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Sample records for term glucocorticoid therapy

  1. Short-term versus longer duration of glucocorticoid therapy for exacerbations of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Ma, Zhao; Zhang, Wei

    2016-10-01

    Systemic glucocorticoid has been shown to improve the outcome of acute exacerbation of chronic obstructive pulmonary disease (COPD). However, the optimal duration remains controversial. To investigate whether a short-term (seven days or fewer) systemic glucocorticoid treatment in patients with COPD exacerbation is non inferior to longer duration (more than seven days) treatment in clinical outcome. We searched PubMed, EMBASE, CENTRAL databases, China Clinical Trials, CNKI, The Chinese biomedical literature database (CBM) and wanfang database to identify randomized controlled trials using systemic glucocorticoid in COPD. At least two review authors independently assessed each potentially eligible trial for its inclusion in the review and its quality. Glucocorticoid is given for a period of seven days or fewer versus systemic given for more than seven days. We retrieved time from building to Apr 20, 2016, and supplemented by manual retrieval into literature references. By adopting the combination of keywords and free word retrieval methods, we performed a routine meta-analysis to evaluate the effects of glucocorticoid on FEV1, FEV1/FVC, PaO2, clinical symptoms, relapse, treatment failure, mortality and side-effects between the two treatment groups. Our search yielded 9 studies involving 874 patients. Six studies were fully published and three were published as abstracts. We obtained data for one study published as abstracts from authors. Short-term treatment varied between three and seven days and longer duration 10-15 days, at equivalent daily doses of glucocorticoid. Mean ages of participants ranged from 60 to 90 years. The FEV1, FEV1/FVC, PaO2 and clinical symptoms between the two treatment groups did not differ significantly by treatment duration. There was no significant difference of relapse, treatment failure, mortality and side-effects between the two treatment groups. These data show that short-term glucocorticoid is as effective as and possibly safer than

  2. Short-term assessment of BCR repertoires of SLE patients after high dose glucocorticoid therapy with high-throughput sequencing.

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    Shi, Bin; Yu, Jiang; Ma, Long; Ma, Qingqing; Liu, Chunmei; Sun, Suhong; Ma, Rui; Yao, Xinsheng

    2016-01-01

    We analyze and assess BCR repertoires of SLE patients before and after high dose glucocorticoid therapy to address two fundamental questions: (1) After the treatment, how the BCR repertoire of SLE patient change on the clone level? (2) How to screen putative autoantibody clone set from BCR repertoire of SLE patients? The PBMCs of two SLE patients (P1 and P2) at different time points were collected, and DNA of these samples were extracted. High-throughput sequencing technology was applied in detection of BCR repertoire. Finally, we used bioinformatic methodology to analyse sequence data. We found that these two patients lost some IGHV3 family genes usage after treatment compared with before treatment. For pairing of IGHV-IGHJ gene, no significant change was shown for each patient. In addition, analyses of the composition of H-CDR3 showed overall AA compositions of H-CDR3 at three time points in each SLE patients were very similar, and the results of H-CDR3 AA usage that had the same length (14 AA) and the same position were similar. Antinuclear antibody tests of SLE patients showed that level of some antinuclear antibodies reduced after treatment; however, there was no sign that the percentage of autoantibody clones in BCR repertoires would reduce. High dose glucocorticoid treatment in short term will have little impact on composition of BCR repertoire of SLE patient. Treatment can reduce the amount of autoantibody in the protein level, but may not reduce the percentage of autoantibody clones in BCR repertoire in the clonal level.

  3. Timing of glucocorticoid therapy for liver failure

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    MENG Qinghua

    2017-09-01

    Full Text Available There are still controversies over the use of glucocorticoids in the treatment of liver failure, and current guidelines for liver failure recommend that glucocorticoids should be used with great caution. However, some latest studies have shown that the use of glucocorticoid therapy in the early stage of liver failure can bring more benefits to patients. Age, disease progression rate and severity, and complications of liver failure may affect the treatment outcome. Further studies are still needed for the selection of right patients, drugs and dose, and treatment timing.

  4. From receptor balance to rational glucocorticoid therapy.

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    de Kloet, E Ron

    2014-08-01

    Corticosteroids secreted as end product of the hypothalamic-pituitary-adrenal axis act like a double-edged sword in the brain. The hormones coordinate appraisal processes and decision making during the initial phase of a stressful experience and promote subsequently cognitive performance underlying the management of stress adaptation. This action exerted by the steroids on the initiation and termination of the stress response is mediated by 2 related receptor systems: mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs). The receptor types are unevenly distributed but colocalized in abundance in neurons of the limbic brain to enable these complementary hormone actions. This contribution starts from a historical perspective with the observation that phasic occupancy of GR during ultradian rhythmicity is needed to maintain responsiveness to corticosteroids. Then, during stress, initially MR activation enhances excitability of limbic networks that are engaged in appraisal and emotion regulation. Next, the rising hormone concentration occupies GR, resulting in reallocation of energy to limbic-cortical circuits with a role in behavioral adaptation and memory storage. Upon MR:GR imbalance, dysregulation of the hypothalamic-pituitary-adrenal axis occurs, which can enhance an individual's vulnerability. Imbalance is characteristic for chronic stress experience and depression but also occurs during exposure to synthetic glucocorticoids. Hence, glucocorticoid psychopathology may develop in susceptible individuals because of suppression of ultradian/circadian rhythmicity and depletion of endogenous corticosterone from brain MR. This knowledge generated from testing the balance hypothesis can be translated to a rational glucocorticoid therapy.

  5. Perinatal glucocorticoid treatment and perspectives for antioxidat therapy

    NARCIS (Netherlands)

    Tijsseling, D.|info:eu-repo/dai/nl/338666885

    2014-01-01

    Pre- and postnatal glucocorticoids are a life-saving therapy for prematurely born infants. However, glucocorticoids also trigger unwanted side effects. In part I we investigated the effects of antenatal glucocorticoids on hippocampal development. First in a mice model using a clinically relevant

  6. Long-term safety, efficacy, and patient acceptability of teriparatide in the management of glucocorticoid-induced osteoporosis

    Directory of Open Access Journals (Sweden)

    Dore RK

    2013-05-01

    Full Text Available Robin K DoreDavid Geffen School of Medicine, University of California, Los Angeles, CA, USAAbstract: Glucocorticoids are commonly prescribed medications to treat multiple diseases across many medical specialties. One of the most common yet largely unappreciated side effect of glucocorticoid use is increased risk of fracture. Many different therapies are indicated to prevent and treat this condition; many guidelines exist that suggest appropriate use of both glucocorticoids and the medications approved to prevent this common side effect of glucocorticoid therapy. Nevertheless, 30%–50% of patients on long-term glucocorticoid therapy sustain a fracture. Teriparatide, recombinant human parathyroid hormone (1–34, is a daily self-injectable therapy for 24 months approved for use in patients taking long-term glucocorticoids. Teriparatide has been shown to increase bone mineral density and reduce vertebral fracture risk in glucocorticoid-treated patients. Glucocorticoids have many adverse effects on bone that teriparatide has been shown to prevent or negate. Given the fact that preventive therapy for glucocorticoid-induced osteoporosis is often not prescribed, one wonders whether a daily self-injectable therapy for this condition would be prescribed by physicians and accepted by patients. This article reviews the epidemiology, pathophysiology, treatment, guidelines, and persistence data (when available for patients with glucocorticoid-induced osteoporosis treated with teriparatide.Keywords: glucocorticoid-induced osteoporosis, teriparatide, anabolic, PTH, parathyroid hormone

  7. Addison disease in patients treated with glucocorticoid therapy.

    LENUS (Irish Health Repository)

    Cronin, C C

    2012-02-03

    Acute adrenal crisis in patients with unrecognized chronic adrenocortical failure is difficult to diagnose and potentially fatal. We describe 2 patients with acute adrenal crisis whose diagnoses were hindered because of concomitant glucocorticoid treatment. Acute adrenal insufficiency is primarily a state of mineralocorticoid deficiency. Prednisolone and prednisone, the most frequently prescribed anti-inflammatory corticosteroid agents, have minimal mineralocorticoid activity. Several conditions that may be treated with pharmacological glucocorticoids are associated with an increased risk of Addison disease. An acute adrenal crisis, against which concurrent glucocorticoid therapy does not confer adequate protection, may develop in such patients.

  8. Glucocorticoid therapy-induced memory deficits: acute versus chronic effects.

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    Coluccia, Daniel; Wolf, Oliver T; Kollias, Spyros; Roozendaal, Benno; Forster, Adrian; de Quervain, Dominique J-F

    2008-03-26

    Conditions with chronically elevated glucocorticoid levels are usually associated with declarative memory deficits. Considerable evidence suggests that long-term glucocorticoid exposure may cause cognitive impairment via cumulative and long-lasting influences on hippocampal function and morphology. However, because elevated glucocorticoid levels at the time of retention testing are also known to have direct impairing effects on memory retrieval, it is possible that such acute hormonal influences on retrieval processes contribute to the memory deficits found with chronic glucocorticoid exposure. To investigate this issue, we examined memory functions and hippocampal volume in 24 patients with rheumatoid arthritis who were treated either chronically (5.3 +/- 1.0 years, mean +/- SE) with low to moderate doses of prednisone (7.5 +/- 0.8 mg, mean +/- SE) or without glucocorticoids. In both groups, delayed recall of words learned 24 h earlier was assessed under conditions of either elevated or basal glucocorticoid levels in a double-blind, placebo-controlled crossover design. Although the findings in this patient population did not provide evidence for harmful effects of a history of chronic prednisone treatment on memory performance or hippocampal volume per se, acute prednisone administration 1 h before retention testing to either the steroid or nonsteroid group impaired word recall. Thus, these findings indicate that memory deficits observed under chronically elevated glucocorticoid levels result, at least in part, from acute and reversible glucocorticoid effects on memory retrieval.

  9. Salivary cortisol day curves in assessing glucocorticoid replacement therapy in Addison's disease

    NARCIS (Netherlands)

    Smans, L.; Lentjes, E.G.W.M.; Hermus, A.R.; Zelissen, P.

    2013-01-01

    OBJECTIVE: Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal physiology. As a consequence, under- and especially overtreatment can occur. Suboptimal GRT may lead to various side effects.

  10. Glucocorticoid Induced Cerebellar Toxicity in the Developing Neonate: Implications for Glucocorticoid Therapy during Bronchopulmonary Dysplasia

    Directory of Open Access Journals (Sweden)

    Kevin K. Noguchi

    2014-01-01

    Full Text Available Prematurely born infants commonly suffer respiratory dysfunction due to the immature state of their lungs. As a result, clinicians often administer glucocorticoid (GC therapy to accelerate lung maturation and reduce inflammation. Unfortunately, several studies have found GC therapy can also produce neuromotor/cognitive deficits and selectively stunt the cerebellum. However, despite its continued use, relatively little is known about how exposure to this hormone might produce neurodevelopmental deficits. In this review, we use rodent and human research to provide evidence that GC therapy may disrupt cerebellar development through the rapid induction of apoptosis in the cerebellar external granule layer (EGL. The EGL is a transient proliferative region responsible for the production of over 90% of the neurons in the cerebellum. During normal development, endogenous GC stimulation is thought to selectively signal the elimination of the EGL once production of new neurons is complete. As a result, GC therapy may precociously eliminate the EGL before it can produce enough neurons for normal cerebellar function. It is hoped that this review may provide information for future clinical research in addition to translational guidance for the safer use of GC therapy.

  11. Fatal and non-fatal adverse events of glucocorticoid therapy for Graves' orbitopathy

    DEFF Research Database (Denmark)

    Marcocci, Claudio; Watt, Torquil; Altea, Maria Antonietta

    2012-01-01

    The objective of this study was to investigate the side effects of glucocorticoid (GC) therapy observed by European thyroidologists during the treatment of Graves' orbitopathy (GO).......The objective of this study was to investigate the side effects of glucocorticoid (GC) therapy observed by European thyroidologists during the treatment of Graves' orbitopathy (GO)....

  12. Nutritonal evaluation of pemphigus foliaceus patients on long term glucocorticoid therapy Avaliação do estado nutricional de pacientes com pênfigo foliáceo sob corticoterapia prolongada

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    Daniel Ferreira da CUNHA

    2000-02-01

    Full Text Available Our objective was to compare food intake and nutritional status of Pemphigus Foliaceus patients (PG on long term glucocorticoid therapy to a Control Group (CG. Fourteen PG female inpatients receiving prednisone (0.33 ± 0.22mg/kg for at least 12 months and twelve CG subjects were submitted to nutritional evaluation, including anthropometry, urinary creatinine determination and serum biochemical measurements, besides 48-h-based food intake records. Groups were compared by Chi-square, Mann-Whitney and "t" tests. PG patients and CG were paired, respectively, in relation to age (24.7 ± 14.1 vs. 22.0 ± 12.0 years, body mass index (25.8 ± 6.4 vs. 24.0 ± 5.6kg/m2, daily protein intake (132.9 ± 49.8 vs. 95.2 ± 58.9g, and serum albumin (median; range (3.8; 3.5-4.1 vs. 3.8; 3.6-5.0g/dl. However, PG patients had lower height-creatinine index (64.8 ± 17.6 vs. 90.1 ± 33.4%, and higher daily energy (3080 ± 1099 vs. 2187 ± 702kcal and carbohydrate (376.8 ± 135.8 vs. 242.0 ± 80.7g intakes. Despite high food, protein and energy consumption, PG patients on long term glucocorticoid therapy had lower body muscle mass than controls, while showing high body fat stores. These findings are possibly related to combined metabolic effects of long term corticotherapy and inflammatory disease plus corticosteroid-induced increased appetite.O objetivo deste trabalho foi comparar o estado nutricional e dados de ingestão alimentar de pacientes com Pênfigo Foliáceo (PF, n=14 sob corticoterapia prolongada (prednisona, 0,33 ± 0,22mg/kg/dia há mais de 12 meses com um Grupo Controle (GC, n=12. A avaliação constou de inquérito alimentar de 48 horas, antropometria e determinação de creatinina urinária de 24h e albumina sérica. Os grupos PF e GC foram pareados, respectivamente, quanto à idade (24,7 ± 14,1 vs 22,0 ± 12,0 anos, índice de massa corporal (25,8 ± 6,4 vs 24,0 ± 5,6kg/m2, ingestão diária de proteína (132,9 ± 49,8 vs 95,2 ± 58,9g e albumina s

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

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    Yehuda, Rachel; Bierer, Linda M; Pratchett, Laura; Malowney, Monica

    2010-01-01

    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. 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. 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.

  14. 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.

  15. Clinical aspects of glucocorticoid sensitivity

    OpenAIRE

    Lamberts, Steven; Huizenga, Nannette; Lange, Pieter; Jong, Frank; Koper, Jan

    1996-01-01

    textabstractRecent studies demonstrate that primary (hereditary) abnormalities in the glucocorticoid receptor gene make 6.6% of the normal population relatively 'hypersensitive' to glucocorticoids, while 2.3% are relatively 'resistant.' These abnormalities might explain why some individuals develop severe adverse effects during low dose glucocorticoid therapy, while others do not develop side effects even during long-term therapy with a much higher dose. Awareness of this heterogeneity in glu...

  16. Long-Term Outcome of Interdisciplinary Management of Patients with Duchenne Muscular Dystrophy Receiving Daily Glucocorticoid Treatment.

    Science.gov (United States)

    Wong, Brenda L; Rybalsky, Irina; Shellenbarger, Karen C; Tian, Cuixia; McMahon, Mary A; Rutter, Meilan M; Sawnani, Hemant; Jefferies, John L

    2017-03-01

    To evaluate clinical outcomes and steroid side effects in a cohort of patients with Duchenne muscular dystrophy (DMD) treated with long-term daily glucocorticoid therapy. Although daily glucocorticoid therapy has been shown to extend ambulatory function in DMD, less frequent dosing is often used because of side effect concerns. Retrospective study of 97 patients with DMD aged 10 to gastrointestinal symptoms, behavior, hypertrichosis, and need for medication interventions. For 13- to 16-year-old patients, 40% could rise from the floor and 50% could perform the 30-foot run test. Forced vital capacity for the entire cohort was well preserved. Thirteen percent of younger (10- to 20 degrees). Eighty-six percent had normal weight velocities; 30% had no increased facial fullness; 72% had short stature; and 19% had asymptomatic cataracts. Asymptomatic spine compression deformities were noted in 76% and long bone fractures in 30%. One patient stopped glucocorticoid because of behavioral concerns. With evidence for improved outcomes and manageable side effects, we recommend use of daily glucocorticoid therapy for patients with DMD with anticipatory management of side effects and a coordinated interdisciplinary care approach. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Clinical efficacy of glucocorticoid therapy in treatment of drug-induced cholestatic liver disease

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    GE Hongyan

    2015-10-01

    Full Text Available ObjectiveTo analyze the clinical efficacy of glucocorticoid therapy in addition to conventional treatment for patients with drug-induced cholestatic liver disease. MethodsA total of 115 patients with drug-induced cholestatic liver disease who were admitted to Affiliated Hospital of Inner Mongolia University for the Nationalities from January 2010 to December 2014 were collected and divided into glucocorticoid treatment group and non-glucocorticoid treatment group. The glucocorticoid treatment group was given methylprednisolone sodium succinate 120 mg once daily by intravenous injection in addition to conventional treatment. The indicator for glucocorticoid response was defined as 10% decrease of total bilirubin (TBil on the third day or 30% decrease on the seventh day. Then the patients were orally given prednisone tablets 10 mg three times daily based on the level of TBil, and the administration of prednisone tablets was adjusted to twice daily a week later. The course of treatment was less than three weeks. Comparison of continuous data in normal distribution between the two groups was made by t test, and comparison of continuous data not in normal distribution between the two groups was made by rank sum test. ResultsThe levels of gamma-glutamyl transpeptidase (GGT, alanine aminotransferase (ALT, and TBil in the glucocorticoid treatment group decreased significantly on days 3, 7, and 14 of treatment compared with those before treatment (tGGT=3.64, 13.08, 16.22; tALT=2.39, 4.73, 8.36; tTBil=3.46, 7.41, 13.17; all P<0.05. Compared with the non-glucocorticoid treatment group, the glucocorticoid treatment group had significantly lower AST and ALT levels before treatment and on days 3 and 7 of treatment (all P>0.05. The GGT, AST, and TBil levels in the glucocorticoid treatment group were significantly lower than those in the non-glucocorticoid treatment group on day 14 of treatment (t=7.074, 2.929, 2.018; all P<0.05. The average decreasing

  18. Optimising glucocorticoid therapy in rheumatic diseases : an incompatible triangle?

    OpenAIRE

    Hoes, J N

    2011-01-01

    As this thesis discusses, an incompatible situation arises when toxicity predominates over efficacy particularly in case high cumulative doses of GCs have been used. This has stigmatised their usage, which is often unwarranted when GC therapy is applied with sufficient precautionary measures (safety). The most obvious example is osteoporosis prophylaxis in patients on long-term GC therapy. When the three dimensions or axes related to the use of GCs namely efficacy, toxicity and safety of GC t...

  19. Efficacy of Puls-therapy with Glucocorticoids in Patients with Autoimmune Ophtalmopatay

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    E V Bogomazova

    2008-09-01

    Full Text Available The article is presents the results of estimation efficiency of various schemes pathogenetic glucocorticoids treatment of autoimmune ophthalmopathy. Research of clinical parameters dynamics including subjective and objective attributes, proptosis, dynamics of the soluble form of intercellular molecule adhesion-1 levels was made before treatment and at the end of research (in 6 month follow up after complete course of pathogenetic treatment. The study has demonstrated that combination of glucocorticoids pulse-therapy and mean volume plasmapheresis is the most effective pathogenetic method of autoimmune ophthalmopathy treatment; absence of advantages of the used schemes of treatment for reduction proptosis. Advantages of use of the combined therapy are marked in comparison with monotherapy by glucocorticoids at estimation of subjective attributes.

  20. Investigation of subclinical bacteriuria in cats with dermatological disease receiving long-term glucocorticoids and/or ciclosporin.

    Science.gov (United States)

    Lockwood, Samantha L; Schick, Anthea E; Lewis, Thomas P; Newton, Heide

    2017-08-18

    Dogs receiving long-term glucocorticoids or ciclosporin have an increased frequency of bacteriuria. No studies have investigated the frequency of bacteriuria in cats receiving long-term glucocorticoids and/or ciclosporin. To document whether subclinical bacteriuria occurs in cats receiving long-term glucocorticoid and/or ciclosporin for management of chronic disease. Thirty two cats treated with parenteral glucocorticoids and/or oral glucocorticoids and/or ciclosporin were included. Thirty two cats receiving oral glucocorticoids and/or ciclosporin for at least three months or at least two injections of long-acting glucocorticoids within the preceding six months were evaluated. Thirty four healthy cats were used as a control group. Urinalysis and urine culture was performed on urine samples collected by cystocentesis from each cat. In the glucocorticoid/ciclosporin group, none of 32 cats had a positive urine culture. In the control group, one of 34 cats had a positive urine culture. There were no statistically significant differences between the urinalyses from either group. There was no evidence to suggest that administration of long-term glucocorticoids and/or ciclosporin is associated with bacteriuria in cats. © 2017 ESVD and ACVD.

  1. Glucocorticoids enhance in vivo exposure-based therapy of spider phobia.

    Science.gov (United States)

    Soravia, Leila M; Heinrichs, Markus; Winzeler, Livia; Fisler, Melanie; Schmitt, Wolfgang; Horn, Helge; Dierks, Thomas; Strik, Werner; Hofmann, Stefan G; de Quervain, Dominique J-F

    2014-05-01

    Preclinical and clinical studies indicate that the administration of glucocorticoids may promote fear extinction processes. In particular, it has been shown that glucocorticoids enhance virtual reality based exposure therapy of fear of heights. Here, we investigate whether glucocorticoids enhance the outcome of in vivo exposure-based group therapy of spider phobia. In a double blind, block-randomized, placebo-controlled, between-subject study design, 22 patients with specific phobia of spiders were treated with two sessions of in vivo exposure-based group therapy. Cortisol (20 mg) or placebo was orally administered 1 hr before each therapy session. Patients returned for a follow-up assessment one month after therapy. Exposure-based group therapy led to a significant decrease in phobic symptoms as assessed with the Fear of Spiders Questionnaire (FSQ) from pretreatment to immediate posttreatment and to follow-up. The administration of cortisol to exposure therapy resulted in increased salivary cortisol concentrations and a significantly greater reduction in fear of spiders (FSQ) as compared to placebo at follow-up, but not immediately posttreatment. Furthermore, cortisol-treated patients reported significantly less anxiety during standardized exposure to living spiders at follow-up than placebo-treated subjects. Notably, groups did not differ in phobia-unrelated state-anxiety before and after the exposure sessions and at follow-up. These findings indicate that adding cortisol to in vivo exposure-based group therapy of spider phobia enhances treatment outcome. © 2013 Wiley Periodicals, Inc.

  2. [Glucocorticoid therapy: what is the information sought by patients? Traffic analysis of the website cortisone-info.fr].

    Science.gov (United States)

    Poisson, J; Six, M; Morin, C; Fardet, L

    2013-05-01

    About 1% of the general population are receiving systemic glucocorticoids. The information about this treatment sought by patients is unknown. The website www.cortisone-info.fr aims to provide therapeutic information about glucocorticoids and glucocorticoid therapy. It was posted on January 16, 2012. The information available on the website is documented and based on the recent medical literature. The website is made of 43 pages divided into five main sections (generalities about glucocorticoids, adverse events, measures associated with glucocorticoid therapy, discontinuation of glucocorticoids and, situations requiring attention). The website traffic between February 1st, 2012 and January 4, 2013 was analyzed using Google Analytics. During the study period, the website was visited by 67,496 people (average number of visitors per day: 33 in February 2012, 326 in December 2012). The number of page views was 230,496 or an average of 3.5 pages per visitor. Of these 230,496 page views, 145,431 (63.1%) were related to adverse events and 37,722 (16.4%) were related to generalities about glucocorticoids (e.g., what is cortisone? For which disease? How does it work?). Information particularly sought by visitors was related to the diet to follow during glucocorticoid therapy (page accessed 11,946 times), data about what cortisone is (page accessed 11,829 times) and the effects of glucocorticoids on weight (page accessed 10,442 times). Knowledge of glucocorticoid-treated patients' expectations may help physicians to optimize information they give, thereby helping to reduce patients' concerns about glucocorticoids and to improve adherence to the treatment. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  3. Steatohepatitis secondary to long-term glucocorticoid treatment for congenital adrenal hyperplasia: a potential diagnostic pitfall.

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    Ding, Xianzhong; Thung, Swan N; Grewal, Priya

    2013-11-01

    A 24-year-old woman with congenital adrenal hyperplasia (CAH) was referred for evaluation of elevated liver enzyme activities over the preceding 6 months. The patient was diagnosed with CAH at the age 12 when she presented with irregular menses and hirsutism. Since then, she had been on dexamethasone to maintain a normal menstrual cycle and prevent hirsutism and acne. She had no history of chronic liver disease and drank alcohol socially. An extensive workup for other treatable causes of liver disease was unrevealing. Therefore, a liver biopsy was performed, which revealed extensive ballooned degenerative hepatocytes containing Mallory-Denk hyalines. The ballooned hepatocytes were located predominantly in centrilobular areas and without any accompanying steatosis. Even though the histopathologic features are most compatible with alcoholic and/or nonalcoholic steatohepatitis, it was not supported by the patient's medical history and clinical presentation. The patient had a normal body mass index and only occasional alcohol use. Based on the biopsy finding and clinical presentation, we postulated that the abnormal liver enzyme and pathological features seen on the liver biopsy were secondary to CAH and long-term use of glucocorticoid. A few studies have shown that patients with CAH often develop metabolic abnormalities and insulin resistance, particularly women treated with glucocorticoid for several years. To our knowledge, this is the first report describing steatohepatitis secondary to CAH and prolonged glucocorticoid treatment. It is important to be aware that steatohepatitis can develop in these patients due to long-term glucocorticoid use and potentially lead to progressive liver damage. Furthermore, in patients with CAH who develop abnormal liver enzyme activities a liver biopsy is warranted to assess for steatohepatitis and any associated fibrosis. If indeed fibrosis is already present, a consultation with the endocrinologist should be undertaken in an effort

  4. Optimising glucocorticoid therapy in rheumatic diseases : an incompatible triangle?

    NARCIS (Netherlands)

    Hoes, J.N.|info:eu-repo/dai/nl/304815276

    2011-01-01

    As this thesis discusses, an incompatible situation arises when toxicity predominates over efficacy particularly in case high cumulative doses of GCs have been used. This has stigmatised their usage, which is often unwarranted when GC therapy is applied with sufficient precautionary measures

  5. [High-dosage glucocorticoid therapy in acute heart infarct and in cardiogenic shock].

    Science.gov (United States)

    Krosch, H; Schäbitz, J

    1977-11-15

    40 patients with cardiogenic shock in consequence of contractility insufficiency of the heart were treated with high doses of prednisolon for short time. In 10 cases a good result of the treatment was to be seen so that the lethality quota was smaller than that of a reference group of the same age. The pharmacodynamic effect is seen in an improvement of the micro-circulation by a peripheric vasodilatation. 10 patients with acute myocardial infarction got a therapy with glucocorticoid combined with a treatment with anti-coagulants during the first both weeks. In this connection modern experimental examinations of animals are discussed which showed that glucocorticoides improve the anoxy tolerance of the heart muscle cell.

  6. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia.

    Science.gov (United States)

    Rensen, Niki; Gemke, Reinoud Jbj; van Dalen, Elvira C; Rotteveel, Joost; Kaspers, Gertjan Jl

    2017-11-06

    for this update) including two randomised controlled trials (RCTs) that assessed adrenal function. None of the included studies assessed the HPA axis at the level of the hypothalamus, the pituitary, or both. Owing to substantial differences between studies, we could not pool results. All studies had risk of bias issues. Included studies demonstrated that adrenal insufficiency occurs in nearly all children during the first days after cessation of glucocorticoid treatment for childhood ALL. Most children recovered within a few weeks, but a small number of children had ongoing adrenal insufficiency lasting up to 34 weeks.Included studies evaluated several risk factors for (prolonged) adrenal insufficiency. First, three studies including two RCTs investigated the difference between prednisone and dexamethasone in terms of occurrence and duration of adrenal insufficiency. The RCTs found no differences between prednisone and dexamethasone arms. In the other (observational) study, children who received prednisone recovered earlier than children who received dexamethasone. Second, treatment with fluconazole appeared to prolong the duration of adrenal insufficiency, which was evaluated in two studies. One of these studies reported that the effect was present only when children received fluconazole at a dose higher than 10 mg/kg/d. Finally, two studies evaluated the presence of infection, stress episodes, or both, as a risk factor for adrenal insufficiency. In one of these studies (an RCT), trial authors found no relationship between the presence of infection/stress and adrenal insufficiency. The other study found that increased infection was associated with prolonged duration of adrenal insufficiency. We concluded that adrenal insufficiency commonly occurs in the first days after cessation of glucocorticoid therapy for childhood ALL, but the exact duration is unclear. No data were available on the levels of the hypothalamus and the pituitary; therefore, we could draw no

  7. Modulation of central glucocorticoid receptors in short- and long-term experimental hyperthyroidism.

    Science.gov (United States)

    Nikolopoulou, Elena; Mytilinaios, Dimitrios; Calogero, Aldo E; Kamilaris, Themis C; Troupis, Theodore; Chrousos, George P; Johnson, Elizabeth O

    2015-08-01

    Hyperthyroidism is associated with a significant increase in circulating glucocorticoid levels and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to examine whether the HPA axis hyperactivity observed in hyperthyroidism may be explained by a disturbed feedback inhibition of endogenous glucocorticoids through two specific intracellular receptors in the brain: the high affinity mineralocorticoid receptor (MR) and the lower affinity glucocorticoid receptor (GR). Cytosolic receptor binding and gene expression was assessed in rats with short (7 days) and long standing (60 days) eu- and hyperthyroidism. Glucocorticoid receptor number and binding affinity (Kd) in the hippocampus were measured using [(3)H2]-dexamethasone radioreceptor assay. In situ hybridization was employed to examine the effects of hyperthyroidism on the GR and MR mRNA levels in the hippocampus and the pituitary. Both short- and long-term hyperthyroid rats showed pronounced reduction in the concentration of cytosolic GR in the hippocampus, without changes in binding affinity or changes in GR expression. In contrast, GR mRNA in the pituitary increased after 7 days and decreased after 60 days of thyroxin treatment. MR mRNA was moderately affected. Hyperthyroidism is associated with significant decreases in hippocampal GR levels supporting the hypothesis that hyperactivity of the HPA axis observed in experimentally induced hyperthyroidism may be attributed, at least in part, to decreased negative feedback at the level of the hippocampus. These findings further support the notion that a central locus is principally responsible for the hyperactivity of the HPA axis observed in hyperthyroidism.

  8. Sitaxsentan-Induced Acute Severe Hepatitis Treated with Glucocorticoid Therapy

    Directory of Open Access Journals (Sweden)

    Marcus W Chin

    2012-01-01

    Full Text Available Endothelin receptor antagonists are commonly used in the treatment of pulmonary hypertension. Sitaxsentan, a selective endothelin A receptor blocker, induces a mild transaminitis in approximately 3% to 5% of patients, but rarely an acute severe hepatitis. A case involving a 61-year-old female with sitaxsentan-induced acute severe liver failure is presented. Depite withdrawal of therapy, her liver tests failed to improve. After six weeks of monitoring, the patient was administered high-dose corticosteroids, with a good clinical and biochemical response. While endothelin receptor antagonists are postulated to cause hepatitis by inhibition of a bile salt transporter pump, an immune-mediated or idiosyncratic mechanism should be considered.

  9. Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy

    Directory of Open Access Journals (Sweden)

    Keith Bruce D

    2008-03-01

    therapy does not change the long term outcome. In GI cancer, glucocorticoids most likely have a neutral effect. High dose continuous glucocorticoids have a detrimental effect in nonhematologic malignancy. Glucocorticoid therapy might have a deleterious impact in lung cancer.

  10. Long-term glucocorticoid effect on bone mineral density in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

    Science.gov (United States)

    Ceccato, Filippo; Barbot, Mattia; Albiger, Nora; Zilio, Marialuisa; De Toni, Pietro; Luisetto, Giovanni; Zaninotto, Martina; Greggio, Nella Augusta; Boscaro, Marco; Scaroni, Carla; Camozzi, Valentina

    2016-08-01

    Patients with 21-hydroxylase deficiency (21OHD) assume a lifelong glucocorticoid (GC) therapy. Excessive GC treatment increases the risk of osteoporosis and bone fractures, even though the role of substitutive therapy is not fully established: we analyzed the effect of GC dose on bone metabolism and bone mineral density (BMD) over time in patients with 21OHD. We studied bone metabolism markers and BMD in 38 adult patients with 21OHD (19-47 years, 24 females and 14 males) and 38 matched healthy control. In 15 patients, BMD data were available at both baseline and after a long-term follow-up. BMD was lower in patients than in controls at lumbar spine (0.961±0.1g/cm(2) vs 1.02±0.113g/cm(2), P=0.014) and femur neck (0.736±0.128g/cm(2) vs 0.828±0.103g/cm(2), P=0.02); otherwise, after height correction, only femoral neck BMD was lower in patients (0.458±0.081g/cm(2) vs 0.498±0.063g/cm(2), P=0.028). In those 21OHD subjects with at least 10 years follow-up, we observed an increase in lumbar BMD (P=0.0429) and a decrease in femur neck BMD values (P=0.004). Cumulative GC dose was not related to bone metabolism or BMD. No patient experienced clinical fragility fractures. BMD values are decreased in patients with 21OHD, which are in part explained by decreased height, but not by the dose of glucocorticoids. Nevertheless, bone status should be carefully monitored in patients with 21OHD. © 2016 European Society of Endocrinology.

  11. Secondary Antibody Deficiency in Glucocorticoid Therapy Clearly Differs from Primary Antibody Deficiency.

    Science.gov (United States)

    Wirsum, Clemens; Glaser, Cornelia; Gutenberger, Sylvia; Keller, Baerbel; Unger, Susanne; Voll, Reinhard E; Vach, Werner; Ness, Thomas; Warnatz, Klaus

    2016-05-01

    The aim of this study was to identify characteristics of hypogammaglobulinemia secondary to glucocorticoid therapy and their value in the differential diagnosis to primary forms of antibody deficiency. We investigated prevalence and character of hypogammaglobulinemia in a cohort of 36 patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) on glucocorticoid therapy in comparison to a gender- and age-matched cohort of hospital controls. We therefore determined serum immunoglobulin levels as well as B- and T cell-subsets in the peripheral blood of all participants. In addition, prior serum immunoglobulin levels and clinical data of the GCA and PMR patients were extracted from the electronic patient data-base. 21/36 GCA/PMR patients on glucocorticoid treatment developed antibody deficiency. In 19 patients this included IgG and in 13 patients IgG was the only affected isotype. The reduction of IgG was persistent in nearly 50 % of these patients during the observed period. GCA/PMR patients had reduced circulating naive and transitional B cells (p = 0.0043 and p = 0.0002 respectively) while IgM, IgG and IgA memory B cells were preserved. Amongst T-cell subsets, we found a reduction of CD4 memory T cells (p IgG deficiency, preserved IgA production and class-switched memory B cells, by these markers this form of secondary hypogammaglobulinemia can be clearly distinguished from common variable immunodeficiency (CVID).

  12. Osteoporotic Vertebral Fractures, Secondary Developing to Long Term Glucocorticoid and Cyclosyporin-A Use: A Case Report

    Directory of Open Access Journals (Sweden)

    Selda Çiftci

    2018-01-01

    Full Text Available Many side effects are encountered during the use of glucocorticoids. Osteoporosis is a common side effect of bone metabolism. The side effect increase with high dose and long-term use of steroids. In this article, we report a case of uncontrolled glucocorticoid use for 6 years due to ocular involvement due to Behçet’s disease and a young male with osteoporotic fracture of the dorsal and lumbar vertebrae due to cyclosporine use for 3 years. To sum up, this case shows that steroids and combination treatments should be used with appropriate dose and duration in absolute indications and patients should be monitored in order.

  13. Membrane-associated glucocorticoid activity Is necessary for modulation of long-term memory via chromatin modification

    NARCIS (Netherlands)

    Roozendaal, Benno; Hernandez, Angelina; Cabrera, Sara M.; Hagewoud, Roelina; Malvaez, Melissa; Stefanko, Daniel P.; Haettig, Jakob; Wood, Marcelo A.

    2010-01-01

    Glucocorticoid hormones enhance the consolidation of long-term memory of emotionally arousing training experiences. This memory enhancement requires activation of the cAMP-dependent kinase pathway and the subsequent phosphorylation of cAMP response-element binding (CREB) protein. Here, we

  14. Prevalence of fractures in women with rheumatoid arthritis and/or systemic lupus erythematosus on chronic glucocorticoid therapy

    OpenAIRE

    Rentero, Maria Luz; Amigo, Encarna; Chozas, Nicolas; Fernández Prada, Manuel; Silva-Fernández, Lucia; Abad Hernandez, Miguel Angel; Rodriguez Barrera, Jose Maria; del Pino-Montes, Javier

    2015-01-01

    Background Glucocorticoid (GC) therapy is associated with an increased risk of fractures. The main objective of this study was to determine the prevalence of undiagnosed vertebral fractures in women chronically using GC therapy for autoimmune disorders. We also determined the prevalence of non-vertebral fractures, and investigated whether factors such as quality-of-life and future fracture risk are associated with vertebral/non-vertebral fractures. Methods This was a multicenter cross-section...

  15. [Clinical efficacy of adjuvant therapy with glucocorticoids in children with lobar pneumonia caused by Mycoplasma pneumoniae].

    Science.gov (United States)

    Wu, Yue-Jin; Sun, Jie; Zhang, Jian-Hua; Feng, Ling-Ling

    2014-04-01

    To study the clinical efficacy of adjuvant therapy with glucocorticoids in children with lobar pneumonia caused by Mycoplasma pneumoniae. One hundred and eight children with lobar pneumonia caused by Mycoplasma pneumoniae were randomly divided into routine treatment and hormone treatment groups. Both groups were treated with azithromycin and other symptomatic therapies. In addition to the basic treatment, the hormone treatment group was given dexamethasone 0.25-0.3 mg/(kg·d) by intravenous drip until the body temperature was normal. Then given oral prednisone tablets 0.5-1 mg/(kg·d) (gradually reduced) for a total treatment course of 7-10 days. Before and after treatment pulmonary functions were examined, and serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-2 (IL-2) and interleukin-6 (IL-6) were measured. The duration of fever, cough relief time and pulmonary shadow absorption time on chest X-ray were significantly shorter in the hormone treatment group than in the routine treatment group (PMycoplasma pneumoniae.

  16. Chronic ethanol exposure increases the non-dominant glucocorticoid, corticosterone, in the near-term pregnant guinea pig.

    Science.gov (United States)

    Hewitt, Amy J; Dobson, Christine C; Brien, James F; Wynne-Edwards, Katherine E; Reynolds, James N

    2014-08-01

    Maternal-fetal signaling is critical for optimal fetal development and postnatal outcomes. Chronic ethanol exposure alters programming of the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in a myriad of neurochemical and behavioral alterations in postnatal life. Based on a recent study which showed that human intra-partum fetal stress increased fetal secretion of corticosterone, the non-dominant glucocorticoid, this investigation tested the hypothesis that an established model of HPA axis programming, chronic maternal ethanol administration to the pregnant guinea pig, would result in preferential elevation of corticosterone, which is also the non-dominant glucocorticoid. Starting on gestational day (GD) 2, guinea pigs received oral administration of ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding. Each treatment was administered daily and continued until GD 45, 55, or 65 (approximately 3 days pre-term), when pregnant animals were euthanized and fetuses delivered by Caesarean section. Maternal and fetal plasma samples were collected. After sample preparation (protein precipitation and C-18 solid phase extraction), plasma cortisol and corticosterone concentrations were determined simultaneously by liquid chromatography coupled to tandem mass spectrometry. As predicted, chronic ethanol exposure increased both fetal and maternal plasma corticosterone concentration in late gestation. In contrast, plasma cortisol did not differ across maternal treatments in maternal or fetal samples. The plasma concentration of both maternal glucocorticoids increased with gestational age. Thus, corticosterone, the non-dominant glucocorticoid, but not cortisol, was elevated by chronic ethanol exposure, which may have effects on HPA function in later life. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies

    Science.gov (United States)

    Finsterwald, Charles; Alberini, Cristina M.

    2013-01-01

    A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitaryadrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the effects of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the

  18. Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies.

    Science.gov (United States)

    Finsterwald, Charles; Alberini, Cristina M

    2014-07-01

    A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitary-adrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the formation of

  19. Effects of glucocorticoids on mood, memory, and the hippocampus. Treatment and preventive therapy.

    Science.gov (United States)

    Brown, E Sherwood

    2009-10-01

    Corticosteroids, such as prednisone and dexamethasone, are commonly prescribed medications that suppress the immune system and decrease inflammation. Common side effects of long-term treatment with corticosteroids include weight gain, osteoporosis, and diabetes mellitus. This paper reviews the literature on psychiatric and cognitive changes during corticosteroid therapy and potential treatment options. Hypomania and mania are the most common mood changes during acute corticosteroid therapy, although depression has also been reported. However, depression is reported to be more common than mania during long-term treatment with corticosteroids. A decline in declarative and working memory is also reported during corticosteroid therapy. Corticosteroids are associated with changes in the temporal lobe, detected by structural, functional, and spectroscopic imaging. The mood and cognitive symptoms are dose dependent and frequently occur during the first few weeks of therapy. Other risk factors are not well characterized. Controlled trials suggest that lithium and phenytoin can prevent mood symptoms associated with corticosteroids. Lamotrigine and memantine also have been shown to reverse, at least partially, the declarative memory effects of corticosteroids. Uncontrolled trials suggest that antipsychotics, anti-seizure medications, and perhaps some antidepressants can also be useful for normalizing mood changes associated with corticosteroids. Thus, both the symptoms and treatment response are similar to those of bipolar disorder. Moreover, corticosteroid-induced mood and cognitive alterations have been shown to be reversible with dose reduction or discontinuation of treatment.

  20. Effect of long term glucocorticoid treatment on human growth hormone secretion in children and adolescents and the safety and effectiveness of recombinant human growth hormone treatment.

    Science.gov (United States)

    Kang, Li; Dian-Chi, Zhang; Qi-Yong, Wu; Hui-Juan, Zhu; Feng-Yang, Gong; Hui, Pan; Zi-meng, Jin; Jie-ying, Deng; Yi-fan, Shi

    2011-02-01

    Long term glucocorticoid (prednisolone) treatment on human growth hormone (hGH) secretion in children and adolescents and to investigate the effectiveness and safety of the recombinant human growth hormone (rhGH) treatment. Twelve patients (age: 10.4∓1.2 years) who were treated in Peking Union Medical College Hospital from September 1999 to November 2009 were enrolled in this study. All of them had taken prednisolone with a dose of 0.5∓2.0 mg/(kg.d) for 6~18 months. Two different hGH stimulating tests was done and their growth and development was evaluated at regular intervals. Seven patients were given rhGH with a dose of 0.1 U/(kg.d) for 6~12 months to improve their growth and development after half a year of prednisolone withdrawal when their disease conditions were improved. The growth speed of these 12 children decreased significantly during prednisolone treatment compared with before prednisolone treatment (1.2∓0.3cm/year vs.3.7∓1.2 cm/year,P12 months than those with a 6~12 months course (P0.05). The growth speed of seven children who received rhGH therapy for half a year were increased from 2.2∓0.1cm/year to 7.8∓0.5cm/year (Pgrowth and development in these children after their primary diseases are improved and glucocorticoids are withdrawn.

  1. Neonatal glucocorticoid treatment : Long-term effects on the hypothalamus-pituitary-adrenal axis, immune system, and problem behavior in 14-17 year old adolescents

    NARCIS (Netherlands)

    ter Wolbeek, Maike; Kavelaars, Annemieke; de Vries, Willem B.; Tersteeg-Kamperman, Marijke; Veen, Sylvia; Kornelisse, René F.; van Weissenbruch, Mirjam; Baerts, Wim; Liem, Kian D.; van Bel, Frank; Heijnen, Cobi J.

    2015-01-01

    Neonatal glucocorticoid (GC) treatment is used to prevent bronchopulmonary dysplasia (BPD) in prematurely born babies. In the 1990s, treatment regimens with relatively high doses of dexamethasone (DEX) were common. As an alternative, hydrocortisone (HC) was used. Earlier, we compared long-term

  2. Neonatal glucocorticoid treatment: Long-term effects on the hypothalamus-pituitary-adrenal axis, immune system, and problem behavior in 14-17 year old adolescents

    NARCIS (Netherlands)

    Wolbeek, M. ter; Kavelaars, A.; Vries, W.B. de; Tersteeg-Kamperman, M.; Veen, S.; Kornelisse, R.F.; Weissenbruch, M. van; Baerts, W.; Liem, K.D.; Bel, F. van; Heijnen, C.J.

    2015-01-01

    Neonatal glucocorticoid (GC) treatment is used to prevent bronchopulmonary dysplasia (BPD) in prematurely born babies. In the 1990s, treatment regimens with relatively high doses of dexamethasone (DEX) were common. As an alternative, hydrocortisone (HC) was used. Earlier, we compared long-term

  3. Glucocorticoids as cytokine inhibitors: role in neuroendocrine control and therapy of inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Giamila Fantuzzi

    1993-01-01

    Full Text Available Glucocorticoids are potent inhibitors of inflammation and endotoxic shock. This probably occurs through an inhibition of the synthesis of pro-inflammatory cytokines as well as of many of their toxic activities. Therefore, endogenous glucocorticoids (GC might represent a major mechanism in the control of cytokine mediated pathologies. GC inhibit the synthesis of cytokines in various experimental models. Adrenalectomy or GC antagonists potentiate TNF, IL-1 and IL-6 production in LPS treated mice. GC inhibit the formation of arachidonic acid metabolites and the induction of NO synthase. They also inhibit various activities of cytokines including toxicity, haemodynamic shock and fever. Adrenalectomy sensitizes to the toxic effects of LPS, TNF and IL-1. On the other hand, GC potentiate the synthesis of several cytokine induced APP by the liver. Since many of these proteins have anti-toxic activities (antioxidant, antiprotease etc. or bind cytokines, this might well represent a GC mediated protective feedback mechanism involving the liver. Not only do GC inhibit cytokines, but in vivo LPS and various cytokines (TNF, IL-1, IL-6 increase blood GC levels through a central mechanism involving the activation of the HPA. Thus, this neuroendocrine response to cytokines constitutes an important immunoregulatory feedback involving the brain.

  4. Self-perceived health status of patients with adrenal insufficiency receiving glucocorticoid replacement therapy - French data from a worldwide patient survey.

    Science.gov (United States)

    Touraine, Philippe; Chenuc, Gaëlle; Colin, Claudine

    2015-02-01

    An international survey was undertaken to investigate current practices in glucocorticoid replacement therapy and self-perceived health status of patients with adrenal insufficiency, using a 39-item questionnaire. Results were published in 2012. We analyzed data from French patients, extracted from the database. Participants were recruited via a patient advocacy group to respond anonymously to a questionnaire developed by clinical experts. Ninety-four patients participated (primary adrenal insufficiency 79% and secondary adrenal insufficiency 16%). They were treated mainly with hydrocortisone (97.5%). Dosing regimens were once daily (8%), twice daily (38%), thrice daily (30%) or other (24%). Nearly 80% of the participants considered their affection to have an impact on their physical activity, work, family or social life and 38% reported absence from work/school in the last 3 months. Fatigue in the morning or during the day was a problem for 57% and 69% of respondents respectively. Eighty percent were concerned about long-term side effects of therapy, mainly osteoporosis (79%), fatigue (57%) and obesity (43%). Despite obvious biases in the survey, we should be alerted by the high number of patients' complaints and the clear signs of quality of life impairment in this population, and think about strategies to improve their management. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  5. Long-term results of golimumab therapy for rheumatoid arthritis. Therapy compliance issues

    Directory of Open Access Journals (Sweden)

    N. V. Chichasova

    2016-01-01

    Full Text Available The goal of therapy for rheumatoid arthritis (RA is to suppress inflammation, to prevent or delay destructive changes in the joints, and to normalize functions during the longest monitoring of the course of RA. The data of randomized controlled trials and national registries are of great importance to a clinician. The paper reviews the literature data characterizing the long-term results of RA therapy with the tumor necrosis factor-α inhibitor golimumab (GLM and patient compliance with the therapy. Treatment with GLM at the registered subcutaneous dose of 50 mg once every 4 weeks gives rise to an effect in the vast majority of patients regardless of the type of previous ineffective therapy, the dose of concurrently administered methotrexate, the number of previous ineffective disease-modifying antirheumatic drugs, and the use and nonuse of glucocorticoids. GLM is characterized by a long-term (as long as 5 years effect with suppressed progression of destruction, functional recovery, and satisfactory tolerability with no additional risk for adverse events as the therapy is continued.

  6. Glucocorticoid treatment earlier in childhood and adolescence show dose-response associations with diurnal cortisol levels

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Holm, Sara K; Uldall, Peter

    2017-01-01

    Heightened levels of glucocorticoids in children and adolescents have previously been linked to prolonged changes in the diurnal regulation of the stress-hormone cortisol, a glucocorticoid regulated by the hypothalamic-pituitary-adrenal-axis (HPA-axis). To address this question, we examined...... the salivary cortisol awakening response (CAR) and daily cortisol output in 36 children and adolescents (25 girls/11 boys) aged 7-16 years previously treated with glucocorticoids for nephrotic syndrome or rheumatic disorder and 36 healthy controls. Patients and controls did not significantly differ in the CAR...... patients showed a positive linear relationship with the mean daily glucocorticoid doses administered during treatment. The observed dose-response associations suggest that glucocorticoid therapy during childhood and adolescence might trigger long-term changes in HPA-axis regulation, which may differ...

  7. Optimising glucocorticoid replacement therapy in severely adrenocorticotropin (ACTH) deficient hypopituitary male patients.

    LENUS (Irish Health Repository)

    Behan, Lucy-Ann

    2011-04-18

    Context:  The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15mg to 30mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens. Objective:  Primarily to define the hydrocortisone regimen which results in a 24hour cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL). Design:  10 male hypopituitary patients with severe ACTH deficiency (basal cortisol <100nM and peak response to stimulation <400nM) were enrolled in a prospective, randomised, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24hour serum cortisol sampling and QoL assessment with the Short Form 36 and the Nottingham Health Profile questionnaires. Free cortisol was calculated using Coolen\\'s equation. All results were compared to those of healthy, matched controls. Results:  CBG was significantly lower across all dose regimens compared to controls (p<0.05). The lower dose regimen C(10mg mane\\/5mg tarde) produced a 24hour free cortisol profile which most closely resembled that of controls. Both regimen A(20mg mane\\/10mg tarde) and B(10mg mane\\/10mg tarde) produced supraphysiological post-absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls (p<0.001). Conclusions:  The lower dose of HC(10mg\\/5mg) produces a more physiological cortisol profile, without compromising quality of life, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality.

  8. Optimizing glucocorticoid replacement therapy in severely adrenocorticotropin-deficient hypopituitary male patients.

    LENUS (Irish Health Repository)

    Behan, Lucy-Ann

    2012-02-01

    BACKGROUND: The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15-30 mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens. OBJECTIVE: Primarily to define the hydrocortisone regimen which results in a 24 h cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL). DESIGN: Ten male hypopituitary patients with severe ACTH deficiency (basal cortisol <100 nm and peak response to stimulation <400 nm) were enrolled in a prospective, randomized, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24 h serum cortisol sampling and QoL assessment with the Short Form 36 (SF36) and the Nottingham Health Profile (NHP) questionnaires. Free cortisol was calculated using Coolen\\'s equation. All results were compared to those of healthy, matched controls. RESULTS: Corticosteroid binding globulin (CBG) was significantly lower across all dose regimens compared to controls (P < 0.05). The lower dose regimen C (10 mg mane\\/5 mg tarde) produced a 24 h free cortisol profile (FCP) which most closely resembled that of controls. Both regimen A(20 mg mane\\/10 mg tarde) and B(10 mg mane\\/10 mg tarde) produced supraphysiological post-absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls (P < 0.001). CONCLUSIONS: The lower dose of hydrocortisone (10 mg\\/5 mg) produces a more physiological cortisol profile, without compromising QoL, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality.

  9. Glucocorticoid Regulation of Reproduction.

    Science.gov (United States)

    Geraghty, Anna C; Kaufer, Daniela

    2015-01-01

    It is well accepted that stress, measured by increased glucocorticoid secretion, leads to profound reproductive dysfunction. In times of stress, glucocorticoids activate many parts of the fight or flight response, mobilizing energy and enhancing survival, while inhibiting metabolic processes that are not necessary for survival in the moment. This includes reproduction, an energetically costly procedure that is very finely regulated. In the short term, this is meant to be beneficial, so that the organism does not waste precious energy needed for survival. However, long-term inhibition can lead to persistent reproductive dysfunction, even if no longer stressed. This response is mediated by the increased levels of circulating glucocorticoids, which orchestrate complex inhibition of the entire reproductive axis. Stress and glucocorticoids exhibits both central and peripheral inhibition of the reproductive hormonal axis. While this has long been recognized as an issue, understanding the complex signaling mechanism behind this inhibition remains somewhat of a mystery. What makes this especially difficult is attempting to differentiate the many parts of both of these hormonal axes, and new neuropeptide discoveries in the last decade in the reproductive field have added even more complexity to an already complicated system. Glucocorticoids (GCs) and other hormones within the hypothalamic-pituitary-adrenal (HPA) axis (as well as contributors in the sympathetic system) can modulate the hypothalamic-pituitary-gonadal (HPG) axis at all levels-GCs can inhibit release of GnRH from the hypothalamus, inhibit gonadotropin synthesis and release in the pituitary, and inhibit testosterone synthesis and release from the gonads, while also influencing gametogenesis and sexual behavior. This chapter is not an exhaustive review of all the known literature, however is aimed at giving a brief look at both the central and peripheral effects of glucocorticoids on the reproductive function.

  10. [Glucocorticoids in pediatrics].

    Science.gov (United States)

    Radmanović, S Z

    1995-06-01

    Glucocorticoids (GCs) are among the most commonly used drugs. They have been employed to treat almost every known disease, from urticaria to leukemia. GCs are so termed because of their action to increase plasma glucose as a result of enhanced hepatic gluconeogenesis, but they play, also, key regulatory roles in a wide variety of physiologic processes. They are essential for survival under stress. GC effect is mediated through receptors localised in cytosol. Receptor-GC complexes bind to hormone response elements in nuclear DNA, affect transcription of genes, either stimulating or inhibiting mRNAs. Proteins so produced (enzymes, hormones) are responsible for the steroid response. There is one type of GC receptor and all GCs will affect all tissues in the same way. At present rational use of GCs falls into two categories: replacement therapy (in Addison's diseasse and in congenital adrenal hyperplasia) and pharmacotherapy, mostly for their anti-inflammatory and immunosuppressive properties, but also to lyse leukemic lymphocytes or to reduce brain edema. GC therapy does not cure the primary disease--it only ameliorates its manifestations and provides time for the body natural defenses to work. After the withdrawal of steroid therapy manifestations of primary process usually return. So, as a result, there is no positive effect on long-term prognosis. Most common indications for prologned high-dose GC therapy are in organ transplantation, tumour chemotherapy, collagen vascular syndromes, ulcerative colitis, nephrotic syndrome and regional enteritis. Asthma, allergic diseases, inflammatory eye diseases and blood dyscrasias are also often treated with GCs. Used in pharmacological doses GCs have a number of adverse side effects. The use of alternate 0 day therapy can decrease most GC side effects (less suppression of hypothalamic-pituitary-adrenal axis, growth inhibition, cushingoid features, infections and myopathy). Discontinuation of long-term therapy is potentially

  11. Prevalence and incidence of osteoporotic fractures in patients on long-term glucocorticoid treatment for rheumatic diseases: the Glucocorticoid Induced OsTeoporosis TOol (GIOTTO study

    Directory of Open Access Journals (Sweden)

    M. Rossini

    2017-05-01

    Full Text Available Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA, Polymyalgia Rheumatica (PMR and Connective Tissue Diseases (CTDs and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score <-2.5 were observed in 28%, 38% and 35% of patients with CTDs, PMR or RA at the lumbar spine, and in 18%, 29% and 26% at the femoral neck, respectively. Before GC treatment, prevalent clinical fractures were reported by 12%, 37% and 17% of patients with CTDs, PMR, or RA, respectively. New clinical fragility fractures during GC treatment were reported by 12%, 10% and 23% of CTDs, PMR and RA patients, respectively. Vertebral fractures were the prevailing type of fragility fracture. More than 30% of patients had recurrence of fracture. An average of 80% of patients were in supplementation with calcium and/or vitamin D during treatment with GCs. Respectively, 64%, 80%, and 72% of the CTDs, PMR and RA patients were on pharmacological treatment for GIOP, almost exclusively with bisphosphonates. The GIOTTO study might provide

  12. Why glucocorticoid withdrawal may sometimes be as dangerous as the treatment itself

    DEFF Research Database (Denmark)

    Dinsen, Stina; Baslund, Bo; Klose, Marianne

    2013-01-01

    Glucocorticoid therapy is widely used, but withdrawal from glucocorticoids comes with a potential life-threatening risk of adrenal insufficiency. Recent case reports document that adrenal crisis after glucocorticoid withdrawal remains a serious problem in clinical practice. Partly due to difficul......Glucocorticoid therapy is widely used, but withdrawal from glucocorticoids comes with a potential life-threatening risk of adrenal insufficiency. Recent case reports document that adrenal crisis after glucocorticoid withdrawal remains a serious problem in clinical practice. Partly due...

  13. Short course of glucocorticoids in patients with protracted and chronic gout arthritis. Part I: predictors of therapy efficacy

    Directory of Open Access Journals (Sweden)

    A A Fedorova

    2008-01-01

    Full Text Available Objective. To reveal short course of glucocorticoid (GC therapy efficacy predictors in pts with gout arthritis. Material and methods. 59 pts with tophaceous gout (crystal-verified diagnosis and arthritis of three and more joints lasting more than a months in spite of treatment with sufficient doses of nonsteroidal anti-inflammatory drugs were included. Median age of pts was 56 [48;63], median disease duration - 15,2 years [7,4;20], median swollen joint count at the examination — 8 [5; 11]. The patients were randomized into 2 groups. Methylprednisolone was administered in one of them, betamethasone — in the other. Results, four variants of treatment response were described: full resolution of arthritis — 24 (41%, recurrent exacerbation — 28 (48%, insufficient arthritis resolution — 2 (3% and clinically insignificant (unresponders — 5 (8% pts. Pts in group with arthritis recurrence at the entry were significantly younger than pts with resolved arthritis (52 [47;60] and 59 [52;68] respectively, U-test p=0,02, had more inflamed joints (9 [7,5; 11 ] and 5 [4;9[ respectively, U-test p=0,02, longer duration of last exacerbation (52 [8;52[ and 13 [7,5;52J respectively, U-test p>0,05, higher values of pain, joint index and swelling index (U-test p<0,04. Pts with insufficient arthritis resolution and unresponders had most severe gout course. Conclusion. The study allowed to reveal features which determine efficacy of short course of GC therapy in pts with protracted and chronic gout arthritis: inflamed joint count, duration of the last exacerbation and chronic renal insufficiency. Proposed an algorithm allowing to predict efficacy of GC short course in each pt.

  14. Dexamethasone enhances programmed cell death 1 (PD-1) expression during T cell activation: an insight into the optimum application of glucocorticoids in anti-cancer therapy.

    Science.gov (United States)

    Xing, Kailin; Gu, Bingxin; Zhang, Ping; Wu, Xianghua

    2015-06-26

    Programmed cell death 1 (PD-1) is a key cell-surface receptor of CD28 superfamily that triggers inhibitory pathways to attenuate T-cell responses and promote T-cell tolerance. As a crucial role in tumor immunity, PD-1 has been a focus of studies in anti-cancer therapy. It has been approved that tumors could exploit PD-1-dependent immune suppression for immune evasion. Considering the wide use of glucocorticoids (GCs) in anti-cancer therapy and their immunosuppressive effects, we explored whether GCs could influence the expression of PD-1. In our study, we used dexamethasone (DEX) as a model glucocorticoid and demonstrated that DEX could enhance PD-1 expression in a dose-dependent manner. The effects were completely inhibited by the glucocorticoid receptor (GR) antagonist mifepristone (RU486), indicating that the effect of DEX on PD-1 is mediated through GR. We further found the sensitivity to DEX-induced upregulation of PD-1 expression had a significant difference between different T cell subsets, with memory T cells more susceptible to this effect. We also showed that DEX could suppress T cell functions via inhibition of cytokines production such as IL-2, IFN-γ, TNF-α and induction of apoptosis of T cells. Our findings suggest a novel way by which DEX suppress the function of activated T lymphocytes by enhancing expression of PD-1 and provide an insight into the optimum clinical application of GCs.

  15. Exogenous Cushing's syndrome and glucocorticoid withdrawal.

    Science.gov (United States)

    Hopkins, Rachel L; Leinung, Matthew C

    2005-06-01

    Glucocorticoid therapy in various forms is extremely common for a wide range of inflammatory, autoimmune, and neoplastic disorders. It is therefore important for the physician to be aware of the possibility of both iatrogenic and factitious Cushing's syndrome. Although most common with oral therapy, it is also important to be alert to the fact that all forms of glucocorticoid delivery have the potential to cause Cushing's syndrome. Withdrawal from chronic glucocorticoid therapy presents significant challenges. These include the possibility of adrenal insufficiency after discontinuation of steroid therapy, recurrence of underlying disease as the glucocorticoid is being withdrawn, and the possibility of steroid withdrawal symptoms. Nonetheless, with patience and persistence, a reasonable approach to withdrawal of glucocorticoid therapy can be achieved.

  16. Long-term programing of psychopathology-like behaviors in male rats by peripubertal stress depends on individual's glucocorticoid responsiveness to stress.

    Science.gov (United States)

    Walker, Sophie E; Sandi, Carmen

    2018-02-07

    Experience of adversity early in life and dysregulation of hypothalamus-pituitary-adrenocortical (HPA) axis activity are risk factors often independently associated with the development of psychopathological disorders, including depression, PTSD and pathological aggression. Additional evidence suggests that in combination these factors may interact to shape the development and expression of psychopathology differentially, though little is known about underlying mechanisms. Here, we studied the long-term consequences of early life stress exposure on individuals with differential constitutive glucocorticoid responsiveness to repeated stressor exposure, assessing both socio-affective behaviors and brain activity in regions sensitive to pathological alterations following stress. Two rat lines, genetically selected for either low or high glucocorticoid responsiveness to repeated stress were exposed to a series of unpredictable, fear-inducing stressors on intermittent days during the peripuberty period. Results obtained at adulthood indicated that having high glucocorticoid responses to repeated stress and having experience of peripuberty stress independently enhanced levels of psychopathology-like behaviors, as well as increasing basal activity in several prefrontal and limbic brain regions in a manner associated with enhanced behavioral inhibition. Interestingly, peripuberty stress had a differential impact on aggression in the two rat lines, enhancing aggression in the low-responsive line but not in the already high-aggressive, high-responsive rats. Taken together, these findings indicate that aberrant HPA axis activity around puberty, a key period in the development of social repertoire in both rats and humans, may alter behavior such that it becomes anti-social in nature.

  17. [Long-term steroid therapy in children: is adjunct therapy relevant in nephrotic syndrome?].

    Science.gov (United States)

    Bacchetta, J; Harambat, J; Cochat, P

    2008-11-01

    The impact of glucocorticoids on bone is specifically relevant in children exposed to a long course of treatment. Corticosteroids lead to a decrease in bone formation, mainly by osteoblastic inhibition in trabecular bone. They also play an indirect role in bone metabolism through systemic actions, such as bone maturation delay, hypogonadism, pubertal delay, and IGF1 inhibition. A systematic review of the literature was conducted. We found 12 clinical trials of interventions including calcium, vitamin D, growth hormone, calcitonin, and bisphosphonates for preventing bone disease in children receiving steroid therapy. There were few randomized controlled trials (n=7), with a limited number of patients, so that a meta-analysis could not be performed. Calcium and vitamin D supplementation may, however, have a beneficial effect on bone in children with nephrotic syndrome receiving long-term steroid therapy. We, therefore, recommend routine vitamin D supplementation, use of steroid-sparing protocols, and global prevention of risk to bone (adequate calcium intake, sun exposure, and physical activity).

  18. CHANGES OF CLINICAL AND RADIOGRAPHIC PARAMETERS DURING DENOSUMAB THERAPY IN RHEUMATOID ARTHRITIS PATIENTS RECEIVING GLUCOCORTICOIDS: PRELIMINARY RESULTS

    Directory of Open Access Journals (Sweden)

    P. S. Dydykina

    2015-01-01

    Full Text Available When treating rheumatoid arthritis (RA, it is important not only to suppress inflammation, but also to prevent local and generalized bone loss, particularly in patients receiving glucocorticoids (GC. Denosumab is a fully human monoclonal antibody that binds receptor activator of nuclear factor kappa B ligand (RANKL, prevents its interaction with receptor on osteoclasts, reduces their activity, and inhibits bone resorption.Objective: to evaluate the effect of 12-month therapy with denosumab on bone mineral density (BMD of the axialand peripheral skeleton and destructive changes in the hand and foot joints of RA patients receiving GC.Subjects and methods. Fifty-two postmenopausal women with RA concurrent with osteoporosis received subcutaneous denosumab 60 mg twice: at baseline and 6 months later. BMD was measured before drug administration and after 12 months of a follow-up, by applying dual-energy X-ray absorptiometry of three sections: the lumbar spine (LI–IV, femoral neck (FN, and distal forearm (DF. Radiographic changes in the hand and foot joints were assessed using the Sharp method modified by van der Heijde (SVH at baseline and 12 months later.Results and discussion. The patients’ mean age was 58.4±6.4 years; the mean RA duration – 19.0±10.9 years. Antiinflammatorytherapy was performed in all the patients, including 30 (57.7% who received GC. The mean BMD during follow-up increased from 0.814±0.101 to 0.848±0.103 g/cm2 in LI–IV (p<0.001, from 0.629±0.089 to 0.641±0.090 g/cm2 in FN (p=0.02, and from 0.497±0.094 to 0.502±0.091 g/cm2 in DF (р=0.34. The patients receiving and not  receiving GC showed a significant increase in LI–IV BMD and a tendency for its rise in FN and DF. There was a significant increase of X-ray changes in the hand and foot joints. Seven of the 52 patients were found to have a larger number of erosions: 33.0 [4.0; 78.0] at baseline and 39.0 [5.0; 90.0] after 12 months (p=0.017; 5 patients had

  19. Short-Term Play Therapy for Children.

    Science.gov (United States)

    Kaduson, Heidi Gerard, Ed.; Schaefer, Charles E., Ed.

