure and Response Prevention (ERP). Regression analysis using Generalized Estimation Equations and cross-lagged panel analysis (CLPA) were conducted to model anxiety change within and across sessions, to determine formal mediators of anxiety change, and to establish sequence of effects. Anxiety ratings decreased linearly across exposures within sessions. Youth coping and therapist interventions significantly mediated anxiety change across exposures, and youth-interfering behavior mediated anxiety change at the trend level. In CLPA, youth-interfering behaviors predicted, and were predicted by, changes in anxiety. Youth coping was predicted by prior anxiety change. The study provides a preliminary examination of specificity and temporal sequence among child and therapist behaviors in predicting youth anxiety. Results suggest that therapists should educate clients in the natural rebound effects of anxiety between sessions and should be aware of the negatively reinforcing properties of avoidance during exposure. Copyright © 2015. Published by Elsevier Ltd.

  8. Using the Single Prolonged Stress Model to Examine the Pathophysiology of PTSD

    Directory of Open Access Journals (Sweden)

    Rimenez R. Souza

    2017-09-01

    Full Text Available The endurance of memories of emotionally arousing events serves the adaptive role of minimizing future exposure to danger and reinforcing rewarding behaviors. However, following a traumatic event, a subset of individuals suffers from persistent pathological symptoms such as those seen in posttraumatic stress disorder (PTSD. Despite the availability of pharmacological treatments and evidence-based cognitive behavioral therapy, a considerable number of PTSD patients do not respond to the treatment, or show partial remission and relapse of the symptoms. In controlled laboratory studies, PTSD patients show deficient ability to extinguish conditioned fear. Failure to extinguish learned fear could be responsible for the persistence of PTSD symptoms such as elevated anxiety, arousal, and avoidance. It may also explain the high non-response and dropout rates seen during treatment. Animal models are useful for understanding the pathophysiology of the disorder and the development of new treatments. This review examines studies in a rodent model of PTSD with the goal of identifying behavioral and physiological factors that predispose individuals to PTSD symptoms. Single prolonged stress (SPS is a frequently used rat model of PTSD that involves exposure to several successive stressors. SPS rats show PTSD-like symptoms, including impaired extinction of conditioned fear. Since its development by the Liberzon lab in 1997, the SPS model has been referred to by more than 200 published papers. Here we consider the findings of these studies and unresolved questions that may be investigated using the model.

  9. Prolonged Intermittent Renal Replacement Therapy.

    Science.gov (United States)

    Edrees, Fahad; Li, Tingting; Vijayan, Anitha

    2016-05-01

    Prolonged intermittent renal replacement therapy (PIRRT) is becoming an increasingly popular alternative to continuous renal replacement therapy in critically ill patients with acute kidney injury. There are significant practice variations in the provision of PIRRT across institutions, with respect to prescription, technology, and delivery of therapy. Clinical trials have generally demonstrated that PIRRT is non-inferior to continuous renal replacement therapy regarding patient outcomes. PIRRT offers cost-effective renal replacement therapy along with other advantages such as early patient mobilization and decreased nursing time. However, due to lack of standardization of the procedure, PIRRT still poses significant challenges, especially pertaining to appropriate drug dosing. Future guidelines and clinical trials should work toward developing consensus definitions for PIRRT and ensure optimal delivery of therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  10. Beyond recidivism: changes in health and social service involvement following exposure to drug treatment court.

    Science.gov (United States)

    Rezansoff, Stefanie N; Moniruzzaman, Akm; Clark, Elenore; Somers, Julian M

    2015-10-31

    The majority of Drug Treatment Court (DTC) research has examined the impact of DTCs on criminal recidivism. Comparatively little research has addressed the association between DTC participation and engagement with community-based health and social services. The present study investigated changes in participant involvement with outpatient healthcare and income assistance within a DTC cohort. We hypothesized that involvement with community-based (outpatient) health and social services would increase post-DTC participation, and that service levels would be higher among program graduates and offenders with histories of co-occurring mental and substance use disorders. Participants were 631 offenders at the DTC in Vancouver, Canada (DTCV). Administrative data representing hospital, outpatient medical care, and income assistance were examined one-year pre/post program to assess differences over time. Generalized estimating equations were used to investigate the association between changes in service use and program involvement. We also examined the relationship between level of service use and offender characteristics. Members of the cohort were disproportionately Aboriginal (33 %), had been sentenced 2.7 times in the 2 years preceding their index offence, and 50 % had been diagnosed with a non substance-related mental disorder in the five years preceding the index offence. The mean number of outpatient services post DTCV was 51, and the mean amount of social assistance paid was $5,897. Outpatient service use increased following exposure to DTCV (Adjusted Rate Ratio (ARR) = 1.45) and was significantly higher among women (ARR = 1.47), program graduation (ARR = 1.23), and those previously diagnosed with concurrent substance use and mental disorders (ARR = 4.92). Overall, hospital admissions did not increase post-program, although rates were significantly higher among women (ARR = 1.76) and those with concurrent disorders (ARR = 2.71). Income

  11. UV and hydrogen peroxide treatment restores changes in innate immunity caused by exposure of fish to reuse water.

    Science.gov (United States)

    Singh, Arvinder; Havixbeck, Jeffrey J; Smith, Matthew K; Shu, Zengquan; Tierney, Keith B; Barreda, Daniel R; El-Din, Mohamed Gamal; Belosevic, Miodrag

    2015-03-15

    The purpose of this study was to assess the innate immunity of goldfish exposed to reuse water, and UV/H2O2-treated reuse water, using a real-time flow-through exposure system. The reuse water generated by ultrafiltration of finished wastewater from the municipal wastewater treatment plant was analyzed for the presence of a panel of 20 herbicides/fungicides and 46 pharmaceuticals and personal care products (PPCP). There was a seasonal variation in the profile and concentrations of xenobiotics in reuse water with lowest levels occurring in the summer. The innate immunity parameters assessed were cytokine (IFNγ, IL-1β, IL-10, TNFα2), and cytokine receptor (TNFR1, TNFR2, IFNGR1, IFNGR2) gene expression, and phagocytosis of kidney leukocyte subpopulations. Assessment of innate immunity parameters was done after acute (7 days) and sub chronic (30 and 60 days) exposure to reuse water, UV/H2O2-treated reuse water, and activated carbon-treated reuse water (ACT; control), during spring, summer and fall of 2012. Temporal (acute versus sub chronic) as well as seasonal differences in innate immunity of fish exposed to reuse water were observed. The acute exposure of fish to reuse water caused significant down-regulation in cytokine gene expression in different organs of fish (kidney, spleen, liver) and phagocytic ability of different kidney leukocyte subpopulations. The immune gene expression and phagocytosis of kidney leukocytes of fish returned to ACT control levels after sub chronic exposure suggesting that fish have habituated to the reuse water exposure. The changes in gene expression after acute exposure were related to variations in the profile of xenobiotics in reuse water during different seasons. The efficiency of xenobiotic removal using UV/H2O2 ranged between 1.6 and 100% indicating that treatment of reuse water using high dose UV/H2O2 was only partially effective in removing the xenobiotics, as assessed by both chemical analyses and measurement of innate immune

  12. Disseminated Mycobacterium celatum disease with prolonged pulmonary involvement

    DEFF Research Database (Denmark)

    Patsche, Cecilie Blenstrup; Svensson, Erik; Wejse, Christian

    2014-01-01

    Mycobacterium celatum is a rare cause of human infection, causing disseminated disease in immunosuppressed individuals. Infections localized to the lungs and the lymph nodes have also been reported in immunocompetent individuals. The existing literature on the subject is limited as are experiences...... with treatment regimens and durations. In the case presented herein, two different treatment regimens were applied to an immunocompromised HIV-negative patient with primary skin involvement and extensive pulmonary involvement due to suspected relapse on isoniazid, ethambutol, and clarithromycin treatment....... The treatment regimen was changed to azithromycin, ciprofloxacin, and pyrazinamide and the treatment duration was prolonged to a total of 24 months, with good effect....

  13. Comparison of two pre-exposure treatment regimens in acute organophosphate (paraoxon) poisoning in rats: Tiapride vs. pyridostigmine

    International Nuclear Information System (INIS)

    Petroianu, G.A.; Hasan, M.Y.; Nurulain, S.M.; Arafat, K.; Sheen, R.; Nagelkerke, N.

    2007-01-01

    Recently, the FDA approved the medical use of oral pyridostigmine as prophylactic treatment of possible nerve agent exposure: the concept is to block the cholinesterase transitorily using the carbamate (pyridostigmine) in order to deny access to the active site of the enzyme to the irreversible inhibitor (nerve agent) on subsequent exposure. We have shown previously that tiapride is in vitro a weak inhibitor of acetylcholinesterase and that in rats administration of tiapride before the organophosphate paraoxon significantly decreases mortality. The purpose of the present study was to compare tiapride- and pyridostigmine-based pretreatment strategies, either alone or in combination with pralidoxime reactivation, by using a prospective, non-blinded study in a rat model of acute high-dose paraoxon exposure. Groups 1-6 received 1 μMol paraoxon (∼ LD 75 ) groups 2-6 received in addition: G 2 50 μMol tiapride 30 min before paraoxon; G 3 50 μMol tiapride 30 min before paraoxon and 50 μMol pralidoxime 1 min after paraoxon; G 4 1 μMol pyridostigmine 30 min before paraoxon; G 5 1 μMol pyridostigmine 30 min before paraoxon and 50 μMol pralidoxime 1 min after paraoxon; G 6 50 μMol pralidoxime 1 min after paraoxon; Mortality data were compared using Kaplan-Meier plots and logrank tests. Mortality is statistically significantly influenced by all treatment strategies. Tiapride pretreatment followed by pralidoxime treatment (G 3 ) is aux par with pyridostigmine pretreatment followed by pralidoxime treatment (G 5 ). Tiapride pretreatment only (G 2 ) is inferior to pyridostigmine pretreatment only (G 4 ). The best results are achieved with pyridostigmine pretreatment only or pralidoxime treatment only (G 4 and G 6 )

  14. Antibiotic treatment attenuates behavioral and neurochemical changes induced by exposure of rats to group a streptococcal antigen.

    Directory of Open Access Journals (Sweden)

    Dafna Lotan

    Full Text Available Post-streptococcal A (GAS sequelae including movement and neuropsychiatric disorders have been associated with improvement in response to antibiotic therapy. Besides eradication of infection, the underlying basis of attenuation of neuropsychiatric symptoms following antibiotic treatment is not known. The aim of the present study was to test the efficacy of antibiotic treatment in a rat model of GAS-related neuropsychiatric disorders. In the model, rats were not infected but were exposed to GAS-antigen or to adjuvants only (Control rats and treated continuously with the antibiotic ampicillin in their drinking water from the first day of GAS-antigen exposure. Two additional groups of rats (GAS and Control did not receive ampicillin in their drinking water. Behavior of the four groups was assessed in the forced swim, marble burying and food manipulation assays. We assessed levels of D1 and D2 dopamine receptors and tyrosine hydroxylase in the prefrontal cortex and striatum, and IgG deposition in the prefrontal cortex, striatum and thalamus. Ampicillin treatment prevented emergence of the motor and some of the behavioral alterations induced by GAS-antigen exposure, reduced IgG deposition in the thalamus of GAS-exposed rats, and tended to attenuate the increase in the level of TH and D1 and D2 receptors in their striatum, without concomitantly reducing the level of sera anti-GAS antibodies. Our results reinforce the link between exposure to GAS antigen, dysfunction of central dopaminergic pathways and motor and behavioral alterations. Our data further show that some of these deleterious effects can be attenuated by antibiotic treatment, and supports the latter's possible efficacy as a prophylactic treatment in GAS-related neuropsychiatric disorders.

  15. Oxygen plasma treatment of HKUST-1 for porosity retention upon exposure to moisture.

    Science.gov (United States)

    Bae, Jaeyeon; Jung, Jin-Woo; Park, Hyo Yul; Cho, Chang-Hee; Park, Jinhee

    2017-11-07

    Despite their remarkable properties, metal-organic frameworks (MOFs) present vulnerable structures that are sensitive to moisture; therefore, their application to real field situations is challenging. Herein, an O 2 plasma technique was introduced as a new method for the activation and protection of porosity in HKUST-1. In an unprecedented manner, O 2 plasma-treated HKUST-1 retains its porosity after a long exposure to moisture as compared to pristine HKUST-1. Porosity retention was examined by N 2 adsorption/desorption measurements of non-activated HKUST-1 after exposure to moisture.

  16. Exposure to Mobile Phone Radiation Opens New Horizons in Alzheimer’s Disease Treatment

    OpenAIRE

    Mortazavi SAR; Shojaei-Fard MB; Haghani M; Shokrpour N; Mortazavi SMJ

    2013-01-01

    Alzheimer’s disease, the most common type of dementia and a progressive neurodegenerative disease, occurs when the nerve cells in the brain die. Although there are medications that can help delay the development of Alzheimer’s disease, there is currently no cure for this disease. Exposure to ionizing and non-ionizing radiation may cause adverse health effects such as cancer.  Looking at the other side of the coin, there are reports indicating stimulatory or beneficial effects after exposure t...

  17. Prolonged pregnancy: Methods, Causal Determinants and Outcome

    DEFF Research Database (Denmark)

    Olesen, Annette Wind

    Summary Prolonged pregnancy, defined as a pregnancy with a gestational length of 294 days or more, is a frequent condition. It is associated with an increased risk of fetal and maternal complications. Little is known about the aetiology of prolonged pregnancy. The aims of the thesis were 1......) to study the incidence of prolonged pregnancy as a function of methods for determining gestational age; 2) to determine the risk of obstetrical and fetal complications in prolonged pregnancy; 3) to validate the self-reported gestational age in the National Birth Cohort; 4) to determine whether...... the risk of recurrence of prolonged pregnancy as a function of change in male partner and social conditions (IV). The National Birth Cohort provided data for the study on prenatal risk indicators of prolonged pregnancy in a follow-up design (V). The self-reported gestational ages from this database...

  18. Cognitions in prolonged exposure therapy for posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Muriel A. Hagenaars

    2010-01-01

    Full Text Available Este estudio cuasi-experimental investiga el impacto del tratamiento de exposición prolongada en los cambios cognitivos en pacientes con trastorno por estrés postraumático (TEPT. Setenta y siete pacientes con TEPT con traumas mixtos pasaron por 8-12 sesiones de exposición en imaginación y en vivo, sin ninguna intervención cognitiva. La reexperimentación de los síntomas y las cogniciones más importantes (i.e. su frecuencia y credibilidad fueron evaluadas semanalmente. El tratamiento de exposición redujo de forma significativa las cogniciones negativas relacionadas con el trauma, aunque no se prestó atención a éstas durante el tratamiento. La reducción en cogniciones se relacionó con la reducción en los síntomas del TEPT. La reducción en las cogniciones pre y post-tratamiento no predijo el TEPT en el seguimiento habiendo controlado la reducción en los síntomas del TEPT pre y post-tratamiento. Finalmente, la disminución en la frecuencia de la reexperimentación y de las cogniciones relacionadas con el trauma fue precedida por la reducción del sufrimiento causado por la reexperimentación. La credibilidad de las cogniciones relacionadas con el trauma fue la última variable que disminuyó. El hecho de que el sufrimiento causado por la reexperimentación fuera el primer síntoma en disminuir puede significar que la reducción de las cogniciones relacionadas con el trauma es el resultado de la reducción de los síntomas del TEPT. Esta complicada relación entre las cogniciones y el cambio en los síntomas, sin duda, merece ser explorada en el futuro.

