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

Glucocorticoid augmentation of prolonged exposure therapy: rationale and case report

Directory of Open Access Journals (Sweden)

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.

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

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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.

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…

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

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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.

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

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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.

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).

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

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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.

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

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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.

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

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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

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

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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

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

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

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...

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

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.

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

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

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

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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.

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.

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

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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

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

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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

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

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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

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…

Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.

Directory of Open Access Journals (Sweden)

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.

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

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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

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

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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...

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

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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.

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

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

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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

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

Prolonged Remission in Neuromyelitis Optica Following Cessation of Rituximab Treatment.

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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.

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

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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.

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;

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

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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.

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

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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.

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

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

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...

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

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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.

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

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

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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.

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.

Prolonged Exposure Therapy For Post Traumatic Stress Disorder

OpenAIRE

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 ...

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

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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.

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...

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.

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

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

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...

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

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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.

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

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

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.

Treatment preferences of psychotherapy patients with chronic PTSD.

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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.

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

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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.

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.

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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.

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

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

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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.

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

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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.

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

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

Directory of Open Access Journals (Sweden)

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.

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.

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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

Coexistence of Ureaplasma and chorioamnionitis is associated with prolonged mechanical ventilation.

Science.gov (United States)

Jung, Euiseok; Choi, Chang Won; Kim, Su Yeong; Sung, Tae-Jung; Kim, Haeryoung; Park, Kyoung Un; Kim, Han-Suk; Kim, Beyong Il; Choi, Jung-Hwan

2017-01-01

Both histologic chorioamnionitis (HCAM) and Ureaplasma infection are considered important contributors to perinatal lung injury. We tested the hypothesis that coexistence of maternal HCAM and perinatal Ureaplasma exposure increases the risk of prolonged mechanical ventilation in extremely low-birthweight (ELBW) infants. A retrospective cohort study was carried out of all ELBW infants born between January 2008 and December 2013 at a single academic center. Placental pathology and gastric fluid Ureaplasma data were available for all infants. Culture and polymerase chain reaction were used to detect Ureaplasma in gastric fluid. Prolonged mechanical ventilation was defined as mechanical ventilation that began within 28 days after birth and continued. Of 111 ELBW infants enrolled, 84 survived beyond 36 weeks of postmenstrual age (PMA) and were included in the analysis. Eighteen infants (21.4%) had both HCAM and Ureaplasma exposure. Seven infants (8.3%) required mechanical ventilation beyond 36 weeks of PMA. Coexistence of HCAM and Ureaplasma in gastric fluid was significantly associated with prolonged mechanical ventilation after adjustment for gestational age, sex, mode of delivery, and use of macrolide antibiotics (OR, 8.7; 95%CI: 1.1-67.2). Coexistence of maternal HCAM and perinatal Ureaplasma exposure significantly increases the risk of prolonged mechanical ventilation in ELBW infants. © 2016 Japan Pediatric Society.

Exposure Plus Response-Prevention Treatment of Bulimia Nervosa.

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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…

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.

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

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

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.

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.

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.

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.

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...

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.

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

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.

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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.

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.

Competing for Consciousness: Prolonged Mask Exposure Reduces Object Substitution Masking

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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…

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

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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

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

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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...

Prolonged response without prolonged chemotherapy: a lesson from PCV chemotherapy in low-grade gliomas

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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

"Dwelling in the Past": The Role of Rumination in the Treatment of Posttraumatic Stress Disorder

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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…

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

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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.

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

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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.

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

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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.

Prolonged acid rain facilitates soil organic carbon accumulation in a mature forest in Southern China.

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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.

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

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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

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.

Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight

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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

Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight

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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.

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

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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.

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

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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.

Narrative reconstruction therapy for prolonged grief disorder—rationale and case study

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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.

Neonatal survival after prolonged preterm premature rupture of membranes before 24 weeks of gestation.

Science.gov (United States)

Brumbaugh, Jane E; Colaizy, Tarah T; Nuangchamnong, Nina; O'Brien, Emily A; Fleener, Diedre K; Rijhsinghani, Asha; Klein, Jonathan M

2014-11-01

To evaluate neonatal survival after prolonged preterm premature rupture of membranes (PROM) in the era of antenatal corticosteroids, surfactant, and inhaled nitric oxide. A single-center retrospective cohort study of neonates born from 2002-2011 after prolonged (1 week or more) preterm (less than 24 weeks of gestation) rupture of membranes was performed. The primary outcome was survival to discharge. Neonates whose membranes ruptured less than 24 hours before delivery (n=116) were matched (2:1) on gestational age at birth, sex, and antenatal corticosteroid exposure with neonates whose membranes ruptured 1 week or more before delivery (n=58). Analysis used conditional logistic regression for categorical data and Wilcoxon signed rank test for continuous data. The prolonged preterm PROM exposed and unexposed cohorts had survival rates of 90% and 95%, respectively, although underpowered to assess the statistical significance (P=.313). Exposed neonates were more likely have pulmonary hypoplasia (26/58 exposed, 1/114 unexposed, Prupture (20.4 weeks exposed, 22.3 weeks unexposed, P=.189), length of rupture (3.7 weeks exposed, 6.4 weeks unexposed, P=.717), and lowest maximal vertical pocket before 24 weeks of gestation (0 cm exposed, 1.4 cm unexposed, P=.114) did not discriminate between survivors and nonsurvivors after exposure to prolonged preterm PROM. With antenatal steroid exposure and aggressive pulmonary management, survival to discharge after prolonged preterm PROM was 90%. Pulmonary morbidities were common. Of note, the data were limited to women who remained pregnant 1 week or longer after rupture of membranes.

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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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

Tolerance and withdrawal from prolonged opioid use in critically ill children.

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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.

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...

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.

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

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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

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.

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

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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.

Using the Single Prolonged Stress Model to Examine the Pathophysiology of PTSD

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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.

Effects on respiratory homeostasis of prolonged, continuous hyperoxia at 1.5 to 3.0 ATA in man in Predictive Studies V

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Gelfand, R.; Clark, J. M.; Lambertsen, C. J.; Pisarello, J. B.

1987-01-01

Prolonged exposures of men to continuous hyperoxia at 3.0, 2.5, 2.0, and 1.5 ATA were conducted to define CNS oxygen tolerance and to investigate the effects of prolonged hyperoxia on CNS and other organ functions. Altered respiratory homeostasis was evident during exposures of men to 2.5 and 3.0 ATA O2 as nonprogressive increment in ventilation and reciprocal decrement in PET(CO2). These changes were progressive during exposure at 1.5 ATA O2. Mean values of respiratory reactivity at CO2 were somewhat increased following prolonged hyperoxia at 1.5 and 2.5 ATA, compared to preexposure mean values. Hypoxic ventilatory response was unchanged or enhanced after oxygen exposures at 1.5 and 2.5 ATA. Observed respiratory and body temperature changes were not of sufficient magnitude to impair function.

Prolonged sedation and/or analgesia and 5-year neurodevelopment outcome in very preterm infants: results from the EPIPAGE cohort.

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Rozé, Jean-Christophe; Denizot, Sophie; Carbajal, Ricardo; Ancel, Pierre-Yves; Kaminski, Monique; Arnaud, Catherine; Truffert, Patrick; Marret, Stéphane; Matis, Jaqueline; Thiriez, Gérard; Cambonie, Gilles; André, Monique; Larroque, Béatrice; Bréart, Gérard

2008-08-01

To describe the long-term outcome of very preterm infants receiving prolonged sedation and/or analgesia and examine the relationship between prolonged sedation and/or analgesia and this long-term outcome. A prospective population-based study (Etude EPIdémiologique sur les Petits Ages GEstationnels [EPIPAGE]). To reduce bias, the propensity score method was used. Nine regions of France. The study population included very preterm infants of fewer than 33 weeks' gestational age, born in 1997, who received mechanical ventilation and/or surgery. Main Exposure Prolonged exposure to sedative and/or analgesic drugs in the neonatal period, defined as exposure of more than 7 days to sedative and/or opioid drugs. Presence of moderate or severe disability at 5 years of age. The analysis concerns 1572 premature infants who received mechanical ventilation for whom information about exposure to prolonged sedation and/or analgesia in the neonatal period was available. A total of 115 were exposed and 1457 were not exposed. There was no significant difference between the number of patients lost to follow-up from the group of very preterm infants who were exposed to prolonged sedation and/or analgesia and the group who were not. Exposed very preterm infants had severe or moderate disability at 5 years (41/97; 42%) more often than those who were not exposed (324/1248; 26%). After adjustment for gestational age and propensity score, this association was no longer statistically significant (adjusted relative risk, 1.0; 95% confidence interval, 0.8-1.2). Prolonged sedation and/or analgesia is not associated with a poor 5-year neurological outcome after adjustment for the propensity score.

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

Ways to Optimize Therapy of Prolonged Conjugation Jaundice in Infants

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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.

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.

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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.

Computer mouse use predicts acute pain but not prolonged or chronic pain in the neck and shoulder

DEFF Research Database (Denmark)

Andersen, Johan Hviid; Harhoff, Mette; Grimstrup, Søren

2007-01-01

BACKGROUND: Computer use is one of the commonest work place exposures in modern society. An adverse effect on musculoskeletal outcomes has been claimed for decades, mainly on the basis of self reports of exposure. The purpose of this study was to assess the risk of neck and shoulder pain associat...... psychosocial factors predicted the risk of prolonged pain. CONCLUSIONS: From the NUDATA-study we can conclude that most computer workers have no or minor neck and shoulder pain, few experience prolonged pain, and even fewer, chronic neck and shoulder pain....

Prior Trauma Exposure for Youth in Treatment Foster Care

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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…

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

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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.

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

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

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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.

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

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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.

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

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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.

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

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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,…

Identifying Molecular Targets For PTSD Treatment Using Single Prolonged Stress

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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

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.

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

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

Intraperitoneal exposure of whitefish to microcystin-LR induces rapid liver injury followed by regeneration and resilience to subsequent exposures

International Nuclear Information System (INIS)

Woźny, Maciej; Lewczuk, Bogdan; Ziółkowska, Natalia; Gomułka, Piotr; Dobosz, Stefan; Łakomiak, Alicja; Florczyk, Maciej; Brzuzan, Paweł

2016-01-01

To date, there has been no systematic approach comprehensively describing the sequence of pathological changes in fish during prolonged exposure to microcystin-LR (MC-LR). Towards this aim, juvenile whitefish individuals received an intraperitoneal injection with pure MC-LR, and the injection was repeated every week to maintain continuous exposure for 28 days. During the exposure period, growth and condition of the fish were assessed based on biometric measurements. Additionally, selected biochemical markers were analysed in the fishes' blood, and their livers were carefully examined for morphological, ultrastructural, and molecular changes. The higher dose of MC-LR (100 μg·kg −1 ) caused severe liver injury at the beginning of the exposure period, whereas the lower dose (10 μg·kg −1 ) caused less, probably reversible injury, and its effects began to be observed later in the exposure period. These marked changes were accompanied by substantial MC-LR uptake by the liver. However, starting on the 7th day of exposure, cell debris began to be removed by phagocytes, then by 14th day, proliferation of liver cells had markedly increased, which led to reconstruction of the liver parenchyma at the end of the treatment. Surprisingly, despite weekly-repeated intraperitoneal injections, MC-LR did not accumulate over time of exposure which suggests its limited uptake in the later phase of exposure. In support, mRNA expression of the membrane transport protein oatp1d was decreased at the same time as the regenerative processes were observed. Our study shows that closing of active membrane transport may serve as one defence mechanism against further MC-LR intoxication. - Highlights: • The study presents pathological changes in whitefish during prolonged MC-LR exposure. • After early, severe injury, the damaged liver parenchyma of the fish regenerated. • Endoplasmic reticulum, cytoskeleton, and chromatin were the main targets for MC-LR. • MC-LR did not

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...

[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.

Feasibility of brief intensive exposure therapy for PTSD patients with childhood sexual abuse: a brief clinical report

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Lotte Hendriks

2010-12-01

Full Text Available Despite the strong empirical support for the effectiveness of exposure-based treatments in ameliorating post-traumatic stress disorder (PTSD, improvement of treatment is wanted given relatively high dropout rates and challenges of treating patients with high comorbidity and treatment-interfering stressors. The purpose of the current paper is to introduce an intensive exposure treatment program, illustrated by four case descriptions of PTSD patients, who suffered multiple (sexual traumas in childhood, had high levels of comorbidity and psychosocial stressors, and failed to improve during “regular” trauma-focused treatment programs. The program consisted of psychoeducation, prolonged imaginal exposure, exposure in vivo, exposure by drawings combined with narrative reconstructing, and writing assignments about central trauma-related cognitions. The treatment included 5 working days with individual sessions (in total 30 h of treatment provided by a team of four therapists. The PTSD symptoms of all patients decreased substantially and the effect sizes were large (Cohen's d resp. 1.5 [pre–post], 2.4 [pre-FU1 month], and 2.3 [pre-FU3 months]. Also, none of the patients showed symptom worsening or dropped out. The evaluation of these four pilot cases suggests that it is possible to intensify exposure treatment, even for multiple traumatized PTSD patients with high comorbidity. We concluded that the first results of this new, intensive exposure program for PTSD patients with childhood sexual abuse are promising.

Prolonged QRS Widening After Aripiprazole Overdose.

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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.

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

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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.

Developmental and neurobehavioral effects of perinatal exposure to polychlorinated biphenyls in mice.

Science.gov (United States)

Sugawara, Norio; Nakai, Kunihiko; Nakamura, Tomoyuki; Ohba, Takashi; Suzuki, Keita; Kameo, Satomi; Satoh, Chieko; Satoh, Hiroshi

2006-05-01

Because behavioral deficits associated with gestational exposure to polychlorinated biphenyls (PCBs) have been a concern, we studied the developmental and neurobehavioral effects of perinatal exposure to Aroclor 1254 (A1254), a commercial mixture of PCBs, in mice. The PCB mixture (A1254; 0, 6, 18, and 54 mg/kg body weight) was administered to pregnant mice (C57BL/6Cr) every 3 days by gavage from gestational day (GD) 6 to postnatal day (PND) 20. Compared with the control, treatment with A1254 did not alter the maternal body weight during the gestation and lactation periods. The body weight of the offspring did not differ among treatments. To assess the effects on offspring following such exposure, physical and neurobehavioral development (i.e., pinna detachment, hair growth, eye opening, incisor eruption, grasp reflex, righting reflex, walking, negative geotaxis, and cliff avoidance) was observed before weaning. At PND 7, poor adult-like responses in negative geotaxis were observed in all exposed groups. When the offspring were at 8-week old, the PCB-treated (18 mg/kg body weight) mice showed a decreased walking speed in the open-field test, and a prolonged time to reach the platform in the water maze test. Spontaneous locomotion activity was not affected by PCB exposure at 9 weeks . These results showed that perinatal exposure to PCBs produces several behavioral alterations in mice. Although dose-dependent changes were not observed, the neurobehavioral effects such as a decreased walking speed in the open-field test and a prolonged time to reach the platform in the water maze test remained in adulthood after the seeming recovery from the transient delay in development before weaning.

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

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

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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.

Virtual reality exposure therapy in the treatment of driving phobia

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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.

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.

Ozone exposure of a weed community produces adaptive changes in seed populations of Spergula arvensis.

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Jennifer B Landesmann

Full Text Available Tropospheric ozone is one of the major drivers of global change. This stress factor alters plant growth and development. Ozone could act as a selection pressure on species communities composition, but also on population genetic background, thus affecting life history traits. Our objective was to evaluate the consequences of prolonged ozone exposure of a weed community on phenotypic traits of Spergulaarvensis linked to persistence. Specifically, we predicted that the selection pressure exerted by high ozone concentrations as well as the concomitant changes in the weed community would drive population adaptive changes which will be reflected on seed germination, dormancy and longevity. In order to test seed viability and dormancy level, we conducted germination experiments for which we used seeds produced by S. arvensis plants grown within a weed community exposed to three ozone treatments during four years (0, 90 and 120 ppb. We also performed a soil seed bank experiment to test seed longevity with seeds coming from both the four-year ozone exposure experiment and from a short-term treatment conducted at ambient and added ozone concentrations. We found that prolonged ozone exposure produced changes in seed germination, dormancy and longevity, resulting in three S. arvensis populations. Seeds from the 90 ppb ozone selection treatment had the highest level of germination when stored at 75% RH and 25 °C and then scarified. These seeds showed the lowest dormancy level when being subjected to 5 ºC/5% RH and 25 ºC/75% followed by 5% RH storage conditions. Furthermore, ozone exposure increased seed persistence in the soil through a maternal effect. Given that tropospheric ozone is an important pollutant in rural areas, changes in seed traits due to ozone exposure could increase weed persistence in fields, thus affecting weed-crop interactions, which could ultimately reduce crop production.

Ozone exposure of a weed community produces adaptive changes in seed populations of Spergula arvensis.

Science.gov (United States)

Landesmann, Jennifer B; Gundel, Pedro E; Martínez-Ghersa, M Alejandra; Ghersa, Claudio M

2013-01-01

Tropospheric ozone is one of the major drivers of global change. This stress factor alters plant growth and development. Ozone could act as a selection pressure on species communities composition, but also on population genetic background, thus affecting life history traits. Our objective was to evaluate the consequences of prolonged ozone exposure of a weed community on phenotypic traits of Spergulaarvensis linked to persistence. Specifically, we predicted that the selection pressure exerted by high ozone concentrations as well as the concomitant changes in the weed community would drive population adaptive changes which will be reflected on seed germination, dormancy and longevity. In order to test seed viability and dormancy level, we conducted germination experiments for which we used seeds produced by S. arvensis plants grown within a weed community exposed to three ozone treatments during four years (0, 90 and 120 ppb). We also performed a soil seed bank experiment to test seed longevity with seeds coming from both the four-year ozone exposure experiment and from a short-term treatment conducted at ambient and added ozone concentrations. We found that prolonged ozone exposure produced changes in seed germination, dormancy and longevity, resulting in three S. arvensis populations. Seeds from the 90 ppb ozone selection treatment had the highest level of germination when stored at 75% RH and 25 °C and then scarified. These seeds showed the lowest dormancy level when being subjected to 5 ºC/5% RH and 25 ºC/75% followed by 5% RH storage conditions. Furthermore, ozone exposure increased seed persistence in the soil through a maternal effect. Given that tropospheric ozone is an important pollutant in rural areas, changes in seed traits due to ozone exposure could increase weed persistence in fields, thus affecting weed-crop interactions, which could ultimately reduce crop production.

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.

Physiologic effects of prolonged conducted electrical weapon discharge in ethanol-intoxicated adults.

Science.gov (United States)

Moscati, Ronald; Ho, Jeffrey D; Dawes, Donald M; Miner, James R

2010-06-01

This study examines the physiologic effects of prolonged conducted electrical weapon (CEW) exposure on alcohol-intoxicated adult subjects. Adult volunteers were recruited at a TASER International training conference. All subjects ingested mixed drinks until clinical intoxication or until a minimum breath alcohol level of 0.08 mg/dL was achieved. Blood samples for venous pH, Pco(2), bicarbonate, and lactate were measured in all subjects at baseline, immediately after alcohol ingestion, immediately after exposure to a 15-second TASER X26 discharge (Taser International Inc, Scottsdale, AZ), and 24 hours post-alcohol ingestion. Laboratory values were compared at sampling times using repeated-measure analysis of variance. A focused analysis comparing time points within groups was then performed using paired t tests. Twenty-two subjects were enrolled into the study. There was a decrease in pH and bicarbonate and an increase in lactate after alcohol ingestion. There was a further increase in lactate and drop in pH after CEW exposure. No subject experienced a significant adverse event. All values had returned to baseline levels at 24 hours except lactate, which demonstrated a small but clinically insignificant increase. Prolonged continuous CEW exposure in the setting of acute alcohol intoxication has no clinically significant effect on subjects in terms of markers of metabolic acidosis. The acidosis seen is consistent with what occurs with ethanol intoxication or moderate exertion. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Intraperitoneal exposure of whitefish to microcystin-LR induces rapid liver injury followed by regeneration and resilience to subsequent exposures

Energy Technology Data Exchange (ETDEWEB)

Woźny, Maciej, E-mail: maciej.wozny@uwm.edu.pl [Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. Słoneczna 45G, 10-709 Olsztyn (Poland); Lewczuk, Bogdan; Ziółkowska, Natalia [Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, ul. M. Oczapowskiego 13, 10-713 Olsztyn (Poland); Gomułka, Piotr [Department of Ichthyology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. M. Oczapowskiego 5, 10-719 Olsztyn (Poland); Dobosz, Stefan [Department of the Salmonid Research in Rutki, Inland Fisheries Institute in Olsztyn, Rutki, 83-330 Żukowo (Poland); Łakomiak, Alicja; Florczyk, Maciej; Brzuzan, Paweł [Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. Słoneczna 45G, 10-709 Olsztyn (Poland)

2016-12-15

To date, there has been no systematic approach comprehensively describing the sequence of pathological changes in fish during prolonged exposure to microcystin-LR (MC-LR). Towards this aim, juvenile whitefish individuals received an intraperitoneal injection with pure MC-LR, and the injection was repeated every week to maintain continuous exposure for 28 days. During the exposure period, growth and condition of the fish were assessed based on biometric measurements. Additionally, selected biochemical markers were analysed in the fishes' blood, and their livers were carefully examined for morphological, ultrastructural, and molecular changes. The higher dose of MC-LR (100 μg·kg{sup −1}) caused severe liver injury at the beginning of the exposure period, whereas the lower dose (10 μg·kg{sup −1}) caused less, probably reversible injury, and its effects began to be observed later in the exposure period. These marked changes were accompanied by substantial MC-LR uptake by the liver. However, starting on the 7th day of exposure, cell debris began to be removed by phagocytes, then by 14th day, proliferation of liver cells had markedly increased, which led to reconstruction of the liver parenchyma at the end of the treatment. Surprisingly, despite weekly-repeated intraperitoneal injections, MC-LR did not accumulate over time of exposure which suggests its limited uptake in the later phase of exposure. In support, mRNA expression of the membrane transport protein oatp1d was decreased at the same time as the regenerative processes were observed. Our study shows that closing of active membrane transport may serve as one defence mechanism against further MC-LR intoxication. - Highlights: • The study presents pathological changes in whitefish during prolonged MC-LR exposure. • After early, severe injury, the damaged liver parenchyma of the fish regenerated. • Endoplasmic reticulum, cytoskeleton, and chromatin were the main targets for MC-LR. • MC-LR did not

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)

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.

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

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.

Ibrutinib does not prolong the corrected QT interval in healthy subjects: results from a thorough QT study.