    Play therapy offers a powerful means of helping children resolve a wide range of psychological difficulties, and many play approaches are ideally suited to short-term work. This book brings together leading play therapists to share their expertise on facilitating children's healing in a shorter time frame. The book provides knowledge and skills…

  20. The impact of glucocorticoids and anti-cd20 therapy on cervical human papillomavirus infection risk in women with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Claudia Mendoza-Pinto

    2013-12-01

    Full Text Available OBJECTIVE: To identify the prevalence and factors associated with cervical human papillomavirus infection in women with systemic lupus erythematosus METHODS: This cross-sectional study collected traditional and systemic lupus erythematosus-related disease risk factors, including conventional and biologic therapies. A gynecological evaluation and cervical cytology screen were performed. Human papillomavirus detection and genotyping were undertaken by PCR and linear array assay. RESULTS: A total of 148 patients were included, with a mean age and disease duration of 42.5±11.8 years and 9.7±5.3 years, respectively. The prevalence of squamous intraepithelial lesions was 6.8%. The prevalence of human papillomavirus infection was 29%, with human papillomavirus subtype 59 being the most frequent. Patients with human papillomavirus were younger than those without the infection (38.2±11.2 vs. 44.2±11.5 years, respectively; p = 0.05, and patients with the virus had higher daily prednisone doses (12.8±6.8 vs. 9.7±6.7 mg, respectively; p = 0.01 and cumulative glucocorticoid doses (14.2±9.8 vs. 9.7±7.3 g, respectively; p = 0.005 compared with patients without. Patients with human papillomavirus infection more frequently received rituximab than those without (20.9% vs. 8.5%, respectively; p = 0.03. In the multivariate analysis, only the cumulative glucocorticoid dose was associated with human papillomavirus infection. CONCLUSIONS: The cumulative glucocorticoid dose may increase the risk of human papillomavirus infection. Although rituximab administration was more frequent in patients with human papillomavirus infection, no association was found. Screening for human papillomavirus infection is recommended in women with systemic lupus erythematosus.

  1. Regulation of Corticoid and Serotonin Receptor Brain System following Early Life Exposure of Glucocorticoids: Long Term Implications for the Neurobiology of Mood

    Science.gov (United States)

    Vázquez, Delia M.; Neal, Charles R.; Patel, Paresh D.; Kaciroti, Niko; López, Juan F.

    2011-01-01

    Potent glucocorticoids (GC) administered early in life has improved premature infant survival dramatically. However, these agents may increase the risk for physical, neurological and behavior alterations. Anxiety, depression and attention difficulties are commonly described in adolescent and young adult survivors of prematurity. In the present study we administered vehicle, dexamethasone, or hydrocortisone to Sprague-Dawley rat pups on postnatal days 5 and 6, mimicking a short term clinical protocol commonly used in human infants. Two systems that are implicated in the regulation of stress and behavior were assessed: the limbic-hypothalamic-pituitary-adrenal axis [LHPA, glucocorticoid and mineralocorticoid receptors within] and the Serotonin (5-HT) system. We found that as adults, male Sprague-Dawley pups treated with GC showed agent specific altered growth, anxiety-related behavior, changes in corticoid response to novelty and gene expression changes within LHPA and 5-HT–related circuitry. The data suggest that prolonged GC-receptor stimulation during the early neonatal period can contribute to the development of individual differences in stress response and anxiety-related behavior later in life. PMID:21855221

  2. Short-term glucocorticoid administration in patients with protracted and chronic gout arthritis. Part 2 — comparison of different medication forms efficacy

    Directory of Open Access Journals (Sweden)

    A A Fedorova

    2008-01-01

    Full Text Available Objective. To compare efficacy of different glucocorticoid (GC medication forms in protracted and chronic gout arthritis. Material and methods. 59 pts with tophaceous gout (crystal-verified diagnosis and arthritis of three and more joints lasting more than a months in spite of treatment with sufficient doses of nonsteroidal anti-inflammatory drugs were included. Median age of pts was 56 [48;63], median disease duration — 15,2 years [7,4;20], median swollen joint count at the examination — 8 [5; 11]. The patients were randomized into 2 groups. Methylprednisolone (MP 500 mg/day iv during 2 days and placebo im once was administered in one of them, betamethasone (BM 7 mg im once and placebo iv twice — in the other. Results. Number of pts with full resolution of arthritis, recurrent exacerbation, insufficient arthritis resolution or clinically insignificant response was comparable in both groups. More rapid decrease of pain at moving was achieved during the first 2-3 days after GC administration in pts with full resolution of arthritis (p=0,03 in group receiving MP in comparison with BM. At day 14 joint damage measures did not differ between groups. Conclusion. Efficacy of short-term glucocorticoid administration does not depend on mode of administration and GC medication form (methylprednisolone 500 mg/day iv during 2 days or betamethasone 7 mg im once.

  3. Systemic glucocorticoid therapy: risk factors for reported adverse events and beliefs about the drug. A cross-sectional online survey of 820 patients.

    Science.gov (United States)

    Morin, Clément; Fardet, Laurence

    2015-12-01

    speech, therapeutic education, and clinical and laboratory monitoring of patients prescribed glucocorticoid therapy.

  4. [Treatment of patients with severe glucocorticoid-refractory ulcerative colitis: cyclosporine or infliximab?

    NARCIS (Netherlands)

    Lowenberg, M.; Boer, N.K. de; Dewint, P.; Hoentjen, F.

    2013-01-01

    - Cyclosporine and infliximab are so-called 'rescue-therapies' as last resort for the treatment of patients with severe glucocorticoid-refractory ulcerative colitis.- A recent study found that cyclosporine and infliximab are similar in terms of efficacy in the treatment of patients with severe

  5. Glucocorticoid programming of neuroimmune function.

    Science.gov (United States)

    Walker, David J; Spencer, Karen A

    2018-01-15

    Throughout life physiological systems strive to maintain homeostasis and these systems are susceptible to exposure to maternal or environmental perturbations, particularly during embryonic development. In some cases, these perturbations may influence genetic and physiological processes that permanently alter the functioning of these physiological systems; a process known as developmental programming. In recent years, the neuroimmune system has garnered attention for its fundamental interactions with key hormonal systems, such as the hypothalamic pituitary adrenal (HPA) axis. The ultimate product of this axis, the glucocorticoid hormones, play a key role in modulating immune responses within the periphery and the CNS as part of the physiological stress response. It is well-established that elevated glucocorticoids induced by developmental stress exert profound short and long-term physiological effects, yet there is relatively little information of how these effects are manifested within the neuroimmune system. Pre and post-natal periods are prime candidates for manipulation in order to uncover the physiological mechanisms that underlie glucocorticoid programming of neuroimmune responses. Understanding the potential programming role of glucocorticoids may be key in uncovering vulnerable windows of CNS susceptibility to stressful experiences during embryonic development and improve our use of glucocorticoids as therapeutics in the treatment of neurodegenerative diseases. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  6. Glucocorticoid-induced impairment of long-term memory retrieval in female rats: influences of estrous cycle and estrogen.

    Science.gov (United States)

    Mohammadkhani, Raziyeh; Darbandi, Niloufar; Vafaei, Abbas Ali; Ahmadalipour, Ali; Rashidy-Pour, Ali

    2015-02-01

    Using an inhibitory avoidance (IA) task, the effects of glucocorticoids on memory retrieval in intact and ovariectomized (OVX) female rats were investigated. Young adult female rats were trained in a one trial IA task (1-mA, 3-s footshock). The latency to reenter the dark compartment of the apparatus was recorded in the retention test performed 48h after training. Pre-retrieval injection of corticosterone (CORT, 1, 3, and 10mg/kg) to OVX rats impaired memory retrieval at all doses tested. Similar administration of CORT (3mg/kg) in intact female rats impaired memory retrieval in the estrus phase (when endogenous plasma levels of estrogen are low) but not in the proestrus phase (when endogenous levels of estrogen are high). Concurrent administration of CORT (3mg/kg) and 17-β-estradiol (15μg/kg) in both proestrus and estrous phases impaired memory retrieval. Our findings indicate that the effects of corticosterone on memory retrieval are modulated by the estrous cycle and 17-β-estradiol. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Long-term opioid therapy in Denmark

    DEFF Research Database (Denmark)

    Birke, H; Ekholm, O; Sjøgren, P

    2017-01-01

    BACKGROUND: Longitudinal population-based studies of long-term opioid therapy (L-TOT) in chronic non-cancer pain (CNCP) patients are sparse. Our study investigated incidence and predictors for initiating L-TOT and changes in self-rated health, pain interference and physical activities in long...... defined as those who were dispensed at least one opioid prescription in six separate months within a year. RESULTS: The incidence of L-TOT was substantially higher in CNCP patients at baseline than in others (9/1000 vs. 2/1000 person-years). Smoking behaviour and dispensed benzodiazepines were...... individuals indicated a dose-response relationship between longer treatment duration and the risk of experiencing negative changes. CONCLUSIONS: Individuals on L-TOT seemed not to achieve the key goals of opioid therapy: pain relief, improved quality of life and functional capacity. SIGNIFICANCE: Long...

  8. Glucocorticoids as mediators of developmental programming effects.

    Science.gov (United States)

    Khulan, Batbayar; Drake, Amanda J

    2012-10-01

    Epidemiological evidence suggests that exposure to an adverse environment in early life is associated with an increased risk of cardio-metabolic and behavioral disorders in adulthood, a phenomenon termed 'early life programming'. One major hypothesis for early life programming is fetal glucocorticoid overexposure. In animal studies, prenatal glucocorticoid excess as a consequence of maternal stress or through exogenous administration to the mother or fetus is associated with programming effects on cardiovascular and metabolic systems and on the brain. These effects can be transmitted to subsequent generations. Studies in humans provide some evidence that prenatal glucocorticoid exposure may exert similar programming effects on glucose/insulin homeostasis, blood pressure and neurodevelopment. The mechanisms by which glucocorticoids mediate these effects are unclear but may include a role for epigenetic modifications. This review discusses the evidence for glucocorticoid programming in animal models and in humans. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Iatrogenic Cushing's syndrome due to drug interaction between glucocorticoids and the ritonavir or cobicistat containing HIV therapies.

    Science.gov (United States)

    Elliot, Emilie R; Theodoraki, Aikaterini; Jain, Lakshmi R; Marshall, Neal J; Boffito, Marta; Baldeweg, Stephanie E; Waters, Laura J

    2016-10-01

    Ritonavir and cobicistat, used as pharmacokinetic enhancers in combination with some antiretrovirals (ARVs) for the treatment of HIV, are potent inhibitors of the CYP3A4 isoenzyme. Most glucocorticoids are metabolised via the CYP3A4 pathway and iatrogenic Cushing's syndrome (ICS), with possible secondary adrenal insufficiency (SAI), is a recognised complication following co-administration with ritonavir or cobicistat. A structured approach for identifying and managing potentially affected individuals has not been established.We systematically identified patients with ICS/SAI and found substantial heterogeneity in clinical practice across three large London HIV centres. While this significant drug interaction and its complications are now well-recognised, it is apparent that there is no standardised approach to management or guidance for the general physician. Here we describe the management of ICS/SAI in our current practice, review the available evidence and suggest practice recommendations. © Royal College of Physicians 2016. All rights reserved.

  10. The association between systemic glucocorticoid therapy and the risk of infection in patients with rheumatoid arthritis: systematic review and meta-analyses

    Science.gov (United States)

    2011-01-01

    Introduction Infection is a major cause of morbidity and mortality in patients with rheumatoid arthritis (RA). The objective of this study was to perform a systematic review and meta-analysis of the effect of glucocorticoid (GC) therapy on the risk of infection in patients with RA. Methods A systematic review was conducted by using MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials database to January 2010 to identify studies among populations of patients with RA that reported a comparison of infection incidence between patients treated with GC therapy and patients not exposed to GC therapy. Results In total, 21 randomised controlled trials (RCTs) and 42 observational studies were included. In the RCTs, GC therapy was not associated with a risk of infection (relative risk (RR), 0.97 (95% CI, 0.69, 1.36)). Small numbers of events in the RCTs meant that a clinically important increased or decreased risk could not be ruled out. The observational studies generated a RR of 1.67 (1.49, 1.87), although significant heterogeneity was present. The increased risk (and heterogeneity) persisted when analyses were stratified by varying definitions of exposure, outcome, and adjustment for confounders. A positive dose-response effect was seen. Conclusions Whereas observational studies suggested an increased risk of infection with GC therapy, RCTs suggested no increased risk. Inconsistent reporting of safety outcomes in the RCTs, as well as marked heterogeneity, probable residual confounding, and publication bias in the observational studies, limits the opportunity for a definitive conclusion. Clinicians should remain vigilant for infection in patients with RA treated with GC therapy. PMID:21884589

  11. Long-term opioid therapy in Denmark

    DEFF Research Database (Denmark)

    Birke, H; Ekholm, Ola; Sjøgren, P

    2017-01-01

    BACKGROUND: Longitudinal population-based studies of long-term opioid therapy (L-TOT) in chronic non-cancer pain (CNCP) patients are sparse. Our study investigated incidence and predictors for initiating L-TOT and changes in self-rated health, pain interference and physical activities in long......-term opioid users. METHODS: Data were obtained from the national representative Danish Health and Morbidity Surveys and The Danish National Prescription Registry. Respondents with no dispensed opioids the year before the survey were followed from 2000 and from 2005 until the end of 2012 (n = 12...... defined as those who were dispensed at least one opioid prescription in six separate months within a year. RESULTS: The incidence of L-TOT was substantially higher in CNCP patients at baseline than in others (9/1000 vs. 2/1000 person-years). Smoking behaviour and dispensed benzodiazepines were...

  12. Glucocorticoids are ineffective in alcoholic hepatitis

    DEFF Research Database (Denmark)

    Christensen, E; Gluud, C

    1995-01-01

    The aim of this study was to perform a meta-analysis of controlled clinical trials of glucocorticoid treatment in clinical alcoholic hepatitis, adjusting for prognostic variables and their possible interaction with therapy, because these trials have given appreciably different results. Weighted...... may be different (beneficial or harmful) in special patient subgroups. These results do not support the routine use of glucocorticoids in patients with alcoholic hepatitis, including those with encephalopathy. Whether other subgroups may benefit needs further investigation using the individual patient...

  13. Glucocorticoids for acute viral bronchiolitis in infants and young children.

    Science.gov (United States)

    Fernandes, Ricardo M; Bialy, Liza M; Vandermeer, Ben; Tjosvold, Lisa; Plint, Amy C; Patel, Hema; Johnson, David W; Klassen, Terry P; Hartling, Lisa

    2013-06-04

    large factorial low risk of bias RCT found combined high-dose systemic dexamethasone and inhaled epinephrine reduced admissions by day 7 (baseline risk of admission 26%; RR 0.65; 95% CI 0.44 to 0.95; number needed to treat 11; 95% CI 7 to 76), with no differences in short-term adverse effects. No other comparisons showed relevant differences in primary outcomes. Current evidence does not support a clinically relevant effect of systemic or inhaled glucocorticoids on admissions or length of hospitalisation. Combined dexamethasone and epinephrine may reduce outpatient admissions, but results are exploratory and safety data limited. Future research should further assess the efficacy, harms and applicability of combined therapy.

  14. Short term administration of glucocorticoids in patients with protracted and chronic gout arthritis. Part III – frequency of adverse events

    Directory of Open Access Journals (Sweden)

    A A Fedorova

    2009-01-01

    Full Text Available Objective. To assess frequency of adverse events during short term administration of gluco- corticoid (GC in protracted and chronic gout arthritis. Material and methods. 59 pts with tophaceous gout (crystal-verified diagnosis and arthritis of three and more joints lasting more than a months in spite of treatment with sufficient doses of nonsteroidal anti-inflammatory drugs were included. Median age of pts was 56 [48;63], median disease duration – 15,2 years [7,4;20], median swollen joint count at the examination – 8 [5;11]. The patients were randomized into 2 groups. Methylprednisolone (MP 500 mg/day iv during 2 days and placebo im once was administered in one of them, betamethasone (BM 7 mg im once and placebo iv twice – in the other. Clinical evaluation of inflamed joints was performed every day. Standard laboratory examination and ECG were done before drug administration, at 3rd, 7th, and 14th day of follow up. Immunoreactive insulin level was evaluated before drug administration and at day 14. Blood pressure (BP was measured every day. Results. After first GC administration BP elevated in 28 (47% pts. In pts not having appropriate BP values BP elevated in 73% of cases. Pts with appropriate BP values showed less frequent BP elevation – 38% (p=0,02. In 8 (13% pts at day 3 after GC administration ECG signs of myocardial blood supply deterioration were revealed. Glucose level elevated in 10 (17% pts and after the second BM administration – in 5 (8% pts. Cholesterol level did not significantly change after 14 days of follow up but in 28 (47% pts it increased in comparison with baseline. Trigliceride level significantly decreased at day 14 from 149 [106; 187] to 108 [66,5; 172] mg/dl (p=0,02. 26 (44% pts had face hyperemia, 4 (7% –42 palpitation and 2 (3,4% – bitter taste. Conclusion. Administration of short course of GC in pts with gout requires monitoring of possible adverse events. Antihypertensive therapy providing appropriate BP

  15. [Glucocorticoids in rheumatology].

    Science.gov (United States)

    Dziurla, R; Buttgereit, F

    2008-11-01

    Glucocorticoids (GC) are effective drugs which are often used in rheumatology. However, they have a considerable potential for frequent and sometimes serious side effects that restrict their use. Their mechanisms of action are either receptor dependent (specific) or independent (unspecific) on the genomic as well as the non-genomic level. Many adverse effects are predominantly caused by transactivation while the desired effects are mostly mediated by transrepression. Treatment strategies are sub-classified into low, medium, high, very high dose and pulse therapy based on criteria such as dose, indication, duration of treatment and potential risk of adverse events. The musculoskeletal, gastrointestinal, neuro-endocrino-immunological, opthalmological and neuropsychiatric systems are examples where adverse effects may occur.

  16. Neonatal glucocorticoid treatment: long-term effects on the hypothalamus-pituitary-adrenal axis, immune system, and problem behavior in 14-17 year old adolescents.

    Science.gov (United States)

    Ter Wolbeek, Maike; Kavelaars, Annemieke; de Vries, Willem B; Tersteeg-Kamperman, Marijke; Veen, Sylvia; Kornelisse, René F; van Weissenbruch, Mirjam; Baerts, Wim; Liem, Kian D; van Bel, Frank; Heijnen, Cobi J

    2015-03-01

    Neonatal glucocorticoid (GC) treatment is used to prevent bronchopulmonary dysplasia (BPD) in prematurely born babies. In the 1990s, treatment regimens with relatively high doses of dexamethasone (DEX) were common. As an alternative, hydrocortisone (HC) was used. Earlier, we compared long-term effects of both GCs in children aged 7-10 and detected adverse effects of neonatal DEX treatment, but not of HC, on a range of outcomes. The aim of the current cohort study was to investigate whether long-term effects of neonatal DEX were maintained and whether effects of HC remained absent at adolescent age (14-17years). We compared 71 DEX-treated and 67 HC-treated adolescents. In addition, 71 adolescents who were not neonatally treated with GCs participated. All were born dexamethasone suppression test did not differ between groups. In contrast to our observations at the age of 7-10years, we did not observe group differences in mitogen-induced cytokine production at the age of 14-17years. DEX-treated girls showed more social problems and anxious/depressed behavior than HC-treated girls. Untreated girls showed more problem behavior as well. In conclusion, our results suggest that, especially in girls, neonatal DEX has a programming effect on the HPA-axis and on the ability to adjust to the environment. The loss of group differences on immune system measures indicate that potentially negative effects detected at a younger age subsided. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Suppression of cortisol responses to exogenous adrenocorticotrophic hormone, and the occurrence of side effects attributable to glucocorticoid excess, in cats during therapy with megestrol acetate and prednisolone.

    Science.gov (United States)

    Middleton, D J; Watson, A D; Howe, C J; Caterson, I D

    1987-01-01

    The major purpose of this investigation was to determine the effect of prednisolone and megestrol acetate in cats on the adrenal cortisol response to exogenous adrenocorticotrophic hormone during drug administration at dose rates employed for management of some inflammatory feline dermatoses. Prednisolone (at least 2 mg/kg/day) and megestrol acetate (5 mg/cat/day) were each administered orally to seven cats from days 1 to 16. Three additional cats received no therapy. Basal and stimulated cortisol concentrations, food and water intake, hematology, blood biochemistry, urinalyses, and hepatic and cutaneous histology were studied in all cats before, during, and two weeks following the end of treatment. Cats given prednisolone or megestrol acetate had significant suppression of stimulated cortisol levels on day 8. This change was more marked on day 15, when the suppression in cats given megestrol acetate was also significantly more severe than in those receiving prednisolone. Recovery of adrenal reserve was considered present on day 30 in six of seven cats given prednisolone, but in only three of seven receiving megestrol acetate. Eosinopenia, glycosuria and hepatocyte swelling from glycogen deposition were occasionally recorded in treated cats of both groups, providing additional circumstantial evidence for glucocorticoid activity of megestrol acetate in cats. It is advised that abrupt withdrawal of prednisolone or megestrol acetate therapy be avoided in this species to reduce the chance of precipitating clinical signs of hypoadrenocorticism, even after treatment for as little as one week. Images Fig. 2. PMID:3032391

  18. Very high frequency of fragility fractures associated with high-dose glucocorticoids in postmenopausal women: A retrospective study

    Directory of Open Access Journals (Sweden)

    Goichi Kageyama

    2017-06-01

    Fragility fractures associated with high-dose glucocorticoid therapy are common among postmenopausal women. Extreme care should be taken especially for postmenopausal women when high-dose glucocorticoid therapy is required.

  19. Relationship of a common polymorphism of the glucocorticoid receptor gene to traumatic memories and posttraumatic stress disorder in patients after intensive care therapy

    NARCIS (Netherlands)

    Hauer, Daniela; Weis, Florian; Papassotiropoulos, Andreas; Schmoeckel, Michael; Beiras-Fernandez, Andres; Lieke, Julia; Kaufmann, Ines; Kirchhoff, Fabian; Vogeser, Michael; Roozendaal, Benno; Briegel, Josef; de Quervain, Dominique; Schelling, Gustav

    Objective: Glucocorticoids play a major role in the consolidation and retrieval of traumatic information. They act through the glucocorticoid receptor, for which, in humans, several polymorphisms have been described. In particular, the BclI single-nucleotide polymorphism is associated with

  20. Treatment of lateral epicondylitis with platelet-rich plasma, glucocorticoid, or saline: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Krogh, Thøger Persson; Fredberg, Ulrich; Stengaard-Pedersen, Kristian; Christensen, Robin; Jensen, Pia; Ellingsen, Torkell

    2013-03-01

    glucocorticoid had a short-term pain-reducing effect at 1 month in contrast to the other therapies. Injection of glucocorticoid in LE reduces both color Doppler activity and tendon thickness compared with PRP and saline.

  1. Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids.

    Directory of Open Access Journals (Sweden)

    Benjamin D Weger

    2016-12-01

    Full Text Available Altered daily patterns of hormone action are suspected to contribute to metabolic disease. It is poorly understood how the adrenal glucocorticoid hormones contribute to the coordination of daily global patterns of transcription and metabolism. Here, we examined diurnal metabolite and transcriptome patterns in a zebrafish glucocorticoid deficiency model by RNA-Seq, NMR spectroscopy and liquid chromatography-based methods. We observed dysregulation of metabolic pathways including glutaminolysis, the citrate and urea cycles and glyoxylate detoxification. Constant, non-rhythmic glucocorticoid treatment rescued many of these changes, with some notable exceptions among the amino acid related pathways. Surprisingly, the non-rhythmic glucocorticoid treatment rescued almost half of the entire dysregulated diurnal transcriptome patterns. A combination of E-box and glucocorticoid response elements is enriched in the rescued genes. This simple enhancer element combination is sufficient to drive rhythmic circadian reporter gene expression under non-rhythmic glucocorticoid exposure, revealing a permissive function for the hormones in glucocorticoid-dependent circadian transcription. Our work highlights metabolic pathways potentially contributing to morbidity in patients with glucocorticoid deficiency, even under glucocorticoid replacement therapy. Moreover, we provide mechanistic insight into the interaction between the circadian clock and glucocorticoids in the transcriptional regulation of metabolism.

  2. The glucocorticoid receptor: a revisited target for toxins.

    Science.gov (United States)

    Marketon, Jeanette I Webster; Sternberg, Esther M

    2010-06-01

    The hypothalamic-pituitary-adrenal (HPA) axis activation and glucocorticoid responses are critical for survival from a number of bacterial, viral and toxic insults, demonstrated by the fact that removal of the HPA axis or GR blockade enhances mortality rates. Replacement with synthetic glucocorticoids reverses these effects by providing protection against lethal effects. Glucocorticoid resistance/insensitivity is a common problem in the treatment of many diseases. Much research has focused on the molecular mechanism behind this resistance, but an area that has been neglected is the role of infectious agents and toxins. We have recently shown that the anthrax lethal toxin is able to repress glucocorticoid receptor function. Data suggesting that the glucocorticoid receptor may be a target for a variety of toxins is reviewed here. These studies have important implications for glucocorticoid therapy.

  3. The Glucocorticoid Receptor: A Revisited Target for Toxins

    Directory of Open Access Journals (Sweden)

    Jeanette I. Webster Marketon

    2010-06-01

    Full Text Available The hypothalamic-pituitary-adrenal (HPA axis activation and glucocorticoid responses are critical for survival from a number of bacterial, viral and toxic insults, demonstrated by the fact that removal of the HPA axis or GR blockade enhances mortality rates. Replacement with synthetic glucocorticoids reverses these effects by providing protection against lethal effects. Glucocorticoid resistance/insensitivity is a common problem in the treatment of many diseases. Much research has focused on the molecular mechanism behind this resistance, but an area that has been neglected is the role of infectious agents and toxins. We have recently shown that the anthrax lethal toxin is able to repress glucocorticoid receptor function. Data suggesting that the glucocorticoid receptor may be a target for a variety of toxins is reviewed here. These studies have important implications for glucocorticoid therapy.

  4. Glucocorticoids and fetal programming part 2: Mechanisms.

    Science.gov (United States)

    Moisiadis, Vasilis G; Matthews, Stephen G

    2014-07-01

    The lifelong health of an individual is shaped during critical periods of development. The fetus is particularly susceptible to internal and external stimuli, many of which can alter developmental trajectories and subsequent susceptibility to disease. Glucocorticoids are critical in normal development of the fetus, as they are involved in the growth and maturation of many organ systems. The surge in fetal glucocorticoid levels that occurs in most mammalian species over the last few days of pregnancy is an important developmental switch leading to fundamental changes in gene regulation in many organs, including the brain. These changes are important for the transition to postnatal life. Exposure of the fetus to increased levels of glucocorticoids, resulting from maternal stress or treatment with synthetic glucocorticoids, can lead to long-term 'programming' of hypothalamic-pituitary-adrenal function and behaviours. Glucocorticoids act at multiple levels within the fetal brain. Growing evidence indicates that they can exert powerful effects on the epigenome, including on DNA methylation, histone acetylation and microRNA, to influence gene expression. Such influences probably represent a critical component of the 'programming' process, and might be partly responsible for the transgenerational effects of antenatal glucocorticoid exposure on neurologic, cardiovascular and metabolic function.

  5. Glucocorticoid administration for Graves' hyperthyroidism treated by radioiodine. A questionnaire survey among members of the European Thyroid Association

    NARCIS (Netherlands)

    Lazarus, J. H.; Bartalena, L.; Marcocci, C.; Kahaly, G. J.; Krassas, G.; Wiersinga, W. M.; Baldeschi, L.; Boboridis, K.; Boschi, A.; Currò, N.; Daumerie, C.; Dickinson, A. J.; Eckstein, A.; Kendall-Taylor, P.; Lane, C. M.; Ludgate, M. E.; Mann, K.; Marinò, M.; Mourits, M. P.; Nardi, M.; Neoh, C.; Orgiazzi, J.; Pearce, S.; Perros, P.; Pinchera, A.; Pitz, S.; Salvi, M.; Sivelli, P.; Stahl, M.; von Arx, G.

    2010-01-01

    Background: Glucocorticoid prophylaxis is required in some instances after radioiodine (RAI) treatment for Graves' hyperthyroidism to prevent progression of Graves' orbitopathy (GO). However, no randomized clinical trial has been performed to ascertain the optimum glucocorticoid therapy. Aim and

  6. Atypical fractures on long term bisphosphonates therapy.

    LENUS (Irish Health Repository)

    Hussein, W

    2011-01-01

    Bisphosphonates reduce fractures risk in patients with osteoporosis. A new pattern of fractures is now being noted in patients on prolonged bisphosphonate therapy. We report a case of an atypical femoral fracture with preceding pain and highlight the characteristics of these fractures.

  7. Glucocorticoids induce autophagy in rat bone marrow mesenchymal stem cells

    DEFF Research Database (Denmark)

    Wang, L.; Fan, J.; Lin, Y. S.

    2015-01-01

    Glucocorticoidinduced osteoporosis (GIOP) is a widespread clinical complication following glucocorticoid therapy. This irreversible damage to boneforming and resorbing cells is essential in the pathogenesis of osteoporosis. Autophagy is a physiological process involved in the regulation of cells ...... that in response to glucocorticoid administration, induced autophagy aids to maintain proliferation and prevent apoptosis of BMSCs. Thus, it is hypothesized that autophagy may be a novel target in the treatment or prevention of osteoporosis.......Glucocorticoidinduced osteoporosis (GIOP) is a widespread clinical complication following glucocorticoid therapy. This irreversible damage to boneforming and resorbing cells is essential in the pathogenesis of osteoporosis. Autophagy is a physiological process involved in the regulation of cells...

  8. Glucocorticoids and fetal programming part 1: Outcomes.

    Science.gov (United States)

    Moisiadis, Vasilis G; Matthews, Stephen G

    2014-07-01

    Fetal development is a critical period for shaping the lifelong health of an individual. However, the fetus is susceptible to internal and external stimuli that can lead to adverse long-term health consequences. Glucocorticoids are an important developmental switch, driving changes in gene regulation that are necessary for normal growth and maturation. The fetal hypothalamic-pituitary-adrenal (HPA) axis is particularly susceptible to long-term programming by glucocorticoids; these effects can persist throughout the life of an organism. Dysfunction of the HPA axis as a result of fetal programming has been associated with impaired brain growth, altered behaviour and increased susceptibility to chronic disease (such as metabolic and cardiovascular disease). Moreover, the effects of glucocorticoid-mediated programming are evident in subsequent generations, and transmission of these changes can occur through both maternal and paternal lineages.

  9. Retinoids enhance glucocorticoid-induced apoptosis of T cells by facilitating glucocorticoid receptor-mediated transcription

    Science.gov (United States)

    Tóth, K; Sarang, Z; Scholtz, B; Brázda, P; Ghyselinck, N; Chambon, P; Fésüs, L; Szondy, Z

    2011-01-01

    Glucocorticoid-induced apoptosis of thymocytes is one of the first recognized forms of programmed cell death. It was shown to require gene activation induced by the glucocorticoid receptor (GR) translocated into the nucleus following ligand binding. In addition, the necessity of the glucocorticoid-induced, but transcription-independent phosphorylation of phosphatidylinositol-specific phospholipase C (PI-PLC) has also been shown. Here we report that retinoic acids, physiological ligands for the nuclear retinoid receptors, enhance glucocorticoid-induced death of mouse thymocytes both in vitro and in vivo. The effect is mediated by retinoic acid receptor (RAR) alpha/retinoid X receptor (RXR) heterodimers, and occurs when both RARα and RXR are ligated by retinoic acids. We show that the ligated RARα/RXR interacts with the ligated GR, resulting in an enhanced transcriptional activity of the GR. The mechanism through which this interaction promotes GR-mediated transcription does not require DNA binding of the retinoid receptors and does not alter the phosphorylation status of Ser232, known to regulate the transcriptional activity of GR. Phosphorylation of PI-PLC was not affected. Besides thymocytes, retinoids also promoted glucocorticoid-induced apoptosis of various T-cell lines, suggesting that they could be used in the therapy of glucocorticoid-sensitive T-cell malignancies. PMID:21072052

  10. Withdrawal of inhaled glucocorticoids and exacerbations of COPD

    DEFF Research Database (Denmark)

    Magnussen, Helgo; Disse, Bernd; Rodriguez-Roisin, Roberto

    2014-01-01

    BACKGROUND: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long......-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid...... findings, health status, and dyspnea were also monitored. RESULTS: As compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD...

  11. The Regulation of Muscle Mass by Endogenous Glucocorticoids

    Directory of Open Access Journals (Sweden)

    Daniel L Marks

    2015-02-01

    Full Text Available Glucocorticoids are highly conserved fundamental regulators of energy homeostasis. In response to stress in the form of perceived danger or acute inflammation, glucocorticoids are released from the adrenal gland, rapidly mobilizing energy from carbohydrate, fat and protein stores. In the case of inflammation, mobilized protein is critical for the rapid synthesis of acute phase reactants and an efficient immune response to infection. While adaptive in response to infection, chronic mobilization can lead to a p rofound depletion of energy stores. Skeletal muscle represents the major body store of protein, and can become substantially atrophied under conditions of chronic inflammation. Glucocorticoids elicit the atrophy of muscle by increasing the rate of protein degradation by the ubiquitin-proteasome system and autophagy lysosome system. Protein synthesis is also suppressed at the level of translational initiation, preventing the production of new myofibrillar protein. Glucocorticoids also antagonize the action of anabolic regulators such as insulin further exacerbating the loss of protein and muscle mass. The loss of muscle mass in the context of chronic disease is a key feature of cachexia and contributes substantially to morbidity and mortality. A growing body of evidence demonstrates that glucocorticoid signaling is a common mediator of wasting, irrespective of the underlying initiator or disease state. This review will highlight fundamental mechanisms of glucocorticoid signaling and detail the mechanisms of glucocorticoid-induced muscle atrophy. Additionally, the evidence for glucocorticoids as a driver of muscle wasting in numerous disease states will be discussed. Given the burden of wasting diseases and the nodal nature of glucocorticoid signaling, effective anti-glucocorticoid therapy would be a valuable clinical tool. Therefore, the progress and potential pitfalls in the development of glucocorticoid antagonists for muscle wasting will

  12. Glucocorticoid-induced hypertension.

    Science.gov (United States)

    Goodwin, Julie E; Geller, David S

    2012-07-01

    Glucocorticoid-induced hypertension is a common clinical problem that is poorly understood, thus rendering treatment strategies sub-optimal. This form of hypertension has been commonly thought to be mediated by excess sodium and water reabsorption by the renal mineralocorticoid receptor. However, experimental and clinical data in both humans and animal models suggest important roles for the glucocorticoid receptor as well, in both the pathogenesis and maintenance of this hypertension. The glucocorticoid receptor is widely expressed in a number of organ systems relevant to blood pressure regulation, including the kidney, the brain and the vasculature. In vitro studies in isolated kidney tissues as well as in vascular smooth muscle and vascular endothelial cells have attempted to elucidate the molecular physiology of glucocorticoid-induced hypertension, but have generally been limited by the inability to study signaling pathways in an intact organism. More recently, the power of mouse genetics has been employed to examine the tissue-specific contributions of vascular and extra-vascular tissues to this form of hypertension. Here we review recent developments in our understanding of the pathogenesis of glucocorticoid-induced hypertension.

  13. [Glucocorticoids and metabolism].

    Science.gov (United States)

    Tourniaire, J; Daumont, M

    1976-01-01

    After a brief historical account, the physiological effect of glucocorticoid hormones are analysed. Their main point of impact is neoglucogenesis from proteins. To this is added their direct action on carbohydrates, their intervention in the use of lipids, and in the movement of water and salts. Cortisone penetrates into the cell, is fixed by a cortisone receptor in order to be transferred into the nucleus and to act on the transformation of ADN-ARN. Its relationships with cyclic AMP are discussed. The hormonal correlations of glucocorticoids are numerous. (insulin, catecholamine, glucagon, growth hormone, androgen). Synthetic cordicoids have biological actions which are close to those of glucocorticoids, but vary depending on their structure. These physiological and pharmacological notions imply certain precautions in the use of this type of hormone derivative.

  14. Osteoporosis inducida por glucocorticoides Glucocorticoid induced osteoporosis

    OpenAIRE

    R. Gutiérrez-Polo

    2003-01-01

    Los glucocorticoides son un grupo de fármacos que se emplean muy frecuentemente en la práctica médica por su indiscutible utilidad. La osteoporosis inducida por éstos supone el principal efecto adverso derivado de su administración sistémica y prolongada, constituyendo la causa más frecuente de osteoporosis secundaria. Comporta además una importante repercusión sanitaria y socioeconómica como consecuencia de las complicaciones que ocasiona, como son las diferentes fracturas óseas por fragilid...

  15. Safety and tolerability of high doses of glucocorticoides

    Directory of Open Access Journals (Sweden)

    Rakić Branislava D.

    2016-01-01

    Full Text Available Introduction: Treatment of acute lymphoblastic leukemia includes the use of high doses of glucocorticoides (prednisone and dexamethasone, which significantly increase the success of therapy due to lymphocytolitic effect. The aim: The aim of the study was to determine tolerability of high doses of prednisone and dexamethasone in children with acute lymphoblastic leukemia and the structure and the intensity of adverse effects, occurred after application of these medicines. Subjects and methods: In a prospective study, we analyzed adverse effects of high doses of glucocorticoides in children suffering acute lymphoblastic leukemia treated in the Institute for Child and Youth Health Care of Vojvodina, since December 2010. until October 2014, were analyzed. This study included 18 patients, aged from 2 to 15 years. Results: Hyperglycemia appeared in 89% of patients treated with prednisone and in 61% of patients treated with dexamethasone. In order to control the high blood glucose level (above 10 mmol /L, in 11% of patients insulin was used. Hypertension appeared in 28% patients treated with prednisone and dexamethasone. Antihypertensives were needed for regulation in 17% patients. Hypopotassemia and hypocalcaemia were significantly more expressed after the use of prednisone in comparison to dexamethasone. In 11% of patients, the treatment with dexamethasone caused depressive behavior, followed by agitation. Conclusion: Adverse effects of dexamethasone and prednisone, administered in high doses in children with ALL were known, expected and reversible. Adverse reactions usually disappeared spontaneously or after short-term symptomatic therapy.

  16. Vertebral fractures assessed with dual-energy X-ray absorptiometry in patients with Addison's disease on glucocorticoid and mineralocorticoid replacement therapy.

    Science.gov (United States)

    Camozzi, Valentina; Betterle, Corrado; Frigo, Anna Chiara; Zaccariotto, Veronica; Zaninotto, Martina; De Caneva, Erica; Lucato, Paola; Gomiero, Walter; Garelli, Silvia; Sabbadin, Chiara; Salvà, Monica; Costa, Miriam Dalla; Boscaro, Marco; Luisetto, Giovanni

    2018-02-01

    to assess bone damage and metabolic abnormalities in patients with Addison's disease given replacement doses of glucocorticoids and mineralocorticoids. A total of 87 patients and 81 age-matched and sex-matched healthy controls were studied. The following parameters were measured: urinary cortisol, serum calcium, phosphorus, creatinine, 24-h urinary calcium excretion, bone alkaline phosphatase, parathyroid hormone, serum CrossLaps, 25 hydroxyvitamin D, and 1,25 dihydroxyvitamin D. Clear vertebral images were obtained with dual-energy X-ray absorptiometry in 61 Addison's disease patients and 47 controls and assessed using Genant's classification. Nineteen Addison's disease patients (31.1%) had at least one morphometric vertebral fracture, as opposed to six controls (12.8%, odds ratio 3.09, 95% confidence interval 1.12-8.52). There were no significant differences in bone mineral density parameters at any site between patients and controls. In Addison's disease patients, there was a positive correlation between urinary cortisol and urinary calcium excretion. Patients with fractures had a longer history of disease than those without fractures. Patients taking fludrocortisone had a higher bone mineral density than untreated patients at all sites except the lumbar spine. Addison's disease patients have more fragile bones irrespective of any decrease in bone mineral density. Supra-physiological doses of glucocorticoids and longer-standing disease (with a consequently higher glucocorticoid intake) might be the main causes behind patients' increased bone fragility. Associated mineralocorticoid treatment seems to have a protective effect on bone mineral density.

  17. Selective Glucocorticoid Receptor modulators.

    Science.gov (United States)

    De Bosscher, Karolien

    2010-05-31

    The ancient two-faced Roman god Janus is often used as a metaphor to describe the characteristics of the Glucocorticoid Receptor (NR3C1), which exhibits both a beneficial side, that serves to halt inflammation, and a detrimental side responsible for undesirable effects. However, recent developments suggest that the Glucocorticoid Receptor has many more faces with the potential to express a range of different functionalities, depending on factors that include the tissue type, ligand type, receptor variants, cofactor surroundings and target gene promoters. This behavior of the receptor has made the development of safer ligands, that trigger the expression program of only a desirable subset of genes, a real challenge. Thus more knowledge-based fundamental research is needed to ensure the design and development of selective Glucocorticoid Receptor modulators capable of reaching the clinic. Recent advances in the characterization of novel selective Glucocorticoid Receptor modulators, specifically in the context of anti-inflammatory strategies, will be described in this review. 2010 Elsevier Ltd. All rights reserved.

  18. Glucocorticoid-induced osteoporosis – a disorder of mesenchymal stromal cells?

    Directory of Open Access Journals (Sweden)

    Mark Stuart Cooper

    2011-08-01

    Full Text Available Glucocorticoids are a class of steroid hormones that are essential to life but cause serious harm in excess. The main clinical features of glucocorticoid excess are due to adverse effects on cells and tissues that arise from a common developmental precursor – the mesenchymal stromal cell (MSC; sometimes referred to as the mesenchymal stem cell. Interestingly glucocorticoids appear essential for the differentiation of cells and tissues that arise from MSCs. High levels of glucocorticoids are used in tissue engineering strategies to enhance the formation of tissues such as bone, cartilage and muscle. This article discusses the paradox that glucocorticoids both enhance and impair MSC development and function. It will describe how endogenous glucocorticoids are likely to be important in these processes in vivo and will discuss the implications for therapies aimed at reducing the damage associated with the use of therapeutic glucocorticoids.

  19. Epidural glucocorticoid use for vertebrogenic pain

    Directory of Open Access Journals (Sweden)

    M.V. Churyukanov

    2014-01-01

    Full Text Available The literature review deals with the use of glucocorticoids (GC for nonspecific vertebrogenic pain and radiculopathy. The pathophysiology of radiculopathy and the role of mechanical and chemical components in the development of pain syndrome are discussed. The data of clinical trials analyzing the efficiency of epidural GC use, as well as possible indications for this therapy and its adverse reactions are under consideration. The available concepts of the analgesic effect of epidural CG are discussed.

  20. Long-term Effectiveness of Intensive Therapy in Chronic Stroke.

    Science.gov (United States)

    Wu, Xiaotian; Guarino, Peter; Lo, Albert C; Peduzzi, Peter; Wininger, Michael

    2016-07-01

    Background While recent clinical trials involving robot-assisted therapy have failed to show clinically significant improvement versus conventional therapy, it is possible that a broader strategy of intensive therapy-to include robot-assisted rehabilitation-may yield clinically meaningful outcomes. Objective To test the immediate and sustained effects of intensive therapy (robot-assisted therapy plus intensive conventional therapy) on outcomes in a chronic stroke population. Methods A multivariate mixed-effects model adjusted for important covariates was established to measure the effect of intensive therapy versus usual care. A total of 127 chronic stroke patients from 4 Veterans Affairs medical centers were randomized to either robot-assisted therapy (n = 49), intensive comparison therapy (n = 50), or usual care (n = 28), in the VA-ROBOTICS randomized clinical trial. Patients were at least 6 months poststroke, of moderate-to-severe upper limb impairment. The primary outcome measure was the Fugl-Meyer Assessment at 12 and 36 weeks. Results There was significant benefit of intensive therapy over usual care on the Fugl-Meyer Assessment at 12 weeks with a mean difference of 4.0 points (95% CI = 1.3-6.7); P = .005; however, by 36 weeks, the benefit was attenuated (mean difference 3.4; 95% CI = -0.02 to 6.9; P = .05). Subgroup analyses showed significant interactions between treatment and age, treatment and time since stroke. Conclusions Motor benefits from intensive therapy compared with usual care were observed at 12 and 36 weeks posttherapy; however, this difference was attenuated at 36 weeks. Subgroups analysis showed that younger age, and a shorter time since stroke were associated with greater immediate and long-term improvement of motor function. © The Author(s) 2015.

  1. Short-term, high-dose glucocorticoid treatment does not contribute to reduced bone mineral density in patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Olsson, A.; Oturai, D B; Sørensen, P S

    2015-01-01

    population (Z-scores). Data regarding GCs, age, body mass index (BMI), serum 25(OH)D, disease duration and severity were collected retrospectively and analysed in a multiple linear regression analysis to evaluate the association between each risk factor and BMD. RESULTS: Osteopenia was present in 38......% and osteoporosis in 7% of the study population. Mean Z-score was significantly below zero, indicating a decreased BMD in our MS patients. Multiple linear regression analysis showed no significant association between GCs and BMD. In contrast, age, BMI and disease severity were independently associated with both......BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of reduced bone mineral density (BMD). A contributing factor might be treatment with high-dose glucocorticoids (GCs). OBJECTIVES: The objective of this paper is to assess bone mass in patients with MS and evaluate...

  2. Neuropsychiatric findings in Cushing syndrome and exogenous glucocorticoid administration.

    Science.gov (United States)

    Starkman, Monica N

    2013-09-01

    This article reviews the neuropsychiatric presentations elicited by spontaneous hypercortisolism and exogenous supraphysiologic glucocorticoids. Patients with Cushing disease and syndrome develop a depressive syndrome: irritable and depressed mood, decreased libido, disrupted sleep and cognitive decrements. Exogenous short-term glucocorticoid administration may elicit a hypomanic syndrome with mood, sleep and cognitive disruptions. Treatment options are discussed. Brain imaging and neuropsychological studies indicate elevated cortisol and other glucocorticoids are especially deleterious to hippocampus and frontal lobe. The research findings also shed light on neuropsychiatric abnormalities in conditions that have substantial subgroups exhibiting elevated and dysregulated cortisol: aging, major depressive disorder and Alzheimer's disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. [Conservative therapy of chronic sinusitis].

    Science.gov (United States)

    Reiss, Michael; Reiss, Gilfe

    2012-01-01

    The chronic rhinosinusitis is defined as chronic inflammation of the nose and nasal sinuses, with or without nasal polyps. Patients suffering from chronic rhinosinusitis report about nasal obstruction and secretion, olfactory impairment, head and facial pain. These symptoms cause also considerable impact on quality of life. Therefore, an adequate rhinological diagnostics as well as therapies are essential. This paper reviews the pharmacologic and non-pharmacologic therapy of chronic rhinosinusitis. First choice of therapy should be topical glucocorticoids. The application of glucocorticoids causes anti-inflammatory and certain curative effects. Hypertonic salt solutions improve nasal symptoms. Long-term therapy with oral macrolides might improve median to severe symptoms of chronic rhinosinusitis without nasal polyps. An additional therapy with antihistamines is possible in patients with an allergy. Adaptive desensitization in patients suffering from analgesic-intolerance associating among other with nasal polyps is currently the single causal therapy. Therefore, frequency of endonasal revision surgery is reduced after desensitization.

  4. Fetal glucocorticoid exposure is associated with preadolescent brain development.

    Science.gov (United States)

    Davis, Elysia Poggi; Sandman, Curt A; Buss, Claudia; Wing, Deborah A; Head, Kevin

    2013-11-01

    Glucocorticoids play a critical role in normative regulation of fetal brain development. Exposure to excessive levels may have detrimental consequences and disrupt maturational processes. This may especially be true when synthetic glucocorticoids are administered during the fetal period, as they are to women in preterm labor. This study investigated the consequences for brain development and affective problems of fetal exposure to synthetic glucocorticoids. Brain development and affective problems were evaluated in 54 children (56% female), aged 6 to 10, who were full term at birth. Children were recruited into two groups: those with and without fetal exposure to synthetic glucocorticoids. Structural magnetic resonance imaging scans were acquired and cortical thickness was determined. Child affective problems were assessed using the Child Behavior Checklist. Children in the fetal glucocorticoid exposure group showed significant and bilateral cortical thinning. The largest group differences were in the rostral anterior cingulate cortex (rACC). More than 30% of the rACC was thinner among children with fetal glucocorticoid exposure. Furthermore, children with more affective problems had a thinner left rACC. Fetal exposure to synthetic glucocorticoids has neurologic consequences that persist for at least 6 to 10 years. Children with fetal glucocorticoid exposure had a thinner cortex primarily in the rACC. Our data indicating that the rACC is associated with affective problems in conjunction with evidence that this region is involved in affective disorders raise the possibility that glucocorticoid-associated neurologic changes increase vulnerability to mental health problems. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  5. Attitudes toward postmenopausal long-term hormone therapy.

    Science.gov (United States)

    Kolip, Petra; Hoefling-Engels, Nicole; Schmacke, Norbert

    2009-02-01

    In this article we address the question of why postmenopausal women undergo hormone therapy. Thirty-five women aged 46 to 75 years living in Bremen (Germany) and taking postmenopausal hormones for at least 12 months were interviewed. Following Fritz Schütze, the interviews were analyzed according to a reconstructive analytical procedure. Five different types of users were identified. They differed from each other in terms of their reasons for using hormones, their expectations of this type of therapy, and their personal habits and circumstances, including an integrity-preserving attitude, a performance-oriented attitude, a searching attitude, a faith-in-medicine attitude, and a benefit-generalizing attitude. The interviews show that there is a need for target-oriented counseling, taking into account the individual attitudes toward menopause and postmenopausal hormone therapy.

  6. Clinical aspects of glucocorticoid sensitivity

    NARCIS (Netherlands)

    S.W.J. Lamberts (Steven); N.A.T.M. Huizenga (Nannette); P. de Lange (Pieter); F.H. de Jong (Frank); J.W. Koper (Jan)

    1996-01-01

    textabstractRecent studies demonstrate that primary (hereditary) abnormalities in the glucocorticoid receptor gene make 6.6% of the normal population relatively 'hypersensitive' to glucocorticoids, while 2.3% are relatively 'resistant.' These abnormalities might explain why some individuals develop

  7. Glucocorticoids, chronic stress, and obesity

    NARCIS (Netherlands)

    Dallman, Mary F.; Pecoraro, Norman C.; la Fleur, Susanne E.; Warne, James P.; Ginsberg, Abigail B.; Akana, Susan F.; Laugero, Kevin C.; Houshyar, Hani; Strack, Alison M.; Bhatnagar, Seema; Bell, Mary E.

    2006-01-01

    Glucocorticoids either inhibit or sensitize stress-induced activity in the hypothalamo-pituitary-adrenal (HPA) axis, depending on time after their administration, the concentration of the steroids, and whether there is a concurrent stressor input. When there are high glucocorticoids together with a

  8. [Effect of transfer factor on treatment with glucocorticoids in a group of pediatric patients with persistent moderate allergic asthma].

    Science.gov (United States)

    Espinosa Padilla, Sara E; Orozco, Socorro; Plaza, Angélica; Estrada Parra, Sergio; Estrada García, Iris; Rosales González, Manuel Gerardo; Villaverde Rosa, Rodrigo; Espinosa Rosales, Francisco J

    2009-01-01

    Inhaled glucocorticoids are the most effective and potent drugs used to control the inflammatory bronchial reaction in patients with asthma. There are several research projects evaluating the use of immune modulators in the treatment of the asthma related inflammatory process. To evaluate the effect of transfer factor in the treatment of pediatric patients with moderate persistent allergic asthma in terms of inhaled glucocorticoid dosing and time of using. Randomized, double blind, placebo controlled pilot clinical trial in a cohort of pediatric patients (6-17 years old) with moderate persistent allergic asthma. Two groups were formed. Group one received transfer factor and group two was given placebo. Both groups received conventional therapy with inhaled budesonide and formoterol. Daily respiratory symptoms (cough during day, or at night, and wheezing episodes) were recorded in a personal diary. Spirometric evaluations were performed before enrolling patients, and at 1, 3 and 6 months after. Eleven patients were enrolled in each group. Patients in the transfer factor group showed a statistical significant reduction in the inhaled glucocorticoid doping since month 3, and this difference was maintained until the end of study. Patients on TF group showed also a non statistical significant improvement in spirometrical findings and also showed a better asthma control. Transfer factor helps to reduce inhaled glucocorticoids dose in patients with allergic rhinitis; however, studies with a larger number of patients should be done in order to obtain better results.

  9. The treatment of anorgasmia: long-term effectiveness of a short-term behavioral group therapy.

    Science.gov (United States)

    Kuriansky, J B; Sharpe, L; O'Connor, D

    1982-01-01

    A long-term follow-up of 19 women who participated in short-term group therapy for anorgasmia using masturbation and assertiveness training showed that the majority of women maintained treatment gains and progressed further in orgasm response and other aspects of sexual functioning, including assertiveness and liberalness of sexual attitudes. However, several women regressed, and four additional women who dropped out of treatment also improved dramatically in orgasm response, suggesting that other patient characteristics and factors affect apparent treatment outcome. Independent evaluations, standardized assessment scales, long-term, in-person follow-ups and multidimensional assessment are useful in evaluating treatment effectiveness.

  10. Impact of long-term and short-term therapies on seminal parameters

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    Jlenia Elia

    2013-04-01

    Full Text Available Aim: The aim of this work was: i to evaluate the prevalence of male partners of subfertile couples being treated with long/short term therapies for non andrological diseases; ii to study their seminal profile for the possible effects of their treatments on spermatogenesis and/or epididymal maturation. Methods: The study group was made up of 723 subjects, aged between 25 and 47 years. Semen analysis was performed according to World Health Organization (WHO guidelines (1999. The Superimposed Image Analysis System (SIAS, which is based on the computerized superimposition of spermatozoa images, was used to assess sperm motility parameters. Results: The prevalence of subjects taking pharmacological treatments was 22.7% (164/723. The prevalence was 3.7% (27/723 for the Short-Term Group and 18.9% (137/723 for the Long-Term Group. The subjects of each group were also subdivided into subgroups according to the treatments being received. Regarding the seminal profile, we did not observe a significant difference between the Long-Term, Short-Term or the Control Group. However, regarding the subgroups, we found a significant decrease in sperm number and progressive motility percentage in the subjects receiving treatment with antihypertensive drugs compared with the other subgroups and the Control Group. Conclusions: In the management of infertile couples, the potential negative impact on seminal parameters of any drugs being taken as Long-Term Therapy should be considered. The pathogenic mechanism needs to be clarified.

  11. Long-term therapy of antitachycardia pacing for supraventricular tachycardia.

    Science.gov (United States)

    Jung, W; Mletzko, R; Manz, M; Lüderitz, B

    1992-02-01

    Long-term antitachycardia pacing therapy with the InterTach 262-12 and 262-16 was evaluated in 32 consecutive patients (mean age 50 +/- 13 years) with recurrent, drug refractory supraventricular tachycardia. AV nodal reentrant tachycardia was present in 20 patients, Wolff-Parkinson-White syndrome in ten patients, and a reentrant tachycardia due to Mahaim fibers in one patient. During follow-up of 39 +/- 17 months, 250 persistent tachycardia episodes occurred in 22 patients. By adjusting detection and termination mode, recurrent supraventricular tachycardia could be controlled in 19 of 32 patients (60%) by antitachycardia pacing alone. Concomitant antiarrhythmic drug therapy was required in ten of 32 patients (30%). During follow-up antitachycardia pacing became ineffective in three patients (10%). Thus, chronic antitachycardia pacing proved to be safe and effective in selected patients with drug refractory supraventricular tachycardia and could significantly improve quality of life by rapid termination of recurrent supraventricular tachycardia episodes.

  12. In vivo and in vitro IL-18 production during uveitis associated with Behçet disease: effect of glucocorticoid therapy.

    Science.gov (United States)

    Belguendouz, H; Messaoudene, D; Lahmar-Belguendouz, K; Djeraba, Z; Otmani, F; Terahi, M; Tiar, M; Hartani, D; Lahlou-Boukoffa, O S; Touil-Boukoffa, C

    2015-03-01

    Uveitis represents one of the major diagnostic criteria in Behçet's disease. It is most prevalent in the countries of the Mediterranean area, including Algeria, and along the Silk Road. Clinical features include oral and genital ulcers, ocular and skin lesions, as well as central nervous system, joint, vascular, gastrointestinal, or pulmonary manifestations. Many studies have reported that Th1 immune responses are involved in the physiopathology. We have previously studied the production of IL-12 and IFN-γ, cytokine markers in the Th1 pathway involved in Behçet's disease. In our study, we investigate in vivo and in vitro IL-18 production in Algerian patients with Behçet's disease with ocular manifestations in various stages of the disease. We examined the effect of glucocorticoids on IL-18 production during the active stage of the disease. Our results suggest that IL-18 could be a good biomarker for monitoring disease activity and its regression, demonstrating the effectiveness of treatment on the underlying immunopathologic process. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. Long Term Results of Radiation Therapy in Early Glottic Cancer

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    Kim, Jin Hee; Byun, Sang Jun [Dongsan Medical Center, Daegu (Korea, Republic of)

    2009-03-15

    This study was designed to evaluate long-term results in terms of failure, survival and voice preservation after radiation therapy for early glottic cancer. From February 1988 to December 2003, 70 patients with early glottic cancer were treated with radiation therapy at Keimyung University Dongsan Medical Center. Patient age distribution was from 39 to 79 years, with a median age of 62 years. All patients had squamous cell carcinoma. According to the TNM stage, 58 patients had stage I disease, 12 patients had stage II disease; 67 patients were male. The laryngeal area was irradiated with the use of bilateral opposing fields with/without a wedge filter with 6 MV photons at a total dose of 54{approx}70.2 Gy in 1.8{approx}2.2 Gy fractions over 6{approx}8 weeks. We delivered a median radiation dose of 60 Gy for stage I patients and a median radiation dose of 66 Gy for stage II patients. Salvage surgery was performed in patients with local recurrence. The voice preservation rate was analyzed after all treatments including salvage surgery. Follow-up periods were from 13 to 180 months, with a median follow-up period of 77.5 months. The survival rate was analyzed by the use of the Kaplan Meier method and log rank test. A comparison of two groups was performed with the use of the chi-squared test. The local control rate was 98.5% (69/70). The five-year-overall survival rate was 93.9%. The five-year disease free survival rate (5YDFS) was 84.1% and the 5YDFS after radiation and salvage surgery was 92.8%. According to stage, the 5YDFS was 93.1% and 91.7% for stage I and stage II respectively. Thirteen patients (18.5%) had local failure with 24 months of median time to local failure and nine patients received salvage surgery; however, four patients were lost to follow-up after a diagnosis of recurrence. Only two patients died due to a distant metastasis at 33 months and 71 months after radiation therapy, respectively. Nine patients died due to other diseases with a median time

  14. Long-term liposteroid therapy for idiopathic pulmonary hemosiderosis.

    Science.gov (United States)

    Doi, Takehiko; Ohga, Shouichi; Ishimura, Masataka; Takada, Hidetoshi; Ishii, Kanako; Ihara, Kenji; Nagai, Hideyuki; Hara, Toshiro

    2013-11-01

    Control of refractory bleeding in idiopathic pulmonary hemosiderosis (IPH) is challenging. Based on the effect of liposteroid (dexamethasone palmitate) for acute bleeding in two reported cases, the long-term utility was assessed in all nine IPH children (including the first two cases) treated in a tertiary center for 20 years. The median at disease onset was 2.3 years (range, 1.2 to 8.6). All had life-threatening and/or repetitive bleeding on prednisolone (PSL) therapy. Liposteroid was intravenously infused at 0.8 mg/kg/day for three consecutive days at the time of acute bleeding. Single infusion was followed by a longer interval from weekly to monthly accompanied by low-dose PSL (less than 0.3 mg/kg/day). Monthly infusion as maintenance therapy was continued for prophylaxis of bleeding. Treatment outcomes were retrospectively analyzed. During the observation period of a median of 11.0 years (range 2.4-16.9 years), no one died. Five patients were weaned and the other one was being weaned from liposteroid for the cure or long remission (median, 5.5 years). Three others were on liposteroid therapy because of active disease. Neither patient had respiratory symptoms, although three showed subnormal %vital capacity. Serum levels of KL-6 and ferritin were normal in all and all but one patient(s), respectively. Four patients (three on liposteroid therapy) showed low bone mineral density. There were no obese patients. Height SD score did not significantly decrease except for one patient. The liposteroid therapy might improve the survival of IPH patients with reducing the adverse effects of steroids, although prospective control studies are needed.

  15. A retrospective evaluation of term infants treated with surfactant therapy

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    Özge Sürmeli-Onay

    2015-04-01

    Full Text Available Aim: To investigate the clinical and therapeutic characteristics and outcomes of term infants who received surfactant therapy (ST for severe respiratory failure in our neonatal intensive care unit (NICU. Methods: The medical records of term infants (gestational age ≥ 370/7 weeks who received ST between 2003-2012 in NICU of Hacettepe University Ihsan Dogramaci Children’s Hospital were evaluated retrospectively. Results: During ten years period, 32 term infants received ST; the mean gestational age was 38.1 ± 0.88 wk and the mean birth weight was 2,936 ± 665 g. The underlying lung diseases were severe congenital pneumonia (CP in 13 (40.6%, acute respiratory distress syndrome (ARDS in 5 (15.6%, meconium aspiration syndrome (MAS in 5 (15.6%, congenital diaphragmatic hernia (CDH in 4 (12.5%, respiratory distress syndrome in 3 (9.4% and pulmonary hemorrhage in 2 (6.3% infants. The median time of the first dose of ST was 7.75 (0.5-216 hours. Pulmonary hypertension accompanied the primary lung disease in 9 (28.1% infants. Mortality rate was 25%. Conclusion: In term infants, CP, ARDS and MAS were the main causes of respiratory failure requiring ST. However, further prospective studies are needed for defining optimal strategies of ST in term infants with respiratory failure.

  16. Long-term follow-up of severely symptomatic women with adenomyoma treated with combination therapy

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    Wei-Min Liu

    2013-03-01

    Conclusion: Combination therapy for adenomyoma provides an effective treatment option for long-term symptom control and uterine preservation in severely symptomatic women for whom previous long-term drug therapy has failed or proven to be intolerable.

  17. Glucocorticoids suppress vasopressin gene expression in human suprachiasmatic nucleus.

    NARCIS (Netherlands)

    Liu, R.-Y.; Unmehopa, U.A.; Zhou, J.-N.; Swaab, D.F.

    2006-01-01

    Sleep impairment is one of the major side effects of glucocorticoid therapy. The mechanism responsible for this circadian disorder is unknown, but alterations in the suprachiasmatic nucleus (SCN), the biological clock of the human brain, are presumed to play a major role. In the present study, the

  18. Glucocorticoids suppress vasopressin gene expression in human suprachiasmatic nucleus

    NARCIS (Netherlands)

    Liu, Rong-Yu; Unmehopa, Unga A.; Zhou, Jiang-Ning; Swaab, Dick F.

    2006-01-01

    Sleep impairment is one of the major side effects of glucocorticoid therapy. The mechanism responsible for this circadian disorder is unknown, but alterations in the suprachiasmatic nucleus (SCN), the biological clock of the human brain, are presumed to play a major role. In the present study, the

  19. Long-term oxygen therapy: Are we prescribing appropriately?

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    Mª Rosa Güell Rous

    2008-06-01

    Full Text Available Mª Rosa Güell RousDepartament de Pneumologia, Hospital de la Santa Creu I de Sant Pau, Barcelona, SpainAbstract: Long-term oxygen therapy (LTOT is the treatment proven to improve survival in chronic obstructive pulmonary disease (COPD patients with chronic respiratory failure. It also appears to reduce the number of hospitalizations, increase effort capacity, and improve health-related quality of life. Standard LTOT criteria are related to COPD patients who have PaO2 <60 mmHg, are in a clinical stable situation, and are receiving optimal pharmacological treatment. According to LTOT guidelines, oxygen should be prescribed for at least 18 hours per day although some authors consider 24 hours would be more beneficial. The benefits of LTOT depend on correction of hypoxemia. Arterial blood gases should be measured at rest. During exercise, an effort test should be done to assure adequate SaO2. During sleep, continuous monitoring of SaO2 and PaCO2 should be performed to confirm correction of SaO2 overnight. An arterial blood gas sample should be taken at awakening to assess PaCO2 in order to prevent hypoventilation from the oxygen therapy. Several issues that need to be addressed are the use of LTOT in COPD patients with moderate hypoxemia, the efficacy of LTOT in patients who desaturate during exercise or during sleep, the optimal dosage of oxygen supplementation, LTOT compliance, and the LTOT prescription in diseases other than COPD.Keywords: long-term oxygen therapy, COPD, oxygen supplementation, chronic respiratory failure, hypoxemia

  20. Light therapy for seniors in long term care.

    Science.gov (United States)

    Royer, Michael; Ballentine, Noel H; Eslinger, Paul J; Houser, Kevin; Mistrick, Richard; Behr, Richard; Rakos, Kirk

    2012-02-01

    To investigate the effects of light therapy on cognition, depression, sleep, and circadian rhythms in a general, nonselected population of seniors living in a long term care facility. A double-blind, placebo-controlled trial. The experiment took place at a long term care facility in Pennsylvania. Study participants (15 treatment, 13 placebo) were residents receiving either personal care or skilled nursing care. Treatment consisted of approximately 400 lux of blue light administered for 30 minutes per day, Monday through Friday, for 4 weeks. The placebo was approximately 75 lux of red light generated from the same device. Behavioral assessments were made using the MicroCog Assessment of Cognitive Functioning, Geriatric Depression Scale, and Profile of Mood States. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale. Three of the 4 composite scores from the MicroCog as well as the mean Tension/Anxiety score from the Profile of Mood States showed a significant treatment versus placebo effect. Blue light treatment led to significant cognitive improvements compared with placebo red light and may be a promising environmental intervention to reduce cognitive symptoms in elderly, long-term care residents. Copyright © 2012 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

  1. Piper sarmentosum Effects on 11β-Hydroxysteroid Dehydrogenase Type 1 Enzyme in Serum and Bone in Rat Model of Glucocorticoid-Induced Osteoporosis.

    Science.gov (United States)

    Mohamad Asri, Siti Fadziyah; Mohd Ramli, Elvy Suhana; Soelaiman, Ima Nirwana; Mat Noh, Muhamad Alfakry; Abdul Rashid, Abdul Hamid; Suhaimi, Farihah

    2016-11-15

    Glucocorticoid-induced osteoporosis is one of the common causes of secondary osteoporosis. Piper sarmentosum (Ps) extract possesses antioxidant and anti-inflammatory activities. In this study, we determined the correlation between the effects of Ps leaf water extract with the regulation of 11β-hydroxysteroid dehydrogenase (HSD) type 1 enzyme activity in serum and bone of glucocorticoid-induced osteoporotic rats. Twenty-four Sprague-Dawley rats were grouped into following: G1: sham-operated group administered with intramuscular vehicle olive oil and vehicle normal saline orally; G2: adrenalectomized (adrx) control group given intramuscular dexamethasone (120 μg/kg/day) and vehicle normal saline orally; G3: adrx group given intramuscular dexamethasone (120 μg/kg/day) and water extract of Piper sarmentosum (125 mg/kg/day) orally. After two months, the femur and serum were taken for ELISA analysis. Results showed that Ps leaf water extract significantly reduced the femur corticosterone concentration (p < 0.05). This suggests that Ps leaf water extract was able to prevent bone loss due to long-term glucocorticoid therapy by acting locally on the bone cells by increasing the dehydrogenase action of 11β-HSD type 1. Thus, Ps may have the potential to be used as an alternative medicine against osteoporosis and osteoporotic fracture in patients on long-term glucocorticoid treatment.

  2. [Treatment of iatrogenic Cushing syndrome: questions of glucocorticoid withdrawal].