  19. Effect of Prolong Exposure to Gas Flaring on some Haematological ...

    African Journals Online (AJOL)

    MICHAEL

    Pollution of the air, land and water from gas flares or common oil blowouts and spill are regular occurrence in the region (Njeze, 1983). It has being suggested that though complete combustion process creates relatively innocuous gases such as carbon dioxide and water, such complete combustion is rarely achieved by ...

  20. Effects of prolonged UV-B exposure in plants

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... effects of UV radiation on plants and other organisms. .... competitive interactions may also be altered indirectly by ..... lesions show a high degree of evolutionary conservation ... period between anther dehiscence pollination, and there- .... ultraviolet climate and the ecological consequences for higher ...

  1. Narrative reconstruction therapy for prolonged grief disorder—rationale and case study

    Directory of Open Access Journals (Sweden)

    Tuvia Peri

    2016-05-01

    Full Text Available Background: Prolonged grief disorder (PGD is a potentially disabling condition affecting approximately 10% of bereaved people. It has been suggested that the impaired integration of the loss memory, as expressed in recurrent memories of the loss and disorganization of memory, is involved in the development of PGD. Narrative reconstruction (NR, originally designed for the treatment of posttraumatic stress disorder (PTSD in an integrative therapy module, and consisting of exposure to the loss memory, detailed written reconstruction of the loss memory narrative and an elaboration of the personal significance of that memory for the bereaved, has been shown to be effective in the treatment of intrusion symptoms. Objective: In light of findings that cognitive behavior therapy (CBT, including cognitive restructuring and exposure, is effective in the treatment of PGD, we suggest the implementation of a somewhat novel therapy module, NR, for the treatment of intrusive phenomena in bereaved patients. Method: The rationale for the implementation of NR for PGD and a case study of the treatment of a woman suffering from PGD after the death of her father are presented. Therapy took place in a university outpatient training clinic. Results: Evaluations conducted before and after treatment and at a 3-month follow-up demonstrated the effectiveness of NR in reducing symptoms of PGD and depression. The analysis of spontaneous narratives recorded before and after treatment showed an increased organization of the narratives. Conclusions: This case report demonstrates an adaptation of NR for the treatment of PGD. The results provide preliminary support for the effectiveness of NR for PGD. The significance of the study and its limitations are discussed.

  2. CARL: a LabVIEW 3 computer program for conducting exposure therapy for the treatment of dental injection fear.

    Science.gov (United States)

    Coldwell, S E; Getz, T; Milgrom, P; Prall, C W; Spadafora, A; Ramsay, D S

    1998-04-01

    This paper describes CARL (Computer Assisted Relaxation Learning), a computerized, exposure-based therapy program for the treatment of dental injection fear. The CARL program operates primarily in two different modes; in vitro, which presents a video-taped exposure hierarchy, and in vivo, which presents scripts for a dentist or hygienist to use while working with a subject. Two additional modes are used to train subjects to use the program and to administer behavioral assessment tests. The program contains five different modules, which function to register a subject, train subjects to use physical and cognitive relaxation techniques, deliver an exposure hierarchy, question subjects about the helpfulness of each of the therapy components, and test for memory effects of anxiolytic medication. Nine subjects have completed the CARL therapy program and 1-yr follow-up as participants in a placebo-controlled clinical trial examining the effects of alprazolam on exposure therapy for dental injection phobia. All nine subjects were able to receive two dental injections, and all reduced their general fear of dental injections. Initial results therefore indicate that the CARL program successfully reduces dental injection fear.

  3. One-Session Exposure Treatment for Social Anxiety with Specific Fear of Public Speaking

    Science.gov (United States)

    Hindo, Cindy S.; Gonzalez-Prendes, A. Antonio

    2011-01-01

    Objectives: This pilot study evaluated the effectiveness of one-session, exposure-based therapy, to treat social anxiety disorder (SAD) with specific fear of public speaking. Methods: A quasi-experimental pre-posttest design with repeated measures-within-subject Analysis of Variance and paired sample t-tests was used to compare pretest, posttest…

  4. Cue exposure therapy for the treatment of opiate addiction: results of a randomized controlled clinical trial

    NARCIS (Netherlands)

    Marissen, Marlies A. E.; Franken, Ingmar H. A.; Blanken, Peter; van den Brink, Wim; Hendriks, Vincent M.

    2007-01-01

    BACKGROUND: Persistent cue reactivity to drug-related stimuli is a well-known phenomenon among abstinent drug users and has been found to be a predictor of relapse. Cue exposure therapy (CET) aims to reduce this cue reactivity by exposing abstinent drug users to conditioned drug-related stimuli

  5. Behavioural treatment of tics: Habit reversal and exposure with response prevention

    NARCIS (Netherlands)

    Griendt, J.M.T.M. van de; Verdellen, C.W.J.; Dijk, M.K. van; Verbraak, M.J.P.M.

    2013-01-01

    Behaviour therapy has been shown to be an effective strategy in treating tics; both habit reversal (HR) and exposure and response prevention (ER) are recommended as first-line interventions. This review provides an overview of the history, theoretical concepts and evidence at present for HR and ER.

  6. Treatment of Challenging Behavior Exhibited by Children with Prenatal Drug Exposure

    Science.gov (United States)

    Kurtz, Patricia F.; Chin, Michelle D.; Rush, Karena S.; Dixon, Dennis R.

    2008-01-01

    A large body of literature exists describing the harmful effects of prenatal drug exposure on infant and child development. However, there is a paucity of research examining strategies to ameliorate sequelae such as externalizing behavior problems. In the present study, functional analysis procedures were used to assess challenging behavior…

  7. The role of treatment delivery factors in exposure-based cognitive behavioral therapy for panic disorder with agoraphobia.

    Science.gov (United States)

    Weck, Florian; Grikscheit, Florian; Höfling, Volkmar; Kordt, Anne; Hamm, Alfons O; Gerlach, Alexander L; Alpers, Georg W; Arolt, Volker; Kircher, Tilo; Pauli, Paul; Rief, Winfried; Lang, Thomas

    2016-08-01

    Treatment delivery factors (i.e., therapist adherence, therapist competence, and therapeutic alliance) are considered to be important for cognitive behavioral therapy (CBT) for panic disorder and agoraphobia (PD/AG). In the current study, four independent raters conducted process evaluations based on 168 two-hour videotapes of 84 patients with PD/AG treated with exposure-based CBT. Two raters evaluated patients' interpersonal behavior in Session 1. Two raters evaluated treatment delivery factors in Session 6, in which therapists provided the rationale for conducting exposure exercises. At the 6-month follow-up, therapists' adherence (r=0.54) and therapeutic alliance (r=0.31) were significant predictors of changes in agoraphobic avoidance behavior; therapist competence was not associated with treatment outcomes. Patients' interpersonal behavior in Session 1 was a significant predictor of the therapeutic alliance in Session 6 (r=0.17). The findings demonstrate that treatment delivery factors, particularly therapist adherence, are relevant to the long-term success of CBT for PD/AG. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Quantifying public radiation exposure related to lutetium-177 octreotate therapy for the development of a safe outpatient treatment protocol.

    Science.gov (United States)

    Olmstead, Craig; Cruz, Kyle; Stodilka, Robert; Zabel, Pamela; Wolfson, Robert

    2015-02-01

    Radionuclide therapies, including treatment of neuroendocrine tumors with lutetium-177 (Lu-177) octreotate, often involve hospital admission to minimize radiation exposure to the public. Overnight admission due to Lu-177 octreotate therapy incurs additional cost for the hospital and is an inconvenience for the patient. This study endeavors to characterize the potential radiation risk to caregivers and the public should Lu-177 octreotate therapies be performed on an outpatient basis. Dose rate measurements of radiation emanating from 10 patients were taken 30 min, 4, and 20 h after initiation of Lu-177 octreotate therapy. Instadose radiation dose measurement monitors were also placed around the patients' rooms to assess the potential cumulative radiation exposure during the initial 30 min-4 h after treatment (simulating the hospital-based component of the outpatient model) as well as 4-20 h after treatment (simulating the discharged outpatient portion). The mean recorded dose rate at 30 min, 4, and 20 h after therapy was 20.4, 14.0, and 6.6 μSv/h, respectively. The majority of the cumulative dose readings were below the minimum recordable threshold of 0.03 mSv, with a maximum dose recorded of 0.18 mSv. Given the low dose rate and cumulative levels of radiation measured, the results support that an outpatient Lu-177 octreotate treatment protocol would not jeopardize public safety. Nevertheless, the concept of ALARA still requires that detailed radiation safety protocols be developed for Lu-177 octreotate outpatients to minimize radiation exposure to family members, caregivers, and the general public.

  9. Smoking prolongs the infectivity of patients with tuberculosis.

    LENUS (Irish Health Repository)

    Siddiqui, U A

    2010-10-01

    We sought to establish if smokers on anti-tuberculosis treatment are more likely to have a prolonged period of infectivity, compared to non-smoking tuberculosis patients, in a low tuberculosis prevalence country. We conducted a cross-sectional, retrospective study in Ireland that recruited 53 microbiologically confirmed cases of pulmonary tuberculosis (PTB). The age-sex adjusted odds ratios (AOR) suggest that the infectivity status of PTB on treatment was four times more likely to be prolonged beyond 6-8 weeks, if the cases had a smoking history (AOR: 4.42; 95% CI: 1.23; 15.9). Smoking was associated with delayed sputum smear conversion in PTB patients on treatment.

  10. Effect of antioxidants treatments to control hazard of radiation exposure and food aflatoxin contamination

    International Nuclear Information System (INIS)

    Abdel Rahman, N.A

    2008-01-01

    The objective of this study was to evaluate the protective role of diadezin and/or lycopene (prolonged administration) against biochemical and histopathological changes in male rats exposed to gamma radiation and / or aflatoxin B1.Irradiated rats were whole body exposed to fractionated 8 Gy γradiations (4 x 2 Gy, every other day). Aflatoxin B1 (AFB1)exposed rats were received 10μg/kg body weight for 7 consecutive days. Daidzein delivered to rats via stomach tube at a concentration of 63 mg/kg body weight/day. Whereas lycopene was ingested at a concentration of 10 mg/kg body weight/day. Animals were sacrificed on the 1 st day post the last irradiation dose. The results obtained showed that irradiation and/or AFB1 induced significant change in blood enzymes (alanine aminotransferase; ALT and aspartate aminotransferase; AST) activity as well as in the level of serum cholesterol. triglycerides, phospholipids, uric acid, urea, creatinine, total proteins and albumin. These changes were accompanied with a significant alteration in the antioxidant status (superoxide dismutase; SOD, catalase; CAT activity and glutathione concentration; GSH) and a significant increase in the peroxidation processes (TBARS). In addition , the histological investigation displayed remarkable changes in liver photomicrographs compared to the sections of liver in control rats.

  11. Purging of the neuroblastoma stem cell compartment and tumor regression on exposure to hypoxia or cytotoxic treatment.

    Science.gov (United States)

    Marzi, Ilaria; D'Amico, Massimo; Biagiotti, Tiziana; Giunti, Serena; Carbone, Maria Vittoria; Fredducci, David; Wanke, Enzo; Olivotto, Massimo

    2007-03-15

    We worked out an experimental protocol able to purge the stem cell compartment of the SH-SY5Y neuroblastoma clone. This protocol was based on the prolonged treatment of the wild-type cell population with either hypoxia or the antiblastic etoposide. Cell fate was monitored by immunocytochemical and electrophysiologic (patch-clamp) techniques. Both treatments produced the progressive disappearance of neuronal type (N) cells (which constitute the bulk of the tumor), leaving space for a special category of epithelial-like substrate-adherent cells (S(0)). The latter represent a minimal cell component of the untreated population and are endowed with immunocytochemical markers (p75, c-kit, and CD133) and the electrophysiologic "nude" profile, typical of the neural crest stem cells. S(0) cells displayed a highly clonogenic potency and a substantial plasticity, generating both the N component and an alternative subpopulation terminally committed to the fibromuscular lineage. Unlike the N component, this lineage was highly insensitive to the apoptotic activity of hypoxia and etoposide and developed only when the neuronal option was abolished. Under these conditions, the fibromuscular progeny of S(0) expanded and progressed up to the exhaustion of the staminal compartment and to the extinction of the tumor. When combined, hypoxia and etoposide cooperated in abolishing the N cell generation and promoting the conversion of the tumor described. This synergy might mirror a natural condition in the ischemic areas occurring in cancer. These results have relevant implications for the understanding of the documented tendency of neuroblastomas to regress from a malignant to a benign phenotype, either spontaneously or on antiblastic treatment.

  12. Changes in transcript expression patterns as a result of cryoprotectant treatment and liquid nitrogen exposure in Arabidopsis shoot tips.

    Science.gov (United States)

    Gross, Briana L; Henk, Adam D; Bonnart, Remi; Volk, Gayle M

    2017-03-01

    Transcripts related to abiotic stress, oxidation, and wounding were differentially expressed in Arabidopsis shoot tips in response to cryoprotectant and liquid nitrogen treatment. Cryopreservation methods have been implemented in genebanks as a strategy to back-up plant genetic resource collections that are vegetatively propagated. Cryopreservation is frequently performed using vitrification methods, whereby shoot tips are treated with cryoprotectant solutions, such as Plant Vitrification Solution 2 (PVS2) or Plant Vitrification Solution 3 (PVS3); these solutions remove and/or replace freezable water within the meristem cells. We used the model system Arabidopsis thaliana to identify suites of transcripts that are up- or downregulated in response to PVS2 and PVS3 treatment and liquid nitrogen (LN) exposure. Our results suggest that there are many changes in transcript expression in shoot tips as a result of cryoprotection and that these changes exceed the number detected as a result of LN exposure. In total, 180 transcripts showed significant changes in expression level unique to treatment with either the cryoprotectant or cryopreservation followed by recovery. Of these 180 transcripts, 67 were related to stress, defense, wounding, lipid, carbohydrate, abscisic acid, oxidation, temperature (cold/heat), or osmoregulation. The responses of five transcripts were confirmed using qPCR methods. The transcripts responding to PVS2 + LN suggest an oxidative response to this treatment, whereas the PVS3 + LN treatment invoked a more general metabolic response. This work shows that the choice of cryoprotectant can have a major influence on the patterns of transcript expression, presumably due to the level and extent of stress experienced by the shoot tip. As a result, there may be divergent responses of study systems to PVS2 and PVS3 treatments.