Science.gov (United States)

de Jong, Jan; Hellemans, Peter; Jiao, James Juhui; Huang, Yuhan; Mesens, Sofie; Sukbuntherng, Juthamas; Ouellet, Daniele

2017-12-01

Ibrutinib is an orally administered, irreversible Bruton's tyrosine kinase inhibitor for treatment of B-cell malignancy. This study evaluated the effects of single-dose ibrutinib at therapeutic and supratherapeutic exposures on cardiac repolarization in healthy subjects. Part 1 used an open-label, two-period sequential design to assess the safety and pharmacokinetics of single doses of ibrutinib 840 and 1680 mg in eight subjects. Part 2 was a randomized, placebo- and positive (moxifloxacin)-controlled, double-blind, single dose, four-way cross-over study to assess the effect of ibrutinib (840 and 1680 mg) on QT/QTc interval. 64 healthy subjects were planned to be enrolled. Baseline-adjusted QT (QTc) intervals for ibrutinib and moxifloxacin (assay sensitivity) were compared to placebo using linear mixed-effect model. A concentration-QTc analysis was also conducted. No clinically relevant safety observations were noted in Part 1. During Part 2, one subject experienced Grade 4 ALT/AST elevations with ibrutinib 1680 mg, leading to study termination and limiting the enrollment to 20 subjects. Ibrutinib demonstrated dose-dependent increases in exposure. The upper bounds of the 90% CIs for the mean difference in change from baseline in QTc between ibrutinib and placebo were Ibrutinib caused a concentration-dependent mild shortening of QTc and mild PR prolongation, but these effects were not considered clinically meaningful. Therapeutic and supratherapeutic concentrations of ibrutinib do not prolong the QTc interval. CLINICALTRIALS.GOV: NCT02271438.

Decision-making about chronic radiation exposure to the public. New recommendations from the ICRP

Energy Technology Data Exchange (ETDEWEB)

Gonzalez, A.J. [Division of Radiation and Waste Safety, International Atomic Energy Agency, Vienna (Austria)

2000-05-01

The paper discusses decision-making in situations of chronic exposure within the framework of a forthcoming related ICRP report on the subject which has been produced by an ICRP Task Group chaired by the author. This ICRP report will provide guidance on the application of the ICRP System of Radiological Protection to prolonged exposure situations afflicting members of the public. It will address the general application of the System to the control of prolonged exposures resulting from practices and to the undertaking of interventions in prolonged exposure situations, and will provide recommendations on generic reference levels for such interventions. It will also consider some specific situations and will discuss 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 relatively high levels of radioactive substances. Annexes will provide some examples of prolonged exposure situations and will discuss the radiological protection quantities, radiation-induced health effects and aspects of the System of Radiological Protection relevant to prolonged exposure. The quantitative recommendations for prolonged exposures provided in the report will be as follows: generic reference levels for intervention, in terms of existing annual doses, of < or approx. 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 of < or approx.10 mSv, below which intervention is not likely to be justifiable (and above which it may be necessary); intervention exemption

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

Prolonged ultraviolet light-induced erythema and the cutaneous carcinoma phenotype

International Nuclear Information System (INIS)

Tanenbaum, L.; Parrish, J.A.; Haynes, H.A.; Fitzpatrick, T.B.; Pathak, M.A.

1976-01-01

A considerable amount of evidence exists in support of the role of ultraviolet radiation as a major etiologic factor in human skin cancer, both melanoma and carcinoma types. On the basis of epidemiologic studies a phenotype has been described which helps to identify the persons who are more susceptible to skin cancer. In an attempt to further define this population, patients with cutaneous carcinoma and a normal control group were exposed to artificial ultraviolet light (UVL) and the erythema and tanning responses of each group were measured over a 21-day period. UVL-induced erythema was prolonged in a significantly higher percentage of patients with skin cancer than in control patients, lasting two to three weeks after single exposures to 6 and 8 times the patient's minimal erythema dose. The presence of prolonged erythema correlated with this history of previous skin cancer but did not correlate with other established risk factors for cutaneous carcinoma, i.e., fair skin, light hair and light eyes, easy sunburning and poor tanning, and Celtic ancestry. Prolonged erythema following UVL radiation may therefore represent an additional risk factor and help to identify the skin cancer-susceptible population

The Winter Procedure as Management for Prolonged Low-Flow Priapism: A Case Report

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Hsi-Lin Hsiao

2007-10-01

Full Text Available Priapism is a prolonged penile erection that is not associated with sexual stimulation. Although the time course has not been formally defined, it is usually considered to be one that lasts for more than 4–6 hours. Low-flow (ischemic priapism is usually associated with sickle cell disease, hemoglobinopathies, neoplastic syndrome, anticoagulant therapy, psychotropic medication or idiopathic causes. Here, we report a case of prolonged low-flow priapism lasting for 2 weeks, which was successfully treated with the Winter procedure after several attempts of conservative treatment. Although the potency remains unclear and the patient needs a longer period of follow-up, the case reported here still shows that prolonged low-flow priapism can be successfully treated with the Winter procedure when conservative treatments fail.

Chronic caffeine exposure attenuates blast-induced memory deficit in mice.

Science.gov (United States)

Ning, Ya-Lei; Yang, Nan; Chen, Xing; Zhao, Zi-Ai; Zhang, Xiu-Zhu; Chen, Xing-Yun; Li, Ping; Zhao, Yan; Zhou, Yuan-Guo

2015-01-01

To investigate the effects of three different ways of chronic caffeine administration on blast- induced memory dysfunction and to explore the underlying mechanisms. Adult male C57BL/6 mice were used and randomly divided into five groups: control: without blast exposure, con-water: administrated with water continuously before and after blast-induced traumatic brain injury (bTBI), con-caffeine: administrated with caffeine continuously for 1 month before and after bTBI, pre-caffeine: chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI, post-caffeine: chronically administrated with caffeine after bTBI. After being subjected to moderate intensity of blast injury, mice were recorded for learning and memory performance using Morris water maze (MWM) paradigms at 1, 4, and 8 weeks post-blast injury. Neurological deficit scoring, glutamate concentration, proinflammatory cytokines production, and neuropathological changes at 24 h, 1, 4, and 8 weeks post-bTBI were examined to evaluate the brain injury in early and prolonged stages. Adenosine A1 receptor expression was detected using qPCR. All of the three ways of chronic caffeine exposure ameliorated blast-induced memory deficit, which is correlated with the neuroprotective effects against excitotoxicity, inflammation, astrogliosis and neuronal loss at different stages of injury. Continuous caffeine treatment played positive roles in both early and prolonged stages of bTBI; pre-bTBI and post-bTBI treatment of caffeine tended to exert neuroprotective effects at early and prolonged stages of bTBI respectively. Up-regulation of adenosine A1 receptor expression might contribute to the favorable effects of chronic caffeine consumption. Since caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get, the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.

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…

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.

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.

Monitoring and control of occupational radiation exposure in Switzerland

International Nuclear Information System (INIS)

Moser, M.

1997-01-01

Occupational exposure is the most prominent example for the prolonged exposure to low level ionizing radiation characterized by low doses and dose rates. In this paper the occupational exposure in Switzerland is presented and the regulatory control of this exposure in the framework of the new radiation protection regulations is discussed. (author)

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....

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.

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.

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.

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.

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

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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.

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.

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.

Local Gene Delivery System by Bubble Liposomes and Ultrasound Exposure into Joint Synovium

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Yoichi Negishi

2011-01-01

Full Text Available Recently, we have developed novel polyethylene glycol modified liposomes (bubble liposomes; BL entrapping an ultrasound (US imaging gas, which can work as a gene delivery tool with US exposure. In this study, we investigated the usefulness of US-mediated gene transfer systems with BL into synoviocytes in vitro and joint synovium in vivo. Highly efficient gene transfer could be achieved in the cultured primary synoviocytes transfected with the combination of BL and US exposure, compared to treatment with plasmid DNA (pDNA alone, pDNA plus BL, or pDNA plus US. When BL was injected into the knee joints of mice, and US exposure was applied transcutaneously to the injection site, highly efficient gene expression could be observed in the knee joint transfected with the combination of BL and US exposure, compared to treatment with pDNA alone, pDNA plus BL, or pDNA plus US. The localized and prolonged gene expression was also shown by an in vivo luciferase imaging system. Thus, this local gene delivery system into joint synovium using the combination of BL and US exposure may be an effective means for gene therapy in joint disorders.

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.

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.

Hypoxic ventilatory sensitivity in men is not reduced by prolonged hyperoxia (Predictive Studies V and VI)

Science.gov (United States)

Gelfand, R.; Lambertsen, C. J.; Clark, J. M.; Hopkin, E.

1998-01-01

Potential adverse effects on the O2-sensing function of the carotid body when its cells are exposed to toxic O2 pressures were assessed during investigations of human organ tolerance to prolonged continuous and intermittent hyperoxia (Predictive Studies V and VI). Isocapnic hypoxic ventilatory responses (HVR) were determined at 1.0 ATA before and after severe hyperoxic exposures: 1) continuous O2 breathing at 1.5, 2.0, and 2.5 ATA for 17.7, 9.0, and 5.7 h and 2) intermittent O2 breathing at 2.0 ATA (30 min O2-30 min normoxia) for 14.3 O2 h within 30-h total time. Postexposure curvature of HVR hyperbolas was not reduced compared with preexposure controls. The hyperbolas were temporarily elevated to higher ventilations than controls due to increments in respiratory frequency that were proportional to O2 exposure time, not O2 pressure. In humans, prolonged hyperoxia does not attenuate the hypoxia-sensing function of the peripheral chemoreceptors, even after exposures that approach limits of human pulmonary and central nervous system O2 tolerance. Current applications of hyperoxia in hyperbaric O2 therapy and in subsea- and aerospace-related operations are guided by and are well within these exposure limits.

Psychotropic Pharmacotherapy Associated With QT Prolongation Among Veterans With Posttraumatic Stress Disorder.

Science.gov (United States)

Stock, Eileen M; Zeber, John E; McNeal, Catherine J; Banchs, Javier E; Copeland, Laurel A

2018-04-01

In 2012, the Food and Drug Administration issued Drug Safety Communications on several drugs associated with QT prolongation and fatal ventricular arrhythmias. Among these was citalopram, a selective serotonin reuptake inhibitor (SSRI) approved for depression and commonly used for posttraumatic stress disorder (PTSD). Evaluation of the risk for QT prolongation among other psychotropic drugs for individuals with PTSD remains limited. Explore psychotropic drugs associated with QT prolongation among veterans with PTSD. Patients in the Veterans Health Administration in 2006-2009 with PTSD and QT prolongation (176 cases) were matched 1:4 on age, gender, visit date and setting, and physical comorbidity. Classification trees assessed QT prolongation risk among prescribed medications (n=880). Receipt of any drug with known risk of QT prolongation varied by group (23% QT cases vs 15% control, prisks included ziprasidone (3% vs 1%, p=0.02) and buspirone (6% vs 2%, p=0.01). Increased risk was not observed for the SSRIs, citalopram and fluoxetine. Classification trees found that sotalol and amitriptyline carried greater risk among cardiac patients and methadone, especially if prescribed with quetiapine, among noncardiac patients. Per adjusted survival model, patients with QT prolongation were at increased risk for death (hazard ratio=1.60; 95% CI=1.04-2.44). Decision models are particularly advantageous when exploring nonlinear relationships or nonadditive interactions. These findings may potentially affect clinical decision-making concerning treatment for PTSD. For patients at higher risk of QT prolongation, antidepressants other than amitriptyline should be considered. Medications for comorbid conditions should also be closely monitored for heightened QT prolongation risk.

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

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

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

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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.

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.

Role of Sleep Deprivation in Fear Conditioning and Extinction: Implications for Treatment of PTSD

Science.gov (United States)

2015-10-01

mechanism underlying the most successful treatment for PTSD, Prolonged Exposure. In animal models, sleep deprivation has been shown to impair extinction ...2. 3. 9 +Sleep and Extinction Learning  Animal models show fear conditioning:  Disrupts sleep  Disrupted sleep, in turn  Impairs extinction ...Award Number: W81XWH-11-2-0001 TITLE: “Role of Sleep Deprivation in Fear Conditioning and Extinction : Implications for Treatment of PTSD

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.

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

Directory of Open Access Journals (Sweden)

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.

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

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

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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.

Incidence and risk of QTc interval prolongation among cancer patients treated with vandetanib: a systematic review and meta-analysis.

Directory of Open Access Journals (Sweden)

Jiajie Zang

Full Text Available Vandetanib is a multikinase inhibitor that is under assessment for the treatment of various cancers. QTc interval prolongation is one of the major adverse effects of this drug, but the reported incidence varies substantially among clinical trials. We performed a systematic review and meta-analysis to obtain a better understanding in the risk of QTc interval prolongation among cancer patients administered vandetanib.Eligible studies were phase II and III prospective clinical trials that involved cancer patients who were prescribed vandetanib 300 mg/d and that included data on QTc interval prolongation. The overall incidence and risk of QTc interval prolongation were calculated using random-effects or fixed-effects models, depending on the heterogeneity of the included studies. Nine trials with 2,188 patients were included for the meta-analysis. The overall incidence of all-grade and high-grade QTc interval prolongation was 16.4% (95% CI, 8.1-30.4% and 3.7% (8.1-30.4%, respectively, among non-thyroid cancer patients, and 18.0% (10.7-28.6% and 12.0% (4.5-28.0%, respectively, among thyroid cancer patients. Patients with thyroid cancer who had longer treatment duration also had a higher incidence of high-grade events, with a relative risk of 3.24 (1.57-6.71, than patients who had non-thyroid cancer. Vandetanib was associated with a significantly increased risk of all-grade QTc interval prolongation with overall Peto odds ratios of 7.26 (4.36-12.09 and 5.70 (3.09-10.53 among patients with non-thyroid cancer and thyroid cancer, respectively, compared to the controls.Treatment with vandetanib is associated with a significant increase in the overall incidence and risk of QTc interval prolongation. Different cancer types and treatment durations may affect the risk of developing high-grade QTc interval prolongation.

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…

Paternal work stress and prolonged time to pregnancy.

Science.gov (United States)

Lee, Mi-Sun; Paek, Domyung; Eum, Ki-Do; Siegrist, Johannes; Li, Jian; Lee, Hye-Eun; Cho, Sung-Il

2009-01-01

The aim of this study was to explore an association between psychosocial stress at work in married men and their spouses' prolonged time to pregnancy (TTP). All married male workers of a large Korean petrochemical enterprise and their wives fulfilling the selection criteria were included. Main selection criteria were lack of use of contraceptives and experienced pregnancy in recent past. Data were available from 322 couples. Psychosocial stress at work was measured by the effort-reward imbalance questionnaire. Prolonged TTP was measured by the "TTP questionnaire". After adjustment for confounding effects of demographic and life-style characteristics and benzene exposure, delayed TTP, defined by frequency of first-cycle pregnancy, was associated with one standard deviation (SD) increase of the effort-reward ratio in the chronically stressed group of married men (OR = 0.47; 95% CI = 0.22-0.99) in logistic regression analysis. A similar, but somewhat weaker effect, was found for the overall group (OR = 0.67; 95% CI = 0.47-0.94). Paternal stress at work, as measured by effort-reward imbalance, seemed to be associated with a decreased number of conceptions in the first menstrual cycle.

[A case of favourable outcome of the treatment of extremely severe acute poisoning with methanol].

Science.gov (United States)

Batotsyrenov, B V; Livanov, G A; Vasil'ev, S A; Fedorov, A V; Antrianov, A Iu

2013-01-01

A case of favourable outcome of the treatment of extremely severe acute poisoning after prolonged exposure to lethal doses of methanol is reported. The complex treatment included urgent and effective elimination of the poison (multiple gastric lavage, hemodialysis), antidote therapy (administration of ethanol), correction of decompensated metabolic acidosis (alkali therapy and infusion therapy with reamberin). These measures had beneficial effect on the clinical course of poisoning and ensured its favourable outcome.

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.

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.

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.

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)

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

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.

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

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.

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...

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.

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.

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 ...

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.

Repeated morphine treatment influences operant and spatial learning differentially

Institute of Scientific and Technical Information of China (English)

Mei-Na WANG; Zhi-Fang DONG; Jun CAO; Lin XU

2006-01-01

Objective To investigate whether repeated morphine exposure or prolonged withdrawal could influence operant and spatial learning differentially. Methods Animals were chronically treated with morphine or subjected to morphine withdrawal. Then, they were subjected to two kinds of learning: operant conditioning and spatial learning.Results The acquisition of both simple appetitive and cued operant learning was impaired after repeated morphine treatment. Withdrawal for 5 weeks alleviated the impairments. Single morphine exposure disrupted the retrieval of operant memory but had no effect on rats after 5-week withdrawal. Contrarily, neither chronic morphine exposure nor 5-week withdrawal influenced spatial learning task of the Morris water maze. Nevertheless, the retrieval of spatial memory was impaired by repeated morphine exposure but not by 5-week withdrawal. Conclusion These observations suggest that repeated morphine exposure can influence different types of learning at different aspects, implicating that the formation of opiate addiction may usurp memory mechanisms differentially.

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.

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

[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

An observation of histological evidence on internal organ damages in mice caused by repeated exposures to motorcycle emissions

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Wardoyo, Arinto Y. P.; Juswono, Unggul P.; Noor, Johan A. E.

2017-05-01

Motor vehicle emissions have been identified as a source of ultrafine particles, which have significant impacts on human health. Repeated and prolonged exposure to ultrafine particles may have a significant association with organ damage. Here, we evaluated the correlation between repeated exposure to ultrafine particles and organ damage in mice. Motorcycle emissions were injected into an exposure chamber with mice for a period of 20 seconds. This treatment was conducted over 10 days. The mice were sacrificed on the 2nd, 4th, 6th, 8th, and 10th days for organ preparations. Based on the results, motorcycle emission exposure caused organ damage in mice, with different severities depending on the organ. The highest damage was found for the lung, followed by the kidney, erythrocytes, and liver.

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.

Licence prolongations of US nuclear power plants; Les prolongations de licence des centrales nucleaires americaines

Energy Technology Data Exchange (ETDEWEB)

NONE

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.)

Quantification of acute vocal fold epithelial surface damage with increasing time and magnitude doses of vibration exposure.

Directory of Open Access Journals (Sweden)

Tsuyoshi Kojima

Full Text Available Because the vocal folds undergo repeated trauma during continuous cycles of vibration, the epithelium is routinely susceptible to damage during phonation. Excessive and prolonged vibration exposure is considered a significant predisposing factor in the development of vocal fold pathology. The purpose of the present study was to quantify the extent of epithelial surface damage following increased time and magnitude doses of vibration exposure using an in vivo rabbit phonation model. Forty-five New Zealand white breeder rabbits were randomized to nine groups and received varying phonation time-doses (30, 60, or 120 minutes and magnitude-doses (control, modal intensity phonation, or raised intensity phonation of vibration exposure. Scanning electron microscopy and transmission electron microscopy was used to quantify the degree of epithelial surface damage. Results revealed a significant reduction in microprojection density, microprojection height, and depth of the epithelial surface with increasing time and phonation magnitudes doses, signifying increased epithelial surface damage risk with excessive and prolonged vibration exposure. Destruction to the epithelial cell surface may provide significant insight into the disruption of cell function following prolonged vibration exposure. One important goal achieved in the present study was the quantification of epithelial surface damage using objective imaging criteria. These data provide an important foundation for future studies of long-term tissue recovery from excessive and prolonged vibration exposure.

Longer oral exposure with modified sham feeding does not slow down gastric emptying of low- and high-energy-dense gastric loads in healthy young men.

Science.gov (United States)

Wijlens, Anne G M; Erkner, Alfrun; Mars, Monica; de Graaf, Cees

2015-02-01

A long oral exposure to food and a high-energy density of food have been shown to increase satiety feelings. The effect of energy density is predominantly caused by an inhibition of gastric emptying. It is hypothesized that prolonging oral exposure may have an additional effect on this inhibition of gastric emptying. However, little human data are available to support this hypothesis. The objective was to assess the effect of the duration of oral exposure to food on gastric emptying rate of gastric loads (GLs) low and high in energy density and on satiety feelings. Twenty-six healthy men [mean ± SD age: 22 ± 3 y; BMI (in kg/m(2)): 23 ± 1] participated in a randomized crossover trial with 4 treatments and a control. Treatments consisted of either 1- or 8-min modified sham feeding (MSF) of cake, and a GL of either 100 or 700 kcal infused in the stomach via a nasogastric tube (500 mL, 62.5 mL/min). The control consisted of no MSF and a GL of 500 mL of water. Gastric emptying rate was assessed with a (13)C breath test. Breath samples and satiety feelings were collected at fixed time points until 90 min after start of the treatment. Gastric emptying rate and satiety feelings were not affected by duration of MSF (P ≥ 0.27). However, the 700-kcal GL treatments slowed gastric emptying [41% lower area under the curve (AUC)] and increased satiety feelings (22-31% higher AUC) compared with the 100-kcal GL treatments (P men. However, prolonging oral exposure to food did not have an additional effect. This study provides more insight in satiety regulation. This trial was registered at trialregister.nl as NTR3601. © 2015 American Society for Nutrition.

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

Directory of Open Access Journals (Sweden)

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.

Heart Rate Variability Frequency Domain Alterations among Healthy Nurses Exposed to Prolonged Work Stress.

Science.gov (United States)

Borchini, Rossana; Veronesi, Giovanni; Bonzini, Matteo; Gianfagna, Francesco; Dashi, Oriana; Ferrario, Marco Mario

2018-01-11

The deregulation of the autonomic nervous system assessed through the heart rate variability (HRV) analysis is a promising pathway linking work stress and cardiovascular diseases. We aim to investigate the associations between HRV High Frequency (HF) and Low Frequency (LF) powers and work stress in a sample of 36 healthy nurses. Perceived work stress was assessed twice one year apart, using the Job Content and Effort Reward Imbalance questionnaires. This allows to classify nurses in three exposure groups: "prolonged high stress" (PHS), "recent high stress" (RHS) and "stable low stress" (SLS). A 24-h ECG monitoring was later performed during a working day (WD) and a subsequent resting day (RD). Statistically significantly lower ( p working periods. In the subsequent resting periods, HF means showed increases over time in the RHS (beta = +0.41, p working and resting periods. Our study evidences that both prolonged and recent perceived high work stress were associated with a reduction of HF and LF powers during work. In addition, prolonged stress was associated with a lack of recovery during not-working and resting periods.

Structural and functional changes in the gastric intramural nervous plexus in emotionally stressed rats exposed to low doses of prolonged ionizing radiation and lead

International Nuclear Information System (INIS)

Lapsha, V.I.; Bocharova, V.N.; Utkina, L.N.; Rolevich, I.V.

1999-01-01

Changes in the catecholamine content in adrenergic fibres, acethylcholinesterase activity, and in the energy metabolism enzymes lactate dehydrogenase and succinate dehydrogenase in neurons of the gastric intramural plexus during emotional stress in rats a day after combined exposure to prolonged (30 days) ionizing radiation at a total dose 1.0 Gy and 0.6 mg/kg lead were studied. A decrease in catecholamines in adrenergic fibres and acethylcholinesterase and lactate dehydrogenase activity in neurons was observed. An enhanced sensitivity of the gastric intramural plexus after the prolonged exposure to small doses of ionizing radiation and lead in conditions of emotional stress was suggested [ru

[Diagnosis of congenital endocrinological disease in newborns with prolonged jaundice and hypoglycaemia].

Science.gov (United States)

Braslavsky, D; Keselman, A; Chiesa, A; Bergadá, I

2012-03-01

The association of prolonged neonatal jaundice and hypoglycaemia may be secondary to an endocrinological disease. Pituitary insufficiency and primary adrenal insufficiency are the most likely endocrine diseases that need to be ruled out. We retrospectively analysed the clinical and laboratory characteristics of thirteen patients referred to the Hospital de Niños Ricardo Gutiérrez between years 2003 and 2008 due to prolonged neonatal jaundice and hypoglycaemia secondary to pituitary insufficiency in twelve patients, and in one secondary to primary adrenal insufficiency. All patients had a history of neonatal hypoglycaemia. Ten patients had conjugated hyperbilirubinaemia and six also had elevated transaminases. Combined pituitary hormone deficiency was observed in the twelve hypopituitarism patients. Hormonal replacement normalised liver function and resolved the prolonged jaundice in all the patients. None of them underwent liver biopsy. Hypoglycaemia also remitted after hormonal therapy. Prolonged or cholestatic jaundice associated with neonatal hypoglycaemia is highly likely to be due to pituitary hormone deficiency or primary adrenal insufficiency. Early diagnosis and treatment of these children reverts the prolonged jaundice and prevents morbidity and mortality due to recurrent hypoglycaemia and hormone deficiencies. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Causes of prolonged hospitalization among general internal medicine patients of a tertiary care center.