    Science.gov (United States)

    Igaz, Péter; Rácz, Károly; Tóth, Miklós; Gláz, Edit; Tulassay, Zsolt

    2007-02-04

    Iatrogenic Cushing's syndrome is the most common form of hypercortisolism. Glucocorticoids are widely used for the treatment of various diseases, often in high doses that may lead to the development of severe hypercortisolism. Iatrogenic hypercortisolism is unique, as the application of exogenous glucocorticoids leads to the simultaneous presence of symptoms specific for hypercortisolism and the suppression of the endogenous hypothalamic-pituitary-adrenal axis. The principal question of its therapy is related to the problem of glucocorticoid withdrawal. There is considerable interindividual variability in the suppression and recovery of the hypothalamic-pituitary-adrenal axis, therefore, glucocorticoid withdrawal and substitution can only be conducted in a stepwise manner with careful clinical follow-up and regular laboratory examinations regarding endogenous hypothalamic-pituitary-adrenal axis activity. Three major complications which can be associated with glucocorticoid withdrawal are: i. reactivation of the underlying disease, ii. secondary adrenal insufficiency, iii. steroid withdrawal syndrome. Here, the authors summarize the most important aspects of this area based on their clinical experience and the available literature data.

  3. Socioeconomics of long-term glaucoma therapy in India

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    Bhagabat Nayak

    2015-01-01

    Full Text Available Purpose: To determine the socioeconomic impact of long-term glaucoma therapy. Materials and Methods: One hundred and fifty consecutive glaucoma patients on medical therapy, following up at our glaucoma service for at least 6 months were recruited. A questionnaire regarding monthly income, cost of glaucoma medications prescribed, availability of medications, travel time, time spent in review clinics, compliance, education status, medical insurance and systemic or local side-effects was administered. Results: The patients seen at the tertiary government hospital had an average monthly income of Rs. 10,912/- (range: Rs. 500/- to Rs. 50,000/- with approximately 56% of the patients having an income of less than Rs. 5000/month. The expenditure on anti-glaucoma medications ranged from 0.3% in high income group to 123% of their monthly gross income in low income group (P < 0.0001. The total expenditure including travel, stay, and loss of wages of patients and accompanying persons ranged from 1.6% in high income group to 137% of the monthly income in low income group (P < 0.0001. Mean time required for a glaucoma clinic visit was 15.66 h, (range: 6-96 h/month. About 2.7% experienced systemic side-effects and 21.3% had complaints of ocular adverse effects. About 90% of the patients were compliant. 92% were not covered by any insurance plan/government reimbursement for their treatment. Conclusions: Medical therapy for glaucoma is an economic burden to many patients and should be individualized, according to the socioeconomic status, availability of drugs and the required distance to travel to reach the specialist clinics.

  4. Long term exposure to antiangiogenic therapy, bevacizumab, induces osteonecrosis.

    Science.gov (United States)

    Tabouret, Tessa; Gregory, Thomas; Dhooge, Marion; Brezault, Catherine; Mir, Olivier; Dréanic, Johann; Chaussade, Stanislas; Coriat, Romain

    2015-10-01

    Bevacizumab, a monoclonal VEGF-A antibody, has been identified as an aetiology of osteonecrosis of the femoral head. Long exposure to anti VEGF therapy induced chronic hypoperfusion of normal tissues. Osteonecrosis is a musculo-skeletal disease secondary to cellular death of bone component mainly induced by corticosteroids, alcohol use, or connective tissue disorders. The medical records of patients with metastatic colorectal carcinoma receiving Bevacizumab between January 2006 and November 2013 were retrospectively reviewed and we had looked for osteonecrosis. Every disorder of musculoskeletal mobility were examined by orthopaedist and evaluated by imaging. We report on osteonecrosis of humeral and femoral head in patient with metastatic colon adenocarcinoma receiving a long-term exposure to anti angiogenic based treatment (>6 months), lack of other factors predisposing to osteonecrosis. These observations, according to literature, suggests that long exposure to anti VEGF-A, Bevacizumab, promote bone hypoperfusion and may induced osteonecrosis either on the femoral head or the humeral head with an incidence of 4 out of 1000 patients. With an incidence of 4 out of 1000 patients osteonecrosis is a rare side effect of anti-angiogenic agent. With the increasing utilisation and duration of exposure of anti-VEGF therapy some rare side effect due to chronic ischemia may appear. The clinician should be aware about uncommon symptoms.

  5. Approach in glucocorticoid-induced osteoporosis prevention: results from the Italian multicenter observational EGEO study.

    Science.gov (United States)

    Massafra, U; Migliaccio, S; Bancheri, C; Chiacchiararelli, F; Fantini, F; Leoni, F; Martin, L S; Migliore, A; Muccifora, B; Napolitano, C; Pastore, R; Ragno, A; Ronzoni, S; Rotondi, M; Tibaldi, M; Villa, P; Vinicola, V; D'Erasmo, E; Falaschi, P; Minisola, G

    2013-02-01

    Glucocorticoid-induced osteoporosis (GIO) is the most frequent cause of secondary osteoporosis. GIO is linked to glucocorticoids (GC) daily assumption with maximum effect within first months of treatment and decreasing to basal levels as the therapy is discontinued. In Italy, primary prevention of GIO is suggested when GC therapy (prednisone >5 mg/day or equivalent) is taken for longer than 3 months. Lazio GISMO (Italian Group for Study and Diagnosis of Bone Metabolism Diseases) group organized the GC and Osteoporosis Epidemiology study (EGEO) to evaluate physician's approach in preventing GIO. The study involved 19 osteoporosis centers. Patients taking long-term GC therapy were recruited and information collected: medical history and anthropometric data, GC therapy, primary disease, physician's specialty, osteopororosis screening, and pharmacological intervention. The study included 1334 patients. Mean age was 63 ± 13 yr; 243 (18%) patients had a history of falls from standing position in the previous 12 months, 78 (35%) vertebral fractures, 91 (41%) fractures other than vertebral, 27 (12%) femoral fractures, and 27 (12%) multiple sites fractures. The molecules of GC more often prescribed were prednisone and 6-metil prednisolone. One thousand and forty patients (78%) were taking GC for more than 6 months. GC therapy was prescribed more frequently by rheumatologists (62%). Antiosteoporotic drugs for GIO prevention were prescribed in 431 patients (32%). Among the patients, only 27% (360) received calcium and vitamin D supplements, and 39% (319) treated by rheumatologists received anti-resorptive drugs. In conclusion, our data show that in Italy, as already described elsewhere, only a small subpopulation of GC-treated patients was supported by an anti-osteoporotic therapy, indicating the need to further stimulate awareness of both patients and specialists, prescribing GC therapy, to an appropriate and prompt GIO prevention.

  6. Cyclosporine therapy for uveitis: long-term followup.

    Science.gov (United States)

    Nussenblatt, R B; Palestine, A G; Chan, C C

    1985-01-01

    Long term followup in 52 uveitis patients treated with Cyclosporine (CsA) is presented here. The patients included in this study all had intermediate or posterior uveitis of noninfectious etiology; and all were considered therapeutic failures to systemic corticosteroids and/or cytotoxic agents. Patients were considered a therapeutic success if the visual acuity in either eye improved two lines or more and/or the vitreal haze improved more than two grading levels. While five patients stopped therapy before the three month interval, 41 of 52 patients or 79% were therapeutic successes at three months after the initiation of CsA as the sole systemic immunosuppressive agent for their disease. Twenty-five of a potential 35 patients (71%) remained on CsA after one year's time, with 63% (22/35) of these individuals receiving the medication considered a therapeutic success. The patients who appeared to respond particularly well to CsA therapy were those with pars planitis, intermediate uveitis of the non-pars planitis type, VKH, and Behcet's disease. In vitro S-antigen (S-Ag) testing did not appear to have a predictive value in determining which patients would be therapeutic successes (improvement in visual acuity), however the S-Ag responder group did appear to have a statistically greater improvement in vitreal haze. Renal toxicity was by far the most common adverse effect, which we have found to be reversible with our approach to therapy. However, adverse reactions required a reduction in CsA dosage in some patients, making it not feasible to maintain therapeutically effective CsA levels. In those patients, low dose prednisone was added to these patients' CsA regimens with generally good results. We did not observe opportunistic infections nor CsA associated neoplasms in our patients. This long term study demonstrates the potential efficacy of CsA in the treatment of severe intra-ocular inflammatory disorders. However, we firmly believe that only in the context of a

  7. Glucocorticoid use and abuse in SLE.

    Science.gov (United States)

    Ruiz-Irastorza, Guillermo; Danza, Alvaro; Khamashta, Munther

    2012-07-01

    Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressive agents. They act by two different mechanisms: the genomic and the non-genomic pathways. The genomic pathway is considered responsible for many adverse effects of GCs, most of them are time and dose dependent. Observational studies support a relationship between GCs and damage in SLE. GCs have been associated with the development of osteoporosis, osteonecrosis, cataracts, hyperglycaemia, coronary heart disease and cognitive impairment, among others. Although no clinical trial has compared high vs low doses of GCs, some studies have shown the efficacy of medium doses in severe forms of SLE. The dose below which treatment can be considered safe has not been defined, but daily doses <7.5 mg of prednisone seem to minimize adverse effects. Combination therapy with HCQ and the judicious use of immunosuppressive drugs help to keep prednisone therapy within those limits.

  8. Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects.

    Science.gov (United States)

    Judd, Lewis L; Schettler, Pamela J; Brown, E Sherwood; Wolkowitz, Owen M; Sternberg, Esther M; Bender, Bruce G; Bulloch, Karen; Cidlowski, John A; de Kloet, E Ronald; Fardet, Laurence; Joëls, Marian; Leung, Donald Y M; McEwen, Bruce S; Roozendaal, Benno; Van Rossum, Elisabeth F C; Ahn, Junyoung; Brown, David W; Plitt, Aaron; Singh, Gagandeep

    2014-10-01

    Glucocorticoids are the most commonly prescribed anti-inflammatory/immunosuppressant medications worldwide. This article highlights the risk of clinically significant and sometimes severe psychological, cognitive, and behavioral disturbances that may be associated with glucocorticoid use, as well as ways to prevent and treat these disturbances. An illustrative case vignette is presented describing a patient's experience of cycles of manic-like behavior and depression while on high-dosage prednisone, with long-term cognitive disorganization, vulnerability to stress, and personality changes. Severe neuropsychiatric consequences (including suicide, suicide attempt, psychosis, mania, depression, panic disorder, and delirium, confusion, or disorientation) have been reported to occur in 15.7 per 100 person-years at risk for all glucocorticoid courses, and 22.2 per 100 person-years at risk for first courses. The majority of patients experience less severe but distressing and possibly persistent changes in mood, cognition, memory, or behavior during glucocorticoid treatment or withdrawal. Although prediction of such effects is difficult, risks vary with age, gender, dosage, prior psychiatric history, and several biological markers. Key mechanisms thought to underlie these risk factors are briefly described. Recommendations are given for identifying individual risk factors and for monitoring and managing adverse neuropsychiatric effects of glucocorticoids.

  9. Glucocorticoid management in rheumatoid arthritis: morning or night low dose?

    Science.gov (United States)

    Paolino, Sabrina; Cutolo, Maurizio; Pizzorni, Carmen

    2017-01-01

    Morning symptoms of rheumatoid arthritis (RA) are linked to circadian increase of night inflammation, supported by inadequate cortisol secretion in active disease. Therefore, exogenous glucocorticoid administration in RA is recommended by EULAR and ACR from the beginning of the diagnosis, since may partially act like a "replacement therapy". In addition, the prevention/treatment of the night up-regulation of the immune/inflammatory reaction has been shown more effective when exogenous glucocorticoid administration is managed with a night-time-release formulation. Despite a considerably higher cost than conventional prednisone (immediate release), chronotherapy with night-time-release prednisone has been recognized a cost-effective option for RA patients not on glucocorticoids who are eligible for therapy with biologic disease-modifying antirheumatic drugs (DMARDs). Interestingly, since different cell populations involved in the inflammatory process are particularly activated during the night (i.e. monocytes, macrophages), other therapeutical approaches used in RA, such as conventional DMARDs and non-steroidal anti-inflammatory drugs (NSAIDs) should follow the same concepts of glucocorticoid chronotherapy. Therefore, bedtime methotrexate chronotherapy was found to better manage RA symptoms, and several available NSAIDs (i.e. indomethacin, aceclofenac, ketoprofen, flurbiprofen, lornoxicam) have been recently modified in their formulation, in order to obtain more focused night action.

  10. The role of glucocorticoids, catecholamines and endocannabinoids in the development of traumatic memories and posttraumatic stress symptoms in survivors of critical illness.

    Science.gov (United States)

    Hauer, Daniela; Kaufmann, Ines; Strewe, Claudia; Briegel, Isabel; Campolongo, Patrizia; Schelling, Gustav

    2014-07-01

    Critically ill patients are at an increased risk for traumatic memories and post-traumatic stress disorder (PTSD). Memories of one or more traumatic events play an important part in the symptom pattern of PTSD. Studies in long-term survivors of intensive care unit (ICU) treatment demonstrated a clear and vivid recall of traumatic experiences and the incidence and intensity of PTSD symptoms increased with the number of traumatic memories present. Preclinical evidence has clearly shown that the consolidation and retrieval of traumatic memories is regulated by an interaction between the noradrenergic, the glucocorticoid and the endocannabinoid system. Critically ill patients in the ICU frequently require treatment with adrenenergic or glucocorticoid drugs and often receive sedative medications; among them propofol is known to influence endocannabinoid signaling. Critical illness could therefore represent a useful model for investigating adrenergic, glucocorticoid as well as endocannabinoid effects on traumatic memory and PTSD development in stressed humans. The endocannabinoid system is an important regulator of HPA-axis activity during stress, an effect which has also been demonstrated in humans. Likewise, a single nucleotide polymorphism (SNP) of the glucocorticoid receptor (GR) gene (the BclI-SNP), which enhances the sensitivity of the glucocorticoid receptors to cortisol and possibly HPA-axis feedback function, was associated with enhanced emotional memory performance in healthy volunteers. The presence of the BclI-SNP increased the risk for traumatic memories and PTSD symptoms in patients after ICU therapy and was linked to lower basal cortisol levels. A number of small studies have demonstrated that the administration of cortisol to critically ill or injured patients results in a significant reduction of PTSD symptoms after recovery without influencing the number of traumatic memories. These glucocorticoid effects can possibly be explained by a cortisol

  11. Testosterone Replacement Therapy: Long-Term Safety and Efficacy

    Directory of Open Access Journals (Sweden)

    Giovanni Corona

    2017-08-01

    Full Text Available Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG or late-onset hypogonadism (LOH. The former is the consequence of congenital or acquired “organic” damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T therapy (TTh. In addition, concerns related to cardiovascular (CV safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an “ex-juvantibus” criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented.

  12. Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Joselyn Rojas

    2014-01-01

    Full Text Available Introduction. Insulin allergy is a rare complication of insulin therapy, especially in type 1 diabetes mellitus (T1DM. Key manifestations are hypersensitivity-related symptoms and poor metabolic control. T1DM, as well as insulin allergy, may develop in the context of autoimmune polyendocrine syndrome (APS, further complicating management. Case Report. A 17-year-old male patient, diagnosed with T1DM, was treated with various insulin therapy schemes over several months, which resulted in recurrent anaphylactoid reactions and poor glycemic control, after which he was referred to our Endocrinology and Immunology Department. A prick test was carried out for all commercially available insulin presentations and another insulin scheme was designed but proved unsuccessful. A desensitization protocol was started with Glargine alongside administration of Prednisone, which successfully induced tolerance. Observation of skin lesions typical of vitiligo prompted laboratory workup for other autoimmune disorders, which returned positive for autoimmune gastritis/pernicious anemia. These findings are compatible with APS type 4. Discussion. To our knowledge, this is the first documented case of insulin allergy in type 4 APS, as well as this particular combination in APS. Etiopathogenic components shared by insulin allergy and APS beg for further research in immunogenetics to further comprehend pathophysiologic aspects of these diseases.

  13. Bilateral atypical femoral fractures after long-term alendronate therapy: a case report.

    Science.gov (United States)

    Bamrungsong, Tachchai; Pongchaiyakul, Chatlert

    2010-05-01

    Bisphosphonates therapy has been shown to decrease the risk of vertebral, non-vertebral, and hip fractures in postmenopausal women. However the long-term safety of bisphosphonates use has been questioned. Recent reports have demonstrated the association between long-term alendronate therapy with low-energy subtrochanteric fracture or diaphyseal femoral fractures in a small number of patients. The author reported the first case of bilateral atypical femoral fractures in postmenopausal women with osteoporosis receiving long-term alendronate therapy.

  14. A chemical screening procedure for glucocorticoid signaling with a zebrafish larva luciferase reporter system.

    Science.gov (United States)

    Weger, Benjamin D; Weger, Meltem; Jung, Nicole; Lederer, Christin; Bräse, Stefan; Dickmeis, Thomas

    2013-09-10

    Glucocorticoid stress hormones and their artificial derivatives are widely used drugs to treat inflammation, but long-term treatment with glucocorticoids can lead to severe side effects. Test systems are needed to search for novel compounds influencing glucocorticoid signaling in vivo or to determine unwanted effects of compounds on the glucocorticoid signaling pathway. We have established a transgenic zebrafish assay which allows the measurement of glucocorticoid signaling activity in vivo and in real-time, the GRIZLY assay (Glucocorticoid Responsive In vivo Zebrafish Luciferase activitY). The luciferase-based assay detects effects on glucocorticoid signaling with high sensitivity and specificity, including effects by compounds that require metabolization or affect endogenous glucocorticoid production. We present here a detailed protocol for conducting chemical screens with this assay. We describe data acquisition, normalization, and analysis, placing a focus on quality control and data visualization. The assay provides a simple, time-resolved, and quantitative readout. It can be operated as a stand-alone platform, but is also easily integrated into high-throughput screening workflows. It furthermore allows for many applications beyond chemical screening, such as environmental monitoring of endocrine disruptors or stress research.

  15. Basolateral Amygdala Interacts with Other Brain Regions in Regulating Glucocorticoid Effects on Different Memory Functions

    National Research Council Canada - National Science Library

    NATHAN, SHEILA V; GRIFFITH, QYANA K; MCREYNOLDS, JAYME R; HAHN, EMILY L; ROOZENDAAL, BENNO

    2004-01-01

    ...‐dependently enhance long‐term memory consolidation. We previously reported that such glucocorticoid effects on memory consolidation rely on noradrenergic activation of the basolateral complex of the amygdala (BLA...

  16. Risk of catecholaminergic crisis following glucocorticoid administration in patients with an adrenal mass: a literature review

    NARCIS (Netherlands)

    Barrett, C.; Uum, S.H. van; Lenders, J.W.M.

    2015-01-01

    BACKGROUND: Glucocorticoids as diagnostic or therapeutic agents have been reported to carry an increased risk of catecholaminergic crisis (CC) in patients with pheochromocytoma or paraganglioma (PPGL). METHODS: We searched literature databases using the following terms: pheochromocytoma,

  17. Consistent control of psoriasis by continuous long-term therapy: the promise of biological treatments.

    NARCIS (Netherlands)

    Kerkhof, P.C.M. van de

    2006-01-01

    Psoriasis is a chronic, incurable disease that frequently requires long-term treatment. Although many patients benefit from effective traditional systemic therapies, namely methotrexate, cyclosporin, retinoids and fumaric acid esters, and some patients achieve long-term disease control, unrestricted

  18. Potential significance of physiological and pharmacological glucocorticoids in early pregnancy.

    Science.gov (United States)

    Michael, Anthony E; Papageorghiou, Aris T

    2008-01-01

    Despite extensive studies of the developmental consequences of increased glucocorticoid exposure in mid- to late pregnancy, relatively little is known regarding the significance of glucocorticoids in early pregnancy. The objective of this review was to consider potential roles for this family of corticosteroids that might relate to early pregnancy. Although this is a narrative review, 249 source articles addressing potential effects of glucocorticoids on aspects of early pregnancy and development (published between 1997 and 2007) were identified using a systematic literature search. Additional articles (115) were identified if cited by the primary reference articles identified in the systematic phase of the review. Much of the evidence to implicate glucocorticoids in early pregnancy comes from studies of steroid receptors and the 11beta-hydroxysteroid dehydrogenase enzymes, which modulate cortisol action in the endometrium/decidua, trophoblast, placenta and embryo/fetus. The evidence reviewed suggests that in early pregnancy the actions of glucocorticoids are balanced between positive effects that would promote pregnancy (e.g. stimulation of hCG secretion, suppression of uterine natural killer cells, and promotion of trophoblast growth/invasion) versus adverse effects that would be expected to compromise the pregnancy (e.g. inhibition of cytokine-prostaglandin signalling, restriction of trophoblast invasion following up-regulation of plasminogen activation inhibitor-1, induction of apoptosis, and inhibition of embryonic and placental growth). Glucocorticoids exert many actions that could impact both negatively and positively on key aspects of early pregnancy. These steroids may also be implicated in obstetric complications, including intra-uterine growth restriction, pre-term labour, pre-eclampsia and chorio-aminionitis.

  19. Low-level laser therapy suppresses the oxidative stress-induced glucocorticoids resistance in U937 cells: relevance to cytokine secretion and histone deacetylase in alveolar macrophages.

    Science.gov (United States)

    Souza, N H C; Marcondes, P T; Albertini, R; Mesquita-Ferrari, R A; Fernandes, K P S; Aimbire, F

    2014-01-05

    Oxidative stress is present in severe asthma and contributes to the low response to corticoids through the downregulation of histone deacetylase (HDAC) and the increase of cytokines. Low-level laser therapy (LLLT) has been proven to be an anti-inflammatory. Thus, we investigated the laser effect on lipopolysaccharide (LPS)-induced cytokine secretion and HDAC activity in U937 cells under oxidative stress. U937 cells activated with oxidative stress were treated with dexamethasone (dexa) or laser. Cytokines and phosphoinositide 3-kinase (PI3K) were measured by ELISA whilst the HDAC was detected through colorimetric assay. LPS activated- U937 cells cytokines secretion increased with H2O2 (hydrogen peroxide) as well as with TSA (trichostatin). The HDAC activity in activated U937 cells was decreased. LLLT and dexa inhibited the LPS-stimulated U937 cells cytokines, but dexa effect disappeared with H2O2. With TSA, the LLLT was less effective on H2O2/LPS stimulated- U937 cells cytokines. Dexa failed on H2O2/LPS- induced HDAC, while LLLT restored the HDAC and the dexa effect. LLLT plus prostaglandin E2 (PGE2) increased cyclic adenosine monophosphate (cAMP) and potentiated the laser action on oxidative stress-induced cytokine. LLLT reduced the PI3K and its effects on cytokine and HDAC was suppressed with LY294002. In situations of corticoid resistance, LLLT acts decreasing the cytokines and HDAC through the activation of the protein kinase A via the inhibition of PI3K. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Glucocorticoid-Induced Diabetes Mellitus: An Important but Overlooked Problem

    Directory of Open Access Journals (Sweden)

    Sunghwan Suh

    2017-05-01

    Full Text Available Glucocorticoids are widely used as potent anti-inflammatory and immunosuppressive drugs to treat a wide range of diseases. However, they are also associated with a number of side effects, including new-onset hyperglycemia in patients without a history of diabetes mellitus (DM or severely uncontrolled hyperglycemia in patients with known DM. Glucocorticoid-induced diabetes mellitus (GIDM is a common and potentially harmful problem in clinical practice, affecting almost all medical specialties, but is often difficult to detect in clinical settings. However, scientific evidence is lacking regarding the effects of GIDM, as well as strategies for prevention and treatment. Similarly to nonsteroid-related DM, the principles of early detection and risk factor modification apply. Screening for GIDM should be considered in all patients treated with medium to high doses of glucocorticoids. Challenges in the management of GIDM stem from wide fluctuations in postprandial hyperglycemia and the lack of clearly defined treatment protocols. Together with lifestyle measures, hypoglycemic drugs with insulin-sensitizing effects are indicated. However, insulin therapy is often unavoidable, to the point that insulin can be considered the drug of choice. The treatment of GIDM should take into account the degree and pattern of hyperglycemia, as well as the type, dose, and schedule of glucocorticoid used. Moreover, it is essential to instruct the patient and/or the patient's family about how to perform the necessary adjustments. Prospective studies are needed to answer the remaining questions regarding GIDM.

  1. The Long Term Effectiveness of Intensive Stuttering Therapy: A Mixed Methods Study

    Science.gov (United States)

    Irani, Farzan; Gabel, Rodney; Daniels, Derek; Hughes, Stephanie

    2012-01-01

    Purpose: The purpose of this study was to gain a deeper understanding of client perceptions of an intensive stuttering therapy program that utilizes a multi-faceted approach to therapy. The study also proposed to gain a deeper understanding about the process involved in long-term maintenance of meaningful changes made in therapy. Methods: The…

  2. [Afterload reduction by long-term nitrate therapy].

    Science.gov (United States)

    Wortmann, A; Bachmann, K

    1989-01-01

    Tolerance to arterial and venous effects is a common problem in longterm-therapy with nitrates when dosing schemes with multiple, regulary timed intervals throughout the day are applied. A balanced effect on preload and afterload is essential for a successful therapy of congestive heart failure. Interval therapy, the once daily medication of a nitrate, has a proven tolerancefree effect on preload. This study addresses the problem of afterload reduction under longterm interval therapy with nitrates. Nine patients with coronary heart disease NYHA II-III with congestion under exercise where included in the study. After a washout period they where treated with once-daily 120 mg ISDN s.r. Measuring mean arterial pressure and cardiac output, we compared the effect of the first dose (acute) with the effect after 5 weeks 1 x 1 120 mg ISDN s.r. (chronic). After acute therapy the mean arterial pressure under exercise was reduced by 14% from 121 +/- 12 mmHg to 104 +/- 11 mmHg. The average reduction of blood pressure under exercise was unchanged during chronic therapy (105 +/- 8 mmHg). Peripheral resistance was reduced by 21% from 914 +/- 266 to 722 +/- 190 dynsec/cm5 after the first dose. The afterload reduction was maintained during chronic therapy (727 +/- 176 dynsec/cm5).

  3. A Case Report of Long-Term Bisphosphonate Therapy and Atypical Stress Fracture of Bilateral Femur

    Science.gov (United States)

    Jo, Yil Ryun; Kim, Hye Won; Moon, Seock Ho

    2013-01-01

    Bisphosphonates are potent inhibitors of bone resorption and considered as a gold standard and are generally recommended as first-line therapy in patients with osteoporosis. Though bisphosphonates are shown to significantly reduce the risk of vertebral, non-vertebral and hip fractures, recent reports suggest a possible correlation between long-term bisphosphonate therapy and the occurrence of insufficiency fractures owing to prolonged bone turnover suppression. We report a patient with non-traumatic stress fractures of bilateral femoral shafts related to long-term bisphosphonate therapy indicating the need for a critical evaluation of patients with long-term bisphosphonate therapy. PMID:23869343

  4. Trends in long-term oxygen therapy for COPD in Denmark from 2001 to 2010

    DEFF Research Database (Denmark)

    Ringbaek, Thomas J; Lange, Peter

    2014-01-01

    To evaluate changes in demographics, incidence, prevalence, treatment modalities, and survival of COPD patients on long-term oxygen therapy (LTOT) from year 2001-2010 in Denmark.......To evaluate changes in demographics, incidence, prevalence, treatment modalities, and survival of COPD patients on long-term oxygen therapy (LTOT) from year 2001-2010 in Denmark....

  5. Glucocorticoids enhance extinction-based psychotherapy.

    Science.gov (United States)

    de Quervain, Dominique J-F; Bentz, Dorothée; Michael, Tanja; Bolt, Olivia C; Wiederhold, Brenda K; Margraf, Jürgen; Wilhelm, Frank H

    2011-04-19

    Behavioral exposure therapy of anxiety disorders is believed to rely on fear extinction. Because preclinical studies have shown that glucocorticoids can promote extinction processes, we aimed at investigating whether the administration of these hormones might be useful in enhancing exposure therapy. In a randomized, double-blind, placebo-controlled study, 40 patients with specific phobia for heights were treated with three sessions of exposure therapy using virtual reality exposure to heights. Cortisol (20 mg) or placebo was administered orally 1 h before each of the treatment sessions. Subjects returned for a posttreatment assessment 3-5 d after the last treatment session and for a follow-up assessment after 1 mo. Adding cortisol to exposure therapy resulted in a significantly greater reduction in fear of heights as measured with the acrophobia questionnaire (AQ) both at posttreatment and at follow-up, compared with placebo. Furthermore, subjects receiving cortisol showed a significantly greater reduction in acute anxiety during virtual exposure to a phobic situation at posttreatment and a significantly smaller exposure-induced increase in skin conductance level at follow-up. The present findings indicate that the administration of cortisol can enhance extinction-based psychotherapy.

  6. Regulation of triglyceride metabolism by glucocorticoid receptor

    Directory of Open Access Journals (Sweden)

    Wang Jen-Chywan

    2012-05-01

    Full Text Available Abstract Glucocorticoids are steroid hormones that play critical and complex roles in the regulation of triglyceride (TG homeostasis. Depending on physiological states, glucocorticoids can modulate both TG synthesis and hydrolysis. More intriguingly, glucocorticoids can concurrently affect these two processes in adipocytes. The metabolic effects of glucocorticoids are conferred by intracellular glucocorticoid receptors (GR. GR is a transcription factor that, upon binding to glucocorticoids, regulates the transcriptional rate of specific genes. These GR primary target genes further initiate the physiological and pathological responses of glucocorticoids. In this article, we overview glucocorticoid-regulated genes, especially those potential GR primary target genes, involved in glucocorticoid-regulated TG metabolism. We also discuss transcriptional regulators that could act with GR to participate in these processes. This knowledge is not only important for the fundamental understanding of steroid hormone actions, but also are essential for future therapeutic interventions against metabolic diseases associated with aberrant glucocorticoid signaling, such as insulin resistance, dyslipidemia, central obesity and hepatic steatosis.

  7. Exogenous glucocorticoids and adverse cerebral effects in children

    DEFF Research Database (Denmark)

    Damsted, Sara K.; Born, A P; Paulson, Olaf B

    2011-01-01

    Glucocorticoids are commonly used in treatment of paediatric diseases, but evidence of associated adverse cerebral effects is accumulating. The various pharmacokinetic profiles of the exogenous glucocorticoids and the changes in pharmacodynamics during childhood, result in different exposure...... of nervous tissue to exogenous glucocorticoids. Glucocorticoids activate two types of intracellular receptors, the mineralocorticoid receptor and the glucocorticoid receptor. The two receptors differ in cerebral distribution, affinity and effects. Exogenous glucocorticoids favor activation...... of the glucocorticoid receptor, which is associated with unfavorable cellular outcomes. Prenatal treatment with glucocorticoids can compromise brain growth and is associated with periventricular leukomalacia, attentions deficits and poorer cognitive performance. In the neonatal period exposure to glucocorticoids...

  8. Current and long-term technologies of laser therapy

    Science.gov (United States)

    Ulashcyk, Vladimir S.; Volotovskaya, Anna V.

    2007-06-01

    Laser therapy, using low-energy laser radiation, is being more and more applied. The most applied technology is transcutaneous radiation of tissues by laser radiation. Originally, a direct action on a pathological site was mostly used, but recently more attention is given to reflexogenic areas, acupuncture points, and endocrine organ projection sites. The development of light-conductive engineering made it possible to practically apply intraorgan laser therapy. This technology is widely spread in gynecology, otorhinolaryngology, urology, gastroenterology, etc. Close to it are different versions of intratissue laser therapy (intraosteal, periosteal, myofascial). A special kind of laser therapy is laser hemotherapy. Depending on the techniques and protocol of its application, there are extracorporeal, intravascular, and supravenous ways of action. According to our comparative investigations, supravenous hemotherapy by its therapeutic efficacy and major medicinal effects can be well compared with intravascular laser hemotherapy. With good prospects and efficiency is laser therapy as a combination of laser and other physical factors. Magnetolaser therapy has been scientifically substantiated and practically applied so far. Theoretically and experimentally substantiated is a combined application of laser radiation and physical factors such as ultrasound, direct current field, vacuum, cryotherapy, etc. Experimental research and few so far clinical observations are indicative of prospects of a complex application of laser radiation and drugs. To improve light absorption, laser radiation is combined with different dyes. Photodynamic therapy, originally used in oncology, is applied today in treating different diseases. We showed a possibility of using a number of drugs possessing simultaneously photosensitizing properties to this end. Laser radiation significantly influences pharmacokinetics and pharmacodynamics of drugs, which gives reason to practically implement laser

  9. Long-term improvement in refractory headache following ozone therapy.

    Science.gov (United States)

    Clavo, Bernardino; Santana-Rodriguez, Norberto; Gutierrez, Dominga; Lopez, Juan C; Suarez, Gerardo; Lopez, Laura; Robaina, Francisco; Bocci, Velio

    2013-05-01

    Headache afflicts approximately 10%-15% of the general population. Mixed results are obtained from various therapies, usually drugs, but also oxygen inhalation, behavioral psychology, physical therapy, and peripheral or central neurostimulation. When refractory to treatment, it has severe impact on quality of life. OBJECTIVES/SUBJECTS: Five (5) patients are presented who had suffered from severe/persistent headache refractory to standard management (including 5-HT1 agonist triptan drugs) and were treated with ozone therapy. Ozone administration was by major autohemotherapy. The procedure involved venous blood drawn into a sterile single-use glass bottle containing anticoagulant, gently mixed with an equal volume of O3/O2 gas mixture (prefiltered through a sterile 0.20-μm filter) and slowly reinfused back into the donor patient via the antecubital vein. The analyzed parameters were analgesia requirements, days of sick leave due to headache, number of headache events, and pain intensity according to the visual analogue scale (VAS); these recorded at three time points: pre-ozone therapy, post-ozone therapy, and before the last follow-up (mean: 64.6±36.8 months). The number of headache episodes pretreatment (n=80; range 5-200) was significantly decreased during the first 6 months post-treatment (n=0, range 0-1; p=0.042) and over the 6 months before the last follow-up visit (n=1, range 0-2; p=0.043). The corresponding VAS scores were 8.7±0.8 pretreatment versus 1.1±2.5 the 6 months post-treatment (p=0.003) and versus 3.1±3.3 the 6 months before last follow-up visit (p=0.036). Ozone therapy decreased headache episodes and pain severity over a protracted period. This novel approach is effective and merits further research.

  10. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens : current questions and tentative answers in rheumatology

    NARCIS (Netherlands)

    Buttgereit, F; da Silva, JAP; Burmester, GR; Cutolo, M; Jacobs, J; Kirwan, J; Kohler, L; van Riel, P; Vischer, T; Bijlsma, JWJ

    In rheumatology and other medical specialties there is a discrepancy between the widespread use and the imprecise designation of glucocorticoid treatment regimens. Verbal descriptions of glucocorticoid treatment regimens used in various phases of diseases vary between countries and institutions.

  11. Enhanced sensitivity to glucocorticoids in cytarabine-resistant AML.

    Science.gov (United States)

    Malani, D; Murumägi, A; Yadav, B; Kontro, M; Eldfors, S; Kumar, A; Karjalainen, R; Majumder, M M; Ojamies, P; Pemovska, T; Wennerberg, K; Heckman, C; Porkka, K; Wolf, M; Aittokallio, T; Kallioniemi, O

    2017-05-01

    We sought to identify drugs that could counteract cytarabine resistance in acute myeloid leukemia (AML) by generating eight resistant variants from MOLM-13 and SHI-1 AML cell lines by long-term drug treatment. These cells were compared with 66 ex vivo chemorefractory samples from cytarabine-treated AML patients. The models and patient cells were subjected to genomic and transcriptomic profiling and high-throughput testing with 250 emerging and clinical oncology compounds. Genomic profiling uncovered deletion of the deoxycytidine kinase (DCK) gene in both MOLM-13- and SHI-1-derived cytarabine-resistant variants and in an AML patient sample. Cytarabine-resistant SHI-1 variants and a subset of chemorefractory AML patient samples showed increased sensitivity to glucocorticoids that are often used in treatment of lymphoid leukemia but not AML. Paired samples taken from AML patients before treatment and at relapse also showed acquisition of glucocorticoid sensitivity. Enhanced glucocorticoid sensitivity was only seen in AML patient samples that were negative for the FLT3 mutation (P=0.0006). Our study shows that development of cytarabine resistance is associated with increased sensitivity to glucocorticoids in a subset of AML, suggesting a new therapeutic strategy that should be explored in a clinical trial of chemorefractory AML patients carrying wild-type FLT3.

  12. The relationship between insight gained during therapy and long-term outcome in short-term dynamic psychotherapy and cognitive therapy for cluster C personality disorders.

    Science.gov (United States)

    Kallestad, Håvard; Valen, Jakob; McCullough, Leigh; Svartberg, Martin; Høglend, Per; Stiles, Tore Charles

    2010-09-01

    This study examined whether 49 patients from a randomized controlled trial developed insight during therapy and whether insight predicted long-term outcome in short-term dynamic psychotherapy (STDP) and cognitive therapy (CT) for Cluster C personality disorders. Videotaped sessions early and late in treatment were analyzed using the Achievement of Therapeutic Objectives Scale. Patients' level of insight increased significantly during STDP but not CT. After controlling for early symptom change and early insight, insight near the end of therapy predicted improvement of symptom severity and interpersonal functioning during a 2-year follow-up period. These results support the theoretical assumption that insight may be a factor in the change process, central to STDP. Within CT, gain of insight did not predict long-term improvement.

  13. Hormetic Influence of Glucocorticoids on Human Memory

    OpenAIRE

    Lupien, Sonia J.; Buss, Claudia; Schramek, Tania E.; Maheu, Francoise; Pruessner, Jens

    2005-01-01

    In this paper, we discuss the effects of glucocorticoids on human learning and memory using the recent model of hormesis proposed by Calabrese and collaborators. Although acute increases in glucocorticoids have been shown to impair memory function in humans, other studies report no such impairments or, in contrast, beneficial effects of acute glucocorticoid increases on human memory function. We summarize these studies and assess whether the wealth of data obtained in humans with regard to th...

  14. Comparative effectiveness of injection therapies in lateral epicondylitis

    DEFF Research Database (Denmark)

    Krogh, Thøger Persson; Bartels, Else Marie; Ellingsen, Torkell Juulsgaad

    2013-01-01

    Injection therapy with glucocorticoids has been used since the 1950s as a treatment strategy for lateral epicondylitis (tennis elbow). Lately, several novel injection therapies have become available....

  15. Safety aspects of preoperative high-dose glucocorticoid in primary total knee replacement

    DEFF Research Database (Denmark)

    Jørgensen, C C; Pitter, F T; Kehlet, H

    2017-01-01

    Background: Preoperative single high-dose glucocorticoid may have early outcome benefits in total hip arthroplasty (THA) and knee arthroplasty (TKA), but long-term safety aspects have not been evaluated. Methods: From October 2013, the departments reporting to the prospective Lundbeck Foundation....... Conclusions: In this detailed prospective cohort study, preoperative high-dose glucocorticoid administration was not associated with LOS >4 days, readmissions or infectious complications in TKA patients without contraindications....

  16. Glucocorticoid control of gene transcription in neural tissue

    NARCIS (Netherlands)

    Morsink, Maarten Christian

    2007-01-01

    Glucocorticoid hormones exert modulatory effects on neural function in a delayed genomic fashion. The two receptor types that can bind glucocorticoids, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), are ligand-inducible transcription factors. Therefore, changes in gene

  17. Acute Nontraumatic Clavicle Fracture Associated with Long-Term Bisphosphonate Therapy

    Directory of Open Access Journals (Sweden)

    Shen Hwa Vun

    2014-01-01

    Full Text Available Cases of osteonecrosis of the jaw, insufficiency fractures and atypical low energy or atraumatic fractures of pelvis, femur (subtrochanteric/mid-shaft/distal-third, tibia, fibula, metatarsal, humerus, and ulna related to long-term bisphosphonate therapy have been reported in the literature. We present the case of an acute nontraumatic clavicle fracture, associated with long-term bisphosphonate therapy, which to our knowledge has not been reported previously. This case highlights the need of critical evaluation of patients with atypical fractures during long-term bisphosphonate therapy.

  18. Being a long-term user of nicotine replacement therapy

    DEFF Research Database (Denmark)

    Borup, Gitte; Nørgaard, Lotte Stig; Tønnesen, Philip

    , regarding long-term NRT users’ experiences with continuing the use of NRT. Results from a survey study among long-term NRT-users, who had used NRT for 12 months or more, found that out of 92 former smokers 88 % wished to quit using NRT. The primary causes stated for wishing to quit were being tired...... of feeling addicted, cost of NRT products and fear of adverse health consequences. Aim of study • To get a thorough understanding of the lived experiences of nicotine dependent long-term NRT users. • To investigate what motivates or discourages quitting NRT. Method Semi-structured interviews with long...

  19. SDF-1 improves wound healing ability of glucocorticoid-treated adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Kato, Toshiki; Khanh, Vuong Cat; Sato, Kazutoshi; Takeuchi, Kosuke; Carolina, Erica; Yamashita, Toshiharu; Sugaya, Hisashi; Yoshioka, Tomokazu; Mishima, Hajime; Ohneda, Osamu

    2017-11-18

    Glucocorticoids cause the delayed wound healing by suppressing inflammation that is required for wound healing process. Adipose tissue-derived mesenchymal stem cells (AT-MSCs) play an important role for wound healing by their cytokine productions including stromal derived factor 1 (SDF-1). However, it has not been clear how glucocorticoids affect the wound healing ability of AT-MSCs. In this study, we found that glucocorticoid downregulated SDF-1 expression in AT-MSCs. In addition, glucocorticoid-treated AT-MSCs induced less migration of inflammatory cells and impaired wound healing capacity compared with glucocorticoid-untreated AT-MSCs. Of note, prostaglandin E2 (PGE2) synthesis-related gene expression was downregulated by glucocorticoid and PGE2 treatment rescued not only SDF-1 expression in the presence of glucocorticoid but also their wound healing capacity in vivo. Furthermore, we found SDF-1-overexpressed AT-MSCs restored wound healing capacity even after treatment of glucocorticoid. Consistent with the results obtained from glucocorticoid-treated AT-MSCs, we found that AT-MSCs isolated from steroidal osteonecrosis donors (sAT-MSCs) who received chronic glucocorticoid therapy showed less SDF-1 expression and impaired wound healing capacity compared with traumatic osteonecrosis donor-derived AT-MSCs (nAT-MSCs). Moreover, the SDF-1 level was also reduced in plasma derived from steroidal osteonecrosis donors compared with traumatic osteonecrosis donors. These results provide the evidence that concomitant application of AT-MSCs with glucocorticoid shows impaired biological modulatory effects that induce impaired wound healing. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Selective Glucocorticoid Receptor Properties of GSK866 Analogs with Cysteine Reactive Warheads

    Directory of Open Access Journals (Sweden)

    Chandra S. Chirumamilla

    2017-11-01

    Full Text Available Synthetic glucocorticoids (GC are the mainstay therapy for treatment of acute and chronic inflammatory disorders. Due to the high adverse effects associated with long-term use, GC pharmacology has focused since the nineties on more selective GC ligand-binding strategies, classified as selective glucocorticoid receptor (GR agonists (SEGRAs or selective glucocorticoid receptor modulators (SEGRMs. In the current study, GSK866 analogs with electrophilic covalent-binding warheads were developed with potential SEGRA properties to improve their clinical safety profile for long-lasting topical skin disease applications. Since the off-rate of a covalently binding drug is negligible compared to that of a non-covalent drug, its therapeutic effects can be prolonged and typically, smaller doses of the drug are necessary to reach the same level of therapeutic efficacy, thereby potentially reducing systemic side effects. Different analogs of SEGRA GSK866 coupled to cysteine reactive warheads were characterized for GR potency and selectivity in various biochemical and cellular assays. GR- and NFκB-dependent reporter gene studies show favorable anti-inflammatory properties with reduced GR transactivation of two non-steroidal GSK866 analogs UAMC-1217 and UAMC-1218, whereas UAMC-1158 and UAMC-1159 compounds failed to modulate cellular GR activity. These results were further supported by GR immuno-localization and S211 phospho-GR western analysis, illustrating significant GR phosphoactivation and nuclear translocation upon treatment of GSK866, UAMC-1217, or UAMC-1218, but not in case of UAMC-1158 or UAMC-1159. Furthermore, mass spectrometry analysis of tryptic peptides of recombinant GR ligand-binding domain (LBD bound to UAMC-1217 or UAMC-1218 confirmed covalent cysteine-dependent GR binding. Finally, molecular dynamics simulations, as well as glucocorticoid receptor ligand-binding domain (GR-LBD coregulator interaction profiling of the GR-LBD bound to GSK866 or

  1. Recommendations for long-term home oxygen therapy in children and adolescents

    Directory of Open Access Journals (Sweden)

    Fabíola V. Adde

    2013-01-01

    Conclusions: Long-term home oxygen therapy is increasingly common in pediatrics and has many indications. There are relevant particularities when compared to its use in adults, regarding indications, directions for use, and monitoring.

  2. Hub Group: An Innovative Approach to Group Therapy in a Short-Term Inpatient Adolescent Unit.

    Science.gov (United States)

    Beitel, Ashley; And Others

    1983-01-01

    Describes Hub Group, a short-term ward-based group therapy program for institutionalized adolescents. Backed by a behaviorally-based privilege system, Hub Group contracting methods facilitate rapid investment in group therapy and promote change. Advantages and disadvantages of including mixed levels of functioning in the same group are discussed.…

  3. Proton pump inhibitor therapy and potential long-term harm.

    Science.gov (United States)

    Corleto, Vito Domenico; Festa, Stefano; Di Giulio, Emilio; Annibale, Bruno

    2014-02-01

    This review summarizes the recent literature on the potential side-effects of proton pump inhibitors (PPIs) and known interactions with the metabolism/absorption of other drugs. Data confirm that PPIs are a very well tolerated drug class. Their high safety, efficacy and wide distribution lead to overuse, inappropriate dosage or excessive duration of treatment. Despite the absorption of micronutrients or other plausible effects on the development of bacterial infections linked to PPI-induced hypochlorhydria, it is difficult to demonstrate an association between PPI and specific symptoms. A possible negative effect of PPIs on bone integrity appears weak, but hypomagnesemia is likely a PPI drug class effect. A higher risk of Clostridium difficile infection and other infectious diseases such as small intestinal bacterial overgrowth and spontaneous bacterial peritonitis remain controversial in PPI users. However, the careful use of PPIs in cirrhotic or otherwise fragile patients is mandatory. Short-term or long-term PPI use may trigger microscopic colitis, and the management of this condition may include PPI withdrawal. The effect of PPIs on stimulating exocrine or endocrine gastric cell proliferation is poorly understood. A diagnostic delay or masking of diseases such as gastrinoma is difficult to evaluate. Short-term standard dose PPI treatment is low risk. Long-term PPI use may complicate health conditions by various mechanisms linked to PPIs and/or to hypochlorhydria.

  4. Stress, glucocorticoids and memory: implications for treating fear-related disorders.

    Science.gov (United States)

    de Quervain, Dominique; Schwabe, Lars; Roozendaal, Benno

    2017-01-01

    Glucocorticoid stress hormones are crucially involved in modulating mnemonic processing of emotionally arousing experiences. They enhance the consolidation of new memories, including those that extinguish older memories, but impair the retrieval of information stored in long-term memory. As strong aversive memories lie at the core of several fear-related disorders, including post-traumatic stress disorder and phobias, the memory-modulating properties of glucocorticoids have recently become of considerable translational interest. Clinical trials have provided the first evidence that glucocorticoid-based pharmacotherapies aimed at attenuating aversive memories might be helpful in the treatment of fear-related disorders. Here, we review important advances in the understanding of how glucocorticoids mediate stress effects on memory processes, and discuss the translational potential of these new conceptual insights.

  5. Advances in Glucocorticoid-induced Osteoporosis

    NARCIS (Netherlands)

    den Uyl, D.; Bultink, I.E.M.; Lems, W.F.

    2011-01-01

    Glucocorticoid-induced osteoporosis (GIOP) is one of the most important side effects of glucocorticoid use, as it leads to an increased risk of fractures. Recently, many published studies have focused on the cellular and molecular mechanisms of bone metabolism, the pathophysiology of GIOP, and the

  6. First intention high-frequency oscillatory and conventional mechanical ventilation in premature infants without antenatal glucocorticoid prophylaxis.

    Science.gov (United States)

    Salvo, Vincenzo; Zimmermann, Luc J; Gavilanes, Antonio W; Barberi, Ignazio; Ricotti, Alberto; Abella, Raul; Frigiola, Alessandro; Giamberti, Alessandro; Florio, Pasquale; Tagliabue, Paolo; Tina, Lucia G; Nigro, Francesco; Temporini, Francesca; Gazzolo, Diego

    2012-01-01

    Data comparing the effectiveness of high-frequency oscillatory ventilation and of conventional mechanical ventilation in the treatment of respiratory distress syndrome of very low birth weight infants are, to date, still matter of debate. We investigated the effects of first intention high-frequency oscillatory ventilation or conventional mechanical ventilation support on selected primary and secondary outcomes in very low birth weight infants complicated by respiratory distress syndrome in which antenatal glucocorticoid prophylaxis was not performed. Multicenter randomized control trial. Three tertiary centers of neonatal intensive care units from December 2004 to December 2007. Eighty-eight very low birth weight infants complicated by respiratory distress syndrome, without antenatal glucocorticoids, supported by first intention high-frequency oscillatory ventilation (n = 44) or conventional mechanical ventilation (n = 44). All newborns were monitored by standard monitoring procedure, including routine laboratory variables, neurologic patterns, and ultrasound imaging. Primary outcomes were: the length of ventilatory support, the need of reintubation, and the length of nasal continuous positive airway pressure support in the postextubation period. Secondary outcomes were: the length of stay in neonatal intensive care unit and in hospital, death before discharge, adverse short- and long-term pulmonary and neonatal outcomes, and the need for a second dose of surfactant and of postnatal glucocorticoid treatment. High-frequency oscillatory ventilation infants showed a significant lower duration (p ventilator dependency, lower need of reintubation and of duration of nasal continuous positive airway pressure support in the postextubation period. Among secondary outcomes in the high-frequency oscillatory ventilation infants, the need of a second dose of surfactant administration, and the length of stay in the neonatal intensive care unit and in hospital were significantly

  7. Hair cortisol content in patients with adrenal insufficiency on hydrocortisone replacement therapy.

    Science.gov (United States)

    Gow, Rachel; Koren, Gideon; Rieder, Michael; Van Uum, Stan

    2011-06-01

    Patients with adrenal insufficiency (AI) require life-long replacement therapy with exogenous glucocorticoids. Several studies have shown impaired subjective health status in these patients as well as increased morbidity and mortality risk, which may be caused by glucocorticoid over-replacement. As a measure of long-term cortisol exposure, the usefulness of hair cortisol analysis in patients receiving glucocorticoid replacement therapy was investigated. Hair samples, demographics, medical history and perceived stress scale questionnaires were collected from 93 patients across North America diagnosed with primary or secondary AI. Sixty-two household partners served as a control group. Cortisol was measured in the proximal 2 cm of hair, representing the most recent 2 months of exposure. A modified enzyme immunoassay was used for the measurement of cortisol. The male patients had significantly higher hair cortisol levels than the male controls (P cortisol content correlated significantly with glucocorticoid dose (r = 0·3, P cortisol content correlates with hydrocortisone (HC) dose in patients with AI. Our results suggest that some AI patients may be over-treated and hence may be at risk for the adverse effects of cortisol. Measurement of HC in hair may become a useful monitoring tool for long-term cortisol exposure in patients treated with glucocorticoids. © 2011 Blackwell Publishing Ltd.

  8. Hormetic Influence of Glucocorticoids on Human Memory

    Science.gov (United States)

    Lupien, Sonia J.; Buss, Claudia; Schramek, Tania E.; Maheu, Francoise; Pruessner, Jens

    2005-01-01

    In this paper, we discuss the effects of glucocorticoids on human learning and memory using the recent model of hormesis proposed by Calabrese and collaborators. Although acute increases in glucocorticoids have been shown to impair memory function in humans, other studies report no such impairments or, in contrast, beneficial effects of acute glucocorticoid increases on human memory function. We summarize these studies and assess whether the wealth of data obtained in humans with regard to the effects of acute increase of glucocorticoids on human cognition are in line with a hormetic function. We then discuss several factors that will have to be taken into account in order to confirm the presence of a hormetic function between glucocorticoids and human cognitive performance. PMID:19330155

  9. Identifying Androgen Receptor-Independent Mechanisms of Prostate Cancer Resistance to Second-Generation Antiandrogen Therapy

    Science.gov (United States)

    2016-08-01

    cancers. 15. SUBJECT TERMS Glucocorticoid Receptor, Serum and glucocorticoid -regulated kinase 1, SGK1, epithelial- mesenchymal transition, EMT 16...receptor transcription factor, glucocorticoid receptor (GR), can activate an overlapping set of AR target genes and can mediate resistance to enzalutamide... glucocorticoid -regulated kinase 1 (SGK1), a target gene of the GR transcriptional program, might be more suitable for targeted inhibition. GR and

  10. Short-term efficacy of physical therapy compared to splint therapy in treatment of arthrogenous TMD.

    Science.gov (United States)

    Ismail, F; Demling, A; Hessling, K; Fink, M; Stiesch-Scholz, M

    2007-11-01

    A prospective randomized study was carried out to evaluate the efficacy of physical therapy in addition to splint therapy on treatment outcome in patients with temporomandibular disorders (TMD) with respect to objective and subjective parameters. Twenty-six patients suffering from an arthrogenic TMD and exhibiting a painfully restricted jaw opening were randomized in two groups. Thirteen patients were treated solely with Michigan splint (group I), 13 patients received supplementary physical therapy (group II). Before treatment a clinical examination and electronic recording of jaw movements were performed and subjective pain level was evaluated by visual analogue scales. After 3 months of therapy maintenance of improvement was evaluated. Within treatment groups comparison of data before and after treatment was analysed using Wilcoxon test. Groups were compared by Mann-Withney-U test. A P-value treatment, whereas subjective pain decreased significantly (P treatment outcome of patients with TMD.

  11. A pilot study evaluating therapeutic response of different dosage of oral glucocorticoid in two children with familial glucocorticoid deficiency presenting with diffuse mucocutaneous hyperpigmentation

    Directory of Open Access Journals (Sweden)

    Uttam Kumar Sarkar

    2017-01-01

    Full Text Available Introduction: Familial glucocorticoid deficiency (FGD is a rare autosomal recessive potentially life-threatening condition, characterized by glucocorticoid deficiency, preserved aldosterone/renin secretion, and secondary rise in plasma adrenocorticotropic hormone level. This occurs due to either mutation in adrenocorticotropic receptor (25%, FGD Type-1 or in the MC2 receptor accessory protein (15%–20%. However, in about 50% patients, no identifiable mutations have been identified. Clinically, it manifests with weakness, fatigue, weight loss, anorexia, nausea, vomiting, diarrhea, abdominal pain, hypoglycemia, and hypothermia. Progressive mucocutaneous pigmentation is a conspicuous presentation. Repeated hypoglycemia may result in seizure, persistent neurological, severe mental disability, and even sudden death. Standard therapy is oral glucocorticoids (10–15 mg/m2. Patients and Results: Two familial cases of FGD were put on progressively increasing doses of oral glucocorticoids (10 mg, 15 mg, and 20 mg/m2/day, each for 6 weeks to achieve the best response without any adverse effects. One patient had excellent improvement with 15 mg/m2/day, and another required 20 mg/m2/day. The latter patient had excellent overall improvement with only moderate improvement in pigmentation. Conclusion: Glucocorticoids replacement with optimum dose is necessary in FGD to promote physical and neurological growth and to prevent adrenal crises, hypotension, hypoglycemia, and sudden death. Higher dose than mentioned in literature (15 mg/m2/day may be required in selected cases. Mucocutaneous pigmentation may require even higher dose than we used. More studies are required.

  12. [First experiences with short-term lithium therapy in severe thyrotoxicosis].

    Science.gov (United States)

    Heberling, H J; Heilman, W; Heintze, M; Gauer, J; Lohmann, D

    1981-10-01

    Even nowadays the therapy of severe, particularly of contrast remedy-induced hyperthyroidism is not without any problems. According to reports in literature the application of lithium salts seems to be an expedient from this dilemma. We controlled the effect of a short-term lithium therapy of 7 days in combination with methimazole in comparison to a group with methimazole monotherapy. The examination showed a good effectiveness and tolerability of the lithium methimazole therapy. While the decrease of the thyroxin concentration in the two groups was not different, in the group with combined therapy a more rapid per cent decrease of the triiodothyronine concentration appeared. In primarily strict selection of the therapy severe side-effects are not to be expected. According to the results yielded up to now the described form of therapy is an actual enrichment for selected forms of hyperthyreosis.

  13. Hypertension: diagnosis, acute antihypertension therapy, and long-term management.

    Science.gov (United States)

    Porsche, R

    1995-11-01

    Hypertension remains a major modifiable risk factor for coronary heart disease, cerebrovascular disease, peripheral vascular disease, and renal disease. Although great strides have been made in increasing patient awareness, lifestyle changes, and compliance with treatment protocols, hypertensive emergencies and hypertensive urgencies remain a major concern. Unless treated promptly, irreversible target organ damage will ensue. Therefore, patients with acutely elevated blood pressure, regardless of cause, must be evaluated expeditiously, and appropriate treatment must be initiated. Nurses must be able to assess and monitor patients and their progress and recognize signs and symptoms of complications related to hypertension. Once blood pressure control has been achieved, nurses initiate patient education. However, long-term management must not only include blood pressure monitoring and patient education, but also emphasize lifestyle changes.

  14. Antenatal glucocorticoid treatment and polymorphisms of the glucocorticoid and mineralocorticoid receptors are associated with IQ and behavior in young adults born very preterm

    NARCIS (Netherlands)

    Voorn, B. van der; Pal, S.M. van der; Rotteveel, J.; Finken, M.J.

    2015-01-01

    Context: Preterm survivors exhibit neurodevelopmental impairments. Whether this association is influenced by antenatal glucocorticoid treatment and glucocorticoid sensitivity is unknown. Objectives: To study the effects of antenatal glucocorticoid treatment and glucocorticoid receptor (GR) and

  15. Short Term Intensive Insulin Therapy Improves Insulin Secretion Significantly in Type 2 Diabetic Patients

    OpenAIRE

    Ogo, Astushi; Hiramatsu, Shinsuke; Watanabe, Akimasa; Asano, Tamotsu; Yoshizumi, Hideyuki

    2006-01-01

    To investigate the effects of short-term(1 week)intensive insulin therapy, on glycemic control, insulin secretion, and insulin sensitivity in type 2 diabetic patients, an open prospective study was conducted in sixteen type 2 diabetic patients receiving diet therapy alone or treatment with oral hypoglycemic agents. Of the study subjects, 8 patients were treated with insulin, the remaining 8 patients served as the control group. The metabolic parameters were evaluated once before treatment and...

  16. Effect of long-term Hormone Replacement Therapy on Plasma Homocysteine in Postmenopausal Women

    DEFF Research Database (Denmark)

    Madsen, Jonna S; Kristensen, Søren R; Klitgaard, Niels A

    2002-01-01

    OBJECTIVE: The purpose of this study was to investigate the long-term effect of hormone replacement therapy on total homocysteine and to study whether there was any difference in effect between opposed and unopposed hormone replacement therapy or whether the methylenetetrahydrofolate reductase C677......T polymorphism was associated with the effect of hormone replacement therapy on total homocysteine. STUDY DESIGN: Two hundred nine healthy postmenopausal women were randomized to hormone replacement therapy (n = 103) or no substitution (n = 106) 5 to 7 years earlier. RESULTS: Women who received...... hormone replacement therapy had significantly lower total homocysteine concentrations than women in the control group; median total homocysteine values were 8.6 micromol/L and 9.7 micromol/L, respectively, in a per-protocol analysis (P =.02). The effect was comparable in all methylenetetrahydrofolate...

  17. [Long-term digitalis therapy of elderly patients. Is digitalization unnecessary in the majority of cases?].

    Science.gov (United States)

    Häcki, M A; Angehrn, W; Cavegn, H R; Brändli, O

    1982-12-18

    More than 40% of patients hospitalized in the Wald Altitude Clinic of Zürich are already on long-term digitalis therapy upon admission. During a 6 month period long-term digoxin therapy was discontinued in 97 patients (age 74 +/- 9 years) with stable cardiac insufficiency (NYHA class I-III) and sinus rhythm. During the hospitalization (37 +/- 20 days), clinical signs and symptoms, body weight, radiological heart size, and systolic time intervals were monitored. After an observation period of one week, digoxin was discontinued in all patients. Body weight, cardio-thoracic ratio and left ventricular ejection time remained unchanged after cessation of digoxin therapy during hospitalization. The pre-ejection period showed a significant increase from 89 +/- 17 to 95 +/- 19 msec. Six patients were re-instituted on digoxin therapy, 3 due to progressive cardiac insufficiency, 2 due to atrial fibrillation, and 1 at his own request. After telephone follow-up six months later with the family physician an additional 20 patients were put back on digitalis. Among the total of 26 patients requiring further digitalization an absolute indication was found only in 12 (14%), 8 due to progressive cardiac insufficiency and 4 due to atrial fibrillation. In this study digitalis therapy could be discontinued without ill effects in 86% of elderly clinically stable patients in sinus rhythm. The authors therefore recommend a more cautious use of long-term digitalis therapy and, in already digitalized patients in sinus rhythm, a controlled trial period of discontinuation.

  18. Molecular mechanisms of glucocorticoid receptor signaling

    Directory of Open Access Journals (Sweden)

    Marta Labeur

    2010-10-01

    Full Text Available This review highlights the most recent findings on the molecular mechanisms of the glucocorticoid receptor (GR. Most effects of glucocorticoids are mediated by the intracellular GR which is present in almost every tissue and controls transcriptional activation via direct and indirect mechanisms. Nevertheless the glucocorticoid responses are tissue -and gene- specific. GR associates selectively with corticosteroid ligands produced in the adrenal gland in response to changes of humoral homeostasis. Ligand interaction with GR promotes either GR binding to genomic glucocorticoid response elements, in turn modulating gene transcription, or interaction of GR monomers with other transcription factors activated by other signalling pathways leading to transrepression. The GR regulates a broad spectrum of physiological functions, including cell differentiation, metabolism and inflammatory responses. Thus, disruption or dysregulation of GR function will result in severe impairments in the maintenance of homeostasis and the control of adaptation to stress.

  19. Predictors of non-responding in short-term psychodynamic group therapy

    DEFF Research Database (Denmark)

    Jensen, Hans Henrik; Mortensen, Erik Lykke; Lotz, Martin

    2017-01-01

    Selection for psychotherapy may be improved by identifying predictors of non-responding to treatment, but there are only few studies of non-responding in short-term psychodynamic group therapy. We analyzed potential socio-demographic and clinical predictors in a sample of 239 patients in 39...... to explore before selection of patients to short-term time-limited psychodynamic group therapy....... sessions of psychodynamic group psychotherapy, including self-reported symptoms, personality, and extra-therapeutic events. Non-responding was assessed by the Symptom Check List-90-Revised Global Severity Index (SCL-90-R GSI) according to Jacobson and Truax’s Reliable Change Index. Non...

  20. Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity

    Directory of Open Access Journals (Sweden)

    Burnsides C

    2012-08-01

    Full Text Available Christopher Burnsides,1,* Jacqueline Corry,1,* Jacob Alexander,1 Catherine Balint,1 David Cosmar,1 Gary Phillips,2 Jeanette I Webster Marketon1,31Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, 2Center for Biostatistics, 3Institute for Behavioral Medicine Research, Wexner Medical Center at The Ohio State University, Columbus, OH, USA*JC and CB have equally contributed to this workPurpose: Glucocorticoids are commonly prescribed to treat a number of diseases including the majority of inflammatory diseases. Despite considerable interpersonal variability in response to glucocorticoids, an insensitivity rate of about 30%, and the risk of adverse side effects of glucocorticoid therapy, currently no assay is performed to determine sensitivity.Patients and methods: Here we propose a whole blood ex vivo stimulation assay to interrogate known glucocorticoid receptor (GR up- and downregulated genes to indicate glucocorticoid sensitivity. We have chosen to employ real-time PCR in order to provide a relatively fast and inexpensive assay.Results: We show that the GR-regulated genes, GILZ and FKBP51, are upregulated in whole blood by treatment with dexamethasone and that LPS-induction of cytokines (IL-6 and TNFα are repressed by dexamethasone in a dose responsive manner. There is considerable interpersonal variability in the maximum induction of these genes but little variation in the EC50 and IC50 concentrations. The regulation of the GR-induced genes differs throughout the day whereas the suppression of LPS-induced cytokines is not as sensitive to time of day.Conclusion: In all, this assay would provide a method to determine glucocorticoid receptor responsiveness in whole blood.Keywords: glucocorticoid responsiveness, gene regulation, nuclear receptor, GILZ, FKBP51, cytokines

  1. Agency over Phantom Limb Enhanced by Short-Term Mirror Therapy.

    Science.gov (United States)

    Imaizumi, Shu; Asai, Tomohisa; Koyama, Shinichi

    2017-01-01

    Most amputees experience phantom limb, whereby they feel that the amputated limb is still present. In some cases, these experiences include pain that can be alleviated by "mirror therapy." Mirror therapy consists of superimposing a mirrored image of the moving intact limb onto the phantom limb. This therapy provides a closed loop between the motor command to the amputated limb and its predicted visual feedback. This loop is also involved in the sense of agency, a feeling of controlling one's own body. However, it is unclear how mirror therapy is related to the sense of agency over a phantom limb. Using mirror therapy, we investigated phantom limb pain and the senses of agency and ownership (i.e., a feeling of having one's own body) of the phantom limb. Nine upper-limb amputees, five of whom reported recent phantom limb pain, underwent a single 15-min trial of mirror therapy. Before and after the trial, the participants completed a questionnaire regarding agency, ownership, and pain related to their phantom limb. They reported that the sense of agency over the phantom limb increased following the mirror therapy trial, while the ownership slightly increased but not as much as did the agency. The reported pain did not change; that is, it was comparably mild before and after the trial. These results suggest that short-term mirror therapy can, at least transiently, selectively enhance the sense of agency over a phantom limb, but may not alleviate phantom limb pain.

  2. Inhaled Nitric Oxide Therapy for Pulmonary Disorders of the Term and Preterm Infant

    OpenAIRE

    Sokol, Gregory M.; Konduri, G. Ganesh; Van Meurs, Krisa P.

    2016-01-01

    The 21st century began with the FDA approval of inhaled nitric oxide therapy for the treatment of neonatal hypoxic respiratory failure associated with pulmonary hypertension in recognition of the two randomized clinical trials demostrating a significant reduction in the need for extracorporeal support in the term and near-term infant. Inhaled nitric oxide is one of only a few therapeutic agents approved for use through clinical investigations primarily in the neonate. This article provides an...

  3. Long term azathioprine maintenance therapy in ANCA-associated vasculitis: combined results of long-term follow-up data.

    Science.gov (United States)

    de Joode, Anoek A E; Sanders, Jan Stephan F; Puéchal, Xavier; Guillevin, Loic P; Hiemstra, Thomas F; Flossmann, Oliver; Rasmussen, Nils; Westman, Kerstin; Jayne, David R; Stegeman, Coen A

    2017-11-01

    We studied whether in ANCA-associated vasculitis patients, duration of AZA maintenance influenced relapse rate during long-term follow-up. Three hundred and eighty newly diagnosed ANCA-associated vasculitis patients from six European multicentre studies treated with AZA maintenance were included; 58% were male, median age at diagnosis 59.4 years (interquartile range: 48.3-68.2 years); granulomatosis with polyangiitis, n = 236; microscopic polyangiitis, n = 132; or renal limited vasculitis, n = 12. Patients were grouped according to the duration of AZA maintenance after remission induction: ⩽18 months, ⩽24 months, ⩽36 months, ⩽48 months or > 48 months. Primary outcome was relapse-free survival at 60 months. During follow-up, 84 first relapses occurred during AZA-maintenance therapy (1 relapse per 117 patient months) and 71 after withdrawal of AZA (1 relapse/113 months). During the first 12 months after withdrawal, 20 relapses occurred (1 relapse/119 months) and 29 relapses >12 months after withdrawal (1 relapse/186 months). Relapse-free survival at 60 months was 65.3% for patients receiving AZA maintenance >18 months after diagnosis vs 55% for those who discontinued maintenance ⩽18 months (P = 0.11). Relapse-free survival was associated with induction therapy (i.v. vs oral) and ANCA specificity (PR3-ANCA vs MPO-ANCA/negative). Post hoc analysis of combined trial data suggest that stopping AZA maintenance therapy does not lead to a significant increase in relapse rate and AZA maintenance for more than 18 months after diagnosis does not significantly influence relapse-free survival. ANCA specificity has more effect on relapse-free survival than duration of maintenance therapy and should be used to tailor therapy individually.