  13. Qingyihuaji Formula Inhibits Pancreatic Cancer and Prolongs Survival by Downregulating Hes-1 and Hey-1

    Directory of Open Access Journals (Sweden)

    Yanli Xu

    2015-01-01

    Full Text Available The dire prognosis of pancreatic cancer has not markedly improved during past decades. The present study was carried out to explore the effect of Qingyihuaji formula (QYHJ on inhibiting pancreatic cancer and prolonging survival in related Notch signaling pathway. Proliferation of pancreatic cancer cells (SW1990 and PANC-1 was detected by MTT assay at 24, 48, and 72 h with exposure to various concentrations (0.08–50 mg/mL of QYHJ water extract. Pancreatic tumor models of nude mice were divided into three groups randomly (control, QYHJ, and gemcitabine. mRNA and protein expression of Notch target genes (Hes-1, Hey-1, Hey-2, and Hey-L in dissected tumor tissue were detected. Results showed that proliferation of SW1990 cells and PANC-1 cells was inhibited by QYHJ water extract in a dose-dependent and time-dependent manner. QYHJ effectively inhibited tumor growth and prolonged survival time in nude mice. Expression of both Hes-1 and Hey-1 was decreased significantly in QYHJ group, suggesting that Hes-1 and Hey-1 in Notch signaling pathway might be potential targets for QYHJ treatment. This research could help explain the clinical effectiveness of QYHJ and may provide advanced pancreatic cancer patients with a new therapeutic option.

  14. Tolerance and withdrawal from prolonged opioid use in critically ill children.

    Science.gov (United States)

    Anand, Kanwaljeet J S; Willson, Douglas F; Berger, John; Harrison, Rick; Meert, Kathleen L; Zimmerman, Jerry; Carcillo, Joseph; Newth, Christopher J L; Prodhan, Parthak; Dean, J Michael; Nicholson, Carol

    2010-05-01

    After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. Relevant manuscripts published in the English language were searched in Medline by using search terms "opioid," "opiate," "sedation," "analgesia," "child," "infant-newborn," "tolerance," "dependency," "withdrawal," "analgesic," "receptor," and "individual opioid drugs." Clinical and preclinical studies were reviewed for data synthesis. Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal.

  15. The Importance of Prolonged Provocation in Drug Allergy - Results From a Danish Allergy Clinic.

    Science.gov (United States)

    Fransson, Sara; Mosbech, Holger; Kappel, Mogens; Hjortlund, Janni; Poulsen, Lars K; Kvisselgaard, Ask D; Garvey, Lene H

    Drug provocation is the "Gold Standard" in drug allergy investigation. Recent studies suggest that a negative drug provocation on first dose should be followed by a prolonged provocation over several days. To evaluate drug allergy investigations on the basis of drug provocation, including prolonged provocation. Data from adult patients investigated for drug allergy in a Danish Allergy Clinic during the period 2010 to 2014 were entered into a database. Data included clinical details and results of provocations with suspected culprit drug (for penicillins performed only in specific IgE-negative patients). If provocation was negative on first dose, treatment was continued for 3 to 10 days. A total of 1,913 provocations were done in 1,659 patients, median age 46 years, of whom 1,237 (74.6%) were females. Drugs investigated were antibiotics, 1,776 (92.8%), of which 1,590 (89.5%) were penicillins; analgesics, 59 (3.1%); local anesthetics, 33 (1.7%); and other drugs, 45 (2.4%). In total, 211 of 1,913 (11.0%) provocations were positive. Causes were antibiotics, 198 (93.8%), of which 167 (84.3%) were penicillins; analgesics, 7 (3.3%); local anesthetics, 0; and other drugs, 6 (2.8%). Only 43 (20.4%) provocations were positive on first dose, whereas 95 (45.0%) turned positive more than 3 days later. Only 11.0% of the provocations were positive. Importantly, only 1 of 5 patients tested positive on the first dose, indicating that prolonged exposure should always be considered when drug provocation is included in allergy investigations. Most provocations were with penicillins, reflecting the pattern of antibiotic use in Denmark, which differs from that in other countries, especially outside Northern Europe. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Virtual reality compared with in vivo exposure in the treatment of social anxiety disorder: a three-arm randomised controlled trial.

    Science.gov (United States)

    Bouchard, Stéphane; Dumoulin, Stéphanie; Robillard, Geneviève; Guitard, Tanya; Klinger, Évelyne; Forget, Hélène; Loranger, Claudie; Roucaut, François Xavier

    2017-04-01

    Background People with social anxiety disorder (SAD) fear social interactions and may be reluctant to seek treatments involving exposure to social situations. Social exposure conducted in virtual reality (VR), embedded in individual cognitive-behavioural therapy (CBT), could be an answer. Aims To show that conducting VR exposure in CBT for SAD is effective and is more practical for therapists than conducting exposure in vivo Method Participants were randomly assigned to either VR exposure ( n = 17), in vivo exposure ( n = 22) or waiting list ( n = 20). Participants in the active arms received individual CBT for 14 weekly sessions and outcome was assessed with questionnaires and a behaviour avoidance test. (Trial registration number ISRCTN99747069) Results Improvements were found on the primary (Liebowitz Social Anxiety Scale) and all five secondary outcome measures in both CBT groups compared with the waiting list. Conducting exposure in VR was more effective at post-treatment than in vivo on the primary outcome measure and on one secondary measure. Improvements were maintained at the 6-month follow-up. VR was significantly more practical for therapists than in vivo exposure. Conclusions Using VR can be advantageous over standard CBT as a potential solution for treatment avoidance and as an efficient, cost-effective and practical medium of exposure. © The Royal College of Psychiatrists 2017.

  17. Safety information on QT-interval prolongation

    DEFF Research Database (Denmark)

    Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H

    2014-01-01

    Prolongation of the QT interval can predispose to fatal ventricular arrhythmias. Differences in QT-labeling language can result in miscommunication and suboptimal risk mitigation. We systematically compared the phraseology used to communicate on QT-prolonging properties of 144 drugs newly approve...

  18. Risk factors for QTc interval prolongation

    NARCIS (Netherlands)

    Heemskerk, Charlotte P.M.; Pereboom, Marieke; van Stralen, Karlijn; Berger, Florine A.; van den Bemt, Patricia M.L.A.; Kuijper, Aaf F.M.; van der Hoeven, Ruud T M; Mantel-Teeuwisse, Aukje K.; Becker, Matthijs L

    2018-01-01

    Purpose: Prolongation of the QTc interval may result in Torsade de Pointes, a ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have been described, including the use of certain drugs. In clinical practice, there is much debate about the management of the risks involved. In

  19. Prenatal risk indicators of a prolonged pregnancy

    DEFF Research Database (Denmark)

    Olesen, Annette Wind; Westergaard, Jes Grabow; Olsen, Jørn

    2006-01-01

    BACKGROUND: Few prenatal risk factors of prolonged pregnancy, a pregnancy of 42 weeks or more, are known. The objective was to examine whether sociodemographic, reproductive, toxicologic, or medical health conditions were associated with the risk of prolonged pregnancy. METHODS: Data from...

  20. Surgical exposure dan perawatan ortodontik pada impaksi gigi insisif sentral rahang atas (Surgical exposure and orthodontic treatment on labially impacted maxillary central incisor

    Directory of Open Access Journals (Sweden)

    Bingah Fitri Melati

    2014-06-01

    Full Text Available Background: As a clinician we have to concern for an unerupted teeth especially in mixed dentition. Eruption failure can also be caused by early loss of deciduous teeth. Purpose: To report a case of unerupted maxillary central incisor caused by early loss of deciduous teeth due to trauma and the combination of excisional and orthodontic treatment. Case: A 8-years-old girl in mixed dentition phase came to Universitas Airlangga Dental Hospital with chief complaint of unerupted right maxillary central incisor while the left central incisor and both lateral incisor had erupted already. She had trauma when she was 1 year old and loss mostly her primary maxillary central incisors. An intraoral examination revealed lack of space in #11 region with root retained of #51, bulge was palpated in vestibulum and periapical radiograph showed that a delayed eruption upper central incisor without presence of disturbance. Case management: The exposure of the tooth was under local anesthesia a year after the orthodontic performed to make enough space for traction the tooth. A button was placed at palatal and used elastic strait to traction the tooth. After 3 months, bracket placed at labial to positioning until leveled and aligned with adjacent teeth. Conclusion: A simple excisional and orthodontic treatment were succesfully treated the labially impacted teeth.Latar belakang: Sebagai seorang klinisi kita harus memperhatikan apabila terdapat gigi yang belum erupsi terutama pada fase gigi pergantian. Kegagalan erupsi gigi juga dapat disebabkan karena tanggal premature gigi sulung. Tujuan: Melaporkan kasus impaksi gigi insisif sentral rahang atas yang disebabkan kehilangan premature gigi sulung karena trauma dengan kombinasi eksisi sederhana dan perawatan ortodontik. Kasus: Anak perempuan usia 8 tahun pada fase gigi pergantian datang ke Rumah Sakit Gigi dan Mulut Universitas Airlangga dengan keluhan gigi insisif sentral kanan rahang atasnya (#11 belum erupsi meskipun

  1. [Brain function recovery after prolonged posttraumatic coma].

    Science.gov (United States)

    Klimash, A V; Zhanaidarov, Z S

    2016-01-01

    To explore the characteristics of brain function recovery in patients after prolonged posttraumatic coma and with long-unconscious states. Eighty-seven patients after prolonged posttraumatic coma were followed-up for two years. An analysis of a clinical/neurological picture after a prolonged episode of coma was based on the dynamics of vital functions, neurological status and patient's reactions to external stimuli. Based on the dynamics of the clinical/neurological picture that shows the recovery of functions of the certain brain areas, three stages of brain function recovery after a prolonged episode of coma were singled out: brain stem areas, diencephalic areas and telencephalic areas. These functional/anatomic areas of brain function recovery after prolonged coma were compared to the present classifications.

  2. 9. Nuclear power plant service life prolongation

    International Nuclear Information System (INIS)

    Evropin, S.V.

    1998-01-01

    The problem of prolongation of nuclear power plant service life duration is discussed. A schematic diagram of the program developed in the course of activities dealing with NPP service time prolongation is shown and analyzed in details. It is shown that the basic moment when determining the strategy for NPP service time prolongation is the positive confirmation of the agreement between the NPP safety provisions and modern safety requirements. The other very important aspect of the problem is engineering substantiation of the measures assuring the reactor operation prolongation. The conclusion is made that available methods of recovering reactor materials properties, main components repair and replacement, the modern techniques for nondestructive testing of metals and NPP pipelines, as well as the developed approaches to reactor facility safety improvements make the prolongation of the Russian NPP service lifetimes possible from engineering viewpoint and economically desirable

  3. Human health tradeoffs in wellhead drinking water treatment: Comparing exposure reduction to embedded life cycle risks.

    Science.gov (United States)

    Gifford, Mac; Chester, Mikhail; Hristovski, Kiril; Westerhoff, Paul

    2018-01-01

    Treatment of drinking water decreases human health risks by reducing pollutants, but the required materials, chemicals, and energy emit pollutants and increase health risks. We explored human carcinogenic and non-carcinogenic disease tradeoffs of water treatment by comparing pollutant dose-response curves against life cycle burden using USEtox methodology. An illustrative wellhead sorbent groundwater treatment system removing hexavalent chromium or pentavalent arsenic serving 3200 people was studied. Reducing pollutant concentrations in drinking water from 20 μg L -1 to 10 μg L -1 avoided 37 potential cancer cases and 64 potential non-cancer disease cases. Human carcinogenicity embedded in treatment was 0.2-5.3 cases, and non-carcinogenic toxicity was 0.2-14.3 cases, depending on technology and degree of treatment. Embedded toxicity impacts from treating Cr(VI) using strong-base anion exchange were 90% of the toxicity impacts for treatment options requiring pH control. In scenarios where benefits exceeded burdens, tradeoffs still existed. Benefits are experienced by a local population but burdens are born externally where the materials and energy are produced, thus exporting the health risks. Even when burdens clearly exceeded benefits, cost considerations may still drive selecting a detrimental treatment level or technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Prolonged refractory dysphagia in polymyositis

    OpenAIRE

    Thomas Mathew; Mohan Muvvala; G R K Sarma; Raghunandan Nadig

    2015-01-01

    Herein, we report a patient with polymyositis (biopsy proved) with dysphagia that did not improve with conventional treatment. An upper gastrointestinal (GI) endoscopy showed esophageal stricture and a biopsy taken from the site revealed evidence of squamous cell carcinoma.

  5. Availability of treatment resources for the management of acute toxic exposures and poisonings in emergency departments among various types of hospitals in Palestine: a cross-sectional study

    OpenAIRE

    Zyoud, Sa’ed H; Al-Jabi, Samah W; Bali, Yara I; Al-Sayed, Afnan M; Sweileh, Waleed M; Awang, Rahmat

    2014-01-01

    Background Poisoning exposures continue to be a significant cause of morbidity and mortality worldwide. The lack of facilities, treatment resources, and antidotes in hospitals may affect the treatments provided and outcomes. This study aimed to determine the availability of gastrointestinal (GI) decontamination, stabilisation, elimination enhancement resources, and antidotes for the management of acute toxic exposures and poisonings in emergency departments (EDs) among various types of govern...

  6. Cue exposure treatment in a virtual environment to reduce nicotine craving: a functional MRI study.

    Science.gov (United States)

    Moon, Jiyoon; Lee, Jang-Han

    2009-02-01

    Smokers show an increase in cue reactivity during exposure to smoking-related cues. CET aims at extinguishing cue reactivity by repeated presentation of substance-related cues and has been claimed a potentially effective method of treating addictive behaviors, including cigarette smoking. We applied CET to eight late-adolescent smokers in virtual environments (VEs). When comparing pre-CET regions to those of post-CET, the inferior frontal gyrus and superior frontal gyrus were detected. These regions are consistent with previous studies of activated brain regions related to nicotine craving, and VE-CET seems to be an effective method of treating nicotine craving.

  7. Effect of exposure to wastewater treatment plant effluent on fathead minnow reproduction

    Data.gov (United States)

    U.S. Environmental Protection Agency — Adult fathead minnows were exposed to dilutions of a historically estrogenic wastewater treatment plant effluent in a 21-d reproduction study. This dataset is...

  8. Acute Cyanide Poisoning: Hydroxocobalamin and Sodium Thiosulfate Treatments with Two Outcomes following One Exposure Event.

    Science.gov (United States)

    Meillier, Andrew; Heller, Cara

    2015-01-01

    Cyanide is rapidly reacting and causes arrest of aerobic metabolism. The symptoms are diffuse and lethal and require high clinical suspicion. Remediation of symptoms and mortality is highly dependent on quick treatment with a cyanide antidote. Presently, there are two widely accepted antidotes: sodium thiosulfate and hydroxocobalamin. These treatments act on different components of cyanide's metabolism. Here, we present two cases resulting from the same source of cyanide poisoning and the use of both antidotes separately used with differing outcomes.

  9. Acute Cyanide Poisoning: Hydroxocobalamin and Sodium Thiosulfate Treatments with Two Outcomes following One Exposure Event

    OpenAIRE

    Meillier, Andrew; Heller, Cara

    2015-01-01

    Cyanide is rapidly reacting and causes arrest of aerobic metabolism. The symptoms are diffuse and lethal and require high clinical suspicion. Remediation of symptoms and mortality is highly dependent on quick treatment with a cyanide antidote. Presently, there are two widely accepted antidotes: sodium thiosulfate and hydroxocobalamin. These treatments act on different components of cyanide’s metabolism. Here, we present two cases resulting from the same source of cyanide poisoning and the use...