Science.gov (United States)

Ruangkriengsin, Darat; Phisalprapa, Pochamana

2014-03-01

Unnecessary days of prolonged hospitalization may lead to the increase in hospital-related complications and costs, especially in tertiary care center Currently, there have not been many studies about the causes of prolonged hospitalization. Some identified causes could, however, be prevented and improved. To identify the prevalence, causes, predictive factors, prognosis, and economic burden of prolonged hospitalization in patients who had been in general internal medicine wards of the tertiary care center for 7 days or more. Retrospective chart review study was conducted among all patients who were admitted for 7 days or more in general internal medicine wards of Siriraj Hospital, the largest tertiary care center in Thailand. The period of this study was from 1 August 2012 to 30 September 2012. Demographic data, principle diagnosis, comorbid diseases, complications, discharge status, total costs of admission and percentage of reimbursement were collected. The causes of prolonged hospitalization at day 7, 14, 30, and 90 were assessed. Five hundred and sixty-two charts were reviewed. The average length of stay was 25.9 days. The two most common causes of prolonged admission at day 7 were treatment of main diagnosed disease with stable condition (27.6%) and waiting for completion of intravenous antibiotics administration with stable condition (19.5%). The causes of prolonged hospitalization at day 14 were unstable condition from complications (22.6%) and those waiting for completion of intravenous antibiotics administration with stable condition (15.8%). The causes of prolonged admission at day 30 were unstable conditions from complications (25.6%), difficulty weaning or ventilator dependence (17.6%), and caregiver problems (15.2%). The causes of prolonged hospitalization at day 90 were unstable condition from complications (30.0%), caregiver problems (30.0%), and palliative care (25.0%). Poor outcomes were shown in the patients admitted more than 90 days. Percentage

Anger and guilt in treatment for chronic posttraumatic stress disorder.

Science.gov (United States)

Clifton, Erin G; Feeny, Norah C; Zoellner, Lori A

2017-03-01

Feelings of anger and guilt are important to consider when treating PTSD as they are related to higher PTSD severity and may be related to avoidance during treatment. Avoidance may impede emotional engagement, the process of connecting with distressing, fear-related emotions during imaginal exposure, which is considered an important mechanism for successful PTSD treatment in prolonged exposure (PE). Yet, little research has examined possible complications in achieving emotional engagement, such as anger and guilt. The present study utilized data from 116 individuals with PTSD who received PE to investigate whether anger and guilt were associated with poorer emotional engagement, as captured by pre, peak, post, and mean subjective units of distress (SUDs), during the initial imaginal exposure, and whether anger and guilt predicted worse treatment outcome generally and as a result of lessened emotional engagement. Neither initial anger nor guilt hindered engagement nor predicted worse outcome. Contrary to hypotheses, higher guilt was predictive of greater anticipatory distress and slightly better PTSD outcome. The relationship between pre-treatment guilt cognitions and post-treatment PTSD severity was not mediated by engagement. This study used a trauma-specific measure of guilt and general measure for anger, however both are commonly used. In addition, this study examined emotional engagement during imaginal exposure to the exclusion of engagement with other therapy components, such as in vivo exposure. These findings help dispel concerns that those with higher anger and guilt will avoid emotionally engaging during the initial imaginal exposure due to feeling distressed by intense negative emotionality. Copyright © 2016 Elsevier Ltd. All rights reserved.

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...

Prolonged Hypocalcemia Following a Single Dose of Denosumab for Diffuse Bone Metastasis of Gastric Cancer after Total Gastrectomy.

Science.gov (United States)

Iizumi, Sakura; Shimoi, Tatsunori; Nishikawa, Tadaaki; Kitano, Atsuko; Sasada, Shinsuke; Shimomura, Akihiko; Noguchi, Emi; Yunokawa, Mayu; Yonemori, Kan; Shimizu, Chikako; Fujiwara, Yasuhiro; Tamura, Kenji

2017-11-01

Hypocalcemia is a significant adverse effect of denosumab. We herein report a case of prolonged hypocalcemia in a patient with multiple risk factors for hypocalcemia, including gastrectomy, increased bone turnover, and a poor performance status. Hypocalcemia developed after denosumab treatment for diffuse bone metastasis of gastric cancer, despite oral supplementation with vitamin D and calcium. To avoid serious prolonged hypocalcemia, a thorough assessment of the bone calcium metabolism is required before initiating denosumab treatment.

Effect of prolonged incubation with copper on endothelium-dependent relaxation in rat isolated aorta

Science.gov (United States)

Chiarugi, Alberto; Pitari, Giovanni Mario; Costa, Rosa; Ferrante, Margherita; Villari, Loredana; Amico-Roxas, Matilde; Godfraind, Théophile; Bianchi, Alfredo; Salomone, Salvatore

2002-01-01

We investigated the effects of prolonged exposure to copper (Cu2+) on vascular functioning of isolated rat aorta. Aortic rings were exposed to CuSO4 (3–24 h) in Dulbecco's modified Eagle medium with or without 10% foetal bovine serum (FBS) and then challenged with vasoconstrictors or vasodilators in the absence of Cu2+. Exposure to 2 μM Cu2+ in the absence of FBS did not modify the response to phenylephrine (PE) or acetylcholine (ACh) in aortic rings incubated for 24 h. Identical exposure in the presence of FBS increased the contractile response to 1 μM PE by 30% (P<0.05) and impaired the relaxant response to 3 μM ACh or 1 μM A23187 (ACh, from 65.7±7.1 to 6.2±1.1%, n=8; A23187, from 74.6±8.2 to 12.0±0.8%, n=6; P<0.01 for both). Cu2+ exposure did not affect the relaxant response to NO-donors. Impairment of vasorelaxation appeared 3 h after incubation with 2 μM Cu2+ and required 12 h to attain a steady state. Vasorelaxation to ACh was partially restored by 1 mM tiron (intracellular scavenger of superoxide ions; maximum relaxation 34.2±6.4%, n=10, P<0.01 vs Cu2+ alone), whereas catalase, superoxide dismutase or cycloheximide were ineffective. Twenty-four hour-exposure to 2 μM Cu2+ did not affect endothelium integrity or eNOS expression, and increased the Cu content in arterial rings from 6.8±1.1 to 18.9±2.9 ng mg−1 wet weight, n=8; P<0.01. Our results show that, in the presence of FBS, prolonged exposure to submicromolar concentrations of Cu2+ impaired endothelium-dependent vasorelaxation in aortic rings, probably through an intracellular generation of superoxide ions. PMID:12163352

Effect of belimbing wuluh (averrhoa bilimbi l.) extract gel exposure duration to surface roughness of enamel

Science.gov (United States)

Karima, F.; Eriwati, Y. K.; Triaminingsih, S.

2017-08-01

The purpose of this study was to analyze the effect of Belimbing Wuluh Gel Extract to surface roughness of enamel. Thirty-six premolars teeth that divided into 4 groups (n = 9), were exposed to 37% phosphoric acid gel (pH = 1) for 15 seconds as a control group, and belimbing wuluh extract gel with a concentration of 80% (pH = 1.8) for 15 seconds, 20 seconds, and 25 seconds as the treatment groups. The statistical analysis of paired and unpaired T-test shows that all treatment groups experienced a significant change (p enamel occurred after exposed by belimbing extract gel with an exposure duration of 25 seconds, but the roughness of 37% phosphoric acid gel is still greater. There was a correlation between roughness on the surface of tooth enamel with prolonged exposure belimbing wuluh extract gel with a concentration of 80%.

Potentiation of ghrelin signaling attenuates cancer anorexia–cachexia and prolongs survival

Science.gov (United States)

Fujitsuka, N; Asakawa, A; Uezono, Y; Minami, K; Yamaguchi, T; Niijima, A; Yada, T; Maejima, Y; Sedbazar, U; Sakai, T; Hattori, T; Kase, Y; Inui, A

2011-01-01

Cancer anorexia–cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients. This study aimed to clarify the gut–brain peptides involved in the pathogenesis of the syndrome and determine effective treatment for cancer anorexia–cachexia. We show that both ghrelin insufficiency and resistance were observed in tumor-bearing rats. Corticotropin-releasing factor (CRF) decreased the plasma level of acyl ghrelin, and its receptor antagonist, α-helical CRF, increased food intake of these rats. The serotonin 2c receptor (5-HT2cR) antagonist SB242084 decreased hypothalamic CRF level and improved anorexia, gastrointestinal (GI) dysmotility and body weight loss. The ghrelin receptor antagonist (D-Lys3)-GHRP-6 worsened anorexia and hastened death in tumor-bearing rats. Ghrelin attenuated anorexia–cachexia in the short term, but failed to prolong survival, as did SB242084 administration. In addition, the herbal medicine rikkunshito improved anorexia, GI dysmotility, muscle wasting, and anxiety-related behavior and prolonged survival in animals and patients with cancer. The appetite-stimulating effect of rikkunshito was blocked by (D-Lys3)-GHRP-6. Active components of rikkunshito, hesperidin and atractylodin, potentiated ghrelin secretion and receptor signaling, respectively, and atractylodin prolonged survival in tumor-bearing rats. Our study demonstrates that the integrated mechanism underlying cancer anorexia–cachexia involves lowered ghrelin signaling due to excessive hypothalamic interactions of 5-HT with CRF through the 5-HT2cR. Potentiation of ghrelin receptor signaling may be an attractive treatment for anorexia, muscle wasting and prolong survival in patients with cancer anorexia–cachexia. PMID:22832525

Rapid and Decentralized Human Waste Treatment by Microwave Radiation.

Science.gov (United States)

Nguyen, Tu Anh; Babel, Sandhya; Boonyarattanakalin, Siwarutt; Koottatep, Thammarat

2017-07-01

  This study evaluates the technical feasibility of using microwave radiation for the rapid treatment of human feces. Human feces of 1000 g were radiated with a commercially available household microwave oven (with rotation) at different exposure time lengths (30, 50, 60, 70, and 75 mins) and powers (600, 800, and 1000 W). Volume reduction over 90% occurred after 1000 W microwave radiation for 75 mins. Pathogen eradiation performances of six log units or more at a high range of microwave powers were achieved. Treatments with the same energy input of 1000 Wh, but at lower powers with prolonged exposure times, significantly enhanced moisture removal and volume reduction. Microwave radiation caused carbonization and resulted in a more stable end product. The energy content of the samples after microwave treatment at 1000 W and 75 mins is 3517 ± 8.85 calories/g of dried sample, and the product can also be used as compost.

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

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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.

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

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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

MANAGEMENT OF ENDOCRINE DISEASE: Arguments for the prolonged use of antithyroid drugs in children with Graves' disease.

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Léger, Juliane; Carel, Jean-Claude

2017-08-01

Graves' disease is an autoimmune disorder. It is the leading cause of hyperthyroidism, but is rare in children. Patients are initially managed with antithyroid drugs (ATDs), such as methimazole/carbimazole. A major disadvantage of treatment with ATD is the high risk of relapse, exceeding 70% of children treated for duration of 2 years, and the potential major side effects of the drug reported in exceptional cases. The major advantage of ATD treatment is that normal homeostasis of the hypothalamus-pituitary-thyroid axis may be restored, with periods of drug treatment followed by freedom from medical intervention achieved in approximately 40-50% of cases after prolonged treatment with ATD, for several years, in recent studies. Alternative ablative treatments such as radioactive iodine and, less frequently and mostly in cases of very high volume goiters or in children under the age of 5 years, thyroidectomy, performed by pediatric surgeons with extensive experience should be proposed in cases of non-compliance, intolerance to medical treatment or relapse after prolonged medical treatment. Ablative treatments are effective against hyperthyroidism, but they require the subsequent administration of levothyroxine throughout the patient's life. This review considers data relating to the prognosis for Graves' disease remission in children and explores the limitations of study designs and results; and the emerging proposal for management through the prolonged use of ATD drugs. © 2017 European Society of Endocrinology.

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

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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.

Prolonged hypoxia modulates platelet activating factor receptor-mediated responses by fetal ovine pulmonary vascular smooth muscle cells.

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Renteria, Lissette S; Raj, J Usha; Ibe, Basil O

2010-12-01

Hypoxia augments PAF receptor (PAFr) binding and PAFr protein expression in venous SMC (SMC-PV). We compared effect of acute and prolonged hypoxia (pO(2)<40 torr) on PAFr-mediated responses in arterial SMC (SMC-PA) and SMC-PV. Cells were studied for 30 min (acute) or for 48 h (prolonged) hypoxia and compared to normoxic (pO(2) ~100 torr) conditions. PAF binding was quantified in fmol/10(6) cells (mean ± SEM). PAF binding in normoxia were SMC-PA, 5.2 ± 0.2 and in SMC-PV, 19.3 ± 1.1; values in acute hypoxia were SMC-PA, 7.7 ± 0.4 and in SMC-PV, 27.8 ± 1.7. Prolonged hypoxia produced 6-fold increase in binding in SMC-PA, but only 2-fold increase in SMC-PV, but binding in SMC-PV was still higher. Acute hypoxia augmented inositol phosphate release by 50% and 40% in SMC-PA and SMC-PV, respectively. During normoxia, PAFr mRNA expression by both cell types was similar, but expression in hypoxia by SMC-PA was greater. In SMC-PA, hypoxia and PAF augmented intracellular calcium flux. Re-exposure of cells to 30 min normoxia after 48 h hypoxia decreased binding by 45-60%, suggesting immediate down-regulation of hypoxia-induced PAFr-mediated effects. We speculate that re-oxygenation immediately reverses hypoxia effect probably due to oxygen tension-dependent reversibility of PAFr activation and suggest that exposure of the neonate to prolonged state of hypoxia will vilify oxygen exchange capacity of the neonatal lungs. Copyright © 2010 Elsevier Inc. All rights reserved.

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...

Prolonged CT urography in duplex kidney.

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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.

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

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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.

The effects of intermittent exposure to low-pH and low-oxygen conditions on survival and growth of juvenile red abalone

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Kim, T. W.; Barry, J. P.; Micheli, F.

2013-11-01

Exposure of nearshore animals to hypoxic, low-pH waters upwelled from below the continental shelf and advected near the coast may be stressful to marine organisms and lead to impaired physiological performance. We mimicked upwelling conditions in the laboratory and tested the effect of fluctuating exposure to water with low-pH and/or low-oxygen levels on the mortality and growth of juvenile red abalone (Haliotis rufescens, shell length 5-10 mm). Mortality rates of juvenile abalone exposed to low-pH (7.5, total scale) and low-O2 (40% saturation, mg L-1) conditions for periods of 3 to 6 h every 3-5 days over 2 weeks did not differ from those exposed to control conditions (O2: 100% saturation, 12 mg L-1; pH 8.0). However, when exposure was extended to 24 h, twice over a 15-day period, juveniles experienced 5-20% higher mortality in the low-oxygen treatments compared to control conditions. Growth rates were reduced significantly when juveniles were exposed to low-oxygen and low-pH treatments. Furthermore, individual variation of growth rate increased when juveniles were exposed simultaneously to low-pH and low-O2 conditions. These results indicate that prolonged exposure to low-oxygen levels is detrimental for the survival of red abalone, whereas pH is a crucial factor for their growth. However, the high individual variation in growth rate under low levels of both pH and oxygen suggests that cryptic phenotypic plasticity may promote resistance to prolonged upwelling conditions by a portion of the population.

Evaluation of sphingolipids in Wistar rats treated to prolonged and single oral doses of fumonisin b₁.

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Direito, Glória M; Almeida, Adriana P; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

2009-01-01

The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B(1) (FB(1)). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB(1). Prolonged exposure to FB(1) caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB(1). Animals receiving a single dose of FB(1) presented variations in Sa and So levels and in the Sa/So ratio.

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)

Risk management of QTc-prolongation in patients receiving haloperidol: an epidemiological study in a University hospital in Belgium.

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Vandael, Eline; Vandenberk, Bert; Vandenberghe, Joris; Spriet, Isabel; Willems, Rik; Foulon, Veerle

2016-04-01

Many drugs, including haloperidol, are linked with a risk of QTc-prolongation, which can lead to Torsade de Pointes and sudden cardiac death. To investigate the prevalence of concomitant risk factors for QTc-prolongation in patients treated with haloperidol, and the use of safety measures to minimize this risk. University Hospitals of Leuven, Belgium. Methods A retrospective epidemiological study was performed. On 15 consecutive Mondays, all patients with a prescription for haloperidol were included. A risk score for QTc-prolongation, inspired by the pro-QTc score of Haugaa et al., was calculated based on gender, comorbidities, lab results and concomitant QTc-prolonging drugs (each factor counting for one point). Available electrocardiograms before and during the treatment of haloperidol were registered. Management of the risk of QTc-prolongation. Two hundred twenty-two patients were included (59.0 % men, median age 77 years) of whom 26.6 % had a risk score of ≥4 (known to significantly increase the mortality). Overall, 24.3 % received haloperidol in combination with other drugs with a known risk of Torsade de Pointes. Half of the patients had an electrocardiogram in the week before the start of haloperidol; only in one-third a follow-up electrocardiogram during haloperidol treatment was performed. Of the patients with a moderately (n = 41) or severely (n = 14) prolonged QTc-interval before haloperidol, 48.8 % and 42.9 % respectively had a follow-up electrocardiogram. In patients with a risk score ≥4, significantly more electrocardiograms were taken before starting haloperidol (p = 0.020). Although many patients had risk factors for QTc-prolongation (including the use of other QTc-prolonging drugs) or had a prolonged QTc on a baseline electrocardiogram, follow-up safety measures were limited. Persistent efforts should be taken to develop decision support systems to manage this risk.

The effects of prolonged oral administration of the disinfectant calcium hypochlorite in Nigerian commercial cockerels

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Temitayo O. Iji

2013-11-01

Full Text Available This study was designed to investigate the effects of prolonged oral administration of calcium hypochlorite in the drinking water of commercial cockerels. It was carried out in order to ascertain probable toxicity associated with prolonged exposure to calcium hypochlorite. Thirty-two healthy birds were used; they were grouped into four groups of eight. Group 1, which served as the control, received 10 mL/kg body weight of physiological saline. Groups 2, 3 and 4 received 0.0375 g, 0.375 g and 0.75 g of calcium hypochlorite per 10 litres of drinking water for six weeks respectively. Six weeks after the administration of calcium hypochlorite, blood was collected from the jugular vein to assess liver function, lipid profiles and for markers of oxidative stress. The results revealed a significant (p < 0.05 increase in alanine aminotransferase activity in a dose-dependent manner when compared with the control. Also, there was a significant (p < 0.05 increase in aspartate aminotransferase and alkaline phosphatase activity. Similarly, there was a significant (p < 0.05 increase in total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein levels compared with the control. There was a significant increase in malondialdehyde and hydrogen peroxide generation with a concomitant significant (p < 0.05 decrease in serum glutathione level in a dose-dependent manner when compared with the control. In this study, calcium hypochloriteinduced hepatic damage via oxidative stress and decrease in antioxidant defense system was found. Therefore, prolonged exposure of chickens to calcium hypochlorite is potentially harmful.

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

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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.

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

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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.

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

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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.

Prolonged menstrual cycles in female workers exposed to ethylene glycol ethers in the semiconductor manufacturing industry.

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Hsieh, G-Y; Wang, J-D; Cheng, T-J; Chen, P-C

2005-08-01

It has been shown that female workers exposed to ethylene glycol ethers (EGEs) in the semiconductor industry have higher risks of spontaneous abortion, subfertility, and menstrual disturbances, and prolonged waiting time to pregnancy. To examine whether EGEs or other chemicals are associated with long menstrual cycles in female workers in the semiconductor manufacturing industry. Cross-sectional questionnaire survey during the annual health examination at a wafer manufacturing company in Taiwan in 1997. A three tiered exposure-assessment strategy was used to analyse the risk. A short menstrual cycle was defined to be a cycle less than 24 days and a long cycle to be more than 35 days. There were 606 valid questionnaires from 473 workers in fabrication jobs and 133 in non-fabrication areas. Long menstrual cycles were associated with workers in fabrication areas compared to those in non-fabrication areas. Using workers in non-fabrication areas as referents, workers in photolithography and diffusion areas had higher risks for long menstrual cycles. Workers exposed to EGEs and isopropanol, and hydrofluoric acid, isopropanol, and phosphorous compounds also showed increased risks of a long menstrual cycle. Exposure to multiple chemicals, including EGEs in photolithography, might be associated with long menstrual cycles, and may play an important role in a prolonged time to pregnancy in the wafer manufacturing industry; however, the prevalence in the design, possible exposure misclassification, and chance should be considered.

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.

[Brain function recovery after prolonged posttraumatic coma].

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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.

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.

[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.

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...

The impact of prolonged violent video-gaming on adolescent sleep: an experimental study.

Science.gov (United States)

King, Daniel L; Gradisar, Michael; Drummond, Aaron; Lovato, Nicole; Wessel, Jason; Micic, Gorica; Douglas, Paul; Delfabbro, Paul

2013-04-01

Video-gaming is an increasingly prevalent activity among children and adolescents that is known to influence several areas of emotional, cognitive and behavioural functioning. Currently there is insufficient experimental evidence about how extended video-game play may affect adolescents' sleep. The aim of this study was to investigate the short-term impact of adolescents' prolonged exposure to violent video-gaming on sleep. Seventeen male adolescents (mean age = 16 ± 1 years) with no current sleep difficulties played a novel, fast-paced, violent video-game (50 or 150 min) before their usual bedtime on two different testing nights in a sleep laboratory. Objective (polysomnography-measured sleep and heart rate) and subjective (single-night sleep diary) measures were obtained to assess the arousing effects of prolonged gaming. Compared with regular gaming, prolonged gaming produced decreases in objective sleep efficiency (by 7 ± 2%, falling below 85%) and total sleep time (by 27 ± 12 min) that was contributed by a near-moderate reduction in rapid eye movement sleep (Cohen's d = 0.48). Subjective sleep-onset latency significantly increased by 17 ± 8 min, and there was a moderate reduction in self-reported sleep quality after prolonged gaming (Cohen's d = 0.53). Heart rate did not differ significantly between video-gaming conditions during pre-sleep game-play or the sleep-onset phase. Results provide evidence that prolonged video-gaming may cause clinically significant disruption to adolescent sleep, even when sleep after video-gaming is initiated at normal bedtime. However, physiological arousal may not necessarily be the mechanism by which technology use affects sleep. © 2012 European Sleep Research Society.

Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol

DEFF Research Database (Denmark)

Baandrup, Lone; Fagerlund, Birgitte; Jennum, Poul

2011-01-01

Treatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged...

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.

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.

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.)

Aminoglycoside exposure and renal function before lung transplantation in adult cystic fibrosis patients.