  4. Long-term Metformin Therapy and Monitoring for Vitamin B12 Deficiency Among Older Veterans.

    Science.gov (United States)

    Kancherla, Vijaya; Elliott, John L; Patel, Birju B; Holland, N Wilson; Johnson, Theodore M; Khakharia, Anjali; Phillips, Lawrence S; Oakley, Godfrey P; Vaughan, Camille P

    2017-05-01

    To examine the association between long-term metformin therapy and serum vitamin B12 monitoring. Retrospective cohort study. A single Veterans Affairs Medical Center (VAMC), 2002-2012. Veterans 50 years or older with either type 2 diabetes and long-term metformin therapy (n = 3,687) or without diabetes and no prescription for metformin (n = 13,258). We determined diabetes status from outpatient visits, and defined long-term metformin therapy as a prescription ≥500 mg/d for at least six consecutive months. We estimated the proportion of participants who received a serum B12 test and used multivariable logistic regression, stratified by age, to evaluate the association between metformin use and serum B12 testing. Only 37% of older adults with diabetes receiving metformin were tested for vitamin B12 status after long-term metformin prescription. The mean B12 concentration was significantly lower in the metformin-exposed group (439.2 pg/dL) compared to those without diabetes (522.4 pg/dL) (P = .0015). About 7% of persons with diabetes receiving metformin were vitamin B12 deficient (B12 testing compared to those without metformin exposure, after adjusting for sex, race and ethnicity, body mass index, and number of years treated at the VAMC. Long-term metformin therapy is significantly associated with lower serum vitamin B12 concentration, yet those at risk are often not monitored for B12 deficiency. Because metformin is first line therapy for type 2 diabetes, clinical decision support should be considered to promote serum B12 monitoring among long-term metformin users for timely identification of the potential need for B12 replacement. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  5. Long-Term Effects of Antiviral Therapy in Patients with Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Tatehiro Kagawa

    2010-01-01

    Full Text Available Chronic hepatitis C is a major cause of chronic liver disease globally, and the natural history of progression may lead to cirrhosis with liver failure, hepatocellular carcinoma, and premature liver-related death. Emerging data demonstrates that interferon-based therapy, particularly among those achieving a sustained virologic response (SVR, is associated with long-term persistence of SVR, improved fibrosis and inflammation scores, reduced incidence of hepatocellular carcinoma, and prolonged life expectancy. This reduction in the rate of progression has also been demonstrated in patients with chronic hepatitis C and cirrhosis in some but not all studies. The majority of these results are reported with standard interferon therapy, and long-term results of peginterferon plus ribavirin therapy with a higher likelihood of SVR should have a yet greater impact on the population of treated patients. The impact on slowing progression is greatest in patients with an SVR, less in relapsers, and equivocal in nonresponders. Thus, the natural history of chronic hepatitis C after completion of antiviral therapy is favorable with achievement of an SVR, although further data are needed to determine the likely incremental impact of peginterferon plus ribavirin, late long-term effects of therapy, and the benefit of treatment in patients with advanced hepatic fibrosis.

  6. The terms occupation and activity over the history of official occupational therapy publications.

    Science.gov (United States)

    Bauerschmidt, Bree; Nelson, David L

    2011-01-01

    The history of articles in the American Journal of Occupational Therapy and its predecessors reflects trends and changes in professional terminology and the thoughts underlying that terminology. In this study, we investigate use of occupation, activity, and related terms across 9 decades of occupational therapy literature from the 1920s to the 2000s. The literature for 3 years of each of the 9 decades was scanned electronically. A random numbers table was used to equalize the number of words across decades, and a computer search function was used to determine each term's frequency of use for each decade. Results indicated that the term occupation was widely used in the 1920s but then declined until the 1980s. With a rapid increase in use in the 2000s, the term occupation actually appeared more often than it did in the 1920s. The term activity appeared infrequently in the 1920s but gained popularity from the 1930s to the 1960s. From the 1970s to the 1990s, the use of both terms was quite low. This study shows that basic occupational therapy terminology has fluctuated dramatically over time. Given the essential link between terminology and theory, these changes arguably reflect authors' and editors' changing viewpoints on the profession's fundamental nature.

  7. Primary care veterinary usage of systemic glucocorticoids in cats and dogs in three UK practices.

    Science.gov (United States)

    O'Neill, D; Hendricks, A; Summers, J; Brodbelt, D

    2012-04-01

    To describe systemic glucocorticoid usage in cats and dogs by three primary care -veterinary practices in England and to ascertain risk factors for clinical use. To evaluate consistency of prescribing patterns across clinics. To validate a merged database of primary veterinary clinical data as a functional tool for clinical epidemiological research. A merged database was established from clinical data on 31,273 cat and dog consultations with pharmacotherapy from three veterinary practices in England. Descriptive statistics described systemic glucocorticoid drug use in cats and dogs while mixed-effects logistic regression modelling evaluated risk factors. Individual clinic usage was compared. Overall, 1877 (16·68%) cat consultations and 2913 (14·55%) dog consultations resulted in systemic glucocorticoid therapy. Cats received higher parenteral (Pveterinary clinical database was effective for epidemiological research. © 2012 British Small Animal Veterinary Association.

  8. Making Music, Making Friends: Long-Term Music Therapy with Young Adults with Severe Learning Disabilities

    Science.gov (United States)

    Pavlicevic, Mercédès; O'Neil, Nicky; Powell, Harriet; Jones, Oonagh; Sampathianaki, Ergina

    2014-01-01

    This collaborative practitioner research study emerged from music therapists' concerns about the value of improvisational, music-centred music therapy for young adults with severe learning disabilities (SLDs), given the long-term nature of such work. Concerns included the relevance, in this context, of formulating, and reporting on, therapeutic…

  9. The Effect of Long-Term Outcome Studies on the Therapy of Schizophrenia.

    Science.gov (United States)

    Haley, Jay

    1989-01-01

    Claims since schizophrenia is reversible, professions involved in social control and those doing therapy face new responsibilities. Notes therapists can approach psychotic symptoms expecting the person to become normal. Describes goal as being to help people past periods of acute disturbance without doing them long-term harm. (Author/ABL)

  10. The Effect of Long-Term Outcome Studies on the Therapy of Schizophrenia: A Critique.

    Science.gov (United States)

    Stein, Leonard I.

    1989-01-01

    Comments on Haley's paper "The Effect of Long-Term Outcome Studies on the Therapy of Schizophrenia." Criticizes Haley for making gratuitous, demeaning remarks about psychiatry; concluding that schizophrenia is a psychological and social problem; recommending ineffective treatments for the psychotic phase; and recommending psychotherapy without…

  11. Ethnic Similarity, Therapist Adherence, and Long-Term Multisystemic Therapy Outcomes

    Science.gov (United States)

    Chapman, Jason E.; Schoenwald, Sonja K.

    2011-01-01

    The current study investigated relations among ethnic similarity in caregiver-therapist pairs of youth participating in Multisystemic Therapy, therapist adherence, and youth long-term behavioral and criminal outcomes. Participants were 1,979 youth and families treated by 429 therapists across provider organizations in 45 sites. Relations were…

  12. Magnesium therapy after aneurysmal subarachnoid haemorrhage a dose-finding study for long term treatment

    NARCIS (Netherlands)

    van den Bergh, W. M.; Albrecht, K. W.; Berkelbach van der Sprenkel, J. W.; Rinkel, G. J. E.

    2003-01-01

    BACKGROUND: Magnesium is a neuroprotective agent which might prevent or reverse delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH). Although the dosage for short-term magnesium therapy is well established, there is lack of knowledge on the dosage for extended use of

  13. Prognosis of patients with alpha1-antitrypsine deficiency on long-term oxygen therapy

    DEFF Research Database (Denmark)

    Ringbaek, Thomas J; Seersholm, Niels; Perch, Michael

    2014-01-01

    INTRODUCTION: Data on patients with alpha1-antitrypsine deficiency (AATD) on long-term oxygen therapy (LTOT) is sparse. The aim of this study was to present the incidence of patients with AATD on LTOT, and compare their characteristics, comorbidities and prognosis (lung transplantation, termination...

  14. Burn injury during long-term oxygen therapy in Denmark and Sweden

    DEFF Research Database (Denmark)

    Tanash, Hanan A; Ringbaek, Thomas; Huss, Fredrik

    2017-01-01

    BACKGROUND: Long-term oxygen therapy (LTOT) increases life expectancy in patients with COPD and severe hypoxemia. Smoking is the main cause of burn injury during LTOT. Policy regarding smoking while on LTOT varies between countries. In this study, we compare the incidence of burn injury...

  15. Geographic variation in long-term oxygen therapy in Denmark : factors related to adherence to guidelines for long-term oxygen therapy

    DEFF Research Database (Denmark)

    Ringbæk, Thomas Jørgen; Lange, Peter; Viskum, K

    2001-01-01

    STUDY OBJECTIVES: To evaluate regional differences in adherence to guidelines for long-term oxygen therapy (LTOT) in Denmark and to determine factors related to compliance with these guidelines. DESIGN: Cross-sectional study and analysis of a nationwide database (Danish Oxygen Register). SETTING...... to national guidelines for LTOT was found in 34.4% of the patients for the whole of Denmark and varied regionally from 14 to 63%. Mean compliance with guidelines was 5.3 (range, 2.9 to 9.1) times as likely if the oxygen was prescribed by a pulmonary department compared to LTOT initiated by a GP. CONCLUSIONS...

  16. The long-term effectiveness of Cognitive Behaviour Therapy for Psychosis (CBTp within a routine psychological therapies service

    Directory of Open Access Journals (Sweden)

    Emmanuelle ePeters

    2015-10-01

    Full Text Available Randomised Controlled Trials (RCTs have shown the efficacy of CBTp, however few studies have considered its long-term effectiveness in routine services. This study reports the outcomes of clients seen in a psychological therapies clinic, set up following positive results obtained from an RCT (Peters et al. 2010. The aims were to evaluate the effectiveness of CBTp, using data from the service’s routine assessments for consecutive referrals over a 12 year period, and assess whether gains were maintained at a 6+ months’ follow-up. Of the 476 consenting referrals, all clients (N=358 who received ≥5 therapy sessions were offered an assessment at 4 time points (baseline, pre-, mid- and end of therapy on measures assessing current psychosis symptoms, emotional problems, general well-being and life satisfaction. A sub-set (N=113 was assessed at a median of 12 months after finishing therapy. Following the waiting list (median of 3 months clients received individualised, formulation-based CBTp for a median number of 19 sessions from 121 therapists with a range of experience receiving regular supervision. Clients showed no meaningful change on any measure while on the waiting list (Cohen’s d<=0.23. In contrast, highly significant improvements following therapy, all of which were significantly greater than changes during the waiting list, were found on all domains assessed (Cohen’s d: 0.44-0.75. All gains were maintained at follow-up (Cohen’s d: 0.29-0.82, with little change between end of therapy and follow-up (Cohen’s d<=0.18. Drop-out rate from therapy was low (13%. These results demonstrate the positive and potentially enduring impact of psychological therapy on a range of meaningful outcomes for clients with psychosis. The follow-up assessments were conducted on only a sub-set, which may not generalise to the full sample. Nevertheless this study is the largest of its kind in psychosis, and has important implications for the practice of

  17. Quality of life in Brazilian obese adolescents: effects of a long-term multidisciplinary lifestyle therapy

    Directory of Open Access Journals (Sweden)

    Tufik Sergio

    2009-07-01

    Full Text Available Abstract Background Obesity has adverse physical, social, and economic consequences that can negatively affect quality of life (QOL. Thus the aim of this study was to verify the effects of a long-term multidisciplinary lifestyle intervention on QOL, body image, anxiety, depression and binge eating in obese adolescents. Methods Sixty-six obese adolescents (41 girls and 25 boys; BMI: 35.62 ± 4.18 kg/m2 were recruited from the Multidisciplinary Obesity Intervention Program outpatient clinic, and were submitted to a multidisciplinary lifestyle therapy (short-term = 12 weeks and long-term = 24 weeks, composed of medical, dietary, exercise and psychological programs. Validated self-report questionnaires were used to assess symptoms of anxiety Trait/State (STAI; depression (BDI; binge eating (BES, body image dissatisfaction (BSQ and QOL (SF-36. Data were analyzed by means of scores; comparisons were made by ANOVA for repeated measures, and Tukey's test as post-hoc and Students T test. Results Long-term therapy decreased depression and binge eating symptoms, body image dissatisfaction, and improved QOL in girls, whereas, for boys, 24 weeks, were effective to reduce anxiety trait/state and symptoms of binge eating, and to improve means of dimensions of QOL (p Conclusion A long-term multidisciplinary lifestyle therapy is effective to control psychological aspects and to improve QOL in obese adolescents.

  18. Making music, making friends: Long-term music therapy with young adults with severe learning disabilities.

    Science.gov (United States)

    Pavlicevic, Mercédès; O'Neil, Nicky; Powell, Harriet; Jones, Oonagh; Sampathianaki, Ergina

    2014-03-01

    This collaborative practitioner research study emerged from music therapists' concerns about the value of improvisational, music-centred music therapy for young adults with severe learning disabilities (SLDs), given the long-term nature of such work. Concerns included the relevance, in this context, of formulating, and reporting on, therapeutic aims, development, change; and working in 'goal-oriented' way. Focus groups with the young adults' families and a range of professionals suggest that, rather than leading to developmental change, long-term shared therapeutic musicking provides young adults with ongoing opportunities for experiencing confidence and self-esteem, with feelings of shared acceptance and success, and also provides young adults and their families with opportunities for developing and sustaining friendships. In addition, families experienced meeting other parents and carers in the communal reception area as supportive and countering their isolation. Focus groups assigned intrapersonal, relational and social values to long-term music therapy for young adults with SLDs.

  19. Inhaled Nitric Oxide Therapy for Pulmonary Disorders of the Term and Preterm Infant

    Science.gov (United States)

    Sokol, Gregory M.; Konduri, G. Ganesh; Van Meurs, Krisa P.

    2016-01-01

    The 21st century began with the FDA approval of inhaled nitric oxide therapy for the treatment of neonatal hypoxic respiratory failure associated with pulmonary hypertension in recognition of the two randomized clinical trials demostrating a significant reduction in the need for extracorporeal support in the term and near-term infant. Inhaled nitric oxide is one of only a few therapeutic agents approved for use through clinical investigations primarily in the neonate. This article provides an overview of the pertinent biology and chemistry of nitric oxide, discusses potential toxicities, and reviews the results of pertinent clinical investigations and large randomized clinical trials including neurodevelopmental follow-up in term and preterm neonates. The clinical investigations conducted by the Eunice Kennedy Shriver NICHD Neonatal Research Network will be discussed and placed in context with other pertinent clinical investigations exploring the efficacy of inhaled nitric oxide therapy in neonatal hypoxic respiratory failure. PMID:27480246

  20. Glucocorticoid hypersensitivity syndrome resulting from inhaled corticosteroid: a case report

    Directory of Open Access Journals (Sweden)

    Ejiofor T Ugwu

    2017-01-01

    Full Text Available The termglucocorticoid hypersensitivity syndrome’ is very sparse in the literature. It describes a very rare entity characterized by the appearance of typical Cushingoid features in the presence of normal or low serum cortisol levels. It is also known as cortisol hyper-reactive syndrome or normocortisolemic Cushing’s syndrome. This report illustrates this unusual phenomenon accompanied by metabolic syndrome-like manifestations in a young Nigerian man who was receiving inhaled corticosteroid for bronchial asthma and who experienced a significant improvement following withdrawal of the steroid treatment.

  1. Stereotactic Radiation Therapy for Benign Meningioma: Long-Term Outcome in 318 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Fokas, Emmanouil, E-mail: emmanouil.fokas@kgu.de [Department of Radiotherapy and Radiation Oncology, Philipps-University Marburg, Marburg (Germany); Department of Radiation Therapy and Oncology, Johann Wolfgang Goethe University, Frankfurt (Germany); Henzel, Martin [Department of Radiotherapy and Radiation Oncology, Philipps-University Marburg, Marburg (Germany); Surber, Gunar; Hamm, Klaus [Department for Stereotactic Neurosurgery and Radiosurgery, HELIOS Klinikum Erfurt, Erfurt (Germany); Engenhart-Cabillic, Rita [Department of Radiotherapy and Radiation Oncology, Philipps-University Marburg, Marburg (Germany)

    2014-07-01

    Purpose: To investigate the long-term outcome of stereotactic-based radiation therapy in a large cohort of patients with benign intracranial meningiomas. Methods and Materials: Between 1997 and 2010, 318 patients with histologically confirmed (44.7%; previous surgery) or imaging-defined (55.3%) benign meningiomas were treated with either fractionated stereotactic radiation therapy (79.6%), hypofractionated stereotactic radiation therapy (15.4%), or stereotactic radiosurgery (5.0%), depending on tumor size and location. Local control (LC), overall survival (OS), cause-specific survival (CSS), prognostic factors, and toxicity were analyzed. Results: The median follow-up was 50 months (range, 12-167 months). Local control, OS, and CSS at 5 years were 92.9%, 88.7%, and 97.2%, and at 10 years they were 87.5%, 74.1%, and 97.2%, respectively. In the multivariate analysis, tumor location (P=.029) and age >66 years (P=.031) were predictors of LC and OS, respectively. Worsening of pre-existing neurologic symptoms immediately after radiation therapy occurred in up to 2%. Clinically significant acute toxicity (grade 3°) occurred in 3%. Only grade 1-2 late toxicity was observed in 12%, whereas no new neurologic deficits or treatment-related mortality were encountered. Conclusions: Patients with benign meningiomas predominantly treated with standard fractionated stereotactic radiation therapy with narrow margins enjoy excellent LC and CSS, with minimal long-term morbidity.

  2. Predictors of atypical femoral fractures during long term bisphosphonate therapy: A case series & review of literature

    Directory of Open Access Journals (Sweden)

    Sanjay Kumar Bhadada

    2014-01-01

    Full Text Available Background & objectives: Bisphosphonates (BPs are the most widely prescribed medicines for the treatment of osteoporosis because of their efficacy and favourable safety profile. There have been, several reports on an increased incidence of atypical femoral fractures after long term treatment with BPs. The objective of this study was to evaluate the clinical presentation including prodromal symptoms, skeletal radiograph findings, type and duration of BPs received and treatment outcome of patients who developed atypical femoral fractures during bisphosphonate therapy. Methods: In this retrospective study, eight patients with atypical femoral fractures were analysed based on clinical features, biochemical and radiological investigations. Results: Of the eight patients, who sustained atypical femoral fractures, six were on alendronate and two were on zoledronate therapy before the fractures. In addition to BPs, two patients were on long term corticosteroid therapy for rheumatoid arthritis and Addison′s disease. Three patients had bilateral atypical femoral fractures. Except one, all of them had prodromal symptoms prior to fracture. Skeletal radiograph showed cortical thickening, pointed (beaking of cortical margin and transverse fracture in meta-diaphyseal location. Serum calcium, phosphate, alkaline phosphatase (ALP and intact parathyroid hormone (iPTH concentrations were within the reference range in all patients. Interpretation & conclusions: Long term bisphosphonate therapy may increase the risk of atypical femoral fractures. Presence of prodromal pain, thickened cortex with cortical beaking may be an early clue for predicting the atypical fractures. High risk patients need periodical skeletal survey and a close follow up for early detection of cases.

  3. Long-term safety aspects of systemic therapy with fumaric acid esters in severe psoriasis.

    Science.gov (United States)

    Hoefnagel, J J; Thio, H B; Willemze, R; Bouwes Bavinck, J N

    2003-08-01

    Therapy with fumaric acid esters (FAE) has been shown to be safe and effective in patients with severe psoriasis in several clinical studies with limited follow-up periods. In view of the chronic character of psoriasis, long-term safety aspects are of major importance in determining the suitability of a drug during prolonged periods of treatment. To investigate adverse events of therapy with systemic FAE with follow-up periods of up to 14 years, in order to determine safety aspects of their long-term use in patients with severe psoriasis. Current and/or past therapeutic use of FAE was reviewed in 66 patients with severe psoriasis. Forty-one of 66 patients had received FAE for at least 1 year, and 12 of these 41 patients had received FAE for between 10 and 14 years. Adverse events were reported in 73% of the patients. These were usually mild and mainly consisting of flushing (55%), diarrhoea (42%), nausea (14%), tiredness (14%) and stomach complaints (12%). A relative lymphocytopenia was observed in 76% of patients during therapy with FAE, resulting in a permanent discontinuation of therapy with FAE in four patients. A transient eosinophilia and moderate liver enzyme elevations were observed in 14% and 25% of patients, respectively. The present study indicates that FAE can be considered as a safe long-term treatment in patients with severe psoriasis.

  4. Acute and chronic glucocorticoid treatments regulate astrocyte-enriched mRNAs in multiple brain regions in vivo

    Directory of Open Access Journals (Sweden)

    Bradley S. Carter

    2013-08-01

    Full Text Available Previous studies have primarily interpreted gene expression regulation by glucocorticoids in the brain in terms of impact on neurons; however, less is known about the corresponding impact of glucocorticoids on glia and specifically astrocytes in vivo. Recent microarray experiments have identified glucocorticoid-sensitive mRNAs in primary astrocyte cell culture, including a number of mRNAs that have reported astrocyte-enriched expression patterns relative to other brain cell types. Here, we have tested whether elevations of glucocorticoids regulate a subset of these mRNAs in vivo following acute and chronic corticosterone exposure in adult mice. Acute corticosterone exposure was achieved by a single injection of 10 mg/kg corticosterone, and tissue samples were harvested two hours post-injection. Chronic corticosterone exposure was achieved by administering 10 mg/mL corticosterone via drinking water for two weeks. Gene expression was then assessed in two brain regions associated with glucocorticoid action (prefrontal cortex and hippocampus by qPCR and by in situ hybridization. The majority of measured mRNAs regulated by glucocorticoids in astrocytes in vitro were similarly regulated by acute and/or chronic glucocorticoid exposure in vivo. In addition, the expression levels for mRNAs regulated in at least one corticosterone exposure condition (acute/chronic demonstrated moderate positive correlation between the two conditions by brain region. In situ hybridization analyses suggest that select mRNAs are regulated by chronic corticosterone exposure specifically in astroctyes based on (1 similar general expression patterns between corticosterone-treated and vehicle-treated animals and (2 similar expression patterns to the pan-astrocyte marker Aldh1l1. Our findings demonstrate that glucocorticoids regulate astrocyte-enriched mRNAs in vivo and suggest that glucocorticoids regulate gene expression in the brain in a cell type-dependent fashion.

  5. Short-term combination therapy and long-term relapse prevention in the treatment of severe acne vulgaris.

    Science.gov (United States)

    Tan, Jerry; Stein Gold, Linda; Schlessinger, Joel; Brodell, Robert; Jones, Terry; Cruz, Alma; Kerrouche, Nabil; Jarratt, Michael

    2012-02-01

    Few long-term treatment regimens for severe acne vulgaris have been investigated in clinical trials. Data were combined from two consecutive, randomized, double-blind, controlled studies to evaluate the efficacy, safety and subject satisfaction of four nine-month regimens in severe acne vulgaris treatment. Subjects were first randomized to receive doxycycline (DCN) and adapalene 0.1% - benzoyl peroxide 2.5% (A/BPO) or vehicle once daily for 12 weeks. Subjects who had at least 50% global improvement were subsequently randomized to receive A/BPO or its vehicle once daily for 24 weeks. Over nine months, there were four regimens: A/BPO and DCN followed by A/BPO, vehicle and DCN followed by A/BPO, A/BPO and DCN followed by vehicle, and vehicle and DCN followed by vehicle. Among the four regimens, A/BPO and DCN followed by A/BPO led to the highest percentage of subjects rated "clear" or "almost clear" (50.0% vs. 40.4%, 26.2% and 25.0%, respectively), biggest reduction in total lesion counts (76% vs. 70%, 51% and 47%, respectively) and greatest subject satisfaction (85.0% vs. 75.5%, 63.3% and 52.4%, respectively) at week 36. It provided a faster onset of action compared to groups started with vehicle and DCN (PBPO and DCN followed by vehicle experienced deterioration once the active treatment was discontinued. All regimens were safe and well-tolerated. In conclusion, efficacious initial therapy and long-term treatment are both important. An initial combination therapy with adapalene-BPO and DCN followed by longer-term adapalene-BPO treatment is an efficacious and satisfactory new regimen for severe acne subjects.

  6. Success and problems of long-term levodopa therapy in Parkinson's disease.

    Science.gov (United States)

    Marsden, C D; Parkes, J D

    1977-02-12

    The patient with Parkinson' disease on chronic levodopa therapy, like the diabetic on insulin, is dependent on the drug. Like the diabetic, the patients with Parkinson's disease may run into problems during long-term treatment. Two have emerged as frequent and serious, an insidious and progressive loss of benefit and the appearance of progessively more severe fluctuations in disability. It is concluded that progression of the underlying pathology of the disease is probably responsible. Discovery of the exact causes for loss of benefit may provide a rational basis for new therapy.

  7. Surfactant replacement therapy for preterm and term neonates with respiratory distress.

    Science.gov (United States)

    Polin, Richard A; Carlo, Waldemar A

    2014-01-01

    Respiratory failure secondary to surfactant deficiency is a major cause of morbidity and mortality in preterm infants. Surfactant therapy substantially reduces mortality and respiratory morbidity for this population. Secondary surfactant deficiency also contributes to acute respiratory morbidity in late-preterm and term neonates with meconium aspiration syndrome, pneumonia/sepsis, and perhaps pulmonary hemorrhage; surfactant replacement may be beneficial for these infants. This statement summarizes the evidence regarding indications, administration, formulations, and outcomes for surfactant-replacement therapy. The clinical strategy of intubation, surfactant administration, and extubation to continuous positive airway pressure and the effect of continuous positive airway pressure on outcomes and surfactant use in preterm infants are also reviewed.

  8. A short-term eradication therapy for Helicobacter pylori acute gastritis.

    Science.gov (United States)

    Nomura, H; Miyake, K; Kashiwagi, S; Sugiyama, T; Asaka, M

    2000-12-01

    Acute gastritis, caused by an initial infection of Helicobacter pylori (H. pylori), may resolve spontaneously, but the infection sometimes becomes chronic. We examined the efficacy of a short-term H. pylori eradication therapy on acute gastritis. Among the 15 patients with hemorrhagic acute gastritis who were randomly allocated to group A (eradication therapy) or group B (Lansoprazole, LPZ), 10 of them started to receive treatment within 1 day after the disease onset. The other five patients began the eradication therapy 4-6 days after disease onset (group C). Eradication therapy consisted of a daily oral administration of each of 30 mg lansoprazole (LPZ), once a day; 400 mg clarithromycin, twice a day; 1000 mg amoxicillin, twice a day; and 300 mg rebamipide, three times a day, for one week. If the endoscopy was normal, medication was stopped for the following 4 weeks before gastric endoscopy was performed again in order to assess H. pylori eradication. All group A patients were cured after the 1-week treatment and therefore, they became H. pylori negative. Group B and C patients had erosions or ulcers after the 1-week treatment and so received an additional 3-week administration of LPZ. Four weeks later, their gastritis was cured and except for one group B patient, they became H. pylori-negative. In patients with acute gastritis, caused by an initial H. pylori infection, eradication therapy was efficacious in achieving early healing. This therapy should be started as soon as possible after disease onset.

  9. Short-term and long-term outcomes of intrathoracic vacuum therapy of empyema in debilitated patients

    Directory of Open Access Journals (Sweden)

    Zsolt Sziklavari

    2016-10-01

    Full Text Available Abstract Background This retrospective study analyzed the effectiveness of intrathoracic negative pressure therapy for debilitated patients with empyema and compared the short-term and long-term outcomes of three different intrapleural vacuum-assisted closure (VAC techniques. Methods We investigated 43 consecutive (preseptic patients with poor general condition (Karnofsky index ≤ 50 % and multimorbidity (≥ 3 organ diseases or immunosuppression, who had been treated for primary, postoperative, or recurrent pleural empyema with VAC in combination with open window thoracostomy (OWT-VAC with minimally invasive technique (Mini-VAC, and instillation (Mini-VAC-Instill. Results The overall duration of intrathoracic vacuum therapy was 14 days (5–48 days. Vacuum duration in the Mini-VAC and Mini-VAC-Instill groups (12.4 ± 5.7 and 10.4 ± 5.4 days was significantly shorter (p = 0.001 than in the group treated with open window thoracostomy (OWT-VAC (20.3 ± 9.4 days. No major complication was related to intrathoracic VAC therapy. Chest wall closure rates were significantly higher in the Mini-VAC and Mini-VAC-Instill groups than in the OWT-VAC group (p = 0.034 and p = 0.026. Overall, the mean postoperative length of stay in hospital (LOS was 21 days (median 18, 6–51 days. LOS was significantly shorter (p = 0.027 in the Mini-VAC-Instill group (15.1 ± 4.8 than in the other two groups (23.8 ± 12.3 and 22.7 ± 1.5. Overall, the 30-day and 60-day mortality rates were 4.7 % (2/43 and 9.3 % (4/43, and none of the deaths was related to infection. Conclusions For debilitated patients, immediate minimally invasive intrathoracic vacuum therapy is a safe and viable alternative to OWT. Mini-VAC-Instill may have the fastest clearance and healing rates of empyema.

  10. Changes in Corneal Biomechanical Properties after Long-Term Topical Prostaglandin Therapy.

    Science.gov (United States)

    Wu, Na; Chen, Yuhong; Yu, Xiaobo; Li, Mengwei; Wen, Wen; Sun, Xinghuai

    2016-01-01

    To compare corneal biomechanical properties, measured by a newly developed tonometer (Corneal Visualization Scheimpflug Technology, Corvis ST), in untreated primary open angle glaucoma (POAG) patients, POAG patients with long-term topical prostaglandin analog (PGA) therapy and in normal controls. Further is to investigate the potential effects of PGA on corneal biomechanics. In this case-control study, 35 consecutive medication naïve eyes with POAG, 34 POAG eyes with at least 2 years treatment by PGA and 19 normal eyes were included. Intraocular pressure (IOP), central corneal thickness (CCT) and corneal biomechanical parameters, including deformation amplitude (DA), applanation time (AT1 and AT2), applanation length (AL1 and AL2), applanation velocity (AV1 and AV2), and peak distance and radius were measured using Corvis ST. Axial length and corneal curvature were measured with partial coherence interferometry (IOLMaster, Zeiss, Germany). General linear model analysis was performed to investigate the corneal biomechanical property changes among the normal controls, newly diagnosed POAG patients and POAG patients with long-term PGA treatment, and among the subgroups of different types of PGA treatment, including bimatoprost, latanoprost and travoprost. Furthermore, pairwise comparisons using Bonferroni correction for least squares means were employed. AT1 (pcorneal curvature, a significant difference was detected for DA between glaucoma patients without PGA treatment and patients with long-term PGA therapy (p = 0.0387). Furthermore, there were no statistical significant differences in all of the corneal biomechanical parameters among the 3 types of PGA therapy subgroups, namely bimatoprost, latanoprost and travoprost. Significant changes in corneal deformation parameters were found among untreated POAG patients, POAG patients with long-term topical PGA therapy and normal controls. Long-term topical PGA treatment might have a direct effect on corneal biomechanical

  11. Agency over Phantom Limb Enhanced by Short-Term Mirror Therapy

    Directory of Open Access Journals (Sweden)

    Shu Imaizumi

    2017-10-01

    Full Text Available Most amputees experience phantom limb, whereby they feel that the amputated limb is still present. In some cases, these experiences include pain that can be alleviated by “mirror therapy.” Mirror therapy consists of superimposing a mirrored image of the moving intact limb onto the phantom limb. This therapy provides a closed loop between the motor command to the amputated limb and its predicted visual feedback. This loop is also involved in the sense of agency, a feeling of controlling one’s own body. However, it is unclear how mirror therapy is related to the sense of agency over a phantom limb. Using mirror therapy, we investigated phantom limb pain and the senses of agency and ownership (i.e., a feeling of having one’s own body of the phantom limb. Nine upper-limb amputees, five of whom reported recent phantom limb pain, underwent a single 15-min trial of mirror therapy. Before and after the trial, the participants completed a questionnaire regarding agency, ownership, and pain related to their phantom limb. They reported that the sense of agency over the phantom limb increased following the mirror therapy trial, while the ownership slightly increased but not as much as did the agency. The reported pain did not change; that is, it was comparably mild before and after the trial. These results suggest that short-term mirror therapy can, at least transiently, selectively enhance the sense of agency over a phantom limb, but may not alleviate phantom limb pain.

  12. Glucocorticoids and the regulation of memory in health and disease

    NARCIS (Netherlands)

    de Quervain, Dominique J. -F; Aerni, Amanda; Schelling, Gustav; Roozendaal, Benno

    Over the last decades considerable evidence has accumulated indicating that glucocorticoids - stress hormones released from the adrenal cortex - are crucially involved in the regulation of memory. Specifically, glucocorticoids have been shown to enhance memory consolidation of emotionally arousing

  13. Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects

    NARCIS (Netherlands)

    Judd, L.L.; Schettler, P.J.; Brown, E.S.; Wolkowitz, O.M.; Sternberg, E.M.; Bender, B.G.; Bulloch, K.; Cidlowski, J.A.; Kloet, E.R. de; Fardet, L.; Joels, M.; Leung, D.Y.; McEwen, B.S.; Roozendaal, B.; Rossum, E.F. van; Ahn, J.; Brown, D.W.; Plitt, A.; Singh, G.

    2014-01-01

    Glucocorticoids are the most commonly prescribed anti-inflammatory/immunosuppressant medications worldwide. This article highlights the risk of clinically significant and sometimes severe psychological, cognitive, and behavioral disturbances that may be associated with glucocorticoid use, as well as

  14. Glucocorticoid Receptors and the Pattern of Steroid Response in ...

    African Journals Online (AJOL)

    CD3+) expression of glucocorticoid receptors (GCR) and the response to glucocorticoid treatment in children with idiopathic nephrotic syndrome (NS). The aim of the current study is to determine whether steroid responsiveness is dependent on ...

  15. Adverse Consequences of Glucocorticoid Medication : Psychological, Cognitive, and Behavioral Effects

    NARCIS (Netherlands)

    Judd, Lewis L.; Schettler, Pamela J.; Brown, E. Sherwood; Wolkowitz, Owen M.; Sternberg, Esther M.; Bender, Bruce G.; Bulloch, Karen; Cidlowski, John A.; de Kloet, E. Ronald; Fardet, Laurence; Joëls, Marian; Leung, Donald Y. M.; McEwen, Bruce S.; Roozendaal, Benno; Van Rossum, Elisabeth F. C.; Ahn, Junyoung; Brown, David W.; Plitt, Aaron; Singh, Gagandeep

    2014-01-01

    Glucocorticoids are the most commonly prescribed anti-inflammatory/immunosuppressant medications worldwide. This article highlights the risk of clinically significant and sometimes severe psychological, cognitive, and behavioral disturbances that may be associated with glucocorticoid use, as well as

  16. Change in defense mechanisms during short-term dynamic and cognitive therapy in patients with cluster C personality disorders.

    Science.gov (United States)

    Johansen, Pål-Ørjan; Krebs, Teri S; Svartberg, Martin; Stiles, Tore C; Holen, Are

    2011-09-01

    The aims of this study were to examine whether a change in overall defensive functioning during treatment a) would predict change in symptom distress during the course of treatment and follow-up and b) would be greater in short-term dynamic therapy than in cognitive therapy. Patients (N = 50) who met criteria for cluster C personality disorders were randomized to 40 weekly sessions of short-term dynamic therapy or cognitive therapy. Video recordings of a pretreatment interview and therapy session 36 were evaluated using the Defense Mechanisms Rating Scales. Symptom distress was measured using the revised version of Symptom Checklist-90. Change in overall defensive functioning during treatment predicted change in symptom distress from pretreatment to 2 years after treatment. Both treatment groups showed significant changes in defensive functioning toward greater adaptability but without any significant differences between the short-term dynamic therapy and cognitive therapy groups in a sample of patients with cluster C personality disorders.

  17. The impact of the Danish Oxygen Register on adherence to guidelines for long-term oxygen therapy in COPD patients

    DEFF Research Database (Denmark)

    Ringbaek, Thomas J; Lange, Peter

    2006-01-01

    To evaluate the impact of The Danish Oxygen Register on COPD patients' treatment modalities, survival, and adherence to guidelines for long-term oxygen therapy (LTOT).......To evaluate the impact of The Danish Oxygen Register on COPD patients' treatment modalities, survival, and adherence to guidelines for long-term oxygen therapy (LTOT)....

  18. Long term efficacy of Photodynamic Therapy (PDT) as an ablative therapy of high grade dysplasia in Barrett's oesophagus.

    Science.gov (United States)

    Gray, J; Fullarton, G M

    2013-12-01

    Barrett's high grade dysplasia (HGD) is a pre-malignant condition which requires treatment with either oesophagectomy or ablative endoscopic therapy. Endoscopic ablative techniques have evolved through Photodynamic Therapy (PDT) to more recently radiofrequency ablation (RFA). Although RFA has superseded PDT due to improved efficacy and safety profile there remains a significant cohort of patients previously treated by PDT where the long term outcome is unclear. This study's aim was to assess the long term efficacy of PDT in patients with Barrett's HGD. Between June 2002 and 2007 21 patients (16 male, median age 70) underwent PDT for HGD in Barrett's oesophagus. Patients received intravenous photosensitiser Photofrin (Porfimer sodium) forty eight hours prior to endoscopic light activation by laser light at 630 nm. The patients returned at 6-12 weekly intervals for repeat endoscopy and biopsy. Sixteen patients remained free of HGD at median 62 (range 36-114) months. Three patients developed adenocarcinoma at 47, 48 and 54 months (15%). Two patients were treated endoscopically with RFA and YAG laser, while one patient had surgical resection. Four patients developed recurrent HGD treated with repeat PDT. There was a significant reduction in length of Barrett's segment (from 5 cm to 3 cm) post PDT. The stricture rate requiring endoscopic therapy was 37% and 10% of patients developed photosensitivity reactions. PDT successfully ablated HGD in 84% of patients and could therefore still be considered an effective salvage treatment for this condition in patients with co-morbidities precluding them for surgical resection. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. The Role and Mechanisms of Action of Glucocorticoid Involvement in Memory Storage

    Science.gov (United States)

    Sandi, Carmen

    1998-01-01

    Adrenal steroid hormones modulate learning and memory processes by interacting with specific glucocorticoid receptors at different brain areas. In this article, certain components of the physiological response to stress elicited by learning situations are proposed to form an integral aspect of the neurobiological mechanism underlying memory formation. By reviewing the work carried out in different learning models in chicks (passive avoidance learning) and rats (spatial orientation in the Morris water maze and contextual fear conditioning), a role for brain corticosterone action through the glucocorticoid receptor type on the mechanisms of memory consolidation is hypothesized. Evidence is also presented to relate post-training corticosterone levels to the strength of memory storage. Finally, the possible molecular mechanisms that might mediate the influences of glucocorticoids in synaptic plasticity subserving long-term memory formation are considered, mainly by focusing on studies implicating a steroid action through (i) glutamatergic transmission and (ii) cell adhesion molecules. PMID:9920681

  20. Islet-cell dysfunction induced by glucocorticoid treatment

    DEFF Research Database (Denmark)

    van Raalte, Daniël H; Kwa, Kelly A A; van Genugten, Renate E

    2013-01-01

    Glucocorticoids impair glucose tolerance by inducing insulin resistance. We investigated the dose-dependent effects of glucocorticoid treatment on islet-cell function in healthy males and studied the role of the autonomic nervous system.......Glucocorticoids impair glucose tolerance by inducing insulin resistance. We investigated the dose-dependent effects of glucocorticoid treatment on islet-cell function in healthy males and studied the role of the autonomic nervous system....

  1. Effect of Long-Term Proton Pump Inhibitor Therapy on Nutritional Status in Elderly Hospitalized Patients.

    Science.gov (United States)

    Nakamichi, Mariko; Wakabayashi, Hidetaka

    2016-01-01

    The purpose was to investigate the association between proton pump inhibitor (PPI) therapy and nutritional status in elderly hospitalized patients. Participants were 190 elderly patients admitted to the long-term care wards, convalescence rehabilitation wards, and community integrated care wards in January 2015. Nutritional status was assessed using the mini nutritional assessment short-form (MNA-SF). The PPI use group was compared with the PPI non-use group regarding nutrition status. Logistic regression analysis was used to examine whether the period of PPI therapy was associated independently with malnutrition following adjustment for covariates including gender, age, and serum albumin level. Forty-one patients were male (22%) and 149 patients were female (78%), with a mean age of 85.4±8.4. Fifty-three patients (28%) took PPIs (with a median prescription period of 91 d, ranging from 51 to 227). With a MNA-SF score of 7 points or lower designated as malnutrition, there was no significant difference in nutritional status between the PPI and non-PPI groups (p=0.172). The median MNA-SF scores in the PPI and non-PPI groups were 9 vs 7 points, respectively. Logistic regression analysis showed that long-term PPI therapy (odds ratio, 0.994; 95% confidence interval 0.990-0.999) was significantly associated with improved nutritional status. The presence or absence of PPI therapy is not associated with malnutrition in elderly hospitalized patients. Longer-term PPI therapy may improve nutritional status.

  2. Glucocorticoid enhancement of memory requires arousal-induced noradrenergic activation in the basolateral amygdala

    NARCIS (Netherlands)

    Roozendaal, B; Okuda, S; Van der Zee, EA; McGaugh, JL; McGaugh, James L.

    2006-01-01

    Considerable evidence indicates that glucocorticoid hormones enhance the consolidation of long-term memories for emotionally arousing experiences but not that for less arousing or neutral information. However, previous studies have not determined the basis of such arousal-induced selectivity. Here

  3. Chemotherapy-induced sclerosing cholangitis: long-term response to endoscopic therapy.

    Science.gov (United States)

    Alazmi, Waleed M; McHenry, Lee; Watkins, James L; Fogel, Evan L; Schmidt, Suzette; Sherman, Stuart; Lehman, Glen L

    2006-04-01

    Hepatic arterial infusion of fluoropyrimidines has been widely used for the treatment of hepatic metastasis from colorectal cancer. One major complication of such treatment is biliary sclerosis resembling primary sclerosing cholangitis, which has an incidence ranging from 8% to 26%. We evaluated the efficacy and long-term outcome of endoscopic therapy in the management of chemotherapy-induced sclerosing cholangitis (CISC). With the use of an endoscopic retrograde cholangiopancreatography (ERCP) database, all patients with a diagnosis of CISC who had endoscopic therapy between March 1995 and March 2005 were identified. The indications, findings, therapies, and complications for all patients undergoing ERCP were recorded in this database. Additional information was obtained by review of medical records. Eleven patients (six men and five women) were identified. The mean age at presentation was 59.5 years (range, 36-76 years). Cholangiogram findings revealed stricture confined to the common hepatic duct in two patients, involving the hilum in seven patients, involving the right and/or left main hepatic ducts in nine patients, and extending to the intrahepatic radicals in two patients. All patients had successful endoscopic therapy to alleviate the presenting symptom. The grade and extent of biliary strictures did not change in five patients, improved in one patient, recurred in two patients, and progressed in two patients over the follow-up period of 28.2 months (range, 4-60 months). Although long-term follow-up of patients with CISC is limited by the dismal prognosis of the underlying malignancy, CISC has a recalcitrant pattern that rarely improves with endoscopic therapy. However, endoscopic therapy seems to be an effective method of palliation.

  4. Chronic pain treatment with opioid analgesics: benefits versus harms of long-term therapy.

    Science.gov (United States)

    Sehgal, Nalini; Colson, James; Smith, Howard S

    2013-11-01

    Chronic non-cancer pain (CNCP) is a disabling chronic condition with a high prevalence rate around the world. Opioids are routinely prescribed for treatment of chronic pain (CP). In the past two decades there has been a massive increase in the number of opioid prescriptions, prescribed daily opioid doses and overall opioid availability. Many more patients with CNCP receive high doses of long-acting opioids on a long-term basis. Yet CP and related disability rates remain high, and majority of the patients with CNCP are dissatisfied with their treatments. Intersecting with the upward trajectory in opioid use are the increasing trends in opioid related adverse effects, especially prescription drug abuse, addiction and overdose deaths. This complex situation raises questions on the relevance of opioid therapy in the treatment of CNCP. This article reviews current evidence on opioid effectiveness, the benefits and harms of long-term therapy in CNCP.

  5. Baseline haemoglobin A1c influences retinal function after long-term insulin pump therapy

    DEFF Research Database (Denmark)

    Klefter, Oliver N; Holfort, Stig K; Larsen, Michael

    2016-01-01

    PURPOSE: The purpose of the study was to characterize the long-term effect of insulin pump therapy (CSII) on electroretinography and dark adaptometry and to examine the influence of baseline glycaemic control on retinal function in patients with type 1 diabetes mellitus. METHODS: This prospective...... was associated predominantly with poorer metabolic control before initiation of CSII. Analyses of retinal function may supplement structural and morphological characteristics in the study of diabetic complications.......PURPOSE: The purpose of the study was to characterize the long-term effect of insulin pump therapy (CSII) on electroretinography and dark adaptometry and to examine the influence of baseline glycaemic control on retinal function in patients with type 1 diabetes mellitus. METHODS: This prospective...

  6. Effects of long-term multidisciplinary inpatient therapy on body composition of severely obese adolescents.

    Science.gov (United States)

    Prado, Wagner Luiz do; Siegfried, Alena; Dâmaso, Ana R; Carnier, June; Piano, Aline de; Siegfried, Wolfgang

    2009-01-01

    To describe the effects of long-term multidisciplinary inpatient therapy on body composition of severely obese adolescents. A total of 728 extremely obese adolescents, including 249 boys (aged 15.25+/-1.56 years) and 479 girls (aged 15.34+/-1.59 years) received multidisciplinary therapy during a period of 3 to 9 months. The therapy consisted of reduced energy intake, dietetic education, physical exercises and psychological therapy. Body composition was assessed by bioelectrical impedance analysis, and physical capacity was assessed by the multistage cycle ergometer test. Type and duration of each activity were recorded using a daily controlled activity diary. There was a significant decrease (p < 0.05) in body mass (27.84+/-12.49 kg for boys and 21.60+/-9.87 kg for girls), body mass index (9.19+/-3.88 kg/m(2) for boys and 7.72+/-3.98 kg/m(2) for girls) and fat mass. In addition, the percentage of fat free mass increased significantly (p < 0.05) in boys (from 58.8+/-6.41 to 69.98+/-7.43%) and in girls (from 51.86+/-4.96 to 60.04+/-5.65%). Long-term multidisciplinary approach allows significant reduction in severe obesity, preserving growth and percentage of fat free mass.

  7. Medical and psychological risks and consequences of long-term opioid therapy in women.

    Science.gov (United States)

    Darnall, Beth D; Stacey, Brett R; Chou, Roger

    2012-09-01

    Long-term opioid use has increased substantially over the past decade for U.S. women. Women are more likely than men to have a chronic pain condition, to be treated with opioids, and may receive higher doses. Prescribing trends persist despite limited evidence to support the long-term benefit of this pain treatment approach. To review the medical and psychological risks and consequences of long-term opioid therapy in women. Scientific literature containing relevant keywords and content were reviewed. Long-term opioid use exposes women to unique risks, including endocrinopathy, reduced fertility, neonatal risks, as well as greater risk for polypharmacy, cardiac risks, poisoning and unintentional overdose, among other risks. Risks for women appear to vary by age and psychosocial factors may be bidirectionally related to opioid use. Gaps in understanding and priorities for future research are highlighted. Wiley Periodicals, Inc.

  8. Glucocorticoid Regulation of Food-Choice Behavior in Humans: Evidence from Cushing's Syndrome.

    Science.gov (United States)

    Moeller, Scott J; Couto, Lizette; Cohen, Vanessa; Lalazar, Yelena; Makotkine, Iouri; Williams, Nia; Yehuda, Rachel; Goldstein, Rita Z; Geer, Eliza B

    2016-01-01

    glucocorticoid contributions to food-seeking behavior, enhancing mechanistic understanding of weight fluctuations associated with oral glucocorticoid therapy and/or chronic stress, and informing the neurobiology of neuropsychiatric conditions marked by abnormal cortisol dynamics (e.g., major depression, Alzheimer's disease).

  9. 11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

    Science.gov (United States)

    Chapman, Karen; Holmes, Megan

    2013-01-01

    Glucocorticoid action on target tissues is determined by the density of “nuclear” receptors and intracellular metabolism by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) which catalyze interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone. 11β-HSD type 1, a predominant reductase in most intact cells, catalyzes the regeneration of active glucocorticoids, thus amplifying cellular action. 11β-HSD1 is widely expressed in liver, adipose tissue, muscle, pancreatic islets, adult brain, inflammatory cells, and gonads. 11β-HSD1 is selectively elevated in adipose tissue in obesity where it contributes to metabolic complications. Similarly, 11β-HSD1 is elevated in the ageing brain where it exacerbates glucocorticoid-associated cognitive decline. Deficiency or selective inhibition of 11β-HSD1 improves multiple metabolic syndrome parameters in rodent models and human clinical trials and similarly improves cognitive function with ageing. The efficacy of inhibitors in human therapy remains unclear. 11β-HSD2 is a high-affinity dehydrogenase that inactivates glucocorticoids. In the distal nephron, 11β-HSD2 ensures that only aldosterone is an agonist at mineralocorticoid receptors (MR). 11β-HSD2 inhibition or genetic deficiency causes apparent mineralocorticoid excess and hypertension due to inappropriate glucocorticoid activation of renal MR. The placenta and fetus also highly express 11β-HSD2 which, by inactivating glucocorticoids, prevents premature maturation of fetal tissues and consequent developmental “programming.” The role of 11β-HSD2 as a marker of programming is being explored. The 11β-HSDs thus illuminate the emerging biology of intracrine control, afford important insights into human pathogenesis, and offer new tissue-restricted therapeutic avenues. PMID:23899562

  10. Glucocorticoid receptor haplotype and metabolic syndrome : the Lifelines cohort study

    NARCIS (Netherlands)

    Wester, Vincent L.; Koper, Jan W.; van den Akker, Erica L. T.; Franco, Oscar H.; Stolk, Ronald P.; van Rossum, Elisabeth F. C.

    2016-01-01

    Objective: An excess of glucocorticoids (Cushing's syndrome) is associated with metabolic syndrome (MetS) features. Several single-nucleotide polymorphisms (SNPs) in the glucocorticoid receptor (GR) gene influence sensitivity to glucocorticoids and have been associated with aspects of MetS. However,

  11. Which patients with moderate hypoxemia benefit from long-term oxygen therapy? Ways forward

    OpenAIRE

    Ekström M; Ringbaek T

    2018-01-01

    Magnus Ekström,1 Thomas Ringbaek2 1Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Lund, Sweden; 2Respiratory Department, Hvidovre Hospital, Copenhagen, Denmark Abstract: Long-term oxygen therapy (LTOT) improves prognosis in patients with COPD and chronic severe hypoxemia. The efficacy in moderate hypoxemia (tension of arterial oxygen; on air, 7.4−8.0 kPa) was questioned by a recent large trial. We reviewe...

  12. Conjunctival cytology in glaucomatous patients using long-term topical therapy

    Directory of Open Access Journals (Sweden)

    Sherwani Rana

    2008-01-01

    Full Text Available Background: Long-term use of antiglaucoma drugs induces adverse changes on the conjunctival surface. Aim: To evaluate the cytological changes in the conjunctival scrape smears of patients receiving long-term antiglaucoma medication and their histopathological correlation. Materials and Methods: Conjunctival scrape smears were taken from the eyes of patients on long-term antiglaucoma therapy for over three months (n = 75, patients taking antiglaucoma medication for less than three months (n = 100 and from glaucomatous patients in whom trabeculectomy was done as a primary procedure. Inflammatory cell counts, fibroblasts, and the degree of metaplasia were then evaluated both cytologically and histologically. The t-test was used to determine the predictive values of these parameters for the surgical outcome of trabeculectomies. Results: Long-term use of antiglaucoma therapy leads to a higher stage of metaplasia with an increase in the number of fibroblasts, subepithelial collagen deposition, and inflammatory infiltrate within the substantia propria of the conjunctiva. Conclusions: Long-term antiglaucoma medications induce a significant degree of metaplasia in the conjunctival surface that adversely affects the outcome of filtration surgery.

  13. Antenatal Treatment with Glucocorticoids and the Hypotalamic-Pituitary-Adrenal Axis

    Directory of Open Access Journals (Sweden)

    Manojlović-Stojanoski Milica

    2014-09-01

    Full Text Available Fetal development is a critical period in the life cycle which is why the placenta provides a structural and physiological barrier that protects the fetus from the outer fluctuations and inner disturbances. A variety of influences from the environment, however, might induce fetal overexposure to glucocorticoids that target the fetal hypothalamic-pituitary-adrenal (HPA axis and influence the fetal growth trajecto-r y. Development of the HPA axis starts in the early stages of pregnancy, but the timing of HPA axis maturation and the glucocorticoid receptor (GR expression in relation to birth is highly species-specific. The functional state of the fetal HPA axis plays a key role in the maturation of many organs necessary for intrauterine development and existence after birth. A functional HPA axis in near-term fetuses provides an adequate response to stress and also affects the timing of parturition. Due to their potent effect on the maturation of fetal tissues, synthetic glucocorticoids are used in human pregnancy at risk of preterm delivery. Dexamethasone and betamethasone, as the ones most commonly used, cross the placental enzymatic barrier (11b-hydroxysteroid dehydrogenase type 2 – 11b-HSD2 and have 25-fold higher affinity to the GR than endogenous glucocorticoids, stimulating many aspects of fetal maturation. Despite the numerous positive effects, exposure to synthetic glucocorticoids during fetal development may result in intrauterine growth retardation and fetal programming of the HPA axis function which is associated with cardiovascular, metabolic and psychiatric disorders manifested later in life. Long-term consequences indicate the need for the implementation of new studies that will provide a better understanding of the link between glucocorti-coid overexposure during fetal development and adverse outcomes in adulthood.

  14. No evidence for stopping long-term aspirin therapy before tooth extraction.

    Science.gov (United States)

    Halley, Daphne; Weld-Moore, Robert; Duane, Brett

    2015-12-01

    PubMed, ScienceDirect and EBSCOhost databases. Prospective randomised controlled trials (RCTs) or controlled trials. Two independent investigators extracted data. The primary measured outcomes were rates of haemorrhage and bleeding time. Disagreements were clarified with a third investigator. Relevant authors were contacted if any relevant data was missing. The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system was used to evaluate the overall quality of evidence. The authors used standardised mean difference or relative risk to evaluate each outcome. Ten studies were included, three randomised controlled trials and seven controlled trials. A total of 1752 patients were enrolled in the meta-analysis; the study group comprised 529 patients on long-term aspirin therapy, and the control group comprised 1223 patients. The risk of post-operative haemorrhage was significantly higher in patients on aspirin therapy (relative risk=2.46; 95% confidence interval: 1.45-4.81) but bleeding time was not significantly different between the two groups (standardised mean difference=0.63; 95% CI: - 0.04 to 1.31). Increased rates of haemorrhage are observed in patients on long-term aspirin therapy. The authors recommend not stopping long-term aspirin prior to dental extraction, and local measures for haemostasis should be enhanced when required.

  15. Long-term effects of exercise and physical therapy in people with Parkinson disease.

    Science.gov (United States)

    Mak, Margaret K; Wong-Yu, Irene S; Shen, Xia; Chung, Chloe L

    2017-11-01

    Parkinson disease (PD) is a progressive, neurodegenerative movement disorder with symptoms reflecting various impairments and functional limitations, such as postural instability, gait disturbance, immobility and falls. In addition to pharmacological and surgical management of PD, exercise and physical therapy interventions are also being actively researched. This Review provides an overview of the effects of PD on physical activity - including muscle weakness, reduced aerobic capacity, gait impairment, balance disorders and falls. Previously published reviews have discussed only the short-term benefits of exercises and physical therapy for people with PD. However, owing to the progressive nature of PD, the present Review focuses on the long-term effects of such interventions. We also discuss exercise-induced neuroplasticity, present data on the possible risks and adverse effects of exercise training, make recommendations for clinical practice, and describe new treatment approaches. Evidence suggests that a minimum of 4 weeks of gait training or 8 weeks of balance training can have positive effects that persist for 3-12 months after treatment completion. Sustained strength training, aerobic training, tai chi or dance therapy lasting at least 12 weeks can produce long-term beneficial effects. Further studies are needed to verify disease-modifying effects of these interventions.

  16. [Calcifediol and calcitonin in the therapy of rheumatoid arthritis. A short-term controlled study].

    Science.gov (United States)

    Dottori, L; D'Ottavio, D; Brundisini, B

    1982-11-10

    A short-term study (30 days) has been carried out on 45 patients suffering from rheumatoid arthritis with radiologically verified osteoporosis and definite pain symptomatology. The patients were divided at random into three groups (A, B, C) of 15 each. Group A was given basic therapy (calcium, dichlrophenac, nor-androstenolone) with addition of calcifediol. Group B received basic therapy plus calcitonine in paraphysiological doses. Group C was treated with basic therapy only (highly effective on its own). Observation and treatment were brief but able to provide useful indications regarding the implementation of longer courses of treatment (3-6 months). At the end of treatment, results were submitted to biometric control. With the aid of statistics it can thus be stated that alkaline phosphatase and hydroxyprolinuria fall in group B (basic treatment + calcitonine) and this suggests that the treatment causes some improvement in the exchangeable bone calcium pool. The values of these parameters also fall with the addition of calcifediol to basic therapy, but this fall is not very high. Pain symptomatology is also favourably affected, and to a statistically significant extent, by the three treatments: group A patients (basic + calcifediol) show greater improvement compared with straightforward basic therapy, but the best results are encountered in group B, treated with an association of basic and calcitonine. No side-effects were observed.

  17. Long-term glycaemic control with metformin-sulphonylurea-pioglitazone triple therapy in PROactive (PROactive 17).

    Science.gov (United States)

    Scheen, A J; Tan, M H; Betteridge, D J; Birkeland, K; Schmitz, O; Charbonnel, B

    2009-10-01

    We assessed the long-term glycaemic effects and the safety profile of triple therapy with the addition of pioglitazone vs. placebo in patients with Type 2 diabetes treated with combined metformin-sulphonylurea therapy in the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive). In a post-hoc analysis, we identified patients treated with metformin plus sulphonylurea combination therapy and not receiving insulin at baseline (n = 1314). In those patients, we compared the effects of pioglitazone (force-titrated to 45 mg/day, n = 654) vs. placebo (n = 660) on glycated haemoglobin (HbA(1c)) reduction, concomitant changes in medications and initiation of permanent insulin use (defined as daily insulin use for a period of > or = 90 days or ongoing use at death/final visit). Significantly greater reductions in HbA(1c) and greater proportions of patients with HbA(1c) at target were noted with pioglitazone vs, placebo, despite a decrease in the use of other oral glucose-lowering agents. There was an approximate twofold increase in progression to permanent insulin use in the placebo group vs. the pioglitazone group: 31.1 vs. 16.1%, respectively, when added to combination therapy. The overall safety of the metformin-sulphonylurea-pioglitazone triple therapy was good. Intensifying an existing dual oral therapy regimen to a triple oral regimen by adding pioglitazone to the classical metformin-sulphonylurea combination resulted in sustained improvements in glycaemic control and reduced progression to insulin therapy. The advantages and disadvantages of adding pioglitazone instead of adding basal insulin should be assessed further.

  18. Glucocorticoid Induced Leucine Zipper inhibits apoptosis of cardiomyocytes by doxorubicin

    Energy Technology Data Exchange (ETDEWEB)

    Aguilar, David; Strom, Joshua; Chen, Qin M., E-mail: qchen@email.arizona.edu

    2014-04-01

    Doxorubicin (Dox) is an indispensable chemotherapeutic agent for the treatment of various forms of neoplasia such as lung, breast, ovarian, and bladder cancers. Cardiotoxicity is a major concern for patients receiving Dox therapy. Previous work from our laboratory indicated that glucocorticoids (GCs) alleviate Dox-induced apoptosis in cardiomyocytes. Here we have found Glucocorticoid-Induced Leucine Zipper (GILZ) to be a mediator of GC-induced cytoprotection. GILZ was found to be induced in cardiomyocytes by GC treatment. Knocking down of GILZ using siRNA resulted in cancelation of GC-induced cytoprotection against apoptosis by Dox treatment. Overexpressing GILZ by transfection was able to protect cells from apoptosis induced by Dox as measured by caspase activation, Annexin V binding and morphologic changes. Western blot analyses indicate that GILZ overexpression prevented cytochrome c release from mitochondria and cleavage of caspase-3. When bcl-2 family proteins were examined, we found that GILZ overexpression causes induction of the pro-survival protein Bcl-xL. Since siRNA against Bcl-xL reverses GC induced cytoprotection, Bcl-xL induction represents an important event in GILZ-induced cytoprotection. Our data suggest that GILZ functions as a cytoprotective gene in cardiomyocytes. - Highlights: • Corticosteroids act as a cytoprotective agent in cardiomyocytes • Corticosteroids induce GILZ expression in cardiomyocytes • Elevated GILZ results in resistance against apoptosis induced by doxorubicin • GILZ induces Bcl-xL protein without inducing Bcl-xL mRNA.

  19. Clinical and radiological assessment of effects of long-term corticosteroid therapy on oral health

    Directory of Open Access Journals (Sweden)

    Swapna Sridevi Beeraka

    2013-01-01

    Full Text Available Background: Corticosteroids (Cs are used widely for their anti-inflammatory and immunosuppressive properties. They have the potential to cause dramatic improvement as well as produce equally dramatic adverse effects. The clinical misuse like over prescription of the drug should be avoided. Long-term administration may cause many adverse effects leading to impaired oral health. Oral health is usually not considered during management of patients on long-term corticosteroid therapy. The aim of this study was to assess the oral health status and radiological changes in the jaw bones of the patients under long-term corticosteroid therapy. Materials and Methods: Oral health of 100 patients under long-term corticosteroid therapy with a minimum of 3 months duration was compared with sex- and age-matched 100 healthy controls. The clinical examination included complete examination of the mouth and periodontal status. Radiographic evaluation of bone with the help of intra oral periapical radiograph and digital orthopantomograph and levels of serum calcium, alkaline phosphatase, and random blood sugar were assessed. ′Chi-square test′, ′Kolmogorov-Smirnov test′ and ′Mann-Whitney U test′ were used for statistical analysis. P < 0.05 was considered significant. Results: Patients on steroids exhibited significantly higher levels of candidiasis and clinical attachment loss of the periodontal ligament, probing pocket depth. Bone density was significantly lower in the study group than that in the control group. Random blood glucose was significantly higher and significant lower levels of calcium were observed in patients on steroids. Conclusion: Long-term use of Cs may affect oral health adversely leading to candidiasis as well as impair bone metabolism leading to a considerable decrease in the mandibular bone mineral density.

  20. Changes in Corneal Biomechanical Properties after Long-Term Topical Prostaglandin Therapy.

    Directory of Open Access Journals (Sweden)

    Na Wu

    Full Text Available To compare corneal biomechanical properties, measured by a newly developed tonometer (Corneal Visualization Scheimpflug Technology, Corvis ST, in untreated primary open angle glaucoma (POAG patients, POAG patients with long-term topical prostaglandin analog (PGA therapy and in normal controls. Further is to investigate the potential effects of PGA on corneal biomechanics.In this case-control study, 35 consecutive medication naïve eyes with POAG, 34 POAG eyes with at least 2 years treatment by PGA and 19 normal eyes were included. Intraocular pressure (IOP, central corneal thickness (CCT and corneal biomechanical parameters, including deformation amplitude (DA, applanation time (AT1 and AT2, applanation length (AL1 and AL2, applanation velocity (AV1 and AV2, and peak distance and radius were measured using Corvis ST. Axial length and corneal curvature were measured with partial coherence interferometry (IOLMaster, Zeiss, Germany. General linear model analysis was performed to investigate the corneal biomechanical property changes among the normal controls, newly diagnosed POAG patients and POAG patients with long-term PGA treatment, and among the subgroups of different types of PGA treatment, including bimatoprost, latanoprost and travoprost. Furthermore, pairwise comparisons using Bonferroni correction for least squares means were employed.AT1 (p<0.0001, AV1 (p<0.0001, AT2 (p = 0.0001, AV2 (p<0.0001 and DA (p = 0.0004 in newly diagnosed glaucoma patients were significantly different from those in normal subjects and in patients underwent at least 2 years topical PGA therapy after adjusting for age and gender. After adjusting for age, gender, IOP, CCT, axial length and corneal curvature, a significant difference was detected for DA between glaucoma patients without PGA treatment and patients with long-term PGA therapy (p = 0.0387. Furthermore, there were no statistical significant differences in all of the corneal biomechanical parameters among

  1. Racial differences in long-term adherence to oral antidiabetic drug therapy: a longitudinal cohort study

    Directory of Open Access Journals (Sweden)

    Meigs James B

    2009-02-01

    Full Text Available Abstract Background Adherence to oral antidiabetic medications is often suboptimal. Adherence differences may contribute to health disparities for black diabetes patients, including higher microvascular event rates, greater complication-related disability, and earlier mortality. Methods In this longitudinal retrospective cohort study, we used 10 years of patient-level claims and electronic medical record data (1/1/1992–12/31/2001 to assess differences in short- and long-term adherence to oral antidiabetic medication among 1906 newly diagnosed adults with diabetes (26% black, 74% white in a managed care setting in which all members have prescription drug coverage. Four main outcome measures included: (1 time from diabetes diagnosis until first prescription of oral antidiabetic medication; (2 primary adherence (time from first prescription to prescription fill; (3 time until discontinuation of oral antidiabetic medication from first prescription; and (4 long-term adherence (amount dispensed versus amount prescribed over a 24-month follow-up from first oral antidiabetic medication prescription. Results Black patients were as likely as whites to initiate oral therapy and fill their first prescription, but experienced higher rates of medication discontinuation (HR: 1.8, 95% CI: 1.2, 2.7 and were less adherent over time. These black-white differences increased over the first six months of therapy but stabilized thereafter for patients who initiated on sulfonylureas. Significant black-white differences in adherence levels were constant throughout follow-up for patients initiated on metformin therapy. Conclusion Racial differences in adherence to oral antidiabetic drug therapy persist even with equal access to medication. Early and continued emphasis on adherence from initiation of therapy may reduce persistent racial differences in medication use and clinical outcomes.