  10. Social Justice and HIV Vaccine Research in the Age of Pre-Exposure Prophylaxis and Treatment as Prevention

    Science.gov (United States)

    Bailey, Theodore C.; Sugarman, Jeremy

    2014-01-01

    The advent of pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) as means of HIV prevention raises issues of justice concerning how most fairly and equitably to apportion resources in support of the burgeoning variety of established HIV treatment and prevention measures and further HIV research, including HIV vaccine research. We apply contemporary approaches to social justice to assess the ethical justification for allocating resources in support of HIV vaccine research given competing priorities to support broad implementation of HIV treatment and prevention measures, including TasP and PrEP. We argue that there is prima facie reason to believe that a safe and effective preventive HIV vaccine would offer a distinct set of ethically significant benefits not provided by current HIV treatment or prevention methods. It is thereby possible to justify continued support for HIV vaccine research despite tension with priorities for treatment, prevention, and other research. We then consider a counter-argument to such a justification based on the uncertainty of successfully developing a safe and effective preventive HIV vaccine. Finally, we discuss how HIV vaccine research might now be ethically designed and conducted given the new preventive options of TasP and PrEP, focusing on the ethically appropriate standard of prevention for HIV vaccine trials. PMID:24033297

  11. The effect of UV exposure and heat treatment on crystallization behavior of photosensitive glasses

    Science.gov (United States)

    Kıbrıslı, Orhan; Ersundu, Ali Erçin

    2018-05-01

    In this study, photosensitive glasses in the Na2O-ZnO-Al2O3-SiO2 system with photosensitizing agents (cerium, silver, tin, antimony) and halogenides (NaF and KBr) were synthesized through a conventional melt-quenching technique. The crystallization mechanism was investigated for solely heat-treated and UV-exposed + heat-treated samples using differential thermal analysis (DTA), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS) and scanning electron microscopy (SEM) techniques to understand the effect of UV exposure on crystallization behavior of photosensitive glasses. Accordingly, non-isothermal DTA measurements were performed at different heating rates to determine crystallization peak, T p, and onset, T c, temperatures. For solely heat-treated samples, the kinetic parameters such as the Avrami constant, n, and morphology index, m, were calculated as 1 from the Ozawa method indicating surface crystallization and the value of crystallization activation energy was calculated as 944 kJ/mol using modified Kissinger method. On the contrary, bulk crystallization was found to be predominant for UV exposed + heat-treated samples revealing that UV exposure is the primary cause of bulk crystallization in photosensitive glasses.

  12. [Complex pathogenetic treatment schemes of vascular dyscirculatory disorders in the remote period after exposure to low dose radiation].

    Science.gov (United States)

    Holodova, N B; Zhavoronkova, L A; Ryzhov, B N

    2013-01-01

    Complex studies including modern methods of investigation of structures and functions of nervous system: electroencephalograsphy (EEG), coherent analysis, neuropsychological study and methods of neuroimaging were performed in 517 participants in liquidation of consequences of the accident (LCA) at the Chernobyl NPP in 1986-1987. Dyscirculatory metabolic encephalopathy was revealed to be the main pathology with the etiological mechanism based on dyscirculatorhypoxic and metabolic disorders. Complexity of the revealed symptoms testified to an early organism aging in remote periods after exposure to low dose radiation. Pathogenetic schemes were developed for treatment of dyscirculatory encephalopathy in liquidators, which include drugs improving blood supply, antiaggregants, antioxidants and metabolites of the brains in various combinations. Taking into consideration that early appearance of vascular dyscirculatory disorders observed in liquidators is the sign of early aging of the organism, geroprotectors were added to treatment schemes.

  13. Internalized stigma in adults with early phase versus prolonged psychosis.

    Science.gov (United States)

    Firmin, Ruth L; Lysaker, Paul H; Luther, Lauren; Yanos, Philip T; Leonhardt, Bethany; Breier, Alan; Vohs, Jenifer L

    2018-03-30

    Although internalized stigma is associated with negative outcomes among those with prolonged psychosis, surprisingly little work has focused on when in the course of one's illness stigma is internalized and the impact of internalization on symptoms or social functioning over the course of the illness. Therefore, this study investigated whether (1) internalized stigma is greater among those later in the course of psychosis and (2) whether internalized stigma has a stronger negative relationship with social functioning or symptoms among those with prolonged compared to early phase psychosis. Individuals with early phase (n = 40) and prolonged psychosis (n = 71) who were receiving outpatient services at an early-intervention clinic and a VA medical center, respectively, completed self-report measures of internalized stigma and interview-rated measures of symptoms and social functioning. Controlling for education, race and sex differences, internalized stigma was significantly greater among those with prolonged psychosis compared to early phase. Internalized stigma was negatively related to social functioning and positively related to symptoms in both groups. Furthermore, the magnitude of the relationship between cognitive symptoms and internalized stigma was significantly greater among those with early phase. Stereotype endorsement, discrimination experiences and social withdrawal also differentially related to symptoms and social functioning across the 2 samples. Findings suggest that internalized stigma is an important variable to incorporate into models of early psychosis. Furthermore, internalized stigma may be a possible treatment target among those with early phase psychosis. © 2018 John Wiley & Sons Australia, Ltd.

  14. Chemical pleurodesis for prolonged postoperative air leak in primary spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Cheng-Hung How

    2014-05-01

    Conclusion: Chemical pleurodesis using OK-432 or minocycline is safe and convenient for prolonged air leak after thoracoscopic treatment for PSP. Our experience suggested that OK-432 may be more effective than minocycline in reducing air leak.

  15. Prolonged CT urography in duplex kidney.

    Science.gov (United States)

    Gong, Honghan; Gao, Lei; Dai, Xi-Jian; Zhou, Fuqing; Zhang, Ning; Zeng, Xianjun; Jiang, Jian; He, Laichang

    2016-05-13

    Duplex kidney is a common anomaly that is frequently associated with multiple complications. Typical computed tomography urography (CTU) includes four phases (unenhanced, arterial, parenchymal and excretory) and has been suggested to considerably aid in the duplex kidney diagnosi. Unfortunately, regarding duplex kidney with prolonged dilatation, the affected parenchyma and tortuous ureters demonstrate a lack of or delayed excretory opacification. We used prolonged-delay CTU, which consists of another prolonged-delay phase (1- to 72-h delay; mean delay: 24 h) to opacify the duplicated ureters and affected parenchyma. Seventeen patients (9 males and 8 females; age range: 2.5-56 y; mean age: 40.4 y) with duplex kidney were included in this study. Unenhanced scans did not find typical characteristics of duplex kidney, except for irregular perirenal morphology. Duplex kidney could not be confirmed on typical four-phase CTU, whereas it could be easily diagnosed in axial and CT-3D reconstruction using prolonged CTU (prolonged-delay phase). Between January 2005 and October 2010, in this review board-approved study (with waived informed consent), 17 patients (9 males and 8 females; age range: 2.5 ~ 56 y; mean age: 40.4 y) with suspicious duplex kidney underwent prolonged CTU to opacify the duplicated ureters and confirm the diagnosis. Our results suggest the validity of prolonged CTU to aid in the evaluation of the function of the affected parenchyma and in the demonstration of urinary tract malformations.

  16. Risk Factors of Prolonged Hospitalization in Patients with Hyperemesis Gravidarum

    Directory of Open Access Journals (Sweden)

    Hasan Onur Topcu

    2015-03-01

    Conclusion: Number of vomiting per day and maternal serum TSH levels could help physicians to estimate the risk of prolonged hospitalization; however further investigations are needed in large population studies. Identifying the high risk patients is important both for prevention of HEG and beginning appropriate antiemetic treatment to avoid complications to reduce the economic costs. [Cukurova Med J 2015; 40(1.000: 113-118

  17. Exposure to Violence, Posttraumatic Stress Symptoms, and Borderline Personality Pathology Among Adolescents in Residential Psychiatric Treatment: The Influence of Emotion Dysregulation.

    Science.gov (United States)

    Buckholdt, Kelly E; Weiss, Nicole H; Young, John; Gratz, Kim L

    2015-12-01

    Exposure to violence during adolescence is a highly prevalent phenomenon associated with a range of deleterious outcomes. Theoretical literature suggests that emotion dysregulation is one consequence of exposure to violence associated with the manifestation of posttraumatic stress symptoms (PTSS) and borderline personality (BP) pathology. Thus, the goal of the present study was to examine the mediating role of emotion dysregulation in the relation between exposure to violence and both PTSS and BP pathology in a sample of 144 adolescents (age 10- to 17-years; 51% male; 55% African American) admitted to a psychiatric residential treatment center. Exposure to violence was associated with greater emotion dysregulation, which, in turn, was associated with greater PTSS and BP pathology. Furthermore, emotion dysregulation mediated the associations between exposure to violence and both PTSS and BP pathology. Findings suggest the importance of assessing and treating emotion dysregulation among violence-exposed adolescents in psychiatric residential treatment.

  18. Quantitative expression of osteopontin in nasal mucosa of patients with allergic rhinitis: effects of pollen exposure and nasal glucocorticoid treatment

    Directory of Open Access Journals (Sweden)

    O'Neil Serena E

    2010-11-01

    Full Text Available Abstract Background Osteopontin (OPN is a multifunctional cytokine that has been primarily investigated in Th1 diseases. Recently, it has also been implicated in Th2-mediated allergic diseases, such as asthma. The expression of OPN in allergic rhinitis (AR is currently unknown, as is the effect of intranasal glucocorticosteroids (GCs on that expression. Methods Subjects with AR were randomised to receive treatment with fluticasone propionate (FP (n = 12 or a placebo (n = 16 over the grass pollen season and nasal biopsies were taken prior to, and during the season. OPN expression in the nasal mucosa was examined with immunohistochemistry. Healthy non-AR controls (n = 5 were used as a comparator. Results OPN expression was detected in epithelial cells, subepithelial infiltrating/inflammatory cells and cells lining the vessels and glands of all subjects. Comparison of the pre- and peak-pollen season biopsy sections in placebo treated patients revealed no increase in OPN expression during the grass pollen season (5.7% vs 6.4%. Treatment with a local glucocorticosteroid did not alter the expression of OPN during pollen exposure (6.2% vs 6.7%. Conclusion OPN has been increasingly associated with the pathogenesis of various Th2-mediated diseases. However, our finding that the OPN expression in the nasal mucosa of AR patients is not significantly affected by allergen exposure and is comparable to that of the healthy controls, suggests that intracellular OPN is not directly involved in the pathogenesis of allergic rhinitis.

  19. Treatment preferences of psychotherapy patients with chronic PTSD.

    Science.gov (United States)

    Markowitz, John C; Meehan, Kevin B; Petkova, Eva; Zhao, Yihong; Van Meter, Page E; Neria, Yuval; Pessin, Hayley; Nazia, Yasmin

    2016-03-01

    Patient treatment preference may moderate treatment effect in major depressive disorder (MDD) studies. Little research has addressed preference in posttraumatic stress disorder (PTSD); almost none has assessed actual patients' PTSD psychotherapy preferences. From a 14-week trial of chronic PTSD comparing prolonged exposure, relaxation therapy, and interpersonal psychotherapy, we report treatment preferences of the 110 randomized patients, explore preference correlates, and assess effects on treatment outcome. Patients recruited between 2008 and 2013 with chronic DSM-IV PTSD (Clinician-Administered PTSD Scale [CAPS] score ≥ 50) received balanced, scripted psychotherapy descriptions prerandomization and indicated their preferences. Analyses assessed relationships of treatment attitudes to demographic and clinical factors. We hypothesized that patients randomized to preferred treatments would have better outcomes, and to unwanted treatment worse outcomes. Eighty-seven patients (79%) voiced treatment preferences or disinclinations: 29 (26%) preferred prolonged exposure, 29 (26%) preferred relaxation therapy, and 56 (50%) preferred interpersonal psychotherapy (Cochran Q = 18.46, P psychotherapy (Cochran Q = 22.71, P psychotherapy preferences to outcome. Despite explanations emphasizing prolonged exposure's greater empirical support, patients significantly preferred interpersonal psychotherapy. Preference subtly affected psychotherapy outcome; depression appeared an important moderator of the effect of unwanted treatment on outcome. Potential biases to avoid in future research are discussed. ClinicalTrials.gov identifier: NCT00739765. © Copyright 2015 Physicians Postgraduate Press, Inc.

  20. Potential exposure and treatment efficiency of nanoparticles in water supplies based on wastewater reclamation

    DEFF Research Database (Denmark)

    Kirkegaard, Peter; Hansen, Steffen Foss; Rygaard, Martin

    2015-01-01

    Water scarcity brings an increased focus on wastewater reclamation for drinking water supply. Meanwhile, the production volume of nanoparticles (NPs) is rapidly increasing, but to date there has been little attention given to the fate of NPs in water systems based on wastewater reclamation. We have...... investigated the possible concentrations of silver (Ag), titanium dioxide (TiO2), and zinc oxide (ZnO) nanoparticles in tap water for water supplies based on reclaimed wastewater. Tap water concentrations of the NPs were assessed by mass flow analyses of two typical wastewater reclamation concepts: 1) advanced...... studies are available on the removal efficiencies of NPs by advanced water treatment processes with a majority of the identified studies focusing on removal efficiencies in wastewater treatment plants and fate in surface waters. The NP removal efficiency of several treatment processes is unknown...

  1. Effect of eliminating administrative radiographs on patient exposure and accuracy of provisional treatment plans

    International Nuclear Information System (INIS)

    Kantor, M.L.; Slome, B.A.

    1987-01-01

    Published reports and recommendations suggest that radiographs are often ordered because of administrative policies during the screening and selection of patients for dental school clinics. This study examined the prescription of radiographs for two groups of patients: those who were radiographically examined according to an administrative policy and those whose radiographic needs were determined by a clinical examination. The provisional treatment needs assessment based on the screening examination was compared to the final treatment plan based on a complete diagnostic workup for both groups of patients to assess the effect of a change in school policy. Clinicians ordered half the number of panoramic radiographs as would have been ordered by administrative policy. There was no significant difference in the agreement between the provisional and final treatment plans under the two policies. These results suggest that dental schools can comply with federal recommendations against administrative radiographs without compromising patient selection

  2. Licence prolongations of US nuclear power plants

    International Nuclear Information System (INIS)

    2004-04-01

    Licences of US nuclear reactors were initially attributed for a 40 years duration. However, the vast majority of the reactors can benefit of a licence prolongation for a period of 20 years maximum. This article recalls first the procedure to follow for the licence prolongation demands (safety analysis, components aging, environmental impact statement), and then it makes a status of the accepted prolongations, of the demands under examination, and of the demands that should be presented in the next 5 years. (J.S.)