Science.gov (United States)

Novel-Catin, Etienne; Pelletier, Solenne; Reynaud, Quitterie; Nove-Josserand, Raphaele; Durupt, Stephane; Dubourg, Laurence; Durieu, Isabelle; Fouque, Denis

2018-04-18

Patients with cystic fibrosis (CF) are at risk of kidney injury even before undergoing lung transplantation, because of prolonged exposure to aminoglycosides (AGs), chronic dehydration and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR), such as Cockcroft-Gault and Modification of Diet in Renal Disease, are not adapted to the CF population due to patients' low body weight and reduced muscle mass. The aim of this study was to precisely measure GFR in adult CF patients and to see whether repeated AG treatment would impair renal function before lung transplantation. Inulin or iohexol clearances were performed in 25 adult CF patients when they entered the lung transplant waiting list. No patient was treated with AGs at the time of GFR measurement. Body mass index (BMI), history of diabetes mellitus and blood pressure were recorded. Exposure to intravenous (IV) AGs within 5 years prior to the GFR measurement was obtained from the patient's medical files. Urine samples were collected to check for albuminuria and proteinuria. The population was predominantly female (67%). The mean age was 32 years, the mean BMI was 19 kg/m2 and 28% had CF-related diabetes. Median exposure to IV AG within 5 years before GFR measurement was 155 days with a mean dosage of 7.7mg/kg/day. The mean measured GFR was 106 mL/min/1.73 m2 and the mean estimated GFR according to the Chronic Kidney Disease Epidemiology Collaboration formula was 124 mL/min/1.73 m2. Despite prolonged exposure to high-dose IV AG, no decline in GFR was observed in these patients.

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.

Effect of winter-chilling treatment on flower bud induction in young pomelo trees

International Nuclear Information System (INIS)

Nakajima, Y.; Susanto, S.; Hasegawa, K.

1992-01-01

Two-year-old potted 'Tosa Buntan' pomelo (Citrus grandis (L.) Osbeck) trees on trifoliate orange (Poncirus trifoliata Raf.) rootstock grown in a plastic house were used in this study. The temperature of the plastic house was maintained at a maximum of 20°C during the day and 10°C minimum at night from November 1990 to mid-February 1991. On December 1990, a set of potted trees was transferred to each growth chamber which was kept at day/night temperature of 15°/5°C and 10°/10°C. A subgroup of these trees was exposed to these condition for 15, 30, 45, 60, and 75 days and then transferred to another growth chamber maintained at 30°/25°C (day/night). On 1 December 1990, 15 January, and 15 February 1991, a set of potted trees was transferred directly without chilling from the plastic house to the 30°/25°C growth chamber. No trees sprouted during the low temperature treatments. New buds sprouted early and more buds sprouted during subsequent exposure to 30°/25°C treatment as the low temperature was prolonged. The number of new shoots for 75-day exposure was greater at 15°/5°C than it was at 10°/10°C regimen and those kept in the plastic house. The number of inflorescences, flower buds, and flowers increased for the 60-day and over exposures, but very few flowers developed after a 15- or 30-day exposure. The numbers of flower buds and flowers per node were 2.27 and 2.05, respectively, for a 75-day exposure under the 15°/5°C regimen, whereas they were 0.81 and 0.76, respectively, in the 10°/10°C regimen. Sugar and carbohydrate contents in leaves increased while the N content decreased under prolonged low temperature treatments. (author)

Effect of winter-chilling treatment on flower bud induction in young pomelo trees

Energy Technology Data Exchange (ETDEWEB)

Nakajima, Y. [Kochi Univ., Nankoku (Japan); Susanto, S.; Hasegawa, K.

1992-09-15

Two-year-old potted 'Tosa Buntan' pomelo (Citrus grandis (L.) Osbeck) trees on trifoliate orange (Poncirus trifoliata Raf.) rootstock grown in a plastic house were used in this study. The temperature of the plastic house was maintained at a maximum of 20°C during the day and 10°C minimum at night from November 1990 to mid-February 1991. On December 1990, a set of potted trees was transferred to each growth chamber which was kept at day/night temperature of 15°/5°C and 10°/10°C. A subgroup of these trees was exposed to these condition for 15, 30, 45, 60, and 75 days and then transferred to another growth chamber maintained at 30°/25°C (day/night). On 1 December 1990, 15 January, and 15 February 1991, a set of potted trees was transferred directly without chilling from the plastic house to the 30°/25°C growth chamber. No trees sprouted during the low temperature treatments. New buds sprouted early and more buds sprouted during subsequent exposure to 30°/25°C treatment as the low temperature was prolonged. The number of new shoots for 75-day exposure was greater at 15°/5°C than it was at 10°/10°C regimen and those kept in the plastic house. The number of inflorescences, flower buds, and flowers increased for the 60-day and over exposures, but very few flowers developed after a 15- or 30-day exposure. The numbers of flower buds and flowers per node were 2.27 and 2.05, respectively, for a 75-day exposure under the 15°/5°C regimen, whereas they were 0.81 and 0.76, respectively, in the 10°/10°C regimen. Sugar and carbohydrate contents in leaves increased while the N content decreased under prolonged low temperature treatments. (author)

Specific features of the hemorrhagic syndrome manifestation under chronic, prolonged and acute irradiation

International Nuclear Information System (INIS)

Arlashchenko, N.I.; Gorlov, V.G.; Maksimova, E.N.

1978-01-01

To make the hemorrhagic syndrome manifest itself, two phenomena are necessary to coincide in time, they are: a fall in the elasticity of the vascular wall and reduction in the amount of thrombocytes in blood. Depending upon the radiation dose, the vascular wall and the thrombocytic function may be either simultaneously impaired after acute exposure) or dissociated (following prolonged irradiation). Chronic irradiation at small (subliminal) dose rates fails to induce hemorrhagic disorders and death of rats caused by pathologic hemophilia

What prolongs a butterfly's life?: Trade-offs between dormancy, fecundity and body size.

Directory of Open Access Journals (Sweden)

Elena Haeler

Full Text Available In butterflies, life span often increases only at the expense of fecundity. Prolonged life span, on the other hand, provides more opportunities for oviposition. Here, we studied the association between life span and summer dormancy in two closely related species of Palearctic Meadow Brown butterflies, the endemic Maniola nurag and the widespread M. jurtina, from two climatic provenances, a Mediterranean and a Central European site, and tested the relationships between longevity, body size and fecundity. We experimentally induced summer dormancy and hence prolonged the butterflies' life in order to study the effects of such a prolonged life. We were able to modulate longevity only in Mediterranean females by rearing them under summer photoperiodic conditions (light 16 h : dark 8 h, thereby more than doubling their natural life span, to up to 246 days. Central European individuals kept their natural average live span under all treatments, as did Mediterranean individuals under autumn treatment (light 11: dark 13. Body size only had a significant effect in the smaller species, M. nurag, where it affected the duration of dormancy and lifetime fecundity. In the larger species, M. jurtina, a prolonged adult life span did, surprisingly, not convey any fecundity loss. In M. nurag, which generally deposited fewer eggs, extended life had a fecundity cost. We conclude that Mediterranen M. jurtina butterflies have an extraordinary plasticity in aging which allows them to extend life span in response to adverse environmental conditions and relieve the time limitation on egg-laying while maintaining egg production at equal levels.

Deciding about treatments that prolong life

Science.gov (United States)

... 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: ...

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

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.

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.

Life Threatening Severe QTc Prolongation in Patient with Systemic Lupus Erythematosus due to Hydroxychloroquine

Directory of Open Access Journals (Sweden)

John P. O’Laughlin

2016-01-01

Full Text Available We present a case of a syncopal episode resulting from significant QT interval prolongation in a patient on hydroxychloroquine for the treatment of systemic lupus erythematosus and end stage renal disease. The patient had been treated with hydroxychloroquine for two years prior to presentation. After thorough workup for secondary causes of QT interval prolongation hydroxychloroquine was discontinued and the patient’s QT interval shortened. The patient was treated with mexiletine to prevent sudden ventricular arrhythmias, which was unique compared to other documented cases in which lidocaine was used. The patient was noted to have mild prolongation of the QT interval on electrocardiogram prior to initiation of hydroxychloroquine therapy which was exacerbated by its use and may have been caused due to toxicity from underlying renal failure.

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...

Chemical pleurodesis for prolonged postoperative air leak in primary spontaneous pneumothorax.

Science.gov (United States)

How, Cheng-Hung; Tsai, Tung-Ming; Kuo, Shuenn-Wen; Huang, Pei-Ming; Hsu, Hsao-Hsun; Lee, Jang-Ming; Chen, Jin-Shing; Lai, Hong-Shiee

2014-05-01

Prolonged air leak is the most common complication after thoracoscopic operation for primary spontaneous pneumothorax (PSP), and the role of chemical pleurodesis in treating air leaks remains unclear. This study evaluated the safety and efficacy of chemical pleurodesis with a comparison between minocycline and OK-432. Between 1994 and 2011, 1083 PSP patients were treated by thoracoscopic operation. After the operation, patients with persistent air leak for 3 days or more were managed by minocycline or OK-432 pleurodesis. The demographic and outcome data for these patients were collected by retrospective chart review. Seventy-nine patients (7.3%) with prolonged air leak after thoracoscopy underwent minocycline pleurodesis (60 patients) or OK-432 pleurodesis (19 patients) as the primary treatment. The primary success rate was 63% (38/60) for minocycline pleurodesis and 95% (18/19) for OK-432 pleurodesis (p = 0.009). Postpleurodesis pain was common and comparable between the two groups. No major complications were noted after a total of 121 treatments. Patients undergoing primary OK-432 pleurodesis had shorter durations of postpleurodesis chest drainage (mean 8.5 vs. 2.3 days; p < 0.001) and postoperative hospital stay (mean 11.9 vs. 6.8 days; p < 0.001) than those undergoing primary minocycline pleurodesis. After a median follow-up of 16 months, recurrence was noted in one patient in the OK-432 group and none in the minocycline group. Long-term pulmonary function in the two groups was comparable. 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. Copyright © 2013. Published by Elsevier B.V.

Characterizing prolonged heat effects on mortality in a sub-tropical high-density city, Hong Kong

Science.gov (United States)

Ho, Hung Chak; Lau, Kevin Ka-Lun; Ren, Chao; Ng, Edward

2017-11-01

Extreme hot weather events are likely to increase under future climate change, and it is exacerbated in urban areas due to the complex urban settings. It causes excess mortality due to prolonged exposure to such extreme heat. However, there is lack of universal definition of prolonged heat or heat wave, which leads to inadequacies of associated risk preparedness. Previous studies focused on estimating temperature-mortality relationship based on temperature thresholds for assessing heat-related health risks but only several studies investigated the association between types of prolonged heat and excess mortality. However, most studies focused on one or a few isolated heat waves, which cannot demonstrate typical scenarios that population has experienced. In addition, there are limited studies on the difference between daytime and nighttime temperature, resulting in insufficiency to conclude the effect of prolonged heat. In sub-tropical high-density cities where prolonged heat is common in summer, it is important to obtain a comprehensive understanding of prolonged heat for a complete assessment of heat-related health risks. In this study, six types of prolonged heat were examined by using a time-stratified analysis. We found that more consecutive hot nights contribute to higher mortality risk while the number of consecutive hot days does not have significant association with excess mortality. For a day after five consecutive hot nights, there were 7.99% [7.64%, 8.35%], 7.74% [6.93%, 8.55%], and 8.14% [7.38%, 8.88%] increases in all-cause, cardiovascular, and respiratory mortality, respectively. Non-consecutive hot days or nights are also found to contribute to short-term mortality risk. For a 7-day-period with at least five non-consecutive hot days and nights, there was 15.61% [14.52%, 16.70%] increase in all-cause mortality at lag 0-1, but only -2.00% [-2.83%, -1.17%] at lag 2-3. Differences in the temperature-mortality relationship caused by hot days and hot nights

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.

High level of oxygen treatment causes cardiotoxicity with arrhythmias and redox modulation

Energy Technology Data Exchange (ETDEWEB)

Chapalamadugu, Kalyan C.; Panguluri, Siva K. [Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL (United States); Bennett, Eric S. [Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL (United States); Kolliputi, Narasaiah [Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (United States); Tipparaju, Srinivas M., E-mail: stippara@health.usf.edu [Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL (United States)

2015-01-01

Hyperoxia exposure in mice leads to cardiac hypertrophy and voltage-gated potassium (Kv) channel remodeling. Because redox balance of pyridine nucleotides affects Kv function and hyperoxia alters cellular redox potential, we hypothesized that hyperoxia exposure leads to cardiac ion channel disturbances and redox changes resulting in arrhythmias. In the present study, we investigated the electrical changes and redox abnormalities caused by 72 h hyperoxia treatment in mice. Cardiac repolarization changes were assessed by acquiring electrocardiogram (ECG) and cardiac action potentials (AP). Biochemical assays were employed to identify the pyridine nucleotide changes, Kv1.5 expression and myocardial injury. Hyperoxia treatment caused marked bradycardia, arrhythmia and significantly prolonged (ms) the, RR (186.2 ± 10.7 vs. 146.4 ± 6.2), PR (46.8 ± 3.1 vs. 39.3 ± 1.6), QRS (10.8 ± 0.6 vs. 8.5 ± 0.2), QTc (57.1 ± 3.5 vs. 40 ± 1.4) and JT (13.4 ± 2.1 vs. 7.0 ± 0.5) intervals, when compared with normoxia group. Hyperoxia treatment also induced significant increase in cardiac action potential duration (APD) (ex-APD{sub 90}; 73.8 ± 9.5 vs. 50.9 ± 3.1 ms) and elevated levels of serum markers of myocardial injury; cardiac troponin I (TnI) and lactate dehydrogenase (LDH). Hyperoxia exposure altered cardiac levels of mRNA/protein expression of; Kv1.5, Kvβ subunits and SiRT1, and increased ratios of reduced pyridine nucleotides (NADH/NAD and NADPH/NADP). Inhibition of SiRT1 in H9C2 cells using Splitomicin resulted in decreased SiRT1 and Kv1.5 expression, suggesting that SiRT1 may mediate Kv1.5 downregulation. In conclusion, the cardiotoxic effects of hyperoxia exposure involve ion channel disturbances and redox changes resulting in arrhythmias. - Highlights: • Hyperoxia treatment leads to arrhythmia with prolonged QTc and action potential duration. • Hyperoxia treatment alters cardiac pyridine nucleotide [NAD(P)H/NAD(P)] levels. • SiRT1 and Kv1.5 are co

High level of oxygen treatment causes cardiotoxicity with arrhythmias and redox modulation

International Nuclear Information System (INIS)

Chapalamadugu, Kalyan C.; Panguluri, Siva K.; Bennett, Eric S.; Kolliputi, Narasaiah; Tipparaju, Srinivas M.

2015-01-01

Hyperoxia exposure in mice leads to cardiac hypertrophy and voltage-gated potassium (Kv) channel remodeling. Because redox balance of pyridine nucleotides affects Kv function and hyperoxia alters cellular redox potential, we hypothesized that hyperoxia exposure leads to cardiac ion channel disturbances and redox changes resulting in arrhythmias. In the present study, we investigated the electrical changes and redox abnormalities caused by 72 h hyperoxia treatment in mice. Cardiac repolarization changes were assessed by acquiring electrocardiogram (ECG) and cardiac action potentials (AP). Biochemical assays were employed to identify the pyridine nucleotide changes, Kv1.5 expression and myocardial injury. Hyperoxia treatment caused marked bradycardia, arrhythmia and significantly prolonged (ms) the, RR (186.2 ± 10.7 vs. 146.4 ± 6.2), PR (46.8 ± 3.1 vs. 39.3 ± 1.6), QRS (10.8 ± 0.6 vs. 8.5 ± 0.2), QTc (57.1 ± 3.5 vs. 40 ± 1.4) and JT (13.4 ± 2.1 vs. 7.0 ± 0.5) intervals, when compared with normoxia group. Hyperoxia treatment also induced significant increase in cardiac action potential duration (APD) (ex-APD 90 ; 73.8 ± 9.5 vs. 50.9 ± 3.1 ms) and elevated levels of serum markers of myocardial injury; cardiac troponin I (TnI) and lactate dehydrogenase (LDH). Hyperoxia exposure altered cardiac levels of mRNA/protein expression of; Kv1.5, Kvβ subunits and SiRT1, and increased ratios of reduced pyridine nucleotides (NADH/NAD and NADPH/NADP). Inhibition of SiRT1 in H9C2 cells using Splitomicin resulted in decreased SiRT1 and Kv1.5 expression, suggesting that SiRT1 may mediate Kv1.5 downregulation. In conclusion, the cardiotoxic effects of hyperoxia exposure involve ion channel disturbances and redox changes resulting in arrhythmias. - Highlights: • Hyperoxia treatment leads to arrhythmia with prolonged QTc and action potential duration. • Hyperoxia treatment alters cardiac pyridine nucleotide [NAD(P)H/NAD(P)] levels. • SiRT1 and Kv1.5 are co-regulated in

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....

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

Surgery for subacromial impingement syndrome in relation to intensities of occupational mechanical exposures across 10-year exposure time windows

DEFF Research Database (Denmark)

Dalbøge, Annett; Frost, Poul; Andersen, Johan Hviid

2018-01-01

OBJECTIVES: We aimed to identify intensities of occupational mechanical exposures (force, arm elevation and repetition) that do not entail an increased risk of surgery for subacromial impingement syndrome (SIS) even after prolonged durations of exposure. Additionally, we wanted to evaluate...... if exposure to hand-arm vibration (HAV) is an independent risk factor. METHODS: We used data from a register-based cohort study of the entire Danish working population (n=2 374 403). During follow-up (2003-2008), 14 118 first-time events of surgery for SIS occurred. For each person, we linked register...... of exposure at specific intensities above minimal (low, medium and high). We used a logistic regression technique equivalent to discrete survival analysis adjusting for cumulative effects of other mechanical exposures. RESULTS: We found indications of safe exposure intensities for repetition (median angular...

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

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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

Maintenance of drug metabolism and transport functions in human precision-cut liver slices during prolonged incubation for 5 days

NARCIS (Netherlands)

Starokozhko, Viktoriia; Vatakuti, Suresh; Schievink, Bauke; Merema, Marjolijn T.; Asplund, Annika; Synnergren, Jane; Aspegren, Anders; Groothuis, Geny M. M.

Human precision-cut liver slices (hPCLS) are a valuable ex vivo model that can be used in acute toxicity studies. However, a rapid decline in metabolic enzyme activity limits their use in studies that require a prolonged xenobiotic exposure. The aim of the study was to extend the viability and

[Treatment of hyperthyroidism with radioiodine during hemodialysis: Report of one case].

Science.gov (United States)

Hurtado, Claudia; Báez, María Soledad; Bate, Anabel; Opazo, Claudio; Troncoso, Mauricio

2017-05-01

Although radioiodine (131-I) can be used as treatment of hyperthyroidism for patients in hemodialysis, its use is limited and the experience is mainly related to differentiated thyroid carcinoma. We report a 58 years old female on hemodialysis with recurrent hyperthyroidism after propylthiouracil treatment. She was successfully treated with 131-I and four months after the intervention her euthyroid state was confirmed. We measured 131-I activity in blood, dialysate liquid and other waste products, as well as patient radiation exposure rates. We found that 131-I elimination was prolonged through time with no major dependence on hemodialysis, as opposed to the elimination of 131-I in patients with thyroid carcinoma. This was probably due to high radiotracer uptake in hyper functioning thyroid tissue. Conversely, radiation content in dialysate wastes or equipment was minimal. Furthermore, the rate of both environmental exposure and exposure of nursing staff in charge of hemodialysis sessions, was minimal and met international security standards. In conclusion, I-131 therapy showed both appropriate effectiveness and safety in this case and may be considered as a suitable treatment alternative to thyroidectomy when antithyroid drugs are unsuccessful.

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

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

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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.

Lung morphometry, collagen and elastin content: changes after hyperoxic exposure in preterm rabbits

Directory of Open Access Journals (Sweden)

Renata Suman Mascaretti

2009-11-01

Full Text Available INTRODUCTION: Elastic and collagen fiber deposition increases throughout normal lung development, and this fiber network significantly changes when development of the lung is disturbed. In preterm rats and lambs, prolonged hyperoxic exposure is associated with impaired alveolization and causes significant changes in the deposition and structure of elastic fibers. OBJECTIVES: To evaluate the effects of hyperoxic exposure on elastic and collagen fiber deposition in the lung interstitial matrix and in alveolarization in preterm rabbits. METHODS: After c-section, 28-day preterm New-Zealand-White rabbits were randomized into 2 study groups, according to the oxygen exposure, namely: Room air (oxygen = 21% or Oxygen (oxygen > 95%. The animals were killed on day 11 and their lungs were analyzed for the alveolar size (Lm, the internal surface area (ISA, the alveoli number, and the density and distribution of collagen and elastic fibers. RESULTS: An increase in the Lm and a decrease in the alveoli number were observed among rabbits that were exposed to hyperoxia with no differences regarding the ISA. No difference in the density of elastic fibers was observed after oxygen exposure, however there were fewer collagen fibers and an evident disorganization of fiber deposition. DISCUSSION: This model reproduces anatomo-pathological injuries representing the arrest of normal alveolar development and lung architecture disorganization by just a prolonged exposition to oxygen. CONCLUSIONS: In the preterm rabbit, prolonged oxygen exposure impaired alveolization and also lowered the proportion of collagen fibers, with an evident fiber network disorganization.

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...

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

[Beta lactam antibiotics and the question of dose regimen for severe infection. Prolonged infusion theoretically appealing--yet no evidence of clinical benefit].

Science.gov (United States)

Leander, Gunilla; Eliasson, Erik; Hanberger, Håkan; Giske, Christian

2015-03-24

Patients with severe sepsis/septic shock have a high mortality. Beta-lactam antibiotics are normally first line treatment. This antimicrobial class has been associated with time-dependent efficacy. It is therefore plausible that administration as prolonged infusion will increase the therapeutic effect, as compared to short term bolus injections, which is the most common practice today. We have reviewed 14 randomized controlled studies to investigate whether prolonged infusion provides lower mortality and/or increased clinical cure. In summary, convincing advantages with prolonged infusion could not be found, however randomized studies are heterogeneous, and it cannot be excluded that some subgroups of critically ill patients could benefit from such treatment.

Evaluation of Sphingolipids in Wistar Rats Treated to Prolonged and Single Oral Doses of Fumonisin B1

Science.gov (United States)

Direito, Glória M.; Almeida, Adriana P.; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

2009-01-01

The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B1 (FB1). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB1. Prolonged exposure to FB1 caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB1. Animals receiving a single dose of FB1 presented variations in Sa and So levels and in the Sa/So ratio. PMID:19333435

Prolonged grief: where to after Diagnostic and Statistical Manual of Mental Disorders, 5th Edition?

Science.gov (United States)

Bryant, Richard A

2014-01-01

Although there is much evidence for the construct of prolonged grief, there was much controversy over the proposal to introduce a prolonged grief diagnosis into Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), and it was finally rejected as a diagnosis in DSM-5. This review outlines the evidence for and against the diagnosis, and highlights the implications of the DSM-5 decision. Convergent evidence indicates that prolonged grief characterized by persistently severe yearning for the deceased is a distinct construct from bereavement-related depression and anxiety, is associated with marked functional impairment, is responsive to targeted treatments for prolonged grief, and has been validated across different cultures, age groups, and types of bereavement. Although DSM-5 has rejected the construct as a formal diagnosis, evidence continues to emerge on related mechanisms, including maladaptive appraisals, memory and attentional processes, immunological and arousal responses, and neural circuitry. It is most likely that the International Classification of Diseases (ICD-11) will introduce a diagnosis to recognize prolonged grief, even though DSM-5 has decided against this option. It is probable that the DSM-5 decision may result in more prolonged grief patients being incorrectly diagnosed with depression after bereavement and possibly incorrectly treated. The DSM-5 decision is unlikely to impact on future research agendas.