  2. Effect of maternal intravenous fluid therapy on external cephalic version at term: a prospective cohort study.

    Science.gov (United States)

    Burgos, Jorge; Quintana, Eider; Cobos, Patricia; Osuna, Carmen; Centeno, María del Mar; Melchor, Juan Carlos

    2014-12-01

    We sought to analyze whether maternal intravenous fluid therapy prior to external cephalic version (ECV) increases the amount of amniotic fluid and the success rate of the procedure. This was a prospective single-center cohort study of 200 women with a consecutive cohort of 100 pregnant women with a breech presentation at term who were administered intravenous fluid therapy with 2 L of hypotonic saline before the version attempt, compared to a control cohort of 100 pregnant women not given hydration treatment. The mean increase in the amniotic fluid index (AFI) after intravenous maternal hydration was 3.75 ± 2.71 cm. The amount of fluid before hydration was the only variable found to be associated with increases in amniotic fluid levels, both in absolute and relative terms (odds ratio, -0.21; 95% confidence interval, -0.37 to -0.05 and odds ratio, -4.62; 95% confidence interval, -6.17 to -3.06; P intravenous fluid therapy. The ECV success rate was 43% in the study group compared to 47% in the control group (P = .67). The success rate was significantly lower the larger the relative increase in the AFI, although no correlation was found in absolute terms (χ(2) for linear trend = 0.03 and 0.34, respectively). Maternal intravenous fluid therapy with 2 L of hypotonic saline prior to ECV is an effective and safe technique for increasing the AFI. However, its use in ECV does not increase the success rate of the procedure. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Long-term Effects on Cognitive Trajectories of Postmenopausal Hormone Therapy in Two Age Groups.

    Science.gov (United States)

    Espeland, Mark A; Rapp, Stephen R; Manson, JoAnn E; Goveas, Joseph S; Shumaker, Sally A; Hayden, Kathleen M; Weitlauf, Julie C; Gaussoin, Sarah A; Baker, Laura D; Padula, Claudia B; Hou, Lifang; Resnick, Susan M

    2017-06-01

    Postmenopausal hormone therapy may have long-term effects on cognitive function depending on women's age. Postintervention follow-up was conducted with annual cognitive assessments of two randomized controlled clinical trial cohorts, beginning an average of 6-7 years after study medications were terminated: 1,376 women who had enrolled in the Women's Health Initiative when aged 50-54 years and 2,880 who had enrolled when aged 65-79 years. Women had been randomly assigned to 0.625mg/d conjugated equine estrogens (CEE) for those with prior hysterectomy (mean 7.1 years), CEE with 2.5mg/d medroxyprogesterone acetate for those without prior hysterectomy (mean 5.4 years), or matching placebos. Hormone therapy, when prescribed to women aged 50-54 years, had no significant long-term posttreatment effects on cognitive function and on changes in cognitive function. When prescribed to older women, it was associated with long-term mean (SE) relative decrements (standard deviation units) in global cognitive function of 0.081 (0.029), working memory of 0.070 (0.025), and executive function of 0.054 (0.023), all p therapy regimen, prior use, or years from last menstrual period. Mean intervention effects were small; however, the largest were comparable in magnitude to those seen during the trial's active intervention phase. CEE-based hormone therapy delivered near the time of menopause provides neither cognitive benefit nor detriment. If administered in older women, it results in small decrements in several cognitive domains that remain for many years.

  4. Effects of recombinant human growth hormone for 1 year on body composition and muscle strength in children on long-term steroid therapy: randomized controlled, delayed-start study.

    Science.gov (United States)

    Simon, Dominique; Alberti, Corinne; Alison, Marianne; Le Henaff, Loïc; Chevenne, Didier; Boizeau, Priscilla; Canal, Aurélie; Ollivier, Gwenn; Decostre, Valérie; Jacqz-Aigrain, Evelyne; Carel, Jean-Claude; Czernichow, Paul; Hogrel, Jean-Yves

    2013-07-01

    Recombinant human GH (rhGH) improves growth and body composition in glucocorticoid-treated children. Its effects on muscle strength are poorly evaluated. Our objective was to evaluate rhGH effects on muscle strength in children receiving long-term glucocorticoid therapy; effects on height SD score (SDS) and body composition were assessed also. A randomized, controlled, delayed-start study of rhGH for 12 months was started after randomization (baseline) or 6 months later (M6). Patients included 30 children with various diagnoses. rhGH was administered at 0.065 mg/kg/d for 6 months and then in the dosage maintaining serum IGF-I levels below +2 SDS for chronological age. The primary criterion was the between-group difference in composite index of muscle strength (CIMS) change at M6. Secondary criteria included between-group differences in CIMS SDS(height), lean mass (LM), thigh muscle area (MA), and height SDS changes at M6; these parameters were also assessed in the overall population after 1 year of rhGH therapy. At M6, rhGH therapy did not significantly affect changes in CIMS or CIMS SDS(height) (+17.6% vs +7.5% and +0.14 ± 0.38 vs +0.11 ± 0.62, respectively); the rhGH-treated group had significantly larger changes in height SDS (+0.2 [0.3] vs -0.2 [0.3]; P = 0.003), LM (+7.3% [+3.7%; +21.6%] vs 0% [-4.7%; +3.2%]; P = 0.002), and MA (+8.8% [+5%; +15.6%] vs. -0.6% [-6.3%; +7.7%]; P = 0.01) compared with the untreated group. After 1 year of rhGH, height SDS, LM, and MA increased significantly, CIMS increased by 24.7% (+5.8%; +34.2%), and CIMS SDS(height) remained within the normal range. rhGH increased height, LM, and MA. However, muscle strength did not improve significantly.

  5. Long-term effects of psychotherapy on moderate depression: a comparative study of narrative therapy and cognitive-behavioral therapy.

    Science.gov (United States)

    Lopes, Rodrigo T; Gonçalves, Miguel M; Fassnacht, Daniel B; Machado, Paulo P P; Sousa, Inês

    2014-01-01

    In a previous clinical controlled trial (Lopes et al., 2014), narrative therapy (NT) showed promising results in ameliorating depressive symptoms with comparable outcomes to cognitive-behavioral therapy (CBT) when patients completed treatment. This paper aims to assess depressive symptoms and interpersonal problems in this clinical sample at follow-up. Using the Beck Depression Inventory-II and Outcome Questionnaire-45.2 Interpersonal Relations Scale, naturalistic prospective follow-up assessment was conducted at 21 and 31 months after the last treatment session. At follow-up, patients kept improving in terms of depressive symptoms and interpersonal problems. The odds that a patient maintained recovery from depressive symptoms at follow-up were five times higher than the odds that a patient maintained recovery from interpersonal problems. In the same way, the odds of a patient never recovering from interpersonal problems were five times higher than the odds of never recovering from depressive symptoms. The study did not control for the natural course of depression or treatment continuation. For depressed patients with greater interpersonal disabilities, longer treatment plans and alternative continuation treatments should be considered. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Long-term outcomes of gene therapy for the treatment of Leber's hereditary optic neuropathy

    Directory of Open Access Journals (Sweden)

    Shuo Yang

    2016-08-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a disease that leads to blindness. Gene therapy has been investigated with some success, and could lead to important advancements in treating LHON. This was a prospective, open-label trial involving 9 LHON patients at Tongji Hospital, Wuhan, China, from August 2011 to December 2015. The purpose of this study was to evaluate the long-term outcomes of gene therapy for LHON. Nine LHON patients voluntarily received an intravitreal injection of rAAV2-ND4. Systemic examinations and visual function tests were performed during the 36-month follow-up period to determine the safety and efficacy of this gene therapy. Based on successful experiments in an animal model of LHON, 1 subject also received an rAAV2-ND4 injection in the second eye 12 months after gene therapy was administered in the first eye. Recovery of visual acuity was defined as the primary outcome of this study. Changes in the visual field, visual evoked potential (VEP, optical coherence tomography findings, liver and kidney function, and antibodies against AAV2 were defined as secondary endpoints. Eight patients (Patients 2–9 received unilateral gene therapy and visual function improvement was observed in both treated eyes (Patients 4, 6, 7, and 8 and untreated eyes (Patients 2, 3, 4, 6 and 8. Visual regression fluctuations, defined as changes in visual acuity greater than or equal to 0.3 logMAR, were observed in Patients 2 and 9. Age at disease onset, disease duration, and the amount of remaining optic nerve fibers did not have a significant effect on the visual function improvement. The visual field and pattern reversal VEP also improved. The patient (Patient 1 who received gene therapy in both eyes had improved visual acuity in the injected eye after the first treatment. Unfortunately, visual acuity in this eye decreased 3 months after he received gene therapy in the second eye. Animal experiments suggested that ND4 expression remains

  7. Glucocorticoid Regulation of the Vitamin D Receptor

    Science.gov (United States)

    Hidalgo, Alejandro A.; Trump, Donald L.; Johnson, Candace S.

    2010-01-01

    Many studies indicate calcitriol has potent anti-tumor activity in different types of cancers. However, high levels of vitamin D can produce hypercalcemia in some patients. Glucocorticoids are used to ameliorate hypercalcemia and to enhance calcitriol anti-tumor activity. Calcitriol in combination with the glucocorticoid dexamethasone (Dex) increased vitamin D receptor (VDR) protein levels and ligand binding in squamous cell carcinoma VII (SCC). In this study we found that both calcitriol and Dex induce VDR- and glucocorticoid receptor (GR)-mediated transcription respectively, indicating both hormone receptors are active in SCC. Pre-treatment with Dex increases VDR-mediated transcription at the human CYP24A1 promoter. Whereas, pre-treatment with other steroid hormones, including dihydrotestosterone and R1881, has no effect on VDR-mediated transcription. Real-time PCR indicates treatment with Dex increases Vdr transcripts in a time-dependent manner, suggesting Dex may directly regulate expression of Vdr. Numerous putative glucocorticoid response elements (GREs) were found in the Vdr gene. Chromatin immunoprecipitation (ChIP) assay demonstrated GR binding at several putative GREs located within the mouse Vdr gene. However, none of the putative GREs studied increase GR-mediated transcription in luciferase reporter assays. In an attempt to identify the response element responsible for Vdr transcript regulation, future studies will continue to analyze newly identified GREs more distal from the Vdr gene promoter. PMID:20398752

  8. Glucocorticoid receptor knockdown and adult hippocampal neurogenesis

    NARCIS (Netherlands)

    Hooijdonk, Leonarda Wilhelmina Antonia van

    2010-01-01

    The research in this thesis is aimed at the elucidation of the role of the glucocorticoid receptor (GR) in hippocampal neuroplasticity and functioning. To achieve this, we have developed a novel method to specifically knockdown GR in a discrete cell population of the mouse brain. In this thesis I

  9. Bisphosphonates and glucocorticoid-induced osteoporosis: cons

    NARCIS (Netherlands)

    Lems, W.F.; Saag, K.

    2015-01-01

    During the use of glucocorticoids (GCs), both vertebral and nonvertebral fracture risk are increased, due to the direct and indirect negative effects of GCs on bone, muscles, and the activity of the underlying inflammatory diseases. Inhibition of bone formation and increased apoptosis of osteocytes

  10. On the retinal toxicity of intraocular glucocorticoids.

    Science.gov (United States)

    Torriglia, Alicia; Valamanesh, Fatemeh; Behar-Cohen, Francine

    2010-12-15

    Corticosteroids are hormones involved in many physiological responses such as stress, immune modulation, protein catabolism and water homeostasis. The subfamily of glucocorticoids is used systemically in the treatment of inflammatory diseases or allergic reactions. In the eye, glucocorticoides are used to treat macular edema, inflammation and neovascularization. The most commonly used glucocorticoid is triamcinolone acetonide (TA). The pharmaceutical formulation of TA is not adapted for intravitreal administration but has been selected by ophthalmologists because its very low intraocular solubility provides sustained effect. Visual benefits of intraocular TA do not clearly correlate with morpho-anatomical improvements, suggesting potential toxicity. We therefore studied, non-common, but deleterious effects of glucocorticoids on the retina. We found that the intravitreal administration of TA is beneficial in the treatment of neovascularization because it triggers cell death of endothelial cells of neovessels by a caspase-independent mechanism. However, this treatment is toxic for the retina because it induces a non-apoptotic, caspase-independent cell death related to paraptosis, mostly in the retinal pigmented epithelium cells and the Müller cells. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Diabetes insipidus is an unfavorable prognostic factor for response to glucocorticoids in patients with autoimmune hypophysitis.

    Science.gov (United States)

    Lupi, Isabella; Cosottini, Mirco; Caturegli, Patrizio; Manetti, Luca; Urbani, Claudio; Cappellani, Daniele; Scattina, Ilaria; Martino, Enio; Marcocci, Claudio; Bogazzi, Fausto

    2017-08-01

    Autoimmune hypophysitis (AH) has a variable clinical presentation and natural history; likewise, its response to glucocorticoid therapy is often unpredictable. To identify clinical and radiological findings associated with response to glucocorticoids. 12 consecutive patients with AH, evaluated from 2008 to 2016. AH was the exclusion diagnosis after ruling out other pituitary masses and secondary causes of hypophysitis. Mean follow-up time was 30 ± 27 months (range 12-96 months). MRI identified two main patterns of presentation: global enlargement of the pituitary gland or panhypophysitis ( n  = 4, PH), and pituitary stalk abnormality only, or infundibulo-neuro-hypophysitis ( n  = 8, INH). Multiple tropin defects were more common in PH (100%) than those in INH (28% P  = 0.014), whereas diabetes insipidus was more common in INH (100%) than that in PH (50%; P  = 0.028). All 4 PH and 4 out of 8 INH were treated with glucocorticoids. Pituitary volume significantly reduced in all PH patients ( P  = 0.012), defective anterior pituitary function recovered only in the two patients without diabetes insipidus (50%) and panhypopituitarism persisted, along with diabetes insipidus, in the remaining 2 (50%). In all INH patients, either treated or untreated, pituitary stalk diameter reduced ( P  = 0.008) but diabetes insipidus persisted in all. Glucocorticoid therapy may improve anterior pituitary function in a subset of patients but has no effect on restoring posterior pituitary function. Diabetes insipidus appears as a negative prognostic factor for response to glucocorticoids. © 2017 European Society of Endocrinology.

  12. Therapy duration and long-term outcomes in extra-pulmonary tuberculosis.

    Science.gov (United States)

    Pusch, Tobias; Pasipanodya, Jotam G; Hall, Ronald G; Gumbo, Tawanda

    2014-03-01

    Tuberculosis is classified as either pulmonary or extra-pulmonary (EPTB). While much focus has been paid to pulmonary tuberculosis, EPTB has received scant attention. Moreover, EPTB is viewed as one wastebasket diagnosis, as "the other" which is not pulmonary. This is a retrospective cohort study of all patients treated for EPTB in the state of Texas between January 2000 and December 2005, who had no pulmonary disease. Clinical and epidemiological factors were abstracted from electronic records of the Report of Verified Case of Tuberculosis. The long-term outcome, which is death by December 2011, was established using the Social Security Administration Death Master File database. Survival in EPTB patients was compared to those with latent tuberculosis, as well as between different types of EPTB, using Cox proportional hazard models. A hybrid of the machine learning method of classification and regression tree analyses and standard regression models was used to identify high-order interactions and clinical factors predictive of long-term all-cause mortality. Four hundred and thirty eight patients met study criteria; the median study follow-up period for the cohort was 7.8 (inter-quartile range 6.0-10.1) years. The overall all-cause mortality rate was 0.025 (95% confidence interval [CI]: 0.021-0.030) per 100 person-year of follow-up. The significant predictors of poor long-term outcome were age (hazard ratio [HR] for each year of age-at-diagnosis was 1.05 [CI: 1.04-1.06], treatment duration, type of EPTB and HIV-infection (HR = 2.16; CI: 1.22, 3.83). Mortality in genitourinary tuberculosis was no different from latent tuberculosis, while meningitis had the poorest long-term outcome of 46.2%. Compared to meningitis the HR for death was 0.50 (CI: 0.27-0.91) for lymphatic disease, 0.42 (CI: 0.21-0.81) for bone/joint disease, and 0.59 (CI: 0.27-1.31) for peritonitis. The relationship between mortality and therapy duration for each type of EPTB was a unique "V" shaped

  13. Behavioral neuroadaptation to alcohol : from glucocorticoids to histone acetylation

    Directory of Open Access Journals (Sweden)

    Daniel Beracochea

    2016-10-01

    Full Text Available A prime mechanism that contributes to the development and maintenance of alcoholism is the dysregulation of the hypothalamic-pituitary-adrenal (HPA axis activity and the release of glucocorticoids (cortisol in humans and primates, corticosterone in rodents from the adrenal glands. In the brain, sustained, local elevation of glucocorticoid concentration even long after cessation of chronic alcohol consumption compromises functional integrity of a circuit including the prefrontal cortex, the hippocampus and the amygdala. These structures are implicated in learning and memory processes as well as in orchestrating neuroadaptive responses to stress and anxiety responses. Thus, potentiation of anxiety-related neuroadaptation by alcohol is characterized by an abnormally amygdala hyperactivity coupled with a hypofunction of the prefrontal cortex and the hippocampus. This review describes research on molecular and epigenetic mechanisms by which alcohol causes distinct region-specific adaptive changes in gene expression patterns and ultimately, leads to a variety of cognitive and behavioral impairments on prefrontal- and hippocampal-based tasks. Alcohol-induced neuroadaptations involve the dysregulation of numerous signaling cascades, leading to long-term changes in transcriptional profiles of genes, through the actions of transcription factors such as CREB (cAMP response element binding protein and chromatin remodeling due to post-translational modifications of histone proteins. We describe the role of prefrontal-hippocampus-amygdala circuit in mediating the effects of acute and chronic alcohol on learning and memory, and region-specific molecular and epigenetic mechanisms involved in this process. This review first discusses the importance of brain region-specific dysregulation of glucocorticoid concentration in the development of alcohol dependence and describes on how persistently increased glucocorticoid levels in prefrontal cortex may be involved in

  14. Short-term intensive family therapy for adolescent eating disorders: 30-month outcome.

    Science.gov (United States)

    Marzola, Enrica; Knatz, Stephanie; Murray, Stuart B; Rockwell, Roxanne; Boutelle, Kerri; Eisler, Ivan; Kaye, Walter H

    2015-05-01

    Family therapy approaches have generated impressive empirical evidence in the treatment of adolescent eating disorders (EDs). However, the paucity of specialist treatment providers limits treatment uptake; therefore, our group developed the intensive family therapy (IFT)-a 5-day treatment based on the principles of family-based therapy for EDs. We retrospectively examined the long-term efficacy of IFT in both single-family (S-IFT) and multi-family (M-IFT) settings evaluating 74 eating disordered adolescents who underwent IFT at the University of California, San Diego, between 2006 and 2013. Full remission was defined as normal weight (≥ 95% of expected for sex, age, and height), Eating Disorder Examination Questionnaire (EDE-Q) global score within 1 SD of norms, and absence of binge-purging behaviours. Partial remission was defined as weight ≥ 85% of expected or ≥ 95% but with elevated EDE-Q global score and presence of binge-purging symptoms (<1/week). Over a mean follow-up period of 30 months, 87.8% of participants achieved either full (60.8%) or partial remission (27%), while 12.2% reported a poor outcome, with both S-IFT and M-IFT showing comparable outcomes. Short-term, intensive treatments may be cost-effective and clinically useful where access to regular specialist treatment is limited. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

  15. Fluoride excess and periostitis in transplant patients receiving long-term voriconazole therapy.

    Science.gov (United States)

    Wermers, Robert A; Cooper, Kay; Razonable, Raymund R; Deziel, Paul J; Whitford, Gary M; Kremers, Walter K; Moyer, Thomas P

    2011-03-01

    We describe a heart transplant patient with painful periostitis and exostoses who was receiving long-term therapy with voriconazole, which is a fluoride-containing medication. Elevated plasma and bone fluoride levels were identified. Discontinuation of voriconazole therapy led to improvement in pain and reduced fluoride and alkaline phosphatase levels. To determine whether voriconazole is a cause of fluoride excess, we measured plasma fluoride levels in 10 adult post-transplant patients who had received voriconazole for at least 6 months and 10 post-transplant patients who did not receive voriconazole. To assess the effect of renal insufficiency on fluoride levels in subjects receiving voriconazole, half were recruited on the basis of a serum creatinine level of ≥1.4 mg/dL on their most recent measurement, whereas the other 5 subjects receiving voriconazole had serum creatinine levels periostitis, including exostoses in 2 patients. Discontinuation of voriconazole therapy in patients with periostitis resulted in improvement of pain and a reduction in alkaline phosphatase and fluoride levels. Voriconazole is associated with painful periostitis, exostoses, and fluoride excess in post-transplant patients with long-term voriconazole use.

  16. Manual therapy for cervicogenic dizziness: Long-term outcomes of a randomised trial.

    Science.gov (United States)

    Reid, Susan A; Callister, Robin; Snodgrass, Suzanne J; Katekar, Michael G; Rivett, Darren A

    2015-02-01

    Manual therapy is effective for reducing cervicogenic dizziness, a disabling and persistent problem, in the short term. This study investigated the effects of sustained natural apophyseal glides (SNAGs) and passive joint mobilisations (PJMs) on cervicogenic dizziness compared to a placebo at 12 months post-treatment. Eighty-six participants (mean age 62 years, standard deviation (SD) 12.7) with chronic cervicogenic dizziness were randomised to receive SNAGs with self-SNAGs (n = 29), PJMs with range-of-motion (ROM) exercises (n = 29), or a placebo (n = 28) for 2-6 sessions over 6 weeks. Outcome measures were dizziness intensity, dizziness frequency (rated between 0 [none] and 5 [>once/day]), the Dizziness Handicap Inventory (DHI), pain intensity, head repositioning accuracy (HRA), cervical spine ROM, balance, and global perceived effect (GPE). At 12 months both manual therapy groups had less dizziness frequency (mean difference SNAGs vs placebo -0.7, 95% confidence interval (CI) -1.3, -0.2, p = 0.01; PJMs vs placebo -0.7, -1.2, -0.1, p = 0.02), lower DHI scores (mean difference SNAGs vs placebo -8.9, 95% CI -16.3, -1.6, p = 0.02; PJMs vs placebo -13.6, -20.8, -6.4, p effects. These results provide evidence that both forms of manual therapy have long-term beneficial effects in the treatment of chronic cervicogenic dizziness. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Manual therapy and exercise for adhesive capsulitis (frozen shoulder).

    Science.gov (United States)

    Page, Matthew J; Green, Sally; Kramer, Sharon; Johnston, Renea V; McBain, Brodwen; Chau, Marisa; Buchbinder, Rachelle

    2014-08-26

    ) suggested no clinically important differences between a combination of manual therapy, exercise, and electrotherapy for four weeks and placebo injection compared with glucocorticoid injection alone or placebo injection alone in terms of overall pain, function, active range of motion and quality of life at six weeks, six months and 12 months (though the 95% CI suggested function may be better with glucocorticoid injection at six weeks). The same two trials found that adding a combination of manual therapy, exercise and electrotherapy for four weeks to glucocorticoid injection did not confer clinically important benefits over glucocorticoid injection alone at each time point. Based on one high quality trial (148 participants), following arthrographic joint distension with glucocorticoid and saline, a combination of manual therapy and supervised exercise for six weeks conferred similar effects to those of sham ultrasound in terms of overall pain, function and quality of life at six weeks and at six months, but provided greater patient-reported treatment success and active shoulder abduction at six weeks. One trial (119 participants) found that a combination of manual therapy, exercise, electrotherapy and oral non-steroidal anti-inflammatory drug (NSAID) for three weeks did not confer clinically important benefits over oral NSAID alone in terms of function and patient-reported treatment success at three weeks.On the basis of 25 clinically heterogeneous trials, we are uncertain of the effect of manual therapy or exercise when not delivered together, or one type of manual therapy or exercise versus another, as most reported differences between groups were not clinically or statistically significant, and the evidence is mostly of low quality. The best available data show that a combination of manual therapy and exercise may not be as effective as glucocorticoid injection in the short-term. It is unclear whether a combination of manual therapy, exercise and electrotherapy is an

  18. The hippocampus mediates glucocorticoid-induced impairment of spatial memory retrieval: Dependence on the basolateral amygdala

    Science.gov (United States)

    Roozendaal, Benno; Griffith, Qyana K.; Buranday, Jason; de Quervain, Dominique J.-F.; McGaugh, James L.

    2003-01-01

    Previous studies have indicated that stress-activated glucocorticoid hormones induce temporary memory retrieval impairment. The present study examined whether adrenal steroid receptors in the hippocampus mediate such glucocorticoid effects on spatial memory retrieval. The specific glucocorticoid receptor (GR) agonist 11β, 17β-dihydroxy-6,21-dimethyl-17α-pregna-4,6-trien-20yn-3-one (RU 28362; 5 or 15 ng) infused into the hippocampus of male Sprague–Dawley rats 60 min before water-maze retention testing, 24 h after training, dose-dependently impaired probe-trial retention performance, as assessed both by time spent in the training quadrant and initial latency to cross the platform location. The GR agonist did not affect circulating corticosterone levels immediately after the probe trial, indicating that RU 28362 infusions did not influence retention by altering glucocorticoid feedback mechanisms. As infusions of the GR agonist into the hippocampus 60 min before training did not influence water-maze acquisition or immediate recall, the findings indicated that the GR agonist-induced retention impairment was induced selectively by an influence on information retrieval. In contrast, pretest infusions of the GR agonist administered into the basolateral complex of the amygdala (BLA; 2 or 6 ng) did not alter retention performance in the water maze. However, N-methyl-d-aspartate-induced lesions of the BLA, made 1 week before training, blocked the memory retrieval impairment induced by intrahippocampal infusions of RU 28362 given 60 min before the retention test. These findings indicate that the effects of glucocorticoids on retrieval of long-term spatial memory depend on the hippocampus and, additionally, that neuronal input from the BLA is critical in enabling hippocampal glucocorticoid effects on memory retrieval. PMID:12538851

  19. VBP15, a glucocorticoid analogue, is effective at reducing allergic lung inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Jesse M Damsker

    Full Text Available Asthma is a chronic inflammatory condition of the lower respiratory tract associated with airway hyperreactivity and mucus obstruction in which a majority of cases are due to an allergic response to environmental allergens. Glucocorticoids such as prednisone have been standard treatment for many inflammatory diseases for the past 60 years. However, despite their effectiveness, long-term treatment is often limited by adverse side effects believed to be caused by glucocorticoid receptor-mediated gene transcription. This has led to the pursuit of compounds that retain the anti-inflammatory properties yet lack the adverse side effects associated with traditional glucocorticoids. We have developed a novel series of steroidal analogues (VBP compounds that have been previously shown to maintain anti-inflammatory properties such as NFκB-inhibition without inducing glucocorticoid receptor-mediated gene transcription. This study was undertaken to determine the effectiveness of the lead compound, VBP15, in a mouse model of allergic lung inflammation. We show that VBP15 is as effective as the traditional glucocorticoid, prednisolone, at reducing three major hallmarks of lung inflammation--NFκB activity, leukocyte degranulation, and pro-inflammatory cytokine release from human bronchial epithelial cells obtained from patients with asthma. Moreover, we found that VBP15 is capable of reducing inflammation of the lung in vivo to an extent similar to that of prednisone. We found that prednisolone--but not VBP15 shortens the tibia in mice upon a 5 week treatment regimen suggesting effective dissociation of side effects from efficacy. These findings suggest that VBP15 may represent a potent and safer alternative to traditional glucocorticoids in the treatment of asthma and other inflammatory diseases.

  20. Carbamazepine treatment in patients discontinuing long-term benzodiazepine therapy. Effects on withdrawal severity and outcome.

    Science.gov (United States)

    Schweizer, E; Rickels, K; Case, W G; Greenblatt, D J

    1991-05-01

    Forty patients with a history of difficulty discontinuing long-term, daily benzodiazepine therapy were randomly assigned, under double-blind conditions, to treatment with carbamazepine (200 to 800 mg/d) or placebo. A gradual taper (25% per week reduction) off benzodiazepine therapy was then attempted. Five weeks after taper, significantly more patients who had received carbamazepine than placebo remained benzodiazepine free, this despite the fact that no statistically significant differences in withdrawal severity could be demonstrated. Patients receiving carbamazepine reported a larger reduction in withdrawal severity than patients receiving placebo, but only at a trend level, and only on the daily patient-rated withdrawal checklist. Eleven patients (28%) required antidepressant therapy for depression or panic when assessed at 12-weeks follow-up. The results of this pilot investigation suggest that carbamazepine might have promise as an adjunctive drug therapy for the benzodiazepine withdrawal syndrome, particularly in patients receiving benzodiazepines in daily dosages of 20 mg/d or greater of diazepam equivalents.

  1. [Using focus groups to explore the group music therapy experience of long term care elderly].

    Science.gov (United States)

    Lin, Hui-Chuan; Chen, Shu-Ling

    2007-04-01

    The purpose of this study was to explore the elderly's experience and perceptions of group music therapy. The residents of a long term care institution received group music therapy for one year. Afterwards, three interviews were conducted in focus groups of between six and eight of the elderly. Their ages ranged from 64 to 90. Ninety-five percent of these elderly subjects participated in the therapy for over ten months. The tape-recorded interviews were transcribed and analyzed using content analysis. Six themes emerged regarding the elderly subjects' experiences and perceptions of group music therapy, as follows: (1) becoming more willing to participate; (2) feeling pain relief and more controlled moods; (3) getting physically better; (4) being more motivated to live; (5) learning positive personal interaction and obedience to the rules of the group; and (6) learning skills to improve personal health. This information might be used as a helpful and valuable reference in nursing education and by administrative organizations involved in the planning of therapeutic programs for the elderly.

  2. Radiation therapy for wet type age-related macular degeneration. Long term follow-up results

    Energy Technology Data Exchange (ETDEWEB)

    Sasai, Keisuke; Hiraoka, Masahiro; Mandai, Michiyo; Takahashi, Masayo; Honda, Yoshihito [Kyoto Univ. (Japan). Faculty of Medicine

    1998-12-01

    Between April, 1994 and July, 1995, 33 patients with occult type choroidal neovascularization (CNV) with or without the classical type CNV of the wet type age-related macular degeneration ARMD were treated with radiation therapy (10 Gy/5 fx/1 week or 20 Gy/10 fx/2 weeks). This phase I/II study showed that radiation therapy seems to be useful for CNV during the first 12 months. Some eyes which initially showed good response to irradiation began to lose their visual acuity. However, the dose of 20 Gy in 10 fractions seemed useful to maintain the visual acuity better than 0.1 in this long term follow-up study (24 months). (author)

  3. Long-term Results of Breast-conserving Surgery and Radiation Therapy in Early Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Hee; Byun, Sang Jun [Dongsan Medical Center, Daegu (Korea, Republic of)

    2009-09-15

    To evaluate the long-term results after breast-conserving surgery and radiation therapy in early breast cancer in terms of failure, survival, and cosmesis. One hundred fifty-four patients with stage I and II breast cancer were treated with conservative surgery plus radiotherapy between January 1992 and December 2002 at the Keimyung University Dongsan Medical Center. According to TNM stage, 93 patients were stage I, 50 were IIa, and 11 were IIb. The affected breasts were irradiated with 6 MV photons to 50.4 Gy in 28 fractions over 5.5 weeks with a boost irradiation dose of 10{approx}16 Gy to the excision site. Chemotherapy was administered in 75 patients and hormonal therapy in 92 patients with tamoxifen. Follow-up periods were 13{approx}179 months, with a median of 92.5 months. The 5- and 10-year overall survival rates were 97.3% and 94.5%, respectively. The 5- and 10-year disease-free survival (5YDFS and 10YDFS, respectively) rates were 92.5% and 88.9%, respectively; the ultimate 5YDFS and 10YDFS rates after salvage treatment were 93.9% and 90.2%, respectively. Based on multivariate analysis, only the interval between surgery and radiation therapy ({<=}6 weeks vs. >6 weeks, p=0.017) was a statistically significant prognostic factor for DFS. The major type of treatment failure was distant failure (78.5%) and the most common distant metastatic site was the lungs. The cosmetic results were good-to-excellent in 96 patients (80.7%). Conservative surgery and radiation for early stage invasive breast cancer yielded excellent survival and cosmetic results. Radiation therapy should be started as soon as possible after breast-conserving surgery in patients with early breast cancer, ideally within 6 weeks.

  4. The long-term survival of stage IV gastric cancer patients with conversion therapy.

    Science.gov (United States)

    Yamaguchi, Kazuya; Yoshida, Kazuhiro; Tanahashi, Toshiyuki; Takahashi, Takao; Matsuhashi, Nobuhisa; Tanaka, Yoshihiro; Tanabe, Kazuaki; Ohdan, Hideki

    2017-06-14

    A retrospective study was performed to clarify the role of conversion therapy (surgery with a prospect of R0 resection performed in initially unresectable metastatic cancer that responded to the chemotherapy) in stage IV gastric cancer (GC). We treated 259 stage IV GC patients with systemic chemotherapy at Gifu and Hiroshima University Hospitals between 2001-2013. Of these, 84 patients who were subsequently treated by surgery were classified into four categories according to our previously published classification of stage IV GC, and short- and long-term outcomes were analyzed. Surgery was performed in 84 patients, of which 7 were performed following the neoadjuvant chemotherapy, whereas the other 77 that excluded neoadjuvant chemotherapy cases were considered the conversion therapy. The postoperative mortality and morbidity were comparable with those reported clinical trials. The MSTs of the patients with/without surgery for each category were 28.3/5.8 months for category 1, 30.5/11.0 months for category 2, 31.0/18.5 months for category 3 and 24.7/10.0 months for category 4. The MST of the R0 resected patients (41.3 months) was far better than that of the R1-2 resected patients (21.2 months). The MSTs of the patients with R0/R1-2 resection were 56.2/16.3 months for category 2, 33.3/29.6 months for category 3 and 40.7/17.8 months for category 4. There were long-term survivors who underwent conversion therapy for stage IV GC. Adequate selection of stage IV GC patients for conversion therapy may be an important role for the surgical oncologist in the new era.

  5. Delayed villous maturation in term placentas exposed to opioid maintenance therapy: a retrospective cohort study.

    Science.gov (United States)

    Serra, Allison E; Lemon, Lara S; Mokhtari, Neggin B; Parks, W Tony; Catov, Janet M; Venkataramanan, Raman; Caritis, Steve N

    2017-04-01

    Opioid use disorder among pregnant women is associated with adverse perinatal outcomes and is increasing in the United States. The standard of care for pregnant women with opioid use disorder is opioid maintenance therapy including either methadone or buprenorphine, which can be initiated at any time during pregnancy. These medications are known to cross the placenta but their placental and fetal effects have not been well characterized. Delayed villous maturation, a placental finding associated with stillbirth, was observed in placentas exposed to opioid maintenance therapy. Given the association of delayed villous maturation with stillbirth, and the possible relationship between opioid maintenance therapy and delayed villous maturation, this study was undertaken to explore the association between opioid maintenance therapy and this placental finding. Delayed villous maturation was not previously reported in placentas exposed to opioids or opioid maintenance therapy. This study sought to compare risk of delayed villous maturation in term placentas exposed and unexposed to opioid maintenance therapy with buprenorphine or methadone. This was a retrospective cohort study conducted between 2010 through 2012 at Magee-Womens Hospital comparing delayed villous maturation in placentas of women with opioid use disorder exposed to either buprenorphine (n = 86) or methadone (n = 268) versus women without opioid use disorder (n = 978). Potential covariates were assessed in univariate analyses with none significantly associated with delayed villous maturation. The final model used conditional logistic regression adjusting for smoking status alone. Among women without opioid use disorder (and therefore not exposed to opioid maintenance therapy), delayed villous maturation was identified in 5.7% of placentas while the prevalence among women treated with buprenorphine or methadone was 8.1% and 10.8%. Overall, the crude odds of being diagnosed with delayed villous maturation

  6. VAC therapy with long term continuous saline infusion for secondary septic peritonitis: A new strategy for the reduction of perioperative risks?

    Directory of Open Access Journals (Sweden)

    Fulvio Nisi

    2017-01-01

    Conclusion: Conservative therapy with antibiotic therapy and use of the Vacuum-Assisted Closure® (VAC Therapy with a long term continuous saline infusion led to the resolution of the septic shock and to the wound healing.

  7. A novel conceptual framework for understanding the mechanism of adherence to long term therapies.

    Science.gov (United States)

    Reach, Gérard

    2008-02-02

    The World Health Organization claimed recently that improving patient adherence to long term therapies would be more beneficial than any biomedical progress. First, however, we must understand its mechanisms. In this paper I propose a novel approach using concepts elaborated in a field rarely explored in medicine, the philosophy of mind. While conventional psychological models (eg, the Health Belief Model) provide explanations and predictions which have only a statistical value, the philosophical assumption that mental states (eg, beliefs) are causally efficient (mental causation) can provide the basis for a causal theory of health behaviors. This paper shows that nonadherence to long term therapies can be described as the medical expression of a philosophical concept, that is, weakness of will. I use philosophical explanations of this concept to suggest a mechanistic explanation of nonadherence. I propose that it results from the failure of two principles of rationality. First, a principle of continence, described by the philosopher Donald Davidson in his explanation of weakness of will. This principle exhorts us to act after having considered all available arguments and according to which option we consider best. However, patients conforming to this principle of continence should rationally be nonadherent. Indeed, when patients face a choice between adherence and nonadherence, they must decide, in general, between a large, but delayed reward (eg, health) and a small, but immediate reward (eg, smoking a cigarette). According to concepts elaborated by George Ainslie and Jon Elster, the force of our desires is strongly influenced by the proximity of reward. This inter-temporal choice theory on one hand, and the mere principle of continence on the other, should therefore lead to nonadherence. Nevertheless, adherence to long term therapies is possible, as a result of the intervention of an additional principle, the principle of foresight, which tells us to give

  8. Long-term efficacy of spa therapy in patients with rheumatoid arthritis.

    Science.gov (United States)

    Karagülle, Mine; Kardeş, Sinan; Karagülle, Müfit Zeki

    2018-01-11

    Our previous crossover randomized trial suggested that spa therapy added to usual pharmacotherapy provides benefits that lasted 6 months over pharmacotherapy alone in rheumatoid arthritis patients. We now extend, and report the long-term results of that study. In the crossover trial, patients were randomized to spa therapy first group or control first group (first assignment, period 1, 6 months); after this period and washout phase (9 months), they crossed over to the other arm (second assignment, period 2, 6 months). In this long-term study, we now analyze the 15-month results of the first assignment, and 12-month results of the second assignment in the opposite side with a 6-month extension of the follow-up period. The clinical outcome measures were pain, patient and physician global assessment, Health Assessment Questionnaire, and Disease Activity Score-28. The 15-month results of first assignment revealed no statistically significant differences between the groups in any of the efficacy outcomes (p > 0.05 for all). The 12-month results for the second assignment after crossover revealed a statistically significant decrease between the groups regarding the patient global assessment scores (p = 0.016), physician global assessment scores (p = 0.003) and swollen joints counts (p = 0.030); however, no statistically significant difference was found between the groups in any of the other efficacy outcomes (p > 0.05 for all). The short- and medium-term beneficial effects of the 2-week spa therapy added to the usual pharmacotherapy observed through the initial 6-month evaluation period may be maintained mildly to moderately to the 12-month mark in rheumatoid arthritis patients receiving conventional disease-modifying antirheumatic drugs. Further studies with a larger sample size are needed for the confirmation of the study results.

  9. Long-term follow-up of patients with neuromyelitis optica after repeated therapy with rituximab.

    Science.gov (United States)

    Pellkofer, H L; Krumbholz, M; Berthele, A; Hemmer, B; Gerdes, L A; Havla, J; Bittner, R; Canis, M; Meinl, E; Hohlfeld, R; Kuempfel, T

    2011-04-12

    Neuromyelitis optica (NMO) is a severe autoimmune disease targeting optic nerves and spinal cord. The monoclonal anti-CD20 B-cell antibody rituximab is an emerging therapeutic option in NMO. However, neither long-term efficacy or safety of rituximab, nor the correlation between B-cell counts, B-cell fostering cytokines, aquaporin-4 antibodies (AQP4-ab), and disease activity in NMO, have been investigated prospectively. We performed a prospective long-term cohort study of 10 patients with NMO who were treated up to 5 times with rituximab as a second-line therapy. Clinical examinations, B-cell counts, and serum concentrations of BAFF (B-cell activating factor of the TNF family; also called TNFSF13b), APRIL (a proliferation-inducing ligand; also called TNFSF13), AQP4-ab, and immunoglobulin levels were measured every 3 months. Repeated treatment with rituximab led to sustained clinical stabilization in most patients with NMO. Disease activity correlated with B-cell depletion, but not clearly with AQP4-ab or levels of APRIL. BAFF levels increased after application of rituximab and indicated persisting efficacy of the drug but did not correlate with disease activity. Overall, rituximab was well-tolerated even after up to 5 consecutive treatment courses; however, we observed several severe adverse reactions. Our data indicate that long-term therapy with rituximab is effective in NMO as a second-line therapy and has an acceptable safety profile. Retreatment with rituximab should be applied before reappearance of circulating B cells. This study provides Class IV evidence that repeated doses of rituximab result in stabilization in most patients.

  10. Long-term survival in stage IV melanoma after repetitive surgical therapy.

    Science.gov (United States)

    Tomov, Tsvetomir; Siegel, Robert; Bembenek, Andreas

    2008-05-01

    Surgical therapy in patients with stage IV melanoma is controversial and always an individual decision. We report the case of a young melanoma patient, who underwent resection of 5 distant metastases from 4 different organ systems. Thereby, the patient achieved a stable state of disease and a good quality of life for up to now 67 months without any evidence for further tumor manifestations at present. A systemic chemo- or immunotherapy was never applied. In selected patients with stage IV melanoma, surgery alone can provide long-term survival with good quality of life. (c) 2008 S. Karger AG, Basel

  11. Animal-Assisted Therapy and Application to Older Adults in Long Term Care

    OpenAIRE

    Kimberly Ann Mercer

    2015-01-01

    In the past thirty years animal-assisted therapy (AAT) has moved beyond anecdotal status to a scientific evidence-based intervention. AAT comes in many shapes and sizes. There are a variety of animals which can be used such as dogs, cats, rabbits, horses, guinea pigs, goats, dolphins, and even fish aquariums. Loneliness is a common theme among older adults in long term care (LTC). Many older adults living in LTC facilities feel isolated. Some have little contact with family members or friends...

  12. [Long-term compliance of cpap-therapy--update, predictors and interventions].

    Science.gov (United States)

    Orth, M; Kotterba, S; Walther, J W; Rasche, K; Schultze-Werninghaus, G; Duchna, H-W

    2006-08-01

    CPAP (continuous positive airway pressure) is the therapy of choice for obstructive sleep apnea syndrome (OSAS). About 70 % of patients on CPAP use their device for at least 70 % of nights with an application-time of at least 4 hours per night. Severity of breathing disorder respectively disturbance of sleep architecture, degree of daytime sleepiness and patients' satisfaction with diagnostic and therapeutic procedures are good predictors of long-term CPAP-compliance. CPAP-compliance can be increased by intensive patient education. Alternative devices like for example Bilevel or auto-CPAP respectively cannot augment CPAP compliance.

  13. Topical glucocorticoids and the skin-mechanisms of action: an update

    Directory of Open Access Journals (Sweden)

    A. Ahluwalia

    1998-01-01

    Full Text Available The topical glucocorticoids (GCs represent the treatment of choice for many types of inflammatory dermatoses. Despite the extensive use of this class of drugs as first line therapy the mechanism of their action is uncertain. It is clear that the multiplicity of actions of the topical GCs is an important facet of their scope in the treatment of dermal disorders. The aim of this update is to review past and current theories regarding how these agents might work. Current understanding of the molecular mechanism s of GC action has advanced significantly over the past decade with the realisation that multiple systems are responsible for transduction of GC effects at a molecular level. The two primary modes of action are via interaction directly with DNA or indirectly through modulation of specific transcription factors: the endpoint in both cases being modulation of specific protein synthesis. Both of these mechanisms will be discussed. In particular this review will concentrate on the possibility that a GC-inducible protein, termed lipocortin 1, may have a significant role to play in the anti-inflammatory actions of these drugs. Additionally it has become apparent that several inflammatory enzymes induced in inflamm ation are sites of inhibitory action of the GCs, and the possibility that this occurs in the skin will be discussed paying particular attention to the inducible phospholipase A2, nitric oxide synthase and cyclooxygenase systems.

  14. Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications

    NARCIS (Netherlands)

    van Dussen, Laura; Biegstraaten, Marieke; Dijkgraaf, Marcel Gw; Hollak, Carla Em

    2014-01-01

    Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on

  15. Long term follow-up of a randomized controlled trial of oral appliance therapy in obstructive sleep apnea

    NARCIS (Netherlands)

    Aarab, G.; Lobbezoo, F.; Heijmans, M.W.; Hamburger, H.L.; Naeije, M.

    2011-01-01

    Background: Long-term trials are needed to capture information regarding the persistence of efficacy and loss to follow-up of both mandibular advancement device (MAD) therapy and continuous positive airway pressure (CPAP) therapy. Objectives: The aim of the study was to compare these treatment

  16. Pros and Cons of Long-Term use of Nicotine Replacement Therapies: A Qualitative Study

    DEFF Research Database (Denmark)

    Borup, Gitte; Kaae, Susanne; Nørgaard, Lotte Stig

    2016-01-01

    In the last decade, harm reduction has been increasingly suggested as a method to reduce the harm caused by smoking in smokers who are unable or unwilling to quit all nicotine products. One of these methods includes long-term substitution of tobacco with nicotine replacement therapies (NRTs......, including perceived pros and cons of using NRTs, the risk of relapse to smoking and their motivation to quit using NRTs. The results identified five major themes that entailed pros and cons of the long-term use of NRTs. These were the non-nicotinic factors of NRTs, health risks of NRTs vs. smoking......, intrapersonal processes, the social environment of smoking vs. NRTs and finances. None of the ex-smokers feared to relapse to smoking, and few were motivated to quit NRTs. Non-nicotinic factors were found to have an important role in developing an addiction to NRTs. The use of NRTs yields some of the expected...

  17. Testicular Receptor-4: Novel Regulator of Glucocorticoid Resistance.

    Science.gov (United States)

    Zhang, Dongyun; Du, Li; Heaney, Anthony P

    2016-08-01

    Glucocorticoids are powerful steroid hormones that regulate development, metabolism, and immune response. However, glucocorticoid unresponsiveness or resistance is observed in the treatment of inflammatory, autoimmune, and lymphoproliferative diseases and significantly limits their efficacy. In Cushing's disease, although some glucocorticoid-mediated suppression of pituitary-derived ACTH is seen, corticotroph tumors exhibit relative resistance to glucocorticoid action. We previously demonstrated that testicular orphan receptor 4 (TR4) binds to the pro-opiomelanocortin (POMC) promoter to induce corticotroph tumor POMC expression and ACTH secretion, and we hypothesized that TR4 may interact with glucocorticoid signaling to modulate POMC expression and action. Here we demonstrate that TR4 abrogates glucocorticoid receptor (GR)- or dexamethasone-mediated POMC and activator protein-1 transrepression in both murine and human pituitary corticotroph tumor cells. Co-immunoprecipitation studies indicate that TR4 and GR interact directly with each other, resulting in TR4-mediated disruption of GR binding to the POMC promoter. These results demonstrate that TR4 binds GR to play an important role in glucocorticoid-directed corticotroph tumor POMC regulation in addition to modulating glucocorticoid actions on other GR targets. Characterization of this pathway may offer important insights into glucocorticoid resistance and may identify a novel approach for the treatment of Cushing's disease and the glucocorticoid-resistant states.

  18. Long-Term Effect of Exercise Therapy and Patient Education on Impairments and Activity Limitations in People With Hip Osteoarthritis

    DEFF Research Database (Denmark)

    Svege, Ida; Fernandes, L.; Nordsletten, L

    2016-01-01

    Background. The effect of exercise on specific impairments and activity limitations in people with hip osteoarthritis (OA) is limited. Objective. The study objective was to evaluate the long-term effect of exercise therapy and patient education on range of motion (ROM), muscle strength, physical ...... results for ROM, muscle strength, physical fitness, and walking capacity, but exercise in addition to patient education resulted in less pain during walking in the long term. © 2016 American Physical Therapy Association....

  19. Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic agents on radiographic progression in rheumatoid arthritis: meta-analysis of 70 randomized placebo-controlled or drug-controlled studies, including 112 comparisons

    DEFF Research Database (Denmark)

    Graudal, Niels; Jürgens, Gesche

    2010-01-01

    To define the differences in effects on joint destruction in rheumatoid arthritis (RA) patients between therapy with single and combination disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and biologic agents....

  20. Long-term therapy with glatiramer acetate in multiple sclerosis: effect on T-cells.

    Science.gov (United States)

    Ragheb, S; Abramczyk, S; Lisak, D; Lisak, R

    2001-02-01

    Glatiramer acetate (GA) is an immunotherapeutic drug for multiple sclerosis (MS). Several mechanisms of action have been demonstrated which target and affect T-cells that are specific for myelin antigen epitopes. We measured the in vitro proliferation of GA-responsive T-cells from untreated MS patients and from normal healthy subjects; in addition, we determined the effect of prolonged GA therapy or interferon-beta therapy on the in vitro proliferation of GA-responsive T-cells of MS patients. We found that GA induces the proliferation of T-cells isolated from individuals who have not been previously exposed to GA, and that long-term in vivo therapy of MS patients with GA abrogates the GA-induced proliferative response of T-cells. In GA-treated patients, there is no evidence of generalized immunosuppression; both tetanus toxoid and anti-CD3 induced proliferative responses remain unaffected. We propose that prolonged in vivo exposure to GA may result in the eventual induction of anergy or deletion of a population of GA-responsive cells that may also be T-cells that are pathogenic in MS. This mechanism of action, in addition to other mechanisms that have been demonstrated, suggests that GA has pleiotropic effects on the immune system in MS.

  1. Short-term effects of vibration therapy on motor impairments in Parkinson's disease.

    Science.gov (United States)

    King, Lauren K; Almeida, Quincy J; Ahonen, Heidi

    2009-01-01

    Recent studies have suggested that vibration therapy may have a positive influence on motor symptoms in individuals with Parkinson's disease (PD). However, quantitative evidence of these benefits is scarce, and the concept of "whole-body" vibration in these studies is vague. The objectives of the current study were to evaluate the influence of vibration on motor symptoms and functional measures in PD by delivering sound waves to the entire body. We delivered whole body sound wave vibration to 40 individuals with PD using a Physioacoustic Chair, a piece of equipment with speakers spaced throughout the chair permitting a series of programmed low frequency sound waves through the body. Using a parallel cross-over design we utilized the Unified Parkinson's Disease Rating Scale (UPDRS), quantitative gait assessments, and a grooved pegboard for upper limb control. Improvements were seen in all symptom, motor control and functional outcome measures at the time of assessment. Specifically, a significant decrease in rigidity, and tremor were shown, as well as a significant increase in step length and improved speed on the grooved pegboard task. Results of this initial investigation provide support for vibration therapy as a non-pharmacological treatment alternative. Long-term benefits of vibration therapy will require further research.

  2. Long-Term Outcomes After Proton Beam Therapy for Sinonasal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Russo, Andrea L.; Adams, Judith A.; Weyman, Elizabeth A.; Busse, Paul M.; Goldberg, Saveli I. [Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Varvares, Mark; Deschler, Daniel D.; Lin, Derrick T. [Head and Neck Surgical Oncology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts (United States); Delaney, Thomas F. [Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Chan, Annie W., E-mail: awchan@partners.org [Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2016-05-01

    Purpose: Squamous cell carcinoma (SCC) is the most common sinonasal cancer and is associated with one of the poor outcomes. Proton therapy allows excellent target coverage with maximal sparing of adjacent normal tissues. We evaluated the long-term outcomes in patients with sinonasal SCC treated with proton therapy. Methods and Materials: Between 1991 and 2008, 54 patients with Stage III and IV SCC of the nasal cavity and paranasal sinus received proton beam therapy at our institution to a median dose of 72.8 Gy(RBE). Sixty-nine percent underwent prior surgical resection, and 74% received elective nodal radiation. Locoregional control and survival probabilities were estimated with the Kaplan-Meier method. Multivariate analyses were performed using the Cox proportional-hazards model. Treatment toxicity was scored using the Common Terminology Criteria for Adverse Events version 4.0. Results: With a median follow-up time of 82 months in surviving patients, there were 10 local, 7 regional, and 11 distant failures. The 2-year and 5-year actuarial local control rate was 80%. The 2-year and 5-year rates of overall survival were 67% and 47%, respectively. Only smoking status was predictive for worse locoregional control, with current smokers having a 5-year rate of 23% compared with 83% for noncurrent smokers (P=.004). Karnofsky performance status ≤80 was the most significant factor predictive for worse overall survival in multivariate analysis (adjusted hazard ratio 4.5, 95% confidence interval 1.6-12.5, P=.004). There were nine grade 3 and six grade 4 toxicities, and no grade 5 toxicity. Wound adverse events constituted the most common grade 3-4 toxicity. Conclusions: Our long-term results show that proton radiation therapy is well tolerated and yields good locoregional control for SCC of the nasal cavity and paranasal sinus. Current smokers and patients with poor performance status had inferior outcomes. Prospective study is necessary to compare IMRT with proton

  3. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    Directory of Open Access Journals (Sweden)

    Coventry BJ

    2015-04-01

    Full Text Available Brendon J Coventry, Dominique Baume, Carrie Lilly Discipline of Surgery, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia Background: Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Methods: Cases of long-term survival of ≥3 years' duration (from diagnosis of metastatic disease were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Results: Eighteen cases were identified that identified survival of ≥3 years' duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94% had survived ≥5 years, and eleven patients (61% had survived ≥10 years (range: 3–15 years. The median survival duration with metastatic disease was 11 years; 15 remained alive and three

  4. Deferasirox: appraisal of safety and efficacy in long-term therapy

    Directory of Open Access Journals (Sweden)

    Chaudhary P

    2013-08-01

    Full Text Available Preeti Chaudhary, Vinod PullarkatJane Ann Nohl Division of Hematology, University of Southern California Keck School of Medicine, Los Angeles, CA, USAAbstract: Deferasirox is a once-daily, oral iron chelator that is widely used in the management of patients with transfusional hemosiderosis. Several Phase II trials along with their respective extension studies as well as a Phase III trial have established the efficacy and safety of this novel agent in transfusion-dependent patients with β-thalassemia, sickle-cell disease and bone marrow-failure syndromes, including myelodysplastic syndrome and aplastic anemia. Data from various clinical trials show that a deferasirox dose of 20 mg/kg/day stabilizes serum ferritin levels and liver iron concentration, while a dose of 30–40 mg/kg/day reduces these parameters and achieves negative iron balance in red cell transfusion-dependent patients with iron overload. Across various pivotal clinical trials, deferasirox was well tolerated, with the most common adverse events being gastrointestinal disturbances, skin rash, nonprogressive increases in serum creatinine, and elevations in liver enzyme levels. Longer-term extension studies have also confirmed the efficacy and safety of deferasirox. However, it is essential that patients on deferasirox therapy are monitored regularly to ensure timely management for any adverse events that may occur with long-term therapy.Keywords: deferasirox, iron overload, thalassemia, sickle-cell disease, myelodysplastic syndrome

  5. Long-term follow-up after gene therapy for canavan disease.

    Science.gov (United States)

    Leone, Paola; Shera, David; McPhee, Scott W J; Francis, Jeremy S; Kolodny, Edwin H; Bilaniuk, Larissa T; Wang, Dah-Jyuu; Assadi, Mitra; Goldfarb, Olga; Goldman, H Warren; Freese, Andrew; Young, Deborah; During, Matthew J; Samulski, R Jude; Janson, Christopher G

    2012-12-19

    Canavan disease is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene (ASPA), leading to loss of enzyme activity and increased concentrations of the substrate N-acetyl-aspartate (NAA) in the brain. Accumulation of NAA results in spongiform degeneration of white matter and severe impairment of psychomotor development. The goal of this prospective cohort study was to assess long-term safety and preliminary efficacy measures after gene therapy with an adeno-associated viral vector carrying the ASPA gene (AAV2-ASPA). Using noninvasive magnetic resonance imaging and standardized clinical rating scales, we observed Canavan disease in 28 patients, with a subset of 13 patients being treated with AAV2-ASPA. Each patient received 9 × 10(11) vector genomes via intraparenchymal delivery at six brain infusion sites. Safety data collected over a minimum 5-year follow-up period showed a lack of long-term adverse events related to the AAV2 vector. Posttreatment effects were analyzed using a generalized linear mixed model, which showed changes in predefined surrogate markers of disease progression and clinical assessment subscores. AAV2-ASPA gene therapy resulted in a decrease in elevated NAA in the brain and slowed progression of brain atrophy, with some improvement in seizure frequency and with stabilization of overall clinical status.

  6. Long-term emollient therapy improves xerosis in children with atopic dermatitis.

    Science.gov (United States)

    Boralevi, F; Saint Aroman, M; Delarue, A; Raudsepp, H; Kaszuba, A; Bylaite, M; Tiplica, G S

    2014-11-01

    Hydration with topical emollients forms the backbone of treatment for mild atopic dermatitis (AD), but few randomized controlled trials have assessed their efficacy in young children. Assess the efficacy and tolerability of long-term emollient therapy in the treatment of moderate to severe xerosis in young children with AD. This was a phase III, multicentre, double-blind, randomized, vehicle-controlled trial. Children (n = 251) aged 2-6 years with AD-associated xerosis were randomized 1 : 1 to a 28-day treatment with an emollient combining glycerol and paraffin or its vehicle. Non-responders at the end of the double-blind period were treated open label with emollient until day 84. Responders stopped treatment until reassessment on day 56. Those who relapsed after stopping treatment were treated open label with emollient until day 84. During the double-blind period, xerosis score (XS) of the scoring atopic dermatitis (SCORAD) index, objective SCORAD and visual analogue score decreased and skin hydration increased more in the emollient group than in the vehicle group (P children who did not initially respond. Adverse events were similar in the two groups, and no treatment-related severe adverse events were reported. Long-term therapy with emollient is effective and well tolerated for the treatment of xerosis in children with atopic dermatitis. © 2013 European Academy of Dermatology and Venereology.

  7. Bilateral distal fibula fractures in a woman on long-term bisphosphonate therapy.

    Science.gov (United States)

    Murray, J C; Audet, M C; Bédard, M; Michou, L

    2016-02-01

    We report the case of a 53-year-old female, treated by bisphosphonate for 12 years, who presented atraumatic fractures of both fibulas. Her X-rays showed bilateral distal fibula fractures with radiological features similar to atypical femur fractures. The distal fibula should be considered as a potential site for stress fractures in bisphosphonate users. Bisphosphonates are the most widely used drugs in the treatment of osteoporosis. During the last decade, the occurrence of atypical fractures, mostly subtrochanteric and diaphyseal femoral fractures, has been acknowledged in patients with long-term use of bisphosphonates. We report the case of a 53-year-old female on alendronate therapy for the past 12 years who presented with a few months history of atraumatic right, and subsequently left, lateral ankle pain. Her X-rays showed bilateral distal fibula fractures with radiological features similar to atypical femur fractures. She had been treated conservatively with walking boots and her treatment with bisphosphonate had been stopped 5 months prior to the fractures. Callus was progressively seen on serial follow-up X-rays, and both fractures healed completely within a reasonable period of 1 year. Investigations did not reveal any secondary causes of osteoporosis or metabolic bone disorders. To our knowledge, this is the first reported case of bilateral distal fibula fractures in a patient on long-term bisphosphonate therapy.

  8. Loss of Response to Long-Term Infliximab Therapy in Children with Crohn’s Disease

    Science.gov (United States)

    Gouldthorpe, Oliver; Catto-Smith, Anthony G.; Alex, George; Simpson, Di

    2013-01-01

    Secondary loss of response (LoR) often precludes further use of infliximab in children with Crohn’s disease. Immunomodulators may reduce the incidence of LoR but their combination with infliximab presents safety concerns. We aimed to determine the long-term durability of infliximab response in paediatric Crohn’s, effect of immunomodulators on LoR, and secondarily the effect of infliximab on growth. We retrospectively audited patients on maintenance infliximab at a single centre. Data included height and weight, Paediatric Crohn’s Disease Activity Index (PCDAI), and immunomodulator use. 71 children (32% female, mean age 14.4 years) had been commenced on maintenance infliximab before July 2011. 89% had been on immunomodulators concurrently with infliximab. LoR occurred in 20 (28%), with a median time to LoR of 4.31 years. LoR was significantly increased in children who did not enter remission (PCDAI ≤ 10) after induction (p < 0.05). LoR occurred more frequently in the 72% who ceased immunomodulators, but this failed to reach statistical significance (p = 0.300). Height and weight SDS improved significantly on infliximab. Infliximab is a durable long-term therapy for paediatric Crohn’s refractory to conventional therapy. A large-magnitude increase in the rate of loss of response after immunomodulator cessation was not observed. PMID:24275852

  9. Loss of Response to Long-Term Infliximab Therapy in Children with Crohn’s Disease

    Directory of Open Access Journals (Sweden)

    George Alex

    2013-10-01

    Full Text Available Secondary loss of response (LoR often precludes further use of infliximab in children with Crohn’s disease. Immunomodulators may reduce the incidence of LoR but their combination with infliximab presents safety concerns. We aimed to determine the long-term durability of infliximab response in paediatric Crohn’s, effect of immunomodulators on LoR, and secondarily the effect of infliximab on growth. We retrospectively audited patients on maintenance infliximab at a single centre. Data included height and weight, Paediatric Crohn’s Disease Activity Index (PCDAI, and immunomodulator use. 71 children (32% female, mean age 14.4 years had been commenced on maintenance infliximab before July 2011. 89% had been on immunomodulators concurrently with infliximab. LoR occurred in 20 (28%, with a median time to LoR of 4.31 years. LoR was significantly increased in children who did not enter remission (PCDAI ≤ 10 after induction (p < 0.05. LoR occurred more frequently in the 72% who ceased immunomodulators, but this failed to reach statistical significance (p = 0.300. Height and weight SDS improved significantly on infliximab. Infliximab is a durable long-term therapy for paediatric Crohn’s refractory to conventional therapy. A large-magnitude increase in the rate of loss of response after immunomodulator cessation was not observed.

  10. Pelvic fractures associated with long-term bisphosphonate therapy - case report.

    Science.gov (United States)

    Patel, V; Graves, L; Lukert, B

    2013-06-01

    Long term bisphosphonate use has been associated with "atypical" subtrochanteric and diaphyseal fractures of the femoral shaft. We are reporting a case of pelvic fractures in addition to atypical long bone fractures, in a patient with osteopenia treated with bisphosphonate for 8 years, and teriparatide for 2 years. After 5 years of bisphosphonate therapy the patient suffered an atraumatic fracture of the femoral shaft. With an additional 3 years of bisphosphonate use she fractured both the upper and lower pubic rami on the left side. Bone histomorphometry performed on a biopsy of right iliac crest was negative for malignancy and calcification defects. It showed normal to low/normal bone turnover which correlated well with a low NTX level. Post-surgical X-rays revealed cortical thickening of the femur and beaking at the femoral shaft fracture, the classic findings associated with alendronate-related fractures. The pelvic fractures also reveal beaking at the fracture sites. Spontaneous fracture of the pelvis with unusual characteristics, in a patient with an atypical fracture of the femur suggests that the pelvic fracture may be related to long term bisphosphonate therapy.

  11. Long-term effects of internet-supported cognitive behaviour therapy.

    Science.gov (United States)

    Andersson, Gerhard; Rozental, Alexander; Shafran, Roz; Carlbring, Per

    2018-01-01

    Internet-supported and therapist-guided cognitive behaviour therapy (ICBT) is effective for a range of problems in the short run, but less is known about the long-term effects with follow-ups of two years or longer. Areas covered: This paper reviews studies in which the long-term effects of guided ICBT were investigated. Following literature searches in PubMed and other sources meta-analytic statistics were calculated for 14 studies involving a total of 902 participants, and an average follow-up period of three years. Studies were from Sweden (n = 11) or the Netherlands (n = 3). Long-term outcome studies were found for panic disorder, social anxiety disorder, generalized anxiety disorder, depression, mixed anxiety and depression, obsessive-compulsive disorder, pathological gambling, stress and chronic fatigue. The duration of the treatments was usually short (8-15 weeks). The pre-to follow-up effect size was Hedge's g = 1.52, but with a significant heterogeneity. The average symptom improvement across studies was 50%. Treatment seeking in the follow-up period was not documented and few studies mentioned negative effects. Expert commentary: While effects may be overestimated, it is likely that therapist-supported ICBT can have enduring effects. Long-term follow-up data should be collected for more conditions and new technologies like smartphone-delivered treatments.

  12. Ascending aortic remodelling in Fabry disease after long-term enzyme replacement therapy.

    Science.gov (United States)

    Monney, Pierre; Qanadli, Salah Dine; Hajdu, Steven; Tran, Christel; Schwitter, Juerg; Dormond, Olivier; Barbey, Frédéric

    2017-11-09

    Previous cross-sectional studies reported a high prevalence of ascending aorta dilations/aneurysms in male adults with Fabry disease, independently of cardiovascular risk factors. To characterise the remodelling of the ascending aorta in classic Fabry disease under long-term enzyme replacement therapy. Diameter of the ascending aorta was measured with magnetic resonance imaging at the sino-tubular junction (STJ), and proximal (pAsAo), and distal ascending aorta (dAsAo) at baseline, and after 5 and 10 years of enzyme replacement therapy in 15 adult Fabry patients (10 males; 5 females). Over a mean follow-up of 9.5 years, the annual expansion rates measured in 10 males with Fabry disease were 0.41 ± 0.16, 0.36 ± 0.25 and 0.41 ± 0.26 mm/y at the STJ, pAsAo and dAsAo, respectively. Expansion rate at the pAsAo level in male patients was significantly higher than the expected expansion projected from theoretical normal values: 0.36 ± 0.25 vs 0.13 ± 0.05, p = 0.017. In 5 females, the annual expansion rates at the STJ, pAsAo and dAsAo were 0.14 ± 0.11, 0.21 ± 0.18 and 0.26 ± 0.24 mm/y, respectively. There was no significant difference from the projected normal expansion rate at the level of the pAsAo: 0.21 ± 0.18 vs 0.13 ± 0.04, p = 0.39. Our data suggest that the remodelling of the ascending aorta is more pronounced in male patients with Fabry disease under long-term enzyme replacement therapy compared with the progression observed in a large population study.