  3. The Influence of Methotrexate Treatment on Male Fertility and Pregnancy Outcome After Paternal Exposure.

    Science.gov (United States)

    Grosen, Anne; Kelsen, Jens; Hvas, Christian Lodberg; Bellaguarda, Emanuelle; Hanauer, Stephen B

    2017-04-01

    Inflammatory bowel disease incidence peaks during the reproductive years. Methotrexate (MTX) is frequently used for inflammatory bowel disease, but its use during pregnancy is contraindicated in women because of teratogenic effects. The aim of this review is to investigate the influence of MTX on male fertility and pregnancy outcomes after paternal MTX exposure. A systematic literature search was performed by applying 2 focus areas, "methotrexate" and "male fertility or pregnancy outcome." Terms and keywords were used both as MeSH terms and free-text searches. Pertinent articles were searched for additional relevant references. In animal studies, MTX induces aberrations in sperm DNA that have not been identified in humans. The effects of MTX on human sperm quality have only been described in case reports. A transient adverse effect on sperm quality with low-dose MTX has been reported, but several other cases have not found harmful effects of MTX. MTX has not been measured in human sperm ejaculates; yet, the risk of a direct toxic effect on the fetus through MTX-contaminated seminal plasma seems negligible. Until now, 284 pregnancies with paternal MTX exposure have been reported. The outcomes were 248 live births and a total of 13 malformations, with no overt indication of MTX embryopathy. This review reveals the lack of studies on the safety of MTX with regard to male reproduction. It is not clear whether MTX transiently influences male fertility and sperm DNA integrity, and more studies are needed. Comparative cohort studies found no increased risk of adverse pregnancy outcomes.

  4. Acute Cyanide Poisoning: Hydroxocobalamin and Sodium Thiosulfate Treatments with Two Outcomes following One Exposure Event

    Directory of Open Access Journals (Sweden)

    Andrew Meillier

    2015-01-01

    Full Text Available Cyanide is rapidly reacting and causes arrest of aerobic metabolism. The symptoms are diffuse and lethal and require high clinical suspicion. Remediation of symptoms and mortality is highly dependent on quick treatment with a cyanide antidote. Presently, there are two widely accepted antidotes: sodium thiosulfate and hydroxocobalamin. These treatments act on different components of cyanide’s metabolism. Here, we present two cases resulting from the same source of cyanide poisoning and the use of both antidotes separately used with differing outcomes.

  5. Dextromethorphan as a phenotyping test to predict endoxifen exposure in patients on tamoxifen treatment

    NARCIS (Netherlands)

    Graan, A.J. de; Teunissen, S.F.; Vos, F.Y. de; Loos, W.J.; Schaik, R.H. van; Jongh, F.E. de; Vos, A.I. de; Alphen, R.J. van; Holt, B. van der; Verweij, J.; Seynaeve, C.; Beijnen, J.H.; Mathijssen, R.H.

    2011-01-01

    PURPOSE: Tamoxifen, a widely used agent for the prevention and treatment of breast cancer, is mainly metabolized by CYP2D6 and CYP3A to form its most abundant active metabolite, endoxifen. Interpatient variability in toxicity and efficacy of tamoxifen is substantial. Contradictory results on the

  6. Pregnancy outcome after in utero exposure to local anesthetics as part of dental treatment: A prospective comparative cohort study.

    Science.gov (United States)

    Hagai, Aharon; Diav-Citrin, Orna; Shechtman, Svetlana; Ornoy, Asher

    2015-08-01

    Dental treatment and use of local anesthetics during pregnancy generally are considered harmless because of lack of evidence of adverse pregnancy effects. Data on the safety of dental treatment and local anesthetics during pregnancy are scant. Dental care is often a reason for concern both among women and their health care providers. The primary objective of this study was to evaluate the rate of major anomalies after exposure to local anesthetics as part of dental care during pregnancy. The authors performed a prospective, comparative observational study at the Israeli Teratology Information Services between 1999 and 2005. The authors followed 210 pregnancies exposed to dental local anesthetics (112 [53%] in the first trimester) and compared them with 794 pregnancies not exposed to teratogens. The rate of major anomalies was not significantly different between the groups (4.8% versus 3.3%, P = .300). There was no difference in the rate of miscarriages, gestational age at delivery, or birth weight. The most common types of dental treatment were endodontic treatment (43%), tooth extraction (31%), and tooth restoration (21%). Most women (63%) were not exposed to additional medications. Approximately one-half (51%) of the women were not exposed to dental radiography, and 44% were exposed to radiation, mostly bite-wing radiography. This study's results suggest that use of dental local anesthetics, as well as dental treatment during pregnancy, do not represent a major teratogenic risk. There seems to be no reason to prevent pregnant women from receiving dental treatment and local anesthetics during pregnancy. Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.

  7. Prolonged delirium misdiagnosed as a mood disorder.

    Science.gov (United States)

    Cao, Fei; Salem, Haitham; Nagpal, Caesa; Teixeira, Antonio L

    2017-01-01

    Delirium can be conceptualized as an acute decline in cognitive function that typically lasts from hours to a few days. Prolonged delirium can also affect patients with multiple predisposing and/or precipitating factors. In clinical practice, prolonged delirium is often unrecognized, and can be misdiagnosed as other psychiatric disorders. We describe a case of a 59-year-old male presenting with behavioral and cognitive symptoms that was first misdiagnosed as a mood disorder in a general hospital setting. After prolonged delirium due to multiple factors was confirmed, the patient was treated accordingly with symptomatic management. He evolved with progressive improvement of his clinical status. Early diagnosis and management of prolonged delirium are important to improve patient prognosis and avoid iatrogenic measures.

  8. QT Prolongation due to Graves’ Disease

    Directory of Open Access Journals (Sweden)

    Zain Kulairi

    2017-01-01

    Full Text Available Hyperthyroidism is a highly prevalent disease affecting over 4 million people in the US. The disease is associated with many cardiac complications including atrial fibrillation and also less commonly with ventricular tachycardia and fibrillation. Many cardiac pathologies have been extensively studied; however, the relationship between hyperthyroidism and rate of ventricular repolarization manifesting as a prolonged QTc interval is not well known. Prolonged QTc interval regardless of thyroid status is a risk factor for cardiovascular mortality and life-threatening ventricular arrhythmia. The mechanism regarding the prolongation of the QT interval in a hyperthyroid patient has not been extensively investigated although its clinical implications are relevant. Herein, we describe a case of prolonged QTc in a patient who presented with signs of hyperthyroidism that was corrected with return to euthyroid status.

  9. Prolonged parenteral nutrition after neonatal gastrointestinal surgery

    DEFF Research Database (Denmark)

    Estmann, Anne; Qvist, Niels; Husby, Steffen

    2002-01-01

    to diagnosis and clinical course. METHODOLOGY: This study reviews the clinical course of infants with gastrointestinal disease (gastroschisis, intestinal atresia, omphalocele, volvulus, Hirschsprung's disease and necrotizing enterocolitis) with a prolonged need for parenteral nutrition in the Western part...

  10. Prolonged Pregnancy: Methods, Causal Determinants and Outcome

    DEFF Research Database (Denmark)

    Olesen, Annette Wind

    ) to study the incidence of prolonged pregnancy as a function of methods for determining gestational age; 2) to determine the risk of obstetrical and fetal complications in prolonged pregnancy; 3) to validate the self-reported gestational age in the National Birth Cohort; 4) to determine whether...... an ultrasound scan in the first or second trimester, or menstrual history was best at predicting the day of delivery; 5) to study the risk of recurrence of prolonged pregnancy as a function of change in male partner, social status and municipality; and 6) to detect prenatal risk indicators of prolonged...... of perinatal and obstetrical complications was high in post-term delivery compared to term delivery (OR between 1.2 and 3.1). The risk of perinatal death (OR=1.36 (1.08-1.72)) was also higher in the post-term group (I). The self-reported gestational ages in the National Birth Cohort correlated well with data...

  11. Translating QT interval prolongation from conscious dogs to humans.

    Science.gov (United States)

    Dubois, Vincent F S; Smania, Giovanni; Yu, Huixin; Graf, Ramona; Chain, Anne S Y; Danhof, Meindert; Della Pasqua, Oscar

    2017-02-01

    In spite of screening procedures in early drug development, uncertainty remains about the propensity of new chemical entities (NCEs) to prolong the QT/QTc interval. The evaluation of proarrhythmic activity using a comprehensive in vitro proarrhythmia assay does not fully account for pharmacokinetic-pharmacodynamic (PKPD) differences in vivo. In the present study, we evaluated the correlation between drug-specific parameters describing QT interval prolongation in dogs and in humans. Using estimates of the drug-specific parameter, data on the slopes of the PKPD relationships of nine compounds with varying QT-prolonging effects (cisapride, sotalol, moxifloxacin, carabersat, GSK945237, SB237376 and GSK618334, and two anonymized NCEs) were analysed. Mean slope estimates varied between -0.98 ms μM -1 and 6.1 ms μM -1 in dogs and -10 ms μM -1 and 90 ms μM -1 in humans, indicating a wide range of effects on the QT interval. Linear regression techniques were then applied to characterize the correlation between the parameter estimates across species. For compounds without a mixed ion channel block, a correlation was observed between the drug-specific parameter in dogs and humans (y = -1.709 + 11.6x; R 2  = 0.989). These results show that per unit concentration, the drug effect on the QT interval in humans is 11.6-fold larger than in dogs. Together with information about the expected therapeutic exposure, the evidence of a correlation between the compound-specific parameter in dogs and in humans represents an opportunity for translating preclinical safety data before progression into the clinic. Whereas further investigation is required to establish the generalizability of our findings, this approach can be used with clinical trial simulations to predict the probability of QT prolongation in humans. © 2016 The British Pharmacological Society.

  12. Vaginal Mucosal Flap as a Sling Preservation for the Treatment of Vaginal Exposure of Mesh

    OpenAIRE

    Kim, Sea Young; Park, Jong Yeon; Kim, Han Kwon; Park, Chang Hoo; Kim, Sung Jin; Sung, Gi Teck; Park, Chang Myon

    2010-01-01

    Purpose Tension-free vaginal tape (TVT) procedures are used for the treatment of stress urinary incontinence in women. The procedures with synthetic materials can have a risk of vaginal erosion. We experienced transobturator suburethral sling (TOT) tape-induced vaginal erosion and report the efficacy of a vaginal mucosal covering technique. Materials and Methods A total of 560 female patients diagnosed with stress urinary incontinence underwent TOT procedures at our hospital between January 2...

  13. Escitalopram or novel herbal mixture treatments during or following exposure to stress reduce anxiety-like behavior through corticosterone and BDNF modifications.

    Directory of Open Access Journals (Sweden)

    Ravid Doron

    Full Text Available Anxiety disorders are a major public health concern worldwide. Studies indicate that repeated exposure to adverse experiences early in life can lead to anxiety disorders in adulthood. Current treatments for anxiety disorders are characterized by a low success rate and are associated with a wide variety of side effects. The aim of the present study was to evaluate the anxiolytic effects of a novel herbal treatment, in comparison to treatment with the selective serotonin reuptake inhibitor escitalopram. We recently demonstrated the anxiolytic effects of these treatments in BALB mice previously exposed to one week of stress. In the present study, ICR mice were exposed to post natal maternal separation and to 4 weeks of unpredictable chronic mild stress in adolescence, and treated during or following exposure to stress with the novel herbal treatment or with escitalopram. Anxiety-like behavior was evaluated in the elevated plus maze. Blood corticosterone levels were evaluated using radioimmunoassay. Brain derived neurotrophic factor levels in the hippocampus were evaluated using enzyme-linked immunosorbent assay. We found that (1 exposure to stress in childhood and adolescence increased anxiety-like behavior in adulthood; (2 the herbal treatment reduced anxiety-like behavior, both when treated during or following exposure to stress; (3 blood corticosterone levels were reduced following treatment with the herbal treatment or escitalopram, when treated during or following exposure to stress; (4 brain derived neurotrophic factor levels in the hippocampus of mice treated with the herbal treatment or escitalopram were increased, when treated either during or following exposure to stress. This study expands our previous findings and further points to the proposed herbal compound's potential to be highly efficacious in treating anxiety disorders in humans.

  14. Treatment of actinide exposures: a review of Ca-DTPA injections inside CEA-COGEMA plants

    International Nuclear Information System (INIS)

    Grappin, Louise; Berard, Philippe; Carbone, Lise; Le Goff, Jean-Pierre; Neron, Marie-Odile; Menetrier, Florence; Courtay, Catherine; Castagnet, Xavier; Piechowski, Jean

    2007-01-01

    Calcium diethylenetriamine pent-acetate (Ca-DTPA) has been used for medical treatment of plutonium and americium contaminations in the CEA and COGEMA plants from 1970 to 2003. This paper is a survey of the injections Ca-DTPA administered as a chelating molecule and it will be a part of the authorization process for Ca-DTPA by intravenous administration. Out of 1158 injections administered to 469 persons, 548 events of possible or confirmed contamination were reported. These employees were followed by occupational physicians according to the current French regulations. These incidents took place at work, were most often minor, not requiring follow-up treatment. The authors present (1) a synthesis of the most recent findings. Due to its short biological half-time and its limited action in the blood, Ca-DTPA does not chelate with plutonium and americium as soon as these elements are deposited in the target organs. It justifies an early treatment, even in cases of suspected contamination followed by additional injections if necessary (2) data concerning these 1158 injections (route of contamination, dosage, adverse effects, etc.) The authors also investigated a study on the efficacy of the product on a group of persons having received five or more injections. These results were compared with the efficacy estimated theoretically. Dosages and therapeutic schemes were proposed based on these observations. This synthesis is the result of a collective work having mobilized the occupational medicine departments, the medical laboratories inside a working group CEA-COGEMA-SPRA. (authors)

  15. Comparison of two spreadsheets for calculation of radiation exposure following hyperthyroidism treatment with iodine-131

    Energy Technology Data Exchange (ETDEWEB)

    Vrigneaud, J.M. [CHU Bichat, nuclear medicine department, 75 - Paris (France); Carlier, T. [CHU Hotel Dieu, nuclear medicine department, 44 - Nantes (France)

    2006-07-01

    Comparison of the two spreadsheets did not show any significant differences provided that proper biological models were used to follow 131 iodine clearance. This means that even simple assumptions can be used to give reasonable radiation safety recommendations. Nevertheless, a complete understanding of the formalism is required to use correctly these spreadsheets. Initial parameters must be chosen carefully and validation of the computed results must be done. Published guidelines are found to be in accordance with those issued from these spreadsheets. Furthermore, both programs make it possible to collect biological data from each patient and use it as input to calculate individual tailored radiation safety advices. Also, measured exposure rate may be entered into the spreadsheets to calculate patient-specific close contact delays required to reduce the dose to specified limits. These spreadsheets may be used to compute restriction times for any given radiopharmaceutical, provided that input parameters are chosen correctly. They can be of great help to physicians to provide patients with guidance on how to maintain doses to other individuals as low as reasonably achievable. (authors)

  16. Robustness of tungsten single atom tips to thermal treatment and air exposure

    Energy Technology Data Exchange (ETDEWEB)

    Vesa, Cristian; Urban, Radovan [Department of Physics, University of Alberta, Edmonton, Alberta, Canada T6G 2G7 (Canada); National Institute for Nanotechnology, National Research Council of Canada, Edmonton, Alberta, Canada T6G 2M9 (Canada); Pitters, Jason L., E-mail: jason.pitters@nrc-cnrc.gc.ca [National Institute for Nanotechnology, National Research Council of Canada, Edmonton, Alberta, Canada T6G 2M9 (Canada); Wolkow, Robert A. [Department of Physics, University of Alberta, Edmonton, Alberta, Canada T6G 2G7 (Canada); National Institute for Nanotechnology, National Research Council of Canada, Edmonton, Alberta, Canada T6G 2M9 (Canada)

    2014-05-01

    Highlights: • W(1 1 1) single atom tips (SATs) were exposed to air. • SATs could be regenerated by field assisted chemical etching after exposure. • Warming procedures to minimize tip contamination were developed. • Degassing temperatures for air exposed tips were established. • Tip faceting occurred when SATs and unetched tips were annealed above 1200 °C. - Abstract: Experiments aimed at assessing the robustness of nitrogen-etched, single-atom tips (SATs) prepared using W(1 1 1) single crystal wire were performed. Our experiments showed that single-atoms tips sustain minimal damage when exposed to atmospheric conditions and can be readily and quickly nitrogen-etched to single-atom tips thereafter. The SATs can be annealed at temperatures up to 1100 °C with minimal shape changes. Moreover, annealing temperatures in excess of 1200 °C resulted in an apex faceting which may prove important in further single-atom tip creation. Procedures for warming of the SATs from operating temperatures of 80 K were also evaluated to determine conditions that limit tip contamination. These results show that SATS could be fabricated in a dedicated vacuum system and subsequently transferred to other instruments where they would undergo a brief conditioning procedure to recover the single-atom apex configuration prior to being subjected to operating conditions.