Prolonged antibiotics for non-cystic fibrosis bronchiectasis in children and adults.

Science.gov (United States)

Hnin, Khin; Nguyen, Chau; Carson, Kristin V; Evans, David J; Greenstone, Michael; Smith, Brian J

2015-08-13

The vicious cycle hypothesis for bronchiectasis predicts that bacterial colonisation of the respiratory tract perpetuates inflammatory change. This damages the mucociliary escalator, preventing bacterial clearance and allowing persistence of pro-inflammatory mediators. Conventional treatment with physiotherapy and intermittent antibiotics is believed to improve the condition of people with bronchiectasis, although no conclusive data show that these interventions influence the natural history of the condition. Various strategies have been tried to interrupt this cycle of infection and inflammation, including prolonging antibiotic treatment with the goal of allowing the airway mucosa to heal. To determine the benefits of prolonged antibiotic therapy in the treatment of patients with bronchiectasis. We searched the Cochrane Airways Group Trials Register and reference lists of identified articles. Searches were current as of February 2014. Randomised trials examining the use of prolonged antibiotic therapy (for four or more weeks) in the treatment of bronchiectasis compared with placebo or usual care. Two review authors independently assessed trial quality and extracted data. We contacted study authors to ask for missing information. Eighteen trials met the inclusion criteria, randomly assigning a total of 1157 participants. Antibiotics were given for between four weeks and 83 weeks. Limited meta-analysis was possible because of the diversity of outcomes reported in these trials. Based on the number of participants with at least one exacerbation, the meta-analysis showed significant effects in favour of the intervention (odds ratio (OR) 0.31, 95% confidence interval (CI) 0.19 to 0.52; P value antibiotics with a moderate quality grade of supporting evidence (37 per 1000 in the intervention arm (95% CI 13 to 96) and 87 per 1000 in control (OR 0.40, 95% CI 0.14 to 1.11; P value = 0.08). Drug resistance developed in 36 of 220 participants taking antibiotics compared with

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

Prolonged pain and disability are common after rib fractures.

Science.gov (United States)

Fabricant, Loic; Ham, Bruce; Mullins, Richard; Mayberry, John

2013-05-01

The contribution of rib fractures to prolonged pain and disability may be underappreciated and undertreated. Clinicians are traditionally taught that the pain and disability of rib fractures resolves in 6 to 8 weeks. This study was a prospective observation of 203 patients with rib fractures at a level 1 trauma center. Chest wall pain was evaluated by the McGill Pain Questionnaire (MPQ) pain rating index (PRI) and present pain intensity (PPI). Prolonged pain was defined as a PRI of 8 or more at 2 months after injury. Prolonged disability was defined as a decrease in 1 or more levels of work or functional status at 2 months after injury. Predictors of prolonged pain and disability were determined by multivariate analysis. One hundred forty-five male patients and 58 female patients with a mean injury severity score (ISS) of 20 (range, 1 to 59) had a mean of 5.4 rib fractures (range, 1 to 29). Forty-four (22%) patients had bilateral fractures, 15 (7%) had flail chest, and 92 (45%) had associated injury. One hundred eighty-seven patients were followed 2 months or more. One hundred ten (59%) patients had prolonged chest wall pain and 142 (76%) had prolonged disability. Among 111 patients with isolated rib fractures, 67 (64%) had prolonged chest wall pain and 69 (66%) had prolonged disability. MPQ PPI was predictive of prolonged pain (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.4 to 2.5), and prolonged disability (OR, 2.2; 95% CI, 1.5 to 3.4). The presence of significant associated injuries was predictive of prolonged disability (OR, 5.9; 95% CI, 1.4 to 29). Prolonged chest wall pain is common, and the contribution of rib fractures to disability is greater than traditionally expected. Further investigation into more effective therapies that prevent prolonged pain and disability after rib fractures is needed. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Significant prolongation of hamster liver transplant survival in Lewis rats by total-lymphoid irradiation, cyclosporine, and splenectomy

International Nuclear Information System (INIS)

Yamaguchi, Y.; Halperin, E.C.; Harland, R.C.; Wyble, C.; Bollinger, R.R.

1990-01-01

The effects of total lymphoid irradiation, cyclosporine and splenectomy alone and in combination have been studied in liver transplants from the LVG hamster to the LEW rat. Neither CsA alone, splenectomy alone, nor TLI alone prolonged graft survival. CsA/splenectomy and TLI/CsA produced significant prolongation of graft survival. TLI/CsA/splenectomy prolonged graft survival by over sixfold compared with controls. While CsA alone was ineffective in reducing lymphocytotoxic antidonor antibody, splenectomy alone or CsA/splenectomy did significantly suppress production of antibody. Only very low levels of antibody could be detected in animals treated with TLI/CsA/splenectomy. TLI/CsA/splenectomy has an immunosuppressive effect sufficient to significantly prolong liver graft survival in the LVG hamster to LEW rat combination and may represent a promising treatment protocol in experimental cross-species transplantation

[Prolonged desensitization pretreatment for in vitro fertilization in women with polycystic ovary].

Science.gov (United States)

Kuczyński, W; Czech, R; Redźko, S; Wasilewski, T; Mrugacz, G; Wołczyński, S; Pietrewicz, P; Grochowski, D; Szamatowicz, M

2000-09-01

To analyse the outcome of intracytoplasmic sperm injection (ICSI) in women with severe polycystic ovary disease (PCD), stimulated after prolonged pituitary desensitization in comparison with regular long protocol therapy. The results of controlled ovarian hyperstimulation (COH), fertilization rate, early embryo development parameters and clinical pregnancy rates were compared depending on the duration of pituitary desensitization before gonadotropin administration. A total of 60 patients with severe PCOD were desensitized with GnRH agonist up to 30 days before COH. The results were compared with the group of 213 patients with mild PCOD treated with regular long protocol (control). We observed a slightly higher rate of mature oocytes MII as well as the number of embryos obtained in the control group, however the pregnancy rate in the group with prolonged desensitization was significantly higher (50%) in comparison to the control group (33.8%). The prolonged pituitary desensitization before controlled ovarian hyperstimulation gives better chance for obtaining pregnancy in patients with severe PCOD. It could be recommended facing previous treatment failure.

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

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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.

Inhaled hyaluronic acid microparticles extended pulmonary retention and suppressed systemic exposure of a short-acting bronchodilator

DEFF Research Database (Denmark)

Li, Ying; Han, Meihua; Liu, Tingting

2017-01-01

The aim of this study was to investigate the feasibility of using hyaluronic acid (HA), a biomucoadhesive carbohydrate polymer to prolong the pulmonary retention and reduce the systemic exposure of inhaled medicine. Salbutamol sulphate (SAS), a model bronchodilator, was co-spray dried with HA...... to spray-dried plain SAS powders, the SAS-loaded HA microparticles possessed enhanced biomucoadhesive property in vitro and had much longer pulmonary retention and reduced systemic exposure in vivo. By incorporation, the pulmonary retention time of SAS was prolonged from 2h to 8h while the maximum...

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.

Safety and Efficacy of BAY 94-9027, a Prolonged-Half-Life Factor VIII

DEFF Research Database (Denmark)

Reding, M T; Ng, H J; Poulsen, Lone Hvitfeldt

2017-01-01

BACKGROUND: BAY 94-9027 is a B-domain-deleted prolonged-half-life recombinant factor VIII (FVIII) conjugates in a site-specific manner with polyethylene glycol. OBJECTIVE: Assess efficacy and safety of BAY 94-9027 for prophylaxis and treatment of bleeds in patients with severe hemophilia A PATIEN...

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.)

In vivo assessment of catheter positioning accuracy and prolonged irradiation time on liver tolerance dose after single-fraction 192Ir high-dose-rate brachytherapy

Directory of Open Access Journals (Sweden)

Kropf Siegfried

2011-09-01

Full Text Available Abstract Background To assess brachytherapy catheter positioning accuracy and to evaluate the effects of prolonged irradiation time on the tolerance dose of normal liver parenchyma following single-fraction irradiation with 192 Ir. Materials and methods Fifty patients with 76 malignant liver tumors treated by computed tomography (CT-guided high-dose-rate brachytherapy (HDR-BT were included in the study. The prescribed radiation dose was delivered by 1 - 11 catheters with exposure times in the range of 844 - 4432 seconds. Magnetic resonance imaging (MRI datasets for assessing irradiation effects on normal liver tissue, edema, and hepatocyte dysfunction, obtained 6 and 12 weeks after HDR-BT, were merged with 3D dosimetry data. The isodose of the treatment plan covering the same volume as the irradiation effect was taken as a surrogate for the liver tissue tolerance dose. Catheter positioning accuracy was assessed by calculating the shift between the 3D center coordinates of the irradiation effect volume and the tolerance dose volume for 38 irradiation effects in 30 patients induced by catheters implanted in nearly parallel arrangement. Effects of prolonged irradiation were assessed in areas where the irradiation effect volume and tolerance dose volume did not overlap (mismatch areas by using a catheter contribution index. This index was calculated for 48 irradiation effects induced by at least two catheters in 44 patients. Results Positioning accuracy of the brachytherapy catheters was 5-6 mm. The orthogonal and axial shifts between the center coordinates of the irradiation effect volume and the tolerance dose volume in relation to the direction vector of catheter implantation were highly correlated and in first approximation identically in the T1-w and T2-w MRI sequences (p = 0.003 and p p = 0.001 and p = 0.004, respectively. There was a significant shift of the irradiation effect towards the catheter entry site compared with the planned dose

Near Infrared Photoimmunotherapy with Combined Exposure of External and Interstitial Light Sources.

Science.gov (United States)

Maruoka, Yasuhiro; Nagaya, Tadanobu; Sato, Kazuhide; Ogata, Fusa; Okuyama, Shuhei; Choyke, Peter L; Kobayashi, Hisataka

2018-02-21

Near infrared photoimmunotherapy (NIR-PIT) is a new target-cell-specific cancer treatment that induces highly selective necrotic/immunogenic cell death after systemic administration of a photoabsorber antibody conjugate and subsequent NIR light exposure. However, the depth of NIR light penetration in tissue (approximately 2 cm) with external light sources limits the therapeutic effects of NIR-PIT. Interstitial light exposure using cylindrical diffusing optical fibers can overcome this limitation. The purpose in this study was to compare three NIR light delivery methods for treating tumors with NIR-PIT using a NIR laser system at an identical light energy; external exposure alone, interstitial exposure alone, and the combination. Panitumumab conjugated with the photoabsorber IRDye-700DX (pan-IR700) was intravenously administered to mice with A431-luc xenografts which are epithelial growth factor receptor (EGFR) positive. One and 2 days later, NIR light was administered to the tumors using one of three methods. Interstitial exposure alone and in combination with external sources showed the greatest decrease in bioluminescence signal intensity. Additionally, the combination of external and interstitial NIR light exposure showed significantly greater tumor size reduction and prolonged survival after NIR-PIT compared to external exposure alone. This result suggested that the combination of external and interstitial NIR light exposure was more effective than externally applied light alone. Although external exposure is the least invasive means of delivering light, the combination of external and interstitial exposures produces superior therapeutic efficacy in tumors greater than 2 cm in depth from the tissue surface.

The re-establishment of the normal blood lactate response to exercise in humans after prolonged acclimatization to altitude

DEFF Research Database (Denmark)

Van Hall, Gerrit; Calbet, J A; Søndergaard, H

2001-01-01

1. One to five weeks of chronic exposure to hypoxia has been shown to reduce peak blood lactate concentration compared to acute exposure to hypoxia during exercise, the high altitude 'lactate paradox'. However, we hypothesize that a sufficiently long exposure to hypoxia would result in a blood......, in lowlanders acclimatized for 9 weeks to an altitude of 5260 m, the arterial lactate concentration was similar at 0 m acute hypoxia and 5260 m chronic hypoxia. The net lactate release from the active leg was higher at 5260 m chronic hypoxia compared to 0 m acute hypoxia, implying an enhanced lactate...... utilization with prolonged acclimatization to altitude. The present study clearly shows the absence of a lactate paradox in lowlanders sufficiently acclimatized to altitude....

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

Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice.

Science.gov (United States)

Keller, Guillermo A; Alvarez, Paulino A; Ponte, Marcelo L; Belloso, Waldo H; Bagnes, Claudia; Sparanochia, Cecilia; Gonzalez, Claudio D; Villa Etchegoyen, M Cecilia; Diez, Roberto A; Di Girolamo, Guillermo

2016-01-01

The actual prevalence of drug induced QTc prolongation in clinical practice is unknown. Our objective was to determine the occurrence and characteristics of drug-induced QT prolongation in several common clinical practices. Additionally, a subgroup of patients treated with dextropropoxyphene of particular interest for the regulatory authority was analysed. Medical history and comorbidities predisposing to QT interval prolongation were registered for 1270 patient requiring medical assistance that involved drug administration. Three ionograms and ECGs were performed: baseline, intra- and after treatment; QT interval was corrected with Bazzet formula. Among patients, 9.9% presented QTc >450/470 ms, 3% QTc > 500 ms, 12.7% ΔQTc >30 ms and 5.2% ΔQTc >60 ms. QTc prolongation associated with congestive heart failure, ischemic cardiopathy, diabetes, renal failure, arrhythmias, hypothyroidism, and bradycardia. At univariate analysis, clarithromycin, haloperidol, tramadol, amiodarone, glyceryl trinitrate, amoxicillin + clavulanic acid, amoxicillin + sulbactam, ampicillin + sulbactam, fentanyl, piperacillin + tazobactam, and diazepam prolonged QTc. Prolongation remained significantly associated with furosemide, clarithromycin, glyceryl trinitrate and betalactamase inhibitors after multivariate analysis. QT interval prolongation in everyday practice is frequent, in association to clinical factors and drugs that can be easily identified for monitoring and prevention strategies.

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.

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

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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.

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...

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.

An unusual case of prolonged post-endoscopic retrograde cholangiopancreatography jaundice.

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Tziatzios, Georgios; Gkolfakis, Paraskevas; Papanikolaou, Ioannis S; Dimitriadis, George; Triantafyllou, Konstantinos

2016-04-01

Despite the effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of choledocholithiasis, various complications have been described. We herein report the first case of prolonged post-ERCP jaundice due to toxicity of the contrast agent Iobitridol (®XENETIX, Guerbet, Roissy CdG Cedex, France) in a patient who underwent ERCP with sphincterectomy and common bile duct stone removal. While clinical improvement and normalization of aminotransferases and cholestatic enzymes after the procedure, an unexplained increase of direct bilirubin was noticed. A second ERCP was performed one week later, excluding possible remaining choledocholithiasis. Nevertheless, serum direct bilirubin increased further up to 15 mg/dL. Other potential causes of direct hyperbilirubinemia were ruled out and patient's liver biopsy was compatible with drug-induced liver toxicity. Additionally, the cause-result time connection between the use of Iobitridol and bilirubin increase indicated the possibility of a toxic effect related to the repeated use of the particular contrast agent. Iobitridol, a contrast agent, can induce prolonged direct hyperbilirubinemia.

Therapist-Aided Exposure for Women with Lifelong Vaginismus: Mediators of Treatment Outcome: A Randomized Waiting List Control Trial.

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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.

Does UTI cause prolonged jaundice in otherwise well infants?

Science.gov (United States)

Chowdhury, Tanzila; Kisat, Hamudi; Tullus, Kjell

2015-07-01

The symptoms of urinary tract infections in infants are very non-specific and have historically included prolonged hyperbilirubinaemia. We studied the results of routine urine samples in 319 infants with prolonged jaundice. Convincing findings of UTI was not found in any of these children even if one of them was treated with antibiotics after four consecutive urine cultures with different bacteria. A urine culture might thus not be an appropriate investigation in a child with prolonged jaundice without any other symptoms of UTI. • The symptoms of UTI in infancy are very non-specific. • Old studies suggest that prolonged hyperbilirubinaemia is one such symptom; more modern studies give more conflicting results. What is New: • Our study could not confirm that children with prolonged jaundice have an increased risk of UTI. • Routine urine testing is thus not needed in otherwise healthy infants with prolonged jaundice.

Mixed models for data from thorough QT studies: part 2. One-step assessment of conditional QT prolongation.

Science.gov (United States)

Schall, Robert

2011-01-01

We investigate mixed analysis of covariance models for the 'one-step' assessment of conditional QT prolongation. Initially, we consider three different covariance structures for the data, where between-treatment covariance of repeated measures is modelled respectively through random effects, random coefficients, and through a combination of random effects and random coefficients. In all three of those models, an unstructured covariance pattern is used to model within-treatment covariance. In a fourth model, proposed earlier in the literature, between-treatment covariance is modelled through random coefficients but the residuals are assumed to be independent identically distributed (i.i.d.). Finally, we consider a mixed model with saturated covariance structure. We investigate the precision and robustness of those models by fitting them to a large group of real data sets from thorough QT studies. Our findings suggest: (i) Point estimates of treatment contrasts from all five models are similar. (ii) The random coefficients model with i.i.d. residuals is not robust; the model potentially leads to both under- and overestimation of standard errors of treatment contrasts and therefore cannot be recommended for the analysis of conditional QT prolongation. (iii) The combined random effects/random coefficients model does not always converge; in the cases where it converges, its precision is generally inferior to the other models considered. (iv) Both the random effects and the random coefficients model are robust. (v) The random effects, the random coefficients, and the saturated model have similar precision and all three models are suitable for the one-step assessment of conditional QT prolongation. Copyright © 2010 John Wiley & Sons, Ltd.

Prolonged fever and involuntary weight loss as manifestations of bacterial endocarditis: A case report

Science.gov (United States)

Sukmawati, N. M. D. D.; Merati, T. P.; Somia, A.; Utama, S.; Gayatri, Y.

2018-03-01

We reported an unusual presentation of prolonged fever and involuntary weight loss in older adult as a manifestation of infective bacterial endocarditis. The patient had pre-existing compensated asymptomatic valvular heart disease without treatment. A positive fecal occult blood test is prompting an investigation of malignancy of gastrointestinal as one of other possible cause of prolonged fever with wasting, evaluation of HIV serostatus shows seronegative. The case fulfilled criteria for definitive infective endocarditis: one major criterion of positive blood culture for Streptococcus mitis, which was one of viridans group streptococci and three minor criteria of fever at least 38°Celsius, immunologic phenomena in the form of glomerulonephritis, and a predisposing heart condition. One course of third-generation cephalosporin successfully cleared the Streptococcus mitis infection proven by culture. Infective endocarditis should be considered as one of the causes of prolonged fever with wasting, especially in cases with the previous history of heart disease.

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.

Persistent effects of prior chronic exposure to corticosterone on reward-related learning and motivation in rodents.

Science.gov (United States)

Olausson, Peter; Kiraly, Drew D; Gourley, Shannon L; Taylor, Jane R

2013-02-01

Repeated or prolonged exposure to stress has profound effects on a wide spectrum of behavioral and neurobiological processes and has been associated with the pathophysiology of depression. The multifaceted nature of this disorder includes despair, anhedonia, diminished motivation, and disrupted cognition, and it has been proposed that depression is also associated with reduced reward-motivated learning. We have previously reported that prior chronic corticosterone exposure to mice produces a lasting depressive-like state that can be reversed by chronic antidepressant treatment. In the present study, we tested the effects of prior chronic exposure to corticosterone (50 μg/ml) administered to rats or to mice in drinking water for 14 days followed by dose-tapering over 9 days. The exposure to corticosterone produced lasting deficits in the acquisition of reward-related learning tested on a food-motivated instrumental task conducted 10-20 days after the last day of full dose corticosterone exposure. Rats exposed to corticosterone also displayed reduced responding on a progressive ratio schedule of reinforcement when tested on day 21 after exposure. Amitriptyline (200 mg/ml in drinking water) exposure for 14 days to mice produced the opposite effect, enhancing food-motivated instrumental acquisition and performance. Repeated treatment with amitriptyline (5 mg/kg, intraperitoneally; bid) subsequent to corticosterone exposure also prevented the corticosterone-induced deficits in rats. These results are consistent with aberrant reward-related learning and motivational processes in depressive states and provide new evidence that stress-induced neuroadaptive alterations in cortico-limbic-striatal brain circuits involved in learning and motivation may play a critical role in aspects of mood disorders.

A comparative study of changes in immunological reactivity during prolonged introduction of radioactive and chemical substances into the organism with drinking water

International Nuclear Information System (INIS)

Shubik, V.M.; Nevstrueva, M.A.; Kalnitskij, S.A.; Livshits, R.E.; Merkushev, G.N.; Pilshchik, E.M.; Ponomareva, T.V.

1978-01-01

A comparative study was conducted into the factors of non-specific protection and specific immunity, allergic and autoallergic reactivities during prolonged exposure of experimental animals to 6 different radioactive and 7 harmful chemical substances. Qualitative and quantitative peculiarities were found in the changes in immunological reactivity during the exposure of the organism to radionuclides and stable chemical compounds. Impairment of immunity plays an essential role in the course and the outcome of effects induced by chronic action of the substances examined. (author)

Peculiarities of prolonged neonatal jaundice and possibility of their pharmacological correction

Directory of Open Access Journals (Sweden)

Yablon O.

2017-03-01

Full Text Available Purpose: to study of peculiarities of prolonged neonatal jaundice and the possibility of pharmacological correction based on ursodeoxycholic acid. Patients and methods. Were examined 42 children (29 boys and 13 girls with prolonged neonatal jaundice. The study group included 22 children, who in complex of pharmacological treatment received the ursodeoxycholic acid, the comparison group comprised 20 children who received only basic treatment such as phototherapy. The effectiveness of the treatment was evaluated by biochemical parameters of blood (bilirubin and its fractions, liver transaminase, the level of serum alpha&fetoprotein, epidermal growth factor were determined by ELISA. Results. All children were full term. The mean age of children in the study group was 20.8±1.9 days in the control group and 22±1.5 days. In the main group indirect bilirubin was above on 35 μmol/l, but significant differences in the level of indirect bilirubin were absent at the beginning of treatment in both groups of children included in the study, respectively, 286±14,3 μmol/l and 250±16.4 μmol/l (p>0.05. The average indirect bilirubin after treatment significantly decreased in both groups but in the main group, a decline of 49% in the comparison group decrease of bilirubin was on 30%. It was also noted signs of neonatal cholestasis: every fifth child had the increased level of direct bilirubin, every third child had elevated liver transaminase. Also, there were no significant differenses in the mean levels of serum AFP and EGF, there were higher in children of both study groups, respectively, mean level of serum AFP in the main group was 834±28 ng/ml in the comparison group — 809±26 ng/ml(p>0.05; mean level of serum EGF in the main group 651±57,2 ng/ml in the comparison group — 714±27 ng/ml(p>0.05. However, in children who were treated with ursodeoxycholic acid (UkrlivR suspension the levels of serum AFP and EGF were significantly decreased, in

Prolonged whole body immersion in cold water: hormonal and metabolic changes.