  13. Gastroesophageal Acid Reflux Control 5 Years After Antireflux Surgery, Compared With Long-term Esomeprazole Therapy.

    Science.gov (United States)

    Hatlebakk, Jan G; Zerbib, Frank; Bruley des Varannes, Stanislas; Attwood, Stephen E; Ell, Christian; Fiocca, Roberto; Galmiche, Jean-Paul; Eklund, Stefan; Långström, Göran; Lind, Tore; Lundell, Lars R

    2016-05-01

    We compared the ability of laparoscopic antireflux surgery (LARS) and esomeprazole to control esophageal acid exposure, over a 5-year period, in patients with chronic gastroesophageal reflux disease (GERD). We also studied whether intraesophageal and intragastric pH parameters off and on therapy were associated with long-term outcomes. We analyzed data from a prospective, randomized, open-label trial comparing the efficacy and safety of LARS vs esomeprazole (20 or 40 mg/d) over 5 years in patients with chronic GERD. Ambulatory intraesophageal and intragastric 24-hour pH monitoring data were compared between groups before LARS or the start of esomeprazole treatment, and 6 months and 5 years afterward. A secondary aim was to evaluate the association between baseline and 6-month pH parameters and esomeprazole dose escalation, reappearance of GERD symptoms, and treatment failure over 5 years in patients receiving LARS or esomeprazole. In the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P esomeprazole group (n = 151), the median 24-hour esophageal acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P esomeprazole). Gastric acidity was stable in both groups. Patients who required a dose increase to 40 mg/d had more severe supine reflux at baseline, and decreased esophageal acid exposure (P esomeprazole therapy. However, patients receiving LARS had significantly greater reductions in 24-hour esophageal acid exposure after 6 months and 5 years. Esophageal and gastric pH, off and on therapy, did not predict long-term outcomes of patients. Abnormal supine acid exposure predicted esomeprazole dose escalation. ClinicalTrials.Gov identifier: NCT00251927 (available: http://clinicaltrials.gov/ct2/show/NCT00251927). Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Short-term group schema therapy for mixed personality disorders: a pilot study

    Science.gov (United States)

    Skewes, Sally A.; Samson, Rachel A.; Simpson, Susan G.; van Vreeswijk, Michiel

    2015-01-01

    Schema Therapy has shown promising results for personality disorders but there is a limited evidence base for group schema therapy (ST-g) with mixed personality disorders. The aim of this study was to explore the feasibility, acceptability, and preliminary effectiveness of ST-g in a sample of eight participants with mixed personality disorders (with a predominant diagnosis of avoidant personality disorder) and high levels of comorbidity. Treatment was comprised of 20 sessions which included cognitive, behavioral, and experiential techniques. Specific schema-based strategies were chosen for a diagnostically mixed group of personality disorder clients. Six participants attended until end of treatment and two dropped-out before mid-treatment. All outcome measures showed changes with large effect sizes in avoidant personality disorder symptom severity, depression and anxiety levels between pre-therapy and follow-up. Four participants achieved a loss of personality disorder diagnosis at the end of therapy. By follow-up, five participants had achieved a loss of diagnosis, suggesting that participants derived ongoing benefits from the group even after treatment ended. Six participants no longer met criteria for depression at the end of treatment and this was maintained for all participants at 6-month follow-up. At follow-up, the majority of participants showed clinically significant change on the Global Symptom Index (GSI). For the Schema Mode Inventory (SMI) maladaptive modes, the majority of participants showed improvement at follow-up. At follow-up, 40% of participants showed clinically significant change on the SMI adaptive modes. Qualitative feedback indicates that the group helps to normalize participants' psychological experiences and difficulties and promotes self-expression and self-disclosure, while reducing inhibition. Preliminary results suggest that short-term ST-g may benefit those with mixed personality disorders, but generalizability is limited by the

  15. Short-term group schema therapy for mixed personality disorders: A pilot study

    Directory of Open Access Journals (Sweden)

    Sally Ann Skewes

    2015-01-01

    Full Text Available Schema Therapy has shown promising results for personality disorders but there is a limited evidence base for group Schema Therapy (ST-g with mixed personality disorders. The aim of this study was to explore the feasibility, acceptability and preliminary effectiveness of ST-g in a sample of eight participants with mixed personality disorders (with a predominant diagnosis of avoidant personality disorder and high levels of comorbidity. Treatment was comprised of 20 sessions which included cognitive, behavioural, and experiential techniques. Specific schema-based strategies were chosen for a diagnostically mixed group of personality disorder clients. Six participants attended until end of treatment and two dropped-out before mid-treatment. All outcome measures showed changes with large effect sizes in avoidant personality disorder symptom severity, depression and anxiety levels between pre-therapy and follow-up. Four participants achieved a loss of personality disorder diagnosis at the end of therapy. By follow-up, five participants had achieved a loss of diagnosis, suggesting that participants derived ongoing benefits from the group even after treatment ended. Six participants no longer met criteria for depression at the end of treatment and this was maintained for all participants at six-month follow-up. At follow-up, the majority of participants showed clinically significant change on the GSI. For the SMI maladaptive modes, the majority of participants showed improvement at follow-up. At follow-up 40% of participants showed clinically significant change on the SMI adaptive modes. Qualitative feedback indicates that the group helps to normalize participants’ psychological experiences and difficulties and promotes self-expression and self-disclosure, while reducing disinhibition. Preliminary results suggest that short-term ST-g may benefit those with mixed personality disorders, but generalizability is limited by the small sample size and lack

  16. Short-term group schema therapy for mixed personality disorders: a pilot study.

    Science.gov (United States)

    Skewes, Sally A; Samson, Rachel A; Simpson, Susan G; van Vreeswijk, Michiel

    2014-01-01

    Schema Therapy has shown promising results for personality disorders but there is a limited evidence base for group schema therapy (ST-g) with mixed personality disorders. The aim of this study was to explore the feasibility, acceptability, and preliminary effectiveness of ST-g in a sample of eight participants with mixed personality disorders (with a predominant diagnosis of avoidant personality disorder) and high levels of comorbidity. Treatment was comprised of 20 sessions which included cognitive, behavioral, and experiential techniques. Specific schema-based strategies were chosen for a diagnostically mixed group of personality disorder clients. Six participants attended until end of treatment and two dropped-out before mid-treatment. All outcome measures showed changes with large effect sizes in avoidant personality disorder symptom severity, depression and anxiety levels between pre-therapy and follow-up. Four participants achieved a loss of personality disorder diagnosis at the end of therapy. By follow-up, five participants had achieved a loss of diagnosis, suggesting that participants derived ongoing benefits from the group even after treatment ended. Six participants no longer met criteria for depression at the end of treatment and this was maintained for all participants at 6-month follow-up. At follow-up, the majority of participants showed clinically significant change on the Global Symptom Index (GSI). For the Schema Mode Inventory (SMI) maladaptive modes, the majority of participants showed improvement at follow-up. At follow-up, 40% of participants showed clinically significant change on the SMI adaptive modes. Qualitative feedback indicates that the group helps to normalize participants' psychological experiences and difficulties and promotes self-expression and self-disclosure, while reducing inhibition. Preliminary results suggest that short-term ST-g may benefit those with mixed personality disorders, but generalizability is limited by the

  17. Biochemical endpoints of glucocorticoid hormone action

    Energy Technology Data Exchange (ETDEWEB)

    Young, D.A.; Nicholson, M.L.; Guyette, W.A.; Giddings, S.J.; Mendelsohn, S.L.; Nordeen, S.K.; Lyons, R.T.

    1978-01-01

    Both the rapidly evolving metabolic effects of glucocorticoids and the more slowly developing lethal actions appear to be initiated via the synthesis of new mRNAs and proteins. The chronic suppression of cell growth may be the consequence of suppression of overall rates of protein synthesis (and probably RNA and DNA synthesis as well) that in turn may represent the cellular response to the small changes in ratios of adenine nucleotides that result from the suppression of oxidative ATP production. The inhibition of glucose transport may also play a role here to prevent a compensatory increase in glycolytic ATP production. Some other hormone actions, the decrease in the ability of cells to concentrate AIB and the increase in nuclear fragility are unrelated to, and evolve separately from, the hormonal inhibitions on energy production. Cell killing is not the result of suppression of protein synthesis, nor of hormone-induced increases in calcium uptake. While the mechanisms are unknown, the increase in nuclear fragility appears to be the earliest measure of their operation. In tumor cells resistance to lethal actions of glucocorticoids may emerge via the selection of cells with hardier membranes, that are better able to withstand the intracellular destructive events set in motion by high levels of glucocorticoids.

  18. Early Life Stress Effects on the Glucocorticoid - BDNF interplay in the Hippocampus

    Directory of Open Access Journals (Sweden)

    Nikolaos P Daskalakis

    2015-11-01

    Full Text Available Early life stress (ELS is implicated in the etiology of multiple psychiatric disorders. Important biological effects of ELS are manifested in stress-susceptible regions of the hippocampus and are partially mediated by long-term effects on glucocorticoid and/or neurotrophin signaling pathways. Glucocorticoid (GC signaling mediates the regulation of the stress response to maintain homeostasis, while neurotrophin signaling plays a key role in neuronal outgrowth and is crucial for axonal guidance and synaptic integrity. The neurotrophin and glucocorticoid signaling pathways co-exist throughout the central nervous system (CNS, particularly in the hippocampus, which has high expression of glucocorticoid and mineralocorticoid receptors (GR and MR as well as brain-derived neurotrophic factor (BDNF and its receptor, tropomyosin-related kinase receptor B (TrkB. This review addresses the effects of ELS paradigms on GC- and BDNF- dependent mechanisms and their crosstalk in the hippocampus, including potential implications for the pathogenesis of common stress-related disorders.

  19. The BclI polymorphism of the glucocorticoid receptor gene is associated with emotional memory performance in healthy individuals.

    Science.gov (United States)

    Ackermann, Sandra; Heck, Angela; Rasch, Björn; Papassotiropoulos, Andreas; de Quervain, Dominique J-F

    2013-07-01

    Glucocorticoids, stress hormones released from the adrenal cortex, are important players in the regulation of emotional memory. Specifically, in animals and in humans, glucocorticoids enhance memory consolidation of emotionally arousing experiences, but impair memory retrieval. These glucocorticoid actions are partly mediated by glucocorticoid receptors in the hippocampus, amygdala and prefrontal cortex, key brain regions for emotional memory. In a recent study in patients who underwent cardiac surgery, the BclI polymorphism of the glucocorticoid receptor gene (NR3C1) was associated with traumatic memories and posttraumatic stress disorder symptoms after intensive care therapy. Based on this finding, we investigated if the BclI polymorphism is also associated with emotional memory in healthy young subjects (N=841). We used a picture-learning task consisting of learning and recalling neutral and emotional photographs on two consecutive days. The BclI variant was associated with short-delay recall of emotional pictures on both days, with GG carriers showing increased emotional memory performance as compared to GC and CC carriers. We did not detect a genotype-dependent difference in recall performance for neutral pictures. These findings suggest that the Bcll polymorphism contributes to inter-individual differences in emotional memory also in healthy humans. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Short-term outcome of fluoroscopic-guided steroid injection therapy of lumber facet cyst-induced radicular pain

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Mi Ri; Kwon, Jong Won; Lee, Jong Seo; Kim, Eu Sang [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2015-04-15

    To determine the short-term effect of fluoroscopic-guided steroid injection therapy of lumbar facet cyst-induced radicular pain. Seventeen patients with radiculopathy due to lumbar synovial cysts, who were treated with fluoroscopically guided injection, were retrospectively evaluated. All plain radiographic images and MR images before the therapy were reviewed. Five patients underwent only the facet joint injection, whereas twelve patients underwent the facet joint injection with perineural injection therapy. The clinical course of pain was evaluated on the first follow-up after therapy. Effective pain relief was achieved in 11 (64.7%) of the 17 patients. Among 12 patients who underwent facet joint injection with perineural injection, 9 patients (75%) had an effective pain relief. Of 5 patients, 2 (40%) patients only took the facet joint injection and had an effective pain relief. Fluoroscopic-guided steroid injection therapy shows a good short-term effect in patients with symptomatic lumbar facet joint synovial cysts.

  1. Dibutyltin disrupts glucocorticoid receptor function and impairs glucocorticoid-induced suppression of cytokine production.

    Directory of Open Access Journals (Sweden)

    Christel Gumy

    Full Text Available BACKGROUND: Organotins are highly toxic and widely distributed environmental chemicals. Dibutyltin (DBT is used as stabilizer in the production of polyvinyl chloride plastics, and it is also the major metabolite formed from tributyltin (TBT in vivo. DBT is immunotoxic, however, the responsible targets remain to be defined. Due to the importance of glucocorticoids in immune-modulation, we investigated whether DBT could interfere with glucocorticoid receptor (GR function. METHODOLOGY: We used HEK-293 cells transiently transfected with human GR as well as rat H4IIE hepatoma cells and native human macrophages and human THP-1 macrophages expressing endogenous receptor to study organotin effects on GR function. Docking of organotins was used to investigate the binding mechanism. PRINCIPAL FINDINGS: We found that nanomolar concentrations of DBT, but not other organotins tested, inhibit ligand binding to GR and its transcriptional activity. Docking analysis indicated that DBT inhibits GR activation allosterically by inserting into a site close to the steroid-binding pocket, which disrupts a key interaction between the A-ring of the glucocorticoid and the GR. DBT inhibited glucocorticoid-induced expression of phosphoenolpyruvate carboxykinase (PEPCK and tyrosine-aminotransferase (TAT and abolished the glucocorticoid-mediated transrepression of TNF-alpha-induced NF-kappaB activity. Moreover, DBT abrogated the glucocorticoid-mediated suppression of interleukin-6 (IL-6 and TNF-alpha production in lipopolysaccharide (LPS-stimulated native human macrophages and human THP-1 macrophages. CONCLUSIONS: DBT inhibits ligand binding to GR and subsequent activation of the receptor. By blocking GR activation, DBT may disturb metabolic functions and modulation of the immune system, providing an explanation for some of the toxic effects of this organotin.

  2. Long-Term Outcomes of Cognitive-Behavioral Therapy for Adolescent Body Dysmorphic Disorder.

    Science.gov (United States)

    Krebs, Georgina; de la Cruz, Lorena Fernández; Monzani, Benedetta; Bowyer, Laura; Anson, Martin; Cadman, Jacinda; Heyman, Isobel; Turner, Cynthia; Veale, David; Mataix-Cols, David

    2017-07-01

    Emerging evidence suggests that cognitive-behavioral therapy (CBT) is an efficacious treatment for adolescent body dysmorphic disorder (BDD) in the short term, but longer-term outcomes remain unknown. The current study aimed to follow up a group of adolescents who had originally participated in a randomized controlled trial of CBT for BDD to determine whether treatment gains were maintained. Twenty-six adolescents (mean age = 16.2, SD = 1.6) with a primary diagnosis of BDD received a course of developmentally tailored CBT and were followed up over 12 months. Participants were assessed at baseline, midtreatment, posttreatment, 2-, 6-, and 12-month follow-up. The primary outcome measure was the clinician-rated Yale-Brown Obsessive-Compulsive Scale Modified for BDD. Secondary outcomes included measures of insight, depression, quality of life, and global functioning. BDD symptoms decreased significantly from pre- to posttreatment and remained stable over the 12-month follow-up. At this time point, 50% of participants were classified as responders and 23% as remitters. Participants remained significantly improved on all secondary outcomes at 12-month follow-up. Neither baseline insight nor baseline depression predicted long-term outcomes. The positive effects of CBT appear to be durable up to 12-month follow-up. However, the majority of patients remained symptomatic and vulnerable to a range of risks at 12-month follow-up, indicating that longer-term monitoring is advisable in this population. Future research should focus on enhancing the efficacy of CBT in order to improve long-term outcomes. Copyright © 2017. Published by Elsevier Ltd.

  3. Mid- and long-term clinical results of surgical therapy in unicameral bone cysts

    Directory of Open Access Journals (Sweden)

    Hagmann Sébastien

    2011-12-01

    Full Text Available Abstract Background Unicameral (or simple bone cysts (UBC are benign tumours most often located in long bones of children and adolescents. Pathological fractures are common, and due to high recurrence rates, these lesions remain a challenge to treat. Numerous surgical procedures have been proposed, but there is no general consensus of the ideal treatment. The aim of this investigation therefore was to study the long-term outcome after surgical treatment in UBC. Methods A retrospective analysis of 46 patients surgically treated for UBC was performed for short and mid-term outcome. Clinical and radiological outcome parameters were studied according to a modified Neer classification system. Long-term clinical information was retrieved via a questionnaire at a minimum follow-up of 10 years after surgery. Results Forty-six patients (17 female, 29 male with a mean age of 10.0 ± 4.8 years and with histopathologically confirmed diagnosis of UBC were included. Pathological fractures were observed in 21 cases (46%. All patients underwent surgery for UBC (35 patients underwent curettage and bone grafting as a primary therapy, 4 curettage alone, 3 received corticoid instillation and 4 decompression by cannulated screws. Overall recurrence rate after the first surgical treatment was 39% (18/46, second (17.4% of all patients and third recurrence (4.3% were frequently observed and were addressed by revision surgery. Recurrence was significantly higher in young and in male patients as well as in active cysts. After a mean of 52 months, 40 out of 46 cysts were considered healed. Prognosis was significantly better when recurrence was observed later than 30 months after therapy. After a mean follow-up of 15.5 ± 6.2 years, 40 patients acknowledged clinically excellent results, while five reported mild and casual pain. Only one patient reported a mild limitation of range of motion. Conclusions Our results suggest satisfactory overall long-term outcome for the

  4. Long-term outcome of ablative therapy of postoperative supraventricular tachycardias in patients with univentricular heart: a European multicenter study

    NARCIS (Netherlands)

    de Groot, Natasja M. S.; Lukac, Peter; Blom, Nico A.; van Kuijk, Jan Peter; Pedersen, Anders K.; Hansen, Peter S.; Delacretaz, Etienne; Schalij, Martin J.

    2009-01-01

    BACKGROUND: Catheter ablation has evolved as a possible curative treatment modality for supraventricular tachycardias (SVT) in patients with univentricular heart. However, the long-term outcome of ablation procedures is unknown. We evaluated the procedural and long-term outcome of ablative therapy

  5. Long-Term Efficacy of Voice Therapy in Patients With Voice Problems After Treatment of Early Glottic Cancer

    NARCIS (Netherlands)

    van Gogh, Christine D. L.; Verdonck-de Leeuw, Irma M.; Langendijk, Johannes A.; Kuik, Dirk J.; Mahieu, Hans F.

    Objective. The purpose of the present pilot study is to investigate whether the beneficial short-term effects of voice therapy in patients with voice problems after treatment of early glottic cancer as reported in our earlier study remain present on the long term. Study Design. In this prospective

  6. Long-Term Efficacy of Voice Therapy in Patients With Voice Problems After Treatment of Early Glottic Cancer

    NARCIS (Netherlands)

    van Gogh, C.D.L.; de Leeuw, I.M.; Langendijk, J.A.; Kuik, D.J.; Mahieu, H.F.

    2012-01-01

    Objective: The purpose of the present pilot study is to investigate whether the beneficial short-term effects of voice therapy in patients with voice problems after treatment of early glottic cancer as reported in our earlier study remain present on the long term. Study Design: In this prospective

  7. Swallowed Fluticasone Propionate Is an Effective Long-Term Maintenance Therapy for Children With Eosinophilic Esophagitis.

    Science.gov (United States)

    Andreae, Doerthe A; Hanna, Matthew G; Magid, Margret S; Malerba, Stefano; Andreae, Michael H; Bagiella, Emilia; Chehade, Mirna

    2016-08-01

    Although effective in the treatment of eosinophilic esophagitis (EoE) in children, limited data exist on long-term safety and efficacy of swallowed topical corticosteroids. We investigated whether long-term use of swallowed fluticasone in children with EoE leads to sustained reduction in esophageal eosinophils, and endoscopic and clinical improvement. In an open-label, prospective, single-center study, we offered pediatric patients with active EoE fluticasone 2 puffs to swallow twice a day (strengths in μg/puff: 2-4 years: 44, 5-11 years: 110, ≥12 years: 220). Clinical, endoscopic, and histological assessments were performed at baseline and shortly after therapy. If histological remission was seen, fluticasone was continued with clinical follow-ups every 4 months and endoscopic and histological follow-ups yearly. Clinical scores were derived from eight symptoms (abdominal pain, nausea, vomiting, regurgitation, chest pain, dysphagia, food impaction, and early satiety). Endoscopic scores were derived from six features (rings, exudates, furrows, edema, stricture, and shearing). Scores were expressed as ratio (features present/total). In addition to peak eosinophils/high power field (HPF) (primary outcome), histological features (eosinophilic microabscesses, degranulation, superficial layering, basal zone hyperplasia, dilated intercellular spaces, and lamina propria fibrosis) were assessed. Median clinical and endoscopic scores and individual histologic features were compared over 4 time intervals: 24 months. Growth and adverse effects were monitored. We enrolled 54 patients, 80% male, median age 6.5 years (range 2-17 years), 85% atopic (57% asthma, 68% allergic rhinitis, and 31% atopic dermatitis), and 74% with food allergy. Mean follow-up was 20.4 months, the longest being 68 months (5.7 years). Esophageal eosinophil counts significantly decreased (median peak eosinophils/HPF at baseline 72, 24 months: 12, all P24 months: 39, all P24 months: 0.1, all P24 months: P

  8. Perioperative glucocorticoids in hip and knee surgery - benefit vs. harm?

    DEFF Research Database (Denmark)

    Lunn, T H; Kehlet, H

    2013-01-01

    Glucocorticoids are frequently used to prevent post-operative nausea and vomiting (PONV), and may be part of multimodal analgesic regimes. The objective of this review was to evaluate the overall benefit vs. harm of perioperative glucocorticoids in patients undergoing hip or knee surgery. A wide......-analysis was performed. In conclusion, in addition to PONV reduction with low-dose systemic glucocorticoid, this review supports high-dose systemic glucocorticoid to ameliorate post-operative pain after hip and knee surgery. However, large-scale safety and dose-finding studies are warranted before final recommendations....

  9. Short-term and long-term effects of psychosocial therapy for people after deliberate self-harm

    DEFF Research Database (Denmark)

    Erlangsen, Annette; Lind, Bertel Dam; Stuart, Elizabeth A

    2015-01-01

    BACKGROUND: Although deliberate self-harm is a strong predictor of suicide, evidence for effective interventions is missing. The aim of this study was to examine whether psychosocial therapy after self-harm was linked to lower risks of repeated self-harm, suicide, and general mortality. METHODS......: In this matched cohort study all people who, after deliberate self-harm, received a psychosocial therapy intervention at suicide prevention clinics in Denmark during 1992-2010 were compared with people who did not receive the psychosocial therapy intervention after deliberate self-harm. We applied propensity...... score matching with a 1:3 ratio and 31 matching factors, and calculated odds ratios for 1, 5, 10, and 20 years of follow-up. The primary endpoints were repeated self-harm, death by suicide, and death by any cause. FINDINGS: 5678 recipients of psychosocial therapy (followed up for 42·828 person...

  10. HOMOCYSTEINE-LOWERING THERAPY AND LONG-TERM PROGNOSIS AFTER ELECTIVE PERCUTANEOUS CORONARY INTERVENTION

    Directory of Open Access Journals (Sweden)

    O. O. Shakhmatova

    2011-01-01

    Full Text Available Background. Vitamins В6 В12 and folic acid (FA therapy to reduce cardiovascular risk appears to be unreasonable. Negative results of recent large-scale trials might be due to high daily doses of the vitamins and widespread FA fortification programmes. Russian population is known to have high prevalence of FA and vitamin B12 deficiency. Aim. To evaluate the effect of FA, B6 and B12 vitamins (in doses approximate to daily maintenance on long-term prognosis after elective percutaneous coronary intervention (PCI in stable ischemic heart disease patients. Material and methods. 264 patients (213 male, age 58.8±1.0 years after successful PCI were involved into the trial. Patients with clinical signs of the vitamins deficiency were not included. Patients were randomly assigned to receive combination of FA (0.6 mg/day, B12 (10 μg/day, and B6 (4 mg/day vitamins along with the conventional therapy (n=97 or the conventional therapy only (n=167 for 20 months. The groups were comparable in age, gender and prevalence of coronary risk factors. Composite endpoint was defined as cardiovascular death, acute coronary syndrome, stroke or transient is- chemic attack and need for coronary/carotid revascularization. Results. The vitamins prescription to all of the patients did not reduce composite endpoint incidence according to multivariable regression analysis (RR 0,7; 95%CI 0,4-1,4; p=0,3. Subgroup analysis showed significantly lower composite endpoint incidence in patients who received vitamins and had initially low B12 blood level (<260 pg/ml as compared to the control group (RR 0.09; 95%CI 0.01-0.9; p=0.04. Conclusion. Treatment with FA, B and B vitamins improves prognosis after PCI in patients with initially low blood vitamin B level.

  11. Assessment of cognitive impairment in long-term oxygen therapy-dependent COPD patients.

    Science.gov (United States)

    Karamanli, Harun; Ilik, Faik; Kayhan, Fatih; Pazarli, Ahmet Cemal

    2015-01-01

    A number of studies have shown that COPD, particularly in its later and more severe stages, is associated with various cognitive deficits. Thus, the primary goal of the present study was to elucidate the extent of cognitive impairment in patients with long-term oxygen therapy-dependent (LTOTD) COPD. In addition, this study aimed to determine the effectiveness of two cognitive screening tests, the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), for COPD patients and the ability of oxygen therapy to mitigate COPD-related deficits in cognitive function. The present study enrolled 45 subjects: 24 nonuser and 21 regular-user LTOTD-COPD patients. All subjects had a similar grade of education, and there were no significant differences regarding age or sex. The MoCA (cutoff: therapy increased the risk of cognitive impairment (MoCA, P=0.007 and MMSE, P=0.014), and the MoCA and MMSE scores significantly correlated with the number of emergency admissions and the number of hospitalizations in the last year. In the present study, the nonuser LTOTD-COPD group exhibited a significant decrease in cognitive status compared with the regular-user LTOTD-COPD group. This suggests that the assessment of cognitive function in nonuser LTOTD-COPD patients and the use of protective strategies, such as continuous supplemental oxygen treatment, should be considered during the management of COPD in this population. In addition, the MoCA score was superior to the MMSE score for the determination of cognitive impairment in the nonuser LTOTD-COPD patients.

  12. The short-term effects of physical therapy in different intensities of urodynamic stress incontinence.

    Science.gov (United States)

    Turkan, Akbayrak; Inci, Yuksel; Fazli, Demirturk

    2005-01-01

    The aim of this study was to investigate and compare the short-term effects of a physical therapy program in patients with different intensities of urodynamic stress urinary incontinence (USI). 48 patients with USI were assigned to three groups according to the intensity of their incontinence: group I: 0-2 g (n = 17), group II (mild intensity: >2-10 g, n = 16) and group III (moderate intensity: >10 g, n = 15) as determined by the 1-hour pad test. A physical therapy program composed of Kegel exercises and interferential current was applied to all patients for duration of 5 weeks, with a total of 15 sessions. The number of pads used a day, frequency of voiding (times/day), amount of urinary leakage according to the 1-hour pad test (mg), severity of complaint (as centimeters on visual analogue scale) and pelvic floor muscle strength (cm Hg) were evaluated. Pre-treatment and post-treatment values of these data were compared in each group and among groups. Analyses of the data indicated that the number of pads used a day, frequency of voiding and amount of urinary leakage decreased and pelvic floor muscle strength increased significantly in each group (p < 0.05). Cure in USI was found in 88% of subjects in group I and 18% of subjects in group II (mild intensity). None of the patients in group III (moderate intensity) showed a cure effect. This physical therapy program was found to be more effective in mild and moderate intensities than severe USI. Copyright 2005 S. Karger AG, Basel.

  13. Major Depression in Long-Term Oxygen Therapy Dependent Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Kayhan, Fatih; Ilik, Faik; Karamanli, Harun; Pazarli, Ahmet Cemal; Kayhan, Ayşegül

    2016-05-25

    We aimed to investigate the frequency of major depression (MD) in long-term oxygen therapy (LTOT) dependent chronic obstructive pulmonary disease (COPD) patients and the effect of depression on patients' compliance with the treatment. Fifty-four consecutive patients were enrolled in the study and diagnosed as stage 4 COPD according to Global Initiative for Chronic Obstructive Lung Disease guideline. MD was diagnosed with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition/Clinical Version. Thirty-four (63.0%) patients had MD. MD frequency was significantly higher in patients who were noncompliant with LTOT compared with compliant patients. MD is a common psychiatric disorder in COPD patients receiving LTOT. © 2016 Wiley Periodicals, Inc.

  14. Inpatient cognitive behaviour therapy for adolescents with anorexia nervosa: immediate and longer-term effects

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    Riccardo eDalle Grave

    2014-02-01

    Full Text Available Introduction: Inpatient treatment for anorexia nervosa is often successful in restoring body weight, but a high percentage of patients relapse following discharge. The aim of the present study was to establish the immediate and longer-term effects of a novel inpatient program for adolescents that was designed to produce enduring change. Method: Twenty-seven consecutive patients with severe anorexia nervosa were admitted to a 20-week inpatient treatment program based upon enhanced cognitive behaviour therapy (CBT-E. The patients were assessed before and after hospitalization, and six and 12 months later. Results: Twenty-six patients (96% completed the program. In these patients there was a substantial improvement in weight, eating disorder features and general psychopathology that was well maintained at 12-month follow-up. Conclusions: These findings suggest that inpatient CBT-E is a promising approach to the treatment of adolescents with severe anorexia nervosa.

  15. Animal-Assisted Therapy and Application to Older Adults in Long Term Care

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    Kimberly Ann Mercer

    2015-05-01

    Full Text Available In the past thirty years animal-assisted therapy (AAT has moved beyond anecdotal status to a scientific evidence-based intervention. AAT comes in many shapes and sizes. There are a variety of animals which can be used such as dogs, cats, rabbits, horses, guinea pigs, goats, dolphins, and even fish aquariums. Loneliness is a common theme among older adults in long term care (LTC. Many older adults living in LTC facilities feel isolated. Some have little contact with family members or friends. Many describe feelings of loneliness and withdraw from social activities and interaction with others. Some feel as if they have nothing to look forward to and find no useful purpose in life.  The absence of having another to care for or nurture can also be distressing. The purpose of this project was to explore the use of AAT as an intervention to decrease loneliness in residents living in a LTC setting by introducing visits from a Sphynx cat registered by the Delta Society as a therapy animal. The project sample consisted of seven participants all over the age of 60 years who resided in a LTC facility in Texas. Pre-intervention and post-intervention checklists and open-ended questions were employed to collect data from participants. Analysis of the project findings revealed a notable decrease in loneliness.

  16. [Adherence to long-term therapies and its relevance to epidemiology.

    Science.gov (United States)

    Di Martino, Mirko

    2017-04-01

    In Italy, 40% of the population is affected by chronic pathologies, like diabetes, chronic obstructive pulmonary disease (COPD) or heart failure. Chronic diseases are the leading cause of mortality in the world. Although long-term medications are effective, approximately 50% of patients do not take their medications as prescribed. The lack of medication adherence is associated with an increased risk of hospitalization and death. According to recent research, the low adherence to treatment is a multidimensional problem determined by the interaction of patient-related factors, physician-related factors and health system-related factors. In a study of about 10,000 patients, after a hospital discharge for myocardial infarction, only 63% of patients were adherent to poly-therapy in the following two years. The probability of adherence was influenced by disease severity, therapy-related factors, patient's age and comorbidities, post-hospital follow-up visits, and network organizational forms in primary care. Moreover, a relevant variation in adherence to treatment was observed among health care providers. This heterogeneity raises equity concerns in access to optimal care.

  17. Effect of cinacalcet cessation on hyperparathyroidism in kidney transcaplant patients after long-term dialysis therapy.

    Science.gov (United States)

    Nakai, Kentaro; Fujii, Hideki; Yoshikawa, Mikiko; Kono, Keiji; Yonekura, Yuriko; Goto, Shunsuke; Ishimura, Takeshi; Takeda, Masashi; Fujisawa, Masato; Nishi, Shinichi

    2015-12-01

    Cinacalcet is a promising therapy widely used in dialysis patients with hyperparathyroidism resistant to conventional therapy. However, reports regarding the influence of cinacalcet cessation after long-term use on kidney transplantation patients are few. This retrospective observational study included 40 dialysis patients who underwent kidney transplantation. Creatinine, corrected calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone levels were assessed before and after kidney transplantation according to pretransplant treatment of chronic kidney disease-mineral and bone disorder. Ultrasonography revealed enlargement of the parathyroid in all patients treated with cinacalcet. Although the data at the time of kidney transplantation were comparable, the serum levels of calcium, alkaline phosphatase, and intact parathyroid hormone after kidney transplantation were higher in patients treated with cinacalcet than in those treated without. However, serum phosphate levels in the cinacalcet group were slightly higher at the time of kidney transplantation and significantly lower 3 months later. Mineral abnormalities persisted in kidney transplant patients with enlarged parathyroid glands after discontinuation of cinacalcet treatment. Parathyroidectomy should be considered in kidney transplant candidates with the risk of developing refractory hyperparathyroidism after transplantation.

  18. Sequential Therapy with Minocycline and Candesartan Improves Long-Term Recovery After Experimental Stroke.

    Science.gov (United States)

    Soliman, Sahar; Ishrat, Tauheed; Fouda, Abdelrahman Y; Patel, Ami; Pillai, Bindu; Fagan, Susan C

    2015-08-01

    Minocycline and candesartan have both shown promise as candidate therapeutics in ischemic stroke, with multiple, and somewhat contrasting, molecular mechanisms. Minocycline is an anti-inflammatory, antioxidant, and anti-apoptotic agent and a known inhibitor of matrix metalloproteinases (MMPs). Yet, minocycline exerts antiangiogenic effects both in vivo and in vitro. Candesartan promotes angiogenesis and activates MMPs. Aligning these therapies with the dynamic processes of injury and repair after ischemia is likely to improve success of treatment. In this study, we hypothesize that opposing actions of minocycline and candesartan on angiogenesis, when administered simultaneously, will reduce the benefit of candesartan treatment. Therefore, we propose a sequential combination treatment regimen to yield a better outcome and preserve the proangiogenic potential of candesartan. In vitro angiogenesis was assessed using human brain endothelial cells. In vivo, Wistar rats subjected to 90-min middle cerebral artery occlusion (MCAO) were randomized into four groups: saline, candesartan, minocycline, and sequential combination of minocycline and candesartan. Neurobehavioral tests were performed 1, 3, 7, and 14 days after stroke. Brain tissue was collected on day 14 for assessment of infarct size and vascular density. Minocycline, when added simultaneously, decreased the proangiogenic effect of candesartan treatment in vitro. Sequential treatment, however, preserved the proangiogenic potential of candesartan both in vivo and in vitro, improved neurobehavioral outcome, and reduced infarct size. Sequential combination therapy with minocycline and candesartan improves long-term recovery and maintains candesartan's proangiogenic potential.

  19. Sequential Therapy with Minocycline and Candesartan Improves Long Term Recovery after Experimental Stroke

    Science.gov (United States)

    Soliman, Sahar; Ishrat, Tauheed; Fouda, Abdelrahman Y.; Patel, Ami; Pillai, Bindu; Fagan, Susan C.

    2015-01-01

    Background Minocycline and candesartan have both shown promise as candidate therapeutics in ischemic stroke, with multiple, and somewhat contrasting, molecular mechanisms. Minocycline is an anti-inflammatory, antioxidant and anti-apoptotic agent and a known inhibitor of matrix metalloproteinases (MMPs). Yet, minocycline exerts antiangiogenic effects both in vivo and in vitro. Candesartan promotes angiogenesis and activates MMPs. Aligning these therapies with the dynamic processes of injury and repair after ischemia is likely to improve success of treatment. Objective In this study, we hypothesize that opposing actions of minocycline and candesartan on angiogenesis, when administered simultaneously, will reduce the benefit of candesartan treatment. Therefore, we propose a sequential combination treatment regimen to yield a better outcome and preserve the proangiogenic potential of candesartan. Methods In vitro angiogenesis was assessed using human brain endothelial cells. In vivo, Wistar rats subjected to 90-minute middle cerebral artery occlusion (MCAO) were randomized into 4 groups: saline, candesartan, minocycline and sequential combination of minocycline and candesartan. Neurobehavioral tests were performed 1, 3, 7 and 14 days after stroke. Brain tissue was collected on day 14 for assessment of infarct size and vascular density. Results Minocycline, when added simultaneously, decreased the proangiogenic effect of candesartan treatment in vitro. Sequential treatment, however, preserved the proangiogenic potential of candesartan both in vivo and in vitro, improved neurobehavioral outcome and reduced infarct size. Conclusion Sequential combination therapy with minocycline and candesartan improves long term recovery and maintains candesartan’s proangiogenic potential. PMID:26004281

  20. Dosimetric Inhomogeneity Predicts for Long-Term Breast Pain After Breast-Conserving Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mak, Kimberley S. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Chen, Yu-Hui; Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Punglia, Rinaa S.; Wong, Julia S.; Truong, Linh [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, Massachusetts (United States); Bellon, Jennifer R., E-mail: jbellon@LROC.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, Massachusetts (United States)

    2015-12-01

    Purpose: The objective of this cross-sectional study was to characterize long-term breast pain in patients undergoing breast-conserving surgery and radiation (BCT) and to identify predictors of this pain. Methods and Materials: We identified 355 eligible patients with Tis-T2N0M0 breast cancer who underwent BCT in 2007 to 2011, without recurrent disease. A questionnaire derived from the Late Effects Normal Tissue Task Force (LENT) Subjective, Objective, Management, Analytic (SOMA) scale was mailed with 7 items detailing the severity, frequency, duration, and impact of ipsilateral breast pain over the previous 2 weeks. A logistic regression model identified predictors of long-term breast pain based on questionnaire responses and patient, disease, and treatment characteristics. Results: The questionnaire response rate was 80% (n=285). One hundred thirty-five patients (47%) reported pain in the treated breast, with 19 (14%) having pain constantly or at least daily; 15 (11%) had intense pain. The pain interfered with daily activities in 11 patients (8%). Six patients (4%) took analgesics for breast pain. Fourteen (10%) thought that the pain affected their quality of life. On univariable analysis, volume of breast tissue treated to ≥105% of the prescribed dose (odds ratio [OR] 1.001 per cc, 95% confidence interval [CI] 1.000-1.002; P=.045), volume treated to ≥110% (OR 1.009 per cc, 95% CI 1.002-1.016; P=.012), hormone therapy use (OR 1.95, 95% CI 1.12-3.39; P=.02), and other sites of pain (OR 1.79, 95% CI 1.05-3.07; P=.03) predicted for long-term breast pain. On multivariable analysis, volume ≥110% (OR 1.01 per cc, 95% CI 1.003-1.017; P=.007), shorter time since treatment (OR 0.98 per month, 95% CI 0.96-0.998; P=.03), and hormone therapy (OR 1.84, 95% CI 1.05-3.25; P=.03) were independent predictors of pain. Conclusion: Long-term breast pain was common after BCT. Although nearly half of patients had pain, most considered it tolerable. Dosimetric inhomogeneity

  1. Loss of glucocorticoid receptor expression by DNA methylation prevents glucocorticoid induced apoptosis in human small cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Paul Kay

    Full Text Available Human small cell lung cancer (SCLC is highly aggressive, and quickly develops resistance to therapy. SCLC cells are typically insensitive to glucocorticoids due to impaired glucocorticoid receptor (GR expression. This is important as we have previously shown that expression of a GR transgene induces cell death in-vitro, and inhibits tumor growth in-vivo. However, the underlying mechanism for loss of GR expression is unknown. The SCLC cell line, DMS79, has low GR expression, compared to non-SCLC cell lines and normal bronchial epithelial cells. Retroviral GR expression in DMS79 cells caused activation of the apoptotic pathway as evidenced by marked induction of caspase-3 activity. Methylation analysis of the GR promoter revealed some methylation in the 1D, and 1E promoters of the GR gene, however the ubiquitous constitutively active 1C promoter was heavily methylated. In the 1C promoter there was a highly significant increase in DNA methylation in a panel of 14 human SCLC cell lines compared to a mixed panel of GR expressing, and non-expressing cell lines, and to peripheral blood mononuclear cells. Furthermore, within the panel of SCLC cell lines there was a significant negative correlation seen between methylation of the 1C promoter, and GR protein expression. Reversal of GR gene methylation with DNA methyltransferase inhibition caused increased GR mRNA and protein expression in SCLC but not non-SCLC cells. This resulted in increased Gc sensitivity, decreased Bcl-2 expression and increased caspase-3 activity in SCLC cells. These data suggest that DNA methylation decreases GR gene expression in human SCLC cells, in a similar manner to that for conventional tumor suppressor genes.

  2. Internet-based therapy for adolescents with chronic fatigue syndrome: long-term follow-up.

    Science.gov (United States)

    Nijhof, Sanne L; Priesterbach, Loudy P; Uiterwaal, Cuno S P M; Bleijenberg, Gijs; Kimpen, Jan L L; van de Putte, Elise M

    2013-06-01

    Cognitive behavioral therapy (CBT) is known to be an effective treatment of adolescents with chronic fatigue syndrome (CFS), but its availability is limited. Fatigue in Teenagers on the Internet (FITNET), an Internet-based CBT program for adolescents with CFS, has been developed as an alternative to face-to-face CBT. Recently, its short-term effectiveness has been proven in a randomized clinical trial. Here we aimed to assess the long-term outcome of CFS in adolescents after FITNET treatment and after usual care. In addition, factors related to recovery at long-term follow-up (LTFU) for adolescents treated with the FITNET program were investigated. The study was an LTFU of participants of the FITNET trial. Data were completed for 112 (88.2%) of 127 approached FITNET study participants. Primary outcomes were fatigue severity (Checklist Individual Strength-20), physical functioning (87-item Child Health Questionnaire), and school/work attendance. After a mean follow-up of 2.7 years, 66 (58.9%) adolescents had recovered from CFS. Most adolescents who recovered directly after treatment with FITNET were still recovered at LTFU. At LTFU there was no difference between the recovery rates for the different treatment strategies (original randomization: FITNET [64%] versus any form of usual care [52.8%]). Per additional month of "pretreatment disease duration," the odds for recovery were 4% lower (odds ratio: 0.96; 95% confidence interval: 0.93-0.99; P = .016), and per added point on "focus on bodily symptoms" (Body Consciousness Scale) of the mother (0-20 points) the odds for recovery were 11% lower (odds ratio: 0.89; 95% confidence interval: 0.80-0.99; P = .029). The short-term effectiveness of Internet-based CBT on adolescent CFS is maintained at LTFU. At LTFU, usual care led to similar recovery rates, although these rates were achieved at a slower pace.

  3. Glucocorticoid-cholinergic interactions in the dorsal striatum in memory consolidation of inhibitory avoidance training

    Science.gov (United States)

    Sánchez-Resendis, Oscar; Medina, Andrea C.; Serafín, Norma; Prado-Alcalá, Roberto A.; Roozendaal, Benno; Quirarte, Gina L.

    2012-01-01

    Extensive evidence indicates that glucocorticoid hormones act in a variety of brain regions to enhance the consolidation of memory of emotionally motivated training experiences. We previously reported that corticosterone, the major glucocorticoid in the rat, administered into the dorsal striatum immediately after inhibitory avoidance training dose-dependently enhances memory consolidation of this training. There is also abundant evidence that the intrinsic cholinergic system of the dorsal striatum is importantly involved in memory consolidation of inhibitory avoidance training. However, it is presently unknown whether these two neuromodulatory systems interact within the dorsal striatum in the formation of long-term memory. To address this issue, we first investigated in male Wistar rats whether the muscarinic receptor agonist oxotremorine administered into the dorsal striatum immediately after inhibitory avoidance training enhances 48 h retention of the training. Subsequently, we examined whether an attenuation of glucocorticoid signaling by either a systemic administration of the corticosterone-synthesis inhibitor metyrapone or an intra-striatal infusion of the glucocorticoid receptor (GR) antagonist RU 38486 would block the memory enhancement induced by oxotremorine. Our findings indicate that oxotremorine dose-dependently enhanced 48 h retention latencies, but that the administration of either metyrapone or RU 38486 prevented the memory-enhancing effect of oxotremorine. In the last experiment, corticosterone was infused into the dorsal striatum together with the muscarinic receptor antagonist scopolamine immediately after inhibitory avoidance training. Scopolamine blocked the enhancing effect of corticosterone on 48 h retention performance. These findings indicate that there are mutual interactions between glucocorticoids and the striatal cholinergic system in enhancing the consolidation of memory of inhibitory avoidance training. PMID:22737110

  4. Impact of total cumulative glucocorticoid dose on bone mineral density in patients with 21-hydroxylase deficiency.

    Science.gov (United States)

    Chakhtoura, Zeina; Bachelot, Anne; Samara-Boustani, Dinane; Ruiz, Jean-Charles; Donadille, Bruno; Dulon, Jérôme; Christin-Maître, Sophie; Bouvattier, Claire; Raux-Demay, Marie-Charles; Bouchard, Philippe; Carel, Jean-Claude; Leger, Juliane; Kuttenn, Frédérique; Polak, Michel; Touraine, Philippe

    2008-06-01

    It remains controversial whether long-term glucocorticoids are charged of bone demineralization in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The aim of this study was to know whether cumulative glucocorticoid dose from the diagnosis in childhood to adulthood in patients with CAH had a negative impact on bone mineral density (BMD). This was a retrospective study. Thirty-eight adult patients with classical and non-classical CAH were included. BMD was measured in the lumbar spine and femoral neck. Total cumulative glucocorticoid (TCG) and total average glucocorticoid (TAG) doses were calculated from pediatric and adult files. We showed a difference between final and target heights (-0.82+/-0.92 s.d. for women and -1.31+/-0.84 s.d. for men; P<0.001). Seventeen patients (44.7%) had bone demineralization (35.7% of women and 70% of men). The 28 women had higher BMD than the 10 men for lumbar (-0.26+/-1.20 vs -1.25+/-1.33 s.d.; P=0.02) and femoral T-scores (0.21+/-1.30 s.d. versus -1.08+/-1.10 s.d.; P=0.007). In the salt-wasting group, women were almost significantly endowed with a better BMD than men (P=0.053). We found negative effects of TCG, TAG on lumbar (P<0.001, P=0.002) and femoral T-scores (P=0.006, P<0.001), predominantly during puberty. BMI was protective on BMD (P=0.006). The TCG is an important factor especially during puberty for a bone demineralization in patients with 21-hydroxylase deficiency. The glucocorticoid treatment should be adapted particularly at this life period and preventive measures should be discussed in order to limit this effect.

  5. Dominance rank causally affects personality and glucocorticoid regulation in female rhesus macaques.

    Science.gov (United States)

    Kohn, Jordan N; Snyder-Mackler, Noah; Barreiro, Luis B; Johnson, Zachary P; Tung, Jenny; Wilson, Mark E

    2016-12-01

    Low social status is frequently associated with heightened exposure to social stressors and altered glucocorticoid regulation by the hypothalamic-pituitary-adrenal (HPA) axis. Additionally, personality differences can affect how individuals behave in response to social conditions, and thus may aggravate or protect against the effects of low status on HPA function. Disentangling the relative importance of personality from the effects of the social environment on the HPA axis has been challenging, since social status can predict aspects of behavior, and both can remain stable across the lifespan. To do so here, we studied an animal model of social status and social behavior, the rhesus macaque (Macaca mulatta). We performed two sequential experimental manipulations of dominance rank (i.e., social status) in 45 adult females, allowing us to characterize personality and glucocorticoid regulation (based on sensitivity to the exogenous glucocorticoid dexamethasone) in each individual while she occupied two different dominance ranks. We identified two behavioral characteristics, termed 'social approachability' and 'boldness,' which were highly social status-dependent. Social approachability and a third dimension, anxiousness, were also associated with cortisol dynamics in low status females, suggesting that behavioral tendencies may sensitize individuals to the effects of low status on HPA axis function. Finally, we found that improvements in dominance rank increased dexamethasone-induced acute cortisol suppression and glucocorticoid negative feedback. Our findings indicate that social status causally affects both behavioral tendencies and glucocorticoid regulation, and that some behavioral tendencies also independently affect cortisol levels, beyond the effects of rank. Together, they highlight the importance of considering personality and social status together when investigating their effects on HPA axis function. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Context Modulates Outcome of Perinatal Glucocorticoid Action in the Brain

    Directory of Open Access Journals (Sweden)

    Edo Ronald ede Kloet

    2014-07-01

    Full Text Available Prematurely born infants may be at risk, because of inadequate maturation of tissues. If there are signs of preterm birth, it has become common practice therefore to treat either antenatally the mother or postnatally the infant with glucocorticoids to accelerate tissue development, particularly of the lung. However, this life-saving early glucocorticoid treatment was found to increase the risk of adverse outcome in later life. In one animal study the authors reported a 25% shorter lifespan of rats treated as newborns with the synthetic glucocorticoid dexamethasone, but sofar this finding has not been replicated. After a brief clinical introduction, we discuss studies in rodents designed to examine how perinatal glucocorticoid action affects the developing brain. It appears that the perinatal action of the glucocorticoid depends on the context and the timing as well as the type of administered steroid. The type of steroid is important because the endogenous glucocorticoids cortisol and corticosterone bind to two distinct receptor populations, i.e. mineralocorticoid (MR and glucocorticoid receptors (GR, while synthetic glucocorticoids predominantly bind to the GR. In addition, if given antenatally hydrocortisone is inactivated in the placenta by 11β-HSD type 2, and dexamethasone is not. With respect to timing, the outcome of glucocorticoid effects is different in early vs late phases of brain development. The context refers to the environmental input that can affect the susceptibility to glucocorticoid action in the newborn rodent brain; early handling of pups and maternal care obliterate effects of postnatal dexamethasone treatment. Context also refers to coping with environmental conditions in later life, for which the individual may have been programmed epigenetically by early life experience. This knowledge of determinants affecting the outcome of perinatal glucocorticoid exposure may have clinical implications for the treatment of

  7. Context modulates outcome of perinatal glucocorticoid action in the brain.

    Science.gov (United States)

    de Kloet, E Ronald; Claessens, Sanne E F; Kentrop, Jiska

    2014-01-01

    Prematurely born infants may be at risk, because of inadequate maturation of tissues. If there are signs of preterm birth, it has become common practice therefore to treat either antenatally the mother or postnatally the infant with glucocorticoids to accelerate tissue development, particularly of the lung. However, this life-saving early glucocorticoid treatment was found to increase the risk of adverse outcome in later life. In one animal study, the authors reported a 25% shorter lifespan of rats treated as newborns with the synthetic glucocorticoid dexamethasone, but so far this finding has not been replicated. After a brief clinical introduction, we discuss studies in rodents designed to examine how perinatal glucocorticoid action affects the developing brain. It appears that the perinatal action of the glucocorticoid depends on the context and the timing as well as the type of administered steroid. The type of steroid is important because the endogenous glucocorticoids cortisol and corticosterone bind to two distinct receptor populations, i.e., mineralocorticoid and glucocorticoid receptors (GR), while synthetic glucocorticoids predominantly bind to the GR. In addition, if given antenatally hydrocortisone is inactivated in the placenta by 11β-HSD type 2, and dexamethasone is not. With respect to timing, the outcome of glucocorticoid effects is different in early vs. late phases of brain development. The context refers to the environmental input that can affect the susceptibility to glucocorticoid action in the newborn rodent brain; early handling of pups and maternal care obliterate effects of post-natal dexamethasone treatment. Context also refers to coping with environmental conditions in later life, for which the individual may have been programed epigenetically by early-life experience. This knowledge of determinants affecting the outcome of perinatal glucocorticoid exposure may have clinical implications for the treatment of prematurely born infants.

  8. Long-Term Results of 2-Dimensional Radiation Therapy in Patients with Nasopharyngeal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Nam Kwon; Park, Young Je; Yang, Dae Sik; Yoon, Won Sup; Lee, Suk; Kim, Chul Yong [Dept. of Radiation Oncology, Korea University College of Medicine, Seoul (Korea, Republic of)

    2010-11-15

    To analyze the treatment outcomes, complications, prognostic factors after a long-term follow-up of patients with nasopharyngeal carcinoma treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Between December 1981 and December 2006, 190 eligible patients with non-metastatic nasopharyngeal carcinoma were treated at our department with a curative intent. Of these patients, 103 were treated with RT alone and 87 patients received CCRT. The median age was 49 years (range, 8-78 years). The distributions of clinical stage according to the AJCC 6th edition included I: 7 (3.6%), IIA: 8 (4.2%), IIB: 33 (17.4%), III: 82 (43.2%), IVA: 31 (16.3%), IVB: 29 (15.3%). The accumulated radiation doses to the primary tumor ranged from 66.6-87.0 Gy (median, 72 Gy). Treatment outcomes and prognostic factors were retrospectively analyzed. Acute and late toxicities were assessed using the RTOG criteria. A total of 96.8% (184/190) of patients completed the planned treatment. With a mean follow-up of 73 months (range, 2-278 months; median, 52 months), 93 (48.9%) patients had relapses that were local 44 (23.2%), nodal 13 (6.8%), or distant 49 (25.8%). The 5- and 10-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) rates were 55.6% and 44.5%, 54.8% and 51.3%, in addition to 65.3% and 57.4%, respectively. Multivariate analyses revealed that CCRT, age, gender, and stage were significant prognostic factors for OS. The CCRT and gender were independent prognostic factors for both DFS and DSS. There was no grade 4 or 5 acute toxicity, but grade 3 mucositis and hematologic toxicity were present in 42 patients (22.1%) and 18 patients (9.5%), respectively. During follow-up, grade 3 hearing loss in 9 patients and trismus in 6 patients were reported. The results of our study were in accordance with findings of previous studies and we confirmed that CCRT, low stage, female gender, and young age were related to improvement in OS

  9. Expression and glucocorticoid-regulation of "Bam", a novel BH3-only transcript in acute lymphoblastic leukemia.

    Science.gov (United States)

    Mansha, Muhammad; Wasim, Muhammad; Kofler, Anita; Ploner, Christian

    2012-05-01

    Apoptosis is a morphologically defined form of cell death that plays a major role in cell physiology, pathology and cancer therapy. The Bcl-2 family of pro- and anti-apoptotic molecules is a key regulator of this phenomenon, with the sub-family of BH3-only molecules serving as activators and/or facilitators. Apoptosis induced by glucocorticoids (GC) is a central component in the therapy of acute lymphoblastic leukemia (ALL), and defining its molecular basis and that of GC resistance is crucial for therapeutic improvements. We recently identified a novel transcript from the BCL2L11/Bim locus, termed "Bam", by affymetrix based whole genome expression profiling performed on 27 children (13 were already published) with ALL and many additional biological systems. Most children that induced Bam also induced Bim as well, in some cases Bam induction was more pronounced than that of Bim and in one patient only the Bam, but not Bim was induced. In C7H2, PreB697, Jurkat-GR(wt) and GC-sensitive (S-lines), this transcript was induced by GC in a translation-independent manner, suggesting that direct transcriptional induction of this BH3-only molecule by GC might cause apoptosis in at least ALL children and other biological systems.

  10. Randomized, controlled trial of the effectiveness of short-term dynamic psychotherapy and cognitive therapy for cluster C personality disorders.

    Science.gov (United States)

    Svartberg, Martin; Stiles, Tore C; Seltzer, Michael H

    2004-05-01

    This study compared the effectiveness of short-term dynamic psychotherapy and cognitive therapy for outpatients with cluster C personality disorders. Patients (N=50) who met the criteria for one or more cluster C personality disorders and not for any other personality disorders were randomly assigned to receive 40 weekly sessions of short-term dynamic psychotherapy or cognitive therapy. The most common axis I disorders in the patient group were anxiety and depression diagnoses. Therapists were experienced, full-time clinicians and were receiving manual-guided supervision. Outcome variables included symptom distress, interpersonal problems, and core personality pathology. Measures were administered repeatedly during and after treatment, and change was assessed longitudinally by means of growth modeling procedures. The overall patient group showed, on average, statistically significant improvements on all measures during treatment and also during a 2-year follow-up period. Significant changes in symptom distress after treatment were found for the group of patients who received short-term dynamic psychotherapy but not for the cognitive therapy patients. Despite these differences in intragroup changes, no statistically significant differences between the short-term dynamic psychotherapy group and cognitive therapy group were found on any measure for any time period. Two years after treatment, 54% of the short-term dynamic psychotherapy patients and 42% of the cognitive therapy patients had recovered symptomatically, whereas approximately 40% of the patients in both groups had recovered in terms of interpersonal problems and personality functioning. Both short-term dynamic psychotherapy and cognitive therapy have a place in the treatment of patients with cluster C personality disorders. However, factors other than treatment modality may discriminate better between successful and poor outcomes. Such factors should be explored in future studies.

  11. Glucocorticoids Have Opposing Effects on Liver Fibrosis in Hepatic Stellate and Immune Cells

    OpenAIRE

    Kim, Kang Ho; Lee, Jae Man; Zhou, Ying; Harpavat, Sanjiv; Moore, David D.

    2016-01-01

    Liver fibrosis is a reversible wound-healing process that is protective in the short term, but prolonged fibrotic responses lead to excessive accumulation of extracellular matrix components that suppresses hepatocyte regeneration, resulting in permanent liver damage. Upon liver damage, nonparenchymal cells including immune cells and hepatic stellate cells (HSCs) have crucial roles in the progression and regression of liver fibrosis. Here, we report differential roles of the glucocorticoid rec...

  12. [Long-term outcomes of children treated with continuous renal replacement therapy].

    Science.gov (United States)

    Almarza, S; Bialobrzeska, K; Casellas, M M; Santiago, M J; López-Herce, J; Toledo, B; Carrillo, Á

    2015-12-01

    The objective of this study is to analyze long-term outcomes and kidney function in children requiring continuous renal replacement therapy (CRRT) after an acute kidney injury episode. A retrospective observational study was performed using a prospective database of 128 patients who required CRRT admitted to the pediatric intensive care unit between years 2006 and 2012. The subsequent outcomes were assessed in those surviving at hospital discharge. Of the 128 children who required RRT in the pediatric intensive care unit, 71 survived at hospital discharge (54.4%), of whom 66 (92.9%) were followed up. Three patients had chronic renal failure prior to admission to the NICU. Of the 63 remaining patients, 6 had prolonged or relapses of renal function disturbances, but only one patient with atypical Hemolytic Uremic Syndrome developed end-stage renal failure. The rest had normal kidney function at the last check-up. Most of surviving children that required CRRT have a positive outcome later on, presenting low mortality rates and recovery of kidney function in the medium term. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  13. Music in the mountains: creating sustainable therapy programs from short-term missions

    Directory of Open Access Journals (Sweden)

    Rachel Foxell

    2015-01-01

    Full Text Available This field report describes the experiences of a Registered Music Therapist (RMT living, working, and musicking1 during a short-term health mission to Northern India. Using a sustainability approach, collaboration with several local and global health organisations resulted in the development of a therapeutic music program for children with disabilities. Disability is a complex phenomenon, and in rural areas of India, disability is viewed as a foundation for shame and exclusion. The Community-based project, Samvedna, oversees the therapy, healthcare, and education of over 100 children with a disability in remote villages and is heavily involved in disability advocacy in the area. Sustainable programs are more effective for individuals and communities in both the short and long term. RMTs and other health professionals can be instrumental in setting up sustainable programs, such as teaching specific skills and knowledge to local teams, provided there is thorough preparation and ongoing collaboration to determine the priorities and expectations of the program.

  14. Long-term follow-up after cognitive behaviour therapy for chronic fatigue syndrome.

    Science.gov (United States)

    Janse, Anthonie; Nikolaus, Stephanie; Wiborg, Jan F; Heins, Marianne; van der Meer, Jos W M; Bleijenberg, Gijs; Tummers, Marcia; Twisk, Jos; Knoop, Hans

    2017-06-01

    Cognitive behaviour therapy (CBT) is an effective treatment for chronic fatigue syndrome (CFS). Main aim was to determine whether treatment effects were maintained up to 10years after treatment. Participants (n=583) of previously published studies on the effects of CBT for CFS were contacted for a long-term follow-up assessment. They completed questionnaires on main outcomes fatigue severity (CIS) and physical functioning (SF-36). The course of these outcomes since post-treatment assessment was examined using mixed model analyses. Between 21 and 125months after finishing CBT, 511 persons (response rate 88%) completed a follow-up assessment. At follow-up, mean fatigue severity was significantly increased to 37.60 (SD=12.76) and mean physical functioning significantly decreased to 73.16 (SD=23.56) compared to post-treatment assessment. At follow-up still 37% of the participants had fatigue scores in the normal range and 70% were not impaired in physical functioning. Positive effects of CBT for CFS on fatigue and physical functioning were partly sustained at long-term follow-up. However, a subgroup of patients once again reported severe fatigue, and compromised physical functioning. Further research should elucidate the reasons for this deterioration to facilitate the development of treatment strategies for relapse prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Long-term benefit of enzyme replacement therapy in Pompe disease: A 5-year prospective study.

    Science.gov (United States)

    Kuperus, Esther; Kruijshaar, Michelle E; Wens, Stephan C A; de Vries, Juna M; Favejee, Marein M; van der Meijden, Jan C; Rizopoulos, Dimitris; Brusse, Esther; van Doorn, Pieter A; van der Ploeg, Ans T; van der Beek, Nadine A M E

    2017-12-05

    To determine the effect of enzyme replacement therapy (ERT) after 5 years and to identify predictors for a favorable response because few data are available on the long-term efficacy of ERT in Pompe disease. We included 102 adult patients with Pompe disease in a nationwide, prospective cohort study. We assessed muscle strength (manual muscle testing with Medical Research Council [MRC] grading, handheld dynamometry [HHD]), muscle function (6-minute walk test, Quick Motor Function Test), daily life activities (Rasch-Built Pompe-Specific Activity [R-PAct] Scale), and pulmonary function (forced vital capacity [FVC] in upright and supine positions, maximum inspiratory and expiratory pressures) at 3- to 6-month intervals before and after the start of ERT. Data were analyzed with linear mixed-effects models for repeated measurements. Median follow-up duration was 6.1 years (range 0.4-7.9 years), of which 5.0 years (range 0.2-7.3 years) were during ERT. Treated patients had better muscle strength (MRC sum score +6.6 percentage points [pp]; HHD sum score +9.6 pp, both p Pompe disease, with a peak effect at ≈2 to 3 years of treatment. This study provides Class IV evidence that for patients with Pompe disease, long-term ERT positively affects muscle strength, pulmonary function, and daily life activities. © 2017 American Academy of Neurology.

  16. Glucocorticoid-Induced Osteoporosis in Children with 21-Hydroxylase Deficiency

    Directory of Open Access Journals (Sweden)

    Annamaria Ventura

    2013-01-01

    Full Text Available 21-Hydroxylase deficiency (21-OHD is the most common cause of congenital adrenal hyperplasia (CAH, resulting from deletions or mutations of the P450 21-hydroxylase gene (CYP21A2. Children with 21-OHD need chronic glucocorticoid (cGC therapy, both to replace congenital deficit in cortisol synthesis and to reduce androgen secretion by adrenal cortex. GC-induced osteoporosis (GIO is the most common form of secondary osteoporosis that results in an early, transient increase in bone resorption accompanied by a decrease in bone formation, maintained for the duration of GC therapy. Despite the conflicting results in the literature about the bone status on GC-treated patients with 21-OHD, many reports consider these subjects to be at risk for osteoporosis and fractures. In bone cells, at the molecular level, GCs regulate various functions including osteoblastogenesis, osteoclastogenesis, and the apoptosis of osteoblasts and osteocytes. In this paper, we focus on the physiology and biosynthesis of endogenous steroid hormones as well as on the effects of GCs on bone cells, highlighting the pathogenetic mechanism of GIO in children with 21-OHD.

  17. Evidence for Long-term Efficacy and Safety of Gene Therapy for Wiskott–Aldrich Syndrome in Preclinical Models

    OpenAIRE

    Marangoni, Francesco; Bosticardo, Marita; Charrier, Sabine; Draghici, Elena; Locci, Michela; Scaramuzza, Samantha; Panaroni, Cristina; Ponzoni, Maurilio; Sanvito, Francesca; Doglioni, Claudio; Liabeuf, Marie; Gjata, Bernard; Montus, Marie; Siminovitch, Katherine; Aiuti, Alessandro

    2009-01-01

    Wiskott–Aldrich Syndrome (WAS) is a life-threatening X-linked disease characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancies. Gene therapy could represent a therapeutic option for patients lacking a suitable bone marrow (BM) donor. In this study, we analyzed the long-term outcome of WAS gene therapy mediated by a clinically compatible lentiviral vector (LV) in a large cohort of wasnull mice. We demonstrated stable and full donor engraftment and Wiskott–Aldrich Syn...

  18. Efficacy of short-term Yoga therapy program on quality of life in patients with psychosomatic ailments

    OpenAIRE

    Garg, Sumit; Ramya, C. S.; Shankar, Vinutha; Kutty, Karthiyanee

    2015-01-01

    Objective: The aim was to study the effect of short-term Yoga therapy program on quality of life in patients suffering from psychosomatic ailments. Methods: Sample size and Study period: All the subjects coming to SVYASA AROGYADHAMA in month of July 2011 for Yoga therapy for various psychosomatic ailments and were free of any primary psychiatric illness and volunteering to participate were enrolled in the study after taking informed consent. Their physical condition was healthy enough to prac...

  19. Chromatin Architecture Defines the Glucocorticoid Response

    Science.gov (United States)

    Burd, Craig J.; Archer, Trevor K.

    2013-01-01

    The glucocorticoid receptor (GR) functions to regulate a wide group of physiological processes through hormone inducible interaction with genomic loci and subsequent manipulation of the transcriptional output of target genes. Despite expression in a wide variety of tissues, the GR has diverse roles that are regulated tightly in a cell type specific manner. With the advent of whole genome approaches, the details of that diversity and the mechanisms regulating them are beginning to be elucidated. This review aims describe the recent advances detailing the role chromatin structure plays in dictating GR specificity. PMID:23545159

  20. Antenatal glucocorticoid treatment affects hippocampal development in mice.

    Directory of Open Access Journals (Sweden)

    Cornelle W Noorlander

    Full Text Available Synthetic glucocorticoids are administered to pregnant women at risk for preterm delivery, to enhance fetal lung maturation. The benefit of this treatment is well established, however caution is necessary because of possible unwanted side effects on development of different organ systems, including the brain. Actions of glucocorticoids are mediated by corticosteroid receptors, which are highly expressed in the hippocampus, a brain structure involved in cognitive functions. Therefore, we analyzed the effects of a single antenatal dexamethasone treatment on the development of the mouse hippocampus. A clinically relevant dose of dexamethasone (0.4 mg/kg was administered to pregnant mice at embryonic day 15.5 and the hippocampus was analyzed from embryonic day 16 until adulthood. We investigated the effects of dexamethasone treatment on anatomical changes, apoptosis and proliferation in the hippocampus, hippocampal volume and on total body weight. Our results show that dexamethasone treatment reduced body weight and hippocampal volume transiently during development, but these effects were no longer detected at adulthood. Dexamethasone treatment increased the number of apoptotic cells in the hippocampus until birth, but postnatally no effects of dexamethasone treatment on apoptosis were found. During the phase with increased apoptosis, dexamethasone treatment reduced the number of proliferating cells in the subgranular zone of the dentate gyrus. The number of proliferative cells was increased at postnatal day 5 and 10, but was decreased again at the adult stage. This latter long-term and negative effect of antenatal dexamethasone treatment on the number of proliferative cells in the hippocampus may have important implications for hippocampal network function.

  1. On the HORYZON: moderated online social therapy for long-term recovery in first episode psychosis.

    Science.gov (United States)

    Alvarez-Jimenez, M; Bendall, S; Lederman, R; Wadley, G; Chinnery, G; Vargas, S; Larkin, M; Killackey, E; McGorry, P D; Gleeson, J F

    2013-01-01

    Early intervention services have demonstrated improved outcomes in first episode psychosis (FEP); however, recent evidence shows that treatment benefits may not be sustainable over time. These findings have resulted in repeated recommendations for the implementation of longer term treatment programs. An Internet-based intervention specifically designed for young people with psychosis may provide a cost-effective alternative to prevent loss of treatment benefits from early intervention. Our multi-disciplinary team has developed a highly novel online intervention (HORYZONS) in regular consultation with stakeholders within a specialist early psychosis program. HORYZONS integrates: i) peer-to-peer social networking, ii) individually tailored interactive psychosocial interventions, and iii) expert interdisciplinary and peer-moderation in a coherent platform designed to improve long-term outcomes in FEP. The acceptability, safety and initial clinical benefits of HORYZONS were examined through a 1-month pilot study with 20 participants with FEP. There were no dropouts during the pilot study. Seventy per cent of participants utilised the system for at least 3weeks, 95% used the social networking features, and 60% completed at least 3 therapy modules. System usage was high during the study. There were no incidents and the majority of participants reported feeling safe, empowered and more socially connected using HORYZONS. Analysis revealed a significant reduction in depressive symptoms at follow-up. Our results indicate that HORYZONS is feasible, engaging and safe and may augment social connectedness and empowerment in FEP. These findings have significant implications for the enhancement of specialist FEP services. The potential of HORYZONS to improve long-term recovery is worthy of further investigation. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Long-Term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD)

    Science.gov (United States)

    2012-01-01

    Executive Summary In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions. After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses. The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html. Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive

  3. Glucocorticoid receptors in monocytes in type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    Damm, P; Binder, C

    1989-01-01

    Glucocorticoid receptor binding characteristics were investigated in 8 males with poorly controlled Type 1 diabetes mellitus and 14 healthy males. The cell type studied was monocytes, and a method for correction for heterogeneity in glucocorticoid binding in a mononuclear leucocyte population was...