  17. Comparison of two spreadsheets for calculation of radiation exposure following hyperthyroidism treatment with iodine-131

    International Nuclear Information System (INIS)

    Vrigneaud, J.M.; Carlier, T.

    2006-01-01

    Comparison of the two spreadsheets did not show any significant differences provided that proper biological models were used to follow 131 iodine clearance. This means that even simple assumptions can be used to give reasonable radiation safety recommendations. Nevertheless, a complete understanding of the formalism is required to use correctly these spreadsheets. Initial parameters must be chosen carefully and validation of the computed results must be done. Published guidelines are found to be in accordance with those issued from these spreadsheets. Furthermore, both programs make it possible to collect biological data from each patient and use it as input to calculate individual tailored radiation safety advices. Also, measured exposure rate may be entered into the spreadsheets to calculate patient-specific close contact delays required to reduce the dose to specified limits. These spreadsheets may be used to compute restriction times for any given radiopharmaceutical, provided that input parameters are chosen correctly. They can be of great help to physicians to provide patients with guidance on how to maintain doses to other individuals as low as reasonably achievable. (authors)

  18. Pharmacokinetics of prolonged-release tacrolimus and implications for use in solid organ transplant recipients.

    Science.gov (United States)

    Tanzi, Maria G; Undre, Nasrullah; Keirns, James; Fitzsimmons, William E; Brown, Malcolm; First, M Roy

    2016-08-01

    Prolonged-release tacrolimus was developed as a once-daily formulation with ethylcellulose as the excipient, resulting in slower release and reduction in peak concentration (Cmax ) for a given dose compared with immediate-release tacrolimus, which is administered twice daily. This manuscript reviews pharmacokinetic information on prolonged-release tacrolimus in healthy subjects, in transplant recipients converted from immediate-release tacrolimus, and in de novo kidney and liver transplant recipients. As with the immediate-release formulation, prolonged-release tacrolimus shows a strong correlation between trough concentration (Cmin ) and area under the 24-hour time-concentration curve (AUC24 ), indicating that trough whole blood concentrations provide an accurate measure of drug exposure. We present the pharmacokinetic similarities and differences between the two formulations, so that prescribing physicians will have a better understanding of therapeutic drug monitoring in patients receiving prolonged-release tacrolimus. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Usefulness assessment of secondary shield for the lens exposure dose reduction during radiation treatment of peripheral orbit

    International Nuclear Information System (INIS)

    Kwak, Yong Kuk; Hong, Sun Gi; Ha, Min Yong; Park, Jang Pil; Yoo, Sook Hyun; Cho, Woong

    2015-01-01

    This study presents the usefulness assessment of secondary shield for the lens exposure dose reduction during radiation treatment of peripheral orbit. We accomplished IMRT treatment plan similar with a real one through the computed treatment planning system after CT simulation using human phantom. For the secondary shield, we used Pb plate (thickness 3mm, diameter 25mm) and 3 mm tungsten eye-shield block. And we compared lens dose using OSLD between on TPS and on simulation. Also, we irradiated 200 MU(6 MV, SPD(Source to Phantom Distance)=100 cm, F·S 5×5 cm)on a 5 cm acrylic phantom using the secondary shielding material of same condition, 3 mm Pb and tungsten eye-shield block. And we carried out the same experiment using 8 cm Pb block to limit effect of leakage and transmitted radiation out of irradiation field. We attached OSLD with a 1cm away from the field at the side of phantom and applied a 3mm bolus equivalent to the thickness of eyelid. Using human phantom, the Lens dose on IMRT treatment plan is 315.9 cGy and the real measurement value is 216.7 cGy. And after secondary shield using 3mm Pb plate and tungsten eye-shield block, each lens dose is 234.3, 224.1 cGy. The result of a experiment using acrylic phantom, each value is 5.24, 5.42 and 5.39 cGy in case of no block, 3mm Pb plate and tungsten eye-shield block. Applying O.S.B out of the field, each value is 1.79, 2.00 and 2.02 cGy in case of no block, 3 mm Pb plate and tungsten eye-shield block. When secondary shielding material is used to protect critical organ while irradiating photon, high atomic number material (like metal) that is near by critical organ can be cause of dose increase according to treatment region and beam direction because head leakage and collimator and MLC transmitted radiation are exist even if it's out of the field. The attempt of secondary shield for the decrease of exposure dose was meaningful, but untested attempt can have a reverse effect. So, a preliminary inspection

  20. Management of impacted all canines with surgical exposure and alignment by orthodontic treatment

    Directory of Open Access Journals (Sweden)

    Radha Katiyar

    2013-01-01

    Full Text Available Canine impaction is a dental problem very often encountered in orthodontic practice. After the third molar, the canine is the most frequently impacted tooth. Bringing the impacted canine into a normal position is important for functional occlusion and the final esthetics of the orthodontic treatment. This article illustrates a peculiar case, in which all four permanent canines maintained their unerupted status at age of 16 years. All four impacted canines were surgically exposed, attachment bonded, traction given with K-9 spring and ideally positioned with fixed orthodontic mechanotherapy.

  1. Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Takashige, E-mail: tkawakami@ph.bunri-u.ac.jp; Yoshimi, Masaki; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya

    2014-03-01

    The role of endoplasmic reticulum (ER) stress in pregnancy remains largely unknown. Pregnant mice were subcutaneously administered tunicamycin (Tun), an ER stressor, as a single dose [0, 50, and 100 μg Tun/kg/body weight (BW)] on gestation days (GDs) 8.5, 12.5, and 15.5. A high incidence (75%) of preterm delivery was observed only in the group treated with Tun 100 μg/kg BW at GD 15.5, indicating that pregnant mice during late gestation are more susceptible to ER stress on preterm delivery. We further examined whether prolonged in utero exposure to ER stress affects fetal development. Pregnant mice were subcutaneously administered a dose of 0, 20, 40, and 60 μg Tun/kg from GD 12.5 to 16.5. Tun treatment decreased the placental and fetal weights in a dose-dependent manner. Histological evaluation showed the formation of a cluster of spongiotrophoblast cells in the labyrinth zone of the placenta of Tun-treated mice. The glycogen content of the fetal liver and placenta from Tun-treated mice was lower than that from control mice. Tun treatment decreased mRNA expression of Slc2a1/glucose transporter 1 (GLUT1), which is a major transporter for glucose, but increased placental mRNA levels of Slc2a3/GLUT3. Moreover, maternal exposure to Tun resulted in a decrease in vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, and placental growth factor. These results suggest that excessive and exogenous ER stress may induce functional abnormalities in the placenta, at least in part, with altered GLUT and vascular-related gene expression, resulting in low infant birth weight. - Highlights: • Maternal exposure to excessive ER stress induced preterm birth and IUGR. • Prolonged excessive ER stress altered the formation of the placental labyrinth. • ER stress decreased GLUT1 mRNA expression in the placenta, but increased GLUT3. • ER stress-induced IUGR causes decreased glycogen and altered glucose transport.

  2. Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight

    International Nuclear Information System (INIS)

    Kawakami, Takashige; Yoshimi, Masaki; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya

    2014-01-01

    The role of endoplasmic reticulum (ER) stress in pregnancy remains largely unknown. Pregnant mice were subcutaneously administered tunicamycin (Tun), an ER stressor, as a single dose [0, 50, and 100 μg Tun/kg/body weight (BW)] on gestation days (GDs) 8.5, 12.5, and 15.5. A high incidence (75%) of preterm delivery was observed only in the group treated with Tun 100 μg/kg BW at GD 15.5, indicating that pregnant mice during late gestation are more susceptible to ER stress on preterm delivery. We further examined whether prolonged in utero exposure to ER stress affects fetal development. Pregnant mice were subcutaneously administered a dose of 0, 20, 40, and 60 μg Tun/kg from GD 12.5 to 16.5. Tun treatment decreased the placental and fetal weights in a dose-dependent manner. Histological evaluation showed the formation of a cluster of spongiotrophoblast cells in the labyrinth zone of the placenta of Tun-treated mice. The glycogen content of the fetal liver and placenta from Tun-treated mice was lower than that from control mice. Tun treatment decreased mRNA expression of Slc2a1/glucose transporter 1 (GLUT1), which is a major transporter for glucose, but increased placental mRNA levels of Slc2a3/GLUT3. Moreover, maternal exposure to Tun resulted in a decrease in vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, and placental growth factor. These results suggest that excessive and exogenous ER stress may induce functional abnormalities in the placenta, at least in part, with altered GLUT and vascular-related gene expression, resulting in low infant birth weight. - Highlights: • Maternal exposure to excessive ER stress induced preterm birth and IUGR. • Prolonged excessive ER stress altered the formation of the placental labyrinth. • ER stress decreased GLUT1 mRNA expression in the placenta, but increased GLUT3. • ER stress-induced IUGR causes decreased glycogen and altered glucose transport

  3. Quality of drug label information on QT interval prolongation

    DEFF Research Database (Denmark)

    Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H

    2014-01-01

    BACKGROUND: Information regarding QT-prolongation in the drug label may vary between products. This could lead to suboptimal risk minimization strategies. OBJECTIVE: To systematically assess the variation in the extent and content of information on QT prolongation in the summary of product......-prolongation'/'QT-prolongation') and the advice on cautionary measures pertaining to QT-prolongation in the label were examined, as well as their association. RESULTS: Of the 175 screened products, 44 contained information on QT in the SPC ('no QT-prolongation': 23%, 'unclear drug-QT association': 43%, 'possibly QT-prolongation': 16%, 'QT......-prolongation': 18%). 62% contained advices to act with caution in patients with additional risk factors for QT-prolongation. Products that more likely to have QT-prolonging properties according to the SPC provided more information on QT-prolongation in the SPC ('no prolongation': 10% and for the category 'QT...

  4. Ionizing radiation exposures in treatments of solid neoplasms are not associated with subsequent increased risks of chronic lymphocytic leukemia.

    Science.gov (United States)

    Radivoyevitch, Tomas; Sachs, Rainer K; Gale, Robert Peter; Smith, Mitchell R; Hill, Brian T

    2016-04-01

    Exposure to ionizing radiation is not thought to cause chronic lymphocytic leukemia (CLL). Challenging this notion are recent data suggesting CLL incidence may be increased by radiation exposure from the atomic bombs (after many decades), uranium mining and nuclear power facility accidents. To assess the effects of therapeutic ionizing radiation for the treatment of solid neoplasms we studied CLL risks in data from the Surveillance, Epidemiology, and End Results (SEER) Program. Specifically, we compared the risks of developing CLL in persons with a 1(st) non-hematologic cancer treated with or without ionizing radiation. We controlled for early detection effects on CLL risk induced by surveillance after 1(st) cancer diagnoses by forming all-time cumulative CLL relative risks (RR). We estimate such CLL RR to be 1.20 (95% confidence interval, 1.17, 1.23) for persons whose 1(st) cancer was not treated with ionizing radiation and 1.00 (0.96, 1.05) for persons whose 1(st) cancer was treated with ionizing radiations. These results imply that diagnosis of a solid neoplasm is associated with an increased risk of developing CLL only in persons whose 1(st) cancer was not treated with radiation therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Retrospective analysis of post-exposure to human anti-rabies treatment in Botucatu, São Paulo State, Brazil

    Directory of Open Access Journals (Sweden)

    JA Ayres

    2010-01-01

    Full Text Available This analysis aimed to identify characteristics of accidents that would, probably, provoke rabies infection. A total of 14,409 survey questionnaires for surveillance of human rabies from the Brazilian Information System for Disease Notification (SINAN, from 2000 to 2005, were analyzed. Regarding demographics, it was observed that 7,377 (51.5% of the victims were white, 4,458 (30.93% were children and 8,008 (55.58% were males. Urban cases were prevalent (88.10% while dogs were the animals most frequently involved in accidents, in 11,700 cases (81.19%. Bites (84.35% and scratches (19.15% were the most prevalent exposure types, and occurred predominantly on victims' extremities (38.79%. The prophylactic measure taken in 6,179 cases comprised anti-rabies vaccine; of these victims, 421 (2.92% showed systemic reactions while 693 (4.80% reported no response. The importance of developing awareness in professionals that should correctly report post-exposure immunoprophylaxis cases is emphasized given the high number of individuals who receive this type of treatment annually.

  6. Improvement of attention span and reaction time with hyperbaric oxygen treatment in patients with toxic injury due to mold exposure.

    Science.gov (United States)

    Ezra, N; Dang, K; Heuser, G

    2011-01-01

    It is, by now, well established that mold toxins (mycotoxins) can cause significant adverse health effects. In this study, 15 subjects who developed an attention deficit disorder (ADD) and slowing of reaction time at the time of exposure to mold toxins were identified. Deficits in attention span and reaction time were documented not only by taking a careful history, but also by performing a Test of Variables of Attention (TOVA). The TOVA test provides an objective measure of these two variables. It was found that mold-exposed subjects show statistically significant decreases in attention span and significant increases in reaction time to stimuli compared to controls. After ten sessions of hyperbaric oxygen treatment (HBOT), a statistically significant improvement was seen in both measures. This preliminary study suggests promising outcomes in treating mold-exposed patients with hyperbaric oxygen.