Science.gov (United States)

Smith, D J; Deuster, P A; Ryan, C J; Doubt, T J

1990-03-01

To characterize metabolic and hormonal responses during prolonged whole body immersion, 16 divers wearing dry suits completed four immersions in 5 degrees C water during each of two 5-day air saturation dives at 6.1 meters of sea water. One immersion began in the AM (1000 h) and one began in the PM (2200 h) to evaluate diurnal variations. Venous blood samples were obtained before and after completion of each immersion. Cortisol and ACTH levels demonstrated diurnal variation, with larger increases occurring after PM immersions. A greater than three-fold postimmersion increase occurred in norepinephrine (NE). There were significant increases in triiodothyronine (T3) uptake and epinephrine, but no change in T3, thyroxine, thyrotrophic hormone, and dopamine. Postimmersion free fatty acid levels increased 409% from preimmersion levels; glucose levels declined, and lactate increased significantly. Only changes in NE correlated significantly with changes in rectal temperature. In summary, when subjects are immersed in cold water for prolonged periods, with a slow rate of body cooling afforded by thermal protection and intermittent exercise, hormonal and metabolic changes occur that are similar in direction and magnitude to short-duration unprotected exposures. Except for cortisol and ACTH, none of the other measured variables exhibited diurnal alterations.

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...

Diclofenac prolongs repolarization in ventricular muscle with impaired repolarization reserve.

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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.

Multifactorial QT Interval Prolongation and Takotsubo Cardiomyopathy

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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.

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…

Prolonged labour as indication for emergency caesarean section

DEFF Research Database (Denmark)

Maaløe, Nanna; Sorensen, B L; Onesmo, R

2012-01-01

To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour.......To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour....

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...

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.

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...

An integrative review of attention biases and their contribution to treatment for anxiety disorders

Directory of Open Access Journals (Sweden)

Tom Joseph Barry

2015-07-01

Full Text Available Models of exposure therapy, one of the key components of cognitive behavioural therapy for anxiety disorders, suggest that attention may play an important role in the extinction of fear and anxiety. Evidence from cognitive research suggests that individual differences may play a causal role in the onset and maintenance of anxiety disorders and so it is also likely to influence treatment. We review the evidence concerning attention and treatment outcomes in anxiety disorders. The evidence reviewed here suggests that that attention biases assessed at pre-treatment might actually predict improved response to treatment, and in particular that prolonged engagement with threat as measured in tasks such as the dot probe is associated with greater reductions in anxious symptoms following treatment. We examine this research within a fear learning framework, considering the possible role of individual differences in attention in the extinction of fear during exposure. Theoretical, experimental and clinical implications are discussed, particularly with reference to the potential for attention bias modification programs in augmenting treatment, and also with reference to how existing research in this area might inform best practice for clinicians.

Levo-α-acetylmethadol (LAAM induced QTc-prolongation - results from a controlled clinical trial

Directory of Open Access Journals (Sweden)

Wieneke H

2009-01-01

Full Text Available Abstract Background Due to potential proarrhythmic side-effects levo-α-Acetylmethadol (LAAM is currently not available in EU countries as maintenance drug in the treatment of opiate addiction. However, recent studies and meta-analyses underline the clinical advantages of LAAM with respect to the reduction of heroin use. Thus a reappraisal of LAAM has been demanded. The aim of the present study was to evaluate the relative impact of LAAM on QTc-interval, as a measure of pro-arrhythmic risk, in comparison to methadone, the current standard in substitution therapy. Methods ECG recordings were analysed within a randomized, controlled clinical trial evaluating the efficacy and tolerability of maintenance treatment with LAAM compared with racemic methadone. Recordings were done at two points: 1 during a run-in period with all patients on methadone and 2 24 weeks after randomisation into methadone or LAAM treatment group. These ECG recordings were analysed with respect to QTc-values and QTc-dispersion. Mean values as well as individual changes compared to baseline parameters were evaluated. QTc-intervals were classified according to CPMP-guidelines. Results Complete ECG data sets could be obtained in 53 patients (31 LAAM-group, 22 methadone-group. No clinical cardiac complications were observed in either group. After 24 weeks, patients receiving LAAM showed a significant increase in QTc-interval (0.409 s ± 0.022 s versus 0.418 s ± 0.028 s, p = 0.046, whereas no significant changes could be observed in patients remaining on methadone. There was no statistically significant change in QTc-dispersion in either group. More patients with borderline prolonged and prolonged QTc-intervals were observed in the LAAM than in the methadone treatment group (n = 7 vs. n = 1; p = 0.1. Conclusions In this controlled trial LAAM induced QTc-prolongation in a higher degree than methadone. Given reports of severe arrhythmic events, careful ECG-monitoring is recommended

Cushing’s Syndrome: All variants, detection, and treatment

Science.gov (United States)

Sharma, Susmeeta T.; Nieman, Lynnette K.

2010-01-01

Synopsis Cushing’s syndrome is caused by prolonged exposure to excess glucocorticoids. Diagnosis of Cushing’s syndrome involves a step-wise approach and establishing the cause can be challenging in some cases. Hypertension is present in about 80% of patients with Cushing’s syndrome and can lead to significant morbidity and mortality. Several pathogenic mechanisms have been proposed for glucocorticoid-induced hypertension including a functional mineralocorticoid excess state, up-regulation of the renin angiotensin system and deleterious effects of cortisol on the vasculature. Surgical excision of the cause of excess glucocorticoids remains the optimal treatment for Cushing’s syndrome. Anti-glucocorticoid and antihypertensive agents and steroidogenesis inhibitors can be used as adjunctive treatment modalities in preparation for surgery, and in cases where surgery is contraindicated or has not led to cure. PMID:21565673

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

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.

A detailed description of the short-term musculoskeletal and cognitive effects of prolonged standing for office computer work.

Science.gov (United States)

Baker, Richelle; Coenen, Pieter; Howie, Erin; Lee, Jeremy; Williamson, Ann; Straker, Leon

2018-07-01

Due to concerns about excessive sedentary exposure for office workers, alternate work positions such as standing are being trialled. However, prolonged standing may have health and productivity impacts, which this study assessed. Twenty adult participants undertook two hours of laboratory-based standing computer work to investigate changes in discomfort and cognitive function, along with muscle fatigue, movement, lower limb swelling and mental state. Over time, discomfort increased in all body areas (total body IRR [95% confidence interval]: 1.47[1.36-1.59]). Sustained attention reaction time (β = 18.25[8.00-28.51]) deteriorated, while creative problem solving improved (β = 0.89[0.29-1.49]). There was no change in erector spinae, rectus femoris, biceps femoris or tibialis anterior muscle fatigue; low back angle changed towards less  lordosis, pelvis movement increased, lower limb swelling increased and mental state decreased. Body discomfort was positively correlated with mental state. The observed changes suggest replacing office work sitting with standing should be done with caution. Practitioner Summary: Standing is being used to replace sitting by office workers; however, there are health risks associated with prolonged standing. In a laboratory study involving 2 h prolonged standing discomfort increased (all body areas), reaction time and mental state deteriorated while creative problem-solving improved. Prolonged standing should be undertaken with caution.

Selective lymphoid irradiation: III. Prolongation of cardiac xenografts and allografts in presensitized rats

International Nuclear Information System (INIS)

Hardy, M.A.; Oluwole, S.; Fawwaz, R.; Satake, K.; Nowygrod, R.; Reemtsma, K.

1982-01-01

Selective lymphoid irradiation (SLI) with palladium-109-hematoporphyrin (Pd-H) combined with antilymphocyte globulin (ALG) induces either donor-specific permanent rat heart allograft acceptance or significant allograft prolongation depending on the degree of donor-recipient matching. The purpose of this study was to determine if SLI combined with ALG can affect ACI heart allograft survival in Lewis recipients presensitized to ACI, and of hamster heart xenografts of Lewis rats. SLI combined with ALG delays allograft and xenograft rejection in the presence of induced or preformed antidonor antibodies, and converts primarily a humoral rejection into a cellular rejection by mechanisms as yet uncertain. Such peritransplant treatment had significant effect on the levels of antidonor complement-dependent cytotoxic antibody titers but did not correlate directly with graft survival. Histological analysis of rejected hearts in all groups demonstrated primarily a humoral hyperacute rejection in control animals and in recipients treated with ALG alone, while peritransplant treatment with Pd-H and ALG resulted not only in prolonged graft survival but histologically, primarily a cellular rejection of the graft

QTc interval prolongation in children with Turner syndrome: the results of exercise testing and 24-h ECG.

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Dalla Pozza, Robert; Bechtold, Susanne; Urschel, Simon; Netz, Heinrich; Schwarz, Hans-Peter

2009-01-01

Turner syndrome (TS) is the most common sex chromosome abnormality in females. Recently, a prolongation of the rate-corrected QT (QTc) interval in the electrocardiogram (ECG) of TS patients has been reported. A prolonged QTc interval has been correlated to an increased risk for sudden cardiac death, and medical treatment is warranted in patients with congenital long QT syndrome (LQTS). Additionally, several drugs of common use are contraindicated in LQTS because of their effects on myocardial repolarization. The importance of the QTc prolongation in TS patients is not known at present. Eighteen TS patients with a prolonged QTc interval (group 1) and 11 TS patients with a normal QTc interval (group 2) (mean age 12.6+/-3.1 vs. 11.8+/-2.1 years, respectively) were tested. The QTc interval was calculated during exercise testing and during 24-h ECG recordings. None of the patients experienced adverse cardiac events during the tests. The mean QTc interval decreased from 0.467 to 0.432 s in group 1 and from 0.432 to 0.412 s in group 2. During the 24-h ECG, the maximum QTc interval was significantly prolonged in group 1 (0.51 vs. 0.465 s, pinformation about the cardiac risk in the single TS patient with a prolonged QTc interval. This helps in counseling these girls, as clear therapeutic guidelines are currently lacking.

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

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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.

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

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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.

[Representation of Internal Medicine in G-DRG System - Analysis of Reasons for Prolonged Length of Stay].

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Siam, Kristina; Roeder, Norbert; Fölsch, Ulrich R; Spies, Hans-Friedrich

2017-08-01

Background  There is an ongoing discussion within the German Society of Internal Medicine (DGIM) and the Professional Association of German Internists (BDI) about the appropriate depiction and remuneration of internal medicine in the G-DRG. Method  Therefore, cases with a significantly prolonged length of stay were analyzed in a multicenter study. 124 cases from 6 hospitals were collected for evaluation. Results  The results show that the observed prolongation of hospitalization was mainly due to medical reasons. Discussion  Thus, patients with unclear symptoms and consequently need for a thorough workup could not be identified to cause longer inpatient stay. Instead, treatment complications and comorbidities led to extended hospitalization. The results also reveal prolonged hospitalization as a consequence of unsettled or delayed postdischarge care e. g. in rehabilitation facilities. © Georg Thieme Verlag KG Stuttgart · New York.

Impacted maxillary central incisor: surgical exposure and orthodontic treatment.

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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.

Adapting to warmer climate through prolonged maize grain filling period in the US Midwest

Science.gov (United States)

Zhu, P.; Zhuang, Q.; Jin, Z.

2017-12-01

Climate warming is expected to negatively impact the US food productivity. How to adapt to the future warmer environment and meet the rising food requirement becomes unprecedented urgent. Continuous satellite observational data provides an opportunity to examine the historic responses of crop plants to climate variation. Here 16 years crop growing phases information across US Midwest is generated based on satellite observations. We found a prolonged grain-filling period during 2000-2015, which could partly explain the increasing trend in Midwest maize yield. This longer grain-filling period might be resulted from the adoption of longer maturity group varieties or more resistant varieties to temperature variation. Other management practice changes like advance in planting date could be also an effective way of adapting future warmer climate through lowering the possibility of exposure to heat and drought stresses. If the progress in breeding technology enables the maize grain-filling period to prolong with the current rate, the maize grain filling length could be longer and maize yield in Midwest could adapt to future climate despite of the warming.

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

In vivo relaxation time measurements on a murine tumor model--prolongation of T1 after photodynamic therapy.

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Liu, Y H; Hawk, R M; Ramaprasad, S

1995-01-01

RIF tumors implanted on mice feet were investigated for changes in relaxation times (T1 and T2) after photodynamic therapy (PDT). Photodynamic therapy was performed using Photofrin II as the photosensitizer and laser light at 630 nm. A home-built proton solenoid coil in the balanced configuration was used to accommodate the tumors, and the relaxation times were measured before, immediately after, and up to several hours after therapy. Several control experiments were performed untreated tumors, tumors treated with Photofrin II alone, or tumors treated with laser light alone. Significant increases in T1s of water protons were observed after PDT treatment. In all experiments, 31P spectra were recorded before and after the therapy to study the tumor status and to confirm the onset of PDT. These studies show significant prolongation of T1s after the PDT treatment. The spin-spin relaxation measurements, on the other hand, did not show such prolongation in T2 values after PDT treatment.

SU119. Internalized Stigma in Adults With Early-Phase vs Prolonged Psychosis

Science.gov (United States)

Firmin, Ruth; Vohs, Jenifer; Luther, Lauren; Yanos, Philip; Leonhardt, Bethany; Lysaker, Paul

2017-01-01

Abstract Background: While 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 quality of life 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 quality of life or symptoms among those with prolonged compared to early-phase psychosis. Methods: 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 quality of life. Results: Controlling for education, race, and sex differences, internalized stigma was significantly greater among those with prolonged compared to early-phase psychosis. Internalized stigma was negatively related to quality of life 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 psychosis. Stereotype endorsement, discrimination experiences, and social withdrawal also deferentially related to symptoms and quality of life across the 2 samples. Conclusion: Findings suggest that internalized stigma is an important variable to incorporate into models of early psychosis. Further, internalized stigma may be a possible treatment target among those in their early phase of psychosis.

Heart Rate Variability Frequency Domain Alterations among Healthy Nurses Exposed to Prolonged Work Stress

Directory of Open Access Journals (Sweden)

Rossana Borchini

2018-01-01

Full Text Available The deregulation of the autonomic nervous system assessed through the heart rate variability (HRV analysis is a promising pathway linking work stress and cardiovascular diseases. We aim to investigate the associations between HRV High Frequency (HF and Low Frequency (LF powers and work stress in a sample of 36 healthy nurses. Perceived work stress was assessed twice one year apart, using the Job Content and Effort Reward Imbalance questionnaires. This allows to classify nurses in three exposure groups: “prolonged high stress” (PHS, “recent high stress” (RHS and “stable low stress” (SLS. A 24-h ECG monitoring was later performed during a working day (WD and a subsequent resting day (RD. Statistically significantly lower (p < 0.02 HF and LF means were found in PHS and RHS nurses during the working periods. In the subsequent resting periods, HF means showed increases over time in the RHS (beta = +0.41, p < 0.05, but not in PHS nurses. LF means did not show any substantial increases in the resting periods, in the PHS group with geometric means lower when compared to SLS, in the non-working and resting periods. Our study evidences that both prolonged and recent perceived high work stress were associated with a reduction of HF and LF powers during work. In addition, prolonged stress was associated with a lack of recovery during not-working and resting periods.

Prolonged preconditioning with natural honey against myocardial infarction injuries.

Science.gov (United States)

Eteraf-Oskouei, Tahereh; Shaseb, Elnaz; Ghaffary, Saba; Najafi, Moslem

2013-07-01

Potential protective effects of prolonged preconditioning with natural honey against myocardial infarction were investigated. Male Wistar rats were pre-treated with honey (1%, 2% and 4%) for 45 days then their hearts were isolated and mounted on a Langendorff apparatus and perfused with a modified Krebs-Henseleit solution during 30 min regional ischemia fallowed by 120 min reperfusion. Two important indexes of ischemia-induced damage (infarction size and arrhythmias) were determined by computerized planimetry and ECG analysis, respectively. Honey (1% and 2%) reduced infarct size from 23±3.1% (control) to 9.7±2.4 and 9.5±2.3%, respectively (Phoney (1%) significantly reduced (PHoney (1% and 2%) also significantly decreased number of ventricular ectopic beats (VEBs). In addition, incidence and duration of reversible ventricular fibrillation (Rev VF) were lowered by honey 2% (Phoney produced significant reduction in the incidences of VT, total and Rev VF, duration and number of VT. The results showed cardioprotective effects of prolonged pre-treatment of rats with honey following myocardial infarction. Maybe, the existence of antioxidants and energy sources (glucose and fructose) in honey composition and improvement of hemodynamic functions may involve in those protective effects.

Behavioral changes over time in post-traumatic stress disorder: Insights from a rat model of single prolonged stress.

Science.gov (United States)

Wu, Zhuoyun; Tian, Qing; Li, Feng; Gao, Junqiao; Liu, Yan; Mao, Meng; Liu, Jing; Wang, Shuyan; Li, Genmao; Ge, Dongyu; Mao, Yingqiu; Zhang, Wei; Liu, Zhaolan; Song, Yuehan

2016-03-01

Post-traumatic stress disorder (PTSD) is manifested as a persistent mental and emotional condition after potentially life-threatening events. Different animal models of PTSD have been developed for neuro-pathophysiology and pharmacological evaluations. A single prolonged stress (SPS) induced animal model has demonstrated to result in specific neuro-endocrinological dysregulation, and behavior abnormalities observed in PTSD. However, animal studies of PTSD have mostly been performed at one time point after SPS exposure. To better understand the development of PTSD-like behaviors in the SPS animal model, and to identify an optimal period of study, we examined depressive behavior, anxiety-like behavior, physical activity and body weight in SPS model rats for two weeks. Our results confirmed the SPS-induced PTSD-like behavior and physical activity observed in previous studies, and indicated that the most pronounced symptomatic behavior changes were observed on day 1 and 7 after SPS exposure, which may involve stress-induced acute hormone changes and unclear secondary neurobiological changes, respectively. These results provide a solid basis for further investigation into the neuro-pathophysiology of or neuropharmacology for PTSD using the SPS rat model. However, for chronic (pharmacological) studies longer than 7 days, a prolonged PTSD animal model should be developed, perhaps using enhanced stimulation. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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.

Pulmonary fibrosis and exposure to steel welding fume.

Science.gov (United States)

Cosgrove, M P

2015-12-01

Arc welders who have been exposed to high concentrations of steel welding fume for prolonged periods of time may develop pulmonary fibrosis but the nature of the fibrotic changes has been debated over the last 80 years without any clear international consensus. To characterize the nature of the pulmonary fibrosis that develops in response to steel welding fume exposure and to provide a working hypothesis that would explain the findings of the existing research, to provide a platform for future research and to inform future occupational and clinical management of welders with pulmonary effects from welding fume. Review of the world literature on pulmonary fibrosis and welding of steel in all languages using PubMed, with further secondary search of references in the articles found in the primary search. Google and Reference Manager were used as further confirmatory search tools. Only case series and case reports were found but these provided consistent evidence that the consequence of exposure to steel welding fume at high levels for a prolonged period of time is a type of pulmonary fibrosis similar to, and possibly the same as, respiratory bronchiolitis which eventually develops into desquamative interstitial pneumonia with ongoing exposure. Steel welding fume may cause an occupational respiratory bronchiolitis which may develop into de squamative interstitial pneumonia with ongoing exposure. This concept may explain the difficulties in interpreting the wider literature on welding fume and lung function at lower exposures and may also explain the increased risk of lung cancer in welders. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

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

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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.

Stevioside counteracts the alpha cell hypersecretion caused by long-term palmitate exposure

DEFF Research Database (Denmark)

Hong, Jing; Chen, Jianguo; Jeppesen, Per Bendix

2006-01-01

Long-term exposure to fatty acids impairs beta-cell function in type 2 diabetes, but little is known about the chronic effects of fatty acids on alpha-cells. We therefore studied the prolonged impact of palmitate on alpha-cell function and on the expression of genes related to fuel metabolism. We......-activated receptor-gamma, and stearoyl-CoA desaturase gene expressions in the presence of palmitate (Pacids leads to a hypersecretion of glucagon and an accumulation of TG content in clonal alpha-TC1-6 cells. Stevioside was able to counteract the alpha......-cell hypersecretion caused by palmitate and enhanced the expression of genes involved in fatty acid metabolism. This indicates that stevioside may be a promising antidiabetic agent in treatment of type 2 diabetes....

Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation

International Nuclear Information System (INIS)

Nozaki, Yumiko; Honda, Yayoi; Tsujimoto, Shinji; Watanabe, Hitoshi; Kunimatsu, Takeshi; Funabashi, Hitoshi

2014-01-01

Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K + channel and Ca 2+ channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min for 30 min after drug exposure for the vehicle and each drug concentration. I Kr and I Ks blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca 2+ channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the I Kr blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential. - Highlights: • We focused on hiPS-CMs to replace in vitro assays in preclinical screening studies. • hiPS-CMs FPD is useful as an indicator to predict drug potential for QT prolongation. • MEA assay can help detect EAD for drugs with TdP potentials. • MEA assay in hiPS-CMs is useful for accurately predicting drug TdP risk in humans

Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation

Energy Technology Data Exchange (ETDEWEB)

Nozaki, Yumiko, E-mail: yumiko-nozaki@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Honda, Yayoi, E-mail: yayoi-honda@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Tsujimoto, Shinji, E-mail: shinji-tsujimoto@ds-pharma.co.jp [Regenerative and Cellular Medicine Office, Dainippon Sumitomo Pharma. Co., Ltd., Chuo-ku, Tokyo 104-0031 (Japan); Watanabe, Hitoshi, E-mail: hitoshi-1-watanabe@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Kunimatsu, Takeshi, E-mail: takeshi-kunimatsu@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Funabashi, Hitoshi, E-mail: hitoshi-funabashi@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan)

2014-07-01

Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K{sup +} channel and Ca{sup 2+} channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min for 30 min after drug exposure for the vehicle and each drug concentration. I{sub Kr} and I{sub Ks} blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca{sup 2+} channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the I{sub Kr} blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential. - Highlights: • We focused on hiPS-CMs to replace in vitro assays in preclinical screening studies. • hiPS-CMs FPD is useful as an indicator to predict drug potential for QT prolongation. • MEA assay can help detect EAD for drugs with TdP potentials. • MEA assay in hiPS-CMs is useful for accurately predicting drug TdP risk in humans.

Valsartan Attenuates Atherosclerosis via Upregulating the Th2 Immune Response in Prolonged Angiotensin II–Treated ApoE−/− Mice

Science.gov (United States)

Meng, Kai; Zeng, Qiutang; Lu, Qinghua; Lin, Yingzhong; Wu, Bangwei; Yu, Kunwu; Dong, Zhaoqiang; Zhang, Jianwei; Chai, Meng; Liu, Yuyang; Ji, Qingwei; Zhou, Yujie

2015-01-01

Valsartan has a protective effect against hypertension and atherosclerosis in humans and experimental animal models. This study aimed to determine the effect of prolonged treatment with angiotensin II (Ang II) on atherosclerosis and the effect of valsartan on the activity of CD4+ T lymphocyte subsets. The results showed that prolonged treatment (8 wks) with exogenous Ang II resulted in an increased atherosclerotic plaque size and a switch of stable-to-unstable plaque via modulating on CD4+ T lymphocyte activity, including an increase in the T helper cell type 1 (Th1) and Th17 cells and a decrease in Th2 and regulatory T (Treg) cells. In contrast, valsartan treatment efficiently reversed the imbalance in CD4+ T lymphocyte activity, ameliorated atherosclerosis and elicited a stable plaque phenotype in addition to controlling blood pressure. In addition, treatment with anti-interleukin (IL)-5 monoclonal antibodies weakened the antiatherosclerotic effects of valsartan without affecting blood pressure. PMID:25685964

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.

The impact of Agent Orange exposure on prognosis and management in patients with chronic lymphocytic leukemia: a National Veteran Affairs Tumor Registry Study.