  4. Glucocorticoids facilitate the retention of acquired immobility during forced swimming

    NARCIS (Netherlands)

    Veldhuis, H D; De Korte, C C; De Kloet, E R

    1985-01-01

    The adrenalectomy-induced decrease in the level of immobility during a 5 min retest period in the Porsolt swimming test could be reversed by glucocorticoids administered s.c. 15 min after the initial forced swimming exposure. The synthetic glucocorticoids dexamethasone and RU 28362 were active in

  5. The impact of insulin resistance, gender, genes, glucocorticoids and ...

    African Journals Online (AJOL)

    2010-11-15

    Nov 15, 2010 ... Review: The impact of insulin resistance, gender, genes, glucocorticoids and ethnicity on body fat distribution. 2010 Volume 15 No 3 ... Understanding the factors that regulate body fat distribution should not only give insight ... glucocorticoids may sculpture body fat and change the pathogenicity of obesity.

  6. Profound postanesthetic hypoglycemia attributable to glucocorticoid deficiency in 2 dogs.

    Science.gov (United States)

    Lane, I F; Matwichuk, C L; Carpenter, L G; Behrend, E N

    1999-01-01

    Glucocorticoid deficiency was diagnosed as the cause of severe postanesthetic hypoglycemia in 2 dogs. Prior signs of systemic illness were not described in either dog; however, preoperative hematologic findings were consistent with glucocorticoid deficiency. Fasting hypoglycemia is a possible complication of chronic adrenal insufficiency primarily because of impaired gluconeogenesis. PMID:10416071

  7. Diretrizes para prevenção e tratamento da osteoporose induzida por glicocorticoide Guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis

    Directory of Open Access Journals (Sweden)

    Rosa Maria Rodrigues Pereira

    2012-08-01

    and treated in all patients initiating or already on GC. There are several recommendations on this topic elaborated by several international societies, but consensus still lacks. Recently, the American College of Rheumatology has published new recommendations, but they are based on the WHO Fracture Risk Assessment Tool (FRAX® to evaluate the risk for each individual, and, thus, cannot be completely used for the Brazilian population. Thus, the Committee for Osteoporosis and Bone Metabolic Disorders of the Brazilian Society of Rheumatology, along with the Brazilian Medical Association and the Brazilian Association of Physical Medicine and Rehabilitation, has elaborated the Brazilian Guidelines for Glucocorticoid-Induced Osteoporosis (GIO, based on the better available scientific evidence and/or expert experience. METHOD OF EVIDENCE COLLECTION: The bibliographic review of scientific articles of this guideline was performed in the MEDLINE database. The search for evidence was based on real clinical scenarios, and used the following keywords (MeSH terms: Osteoporosis, Osteoporosis/ chemically induced*= (Glucocorticoids= Adrenal Cortex Hormones, Steroids, Glucocorticoids, Glucocorticoids/administration and dosage, Glucocorticoids/therapeutic use, Glucocorticoids/adverse effects, Prednisone/adverse effects, Dose-Response Relationship, Drug, Bone Density/drug effects, Bone Density Conservation Agents/pharmacological action, Osteoporosis/prevention & control, Calcium, Vitamin D, Vitamin D deficiency, Calcitriol, Receptors, Calcitriol; 1-hydroxycholecalciferol, Hydroxycholecalciferols, 25-Hydroxyvitamin D3 1-alpha-hydroxylase OR Steroid Hydroxylases, Prevention and Control, Spinal fractures/prevention & control, Fractures, Spontaneous, Lumbar Vertebrae/injuries, Lifestyle, Alcohol Drinking, Smoking OR tobacco use disorder, Movement, Resistance Training, Exercise Therapy, Bone density OR Bone and Bones, Dual-Energy X-Ray Absorptiometry OR Absorptiometry Photon OR DXA

  8. Acquired hemophilia as first manifestation of breast carcinoma in a man under long-term spironolactone therapy.

    Science.gov (United States)

    Lamy, Olivier; Elmiger, Hubert; Fiche, Maryse; Bauer, Jean; Livio, FranCoise

    2004-04-01

    A 69-year-old man under long-term spironolactone therapy (16 years) was hospitalized with spontaneous hematoma on the trunk and extremities. Coagulation studies disclosed an acquired hemophilia that was successfully treated with human factor VIII for a few days and immunosuppressive agents for several months. Physical examination revealed bilateral gynecomastia and an upper left quadrant breast nodule. Complete staging was unremarkable. Complete left mastectomy was performed. Histopathology showed invasive ductal carcinoma, expressing positivity for estrogen and progesterone receptors. The acquired hemophilia was considered to be a paraneoplasic syndrome. The question of a linkage between long-term spironolactone therapy and breast carcinoma is discussed.

  9. Nonsurgical Outpatient Therapies for the Management of Female Stress Urinary Incontinence: Long-Term Effectiveness and Durability

    Directory of Open Access Journals (Sweden)

    G. Willy Davila

    2011-01-01

    Results. Thirty-two clinical trial reports were included. Prospective long-term studies of pelvic floor rehabilitation were limited but indicated significant improvements with treatment adherence for at least 12 months. Poor initial tolerability with duloxetine resulted in substantial discontinuation. Most patients receiving transurethral radiofrequency collagen denaturation or urethral bulking agents reported significant long-term improvements, generally good tolerability, and safety. Conclusions. Conservative therapy is an appropriate initial approach for female SUI, but if therapy fails, radiofrequency collagen denaturation or bulking agents may be an attractive intermediate management step or alternative to surgery.

  10. National study of discontinuation of long-term opioid therapy among veterans.

    Science.gov (United States)

    Vanderlip, Erik R; Sullivan, Mark D; Edlund, Mark J; Martin, Bradley C; Fortney, John; Austen, Mark; Williams, James S; Hudson, Teresa

    2014-12-01

    Veterans have high rates of chronic pain and long-term opioid therapy (LTOT). Understanding predictors of discontinuation from LTOT will clarify the risks for prolonged opioid use and dependence among this population. All veterans with at least 90 days of opioid use within a 180-day period were identified using national Veteran's Health Affairs (VHA) data between 2009 and 2011. Discontinuation was defined as 6 months with no opioid prescriptions. We used Cox proportional hazards analysis to determine clinical and demographic correlates for discontinuation. A total of 550,616 veterans met criteria for LTOT. The sample was primarily male (93%) and white (74%), with a mean age of 57.8 years. The median daily morphine equivalent dose was 26 mg, and 7% received high-dose (>100mg MED) therapy. At 1 year after initiation, 7.5% (n=41,197) of the LTOT sample had discontinued opioids. Among those who discontinued (20%, n=108,601), the median time to discontinuation was 317 days. Factors significantly associated with discontinuation included both younger and older age, lower average dosage, and having received less than 90 days of opioids in the previous year. Although tobacco use disorders decreased the likelihood of discontinuation, co-morbid mental illness and substance use disorders increased the likelihood of discontinuation. LTOT is common in the VHA system and is marked by extended duration of use at relatively low daily doses with few discontinuation events. Opioid discontinuation is more likely in veterans with mental health and substance use disorders. Further research is needed to delineate causes and consequences of opioid discontinuation. Published by Elsevier B.V.

  11. Long-term metabolic correction of Wilson's disease in a murine model by gene therapy.

    Science.gov (United States)

    Murillo, Oihana; Luqui, Daniel Moreno; Gazquez, Cristina; Martinez-Espartosa, Debora; Navarro-Blasco, Iñigo; Monreal, Jose Ignacio; Guembe, Laura; Moreno-Cermeño, Armando; Corrales, Fernando J; Prieto, Jesus; Hernandez-Alcoceba, Ruben; Gonzalez-Aseguinolaza, Gloria

    2016-02-01

    Wilson's disease (WD) is an autosomal recessively inherited copper storage disorder due to mutations in the ATP7B gene that causes hepatic and neurologic symptoms. Current treatments are based on lifelong copper chelating drugs and zinc salts, which may cause side effects and do not restore normal copper metabolism. In this work we assessed the efficacy of gene therapy to treat this condition. We transduced the liver of the Atp7b(-/-) WD mouse model with an adeno-associated vector serotype 8 (AAV8) encoding the human ATP7B cDNA placed under the control of the liver-specific α1-antitrypsin promoter (AAV8-AAT-ATP7B). After vector administration we carried out periodic evaluation of parameters associated with copper metabolism and disease progression. The animals were sacrificed 6months after treatment to analyze copper storage and hepatic histology. We observed a dose-dependent therapeutic effect of AAV8-AAT-ATP7B manifested by the reduction of serum transaminases and urinary copper excretion, normalization of serum holoceruloplasmin, and restoration of physiological biliary copper excretion in response to copper overload. The liver of treated animals showed normalization of copper content and absence of histological alterations. Our data demonstrate that AAV8-AAT-ATP7B-mediated gene therapy provides long-term correction of copper metabolism in a clinically relevant animal model of WD providing support for future translational studies. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  12. Long-term trends in adherence to antiretroviral therapy from start of HAART.

    Science.gov (United States)

    Cambiano, Valentina; Lampe, Fiona C; Rodger, Alison J; Smith, Colette J; Geretti, Anna M; Lodwick, Rebecca K; Puradiredja, Dewi I; Johnson, Margaret; Swaden, Leonie; Phillips, Andrew N

    2010-05-15

    People on antiretroviral therapy are likely to be required to maintain good adherence throughout their lives. We aimed to investigate long-term trends in highly active antiretroviral therapy (HAART) adherence to identify the main predictors and to evaluate whether participants experience periods of low adherence (start of HAART until the end of the last recorded ART prescription or death. Follow-up was divided into 6-month periods, and for each period, a value of adherence, measured as the percentage of days in the 6-month period covered by a valid prescription for at least three antiretroviral drugs, was calculated. Patients were assessed for drug coverage adherence for a median of 4.5 years [inter-quartile range (IQR) 2.4-7.2; maximum 9 years] covering a period up to 13 years from start of HAART. There was evidence of a slight increase in adherence over time [adjusted odds ratio (OR) of >95% adherence = 1.02 per year; 95% confidence interval (CI) 1.01-1.04; P = 0.0053]. Independent predictors of adherence were age, demographic group, calendar year period, drug regimen and previous virologic failures. The overall rate of at least one period of low adherence was 0.12 per person-year, but this rate decrease markedly over time to 0.01 in 2007/2008. Adherence, as measured by drug coverage, does not decrease on average over more than a decade from start of HAART. This is encouraging, because it shows that patients could potentially maintain viral suppression for many years.

  13. Long-term results of primary transpupillary thermal therapy for the treatment of choroidal malignant melanoma.

    Science.gov (United States)

    Aaberg, T M; Bergstrom, C S; Hickner, Z J; Lynn, M J

    2008-06-01

    This is a long-term follow-up report investigating primary transpupillary thermal therapy (TTT) for choroidal melanoma. Retrospective case series of 135 patients harbouring choroidal melanoma treated with primary TTT. Patient demographics, tumour characteristics, treatment responses and complications, visual acuity outcomes and mortality data were captured and reported. A statistical analysis was performed for predictors of treatment failure. Successful tumour regression was achieved in 76% of patients. Of the 32 patients who failed, 12 had enucleation, and 20 had irradiation. Metastatic disease has occurred in three patients, and two patients have died (3/135, or 2%). Multivariate analysis determined that tumour diameter, tumour thickness greater than 3 mm and tumours exhibiting high-risk characteristics were significant predictors of failure. Patient age, gender, number of treatments and proximity of the tumour to the disc or fovea were not predictive of failure. Kaplan-Meier cumulative probability predicted a 19% 5-year treatment failure and 33% 10-year treatment failure. Treatment failure occurred as late as 99 months. Final visual acuity was 20/40 or better in 50% of patients; 32% had a final visual acuity of 20/200 or worse. Thirty-two per cent of patients developed one or more complications as a result of the TTT, the most concerning of which was intra- or extrascleral extension of tumour (occurring in 11 patients). Though not as successful as radiation therapy, TTT successfully induced regression in 76% of patients. TTT may still have a role in our treatment paradigm but should probably be reserved for specific cases, such as monocular patients with tumours near critical visual structures, surgically unstable patients or patients with advanced diabetic retinopathy. All patients considering TTT as monotherapy for choroidal melanoma must be selected, counselled and followed appropriately.

  14. Traditional Chinese medicine as adjunctive therapy improves the long-term survival of lung cancer patients.

    Science.gov (United States)

    Liao, Yueh-Hsiang; Li, Chia-Ing; Lin, Cheng-Chieh; Lin, Jaung-Geng; Chiang, Jen-Huai; Li, Tsai-Chung

    2017-12-01

    Traditional Chinese medicine is one of the popular alternative treatments for cancer, mainly enhancing host immune response and reducing adverse effect of chemotherapy. This study first explored traditional Chinese medicine treatment effect on long-term survival of lung cancer patients. This study evaluated whether traditional Chinese medicine combined with conventional cancer treatment improved overall survival of lung cancer patients. We had conducted a retrospective cohort study on 111,564 newly diagnosed lung cancer patients in 2000-2009 from National Health Insurance Program database. A total of 23,803 (21.31%) patients used traditional Chinese medicine for lung cancer care. Eligible participants were followed up until 2011 with a mean follow-up period of 1.96 years (standard deviation 2.55) for non-TCM users and 3.04 years (2.85) for traditional Chinese medicine users. Patients with traditional Chinese medicine utilization were significantly more likely to have a 32% decreased risk of death [hazard ratio = 0.62; 95% confidence interval = 0.61-0.63], compared with patients without traditional Chinese medicine utilization after multivariate adjustment. We also observed a similar significant reduction risk across various subgroups of chronic lung diseases. Qing Zao Jiu Fei Tang was the most effective traditional Chinese medicine agent for mortality reduction both in the entire lung cancer (0.81; 0.72-0.91) and matched populations (0.86; 0.78-0.95). This study demonstrated adjunctive therapy with traditional Chinese medicine may improve overall survival of lung cancer patients. This study also suggested traditional Chinese medicine may be used as an adjunctive therapy for cancer treatment. These observational findings need being validated by future randomized controlled trials to rule out the possibility of effect due to holistic care.

  15. Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder.

    LENUS (Irish Health Repository)

    Frodl, T

    2012-01-01

    Neuroplasticity may have a core role in the pathophysiology of major depressive disorder (MDD), a concept supported by experimental studies that found that excessive cortisol secretion and\\/or excessive production of inflammatory cytokines impairs neuronal plasticity and neurogenesis in the hippocampus. The objective of this study was to examine how changes in the glucocorticoid and inflammatory systems may affect hippocampal volumes in MDD. A multimodal approach with structural neuroimaging of hippocampus and amygdala, measurement of peripheral inflammatory proteins interleukin (IL)-6 and C-reactive protein (CRP), glucocorticoid receptor (GR) mRNA expression, and expression of glucocorticoid-inducible genes (glucocorticoid-inducible genes Leucin Zipper (GILZ) and glucocorticoid-inducible kinase-1 (SGK-1)) was used in 40 patients with MDD and 43 healthy controls (HC). Patients with MDD showed smaller hippocampal volumes and increased inflammatory proteins IL-6 and CRP compared with HC. Childhood maltreatment was associated with increased CRP. Patients with MDD, who had less expression of the glucocorticoid-inducible genes GILZ or SGK-1 had smaller hippocampal volumes. Regression analysis showed a strong positive effect of GILZ and SGK-1 mRNA expression, and further inverse effects of IL-6 concentration, on hippocampal volumes. These findings suggest that childhood maltreatment, peripheral inflammatory and glucocorticoid markers and hippocampal volume are interrelated factors in the pathophysiology of MDD. Glucocorticoid-inducible genes GILZ and SGK-1 might be promising candidate markers for hippocampal volume changes relevant for diseases like MDD. Further studies need to explore the possible clinical usefulness of such a blood biomarker, for example, for diagnosis or prediction of therapy response.

  16. Glucocorticoid regulation of food-choice behavior in humans: Evidence from Cushing’s syndrome

    Directory of Open Access Journals (Sweden)

    Scott J Moeller

    2016-02-01

    may have relevance for elucidating glucocorticoid contributions to food-seeking behavior, enhancing mechanistic understanding of weight fluctuations associated with oral glucocorticoid therapy and/or chronic stress, and informing the neurobiology of neuropsychiatric conditions marked by abnormal cortisol dynamics (e.g., major depression, Alzheimer’s disease.

  17. Tall stature in familial glucocorticoid deficiency.

    Science.gov (United States)

    Elias, L L; Huebner, A; Metherell, L A; Canas, A; Warne, G L; Bitti, M L; Cianfarani, S; Clayton, P E; Savage, M O; Clark, A J

    2000-10-01

    Familial glucocorticoid deficiency (FGD) has frequently been associated with tall stature in affected individuals. The clinical, biochemical and genetic features of five such patients were studied with the aim of clarifying the underlying mechanisms of excessive growth in these patients. Five patients with a clinical diagnosis of FGD are described in whom the disorder resulted from a variety of novel or previously described missense or nonsense mutations of the ACTH receptor (MC2-R). All patients demonstrated excessive linear growth over that predicted from parental indices and increased head circumference. Growth hormone and IGF-I-values were normal. Growth charts suggest that the excessive growth is reduced to normal following the introduction of glucocorticoid replacement. A characteristic facial appearance including hypertelorism, marked epicanthic folds and prominent frontal bossing was noted. These findings indicate that ACTH resistance resulting from a defective ACTH receptor may be associated with abnormalities of cartilage and/or bone growth independently of the GH-IGF-I axis, but probably dependent on ACTH actions through other melanocortin receptors.

  18. Glucocorticoid-induced osteoporosis: 2013 update

    Directory of Open Access Journals (Sweden)

    M. Mazzantini

    2014-07-01

    Full Text Available Glucocorticoids are the most common cause of secondary osteoporosis leading to the so-called glucocorticoidinduced osteoporosis (GIO. A treatment with 10 mg/d of prednisone or equivalent for more than 3 months leads to a 7-fold increase in hip fractures and a 17-fold increase in vertebral fractures. The difference between bone quantity and quality in GIO makes bone mineral density measurements inadequate to detect patients at risk of fracture. The adverse effects of glucocorticoids on the skeleton derive from a direct impact on bone cells with a severe impairment of mechanical competence. Crucial to prevention of GIO is early timing of intervention. The World Health Organization has adopted a fracture prevention algorithm (FRAX intended to estimate fracture risk in GIO. The American College of Rhematology modified its prevention and treatment guidelines taking into account the individual risk of fracture calculated in GIO on the basis of the FRAX algorithm. Recently, also a joint Guideline Working Group of the International Osteoporosis Foundation (IOF and the European Calcified Tissue Society (ECTS published a framework for the development of national guidelines for the management of GIO. Bisphosphonates are the first-line drugs to treat GIO; teriparatide counteracts several fundamental pathophysiologic aspects of GIO; denosumab is useful in patients with renal failure and in potentially pregnant young women. Vertebroplasty and kyphoplasty may be less beneficial in GIO than in primary involutional osteoporosis.

  19. Long-term durability of sacral nerve stimulation therapy for chronic fecal incontinence.

    Science.gov (United States)

    Hull, Tracy; Giese, Chad; Wexner, Steven D; Mellgren, Anders; Devroede, Ghislain; Madoff, Robert D; Stromberg, Katherine; Coller, John A

    2013-02-01

    Limited data have been published regarding the long-term results of sacral nerve stimulation, or sacral neuromodulation, for severe fecal incontinence. The aim was to assess the outcome of sacral nerve stimulation with the use of precise tools and data collection, focusing on the long-term durability of the therapy. Five-year data were analyzed. Patients entered in a multicenter, prospective study for fecal incontinence were followed at 3, 6, and 12 months and annually after device implantation. Patients with chronic fecal incontinence in whom conservative treatments had failed or who were not candidates for more conservative treatments were selected. Patients with ≥ 50% improvement over baseline in fecal incontinence episodes per week during a 14-day test stimulation period received sacral nerve stimulation therapy. Patients were assessed with a 14-day bowel diary and Fecal Incontinence Quality of Life and Fecal Incontinence Severity Index questionnaires. Therapeutic success was defined as ≥ 50% improvement over baseline in fecal incontinence episodes per week. All adverse events were collected. A total of 120 patients (110 women; mean age, 60.5 years) underwent implantation. Seventy-six of these patients (63%) were followed a minimum of 5 years (maximum, longer than 8 years) and are the basis for this report. Fecal incontinence episodes per week decreased from a mean of 9.1 at baseline to 1.7 at 5 years, with 89% (n = 64/72) having ≥ 50% improvement (p < 0.0001) and 36% (n = 26/72) having complete continence. Fecal Incontinence Quality of Life scores also significantly improved for all 4 scales between baseline and 5 years (n = 70; p < 0.0001). Twenty-seven of the 76 (35.5%) patients required a device revision, replacement, or explant. The therapeutic effect and improved quality of life for fecal incontinence is maintained 5 years after sacral nerve stimulation implantation and beyond. Device revision, replacement, or explant rate was acceptable, but future

  20. Long-term effects of prenatal stress and glucocorticoid exposure

    NARCIS (Netherlands)

    Painter, Rebecca C.; Roseboom, Tessa J.; de Rooij, Susanne R.

    2012-01-01

    There is a growing body of evidence suggesting that events during prenatal life can have long-lasting effects on development and adult health. Stress during pregnancy is common and has been linked to increased incidence of a range of affective and behavioral outcomes in the offspring in later life

  1. Analysing patent terms and citations to determine the value of gene therapies

    NARCIS (Netherlands)

    van Dongen, Peter; El Hejazi, Zainab Noor; Claassen, H.J.H.M.

    2017-01-01

    Gene therapies hold great promise for treatment of diseases but so far their market authorisation has been limited. This paper describes the development of patented gene therapies in the sector of life sciences and health.  It was found that the annual number of patented gene therapies increased

  2. Changing glucocorticoid action: 11β-Hydroxysteroid dehydrogenase type 1 in acute and chronic inflammation

    Science.gov (United States)

    Chapman, Karen E.; Coutinho, Agnes E.; Zhang, Zhenguang; Kipari, Tiina; Savill, John S.; Seckl, Jonathan R.

    2013-01-01

    Since the discovery of cortisone in the 1940s and its early success in treatment of rheumatoid arthritis, glucocorticoids have remained the mainstay of anti-inflammatory therapies. However, cortisone itself is intrinsically inert. To be effective, it requires conversion to cortisol, the active glucocorticoid, by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Despite the identification of 11β-HSD in liver in 1953 (which we now know to be 11β-HSD1), its physiological role has been little explored until recently. Over the past decade, however, it has become apparent that 11β-HSD1 plays an important role in shaping endogenous glucocorticoid action. Acute inflammation is more severe with 11β-HSD1-deficiency or inhibition, yet in some inflammatory settings such as obesity or diabetes, 11β-HSD1-deficiency/inhibition is beneficial, reducing inflammation. Current evidence suggests both beneficial and detrimental effects may result from 11β-HSD1 inhibition in chronic inflammatory disease. Here we review recent evidence pertaining to the role of 11β-HSD1 in inflammation. This article is part of a Special Issue entitled ‘CSR 2013’. PMID:23435016

  3. Voice in female-to-male transsexual persons after long-term androgen therapy.

    Science.gov (United States)

    Cosyns, Marjan; Van Borsel, John; Wierckx, Katrien; Dedecker, David; Van de Peer, Fleur; Daelman, Tine; Laenen, Sofie; T'Sjoen, Guy

    2014-06-01

    The aim of the present study was to 1) document voice in a large sample of female-to-male transsexual persons (FMT), 2) compare their vocal characteristics with those of heterosexual biological males, and 3) determine hormonal factors with impact on their fundamental frequency. This was a controlled cross-sectional study. It is the largest study to date on voice and voice change in FMT, and the first to include a control group and FMT who were under long-term androgen administration. Thirty-eight FMT, ranging in age between 22 and 54 years, and 38 controls, frequency matched by age and smoking behavior, underwent a voice assessment that comprised the determination of pitch, intonation, and perturbation parameters measured during sustained vowel production, counting, and reading. Hormonal factors explored were hematocrit, total testosterone level, luteinizing hormone level, and biallelic mean length of the cytosine-adenine-guanine (CAG) trinucleotide repeat sequence in the androgen receptor gene. It was found that the FMT as a group did not differ significantly from controls for any of the acoustic voice variables studied. However, in about 10% pitch lowering was not totally unproblematic. The lowest-pitched (i.e., more male) voices were observed in FMT with higher hematocrit and longer CAG repeats. After long-term androgen therapy, FMT generally demonstrate an acceptable male voice. Pitch-lowering difficulties can be expected in about 10% of cases and appear, at least in part, to be associated with diminished androgen sensitivity. 3b. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  4. Growth in HIV-infected children on long-term antiretroviral therapy.

    Science.gov (United States)

    Feucht, Ute D; Van Bruwaene, Lore; Becker, Piet J; Kruger, Mariana

    2016-05-01

    To describe growth in HIV-infected children on long-term antiretroviral therapy (ART) and to assess social, clinical, immunological and virological factors associated with suboptimal growth. This observational cohort study included all HIV-infected children at an urban ART site in South Africa who were younger than 5 years at ART initiation and with more than 5 years of follow-up. Growth was assessed using weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ) and body mass index (BMI)-for-age Z-scores (BAZ). Children were stratified according to pre-treatment anthropometry and age. Univariate and mixed linear analysis were used to determine associations between independent variables and weight and height outcomes. The majority of the 159 children presented with advanced clinical disease (90%) and immunosuppression (89%). Before treatment underweight, stunting and wasting were common (WAZ<-2 = 50%, HAZ<-2 = 73%, BAZ<-2 = 19%). Weight and BMI improved during the initial 12 months, while height improved over the entire 5-year period. Height at study exit was significantly worse for children with growth impairment at ART initiation (P < 0.001), and infants (<1 year) demonstrated superior improvement in terms of BMI (P = 0.04). Tuberculosis was an independent risk factor for suboptimal weight (P = 0.01) and height (P = 0.02) improvement. Weight gain was also hindered by lack of electricity (P = 0.04). Immune reconstitution and virological suppression were not associated with being underweight or stunted at study endpoint. Malnutrition was a major clinical concern for this cohort of HIV-infected children. Early ART initiation, tuberculosis co-infection management and nutritional interventions are crucial to ensure optimal growth in HIV-infected children. © 2016 John Wiley & Sons Ltd.

  5. Rapid response to and long-term effectiveness of anti-CD20 antibody in conventional therapy resistant Graves' orbitopathy: A five-year follow-up study.

    Science.gov (United States)

    Erdei, Annamaria; Paragh, Gyorgy; Kovacs, Peter; Karanyi, Zsolt; Berenyi, Ervin; Galuska, Laszlo; Lenkey, Agota; Szabados, Lajos; Gyory, Ferenc; Ujhelyi, Bernadett; Berta, Andras; Boda, Judit; Berta, Eszter; Bodor, Miklos; Gazdag, Annamaria; Nagy, Endre V

    2014-12-01

    Abstract The aim of this investigations was to study the effectiveness of anti-CD20 antibody therapy in Graves' orbitopathy (GO) resistant to glucocorticoids. Five patients were entered in the study. The protocol required no improvement of orbital status after a recent course of glucocorticoids. Activity of GO was confirmed by three independent techniques: clinical activity score (CAS), (99m)Tc-labeled diethylene triamine pentaacetic acid ((99m)Tc DTPA) single photon emission computed tomography and magnetic resonance imaging. Rituximab (RTX) was given as weekly infusions of 375 mg/m(2) body surface area for four weeks. The mean follow-up period was 67 (range 58-81) months. Improvement of GO has been observed in all patients: CAS before therapy was 6.5 ± 1.7 and decreased to 3.4 ± 1.6 by one month (p < 0.05) and remained unchanged (3.2 ± 1.7) at 12 months. No further CAS change, in either direction, was detected during the yearly follow-up visits. The mean DTPA uptake before therapy was 16.52 ± 4.51 MBq/cm(3) and decreased to 11.97 ± 2.36 MBq/cm(3) at one year (p < 0.002). The mean of T2 relaxation times before and one year after therapy were 96.91 ± 17.61 ms and 84.29 ± 9.41 ms, respectively (p < 0.001). The mean serum TSH receptor antibody (TRAb) levels before therapy, at the one month and one year control visits were 7.4 ± 3.4 U/L, 5.6 ± 4.5 U/L and 1.7 ± 1.5 U/L, respectively (p < 0.004). No correlation between changes of TRAb and activity parameters has been found. Anti-CD20 treatment seems to influence positively the clinical course of GO, and this effect seems to be stable for five years. To our knowledge, this is the longest published follow-up of RTX treatment in GO.

  6. Hormones, stress, and cognition: The effects of glucocorticoids and oxytocin on memory

    Science.gov (United States)

    Wirth, Michelle M.

    2014-01-01

    Hormones have nuanced effects on learning and memory processes. The degree and direction of the effect (e.g., is memory impaired or enhanced?) depends on the dose, type and stage of memory, and type of material being learned, among other factors. This review will focus on two specific topics within the realm of effects of hormones on memory: (1) How glucocorticoids (the output hormones of the hypothalamic-pituitary-adrenal axis) affect long-term memory consolidation, retrieval, and working memory, with a focus on neural mechanisms and effects of emotion; and (2) How oxytocin affects memory, with emphasis on a speculative hypothesis that oxytocin might exert its myriad effects on human social cognition and behavior via impacts on more general cognitive processes. Oxytocin-glucocorticoid interactions will be briefly addressed. These effects of hormones on memory will also be considered from an evolutionary perspective. PMID:25893159

  7. Animal models for glucocorticoid-induced postmenopausal osteoporosis: An updated review.

    Science.gov (United States)

    Zhang, Zhida; Ren, Hui; Shen, Gengyang; Qiu, Ting; Liang, De; Yang, Zhidong; Yao, Zhensong; Tang, Jingjing; Jiang, Xiaobing; Wei, Qiushi

    2016-12-01

    Glucocorticoid-induced postmenopausal osteoporosis is a severe osteoporosis, with high risk of major osteoporotic fractures. This severe osteoporosis urges more extensive and deeper basic study, in which suitable animal models are indispensable. However, no relevant review is available introducing this model systematically. Based on the recent studies on GI-PMOP, this brief review introduces the GI-PMOP animal model in terms of its establishment, evaluation of bone mass and discuss its molecular mechanism. Rat, rabbit and sheep with their respective merits were chosen. Both direct and indirect evaluation of bone mass help to understand the bone metabolism under different intervention. The crucial signaling pathways, miRNAs, osteogenic- or adipogenic- related factors and estrogen level may be the predominant contributors to the development of glucocorticoid-induced postmenopausal osteoporosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. The Role and Mechanisms of Action of Glucocorticoid Involvement in Memory Storage

    Directory of Open Access Journals (Sweden)

    Carmen Sandi

    1998-01-01

    integral aspect of the neurobiological mechanism underlying memory formation. By reviewing the work carried out in different learning models in chicks (passive avoidance learning and rats (spatial orientation in the Morris water maze and contextual fear conditioning, a role for brain corticosterone action through the glucocorticoid receptor type on the mechanisms of memory consolidation is hypothesized. Evidence is also presented to relate post-training corticosterone levels to the strength of memory storage. Finally, the possible molecular mechanisms that might mediate the influences of glucocorticoids in synaptic plasticity subserving long-term memory formation are considered, mainly by focusing on studies implicating a steroid action through (i glutamatergic transmission and (ii cell adhesion molecules.

  9. Long-term effects of Bio-Electromagnetic-Energy Regulation therapy on fatigue in patients with multiple sclerosis.

    Science.gov (United States)

    Haase, Rocco; Piatkowski, Joachim; Ziemssen, Tjalf

    2011-01-01

    Electromagnetic-field therapy has beneficial short-term effects in multiple sclerosis (MS) patients with major fatigue, but long-term data are lacking. PRIMARY STUDY OBJECTIVES: To evaluate the long-term effects of a specific electromagnetic therapy device (Bio-Electromagnetic- Energy-Regulation [BEMER]) on MS-related fatigue, we designed a crossover control of a previously performed randomized controlled trial and a long-term open-label follow-up trial. Crossover and open-label follow-up trials at a single neurological outpatient center. Patients with relapsing-remitting MS who had major fatigue (N = 37 patients). After a previous randomized controlled trial (exposure to low-frequency pulsed magnetic fields for 8 min twice daily or to placebo treatment for 12 wk), a crossover from control to treatment for another 12 weeks, followed by an open label follow-up trial to 3 years, were done. The outcome criteria were the Modified Fatigue Impact Scale (MFIS), Fatigue Severity Scale (FSS), German long version of the Center for Epidemiologic Studies Depression Scale (CES-D), Multiple Sclerosis Functional Scale (MSFC), and Expanded Disability Status Scale (EDSS). Patients previously on placebo during the randomized controlled trial experienced significant reductions in fatigue after crossing over to treatment. The MFIS and FSS scores were significantly lower in the open-label group than in the control subjects after follow-up. Participation in the open-label treatment was the strongest predictor of low fatigue outcome after followup. Electromagnetic-field therapy was well tolerated. In this long-term study, a beneficial effect of long-term BEMER therapy on MS fatigue was demonstrated. Electromagnetic-field therapy may be a useful therapeutic modality in MS patients with severe fatigue.

  10. Long-term Primary Medical Therapy with Somatostatin Analogs in Acromegaly

    Directory of Open Access Journals (Sweden)

    Deng-Huang Su

    2006-01-01

    Full Text Available To cure acromegalic patients, transsphenoidal surgery is considered first, especially for microadenoma. However, less than 50% of patients with macroadenoma achieve satisfactory biochemical control. Moreover, surgery may cause hypopituitarism. Medical therapy may offer the prospect of near normalization of growth hormone (GH/insulin-like growth factor-1 levels with substantial tumor shrinkage in a significant number of patients. Here, we report two cases of acromegaly under treatment with somato-statin analogs alone for more than 10 years. Case 1 was a 54-year-old man with a pituitary macro-adenoma. He received 4 years of octreotide treatment followed by 6 years of prolonged-release (PR lanreotide resulting in normal GH level. Case 2 was a 60-year-old woman with a 1.3 cm pituitary tumor. She received 8 years of octreotide treatment followed by 6 years of PR lanreotide resulting in subnormal GH level and gallbladder sludge. She had received bilateral total hip replacement for hip osteoarthritis at the age of 59 years. These cases illustrate that long-term treatment with somatostatin analogs offers an alternative choice in selected acromegalic patients, such as those with pituitary tumor who cannot be cured by surgery, those who have unacceptable anesthetic risk and those who refuse surgery.

  11. The Severe Respiratory Insufficiency Questionnaire for Subjects With COPD With Long-Term Oxygen Therapy.

    Science.gov (United States)

    Walterspacher, Stephan; July, Johanna; Kohlhäufl, Martin; Rzehak, Peter; Windisch, Wolfram

    2016-09-01

    Respiratory insufficiency in COPD may present as hypoxic and/or hypercapnic respiratory failure treated with long-term oxygen therapy (LTOT) and/or noninvasive ventilation (NIV) with LTOT. The Severe Respiratory Insufficiency Questionnaire (SRI) is a tool for the assessment of health-related quality of life (HRQOL) in subjects receiving NIV. However, it remains unclear whether the SRI is also capable of assessing and discriminating HRQOL in subjects receiving LTOT. Stable subjects with COPD receiving LTOT or NIV + LTOT (NIV) were prospectively recruited and completed the SRI, lung function tests, and blood gases. Confirmatory factor analysis for construct validity and internal consistency reliability were calculated. One hundred fifty-five subjects were included (113 LTOT, 42 NIV). The Cronbach α coefficient of the 7 subscales ranged between 0.69 and 0.89 (LTOT) and between 0.79 and 0.93 (NIV), respectively. In both groups, confirmatory factor analysis revealed a one-factor model for the SRI summary scale; in 5 subscales, one- or 2-factor models could be established. Group differences in the SRI subsets were all P <.05 (except for physical functioning) with higher scores in subjects receiving NIV. The SRI showed high reliability and validity in subjects with COPD receiving LTOT. Subjects receiving LTOT had lower SRI scores, indicating a poorer HRQOL compared with subjects with established NIV and LTOT. Copyright © 2016 by Daedalus Enterprises.

  12. Spectral moments of the long-term average spectrum: sensitive indices of voice change after therapy?

    Science.gov (United States)

    Tanner, Kristine; Roy, Nelson; Ash, Andrea; Buder, Eugene H

    2005-06-01

    Voice clinicians require an objective, reliable, and relatively automatic method to assess voice change after medical, surgical, or behavioral intervention. This measure must be sensitive to a variety of voice qualities and severities, and preferably should reflect voice in continuous speech. The long-term average spectrum (LTAS) is a fast Fourier transform-generated power spectrum whose properties can be compared with a Gaussian bell curve using spectral moments analysis. Four spectral moments describe features of the LTAS: Spectral mean (Moment 1) and standard deviation (Moment 2) represent the spectrum's central tendency and dispersion, respectively. Skewness (based on Moment 3) and kurtosis (based on Moment 4) represent the spectrum's tilt and peakedness, respectively. To examine whether the first four spectral moments of the LTAS were sensitive to perceived voice improvement after voice therapy, this investigation compared pretreatment and posttreatment voice samples of 93 patients with functional dysphonia using spectral moments analysis. Inspection of the results revealed that spectral mean and standard deviation lowered significantly with perceived voice improvement after successful behavioral management (p voice severity (p < 0.001), indicating that spectral mean (ie, Moment 1) of the LTAS may be one acoustic marker sensitive to improvement in dysphonia severity.

  13. Intraoperative Electron-Beam Radiation Therapy for Pediatric Ewing Sarcomas and Rhabdomyosarcomas: Long-Term Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Sole, Claudio V., E-mail: csole@iram.cl [Department of Radiation Oncology, Instituto de Radiomedicina, Santiago (Chile); School of Medicine, Complutense University, Madrid (Spain); Calvo, Felipe A. [School of Medicine, Complutense University, Madrid (Spain); Department of Oncology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); Polo, Alfredo [Service of Radiation Oncology, Hospital Universitario Ramón y Cajal, Madrid (Spain); Cambeiro, Mauricio [Service of Radiation Oncology, Clínica Universidad de Navarra, Pamplona (Spain); Gonzalez, Carmen [School of Medicine, Complutense University, Madrid (Spain); Service of Radiation Oncology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); Desco, Manuel [School of Medicine, Complutense University, Madrid (Spain); Department of Experimental Surgery and Medicine, Hospital General Universitario Gregorio Marañón, Madrid (Spain); Martinez-Monge, Rafael [Service of Radiation Oncology, Clínica Universidad de Navarra, Pamplona (Spain)

    2015-08-01

    Purpose: To assess long-term outcomes and toxicity of intraoperative electron-beam radiation therapy (IOERT) in the management of pediatric patients with Ewing sarcomas (EWS) and rhabdomyosarcomas (RMS). Methods and Materials: Seventy-one sarcoma (EWS n=37, 52%; RMS n=34, 48%) patients underwent IOERT for primary (n=46, 65%) or locally recurrent sarcomas (n=25, 35%) from May 1983 to November 2012. Local control (LC), overall survival (OS), and disease-free survival were estimated using Kaplan-Meier methods. For survival outcomes, potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. Results: After a median follow-up of 72 months (range, 4-310 months), 10-year LC, disease-free survival, and OS was 74%, 57%, and 68%, respectively. In multivariate analysis after adjustment for other covariates, disease status (P=.04 and P=.05) and R1 margin status (P<.01 and P=.04) remained significantly associated with LC and OS. Nine patients (13%) reported severe chronic toxicity events (all grade 3). Conclusions: A multimodal IOERT-containing approach is a well-tolerated component of treatment for pediatric EWS and RMS patients, allowing reduction or substitution of external beam radiation exposure while maintaining high local control rates.

  14. Angiopep-conjugated nanoparticles for targeted long-term gene therapy of Parkinson's disease.

    Science.gov (United States)

    Huang, Rongqin; Ma, Haojun; Guo, Yubo; Liu, Shuhuan; Kuang, Yuyang; Shao, Kun; Li, Jianfeng; Liu, Yang; Han, Liang; Huang, Shixian; An, Sai; Ye, Liya; Lou, Jinning; Jiang, Chen

    2013-10-01

    To prepare an angiopep-conjugated dendrigraft poly-L-lysine (DGL)-based gene delivery system and evaluate the neuroprotective effects in the rotenone-induced chronic model of Parkinson's disease (PD). Angiopep was applied as a ligand specifically binding to low-density lipoprotein receptor-related protein (LRP) which is overexpressed on blood-brain barrier (BBB), and conjugated to biodegradable DGL via hydrophilic polyethyleneglycol (PEG), yielding DGL-PEG-angiopep (DPA). In vitro characterization was carried out. The neuroprotective effects were evaluated in a chronic parkinsonian model induced by rotenone using a regimen of multiple dosing intravenous administrations. The successful synthesis of DPA was demonstrated via (1)H-NMR. After encapsulating the therapeutic gene encoding human glial cell line-derived neurotrophic factor (hGDNF), DPA/hGDNF NPs showed a sphere-like shape with the size of 119 ± 12 nm and zeta potential of 8.2 ± 0.7 mV. Angiopep-conjugated NPs exhibited higher cellular uptake and gene expression in brain cells compared to unmodified counterpart. The pharmacodynamic results showed that rats in the group with five injections of DPA/hGDNF NPs obtained best improved locomotor activity and apparent recovery of dopaminergic neurons compared to those in other groups. This work provides a practical non-viral gene vector for long-term gene therapy of chronic neurodegenerative disorders.

  15. Long term outcome of boron neutron capture therapy for malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Hiratsuka, J. [Kawasaki Medical School, Kurashiki, Okayama (Japan); Fukuda, H. [Tohoku Univ., Sendai (Japan); Kobayashi, T. [Kyoto Univ. (Japan); Yoshino, K. [Shinshu Univ., Matsumoto, Nagano (Japan); Honda, C.; Ichihashi, M. [Kobe Univ., Kobe, Hyogo (Japan); Mishima, Y. [Mishima Institute for Dermatological Research, Kobe, Hyogo (Japan)

    2000-10-01

    Eighteen patients with cutaneous malignant melanoma were treated by boron neutron capture therapy (BNCT) using {sup 10}B-BPA. Our aim was to assess the long term clinical outcome of BNCT on these patients. The target areas were 15 primary lesions and 5 metastatic lesions. The primary lesions were consisted of acral lentigious melanoma (ALM) in six patients, nodular melanoma (NM) in six and lentigo maligna melanoma (LMM) in three. The complete regression (CR) rates were 73% for the primary lesions, 20% for the metastatic lesions. The CR rates for the primary lesions according to melanoma type were 33% for NM and 100% for non-NM. None of the patients with CR showed local recurrence in the radiation field during follow up ranging from 5.5 to 10.6 years (mean 6.7 years). The five year cause specific survival rate was 92% in the cases without distant metastasis at the time of BNCT. BNCT proves to be a very useful therapeutic modality for the management of cutaneous malignant melanoma. (author)

  16. Long-Term Oxygen Therapy in COPD Patients Who Do Not Meet the Actual Recommendations.

    Science.gov (United States)

    Ergan, Begum; Nava, Stefano

    2017-06-01

    Chronic respiratory failure due to chronic obstructive pulmonary disease (COPD) is an increasing problem worldwide. Many patients with severe COPD develop hypoxemic respiratory failure during the natural progression of disease. Long-term oxygen therapy (LTOT) is a well-established supportive treatment for COPD and has been shown to improve survival in patients who develop chronic hypoxemic respiratory failure. The degree of hypoxemia is severe when partial pressure of oxygen in arterial blood (PaO 2 ) is ≤55 mmHg and moderate if PaO 2 is between 56 and 69 mmHg. Although current guidelines consider LTOT only in patients with severe resting hypoxemia, many COPD patients with moderate to severe disease experience moderate hypoxemia at rest or during special circumstances, such as while sleeping or exercising. The efficacy of LTOT in these patients who do not meet the actual recommendations is still a matter of debate, and extensive research is still ongoing to understand the possible benefits of LTOT for survival and/or functional outcomes such as the sensation of dyspnea, exacerbation frequency, hospitalizations, exercise capacity, and quality of life. Despite its frequent use, the administration of "palliative" oxygen does not seem to improve dyspnea except for delivery with high-flow humidified oxygen. This narrative review will focus on current evidence for the effects of LTOT in the presence of moderate hypoxemia at rest, during sleep, or during exercise in COPD.

  17. Short term oxygen therapy effects in hypoxemic patients measured by drawing analysis.

    Science.gov (United States)

    Fiz, José Antonio; Faundez-Zanuy, Marcos; Monte-Moreno, Enrique; Alcobé, Josep Roure; Andreo, Felipe; Gomez, Rosa; Manzano, Juan Ruiz

    2015-03-01

    Chronic hypoxemia has deleterious effects on psychomotor function that can affect daily life. There are no clear results regarding short term therapy with low concentrations of O2 in hypoxemic patients. We seek to demonstrate, by measuring the characteristics of drawing, these effects on psychomotor function of hypoxemic patients treated with O2. Eight patients (7/1) M/F, age 69.5 (9.9) yr, mean (SD) with hypoxemia (Pa O2 62.2 (6.9) mmHg) performed two drawings of pictures. Tests were performed before and after 30 min breathing with O2. Stroke velocity increased after O2 for the house drawing (i.e. velocity 27.6 (5.5) mm/s basal, 30.9 (7.1) mm/s with O2, mean (SD), pdrawing time 'down' or fraction time the pen is touching the paper during the drawing phase decreased (i.e. time down 20.7 (6.6) s basal, 17.4 (6.3) s with O2, pdrawing analysis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Safety and efficacy of technetium-99 methylene diphosphate combined with glucocorticoid for Graves ophthalmopathy

    Directory of Open Access Journals (Sweden)

    Ri-Qiu Chen

    2016-04-01

    Full Text Available AIM:To evaluate the clinical efficacy and safety of technetium-99 methylene diphosphate(99Tc - MDPwith glucocorticoid therapy for Graves ophthalmopathy. METHODS:A total of 96 patients with Graves ophthalmopathy were randomly divided into two groups, The control group assigned to receive methylprednisolone injection pulse therapy and oral prednisone tablets in the intermittent period. The experimental group was given the treatment of 99Tc - MDP injection based on therapy of the control group. Then the clinical efficacy and safety of the two therapies were compared. RESULTS:The clinical symptoms of the two groups were improved. The efficiency rate of the experimental group was higher than that of the control group, especially on the degree of exophthalmos, and the difference was statistically significant(PP>0.05. The experimental group did not have serious adverse reactions associated with 99Tc-MDP.CONCLUSION:There are obvious improvements in patients with Graves ophthalmopathy treated by 99Tc - MDP combined with glucocorticoid, especially in the degree of exophthalmus and with less adverse reactions, which deserves promotion.

  19. Prolonged glucocorticoid treatment in ARDS: impact on intensive care unit acquired weakness.

    Directory of Open Access Journals (Sweden)

    Gianfranco Umberto Meduri

    2016-08-01

    Full Text Available AbstractSystemic inflammation and duration of immobilization are strong independent risk factors for development of intensive care unit- acquired weakness (ICUAW. Activation of the pro-inflammatory transcription factor nuclear factor-κB (NF-κB results in muscle wasting during disuse-induced skeletal muscle atrophy (ICU bed rest and septic shock. In addition, NF-κB-mediated signaling plays a significant role in mechanical ventilation-induced diaphragmatic atrophy and contractile dysfunction. Older trials investigating high dose glucocorticoid treatment reported a lack of a sustained anti-inflammatory effects and an association with ICUAW. However, prolonged low-to-moderate dose glucocorticoid treatment of sepsis and ARDS is associated with a reduction in NF-κB DNA-binding, decreased transcription of inflammatory cytokines, enhanced resolution of systemic and pulmonary inflammation, leading to fewer days of mechanical ventilation, and lower mortality. Importantly, meta-analyses of a large number of randomized controlled trials (RCTs investigating low-to-moderate glucocorticoid treatment in severe sepsis and ARDS found no increase in ICUAW. Furthermore, while the ARDS network trial investigating methylprednisolone treatment in persistent ARDS is frequently cited to support an association with ICUAW, a re-analysis of the data showed a similar incidence with the control group. Our review concludes that in patients with sepsis and ARDS any potential direct harmful neuromuscular effect of glucocorticoids appears outweighed by the overall clinical improvement and reduced duration of organ failure, in particular ventilator dependency and associated immobilization, which are key risk factors for ICUAW. Acknowledgements: The NHLBI ARDSnetwork graciously provided and assisted with the ARDSnet02 Dataset on the Efficacy of Corticosteroids as Rescue Therapy for the Late Phase of Acute Respiratory Distress Syndrome (LaSRS.

  20. Managing treatment fatigue in patients with multiple sclerosis on long-term therapy: the role of multiple sclerosis nurses

    Directory of Open Access Journals (Sweden)

    Crawford A

    2014-08-01

    Full Text Available Ann Crawford, Sally Jewell,* Holly Mara, Laura McCatty, Regina Pelfrey The Lash Group; Frisco, TX, USA *Sally Jewell is now retired Abstract: This article discusses the many ways that nurses can address the factors that lead to treatment fatigue in patients with multiple sclerosis (MS on long-term disease-modifying therapy, ultimately helping to preserve the patient’s health and quality of life. Patients with MS on long-term therapy may suffer from treatment fatigue and poor adherence due to a variety of different factors, including difficulties with injections, anxiety/depression, financial problems, and inaccurate beliefs about the MS disease process. Because MS nurses have regular interactions with patients, they are ideally situated to help patients cope with these and other factors that may limit adherence. Keywords: multiple sclerosis, disease-modifying therapy, injection, nurse

  1. Developmental Expression and Glucocorticoid Control of the Leptin Receptor in Fetal Ovine Lung.

    Directory of Open Access Journals (Sweden)

    Miles J De Blasio

    Full Text Available The effects of endogenous and synthetic glucocorticoids on fetal lung maturation are well-established, although the role of leptin in lung development before birth is unclear. This study examined mRNA and protein levels of the signalling long-form leptin receptor (Ob-Rb in fetal ovine lungs towards term, and after experimental manipulation of glucocorticoid levels in utero by fetal cortisol infusion or maternal dexamethasone treatment. In fetal ovine lungs, Ob-Rb protein was localised to bronchiolar epithelium, bronchial cartilage, vascular endothelium, alveolar macrophages and type II pneumocytes. Pulmonary Ob-Rb mRNA abundance increased between 100 (0.69 fractional gestational age and 144 days (0.99 of gestation, and by 2-4-fold in response to fetal cortisol infusion and maternal dexamethasone treatment. In contrast, pulmonary Ob-Rb protein levels decreased near term and were halved by glucocorticoid treatment, without any significant change in phosphorylated signal transducer and activator of transcription-3 (pSTAT3 at Ser727, total STAT3 or the pulmonary pSTAT3:STAT3 ratio. Leptin mRNA was undetectable in fetal ovine lungs at the gestational ages studied. These findings demonstrate differential control of pulmonary Ob-Rb transcript abundance and protein translation, and/or post-translational processing, by glucocorticoids in utero. Localisation of Ob-Rb in the fetal ovine lungs, including alveolar type II pneumocytes, suggests a role for leptin signalling in the control of lung growth and maturation before birth.

  2. Fluoride Excess in Coccidioidomycosis Patients Receiving Long-Term Antifungal Therapy: an Assessment of Currently Available Triazoles

    Science.gov (United States)

    Bays, Derek; Cohen, Stuart H.; Pappagianis, Demosthenes

    2012-01-01

    The use of voriconazole, a trifluorinated antifungal, has been associated with the development of fluoride excess and periostitis/exostoses. We evaluated a cohort of patients on long-term triazole therapy and found that other fluorinated triazoles (fluconazole and posaconazole) conferred no risk for the development of hyperfluorosis and its complications in our cohort. PMID:22005993

  3. Acceptance and Commitment Therapy for Depression: A Preliminary Randomized Clinical Trial for Unemployed on Long-Term Sick Leave

    Science.gov (United States)

    Folke, Fredrik; Parling, Thomas; Melin, Lennart

    2012-01-01

    This preliminary study investigated the feasibility of a brief Acceptance and Commitment Therapy (ACT) in a Swedish sample of unemployed individuals on long-term sick leave due to depression. Participants were randomized to a nonstandardized control condition (N = 16) or to the ACT condition (N = 18) consisting of 1 individual and 5 group…

  4. Tissue-Doppler assessment of cardiac left ventricular function during short-term adjuvant epirubicin therapy for breast cancer

    DEFF Research Database (Denmark)

    Appel, Jon M; Sogaard, Peter; Mortensen, Christiane E

    2011-01-01

    It has been hypothesized that the extent of acute anthracycline-induced cardiotoxicity reflects the risk for late development of heart failure. The aim of this study was to examine if short-term changes in cardiac function can be detected even after low-dose adjuvant epirubicin therapy for breast...... cancer when using Doppler tissue imaging of longitudinal left ventricular function....

  5. Neutrophil superoxide-anion generating capacity in chronic smoking: effect of long-term alpha-tocopherol therapy

    NARCIS (Netherlands)

    Tits, van L.; Waart, de F.; Hak-Lemmers, H.L.M.; Graaf, de J.; Demacker, P.N.; Stalenhoef, A.F.

    2003-01-01

    We investigated whether long-term alpha-tocopherol therapy in chronic smoking affects superoxide generating capacity of neutrophils ex vivo. To this purpose, we randomly assigned 128 male chronic smokers (37 21 pack years of smoking) to treatment with placebo (n = 64) or alpha-tocopherol (400 IU

  6. Fasting plasma glucose after intensive insulin therapy predicted long-term glycemic control in newly diagnosed type 2 diabetic patients.

    Science.gov (United States)

    Liu, Jianbin; Liu, Juan; Fang, Donghong; Liu, Liehua; Huang, Zhimin; Wan, Xuesi; Cao, Xiaopei; Li, Yanbing

    2013-01-01

    Short term intensive insulin therapy has been reported to induce long term euglycemia remission in patients with newly diagnosed type 2 diabetes mellitus, but the factors that are responsible for long-term remission or hyperglycemia relapse are unknown. Original data of 188 patients with newly diagnosed type 2 diabetes treated with short term intensive insulin therapy was reanalyzed. Patients who maintained glycemic control for 12 months with only life style intervention were defined as remission while those who failed to maintain glycemic control for 12 months as hyperglycemia relapse. Relationships of metabolic control, β cell function and insulin sensitivity with remission time and hyperglycemia relapse were explored. Totally 93 patients achieved 12-month euglycemic remission. Substantial improvement in blood glucose, parameters of β cell function and insulin sensitivity were obtained in both remission and relapse patients. The duration of remission was correlated with fasting plasma glucose measured after cessation of continuous subcutaneous insulin infusion (CSII) therapy (fasting plasma glucose (FPG) after CSII, r= -0.349, p7.0 mmol/L (Hazard ratio=2.69, pintensive insulin therapy is a convenient and significant predictor for hyperglycemic relapse.

  7. Long-term results after external beam radiation therapy for T1-T2 localized prostate cancer

    NARCIS (Netherlands)

    Lagerveld, B. W.; Laguna, M. P.; de la Rosette, J. J. M. C. H.

    2003-01-01

    The incidence of organ-confined and early-stage prostate cancer has increased. The external beam radiation therapy has proven to be a good therapeutic option in terms of biochemical survival and overall survival. It has been modified throughout the years; consequently, the available data on the

  8. Bone mineral density increases in HIV-infected children treated with long-term combination antiretroviral therapy

    NARCIS (Netherlands)

    Bunders, Madeleine J.; Frinking, Olivier; Scherpbier, Henriette J.; van Arnhem, Lotus A.; van Eck-Smit, Berthe L.; Kuijpers, Taco W.; Zwinderman, Aeilko H.; Reiss, Peter; Pajkrt, Dasja

    2013-01-01

    The long-term treatment of human immunodeficiency virus (HIV)-infected children with combination antiretroviral therapy (cART) requires assessment of potential adverse effects, such as osteoporosis. Longitudinal data on bone mineral density (BMD) in HIV-infected children showed that cumulative

  9. A Review of Potential Adverse Effects of Long-Term Opioid Therapy: A Practitioner’s Guide

    OpenAIRE

    Baldini, AnGee; Von Korff, Michael; Lin, Elizabeth H. B.

    2012-01-01

    Objective:Review, synthesize, and summarize recent evidence on adverse effects of long-term opioid treatment for noncancer pain and present an organ system–based guide for primary care physicians in initiating and monitoring patients receiving chronic opioid therapy.

  10. [Medium-term results of a Day Hospital insulin therapy program for patients with type 2 diabetes mellitus].

    Science.gov (United States)

    Quirós, Carmen; Amor, Antonio J; de Hollanda, Ana M; Yago, Gemma; Ara, Pilar; Conget, Ignacio

    2014-03-20

    The profile of the patient with type 2 diabetes mellitus (DM2) who requires insulin therapy is very diverse as are the results of this intervention and short/middle-term patient management. We evaluated the midterm results of an outpatient program starting insulin therapy with≥2 insulin injections/day in terms of metabolic control in different groups of patients. We analyzed prospectively 131 patients with DM2, without previous insulin treatment, who were prescribed treatment with≥2 insulin injections/day and who were enrolled in a specific ambulatory program in order to start insulin therapy in a Day Hospital for 6 months. The initial glycosylated hemoglobin (HbA1c) was 11.3 (2.3) % and decreased to 6.3 (1.4) % in 6 months, with HbA1c2.5% of them. The group of recently diagnosed patients (2 [12.1] years; P2.1 [1.8] vs 10.5 [2.5] %; P2 groups at study ends according to the final treatment scheme. Counselling patients with DM2 to start insulin with more than one injection per day in Day Hospital setting achieves and maintains a good metabolic control in the medium term in different patient profiles. Among symptomatic and recently diagnosed patients, insulin therapy can be stopped in 50% of them at the medium term. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  11. Long-term effectiveness of exercise therapy in patients with osteoarthritis of hip or knee: a systematic review.

    NARCIS (Netherlands)

    Pisters, M.F.; Veenhof, C.; Meeteren, N.L.U. van; Ostelo, R.W.; Bakker, D. de; Schellevis, F.G.; Dekker, J.

    2007-01-01

    PURPOSE: To determine the long-term effectiveness (= 6 months after treatment) of exercise therapy on pain, physical function and patient global assessment of effectiveness in patients with osteoarthritis (OA) of the hip and/or knee. METHODS: An extensive literature search in PubMed, Embase, CINAHL,

  12. Long-term effectiveness of exercise therapy in patients with osteoarthritis of hip or knee: a systematic review.

    NARCIS (Netherlands)

    Pisters, M.F.; Veenhof, C.; Meeteren, N.L.U. van; Ostelo, R.W.; Bakker, D.H. de; Schellevis, F.G.; Dekker, J.

    2007-01-01

    OBJECTIVE: To determine the long-term effectiveness (>/=6 months after treatment) of exercise therapy on pain, physical function, and patient global assessment of effectiveness in patients with osteoarthritis (OA) of the hip and/or knee. METHODS: We conducted an extensive literature search in

  13. Iatrogenic Cushing's Syndrome Due to Topical Ocular Glucocorticoid Treatment.

    Science.gov (United States)

    Fukuhara, Daisuke; Takiura, Toshihiko; Keino, Hiroshi; Okada, Annabelle A; Yan, Kunimasa

    2017-02-01

    Iatrogenic Cushing's syndrome (CS) is a severe adverse effect of systemic glucocorticoid (GC) therapy in children, but is extremely rare in the setting of topical ocular GC therapy. In this article, we report the case of a 9-year-old girl suffering from idiopathic uveitis who developed CS due to topical ocular GC treatment. She was referred to the ophthalmology department with a complaint of painful eyes, at which time she was diagnosed with bilateral iridocyclitis and started on a treatment of betamethasone sodium phosphate eye drops. Six months after the initiation of topical ocular GC treatment, she was referred to our pediatric department with stunted growth, truncal obesity, purple skin striate, buffalo hump, and moon face. Because her serum cortisol and plasma adrenocorticotropic hormone levels were undetectable, she was diagnosed with iatrogenic CS. After the doses of topical ocular GC were reduced, the clinical symptoms of CS were improved. The fact that the amount of topical ocular GC with our patient was apparently less than that of similar previous cases tempted us to perform genetic analysis of her NR3C1 gene. We found that our patient had a single heterozygous nucleotide substitution in the 3' untranslated region of the NR3C1 gene, which may explain why she developed CS. However, additional investigations are required to determine if our findings can be extrapolated to other patients. In conclusion, clinicians should be aware that even extremely low doses of topical ocular steroid therapy can cause iatrogenic CS. Copyright © 2017 by the American Academy of Pediatrics.

  14. Primary and secondary prophylaxis to the use of inhaled glucocorticoid in primary health care

    DEFF Research Database (Denmark)

    Nielsen, Barbara Rubek; Jørgensen, Niklas Rye; Schwarz, Peter

    2008-01-01

    To investigate the extent of inhaled glucocorticoid (IGC) treatment in general and to what extent general practitioners (GPs) manage the risk of glucocorticoid-induced osteoporosis.......To investigate the extent of inhaled glucocorticoid (IGC) treatment in general and to what extent general practitioners (GPs) manage the risk of glucocorticoid-induced osteoporosis....

  15. The Effect of Glucocorticoid and Glucocorticoid Receptor Interactions on Brain, Spinal Cord, and Glial Cell Plasticity

    Directory of Open Access Journals (Sweden)

    Kathryn M. Madalena

    2017-01-01

    Full Text Available Stress, injury, and disease trigger glucocorticoid (GC elevation. Elevated GCs bind to the ubiquitously expressed glucocorticoid receptor (GR. While GRs are in every cell in the nervous system, the expression level varies, suggesting that diverse cell types react differently to GR activation. Stress/GCs induce structural plasticity in neurons, Schwann cells, microglia, oligodendrocytes, and astrocytes as well as affect neurotransmission by changing the release and reuptake of glutamate. While general nervous system plasticity is essential for adaptation and learning and memory, stress-induced plasticity is often maladaptive and contributes to neuropsychiatric disorders and neuropathic pain. In this brief review, we describe the evidence that stress/GCs activate GR to promote cell type-specific changes in cellular plasticity throughout the nervous system.

  16. Familial glucocorticoid resistance caused by a splice site deletion in the human glucocorticoid receptor gene

    Energy Technology Data Exchange (ETDEWEB)

    Karl, M.; Lamberts, S.W.J.; Detera-Wadleigh, S.D.; Encio, I.J.; Stratakis, C.A.; Hurley, D.M.; Accili, D.; Chrousos, G.P. (National Institutes of Health, Bethesda, MD (United States) Erasmus Univ. of Rotterdam (Netherlands))

    1993-03-01

    The clinical syndrome of generalized, compensated glucocorticoid resistance is characterized by increased cortisol secretion without clinical evidence of hyper- or hypocortisolism, and manifestations of androgen and/or mineralocorticoid excess. This condition results from partial failure of the glucocorticoid receptor (GR) to modulate transcription of its target genes. The authors studied the molecular mechanisms of this syndrome in a Dutch kindred, whose affected members had hypercortisolism and approximately half of normal GRs, and whose proband was a young woman with manifestations of hyperandrogenism. Using the polymerase chain reaction to amplify and sequence each of the nine exons of the GR gene [alpha], along with their 5[prime]- and 3[prime]-flanking regions, the authors identified a 4-base deletion at the 3[prime]-boundary of exon 6 in one GR allele ([Delta][sub 4]), which removed a donor splice site in all three affected members studied. In contrast, the sequence of exon 6 in the two unaffected siblings was normal. A single nucleotide substitution causing an amino acid substitution in the amino terminal domain of the GR (asparagine to serine, codon 363) was also discovered in exon 2 of the other allele (G[sub 1220]) in the proband, in one of her affected brothers and in her unaffected sister. This deletion in the glucocorticoid receptor gene was associated with the expression of only one allele and a decrease of GR protein by 50% in affected members of this glucocorticoid resistant family. The mutation identified in exon 2 did not segregate with the disease and appears to be of no functional significance. The presence of the null allele was apparently compensated for by increased cortisol production at the expense of concurrent hyperandrogenism. 40 refs., 3 figs.

  17. Long-term efficacy of first line antiretroviral therapy in Indian HIV-1 infected patients: a longitudinal cohort study.

    Directory of Open Access Journals (Sweden)

    Ujjwal Neogi

    Full Text Available Short term efficacy of combination antiretroviral therapy (cART in resource-constrained settings is comparable to that found in western studies. However, long term data are limited. India has the third largest HIV infected population in the world but the long-term outcome of first line therapy according to the national guidelines has not been evaluated yet. Therefore, we conducted a long-term longitudinal analysis of the efficacy of the national first-line therapy in India from an observational cohort of Indian patients in two different clinical settings.A total 323 patients who had been on ART for a median of 23 months and achieved virological suppression 2000 copies/mL. Adherence and treatment interruptions (>48 h were assessed via self-report. In the studied patients, the median duration of viral suppression was 44 months; 15.8% of patients showed viral rebound, and 2.8% viral failure. Viral rebound or failure was significantly negatively related to perfect adherence (100% adherence and no treatment interruption >48 hrs. Virological re-suppression in the subsequent visit was observed in three patients without any change in therapy despite the presence of key mutations.Our study reports for the first time, a good long-term response to the first line therapy for a median of nearly four years although a less than perfect adherence increases the risk for treatment failure and subsequent drug resistance development. The empirical findings in this study also indicate the overall success of the Indian ART program in two different settings which likely are representative of other clinics that operate under the national guidelines.

  18. Individual differences in the effects of chronic prazosin hydrochloride treatment on hippocampal mineralocorticoid and glucocorticoid receptors.

    Science.gov (United States)

    Kabbaj, Mohamed; Morley-Fletcher, Sara; Le Moal, Michel; Maccari, Stefania

    2007-06-01

    The aim of this study was to investigate the noradrenergic regulation of mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in high responder (HR) and low responder (LR) male rats, an animal model of individual differences in hypothalamo-pituitary-adrenal axis activity and vulnerability to drugs of abuse. The effects of a chronic treatment with the noradrenergic alpha(1) antagonist (1-[4-amino-6,7-dimethoxy-2-quinazolinyl]-4-[2-furanylcarbonyl] piperazine) hydrochloride (prazosin) (0.5 mg/kg, i.p., 35 days) were assessed on stress-induced corticosterone (CORT) secretion and on hippocampal MRs and GRs in adrenally intact rats. In order to ascertain whether the effects of chronic prazosin treatment on hippocampal MRs and GRs were direct or indirect, through prazosin-induced CORT secretion, we also assessed the effects of the same treatment on adrenalectomized rats with CORT substitutive therapy. When compared with LR rats, HR rats exhibited a delayed return to the basal level of CORT following acute restraint stress; this was associated with a lower binding of MRs and GRs in HR rats than in LR rats. Chronic prazosin treatment had no effect in HR animals but markedly reduced hippocampal MRs and GRs, and increased stress-induced CORT secretion in LR rats. In LR adrenalectomized rats, prazosin reduced hipppocampal MRs but did not change GRs. Our results provide evidence of a differential regulation by noradrenaline of hippocampal MRs and GRs in HR and LR rats. These data could have clinical implications in terms of individual differences in the resistance to antidepressant treatments and individual differences in drug abuse.