  7. Narrative exposure therapy for PTSD increases top-down processing of aversive stimuli - evidence from a randomized controlled treatment trial

    Directory of Open Access Journals (Sweden)

    Adenauer Hannah

    2011-12-01

    Full Text Available Abstract Background Little is known about the neurobiological foundations of psychotherapy for Posttraumatic Stress Disorder (PTSD. Prior studies have shown that PTSD is associated with altered processing of threatening and aversive stimuli. It remains unclear whether this functional abnormality can be changed by psychotherapy. This is the first randomized controlled treatment trial that examines whether narrative exposure therapy (NET causes changes in affective stimulus processing in patients with chronic PTSD. Methods 34 refugees with PTSD were randomly assigned to a NET group or to a waitlist control (WLC group. At pre-test and at four-months follow-up, the diagnostics included the assessment of clinical variables and measurements of neuromagnetic oscillatory brain activity (steady-state visual evoked fields, ssVEF resulting from exposure to aversive pictures compared to neutral pictures. Results PTSD as well as depressive symptom severity scores declined in the NET group, whereas symptoms persisted in the WLC group. Only in the NET group, parietal and occipital activity towards threatening pictures increased significantly after therapy. Conclusions Our results indicate that NET causes an increase of activity associated with cortical top-down regulation of attention towards aversive pictures. The increase of attention allocation to potential threat cues might allow treated patients to re-appraise the actual danger of the current situation and, thereby, reducing PTSD symptoms. Registration of the clinical trial Number: NCT00563888 Name: "Change of Neural Network Indicators Through Narrative Treatment of PTSD in Torture Victims" ULR: http://www.clinicaltrials.gov/ct2/show/NCT00563888

  8. Prenatal exposure to escitalopram and/or stress in rats: a prenatal stress model of maternal depression and its treatment

    Science.gov (United States)

    Bourke, Chase H.; Capello, Catherine F.; Rogers, Swati M.; Yu, Megan L.; Boss-Williams, Katherine A.; Weiss, Jay M.; Stowe, Zachary N.; Owens, Michael J.

    2014-01-01

    Rationale A rigorously investigated model of stress and antidepressant administration during pregnancy is needed to evaluate possible effects on the mother. Objective The objective of this study was to develop a model of clinically relevant prenatal exposure to an antidepressant and stress during pregnancy to evaluate the effects on maternal care behavior. Results Female rats implanted with 28 day osmotic minipumps delivering the SSRI escitalopram throughout pregnancy had serum escitalopram concentrations in a clinically observed range (17-65 ng/mL). A separate cohort of pregnant females exposed to a chronic unpredictable mild stress paradigm on gestational days 10-20 showed elevated baseline (305 ng/mL), and acute stress-induced (463 ng/mL), plasma corticosterone concentrations compared to unstressed controls (109 ng/mL). A final cohort of pregnant dams were exposed to saline (control), escitalopram, stress, or stress and escitalopram to determine the effects on maternal care. Maternal behavior was continuously monitored over the first 10 days post parturition. A reduction of 35% in maternal contact and 11% in nursing behavior was observed due to stress during the light cycle. Licking and grooming behavior was unaffected by stress or drug exposure in either the light or dark cycle. Conclusions These data indicate that: 1) clinically relevant antidepressant treatment during human pregnancy can be modeled in rats using escitalopram; 2) chronic mild stress can be delivered in a manner that does not compromise fetal viability; and 3) neither of these prenatal treatments substantially altered maternal care post parturition. PMID:23436130

  9. Pollutant exposure at wastewater treatment works affects the detoxification organs of an urban adapter, the Banana Bat

    International Nuclear Information System (INIS)

    Naidoo, Samantha; Vosloo, Dalene; Schoeman, M. Corrie

    2016-01-01

    The Banana Bat, Neoromicia nana, exploits pollution-tolerant chironomids at wastewater treatment works (WWTWs). We investigated how pollutant exposure impacts the detoxification organs, namely the liver and kidney of N. nana. (i) We performed SEM-EDS to quantify metal content and mineral nutrients, and found significant differences in essential metal (Fe and Zn) content in the liver, and significant differences in Cu and one mineral nutrient (K) in the kidneys. (ii) We performed histological analysis and found more histopathological lesions in detoxification organs of WWTW bats. (iii) We calculated hepatosomatic/renalsomatic indices (HSI/RSI) to investigate whole organ effects, and found significant increases in organ size at WWTWs. (iv) We quantified metallothionein 1E (MT1E), using Western Blot immunodetection. Contrary to predictions, we found no significant upregulation of MT1E in bats at WWTWs. Ultimately, N. nana exploiting WWTWs may suffer chronic health problems from sub-lethal damage to organs responsible for detoxifying pollutants. - Highlights: • We measured pollutant exposure effects on detoxification organs in bats. • Iron, zinc, copper and potassium levels were altered in pollutant-exposed bats. • There was no significant upregulation of metallothionein in liver or kidney. • Pollutant-exposed bats had increased organ indices and histopathological lesions. • These organ effects suggest health risks and increased mortality in the long-term. - Wastewater treatment plants provide a short-term benefit of abundant pollution-tolerant prey, but cause long-term physiological damage to the liver and kidneys in urban bats.

  10. Carcinogenicity and teratogenicity vs. psychogenicity: Psychological characteristics associated with self-reported Agent Orange exposure among Vietnam combat veterans who seek treatment for substance abuse

    Energy Technology Data Exchange (ETDEWEB)

    Robinowitz, R.; Roberts, W.R.; Dolan, M.P.; Patterson, E.T.; Charles, H.L.; Atkins, H.G.; Penk, W.E. (Univ. of Texas Health Science Center, Dallas (USA))

    1989-09-01

    This study asked, What are the psychological characteristics of Vietnam combat veterans who claim Agent Orange exposure when compared with combat-experienced cohorts who do not report such contamination The question was researched among 153 heroin addicts, polydrug abusers, and chronic alcoholics who were seeking treatment: 58 reported moderate to high defoliant exposure while in combat; 95 reported minimal to no exposure while in Vietnam. The null hypothesis was accepted for measures of childhood and present family social climate, premilitary backgrounds, reasons for seeking treatment, patterns and types of illicit drug and alcohol use, interpersonal problems, intellectual functioning, and short-term memory. The null hypothesis was rejected for personality differences, however, those who self-reported high Agent Orange exposure scored significantly higher on MMPI scales F, Hypochondriasis, Depression, Paranoia, Psychasthenia, Schizophrenia, Mania, and Social interoversion. The results suggest that clinicians carefully assess attributional processing of those who report traumatic experience.

  11. Stability of opiates in hair fibers after exposure to cosmetic treatment.

    Science.gov (United States)

    Pötsch, L; Skopp, G

    1996-08-15

    The stability of opiates in clipped natural human hair was investigated. Hair fibers were incubated with defined solutions of morphine, codeine and dihydrocodeine (pH 7.4) until saturated. Original opiate-positive hair samples collected from drug addicts also were examined. Commercially available bleaching as well as perming formulas (Poly Blonde Ultra, Poly Lock; Henkel, Düsseldorf, Germany) were applied in vitro to the hair strands of both groups under investigation. After these treatments, the drug concentration had decreased for both bleaching and permanent waving. In the spiked hair, only 2-18% of the starting solution could be found after bleaching. About 20-30% of the drug substances could still be detected after perming. In the authentic hair samples, the drug levels of the formerly opiate positive hair fibers had also been reduced but distinct tendencies could not be observed.

  12. Flakka-Induced Prolonged Psychosis

    Directory of Open Access Journals (Sweden)

    Craig Crespi

    2016-01-01

    Full Text Available In South Florida, there has been a highly addictive new synthetic drug flooding the streets for people looking for a cheap high. Alpha-PVP, better known as Flakka, is an illegal substance that sells on the streets for as little as $5 a hit and delivers an instant high that can last from hours to days with lingering effects for weeks after it has been ingested. Although people use Flakka for its potential euphoric high, symptoms are known to easily escalate into frightening delusions, paranoid psychosis, extreme agitation, and a multitude of other altered mental states. According to the National Institute on Drug Abuse, Florida appears to be the nation’s hot spot for reports of Flakka. In this case report, a 17-year-old female with no prior psychiatric diagnosis presents to the hospital under a 72-hour involuntary placement for altered mental status with agitation and psychotic behaviors. After multiple days of symptomatic treatment with benzodiazepines and antipsychotics, the patient became coherent enough to give a history of a “friend” putting Flakka in her food at school as a joke. Although she continues to have residual symptoms including psychomotor agitation and slowing of cognition, she was alert, oriented, and able to be discharged home with proper follow-up.

  13. Exposure to airborne fungi during sorting of recyclable plastics in waste treatment facilities

    Directory of Open Access Journals (Sweden)

    Kristýna Černá

    2017-02-01

    Full Text Available Background: In working environment of waste treatment facilities, employees are exposed to high concentrations of airborne microorganisms. Fungi constitute an essential part of them. This study aims at evaluating the diurnal variation in concentrations and species composition of the fungal contamination in 2 plastic waste sorting facilities in different seasons. Material and Methods: Air samples from the 2 sorting facilities were collected through the membrane filters method on 4 different types of cultivation media. Isolated fungi were classified to genera or species by using a light microscopy. Results: Overall, the highest concentrations of airborne fungi were recorded in summer (9.1×103–9.0×105 colony-forming units (CFU/m3, while the lowest ones in winter (2.7×103–2.9×105 CFU/m3. The concentration increased from the beginning of the work shift and reached a plateau after 6–7 h of the sorting. The most frequently isolated airborne fungi were those of the genera Penicillium and Aspergillus. The turnover of fungal species between seasons was relatively high as well as changes in the number of detected species, but potentially toxigenic and allergenic fungi were detected in both facilities during all seasons. Conclusions: Generally, high concentrations of airborne fungi were detected in the working environment of plastic waste sorting facilities, which raises the question of health risk taken by the employees. Based on our results, the use of protective equipment by employees is recommended and preventive measures should be introduced into the working environment of waste sorting facilities to reduce health risk for employees. Med Pr 2017;68(1:1–9

  14. Exposure to airborne fungi during sorting of recyclable plastics in waste treatment facilities.

    Science.gov (United States)

    Černá, Kristýna; Wittlingerová, Zdeňka; Zimová, Magdaléna; Janovský, Zdeněk

    2017-02-28

    In working environment of waste treatment facilities, employees are exposed to high concentrations of airborne microorganisms. Fungi constitute an essential part of them. This study aims at evaluating the diurnal variation in concentrations and species composition of the fungal contamination in 2 plastic waste sorting facilities in different seasons. Air samples from the 2 sorting facilities were collected through the membrane filters method on 4 different types of cultivation media. Isolated fungi were classified to genera or species by using a light microscopy. Overall, the highest concentrations of airborne fungi were recorded in summer (9.1×103-9.0×105 colony-forming units (CFU)/m3), while the lowest ones in winter (2.7×103-2.9×105 CFU/m3). The concentration increased from the beginning of the work shift and reached a plateau after 6-7 h of the sorting. The most frequently isolated airborne fungi were those of the genera Penicillium and Aspergillus. The turnover of fungal species between seasons was relatively high as well as changes in the number of detected species, but potentially toxigenic and allergenic fungi were detected in both facilities during all seasons. Generally, high concentrations of airborne fungi were detected in the working environment of plastic waste sorting facilities, which raises the question of health risk taken by the employees. Based on our results, the use of protective equipment by employees is recommended and preventive measures should be introduced into the working environment of waste sorting facilities to reduce health risk for employees. Med Pr 2017;68(1):1-9. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  15. Avoidant Coping and Treatment Outcome in Rape-Related Posttraumatic Stress Disorder

    Science.gov (United States)

    Leiner, Amy S.; Kearns, Megan C.; Jackson, Joan L.; Astin, Millie C.; Rothbaum, Barbara O.

    2012-01-01

    Objective: This study investigated the impact of avoidant coping on treatment outcome in rape-related posttraumatic stress disorder (PTSD). Method: Adult women with rape-related PTSD (N = 62) received 9 sessions of prolonged exposure (PE) or eye movement desensitization and reprocessing (EMDR). The mean age for the sample was 34.7 years, and race…

  16. Therapists' and patients' stress responses during graduated versus flooding in vivo exposure in the treatment of specific phobia: A preliminary observational study.

    Science.gov (United States)

    Schumacher, Sarah; Miller, Robert; Fehm, Lydia; Kirschbaum, Clemens; Fydrich, Thomas; Ströhle, Andreas

    2015-12-15

    Exposure therapy is considered an effective treatment strategy for phobic anxiety, however, it is rarely applied in clinical practice. The under-usage might be due to various factors of which heightened stress levels not only in patients but also in therapists are presumed to be of particular relevance. The present study aimed to investigate whether different forms of exposure might lead to varying physiological and psychological stress responses in therapists and phobic patients. 25 patients with specific phobia underwent individual cognitive behavioural therapy, performed by 25 psychotherapist trainees, applying exposure sessions in graduated form or the flooding technique. Patients and therapists provided subjective evaluations of stress and five saliva samples for analysis of salivary cortisol and alpha-amylase either during two graduated exposure sessions or during one flooding session, while a regular therapy session served as control condition. Therapists displayed heightened salivary alpha-amylase release during exposure of the flooding, but not the graduated, type. Patients showed elevated salivary cortisol during flooding exposure numerically, however, not on a statistically significant level. Therapists reported more pronounced subjective stress during flooding compared to graduated exposure. Elevated stress levels should be addressed in clinical training in order to improve application of exposure in routine practice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Health risks of the occupational exposure to microbiological and chemical pollutants in a municipal waste organic fraction treatment plant.

    Science.gov (United States)

    Nadal, Martí; Inza, Isabel; Schuhmacher, Marta; Figueras, María J; Domingo, José L

    2009-11-01

    Composting is a good alternative for the treatment of organic waste. However, an important amount of hazardous agents such as bioaerosols and volatile organic compounds may be released during the process. Therefore, the presence of microbiological and chemical pollutants emitted to air may mean a risk for the health of composting plants workers. We here report the results of an investigation aimed at evaluating the occupational exposure to chemical and biological agents for workers of an organic waste treatment facility (Montcada i Reixac, Catalonia, Spain). Total concentrations of bacteria and fungi (at 25 degrees C and 37 degrees C), including Aspergillus fumigatus, were determined on a 3-month basis in 4 areas of the composting plant (reception, sorting, composting and cogeneration halls). Non-cancer and cancer risks were assessed. Workers in the sorting cabins seemed to be the most exposed to pollutants. Consequently, the use of preventive measures, such as integrated P3 filter masks and gloves are highly recommended. On the other hand, the emission and dispersion of bioaerosols and particles should be minimized during the process through the application of additional measures, such as the humectation of waste and the installation of biofilters. The results of this study can be useful to elaborate occupational risk prevention programs for workers in composting plants.

  18. Efficacy of prolonged antimicrobial chemotherapy for brucellar spondylodiscitis.

    Science.gov (United States)

    Ioannou, S; Karadima, D; Pneumaticos, S; Athanasiou, H; Pontikis, J; Zormpala, A; Sipsas, N V

    2011-05-01

    The standard treatment of brucellar spondylitis with a combination of two antibiotics for 6-12 weeks is associated with high rates of treatment failure and relapse. The present study aimed to assess the safety and efficacy of a treatment strategy based on the prolonged administration of a triple combination of suitable antibiotics. Eighteen patients with brucellar spondylitis were treated with a combination of at least three suitable antibiotics (doxycycline, rifampin, plus intramuscular streptomycin or cotrimoxazole or ciprofloxacin) until the completion of at least 6 months of treatment, when clinical, radiological and serology re-evaluation was performed. If necessary, the treatment was continued with additional 6-month cycles, until resolution or significant improvement of clinical and radiological findings, or for a maximum of 18 months. At presentation, the median age was 66 years (range, 42-85 years) with male predominance. The median duration of therapy was 48 weeks (range 24-72 weeks). Treatment was discontinued early because of side-effects in only one patient. Surgical intervention was required for three patients. At the end of treatment all patients had a complete response. After completion of treatment, all patients were followed up with regular visits. During the follow-up period (duration 1-96 months, median 36.5 months), no relapses were observed. In conclusion, prolonged (at least 6 months) administration of a triple combination of suitable antibiotics appears to be an effective treatment for brucellar spondylitis. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.