Science.gov (United States)

Mescher, Craig; Gilbertson, David; Randall, Nicole M; Tarchand, Gobind; Tomaska, Julie; Baumann Kreuziger, Lisa; Morrison, Vicki A

2018-06-01

Exposure to Agent Orange (AO) has been associated with the development of chronic lymphocytic leukemia (CLL). We performed a retrospective study of 2052 Vietnam veterans identified in the National VA Tumor Registry to assess the impact of AO exposure on CLL prognosis, treatment and survival. Prognostic factors did not differ based on exposure. Veterans exposed to AO were diagnosed younger (63.2 vs. 70.5 years, p < .0001) and had longer overall survival (median not reached vs. 91 months, p < .001). This prolonged survival was in the subgroups of patients aged 60-69 years (p< .0001) and those with 11q deletion (p < .0001). Those exposed to AO were more likely to be treated with fludarabine, chlorambucil and rituximab (38 vs. 21%, p < .001) and bendamustine plus rituximab (25 vs. 18%, p = 0.039) as first line therapy. Exposure to AO was not associated with either poor prognostic factors or shortened overall survival in our large veteran population with CLL.

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

Effects of chronic ammonia exposure on ammonia metabolism and excretion in marine medaka Oryzias melastigma.

Science.gov (United States)

Gao, Na; Zhu, Limei; Guo, Zhiqiang; Yi, Meisheng; Zhang, Li

2017-06-01

Ammonia is highly toxic to aquatic organisms, but whether ammonia excretion or ammonia metabolism to less toxic compounds is the major strategy for detoxification in marine fish against chronic ammonia exposure is unclear to date. In this study, we investigated the metabolism and excretion of ammonia in marine medaka Oryzias melastigma during chronic ammonia exposure. The fish were exposed to 0, 0.1, 0.3, 0.6, and 1.1 mmol l -1  NH 4 Cl spiked seawater for 8 weeks. Exposure of 0.3-1.1 mmol l -1  NH 4 Cl had deleterious effects on the fish, including significant reductions in growth, feed intake, and total protein content. However, the fish could take strategies to detoxify ammonia. The tissue ammonia (T Amm ) in the 0.3-1.1 mmol l -1  NH 4 Cl treatments was significantly higher than those in the 0 and 0.1 mmol l -1  NH 4 Cl treatments after 2 weeks of exposure, but it recovered with prolonged exposure time, ultimately reaching the control level after 8 weeks. The amino acid catabolic rate decreased to reduce the gross ammonia production with the increasing ambient ammonia concentration. The concentrations of most metabolites remained constant in the 0-0.6 mmol l -1  NH 4 Cl treatments, whereas 5 amino acids and 3 energy metabolism-related metabolites decreased in the 1.1 mmol l -1  NH 4 Cl treatment. J Amm steadily increased in ambient ammonia from 0 to 0.6 mmol l -1 and slightly decreased when the ambient ammonia concentration increased to 1.1 mmol l -1 . Overall, marine medaka cope with sublethal ammonia environment by regulating the tissue T Amm via reducing the ammonia production and increasing ammonia excretion. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol

DEFF Research Database (Denmark)

Baandrup, Lone; Fagerlund, Birgitte; Jennum, Poul

2011-01-01

Treatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged...... benzodiazepine administration in patients with schizophrenia. Furthermore, we aim to investigate the association of benzodiazepine dose reduction with the following clinically important variables: sleep, psychophysiology, cognition, social function, and quality of life....

Radiation exposure of nurses in a coronary care unit

International Nuclear Information System (INIS)

Jankowski, C.B.

1984-01-01

In response to increasing awareness of radiation as a possible occupational hazard, nursing personnel staffing a hospital CCU were monitored over a 3-year period to determine occupational exposure. Portable x-ray machines, fluoroscopic units, and patients injected with radiopharmaceuticals were all potential radiation sources on such a unit. Whole-body TLD badges, exchanged monthly, indicated no cumulative exposures over 80 mR during the entire study period. The minimal exposures reported do not justify regular use of dosimeters. Adherence to standard protective measures precludes most exposure to machine-produced radiation. Close, prolonged contact with a patient after an RVG study that utilizes /sup 99m/Tc may account for some exposure. The data indicate that radiation is not a significant occupational hazard for CCU nurses at this hospital; similar minimal exposures would be expected of other nonoccupationally exposed nursing personnel in like environments

Estimating pediatric general anesthesia exposure: Quantifying duration and risk.

Science.gov (United States)

Bartels, Devan Darby; McCann, Mary Ellen; Davidson, Andrew J; Polaner, David M; Whitlock, Elizabeth L; Bateman, Brian T

2018-05-02

Understanding the duration of pediatric general anesthesia exposure in contemporary practice is important for identifying groups at risk for long general anesthesia exposures and designing trials examining associations between general anesthesia exposure and neurodevelopmental outcomes. We performed a retrospective cohort analysis to estimate pediatric general anesthesia exposure duration during 2010-2015 using the National Anesthesia Clinical Outcomes Registry. A total of 1 548 021 pediatric general anesthetics were included. Median general anesthesia duration was 57 minutes (IQR: 28-86) with 90th percentile 145 minutes. Children aged 3 hours. High ASA physical status and care at a university hospital were associated with longer exposure times. While the vast majority (94%) of children undergoing general anesthesia are exposed for risk for longer exposures. These findings may help guide the design of future trials aimed at understanding neurodevelopmental impact of prolonged exposure in these high-risk groups. © 2018 John Wiley & Sons Ltd.

Persistent modification of Nav1.9 following chronic exposure to insecticides and pyridostigmine bromide

International Nuclear Information System (INIS)

Nutter, Thomas J.; Cooper, Brian Y.

2014-01-01

Many veterans of the 1991 Gulf War (GW) returned from that conflict with a widespread chronic pain affecting deep tissues. Recently, we have shown that a 60 day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine bromide (NTPB) had little influence on nociceptor action potential forming Na v 1.8, but increased K v 7 mediated inhibitory currents 8 weeks after treatment. Using the same exposure regimen, we used whole cell patch methods to examine whether the influences of NTPB could be observed on Na v 1.9 expressed in muscle and vascular nociceptors. During a 60 day exposure to NTPB, rats exhibited lowered muscle pain thresholds and increased rest periods, but these measures subsequently returned to normal levels. Eight and 12 weeks after treatments ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch studies revealed little change in voltage dependent activation and deactivation of Na v 1.9, but significant increases in the amplitude of Na v 1.9 were observed 8 weeks after exposure. Cellular studies, at the 8 week delay, revealed that NTPB also significantly prolonged action potential duration and afterhyperpolarization (22 °C). Acute application of permethrin (10 μM) also increased the amplitude of Na v 1.9 in skin, muscle and vascular nociceptors. In conclusion, chronic exposure to Gulf War agents produced long term changes in the amplitude of Na v 1.9 expressed in muscle and vascular nociceptors. The reported increases in K v 7 amplitude may have been an adaptive response to increased Na v 1.9, and effectively suppressed behavioral pain measures in the post treatment period. Factors that alter the balance between Na v 1.9 and K v 7 could release spontaneous discharge and produce chronic deep tissue pain. - Highlights: • Rats were treated 60 days with permethrin, chlorpyrifos and pyridostigmine bromide. • 8 weeks after treatments, Nav1.9 activation and deactivation were unchanged. • The amplitude and

Post-Exposure Prophylaxis (PEP)

Science.gov (United States)

... Child Transmission of HIV Post-Exposure Prophylaxis (PEP) Pre-Exposure Prophylaxis (PrEP) HIV Treatment HIV Treatment: The Basics Just ... to HIV frequently. Another HIV prevention method, called pre-exposure prophylaxis or PrEP, is when people at high risk ...

Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function

OpenAIRE

Lundgaard, Iben; Wang, Wei; Eberhardt, Allison; Vinitsky, Hanna Sophia; Reeves, Benjamin Cameron; Peng, Sisi; Lou, Nanhong; Hussain, Rashad; Nedergaard, Maiken

2018-01-01

Prolonged intake of excessive amounts of ethanol is known to have adverse effects on the central nervous system (CNS). Here we investigated the effects of acute and chronic ethanol exposure and withdrawal from chronic ethanol exposure on glymphatic function, which is a brain-wide metabolite clearance system connected to the peripheral lymphatic system. Acute and chronic exposure to 1.5 g/kg (binge level) ethanol dramatically suppressed glymphatic function in awake mice. Chronic exposure to 1....

Pharmacometabolomic approach to predict QT prolongation in guinea pigs.

Directory of Open Access Journals (Sweden)

Jeonghyeon Park

Full Text Available Drug-induced torsades de pointes (TdP, a life-threatening arrhythmia associated with prolongation of the QT interval, has been a significant reason for withdrawal of several medicines from the market. Prolongation of the QT interval is considered as the best biomarker for predicting the torsadogenic risk of a new chemical entity. Because of the difficulty assessing the risk for TdP during drug development, we evaluated the metabolic phenotype for predicting QT prolongation induced by sparfloxacin, and elucidated the metabolic pathway related to the QT prolongation. We performed electrocardiography analysis and liquid chromatography-mass spectroscopy-based metabolic profiling of plasma samples obtained from 15 guinea pigs after administration of sparfloxacin at doses of 33.3, 100, and 300 mg/kg. Principal component analysis and partial least squares modelling were conducted to select the metabolites that substantially contributed to the prediction of QT prolongation. QTc increased significantly with increasing dose (r = 0.93. From the PLS analysis, the key metabolites that showed the highest variable importance in the projection values (>1.5 were selected, identified, and used to determine the metabolic network. In particular, cytidine-5'-diphosphate (CDP, deoxycorticosterone, L-aspartic acid and stearic acid were found to be final metabolomic phenotypes for the prediction of QT prolongation. Metabolomic phenotypes for predicting drug-induced QT prolongation of sparfloxacin were developed and can be applied to cardiac toxicity screening of other drugs. In addition, this integrative pharmacometabolomic approach would serve as a good tool for predicting pharmacodynamic or toxicological effects caused by changes in dose.

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

Peculiarities of the effect of prolonged gamma-irradiation on the functional state of heart and its adrenergic regulation at hypothyroidism

International Nuclear Information System (INIS)

Lobanok, L.M.; Antonenko, A.N.

2001-01-01

Effect of prolonged gamma radiation on the functional state of heart and its adrenergic regulation in case of hypothyroidism is studied. Rats-females were irradiated during 992 h at the dose of 1.0 Gy, dose rate - 2.8x10 -7 Gy/s. Gammarid - 192/120 plant was used for exposure. Mercazolyl was incorporated into rats before irradiation for modelling hypothyroidism. It is shown that in delayed times, after exposure the contraction function of heart is decreased, but modification of the adrenergic regulation became essentially earlier. Radiation effect on the hyperthyroid organism results in more considerable alterations in biochemical heart function and its adrenergic regulation [ru

Severe adverse effects related to dermal exposure to a glyphosate-surfactant herbicide

DEFF Research Database (Denmark)

Mariager, T P; Madsen, P V; Ebbehøj, N E

2013-01-01

This is a case of severe chemical burns following prolonged accidental exposure to a glyphosate-surfactant herbicide. The patient developed local swelling, bullae and exuding wounds. Neurological impairment followed affecting finger flexion and sensation with reduced nerve conduction. Imaging rev...

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

Exposure to radon in caves and abandoned mines

International Nuclear Information System (INIS)

Dixon, D.W.

1996-01-01

The significance for health of exposure to radon daughters during leisure excursions in discussed mines or caves is considered for visitors with interests in speleology, mineral collecting, mining history and youth training. General members of the public might also enter tunnels. Potential annual exposures based on radon measurements in various mines and caves are estimated and it is concluded that the annual exposure of individuals who undertake frequent and prolonged trips to underground systems might exceed 10 6 Bq h m -3 . Exposures to general members of the public are likely to be much lower. The National Radiological Protection Board has developed proposals for a coherent and comprehensive scheme to promote dose limitation in a wide range of circumstances. These are described, with current initiatives on consultation with National Associations, local Government and many special interest groups. (author)

Study on the method or reducing the operator's exposure dose from a C-Arm system

International Nuclear Information System (INIS)

Kim, Ki Sik; Song, Jong Nam; Kim, Seung Ok

2016-01-01

In this study, C-Arm equipment is being used as we intend to verify the exposure dose on the operator by the scattering rays during the operation of the C-Arm equipment and to provide an effective method of reducing the exposure dose. Exposure dose is less than the Over Tube method utilizes the C-arm equipment Under Tube the scheme, The result showed that the exposure dose on the operator decreased with a thicker shield, and as the operator moved away from the center line. Moreover, as the research time prolongated, the exposure dose increased, and among the three affixed location of the dosimeter, the most exposure dose was measured at gonadal, then followed by chest and thyroid. However, in consideration of the relationship between the operator and the patient, the distance cannot be increased infinitely and the research time cannot be decreased infinitely in order to reduce the exposure dose. Therefore, by changing the thickness of the radiation shield, the exposure dose on the operator was able to be reduced. If you are using a C-Arm equipment discomfort during surgery because the grounds that the procedure is neglected and close to the dose of radiation shielding made can only increase. Because a separate control room cannot be used for the C-Arm equipment due to its characteristic, the exposure dose on the operator needs to be reduced by reinforcing the shield through an appropriate thickness of radiation shield devices, such as apron, etc. during a treatment

Prolonged operative time increases infection rate in tibial plateau fractures.

Science.gov (United States)

Colman, Matthew; Wright, Adam; Gruen, Gary; Siska, Peter; Pape, Hans-Christoph; Tarkin, Ivan

2013-02-01

Fractures of the tibial plateau present a treatment challenge and are susceptible to both prolonged operative times and high postoperative infection rates. For those fractures treated with open plating, we sought to identify the relationship between surgical site infection and prolonged operative time as well as to identify other surgical risk factors. We performed a retrospective controlled analysis of 309 consecutive unicondylar and bicondylar tibial plateau fractures treated with open plate osteosynthesis at our institution's level I trauma centre during a recent 5-year period. We recorded operative times, injury characteristics, surgical treatment, and need for operative debridement due to infection. Operative times of infected cases were compared to uncomplicated surgical cases. Multivariable logistic regression analysis was performed to identify independent risk factors for postoperative infection. Mean operative time in the infection group was 2.8h vs. 2.2h in the non-infected group (p=0.005). 15 fractures (4.9%) underwent four compartment fasciotomies as part of their treatment, with a significantly higher infection rate than those not undergoing fasciotomy (26.7% vs. 6.8%, p=0.01). Open fracture grade was also significantly related to infection rate (closed fractures: 5.3%, grade 1: 14.3%, grade 2: 40%, grade 3: 50%, pinfection rates (13.9% vs. 8.7%, p=0.36). Multivariable logistic regression analysis of the entire study group identified longer operative times (OR 1.78, p=0.013) and open fractures (OR 7.02, psite infection. Operative times approaching 3h and open fractures are related to an increased overall risk for surgical site infection after open plating of the tibial plateau. Dual incision approaches with bicolumnar plating do not appear to expose the patient to increased risk compared to single incision approaches. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

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.

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.

Food cues do not modulate the neuroendocrine response to a prolonged fast in healthy men.

Science.gov (United States)

Snel, Marieke; Wijngaarden, Marjolein A; Bizino, Maurice B; van der Grond, Jeroen; Teeuwisse, Wouter M; van Buchem, Mark A; Jazet, Ingrid M; Pijl, Hanno

2012-01-01

Dietary restriction benefits health and increases lifespan in several species. Food odorants restrain the beneficial effects of dietary restriction in Drosophila melanogaster. We hypothesized that the presence of visual and odorous food stimuli during a prolonged fast modifies the neuroendocrine and metabolic response to fasting in humans. In this randomized, crossover intervention study, healthy young men (n = 12) fasted twice for 60 h; once in the presence and once in the absence of food-related visual and odorous stimuli. At baseline and on the last morning of each intervention, an oral glucose tolerance test (OGTT) was performed. During the OGTT, blood was sampled and a functional MRI scan was made. The main effects of prolonged fasting were: (1) decreased plasma thyroid stimulating hormone and triiodothyronine levels; (2) downregulation of the pituitary-gonadal axis; (3) reduced plasma glucose and insulin concentrations, but increased glucose and insulin responses to glucose ingestion; (4) altered hypothalamic blood oxygenation level-dependent (BOLD) signal in response to the glucose load (particularly during the first 20 min after ingestion); (5) increased resting energy expenditure. Exposure to food cues did not affect these parameters. This study shows that 60 h of fasting in young men (1) decreases the hypothalamic BOLD signal in response to glucose ingestion; (2) induces glucose intolerance; (3) increases resting energy expenditure, and (4) downregulates the pituitary-thyroid and pituitary-gonadal axes. Exposure to visual and odorous food cues did not alter these metabolic and neuroendocrine adaptations to nutrient deprivation. Copyright © 2012 S. Karger AG, Basel.

Resolution of trauma-related guilt following treatment of PTSD in female rape victims: a result of cognitive processing therapy targeting comorbid depression?

Science.gov (United States)

Nishith, Pallavi; Nixon, Reginald D V; Resick, Patricia A

2005-06-01

Although Resick et al. [Resick, P.A., Nishith, P., Weaver, T.L., Astin, M.C., Feuer, C.A., 2002. 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. J. Consult. Clin. Psychol. 70, 867-879.] reported comparable results for treating rape-related posttraumatic stress disorder (PTSD) using either cognitive-processing therapy (CPT) or prolonged exposure (PE), there was some suggestion that CPT resulted in better outcomes than PE for certain aspects of trauma-related guilt. The present study revisited these findings to examine whether this effect was a function of improvement in a subset of participants with both PTSD and major depressive disorder (MDD). Results indicated that CPT was just as effective in treating "pure" PTSD and PTSD with comorbid MDD in terms of guilt. Clinical significance testing underscored that CPT was more effective in reducing certain trauma-related guilt cognitions than PE. Findings cannot be generalized to men, and only one measure of guilt was used. The observed superiority of CPT over PE for treating certain guilt cognitions was not due to participant comorbidity. Further research is recommended to untangle the relationship between guilt, depression and differential response to treatment in PTSD following sexual assault trauma.

Veteran satisfaction and treatment preferences in response to a posttraumatic stress disorder specialty clinic orientation group.

Science.gov (United States)

Schumm, Jeremiah A; Walter, Kristen H; Bartone, Anne S; Chard, Kathleen M

2015-06-01

To maximize accessibility to evidence-based treatments for posttraumatic stress disorder (PTSD), the United States Department of Veterans Affairs (VA) has widely disseminated cognitive processing therapy (CPT) and prolonged exposure (PE) therapy to VA clinicians. However, there is a lack of research on veteran preferences when presented with a range of psychotherapy and medication options. This study uses a mixed-method approach to explore veteran satisfaction with a VA PTSD specialty clinic pre-treatment orientation group, which provides education about available PTSD treatment options. This study also tested differences in treatment preference in response to the group. Participants were 183 US veterans. Most were White, male, and referred to the clinic by a VA provider. Results indicated high satisfaction with the group in providing an overview of services and helping to inform treatment choice. Most preferred psychotherapy plus medications (63.4%) or psychotherapy only (30.1%). Participants endorsed a significantly stronger preference for CPT versus other psychotherapies. PE was significantly preferred over nightmare resolution therapy and present-centered therapy, and both PE and cognitive-behavioral conjoint therapy were preferred over virtual reality exposure therapy. Results suggest that by informing consumers about evidence-based treatments for PTSD, pre-treatment educational approaches may increase consumer demand for these treatment options. Published by Elsevier Ltd.

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

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.

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)

Predictive factors for oropharyngeal dysphagia after prolonged orotracheal intubation.

Science.gov (United States)

Oliveira, Ana Carolina Martins de; Friche, Amélia Augusta de Lima; Salomão, Marina Silva; Bougo, Graziela Chamarelli; Vicente, Laélia Cristina Caseiro

2017-09-13

Lesions in the oral cavity, pharynx and larynx due to endotracheal intubation can cause reduction in the local motility and sensitivity, impairing the swallowing process, resulting in oropharyngeal dysphagia. To verify the predictive factors for the development of oropharyngeal dysphagia and the risk of aspiration in patients with prolonged orotracheal intubation admitted to an intensive care unit. This is an observational, analytical, cross-sectional and retrospective data collection study of 181 electronic medical records of patients submitted to prolonged orotracheal intubation. Data on age; gender; underlying disease; associated comorbidities; time and reason for orotracheal intubation; Glasgow scale on the day of the Speech Therapist assessment; comprehension; vocal quality; presence and severity of dysphagia; risk of bronchoaspiration; and the suggested oral route were collected. The data were analyzed through logistic regression. The level of significance was set at 5%, with a 95% Confidence Interval. The prevalence of dysphagia in this study was 35.9% and the risk of aspiration was 24.9%. As the age increased, the altered vocal quality and the degree of voice impairment increased the risk of the presence of dysphagia by 5-; 45.4- and 6.7-fold, respectively, and of aspiration by 6-; 36.4- and 4.8-fold. The increase in the time of orotracheal intubation increased the risk of aspiration by 5.5-fold. Patients submitted to prolonged intubation who have risk factors associated with dysphagia and aspiration should be submitted to an early speech-language/audiology assessment and receive appropriate and timely treatment. The recognition of these predictive factors by the entire multidisciplinary team can minimize the possibility of clinical complications inherent to the risk of dysphagia and aspiration in extubated patients. Copyright © 2017. Published by Elsevier Editora Ltda.

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.

Fermionic covariant prolongation structure theory for supernonlinear evolution equation

International Nuclear Information System (INIS)

Cheng Jipeng; Wang Shikun; Wu Ke; Zhao Weizhong

2010-01-01

We investigate the superprincipal bundle and its associated superbundle. The super(nonlinear)connection on the superfiber bundle is constructed. Then by means of the connection theory, we establish the fermionic covariant prolongation structure theory of the supernonlinear evolution equation. In this geometry theory, the fermionic covariant fundamental equations determining the prolongation structure are presented. As an example, the supernonlinear Schroedinger equation is analyzed in the framework of this fermionic covariant prolongation structure theory. We obtain its Lax pairs and Baecklund transformation.

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.

Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells

DEFF Research Database (Denmark)

Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Pilgaard, Linda

2011-01-01

Transplantation of mesenchymal stromal cells (MSC), including adipose tissue-derived stem cells (ASC), is a promising option in the treatment of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti-apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxi...

Lumbosacral Plexus Injury and Brachial Plexus Injury Following Prolonged Compression

Directory of Open Access Journals (Sweden)

Chung-Lan Kao

2006-11-01

Full Text Available We report the case of a 36-year-old woman who developed right upper and lower limb paralysis with sensory deficit after sedative drug overdose with prolonged immobilization. Due to the initial motor and sensory deficit pattern, brachial plexus injury or C8/T1 radiculopathy was suspected. Subsequent nerve conduction study/electromyography proved the lesion level to be brachial plexus. Painful swelling of the right buttock was suggestive of gluteal compartment syndrome. Elevation of serum creatine phosphokinase and urinary occult blood indicated rhabdomyolysis. The patient received medical treatment and rehabilitation; 2 years after the injury, her right upper and lower limb function had recovered nearly completely. As it is easy to develop complications such as muscle atrophy and joint contracture during the paralytic period of brachial plexopathy and lumbosacral plexopathy, early intervention with rehabilitation is necessary to ensure that the future limb function of the patient can be recovered. Our patient had suspected gluteal compartment syndrome that developed after prolonged compression, with the complication of concomitant lumbosacral plexus injury and brachial plexus injury, which is rarely reported in the literature. A satisfactory outcome was achieved with nonsurgical management.

Prolonged heart xenograft survival using combined total lymphoid irradiation and cyclosporine

International Nuclear Information System (INIS)

Knechtle, S.J.; Halperin, E.C.; Saad, T.; Bollinger, R.R.

1986-01-01

Total lymphoid irradiation and cyclosporine have profound immunosuppressive properties and permit successful heart allotransplantation. Cyclosporine used alone has not permitted consistently successful transplantation between species in all cases. Total lymphoid irradiation has not been applied to xenotransplantation. The efficacy of total lymphoid irradiation alone and in combination with cyclosporine was examined using an animal model of heart xenotransplantation. Heterotopic heart transplants were performed using inbred Syrian hamsters as donors and Lewis rats as recipients. Total lymphoid irradiation was administered preoperatively over 3 weeks for a total dose of 15 gray. Cyclosporine was started on the day of surgery and was given as a daily intramuscular injection of 2.5, 5, or 10 mg/kg/day until rejection was complete. Neither total lymphoid irradiation nor cyclosporine alone markedly prolonged graft survival. However, combined total lymphoid irradiation and cyclosporine, 5 or 10 mg/kg/day, dramatically prolonged graft survival to greater than 100 days in most recipients. There were no treatment-related deaths. In conclusion, combined total lymphoid irradiation and cyclosporine permit successful long-term survival of heart xenotransplants in this hamster-to-rat model

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)

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.

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.

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…

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.

Effect of prolonged continuous irradiation of humoral immunity of mice

International Nuclear Information System (INIS)

Kirillova, E.N.; Muksinova, K.N.; Skukovskaya, T.L.

1988-01-01

Changes in the content and function of cell populations and subpopulations involved in the humoral response of mice to the thymus-dependent antigen were investigated. The effect was followed during a prolonged continuous exposure to 137 C gamma-emitter (total dose - 5 Gy and daily dose - 12 cGy for 22 hours) and after its termination. The data obtained give evidence for a decrease of the pool of polypotent lymphocyte precursors (CFUs), stable moderate hypoplasia of central and peripheral organs of the immune system, distinct inhibition of antibody production at the expense of reduced activity of precursors of lymphocytes, B-lymphocytes and T-helpers. In the remote post-irradiation period residual radiation damage was seen in polypotent and committed precursors of lymphocytes and T-helpers, which was responsible for the trend towards the decline of antibody production, hypoplasia in the spleen and lymph nodes being persistent

Effect of intravenous ondansetron on QT interval prolongation in patients with cardiovascular disease and additional risk factors for torsades: a prospective, observational study

Directory of Open Access Journals (Sweden)

Hafermann MJ

2011-10-01

Full Text Available Matthew J Hafermann1, Rocsanna Namdar2, Gretchen E Seibold2,3, Robert Lee Page 2nd2,31University of Washington Medical Center, Department of Pharmacy, Seattle, WA; 2University of Colorado Anschutz Medical Campus, School of Pharmacy, Aurora, CO; 3University of Colorado Hospital, Department of Pharmacy, Aurora, CO USABackground: The 5-hydroxytryptamine type 3 antagonists, or setrons (eg, ondansetron, are commonly used for nausea and vomiting in the hospital setting. In 2001, droperidol was given a black box warning because it was found to prolong the QT interval and induce arrhythmias. The setrons share with droperidol the same potential proarrhythmic mechanisms, but limited data exist concerning their effects on the QT interval in individuals at high risk for torsades de pointes.Methods: Forty hospitalized patients admitted for heart failure or acute coronary syndromes with one or more risk factors for torsades de pointes and an order for intravenous ondansetron 4 mg were enrolled in this prospective, observational study. The QT interval corrected for heart rate (QTc was obtained via a 12-lead electrocardiogram on admission and again 120 minutes after the first dose of ondansetron in order to determine the mean change in QTc following ondansetron exposure.Results: The mean time interval between obtaining the baseline electrocardiogram and the second electrocardiogram following ondansetron administration was 3.5 ± 2.14 hours. In the total population, the QTc interval was prolonged by 19.3 ± 18 msec (P < 0.0001 120 minutes after ondansetron administration. For patients with an acute coronary syndrome and those with heart failure, QTc was prolonged by 18.3 ± 20 msec (P < 0.0001 and 20.6 ± 20 msec (P < 0.0012, respectively. Following ondansetron exposure, 31% and 46% in the heart failure and acute coronary syndromes groups, respectively, met gender-related thresholds for a prolonged QTc.Conclusion: Our study found QTc prolongation due to

Short-term pre- and post-operative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception.

Science.gov (United States)

Cao, Jing; Wang, Po-Kai; Tiwari, Vinod; Liang, Lingli; Lutz, Brianna Marie; Shieh, Kun-Ruey; Zang, Wei-Dong; Kaufman, Andrew G; Bekker, Alex; Gao, Xiao-Qun; Tao, Yuan-Xiang

2015-12-02

Chronic stress has been reported to increase basal pain sensitivity and/or exacerbate existing persistent pain. However, most surgical patients have normal physiological and psychological health status such as normal pain perception before surgery although they do experience short-term stress during pre- and post-operative periods. Whether or not this short-term stress affects persistent postsurgical pain is unclear. In this study, we showed that pre- or post-surgical exposure to immobilization 6 h daily for three consecutive days did not change basal responses to mechanical, thermal, or cold stimuli or peak levels of incision-induced hypersensitivity to these stimuli; however, immobilization did prolong the duration of incision-induced hypersensitivity in both male and female rats. These phenomena were also observed in post-surgical exposure to forced swimming 25 min daily for 3 consecutive days. Short-term stress induced by immobilization was demonstrated by an elevation in the level of serum corticosterone, an increase in swim immobility, and a decrease in sucrose consumption. Blocking this short-term stress via intrathecal administration of a selective glucocorticoid receptor antagonist, RU38486, or bilateral adrenalectomy significantly attenuated the prolongation of incision-induced hypersensitivity to mechanical, thermal, and cold stimuli. Our results indicate that short-term stress during the pre- or post-operative period delays postoperative pain recovery although it does not affect basal pain perception. Prevention of short-term stress may facilitate patients' recovery from postoperative pain.

Lung clearance of inhaled particles after exposure to carbon black generated from a resuspension system

International Nuclear Information System (INIS)

Lee, P.S.; Gorski, R.A.; Hering, W.E.; Chan, T.L.

1987-01-01

A system to resuspend carbon black particles for providing submicron aerosols for inhalation exposure studies has been developed. The effect of continuous exposure to carbonaceous material (as a surrogate for the carbonaceous particles in diesel exhaust) on the pulmonary clearance of inhaled diesel tracer particles was studied in male Fischer 344 rats. Submicron carbon black particles with a mass median aerodynamic diameter (MMAD) of 0.22 micron and a size distribution similar to that of exhaust particles from a GM 5.7-liter diesel engine were successfully generated and administered to test animals at a nominal concentration of 6 mg/m3 for 20 hr/day, 7 days/week, for periods lasting 1 to 11 weeks. Immediately after the carbon black exposure, test animals were administered 14 C-tagged diesel particles for 45 min in a nose-only chamber. The pulmonary retention of inhaled radioactive tracer particles was determined at preselected time intervals. Based upon the data collected up to 1 year postexposure, prolonged exposure to carbon black particles exhibits a similar inhibitory effect on pulmonary clearance as does prolonged exposure to diesel exhaust with a comparable particulate dose. This observation indicates that the excessive accumulation of carbonaceous material may be the predominant factor affecting lung clearance

Exposure-lag-response in Longitudinal Studies: Application of Distributed Lag Non-linear Models in an Occupational Cohort.

Science.gov (United States)

Neophytou, Andreas M; Picciotto, Sally; Brown, Daniel M; Gallagher, Lisa E; Checkoway, Harvey; Eisen, Ellen A; Costello, Sadie

2018-02-13

Prolonged exposures can have complex relationships with health outcomes, as timing, duration, and intensity of exposure are all potentially relevant. Summary measures such as cumulative exposure or average intensity of exposure may not fully capture these relationships. We applied penalized and unpenalized distributed lag non-linear models (DLNMs) with flexible exposure-response and lag-response functions in order to examine the association between crystalline silica exposure and mortality from lung cancer and non-malignant respiratory disease in a cohort study of 2,342 California diatomaceous earth workers, followed 1942-2011. We also assessed associations using simple measures of cumulative exposure assuming linear exposure-response and constant lag-response. Measures of association from DLNMs were generally higher than from simpler models. Rate ratios from penalized DLNMs corresponding to average daily exposures of 0.4 mg/m3 during lag years 31-50 prior to the age of observed cases were 1.47 (95% confidence interval (CI) 0.92, 2.35) for lung cancer and 1.80 (95% CI: 1.14, 2.85) for non-malignant respiratory disease. Rate ratios from the simpler models for the same exposure scenario were 1.15 (95% CI: 0.89-1.48) and 1.23 (95% CI: 1.03-1.46) respectively. Longitudinal cohort studies of prolonged exposures and chronic health outcomes should explore methods allowing for flexibility and non-linearities in the exposure-lag-response. © The Author(s) 2018. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

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.

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.

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...

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)

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

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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.

Treatment Preference among Suicidal and Self-Injuring Women with Borderline Personality Disorder and PTSD

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Harned, Melanie S.; Tkachuck, Mathew A.; Youngberg, Kelly A.

2014-01-01

Objectives This study examined treatment preferences among suicidal and self-injuring women with borderline personality disorder (BPD) and PTSD. Method Women (N = 42, Mage =34) with BPD, PTSD and recent intentional self-injury were evaluated upon entry into a psychotherapy outcome study. Results The majority preferred a combined dialectical behavior therapy (DBT) and prolonged exposure (PE) treatment (73.8%), followed by DBT alone (26.2%), and PE alone (0%). Women who preferred the combined treatment were more likely to report a desire to obtain relief from PTSD and to receive specific DBT and PE treatment components as reasons underlying this preference. Few women (21.4%) reported concerns about PE, but those who did were more likely to prefer DBT alone. More severe PTSD re-experiencing symptoms, a childhood index trauma, and less reduction in positive affect after a trauma interview predicted a preference for the combined treatment. Conclusions These results may help to inform treatment for these complex patients. PMID:23444147

Rape treatment outcome research: empirical findings and state of the literature.

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Vickerman, Katrina A; Margolin, Gayla

2009-07-01

This article reviews empirical support for treatments targeting women sexually assaulted during adolescence or adulthood. Thirty-two articles were located using data from 20 separate samples. Of the 20 samples, 12 targeted victims with chronic symptoms, three focused on the acute period post-assault, two included women with chronic and acute symptoms, and three were secondary prevention programs. The majority of studies focus on posttraumatic stress disorder (PTSD), depression, and/or anxiety as treatment targets. Cognitive Processing Therapy and Prolonged Exposure have garnered the most support with this population. Stress Inoculation Training and Eye Movement Desensitization and Reprocessing also show some efficacy. Of the four studies that compared active treatments, few differences were found. Overall, cognitive behavioral interventions lead to better PTSD outcomes than supportive counseling does. However, even in the strongest treatments more than one-third of women retain a PTSD diagnosis at post-treatment or drop out of treatment. Discussion highlights the paucity of research in this area, methodological limitations of examined studies, generalizability of findings, and important directions for future research at various stages of trauma recovery.

Rape Treatment Outcome Research: Empirical Findings and State of the Literature

Science.gov (United States)

Vickerman, Katrina A.; Margolin, Gayla

2009-01-01

This article reviews empirical support for treatments targeting women sexually assaulted during adolescence or adulthood. Thirty-two articles were located using data from 20 separate samples. Of the 20 samples, 12 targeted victims with chronic symptoms, three focused on the acute period post-assault, two included women with chronic and acute symptoms, and three were secondary prevention programs. The majority of studies focus on posttraumatic stress disorder (PTSD), depression, and/or anxiety as treatment targets. Cognitive Processing Therapy and Prolonged Exposure have garnered the most support with this population. Stress Inoculation Training and Eye Movement Desensitization and Reprocessing also show some efficacy. Of the four studies that compared active treatments, few differences were found. Overall, cognitive behavioral interventions lead to better PTSD outcomes than supportive counseling does. However, even in the strongest treatments more than one-third of women retain a PTSD diagnosis at post-treatment or drop out of treatment. Discussion highlights the paucity of research in this area, methodological limitations of examined studies, generalizability of findings, and important directions for future research at various stages of trauma recovery. PMID:19442425

Persistent modification of Na{sub v}1.9 following chronic exposure to insecticides and pyridostigmine bromide

Energy Technology Data Exchange (ETDEWEB)

Nutter, Thomas J., E-mail: tnutter@dental.ufl.edu; Cooper, Brian Y., E-mail: bcooper@dental.ufl.edu

2014-06-15

Many veterans of the 1991 Gulf War (GW) returned from that conflict with a widespread chronic pain affecting deep tissues. Recently, we have shown that a 60 day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine bromide (NTPB) had little influence on nociceptor action potential forming Na{sub v}1.8, but increased K{sub v}7 mediated inhibitory currents 8 weeks after treatment. Using the same exposure regimen, we used whole cell patch methods to examine whether the influences of NTPB could be observed on Na{sub v}1.9 expressed in muscle and vascular nociceptors. During a 60 day exposure to NTPB, rats exhibited lowered muscle pain thresholds and increased rest periods, but these measures subsequently returned to normal levels. Eight and 12 weeks after treatments ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch studies revealed little change in voltage dependent activation and deactivation of Na{sub v}1.9, but significant increases in the amplitude of Na{sub v}1.9 were observed 8 weeks after exposure. Cellular studies, at the 8 week delay, revealed that NTPB also significantly prolonged action potential duration and afterhyperpolarization (22 °C). Acute application of permethrin (10 μM) also increased the amplitude of Na{sub v}1.9 in skin, muscle and vascular nociceptors. In conclusion, chronic exposure to Gulf War agents produced long term changes in the amplitude of Na{sub v}1.9 expressed in muscle and vascular nociceptors. The reported increases in K{sub v}7 amplitude may have been an adaptive response to increased Na{sub v}1.9, and effectively suppressed behavioral pain measures in the post treatment period. Factors that alter the balance between Na{sub v}1.9 and K{sub v}7 could release spontaneous discharge and produce chronic deep tissue pain. - Highlights: • Rats were treated 60 days with permethrin, chlorpyrifos and pyridostigmine bromide. • 8 weeks after treatments, Nav1.9 activation and deactivation were

Drug therapy for congestive heart failure:appropriate choices can prolong life

International Nuclear Information System (INIS)

Sorrentino, M

1997-01-01

Between one purpose of the insufficiency congestive heart is improve and prolong the quality life. A good multidisciplinary health equipment can help to the improving patients with this disease referred to effective handling interned and ambulatory patients groups. The inhibition mechanism compensate that perpetuate heart congestive insufficiency are a way for reach treatment purposes. Between patients with symptomatic cardiac insufficiency and overload volume is indicated digoxin(Lanoxin) and vasodilators. The enzyme inhibition angiotensin converted improve over life range more than an others vasodilators and is preferred for the systole dysfunction patients

Prolonged Exposure Therapy Following Awareness under Anesthesia: A Case Study

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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…

PROLONGED MULTIPLE SPASMS OF SMOOTH CORONARY ARTERIES PRESENTING AS ACUTE MIOCARDIAL INFARCTION, COMPLETE AV BLOCK AND SYNCOPE

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Franci Cesar

2004-11-01

Full Text Available Background. A variant form of angina pectoris (VAP is caused by coronary vessel spasm and occures in patients with and without varying degrees of obstructive coronary artery disease. Although the prognosis of VAP without significant organic stenosis is generally good, multivessel spasm is associated with a high risk of life-threatening abnormalities of rhythm and conduction.Patient and methods. We describe a patient who presented with prolonged chest pain, associated with hypotension, lost of consciousness, complete AV block and widespread ST segment elevations consistent with inferoanterior acute myocardial infarction. Urgent selective coronary angiography revealed spasms in right coronary artery and in left circumflex artery that were relieved by intracoronary injection of nitroglycerin. All coronary arteries were otherwise patient, without signs of atherosclerosis. The patient was treated with diltiazem and nitrates. She made a complete recovery and resumed her normal activities.Conclusions. Simultaneous multiple spasms of native coronary arteries represent a rare syndrome characterized by significantly higher incidence of potentially life-threatening arrhythmia. Less commonly, prolonged coronary spasm may mimic acute myocardial infarction. Modern management of acute coronary syndromes, including urgent coronarography, enables a prompt differentiation between prolonged coronary spasm and atherosclerotic coronary disease, warranting different treatment strategies. Medical treatment with nitrates and calcium channel blockers in most cases prevents recurrence of vasospasms and arrhythmias.

Predictors of Prolonged TB Treatment in a Dutch Outpatient Setting.

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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.

Effectiveness of prolonged use of continuous passive motion (CPM, as an adjunct to physiotherapy, after total knee arthroplasty

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Geesink Ruud JT

2008-04-01

Full Text Available Abstract Background Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty. Although research suggests that Continuous Passive Motion (CPM should be implemented in the first rehabilitation phase after surgery, there is substantial debate about the duration of each session and the total period of CPM application. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. Methods In a randomised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to standardised PT. Efficacy was assessed in terms of faster improvements in range of motion (RoM and functional recovery, measured at the end of the active treatment period, 17 days after surgery. Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were randomised over two treatment groups. The experimental group received CPM + PT for 17 consecutive days after surgery, whereas the usual care group received the same treatment during the in-hospital phase (i.e. about four days, followed by PT alone (usual care in the first two weeks after hospital discharge. From 18 days to three months after surgery, both groups received standardised PT. The primary focus of rehabilitation was functional recovery (e.g. ambulation and regaining RoM in the knee. Results Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-standard PT programme. Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessments. Conclusion Although results

Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty

Science.gov (United States)

Lenssen, Ton AF; van Steyn, Mike JA; Crijns, Yvonne HF; Waltjé, Eddie MH; Roox, George M; Geesink, Ruud JT; Brandt, Piet A van den; De Bie, Rob A

2008-01-01

Background Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty. Although research suggests that Continuous Passive Motion (CPM) should be implemented in the first rehabilitation phase after surgery, there is substantial debate about the duration of each session and the total period of CPM application. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. Methods In a randomised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to standardised PT. Efficacy was assessed in terms of faster improvements in range of motion (RoM) and functional recovery, measured at the end of the active treatment period, 17 days after surgery. Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were randomised over two treatment groups. The experimental group received CPM + PT for 17 consecutive days after surgery, whereas the usual care group received the same treatment during the in-hospital phase (i.e. about four days), followed by PT alone (usual care) in the first two weeks after hospital discharge. From 18 days to three months after surgery, both groups received standardised PT. The primary focus of rehabilitation was functional recovery (e.g. ambulation) and regaining RoM in the knee. Results Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-standard PT programme. Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessments. Conclusion Although results indicate that prolonged CPM use

Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty.

Science.gov (United States)

Lenssen, Ton A F; van Steyn, Mike J A; Crijns, Yvonne H F; Waltjé, Eddie M H; Roox, George M; Geesink, Ruud J T; van den Brandt, Piet A; De Bie, Rob A

2008-04-29

Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty. Although research suggests that Continuous Passive Motion (CPM) should be implemented in the first rehabilitation phase after surgery, there is substantial debate about the duration of each session and the total period of CPM application. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. In a randomised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to standardised PT. Efficacy was assessed in terms of faster improvements in range of motion (RoM) and functional recovery, measured at the end of the active treatment period, 17 days after surgery. Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were randomised over two treatment groups. The experimental group received CPM + PT for 17 consecutive days after surgery, whereas the usual care group received the same treatment during the in-hospital phase (i.e. about four days), followed by PT alone (usual care) in the first two weeks after hospital discharge. From 18 days to three months after surgery, both groups received standardised PT. The primary focus of rehabilitation was functional recovery (e.g. ambulation) and regaining RoM in the knee. Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-standard PT programme. Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessments. Although results indicate that prolonged CPM use might have a small short-term effect

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

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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

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

Study on the method or reducing the operator's exposure dose from a C-Arm system

Energy Technology Data Exchange (ETDEWEB)

Kim, Ki Sik; Song, Jong Nam [Dept. of Radiological Science, Dongshin University, Naju (Korea, Republic of); Kim, Seung Ok [Dept. of Radiology, Catholic Kwangdong Universty International ST.Mary' s Hospital, Incheon (Korea, Republic of)

2016-12-15

In this study, C-Arm equipment is being used as we intend to verify the exposure dose on the operator by the scattering rays during the operation of the C-Arm equipment and to provide an effective method of reducing the exposure dose. Exposure dose is less than the Over Tube method utilizes the C-arm equipment Under Tube the scheme, The result showed that the exposure dose on the operator decreased with a thicker shield, and as the operator moved away from the center line. Moreover, as the research time prolongated, the exposure dose increased, and among the three affixed location of the dosimeter, the most exposure dose was measured at gonadal, then followed by chest and thyroid. However, in consideration of the relationship between the operator and the patient, the distance cannot be increased infinitely and the research time cannot be decreased infinitely in order to reduce the exposure dose. Therefore, by changing the thickness of the radiation shield, the exposure dose on the operator was able to be reduced. If you are using a C-Arm equipment discomfort during surgery because the grounds that the procedure is neglected and close to the dose of radiation shielding made can only increase. Because a separate control room cannot be used for the C-Arm equipment due to its characteristic, the exposure dose on the operator needs to be reduced by reinforcing the shield through an appropriate thickness of radiation shield devices, such as apron, etc. during a treatment.

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

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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…

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

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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.

Inconsistency in the Diagnosis of Functional Heartburn: Usefulness of Prolonged Wireless pH Monitoring in Patients With Proton Pump Inhibitor Refractory Gastroesophageal Reflux Disease

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Penagini, Roberto; Sweis, Rami; Mauro, Aurelio; Domingues, Gerson; Vales, Andres; Sifrim, Daniel

2015-01-01

Background/Aims The diagnosis of functional heartburn is important for management, however it stands on fragile pH monitoring variables, ie, acid exposure time varies from day to day and symptoms are often few or absent. Aim of this study was to investigate consistency of the diagnosis of functional heartburn in subsequent days using prolonged wireless pH monitoring and its impact on patients’ outcome. Methods Fifty proton pump inhibitotor refractory patients (11 male, 48 years [range, 38–57 years]) with a diagnosis of functional heart-burn according to Rome III in the first 24 hours of wireless pH monitoring were reviewed. pH variables were analysed in the following 24-hour periods to determine if tracings were indicative of diagnosis of non-erosive reflux disease (either acid exposure time > 5% or normal acid exposure time and symptom index ≥ 50%). Outcome was assessed by review of hospital files and/or telephone interview. Results Fifteen out of 50 patients had a pathological acid exposure time after the first day of monitoring (10 in the second day and 5 in subsequent days), which changed their diagnosis from functional heartburn to non-erosive reflux disease. Fifty-four percent of non-erosive reflux disease vs 11% of functional heartburn patients (P heartburn patients (P heartburn at 24-hour pH-monitoring can be re-classified as non-erosive reflux disease after a more prolonged pH recording period. This observation has a positive impact on patients’ management. PMID:25843078

SALIVARY ANTIMICROBIAL PROTEIN RESPONSE TO PROLONGED RUNNING

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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.

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

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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.

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

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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

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....

Nickel on the market: a baseline survey of articles in 'prolonged contact' with skin.

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