  19. Cardiovascular drugs inducing QT prolongation: facts and evidence.

    Science.gov (United States)

    Taira, Carlos A; Opezzo, Javier A W; Mayer, Marcos A; Höcht, Christian

    2010-01-01

    Acquired QT syndrome is mainly caused by the administration of drugs that prolong ventricular repolarization. On the other hand, the risk of drug-induced torsades de pointes is increased by numerous predisposing factors, such as genetic predisposition, female sex, hypokalemia and cardiac dysfunction. This adverse reaction is induced by different chemical compounds used for the treatment of a variety of pathologies, including arrhythmias. As it is known, antiarrhythmic agents and other cardiovascular drugs can prolong the QT interval, causing this adverse reaction. Of the 20 most commonly reported drugs, 10 were cardiovascular agents and these appeared in 348 of the reports (46%). Class Ia antiarrhythmic agents have frequently been linked to inducing arrhythmia, including torsades de pointes. Sotalol and amiodarone, class III antiarrhythmics, are known to prolong the QT interval by blocking I(Kr). Due to the severity of events caused by the therapeutic use of these drugs, in this work of revision the cardiovascular drugs that present this property and the factors and evidence will be mentioned.

  20. SU-F-T-317: Skin Exposure Outside the Treatment Field During Treatment of Breast Cancer with Tri-Co-60 MR-IGRT System

    Energy Technology Data Exchange (ETDEWEB)

    Park, J; Kim, J; Park, S [Seoul National University Hospital, Seoul (Korea, Republic of); Kim, S [Nuclear Safety and Security Commission, Seoul (Korea, Republic of); Shin, K [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2016-06-15

    Purpose: To investigate exposure outside the treatment field when treating breast cancer with tri-Co-60 magnetic resonance (MR) image guided radiation therapy (IGRT) system. Methods: A total of 7 patients who treated with accelerated partial breast irradiation (APBI) technique were selected prospectively for this study (prescription dose = 38.5 Gy in 10 fractions). Every patient treated with two plans, one was an initial plan and the other was an adaptive plan generated after finishing 5 fractions (a total of 14 plans). Every plan was calculated with and without magnetic field in the treatment planning system. The EBT3 films were attached on the front and the back of 1 cm bolus, and then it was placed on the patient body vertically to cover patient’s jaw and shoulder. After measurements, the maximum point dose and the mean dose of whole area of EBT3 film were acquired. Results: In the treatment plan with magnetic field, low dose stream outside the patient body was observed, almost reaching the patient’s jaw or shoulder, while it was not observed without magnetic field. The average values of the measured maximum and mean doses at the front of bolus were 30.1 ± 11.1 cGy (7.8% of the daily dose) and 14.7 ± 3.3 cGy (3.8%), respectively. At the back of bolus, those values were 6.0 ± 1.9 cGy (1.6%) and 5.1 ± 1.6 cGy (1.3%), respectively. The largest maximum dose at the front was 54.2 cGy (14.1%) while it was 20.7 cGy (5.4%) at the back. The average decrease of the maximum dose by the bolus was 24.0 ± 11.0 cGy. Conclusion: Due to magnetic field, dose stream outside the patient body can be generated during breast cancer treatment with the tri-Co-60 MR-IGRT system. Since this dose stream irradiated skin outside the treatment field, it should be shielded. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2015R1C1A1A01054192).

  1. The effects of sodium bicarbonate during prolonged cardiopulmonary resuscitation.

    Science.gov (United States)

    Weng, Yi-Ming; Wu, Shih-Hao; Li, Wen-Cheng; Kuo, Chan-Wei; Chen, Shou-Yen; Chen, Jih-Chang

    2013-03-01

    This study was performed to determine the effects of sodium bicarbonate injection during prolonged cardiopulmonary resuscitation (for >15 minutes). The retrospective cohort study consisted of adult patients who presented to the emergency department (ED) with the diagnosis of cardiac arrest in 2009. Data were retrieved from the institutional database. A total of 92 patients were enrolled in the study. Patients were divided into 2 groups based on whether they were treated (group1, n = 30) or not treated (group 2, n = 62) with sodium bicarbonate. There were no significant differences in demographic characteristics between groups. The median time interval between the administration of CPR and sodium bicarbonate injection was 36.0 minutes (IQR: 30.5-41.8 minutes). The median amount of bicarbonate injection was 100.2 mEq (IQR: 66.8-104.4). Patients who received a sodium bicarbonate injection during prolonged CPR had a higher percentage of return of spontaneous circulation, but not statistical significant (ROSC, 40.0% vs. 32.3%; P = .465). Sustained ROSC was achieved by 2 (6.7%) patients in the sodium bicarbonate treatment group, with no survival to discharge. No significant differences in vital signs after ROSC were detected between the 2 groups (heart rate, P = .124; systolic blood pressure, P = .094). Sodium bicarbonate injection during prolonged CPR was not associated with ROSC after adjust for variables by regression analysis (Table 3; P = .615; odds ratio, 1.270; 95% confidence interval: 0.501-3.219) The administration of sodium bicarbonate during prolonged CPR did not significantly improve the rate of ROSC in out-of-hospital cardiac arrest. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Diclofenac prolongs repolarization in ventricular muscle with impaired repolarization reserve.

    Directory of Open Access Journals (Sweden)

    Attila Kristóf

    Full Text Available BACKGROUND: The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. METHODS: Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. RESULTS: Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM. The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl(2 application. Diclofenac (3 mg/kg did not prolong while dofetilide (25 µg/kg significantly lengthened the QT(c interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QT(c. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%. In single ventricular cells diclofenac (30 µM decreased the amplitude of rapid (I(Kr and slow (I(Ks delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (I(Ca was slightly diminished, but the transient outward (I(to and inward rectifier (I(K1 potassium currents were not influenced. CONCLUSIONS: Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve.

  3. Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve

    Science.gov (United States)

    Kristóf, Attila; Husti, Zoltán; Koncz, István; Kohajda, Zsófia; Szél, Tamás; Juhász, Viktor; Biliczki, Péter; Jost, Norbert; Baczkó, István; Papp, Julius Gy; Varró, András; Virág, László

    2012-01-01

    Background The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. Methods Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. Results Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl2 application. Diclofenac (3 mg/kg) did not prolong while dofetilide (25 µg/kg) significantly lengthened the QTc interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QTc. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 µM) decreased the amplitude of rapid (IKr) and slow (IKs) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (ICa) was slightly diminished, but the transient outward (Ito) and inward rectifier (IK1) potassium currents were not influenced. Conclusions Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve. PMID:23300901

  4. Effects of Acute Ozone Exposure and Methyl Jasmonate Treatment on White Pine Monoterpene and Sesquiterpene Emission Rates

    Science.gov (United States)

    Faiola, C. L.; Wagner, D.; Allwine, E.; Harley, P. C.; Vanreken, T. M.

    2010-12-01

    Biogenic volatile organic compounds (BVOCs) are produced by plants and include monoterpenes, sesquiterpenes, and their oxygenated derivatives. These BVOCs are one of the principal factors influencing the oxidative capacity of the atmosphere in forested regions, and impact both ozone concentration and secondary organic aerosol formation. Under unstressed conditions, the release of BVOCs to the atmosphere is primarily controlled by the vapor pressure of the relevant compounds within the plant tissue, which is in turn dependent on temperature as well as complex biochemical production processes. However, various natural and anthropogenic stressors can alter both the quantity and composition of the BVOCs emitted by plants. Many potential stressors are expected to become stronger as climate change effects escalate. The impacts of most stressors on BVOC emissions have not been well characterized, particularly in a field setting where changes in BVOC emissions could have influential feedbacks with climate. This study investigated the effects of two stressors on monoterpene and sesquiterpene emission rates at a field site in northern Michigan: acute ozone exposure and treatment with methyl jasmonate, an herbivory proxy. The study included six repetitions of the same experiment, each time using a new set of sub-canopy eastern white pine specimens. For each experiment, dynamic branch enclosures were simultaneously used on three specimens for sample collection: one ozone treatment tree, one methyl jasmonate treatment tree, and one control tree. Sampling lines were placed in each enclosure and VOCs were collected onto cartridges packed with Tenax GR adsorbent. Samples were collected several times per day for at least two days before treatment and for five days after treatment. Cartridges were analyzed via thermodesorption with an Agilent GC/MS/FID. This analysis allowed the identification and quantification of several monoterpene and sesquiterpene species in the samples

  5. Aripiprazole treatment of irritability associated with autistic disorder and the relationship between prior antipsychotic exposure, adverse events, and weight change.

    Science.gov (United States)

    Mankoski, Raymond; Stockton, Gwen; Manos, George; Marler, Sabrina; McQuade, Robert; Forbes, Robert A; Marcus, Ronald

    2013-10-01

    The purpose of this study was to evaluate the impact of prior antipsychotic exposure (PAE) on safety and tolerability outcomes in pediatric subjects receiving aripiprazole treatment. This study was a post-hoc analysis of pooled data from two 8-week, double-blind, randomized, placebo-controlled studies evaluating aripiprazole for the treatment of irritability in pediatric subjects with autistic disorder, aged 6-17 years. Subjects were stratified by PAE; adverse events (AEs), and changes in weight, and metabolic measures were evaluated. For subjects receiving aripiprazole, regardless of PAE, baseline weight, age, gender, and symptom severity were evaluated in a regression model predicting body weight change. Of 316 randomized subjects, 259 (82.0%) were antipsychotic naïve (AN) and 57 (18.0%) had a PAE. Aripiprazole-treated AN subjects were more likely than PAE subjects to report somnolence (11.9% vs. 2.8%), sedation (22.7% vs. 11.1%), or fatigue (17.0% vs. 13.9%). Rates of extrapyramidal disorder and drooling, but not akathisia or tremor, were marginally higher in AN subjects. Overall, 10.8% of aripiprazole-treated AN subjects had at least one AE leading to discontinuation compared with 8.3% of aripiprazole-treated PAE subjects. AN subjects receiving aripiprazole had a larger change in weight from baseline to endpoint compared with those receiving placebo (1.9 vs. 0.7 kg; treatment difference 1.2 kg, 95% CI: 0.5, 1.9) than PAE subjects receiving aripiprazole compared with subjects receiving placebo (0.4 vs. -0.4 kg; treatment difference 0.9 kg, 95% CI: -0.6, 2.4). Regression analysis identified that younger subjects with higher baseline weight z-score were at highest risk for weight gain. There were no significant changes in metabolic measures compared with placebo in either group. Weight gain was more pronounced in AN subjects and more likely to occur in younger subjects with a higher baseline weight z-score. AN subjects were more likely to experience AEs related

  6. Ultraviolet light immunomodulation of canine islets for prolongation of allograft survival

    International Nuclear Information System (INIS)

    Kenyon, N.S.; Strasser, S.; Alejandro, R.

    1990-01-01

    Ultraviolet (UV) light treatment of donor islets has been shown to be effective for the prolongation of islet allograft survival in rodent models. This study evaluated UV as an immunomodulator of canine islets. The effects of UV irradiation on islet secretory function in vitro revealed a trend of increasing basal insulin release with increasing doses of UV and a corresponding significant decrease in glucose-mediated insulin release (expressed as percentage of basal fractional insulin release) beginning at UV light exposures of 200-300 J/m2 (n = 3, P less than 0.05). Proliferative responses to UV-irradiated allogeneic peripheral blood leukocytes and islets were significantly decreased by 53-112% (P less than 0.05) in 27 of 29 mixed-lymphocyte cultures and by 35-74% (P less than 0.05) in 4 of 5 mixed-lymphocyte islet culture experiments, respectively, beginning at 200-600 J/m2. Autotransplantation of nonirradiated (n = 8) and irradiated islets (600 J/m2, n = 6) resulted in a 1-mo graft survival rate of 75% for the control group and 50% for the irradiated group. Allotransplantation of irradiated islets (600 J/m2) into either nonimmunosuppressed recipients (1 donor to 1 recipient, n = 8) or recipients of subimmunosuppressive doses of cyclosporin (2 donors to 1 recipient, n = 4) resulted in 100% rejection by day 10. In contrast, when islets were cultured for 24 h postirradiation and transplanted into cyclosporin-treated pancreatectomized recipients (2 donors to 1 recipient), 3 of 7 grafts were prolonged beyond day 10 to days 16, 26, and greater than 100

  7. SALIVARY ANTIMICROBIAL PROTEIN RESPONSE TO PROLONGED RUNNING

    Directory of Open Access Journals (Sweden)

    Suzanne Schneider

    2013-01-01

    Full Text Available Prolonged exercise may compromise immunity through a reduction of salivary antimicrobial proteins (AMPs. Salivary IgA (IgA has been extensively studied, but little is known about the effect of acute, prolonged exercise on AMPs including lysozyme (Lys and lactoferrin (Lac. Objective: To determine the effect of a 50-km trail race on salivary cortisol (Cort, IgA, Lys, and Lac. Methods: 14 subjects: (6 females, 8 males completed a 50km ultramarathon. Saliva was collected pre, immediately after (post and 1.5 hrs post race ( 1.5. Results: Lac concentration was higher at 1.5 hrs post race compared to post exercise (p0.05. IgA concentration, secretion rate, and IgA/Osm were lower 1.5 hrs post compared to pre race (p<0.05. Cort concentration was higher at post compared to 1.5 (p<0.05, but was unaltered from pre race levels. Subjects finished in 7.81 ± 1.2 hrs. Saliva flow rate did not differ between time points. Saliva Osm increased at post (p<0.05 compared to pre race. Conclusions: The intensity could have been too low to alter Lys and Lac secretion rates and thus, may not be as sensitive as IgA to changes in response to prolonged running. Results expand our understanding of the mucosal immune system and may have implications for predicting illness after prolonged running.

  8. Prolonged displacement may compromise resilience in Eritrean ...

    African Journals Online (AJOL)

    Objective: to assess the impact of prolonged displacement on the resilience of Eritrean mothers. Methods: an adapted SOC scale (short form) was administered. Complementary qualitative data were gathered from study participants' spontaneous reactions to and commentaries on the SOC scale. Results: Displaced ...

  9. Prolonged Cholestatic Jaundice Associated With Flurbiprofen.

    Science.gov (United States)

    Dogan, Serkan; Celikbilek, Mehmet; Demirkan, Kutay; Yilmaz, Semih; Deniz, Kemal; Gursoy, Sebnem; Yucesoy, Mehmet

    2014-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed drugs throughout the world for pain relief. Although the adverse effects of NSAIDs to the liver are well known, flurbiprofen-induced liver cholestasis is extremely rare. Herein