  19. Long-term Compliance with Oral 5-aminosalicylic Acid Therapy and Risk of Disease Recurrence in Patients with Ulcerative Colitis

    DEFF Research Database (Denmark)

    Prosberg, Michelle V; Vester-Andersen, Marianne K; Andersson, Mikael

    2016-01-01

    BACKGROUND: Noncompliance to long-term medical therapy is a well-known problem among patients treated for ulcerative colitis, but studies of long-term consequences in unselected patients are lacking. The authors aimed to determine the risk of recurrence according to long-term compliance with oral 5......-aminosalicylic acid. Data were collected from medical records and the Danish National Prescription Database. They performed Cox regression analysis with adjustments for demographic and clinical characteristics to examine risk of recurrence (defined by increased use of oral 5-Aminosalicylic Acid, other additional...... not to take their medication....

  20. Addressing Quality of Life Issues in Long Term Survivors of Head & Neck Cancer treated with Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Bishan Basu

    2015-04-01

    Full Text Available The rapid advancement of curative treatment modalities has resulted in improvement of cure rates of head neck cancer leaving us with a larger number of long term survivors from the disease. Unfortunately, long term complications of therapy continue to hurt patients even after cure, compromising their quality of life. This is particularly true for the patients treated with primary radiation/chemo-radiation therapy, where so called organ preservation does not necessarily translate into preservation of organ function. Long term sequelae of treatment, particularly xerostomia and swallowing difficulties compromise the survivors’ quality of life. More studies, particularly suited to our clinical scenario, are warranted to address the quality of life issues in these patients, so that better evidence-based guidelines may be developed for their benefit.

  1. Genetic engineering of the glucocorticoid receptor by fusion with the herpes viral protein VP22 causes selective loss of transactivation.

    Science.gov (United States)

    Soden, J; Stevens, A; Ray, D W

    2002-03-01

    The development of methods for engineering proteins with novel properties opens the way to manipulating intracellular processes in a therapeutically useful way. Glucocorticoids, acting via glucocorticoid receptors (GR), are potent anti-inflammatory agents, acting to oppose nuclear factor kappa B (NF kappa B) function. The herpes viral protein, VP22, has been reported to confer intercellular trafficking activity on 'cargo' proteins, potentially facilitating gene therapy with intracellular proteins. VP22GR, resulting from the addition of VP22 to the N terminal of GR, was equipotent with the wild-type GR in opposing NF kappa B p65-driven expression of an NF kappa B reporter gene. Surprisingly, VP22GR was incapable of inducing transactivation of positive glucocorticoid reporter genes (MMTV-luc and TAT3-luc). Furthermore, the VP22GR had powerful dominant negative activity on both endogenous and exogenous GR transactivation. VP22GR was cytoplasmic in quiescent cells, and after hormone addition underwent nuclear translocation to share the same distribution as the GR. The ability of the VP22GR to selectively confer and enhance glucocorticoid-dependent transrepression of NF kappa B may be of use therapeutically in e.g. transplant rejection, inflammatory arthritis or asthma.

  2. Glucocorticoid programming of the mesopontine cholinergic system

    Directory of Open Access Journals (Sweden)

    Sónia eBorges

    2013-12-01

    Full Text Available Stress perception, response, adaptation and coping strategies are individually distinct, and the sequel of stress and/or glucocorticoids is also distinct between subjects. In the last years, it has become clear that early life stress is a powerful modulator of neuroendocrine stress-responsive circuits, programming intrinsic susceptibility to stress, and potentiating the appearance of stress-related disorders such as depression, anxiety and addiction. Herein we were interested in understanding how early life experiences reset the normal processing of negative stimuli, leading to emotional dysfunction. Animals prenatally exposed to glucocorticoids (iuGC present hyperanxiety, increased fear behaviour and hyper-reactivity to negative stimuli. In parallel, we found a remarkable increase in the number of aversive 22kHz ultrasonic vocalizations in response to an aversive cue. Considering the suggested role of the mesopontine tegmentum cholinergic pathway, arising from the laterodorsal tegmental nucleus (LDT and pedunculopontine tegmental nucleus (PPT, in the initiation of 22kHz vocalizations and hypothetically in the control of emotional arousal and tone, we decided to evaluate the condition of this circuit in iuGC animals. Notably, in a basal situation, iuGC animals present increased choline acetyltransferase (ChAT expression in the LDT and PPT, but not in other cholinergic nuclei, namely in the nucleus basalis of Meynert. In addition, and in accordance with the amplified response to an adverse stimulus of iuGC animals, we found marked changes in the cholinergic activation pattern of LDT and PPT regions. Altogether, our results suggest a specific cholinergic pathway programing by prenatal GC, and hint that this may be of relevance in setting individuals stress vulnerability threshold.

  3. Physiology and molecular mechanism of glucocorticoid action

    Directory of Open Access Journals (Sweden)

    Andrzej Nagalski

    2010-03-01

    Full Text Available Endogenous glucocorticoids (GCs are secreted into the systemic circulation from the adrenal cortex. This release is under the control of the circadian clock and can be enhanced at any time in response to a stressor. The levels of circulating GC are regulated systemically by the hypothalamo-pituitary-adrenal axis and locally by access to target cells and pre-receptor metabolism by 11β-hydroxysteroids dehydrogenase enzymes. GCs mediate their genomic action by binding to two different ligand-inducible transcription factors: high-affinity mineralocorticoid receptor (MR and 10-fold lower affinity glucocorticoid receptors (GRs. Responses to GCs vary among individuals, cells, and tissues. The diversity and specificity in the steroid hormone’s response in the cell is controlled at different levels, including receptor translocation, interaction with specific transcription factors and coregulators, and the regulation of receptor protein levels by microRNA. Moreover, multiple GR isoforms are generated from one single GR gene by alternative splicing and alternative translation initiation. These isoforms all have unique tissue distribution patterns and transcriptional regulatory profiles. Furthermore, each is subjected to various post-translational modifications that affect receptor function. Deciphering the molecular mechanisms of GC action is further complicated by the realization that GCs can induce rapid, non-genomic effects within the cytoplasm. A tight regulation of GC secretion and their cell-specific activity is essential for proper organism function. This is particularly seen under conditions of GC deficiency or excess, as in Addison’s disease and Cushing’s syndrome, respectively.

  4. Long-term safety and efficacy of fractionated stereotactic body radiation therapy for spinal metastases

    Energy Technology Data Exchange (ETDEWEB)

    Mantel, Frederick; Glatz, Stefan; Toussaint, Andre; Flentje, Michael; Guckenberger, Matthias [University Hospital Wuerzburg, Department of Radiation Oncology, Wuerzburg (Germany)

    2014-12-15

    Patients with long life expectancy despite metastatic status might benefit from long-term local control of spinal metastases. Dose-intensified radiotherapy (RT) is believed to control tumor growth better and thus offers longer pain relief. This single-institution study reports on fractionated stereotactic body radiation therapy (SBRT) for spinal metastases in patients with good life expectancy based on performance status, extent of metastases, histology, and time to metastasis. Between 2004 and 2010, 36 treatment sites in 32 patients (median age 55 years; male 61 %; median Karnofsky performance score 85) were treated with fractionated SBRT. The median treatment dose was 60 Gy (range, 48.5-65 Gy) given in a median of 20 fractions (range, 17-33); the median maximum dose to the planning risk volume for the spinal cord (PRV-SC) was 46.6 Gy. All patients suffering from pain prior to RT reported pain relief after treatment; after a median follow-up of 20.3 months, 61 % of treatment sites were pain-free, another 25 % associated with mild pain. In 86 % of treatments, patients were free from neurological symptoms at the time of the last clinical follow-up. Acute grade 1 toxicities (CTCAE 3.0) were observed in 11 patients. Myelopathy did not occur in any patient. Radiologically controlled freedom from local progression was 92 and 84 % after 12 and 24 months, respectively. Median overall survival (OS) was 19.6 months. Patient selection resulted in long OS despite metastatic disease, and dose-intensified fractionated SBRT for spinal metastases was safe and achieved long-term local tumor control and palliation of pain. (orig.) [German] Patienten mit guter Lebenserwartung trotz metastasierter Erkrankung koennten von einer lang andauernden lokalen Kontrolle von Wirbelsaeulenmetastasen profitieren. Eine dosisintensivierte Radiotherapie (RT) kann vermutlich eine bessere Tumorkontrolle und daher eine laengere Schmerzpalliation erreichen. Ausgewertet wurden die monozentrischen

  5. Long-Term Antiplatelet Mono- and Dual Therapies After Ischemic Stroke or Transient Ischemic Attack: Network Meta-Analysis.

    Science.gov (United States)

    Xie, Wuxiang; Zheng, Fanfan; Zhong, Baoliang; Song, Xiaoyu

    2015-08-24

    The latest guidelines do not make clear recommendations on the selection of antiplatelet therapies for long-term secondary prevention of stroke. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy and safety of long-term antiplatelet therapies after ischemic stroke or transient ischemic attack. We performed a network meta-analysis of randomized controlled trials to compare 11 antiplatelet therapies in patients with ischemic stroke or transient ischemic attack. In December 2014, we searched Medline, Embase, and the Cochrane Library database for trials. The search identified 24 randomized controlled trials including a total of 85 667 patients with antiplatelet treatments for at least 1 year. Cilostazol significantly reduced stroke recurrence in comparison with aspirin (odds ratio 0.66, 95% credible interval 0.44 to 0.92) and dipyridamole (odds ratio 0.57, 95% credible interval 0.34 to 0.95), respectively. Cilostazol also significantly reduced intracranial hemorrhage compared with aspirin, clopidogrel, terutroban, ticlopidine, aspirin plus clopidogrel, and aspirin plus dipyridamole. Aspirin plus clopidogrel could not significantly reduce stroke recurrence compared with monotherapies but caused significantly more major bleeding than all monotherapies except terutroban. The pooled estimates did not change materially in the sensitivity analyses of the primary efficacy outcome. Long-term monotherapy was a better choice than long-term dual therapy, and cilostazol had the best risk-benefit profile for long-term secondary prevention after stroke or transient ischemic attack. More randomized controlled trials in non-East Asian patients are needed to determine whether long-term use of cilostazol is the best option for the prevention of recurrent stroke. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  6. Ocular surface evaluation in eyes with chronic glaucoma on long term topical antiglaucoma therapy

    Directory of Open Access Journals (Sweden)

    Manu Saini

    2017-06-01

    Full Text Available AIM: To evaluate ocular surface changes and its correlation with the central corneal subbasal nerve fibre layer in chronic glaucoma patients. METHODS: A prospective comparative study of ocular surface evaluation was performed in 50 eyes of 25 patients using two or more antiglaucoma medications for at least 6mo and 50 eyes of 25 normal subjects without any ocular problems as controls. The study parameters evaluated included visual acuity, intraocular pressure, ocular surface evaluation parameters [fluorescein break-up time (FTBUT, Schirmer’s I test, ocular surface staining scores and ocular surface disease index score (OSDI], central corneal sensation (Cochet Bonnett aesthesiometer, central subbasal nerve fiber layer density (SBNFLD by confocal microscopy. RESULTS: The mean values in the glaucoma cases and control groups respectively were as follows: OSDI score (35.89±16.07/6.02±3.84; P=0.001, Schirmer’s I test score (7.63±2.64 mm/12.86±1.93 mm; P=0.001, FTBUT (9.44±2.76s/11.8±1.88s; P=0.001, corneal (5.7±2.33/ 1.1±0.58; P=0.001 and conjunctival staining score (5.06±1.94/0.84±0.46; P=0.001, corneal sensitivity (4.68±0.44/5.07±0.37; P=0.076, mean subbasal nerve fiber number (3.58±0.99/5.40±1.70; P=0.001, SBNFL length (1101.44±287.56 μm/1963.70±562.56 μm; P=0.001 and density (6883.94±1798.03 μm/mm2/12 273.15±3516.04 μm/mm2; P=0.001. Dry eye severity of level 2 and 3 was seen in 66% of glaucoma group. Corneal (R²=0.86 and conjunctival staining (R²=0.71 and OSDI score (R²=0.67 showed statistically significant negative correlation with central corneal SBNFLD while FTBUT (R²=0.84, corneal sensitivity (R²=0.52 showed positive correlation to central corneal SBNFLD in the long term topical antiglaucoma medication group. CONCLUSION: Ocular surface changes and antiglaucoma therapy induced dry eye is found to be associated with decreased SBNFLD in eyes on long term topical antiglaucoma medications.

  7. Long-term control of refractory hemorrhagic radiation proctitis with ozone therapy.

    Science.gov (United States)

    Clavo, Bernardino; Ceballos, Daniel; Gutierrez, Dominga; Rovira, Gloria; Suarez, Gerardo; Lopez, Laura; Pinar, Beatriz; Cabezon, Auxiliadora; Morales, Victoria; Oliva, Elena; Fiuza, Dolores; Santana-Rodriguez, Norberto

    2013-07-01

    Persistent or severe hemorrhagic radiation proctitis (HRP) has limited therapeutic options. To describe our experience with ozone therapy (O3T) in the management of refractory HRP. Patients (n=17; median age 69 years [range 42-80 years]) previously irradiated for prostate or uterine cancer and suffering persistent or severe HRP without response to conventional treatment were enrolled to receive an O3/O2 gas mixture via rectal insufflations and topical application of ozonized oil. Most of the patients (83%) had Grade 3 or Grade 4 toxicity. Median follow-up post-O3T was 40 months (range 3-56 months). Endoscopic treatments required were: 43 (median 1; range 0-10) pre-O3T; 17 (median 0; range 0-8; P=0.063) during O3T; and five (median 0; range 0-2; P=0.008) during follow-up. Hemoglobin levels were 10.35g/dL (7-14g/dL) pre-O3T and 13g/dL (9-15g/dL) (P=0.001) post-O3T. Median toxicity grades were 3 (range 2-4) pre-O3T, 1 (range 0-2; P<0.001) at the end of O3T, and 0 (range 0-1; P<0.001) at the last follow-up. Persistent advanced HRP was significantly improved with O3T. The addition of O3T can be useful as a complementary treatment in the long-term management of HRP and, as such, merits further evaluation. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  8. Patient Outcomes in Dose Reduction or Discontinuation of Long-Term Opioid Therapy: A Systematic Review.

    Science.gov (United States)

    Frank, Joseph W; Lovejoy, Travis I; Becker, William C; Morasco, Benjamin J; Koenig, Christopher J; Hoffecker, Lilian; Dischinger, Hannah R; Dobscha, Steven K; Krebs, Erin E

    2017-08-01

    Expert guidelines recommend reducing or discontinuing long-term opioid therapy (LTOT) when risks outweigh benefits, but evidence on the effect of dose reduction on patient outcomes has not been systematically reviewed. To synthesize studies of the effectiveness of strategies to reduce or discontinue LTOT and patient outcomes after dose reduction among adults prescribed LTOT for chronic pain. MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library from inception through April 2017; reference lists; and expert contacts. Original research published in English that addressed dose reduction or discontinuation of LTOT for chronic pain. Two independent reviewers extracted data and assessed study quality using the U.S. Preventive Services Task Force quality rating criteria. All authors assessed evidence quality using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Prespecified patient outcomes were pain severity, function, quality of life, opioid withdrawal symptoms, substance use, and adverse events. Sixty-seven studies (11 randomized trials and 56 observational studies) examining 8 intervention categories, including interdisciplinary pain programs, buprenorphine-assisted dose reduction, and behavioral interventions, were found. Study quality was good for 3 studies, fair for 13 studies, and poor for 51 studies. Many studies reported dose reduction, but rates of opioid discontinuation ranged widely across interventions and the overall quality of evidence was very low. Among 40 studies examining patient outcomes after dose reduction (very low overall quality of evidence), improvement was reported in pain severity (8 of 8 fair-quality studies), function (5 of 5 fair-quality studies), and quality of life (3 of 3 fair-quality studies). Heterogeneous interventions and outcome measures; poor-quality studies with uncontrolled designs. Very low quality evidence suggests that several types of interventions may be effective to reduce or

  9. Factors associated with long-term vertical skeletal changes induced by facemask therapy in patients with Class III malocclusion.

    Science.gov (United States)

    Kwak, Hee-Jong; Park, Hae-Jin; Kim, Yoon-Ji; Lee, Dong-Yul

    2017-11-13

    This study investigated the long-term vertical skeletal changes induced by facemask therapy in patients with Class III malocclusion and different vertical skeletal patterns. A total of 54 patients (20 boys and 34 girls; mean age, 7.7 ± 2.0 years) with Class III malocclusion who were successfully treated with facemask therapy were included in this study. Vertical skeletal changes (overbite depth indicator, angle between the Sella-Nasion (SN) plane and Gonion-Gnathion (GoGn) line, angle between the Frankfort horizontal (FH) plane and mandibular plane, gonial angle, and angle between the SN plane and palatal plane) were measured on lateral cephalograms from before treatment (T0) to after facemask therapy (T1) and from T0 to after retention (T2). Multivariate linear regression analysis was used to study the associations of the patients' skeletal patterns with the short-term (T0-T1) and long-term (T0-T2) vertical skeletal changes as a result of facemask therapy. The mean treatment period of facemask therapy (T0-T1) was 1.4 ± 0.6 years, and the mean retention period (T1-T2) was 6.9 ± 2.6 years. Age at T0 was significantly correlated with vertical skeletal changes from T0 to T1. Differences in the treatment results between sexes were not significant. The angle between point A-point B line and mandibular plane to mandibular plane angle at T0 and the angle between the FH plane and mandibular plane at T0 were significant predictors for short-term and long-term changes. Changes in the Sella-Nasion-point A from T0 to T1 and from T1 to T2 significantly affected vertical changes in the short term and long term, respectively. Vertical skeletal changes as a result of facemask therapy are significantly associated with severity of the skeletal Class III malocclusion and mandibular plane angulation before treatment and the amount of forward maxillary growth during the treatment and retention periods.

  10. Short-term intensive insulin therapy at diagnosis in type 2 diabetes: plan for filling the gaps.

    Science.gov (United States)

    Weng, Jianping; Retnakaran, Ravi; Ariachery C, Ammini; Ji, Linong; Meneghini, Luigi; Yang, Wenying; Woo, Jeong-Taek

    2015-09-01

    Short-term intensive insulin therapy is unique amongst therapies for type 2 diabetes because it offers the potential to preserve and improve beta-cell function without additional pharmacological treatment. On the basis of clinical experience and the promising results of a series of studies in newly diagnosed patients, mostly in Asian populations, an expert workshop was convened to assess the available evidence and the potential application of short-term intensive insulin therapy should it be advocated for inclusion in clinical practice. Participants included primary care physicians and endocrinologists. We endorse the concept of short-term intensive insulin therapy as an option for some patients with type 2 diabetes at the time of diagnosis and have identified the following six areas where additional knowledge could help clarify optimal use in clinical practice: (1) generalizability to primary care, (2) target population and biomarkers, (3) follow-up treatment, (4) education of patients and providers, (5) relevance of ethnicity, and (6) health economics. © 2014 The Authors. Diabetes Metabolism Research and Reviews published by John Wiley & Sons, Ltd.

  11. Long term follow-up of infliximab efficacy in pulmonary and extra-pulmonary sarcoidosis refractory to conventional therapy.

    Science.gov (United States)

    Russell, Eric; Luk, Francis; Manocha, Sonia; Ho, Tung; O'Connor, Carolyn; Hussain, Humaira

    2013-08-01

    Infliximab, a humanized, chimeric, monoclonal antibody against tumor necrosis alpha (TNF-α), has been shown to reduce the pulmonary and extra-pulmonary manifestations of sarcoidosis, however, there is little information regarding sustained efficacy with long-term use of infliximab. We retrospectively investigate whether a reduction in disease response is maintained, over a prolonged course of therapy (up to 85 months) with infliximab, and report on adverse events associated with its use. Subjects with multi-organ sarcoidosis were prescribed infliximab, between January 2000 to June 2010 due to failure of conventional therapy and were identified from the Drexel University College of Medicine sarcoidosis clinic. Retrospective patient reported symptom and objective clinical data analyses of pulmonary and extra-pulmonary findings were evaluated pre-infliximab and post or concurrent infliximab therapy. Any adverse events or reasons for discontinuation during infliximab therapy were reported. Twenty-six patients with biopsy proven sarcoidosis received anti-TNF therapy and met the criteria for study inclusion. Clinical evidence of sustained resolution or improvement was demonstrated in 58.5% of all organs assessed (p =<0.001). No clinical change in disease activity was seen in 35.8% of all organs evaluated. Despite infliximab treatment, 5.7% had progressive disease activity. Adverse events were seen in 57.7% of patients treated with infliximab over a 46.2 month average duration of therapy. Three (12%) patients had an adverse event that required permanent discontinuation. Infliximab is efficacious in the treatment of extra-pulmonary sarcoidosis and the efficacy is maintained with prolonged treatment. In patients with pulmonary sarcoid, sustained improvement in pulmonary imaging was seen after initiation of infliximab, however, post-treatment pulmonary function testing was not conclusive. Long-term infliximab therapy was well tolerated for our study group. Copyright © 2012

  12. Focal Segmental Glomerular Sclerosis Ameliorated by Long-term Hemodialysis Therapy with Low-density Lipoprotein Apheresis.

    Science.gov (United States)

    Araki, Hisazumi; Ono, Shinya; Nishizawa, Yuka; Deji, Naoko; Nakazawa, Jun; Morita, Yoshikata; Kume, Shinji; Chin-Kanasaki, Masami; Isshiki, Keiji; Araki, Shin-ichi; Arimura, Tetsuro; Maegawa, Hiroshi; Uzu, Takashi

    2015-01-01

    We report a case involving a 43-year-old Japanese woman with steroid-resistant focal segmental glomerular sclerosis (FSGS) and severe renal dysfunction, which was ameliorated by low-density lipoprotein apheresis (LDL-A). She had been treated with steroid therapy, but had experienced anuria for over 10 weeks and required hemodialysis. She was then treated with LDL-A, which resulted in improved urinary protein excretion and renal function. Her renal function recovered after 97 days of hemodialysis therapy. This case suggests that LDL-A may represent an effective rescue treatment in patients with FSGS and long-term anuria.

  13. Long-term effectiveness of highly active antiretroviral therapy (HAART) in perinatally HIV-infected children in Denmark

    DEFF Research Database (Denmark)

    Bracher, Linda; Valerius, Niels Henrik; Rosenfeldt, Vibeke

    2007-01-01

    The long-term impact of highly active antiretroviral therapy (HAART) on HIV-1 infected children is not well known. The Danish Paediatric HIV Cohort Study includes all patients perinatally infected...... percentage >25% increased to 60-70% over the y of treatment. For the total cohort, 245 patient-y of observation were available with only 1 death. During our observation period there were no signs of a waning impact. The challenge remains to maintain a high adherence to therapy as the children grow...

  14. Discontinuation of hormone replacement therapy after myocardial infarction and short term risk of adverse cardiovascular events

    DEFF Research Database (Denmark)

    Bretler, Ditte-Marie; Hansen, Peter Riis; Sørensen, Rikke

    2012-01-01

    To assess the risk of adverse cardiovascular events in women who discontinue hormone replacement therapy after myocardial infarction compared with those who continue.......To assess the risk of adverse cardiovascular events in women who discontinue hormone replacement therapy after myocardial infarction compared with those who continue....

  15. Prospective controlled cohort studies on long-term therapy of ovairian cancer patients with mistletoe (Viscum album L.) extracts iscador.

    Science.gov (United States)

    Grossarth-Maticek, Ronald; Ziegler, Renatus

    2007-01-01

    Mistletoe extracts such as Iscador are commonly used as complementary/anthroposophic medications for many cancer indications, particularly for solid cancers. The efficacy of this complementary therapy is still controversial. Does long-term therapy with mistletoe extracts Iscador show any effect on survival and psychosomatic self-regulation of patients with ovarian cancer? Prospective recruitment and long-term follow-up in controlled cohort studies. (1) Two randomized matched-pair studies: OvarRand (ovarian cancer patients without distant metastases; 21 pairs) and OvarMetRand (ovarian cancer patients with distant metastases; 20 pairs); patients having no mistletoe therapy were matched for prognostic factors. By paired random allocation, one of the patients of each pair was suggested therapy with mistletoe extracts Iscador to be applied by her attending physician. (2) Two non-randomized matched-pair studies: Ovar (ovarian cancer patients without distant metastases; 75 pairs) and OvarRand (ovarian cancer patients with distant metastases; 62 pairs); patients that already received therapy with mistletoe extracts Iscador were matched by the same criteria to control patients without therapy with mistletoe extracts Iscador. For overall survival in the randomized studies, the effect in favor of therapy with mistletoe extracts Iscador was significant in OvarMetRand but not in OvarRand; hazard ratio estimate and 95% confidence interval: 0.40 (0.15, 1.03) and 0.33 (0.12, 0.92), respectively. In the non-randomized studies Ovar and OvarMet, the results adjusted for relevant prognostic variables were 0.47 (0.31, 0.69) and 0.62 (0.37, 1.05). Psychosomatic self-regulation in the Iscador group increases significantly within 12 months on a scale from 1 to 6 compared with the control group in the randomized study OvarRand as well as in the non-randomized study Ovar on patients with ovarian cancer without distant metastases; estimate of the median difference and 95% confidence interval

  16. Effects of antifracture drugs in postmenopausal, male and glucocorticoid-induced osteoporosis--usefulness of alendronate and risedronate.

    Science.gov (United States)

    Iwamoto, Jun; Takeda, Tsuyoshi; Sato, Yoshihiro

    2007-11-01

    The purpose of this paper is to discuss the effects of antifracture drugs on postmenopausal, male and glucocorticoid-induced osteoporosis, focussing on the efficacy and safety of alendronate and risedronate. A search of the literature was conducted using PubMed for strictly conducted systematic reviews published from 1995 to present with homogeneity, meta-analyses with homogeneity, and randomized controlled trials (RCTs) with a narrow confidence interval. According to the results of the systematic reviews and meta-analyses, alendronate and risedronate are useful for the prevention of vertebral and non-vertebral fractures in postmenopausal women with osteoporosis. The results of RCTs have shown the antifracture efficacy of raloxifene and ibandronate against vertebral fractures and that of strontium and parathyroid hormone against vertebral and non-vertebral fractures in postmenopausal women with osteoporosis. In addition, the long-term safety of alendronate, risedronate and raloxifene has been established. On the other hand, RCTs have shown that, only alendronate prevents vertebral fractures in men with osteoporosis, and that alendronate and risedronate can prevent vertebral fractures in patients receiving glucocorticoid treatment. There seems to be less evidence of the antifracture efficacy of the drugs in male and glucocorticoid-induced osteoporosis. They have limitations related to long-term compliance, gastrointestinal intolerance and poor and variable absorption form gastrointestinal tract. Thus, intermittent intravenous administration of bisphosphonates such as ibandronate and zoledronate or subcutaneous administration of denosumab might address some of these problems, although the antifracture efficacy of these drugs needs be established. However, antifracture efficacy and long-term safety are important points in the choice of drugs for the treatment of osteoporosis. Thus, the evidence derived from the literature, based on strict evidence-based medicine

  17. Long-term success of dental implants in patients with head and neck cancer after radiation therapy.

    Science.gov (United States)

    Curi, M M; Condezo, A F B; Ribeiro, K D C B; Cardoso, C L

    2018-02-06

    The purpose of this study was to analyze the long-term success and factors potentially influencing the success of dental implants placed in patients with head and neck cancer who underwent radiation therapy with a minimum total dose of 50Gy during the years 1995-2010. Thirty-five patients (169 dental implants) were included in this study. Data on demographic characteristics, tumour type, radiation therapy, implant sites, implant dimensions, and hyperbaric oxygen therapy (HBOT) were obtained from the medical records and analyzed. Implant survival was estimated using Kaplan-Meier survival curves. Seventy-nine dental implants were placed in the maxilla and 90 in the mandible. The mean follow-up after implant installation was 7.4 years (range 0.3-14.7 years). The overall 5-year survival rate for all implants was 92.9%. Sex (P<0.001) and the mode of radiation therapy delivery (P=0.005) had a statistically significant influence on implant survival. Age, time of implantation after irradiation, implant brand and dimensions, and HBOT had no statistically significant influence on implant survival. Osseointegrated dental implants can be used successfully in the oral rehabilitation of patients with head and neck cancer with a history of radiation therapy. Risk factors such as sex and the mode of radiation therapy delivery can affect implant survival. Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  18. Effects of Chronic Psychosocial Stress on Reduction of Basal Glucocorticoid Levels and Suppression of Glucocorticoid Levels Following Dexamethasone Administration in Animal Model of PTSD

    Directory of Open Access Journals (Sweden)

    Ana Starcevic

    2014-03-01

    Conclusion: Significant changes in HPA activity, reductions in basal glucocorticoid levels and enhanced dexamethasone induced inhibition of glucocorticoid levels have been manifested. All of this is manifested in PTSD patients also as many other stress induces changes.

  19. Glucocorticoids in nephrology I: pharmacology and side effects

    Directory of Open Access Journals (Sweden)

    Jernej Pajek

    2015-05-01

    Full Text Available Glucocorticoids have been used in clinical medicine since 1940s. Despite the time-long use they are still a subject of active ongoing research. We describe the mode of action, pharmacology and side effects to enable proper prescription of these drugs. Glucocorticoids exert genomic and non-genomic effects, the latter become important at higher doses. The nomenclature of dosage ranges and the principles of dosage adjustments are given. Glucocortioid use is associated with frequent and important side effects in numerous organ systems. Prophylactic treatments for osteoporosis and infections are described. The suppression of hypothalamic-hypophyseal hormonal axis determines the need for gradual glucocorticoid withdrawal and supplementation after discontinuation. Finally, glucocorticoid withdrawal syndrome is described.

  20. Hypersensitivity Reactions from Excipients in Systemic Glucocorticoid Formulations

    DEFF Research Database (Denmark)

    Calogiuri, Gianfranco; Garvey, Lene H; Romita, Paolo

    2016-01-01

    Glucocorticoids are the most widely used drugs for the treatment of hypersensitivity, however these drugs themselves and the excipients contained in commercial corticosteroid formulations are able to induce severe immediate-type hypersensitivity reactions. Reactions involving excipients have been...

  1. Cognitive and Guided Mastery Therapies for Panic Disorder with Agoraphobia: 18-Year Long-Term Outcome and Predictors of Long-Term Change.

    Science.gov (United States)

    Hoffart, Asle; Hedley, Liv M; Svanøe, Karol; Sexton, Harold

    2016-01-01

    In this study, we wished to compare the long-term outcome of (medication-free) panic disorder with agoraphobia patients randomized to cognitive or guided mastery therapy. Thirty-one (67.4%) of 46 patients who had completed treatment were followed up about 18 years after end of treatment. In the combined sample and using intent-to-follow-up analyses, there were large within-group effect sizes of -1.79 and -1.63 on the primary interview-based and self-report outcome measures of avoidance of situations when alone, and 56.5% no longer had a panic disorder and/or agoraphobia diagnosis. No outcome differences between the two treatments emerged. Guided mastery was associated with greater beneficial changes in catastrophic beliefs and self-efficacy. For two of five outcome measures, more reduction in panic-related beliefs about physical and mental catastrophes from pre- to post-treatment predicted lower level of anxiety from post-treatment to 18-year follow-up when the effect of treatment changes in (a) self-efficacy and (b) anxiety was controlled. However, for one of the outcome measures, this effect attenuated with time. Copyright © 2014 John Wiley & Sons, Ltd. The results suggest that the very-long-term outcome of both cognitive therapy and guided mastery therapy for agoraphobia is positive. The results support the role of catastrophic beliefs as mediator of change. The pattern of results suggests that learning processes other than catastrophic beliefs may be important for long-term outcome as well. Copyright © 2014 John Wiley & Sons, Ltd.

  2. Use of Antithrombotic Therapy and Long-Term Clinical Outcome Among Patients Surviving Intracerebral Hemorrhage

    DEFF Research Database (Denmark)

    Ottosen, Tobias Pilgaard; Grijota, Miriam; Hansen, Morten Lock

    2016-01-01

    (43%) died, 497 (17%) had a thromboembolic event, and 536 (18%) had major bleeding. Postdischarge use of oral anticoagulation therapy among patients with indication for oral anticoagulation therapy was associated with a significant lower risk of death (adjusted hazard ratio, 0.59; 95% confidence...... inhibitors was not related to statistically significantly improved clinical outcome. CONCLUSIONS: Approximately 1 of 2 patients surviving intracerebral hemorrhage had a high risk of thromboembolism. Postdischarge use of oral anticoagulation therapy was associated with a lower risk of all-cause mortality...

  3. Glucocorticoids and the regulation of memory in health and disease.

    Science.gov (United States)

    de Quervain, Dominique J-F; Aerni, Amanda; Schelling, Gustav; Roozendaal, Benno

    2009-08-01

    Over the last decades considerable evidence has accumulated indicating that glucocorticoids - stress hormones released from the adrenal cortex - are crucially involved in the regulation of memory. Specifically, glucocorticoids have been shown to enhance memory consolidation of emotionally arousing experiences, but impair memory retrieval and working memory during emotionally arousing test situations. Furthermore, growing evidence indicates that these different glucocorticoid effects all depend on emotional arousal-induced activation of noradrenergic transmission within the basolateral complex of the amygdala (BLA) and on interactions of the BLA with other brain regions, such as the hippocampus and neocortical regions. Here we review findings from both animal and human experiments and present an integrated perspective of how these opposite glucocorticoid effects might act together to serve adaptive processing of emotionally significant information. Furthermore, as intense emotional memories also play a crucial role in the pathogenesis and symptomatology of anxiety disorders, such as posttraumatic stress disorder (PTSD) or phobias, we discuss to what extent the basic findings on glucocorticoid effects on emotional memory might have implications for the understanding and treatment of these clinical conditions. In this context, we review data suggesting that the administration of glucocorticoids might ameliorate chronic anxiety by reducing retrieval of aversive memories and enhancing fear extinction.

  4. The influence of glucocorticoid signaling on tumor progression.

    Science.gov (United States)

    Volden, Paul A; Conzen, Suzanne D

    2013-03-01

    The diagnosis of cancer elicits a broad range of well-characterized stress-related biobehavioral responses. Recent studies also suggest that an individual's neuroendocrine stress response can influence tumor biology. One of the major physiological pathways altered by the response to unrelenting social stressors is the hypothalamic-pituitary-adrenal or HPA axis. Initially following acute stress exposure, an increased glucocorticoid response is observed; eventually, chronic stress exposure can lead to a blunting of the normal diurnal cortisol pattern. Interestingly, recent evidence also links high primary tumor glucocorticoid receptor expression (and associated increased glucocorticoid-mediated gene expression) to more rapid estrogen-independent breast cancer progression. Furthermore, animal models of human breast cancer suggest that glucocorticoids inhibit tumor cell apoptosis. These findings provide a conceptual basis for understanding the molecular mechanisms underlying the influence of the individual's stress response, and specifically glucocorticoid action, on breast cancer and other solid tumor biology. How this increased glucocorticoid signaling might contribute to cancer progression is the subject of this review. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. The Associations Between Physical Therapy and Long-Term Outcomes for Individuals with Lumbar Spinal Stenosis in the SPORT study

    Science.gov (United States)

    Fritz, Julie M.; Lurie, Jon D.; Zhao, Wenyan; Whitman, Julie M.; Delitto, Anthony; Brennan, Gerard P.; Weinstein, James N.

    2013-01-01

    Background/Context A period of non-surgical management is advocated prior to surgical treatment for most patients with lumbar spinal stenosis. Currently, little evidence is available to define optimal non-surgical management. Physical therapy is often used, however its use and effectiveness relative to other non-surgical strategies has not been adequately explored. Purpose Describe the utilization of physical therapy and other non-surgical interventions by patients with lumbar spinal stenosis and examine the relationship between physical therapy and long-term prognosis. Study Design Secondary analysis of the Spine Patient Outcomes Research Trial (SPORT) combining data from randomized and observational studies. Setting 13 spine clinics in 11 states in the United States. Patient Sample Patients with lumbar spinal stenosis receiving non-surgical management including those who did or did not receive physical therapy within 6 weeks of enrollment. Outcome Measures Primary outcome measures included cross-over to surgery, the bodily pain and physical function scales changes from the Survey Short Form 36 (SF-36), and the modified Oswestry Disability Index. Secondary outcome measures were patient satisfaction and the Sciatica Bothersomeness Index. Methods Baseline characteristics and rates of cross-over to surgery were compared between patients who did or did not receive physical therapy. Baseline factors predictive of receiving physical therapy were examined with logistic regression. Mixed effects models were used to compare outcomes between groups at 3 and 6 months, and 1 year after enrollment adjusted for baseline severity and patient characteristics. Results Physical therapy was used in the first 6 weeks by 90 of 244 patients (37%) and was predicted by the absence of radiating pain and being single instead of married. Physical therapy was associated with a reduced likelihood of cross-over to surgery after 1 year (21% vs 33%, p=0.045), and greater reductions on the SF-36

  6. [Prospective multicenter study on long-term ketogenic diet therapy for intractable childhood epilepsy].

    Science.gov (United States)

    2013-04-01

    To evaluate the efficacy and safety of long-term ketogenic diet (KD) on the children with intractable epilepsy. This was a prospective, open-label study of intractable epilepsy patients treated with the classic KD with a lipid-to-nonlipid ratio 4:1 between October 2004 and July 2011 at five Chinese epilepsy centers. A total of 299 patients were enrolled. The patients were divided into different groups according to age (including the below-1-year-old group, 1-to-3-year-old group, 3-to-6-year-old group, 6-to-10-year-old group, and over-10-year-old group), etiology (cryptogenic epilepsy, symptomatic epilepsy, and idiopathic epilepsy), and the seizure types (included infantile spasm, Lennox-Gastaut syndrome, Ohtahara syndrome, tuberous sclerosis, Dravet syndrome, generalized epilepsy, and partial epilepsy). Parents were assigned to write seizure diaries which recorded the seizure presentations, tolerability, and complications associated with the KD. Patients' weight and height were measured every week. Blood β-hydroxybutyric acid, blood sugar, and urinary ketone bodies were monitored closely. Patients were followed up through telephone calls by the nutritionists every month and regular outpatient visits or hospitalizations were recommended at all time-points which included the third, sixth and twelfth month after initiation. Efficacy was measured through seizure frequency. The variables related to the efficacy were also analyzed. SPSS 17.0 was used for all statistical analysis. At 3, 6, and 12 months after initiation, 65.9%, 44.8%, and 26.4% patients remained on the diet, and 37.4%, 26.1%, and 20.4% had a > 50% reduction in their seizure frequency, including 21.7%, 10.7%, and 11.0% who became seizure free, respectively. At 24 months after initiation, 29 patients remained on the diet, and 28 patients had a > 90% seizure reduction, including five became seizure free. At 36 months after initiation, 7 patients remained on the diet, and all of them had a > 90% seizure

  7. The importance of knowing the home conditions of patients receiving long-term oxygen therapy

    Directory of Open Access Journals (Sweden)

    Godoy I

    2012-07-01

    Full Text Available Ilda Godoy,1 Suzana Erico Tanni,2 Carme Hernández,3 Irma Godoy21Department of Nursing, Botucatu School of Medicine, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil; 2Department of Pulmonology, Botucatu School of Medicine, Universidade Estadual Paulista, São Paulo, Brazil; 3Integrated Care Unit, Hospital Clinic, Barcelona, SpainPurpose: Long-term oxygen therapy (LTOT is one of the main treatments for patients with chronic obstructive pulmonary disease. Patients receiving LTOT may have less than optimal home conditions and this may interfere with treatment. The objective of this study was, through home visits, to identify the characteristics of patients receiving LTOT and to develop knowledge regarding the home environments of these patients.Methods: Ninety-seven patients with a mean age of 69 plus or minus 10.5 years were evaluated. This study was a cross-sectional descriptive analysis. Data were collected during an initial home visit, using a questionnaire standardized for the study. The results were analyzed retrospectively.Results: Seventy-five percent of the patients had chronic obstructive pulmonary disease, and 11% were active smokers. The patients’ mean pulse oximetry values were 85.9% plus or minus 4.7% on room air and 92% plus or minus 3.9% on the prescribed flow of oxygen. Most of the patients did not use the treatment as prescribed and most used a humidifier. The extension hose had a mean length of 5 plus or minus 3.9 m (range, 1.5–16 m. In the year prior to the visit, 26% of the patients received emergency medical care because of respiratory problems. Few patients reported engaging in leisure activities.Conclusion: The home visit allowed us to identify problems and interventions that could improve the way LTOT is used. The most common interventions related to smoking cessation, concentrator maintenance and cleaning, use of a humidifier, and adjustments of the length of the connector hose. Therefore, the home visit

  8. Massage therapy has short-term benefits for people with common musculoskeletal disorders compared to no treatment: a systematic review

    Directory of Open Access Journals (Sweden)

    Diederik C Bervoets

    2015-07-01

    Full Text Available Question: Is massage therapy effective for people with musculoskeletal disorders compared to any other treatment or no treatment? Design: Systematic review of randomised clinical trials. Participants: People with musculoskeletal disorders. Interventions: Massage therapy (manual manipulation of the soft tissues as a stand-alone intervention. Outcome: The primary outcomes were pain and function. Results: The 26 eligible randomised trials involved 2565 participants. The mean sample size was 95 participants (range 16 to 579 per study; 10 studies were considered to be at low risk of bias. Overall, low-to-moderate-level evidence indicated that massage reduces pain in the short term compared to no treatment in people with shoulder pain and osteoarthritis of the knee, but not in those with low back pain or neck pain. Furthermore, low-to-moderate-level evidence indicated that massage improves function in the short term compared to no treatment in people with low back pain, knee arthritis or shoulder pain. Low-to-very-low-level evidence from single studies indicated no clear benefits of massage over acupuncture, joint mobilisation, manipulation or relaxation therapy in people with fibromyalgia, low back pain and general musculoskeletal pain. Conclusions: Massage therapy, as a stand-alone treatment, reduces pain and improves function compared to no treatment in some musculoskeletal conditions. When massage is compared to another active treatment, no clear benefit was evident. [Bervoets DC, Luijsterburg PAJ, Alessie JJN, Buijs MJ, Verhagen AP (2015 Massage therapy has short-term benefits for people with common musculoskeletal disorders compared to no treatment: a systematic review. Journal of Physiotherapy 61: 106–116

  9. Long-term follow-up of patients with difficult to treat type 1 autoimmune hepatitis on Tacrolimus therapy.

    Science.gov (United States)

    Than, Nwe Ni; Wiegard, Christiane; Weiler-Normann, Christina; Füssel, Katja; Mann, Jake; Hodson, James; Hirschfield, Gideon M; Lohse, Ansgar W; Adams, David H; Schramm, Christoph; Oo, Ye Htun

    2016-03-01

    Autoimmune hepatitis (AIH) is an immune-mediated liver disease, which requires long-term immunosuppression. Ten to fifteen percent of patients experience insufficient/intolerance response to standard therapy. Although alternate immunosuppression has been applied, there is little long-term data reported on safety, efficacy, steroid-dose reduction and disease evolution in patients with difficult AIH who were on Tacrolimus therapy. Clinical, biochemical, immunological profiles, treatment response and side effects of 17 AIH patients treated with Tacrolimus between 2003 and 2014 were analyzed from two tertiary referral liver centers. Tacrolimus was started on 16/17 (94%) patients due to insufficient response to standard therapy. The median duration of treatment was 24 months and patients were followed up for median of 60 months. Tacrolimus dosage was 2 mg/day (median). During first year of therapy, there was a significant improvement in immunoglobulin G and Aspartate transaminase level. 9/17 (52%) compliant and definite AIH patients remained on Tacrolimus at end of follow-up and prednisolone dose reduction was achieved from 10 to 5 mg. All patients are alive and one patient underwent liver transplantation. 4/17 (24%) patients developed overlap with primary sclerosing cholangitis over follow-up period. No significant side effects were observed with Tacrolimus therapy. Tacrolimus could be used in compliant patients with difficult to treat AIH in experienced centers. Its use is safe and can improve liver biochemistry, IgG and reduce steroid requirement. However, due to the lack of immunomodulatory effect, unmet need for effective immune-regulatory therapies still remain for AIH patients.

  10. Long-term results of cabergoline therapy for macroprolactinomas and analyses of factors associated with remission after withdrawal.

    Science.gov (United States)

    Watanabe, Shinya; Akutsu, Hiroyoshi; Takano, Shingo; Yamamoto, Tetsuya; Ishikawa, Eiichi; Suzuki, Hiroaki; Matsumura, Akira

    2017-02-01

    Withdrawal of cabergoline is generally challenging, especially in patients with large or invasive macroprolactinomas. Therefore, we aimed to assess long-term results of cabergoline therapy for macroprolactinomas and remission achievement results after withdrawal in patients with macroprolactinomas. We also investigated clinical characteristics and factors related to remission after withdrawal. This was an institutional review board-approved retrospective analysis. We studied 46 macroprolactinoma patients who had taken cabergoline during the period from 2003 through 2013. Administration of cabergoline was maintained for 5 years before withdrawal. Median follow-up after the initiation of cabergoline therapy was 54·3 (range 5·3 to 137·2) months. Recurrences of hyperprolactinaemia were observed in 3 of 11 (27%) postwithdrawal patients at a median time of 3·0 (range; 2·9-11·2) months, indicating that a high percentage (73%) maintained remission for at least 12 months after cabergoline cessation. Factors significantly associated with remission were analysed in 21 patients receiving long-term cabergoline administration. On multivariate analysis, the absence of cavernous sinus invasion on pretreatment MRI (≥3/4 tumour encasement of the intracavernous internal carotid artery) (HR; 21·94, 95% CI; 2·06-1071·0, P = 0·006), initial PRL cabergoline therapy (HR; 5·14, 95% CI; 1·10-39·02, P = 0·04) showed statistically significant correlations with remission after withdrawal. Cabergoline therapy can achieve a high percentage (73% in this series) of remission maintenance for at least 12 months after cessation of a 5-year course of therapy, even in patients with macroprolactinomas. The absence of cavernous sinus invasion, serum PRL level lower than 132·7 ng/ml before cabergoline therapy or nadir serum PRL below 1·9 ng/ml were related to more frequent remission after withdrawal of cabergoline in patients receiving this medication for 5 years. © 2016 John Wiley

  11. Evaluation of long-term cosmetic results and complications following breast conserving surgery and radiation therapy for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fujishiro, Satsuki; Mitsumori, Michihide; Kokubo, Masaki; Nagata, Yasushi; Sasai, Keisuke; Hiraoka, Masahiro [Kyoto Univ. (Japan). Hospital; Kodama, Hiroshi

    1999-12-01

    Long-term cosmetic outcomes and complications were evaluated in 109 patients with breast cancer who had been treated by breast conservation therapy. Patients received radiation therapy at Kyoto University Hospital following quadrantectomy and level II or III axillary node dissection. Factors that might influence long-term cosmetic results were also analyzed. Irradiation to the breast was administered in 2 Gy fractions, 5 times a week for a total of 50 Gy in all patients. Cobalt-60 {gamma}-rays were used in 108 patients with the exception of 1 patient who received 6 Mev X-ray. Some patients with positive or close margins received boost irradiation of 10 Gy using electron beams to the primary tumor bed. Cosmetic outcome was assessed by both a scoring method and breast retraction assessment (BRA). Forty-seven percent of patients were assessed as excellent to good before radiation therapy. The percent of excellent to good decreased shortly after termination of radiation therapy, but gradually improved and stabilized by 3 years. Seventy percent of patients showed a score of excellent to good 5 years after treatment. The average BRA of the 109 patients was 3.0 cm. This did not change between 3 and 5 years after treatment. A significant correlation between cosmetic score and BRA was shown at all follow-up times. Factors such as age over 50 years (p=0.008), tumor location in the outer quadrant (p=0.02) and boost irradiation (p=0.03) significantly affected the cosmetic score. Arm edema and restriction of shoulder movement were observed in 22% and 49% at the start of radiation therapy, these improved within approximately 3 years and 1 year after treatment, respectively. Mild skin change was observed in 60% of patients even 5 years after treatment. The results indicate that cosmetic outcome after breast conservation therapy is clinically acceptable, and the complication rate is low. (author)

  12. [Glucocorticoid and Bone. The effect of glucocorticoid and PTH in osteoblast apoptosis and differentiation via interleukin 11 expression].

    Science.gov (United States)

    Endo, Itsuro

    2014-09-01

    Intermittent PTH administration stimulates bone formation and counteracts the inhibition of bone formation by glucocorticoid excess. We have previously demonstrated that PTH enhances interleukin (IL) -11 gene transcription by a rapid induction of delta-fosB expression and Smad1/5 phosphorylation. On the other hand, glucocorticoid can suppress osteoblast differentiation and enhance apoptosis of osteoblast cells via down-regulation of IL-11 expression. PTH could reverse glucocorticoid-induced these damage of osteoblast via stimulation of IL-11 expression. Our data also suggested that IL-11 mediates stimulatory and inhibitory signals of osteoblast differentiation by affecting Wnt signaling. These data demonstrates that PTH and glucocorticoid may regulate osteoblast differentiation and apoptosis via their effect on IL-11 expression.

  13. Long-term effects of electrical neurostimulation in patients with unstable angina : Refractory to conventional therapies

    NARCIS (Netherlands)

    de Vries, Jessica; DeJongste, Mike J. L.; Zijlstra, Felix; Staal, Michiel

    2007-01-01

    Background. Patients with unstable angina pectoris may become refractory to conventional therapies. Electrical neurostimulation with transcutaneous electrical stimulation and/or spinal cord stimulation has been shown to be effective for patients with refractory unstable angina pectoris in hospital

  14. Long-term efficacy of catheter ablation as first-line therapy for paroxysmal atrial fibrillation

    DEFF Research Database (Denmark)

    Nielsen, Jens Cosedis; Johannessen, Arne; Raatikainen, Pekka

    2016-01-01

    OBJECTIVE: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial compared radiofrequency catheter ablation (RFA) with antiarrhythmic drug therapy (AAD) as first-line treatment for paroxysmal atrial fibrillation (AF). Endpoint...

  15. Massage therapy has short-term benefits for people with common musculoskeletal disorders compared to no treatment: a systematic review.

    Science.gov (United States)

    Bervoets, Diederik C; Luijsterburg, Pim A J; Alessie, Jeroen J N; Buijs, Martijn J; Verhagen, Arianne P

    2015-07-01

    Is massage therapy effective for people with musculoskeletal disorders compared to any other treatment or no treatment? Systematic review of randomised clinical trials. People with musculoskeletal disorders. Massage therapy (manual manipulation of the soft tissues) as a stand-alone intervention. The primary outcomes were pain and function. The 26 eligible randomised trials involved 2565 participants. The mean sample size was 95 participants (range 16 to 579) per study; 10 studies were considered to be at low risk of bias. Overall, low-to-moderate-level evidence indicated that massage reduces pain in the short term compared to no treatment in people with shoulder pain and osteoarthritis of the knee, but not in those with low back pain or neck pain. Furthermore, low-to-moderate-level evidence indicated that massage improves function in the short term compared to no treatment in people with low back pain, knee arthritis or shoulder pain. Low-to-very-low-level evidence from single studies indicated no clear benefits of massage over acupuncture, joint mobilisation, manipulation or relaxation therapy in people with fibromyalgia, low back pain and general musculoskeletal pain. Massage therapy, as a stand-alone treatment, reduces pain and improves function compared to no treatment in some musculoskeletal conditions. When massage is compared to another active treatment, no clear benefit was evident. Copyright © 2015 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

  16. [Effect of quality of root canal obturation on the long-term results of root canal therapy].

    Science.gov (United States)

    Zhu, Ya-ping; Zhu, Ya-qin; Fan, Lin-feng; DU, Rong; Gu, Ying-xin; Qin, Feng

    2007-06-01

    The purpose of this study was to analyze the quality of obturation affecting the long-term results of root canal therapy (RCT) by radiographic evaluation. Teeth of RCT for 2 or more than 2 years were chosen, and periapical radiographs were taken with paralleling technique. The patients' age, gender, etiology, the time of therapy were recorded. The current apical periodontal status of these endodontically treated teeth were examined and recorded. The data were subjected to univariate and multivariate analysis with SPSS13.0 software package. This study investigated 215 cases with 376 endodontically treated teeth. The success rate was 54.79%. If counted by root canal, there were 513 root canals, the success rate was 61.4%. The quality of obturation including obturation position and obturation density affected significantly the results of root canal therapy (Pobturation position for successful treated canals was 0.5-2mm from the radiographic apex. The success rate was higher for a good obturation density, especially in the apical third. No statistically significant differences were found based on gender, age and obturation time. The quality of root canal obturation significantly affected the long-term results of root canal therapy.

  17. Development of new osteonecrosis in systemic lupus erythematosus patients in association with long-term corticosteroid therapy after disease recurrence.

    Science.gov (United States)

    Nakamura, J; Ohtori, S; Sakamoto, M; Chuma, A; Abe, I; Shimizu, K

    2010-01-01

    Systemic lupus erythematosus (SLE) patients are at high risk of developing osteonecrosis, as they require corticosteroid therapy for life. The purpose of this study was to use periodic MRI analysis to clarify (1) the incidence of new osteonecrosis associated with long-term corticosteroid therapy in SLE patients, and (2) the risk factors for delayed osteonecrosis in SLE patients. We prospectively studied 291 joints (134 hips and 157 knees) in 106 SLE patients without osteonecrosis after initial corticosteroid therapy, with a mean follow-up period of 13.6 years and a follow-up rate of 71%. All patients had undergone periodic MRI examination of the hip and knee joints for >10 years. New osteonecrosis developed in 6 joints (3%) and only occurred after SLE recurrence in association with increased corticosteroid doses (to>30 mg/day [p=0.008]). New lesions were delayed for a mean 5.9 years after initial corticosteroid administration. The mean time from SLE recurrence to appearance of new lesions was 6.2 months. SLE recurrence occurred in 131 joints (45%), while SLE was well controlled in 160 joints (55%). We suggest that with respect to long-term effects, total cumulative dose and duration of corticosteroid therapy do not contribute to osteonecrosis. However, SLE recurrence is a risk factor for new osteonecrosis. We recommend MRI screening for osteonecrosis at SLE recurrence.

  18. Acute glucocorticoid effects on the multicomponent model of working memory.

    Science.gov (United States)

    Vaz, Leonardo José; Pradella-Hallinan, Márcia; Bueno, Orlando Francisco Amodeo; Pompéia, Sabine

    2011-10-01

    In comparison with basal physiological levels, acute, high levels of cortisol affect learning and memory. Despite reports of cortisol-induced episodic memory effects, no study has used a comprehensive battery of tests to evaluate glucocorticoid effects on the multicomponent model of working memory. Here, we report the results of a double-blind, placebo-controlled, between-subjects study. Twenty healthy young men were randomly assigned to either acute cortisol (30 mg hydrocortisone) or placebo administration. Participants were subjected to an extensive cognitive test battery that evaluated all systems of the multicomponent model of working memory, including various executive domains (shifting, updating, inhibition, planning and access to long-term memory). Compared with placebo, hydrocortisone administration increased cortisol blood levels and impaired working memory in storage of multimodal information in the episodic buffer and maintenance/reverberation of information in the phonological loop. Hydrocortisone also decreased performance in planning and inhibition tasks, the latter having been explained by changes in storage of information in working memory. Thus, hydrocortisone acutely impairs various components of working memory, including executive functioning. This effect must be considered when administering similar drugs, which are widely used for the treatment of many clinical disorders. Copyright © 2011 John Wiley & Sons, Ltd.

  19. Evolution of Long-Term Adjuvant Anti-hormone Therapy: Consequences and Opportunities. The St. Gallen Prize Lecture

    Science.gov (United States)

    Jordan, V. Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R.; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

    2012-01-01

    The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5-years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of “longer is better” for adjuvant therapy in pre-menopausal patients. One-year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five-years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten-years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective nor-epinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical

  20. The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities.

    Science.gov (United States)

    Jordan, V Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

    2011-10-01

    The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5 years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of "longer is better" for adjuvant therapy in pre-menopausal patients. One year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective norepinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical experience

  1. Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zumsteg, Zachary S.; Spratt, Daniel E.; Pei, Xin; Yamada, Yoshiya; Kalikstein, Abraham [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kuk, Deborah; Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-03-15

    Purpose: We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. Methods and Materials: The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. Results: The median follow-up was 7.9 years. Despite being more likely to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Conclusions: Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy.

  2. Adherence to nebulised therapies in adolescents with cystic fibrosis is best on week-days during school term-time.

    Science.gov (United States)

    Ball, Rosemary; Southern, Kevin W; McCormack, Pamela; Duff, Alistair J A; Brownlee, Keith G; McNamara, Paul S

    2013-09-01

    Treatment regimen for families of children with cystic fibrosis (CF) is considerable, particularly when nebulised therapies for chronic Pseudomonas aeruginosa airway infection are prescribed. Adherence to these regimens is variable, particularly in adolescence. Previously, we reported children to be more adherent in evenings compared to mornings, suggesting an association with time-pressure. The aim of this study was to determine whether adherence would be better in adolescent patients at weekends and during school holidays when time-pressures may be less. 24 patients (14 male, median [range] age 13.9 [11.1-16.8] years) were enrolled from two regional paediatric CF centres in the United Kingdom. Data for a full scholastic year, were downloaded openly from a breath-activated data logging nebuliser (I-neb™). Adherence (% of doses taken÷expected number) was calculated during term-times, holidays, weekends and weekdays, for each patient. Large variations in adherence were seen between patients. However, adherence during term-time was significantly better than holidays (pday, a similar number to those prescribed two daily treatments. Overall adherence to inhaled therapies was reasonable, but significantly reduced during holiday periods. This suggests a need for families to have not only time, but also structure in their daily routine to maintain optimal adherence to long-term therapies. It is important for CF teams to appreciate these factors when supporting families. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  3. Efficacy of short-term Yoga therapy program on quality of life in patients with psychosomatic ailments.

    Science.gov (United States)

    Garg, Sumit; Ramya, C S; Shankar, Vinutha; Kutty, Karthiyanee

    2015-01-01

    The aim was to study the effect of short-term Yoga therapy program on quality of life in patients suffering from psychosomatic ailments. Sample size and Study period: All the subjects coming to SVYASA AROGYADHAMA in month of July 2011 for Yoga therapy for various psychosomatic ailments and were free of any primary psychiatric illness and volunteering to participate were enrolled in the study after taking informed consent. Their physical condition was healthy enough to practice Yoga as judged clinically. All subjects (n = 94) who were enrolled in the study underwent Integrated Approach to Yoga Therapy, which included Asanas, Pranayamas, meditation, Kriyas and lectures on practice of Yoga and derived special techniques in their respective sections. The quality of life was assessed by SF-12 questionnaire and thereby calculating Physical and Mental Composite Scores (PCS and MCS) before and after 1 week of Yoga therapy. Data thus obtained was analyzed using paired t-test. A significant improvement (P Yoga therapy program leads to a remarkable improvement in the quality of life of the subjects and can contribute favorably in the management of psychosomatic disorders.

  4. Low-dose glucocorticoids in hyperandrogenism Efecto de bajas dosis de glucocorticoides en el hiperandrogenismo

    OpenAIRE

    Leonardo Rizzo; Viviana Dobrovsky; Karina Danilowicz; Martha Kral; Graciela Cross; Héctor A. Serra; Oscar D. Bruno

    2007-01-01

    To investigate the effect of low-doses of glucocorticoids on androgen and cortisol secretion during the course of the day, we evaluated clinical signs of hyperandrogenism and total, free and bioavailable testosterone, SHBG, and cortisol following two different protocols: A) fourteen patients received betamethasone 0.6 mg/day (n=8) or methylprednisolone 4 mg/day (n=6), as single daily oral dose at 11.00 PM, during 30 days, B) fourteen patients were evaluated under betamethasone 0.3 mg in a sin...

  5. Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis, neuropathology and glucocorticoid-based therapeutics.

    Science.gov (United States)

    Kalafatakis, Konstantinos; Russell, Georgina M; Zarros, Apostolos; Lightman, Stafford L

    2016-02-01

    Glucocorticoids mediate plethora of actions throughout the human body. Within the brain, they modulate aspects of immune system and neuroinflammatory processes, interfere with cellular metabolism and viability, interact with systems of neurotransmission and regulate neural rhythms. The influence of glucocorticoids on memory and emotional behaviour is well known and there is increasing evidence for their involvement in many neuropsychiatric pathologies. These effects, which at times can be in opposing directions, depend not only on the concentration of glucocorticoids but also the duration of their presence, the temporal relationship between their fluctuations, the co-influence of other stimuli, and the overall state of brain activity. Moreover, they are region- and cell type-specific. The molecular basis of such diversity of effects lies on the orchestration of the spatiotemporal interplay between glucocorticoid- and mineralocorticoid receptors, and is achieved through complex dynamics, mainly mediated via the circadian and ultradian pattern of glucocorticoid secretion. More sophisticated methodologies are therefore required to better approach the study of these hormones and improve the effectiveness of glucocorticoid-based therapeutics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. MULTIDIMETIONAL OUTCOME AND LONG-TERM EVALUATION OF NON-AVOIDANCE STUTTERUNG THERAPY

    Directory of Open Access Journals (Sweden)

    Dobrinka GEORGIEVA

    2015-11-01

    Full Text Available nternational Classification of Functioning, Disability, and Health (ICF, WHO, 2001 is a constructive framework for quality assessment and treatment in Logopedics (Speech Language Therapy. The current research study makes an attempt to introduce this standard into logopedical practice and applied research to measure the quality of life of persons with fluency disorders, such as stuttering. The quality of life is a modern multidimensional construct that covers health-medical, psychological, social and economic factors. Good level of communication and stabilized fluency is of key importance to improve the quality of life of persons who stutter. The purpose of the study was to show a model of assessment, treatment and evaluation of the efficacy of the non-avoidance approach in adult stuttering therapy. According to the results of the Index of disability, 47% of the people with multiple sclerosis have limited independence in providing daily activities leading up to 31% of the examinees with rare participation in the everyday social activities, the result obtained by the Frenchay Index of activities. We can conclude that the Index of disability is higher with older respondents and it is often followed by a drop of the daily activity frequency. Methods: CharlesVan Riper’s non-avoidance approach for an intensive therapy. Participants were 15 adults who stutter with an average age 25.2 years. Results: Specific significant decreasing of the two main parameters: index of dysfluencies immediately after the intensive therapy as well as duration of disfluences in seconds. The changes in speech fluency before and after the intensive therapy as well as 3 years after this therapy were obtained regarding the duration of disfluencies and index of dysfluency. Conclusion: The present model of an intensive non-avoidance therapy format for adults with stuttering disorders was successfully applied for the Bulgarian conditions. Improved fluency is an important factor

  7. Functional imaging in obese children responding to long-term sports therapy.

    Science.gov (United States)

    Kinder, M; Lotze, M; Davids, S; Domin, M; Thoms, K; Wendt, J; Hirschfeld, H; Hamm, A; Lauffer, H

    2014-10-01

    Functional imaging studies on responders and non-responders to therapeutic interventions in obese children are rare. We applied fMRI before and after a one-year sports therapy in 14 obese or overweight children aged 7-16 years. During scanning, participants observed a set of standardized pictures from food categories, sports, and pleasant and neutral images. We were interested in alterations of the cerebral activation to food images in association with changes in the BMI-standard deviation score (BMI-SDS) after therapy and therefore separated the observation group into two outcome subgroups. One with reduction of BMI-SDS >0.2 (responder group) and one without (non-responder group). Before therapy fMRI-activation between groups did not differ. After therapy we found the following results: in response to food images, obese children of the responder group showed increased activation in the left putamen when compared with the non-responder group. Pleasant images evoked increased insula activation in the responder group. Only the responder group showed enhanced activity within areas known to store trained motor patterns in response to sports images. Both the putamen and the insula are involved in the processing of emotional valence and were only active for the therapy responders during the observation of food or pleasant stimuli. Elevated activity in these regions might possibly be seen in the context of an increase of dopaminergic response to emotional positive stimuli during intervention. In addition, sport images activated motor representations only in those subjects who profited from the sports therapy. Overall, an altered response to rewarding and pleasant images and an increased recruitment of motor engrams during observations of sports pictures indicates a more normal cerebral processing in response to these stimuli after successful sports therapy in obese children. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke.

    Science.gov (United States)

    Saver, Jeffrey L; Carroll, John D; Thaler, David E; Smalling, Richard W; MacDonald, Lee A; Marks, David S; Tirschwell, David L

    2017-09-14

    Whether closure of a patent foramen ovale reduces the risk of recurrence of ischemic stroke in patients who have had a cryptogenic ischemic stroke is unknown. In a multicenter, randomized, open-label trial, with blinded adjudication of end-point events, we randomly assigned patients 18 to 60 years of age who had a patent foramen ovale (PFO) and had had a cryptogenic ischemic stroke to undergo closure of the PFO (PFO closure group) or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole; medical-therapy group). The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization. The results of the analysis of the primary outcome from the original trial period have been reported previously; the current analysis of data from the extended follow-up period was considered to be exploratory. We enrolled 980 patients (mean age, 45.9 years) at 69 sites. Patients were followed for a median of 5.9 years. Treatment exposure in the two groups was unequal (3141 patient-years in the PFO closure group vs. 2669 patient-years in the medical-therapy group), owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat population, recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical-therapy group, resulting in rates of 0.58 events per 100 patient-years and 1.07 events per 100 patient-years, respectively (hazard ratio with PFO closure vs. medical therapy, 0.55; 95% confidence interval [CI], 0.31 to 0.999; P=0.046 by the log-rank test). Recurrent ischemic stroke of undetermined cause occurred in 10 patients in the PFO closure group and in 23 patients in the medical-therapy group (hazard ratio, 0.38; 95% CI, 0.18 to 0.79; P=0.007). Venous thromboembolism (which comprised events of pulmonary embolism and deep-vein thrombosis) was more common in the PFO closure group

  9. Cardiac resynchronization therapy in patients with chronic Chagas cardiomyopathy: long-term follow up

    Science.gov (United States)

    de Araújo, Edgard Ferreira; Chamlian, Eduardo Gregório; Peroni, Alexey Pomares; Pereira, Wilson Lopes; Gandra, Sylvio Matheus de Aquino; Rivetti, Luiz Antonio

    2014-01-01

    Introduction Chagas disease is a major cause of cardiomyopathy and sudden death in our country. It has a high mortality when their patients develop New York Heart Association (NYHA) class IV. Objective The objective of this study is to analyze the clinical outcome of patients with Chagas' cardiomyopathy with congestive heart failure with optimized pharmacological therapy, undergoing cardiac resynchronization therapy. Methods Between January 2004 and February 2009, 72 patients with Chagas' cardiomyopathy in NYHA class III and IV underwent cardiac resynchronization therapy and were monitored to assess their clinical evolution. We used the t test or the Wilcoxon test to compare the same variable in two different times. A P value < 0.05 was established as statistically significant. Results The average clinical follow-up was 46.6 months (range 4-79 months). At the end of the evaluation, 87.4% of patients were in NYHA class I or II (P<0.001). There was response to therapy in 65.3% of patients (P<0.001), with an overall mortality of 34.7%. Conclusion In patients with chronic Chagas cardiomyopathy undergoing cardiac resynchronization therapy, we found the following statistically significant changes: improvement in NYHA class and increase of left ventricle ejection fraction, a decrease of the systolic final diameter and systolic final left ventricle volume and improvement of patient survival. PMID:24896160

  10. Non-specific aortoarteritis: long-term follow-up on immunosuppressive therapy.

    Science.gov (United States)

    Talwar, K K; Vasan, R S; Sharma, S; Chopra, P; Shrivastava, S; Malhotra, A

    1993-04-01

    Thirteen patients with non-specific aortoarteritis and endomyocardial biopsy evidence of myocarditis were followed-up on immunosuppressive therapy comprising of prednisolone and cyclophosphamide in addition to conventional treatment for hypertension and/or congestive heart failure. Serial determinations of erythrocyte sedimentation rate, chest roentgenogram, radionuclide ventriculogram and hemodynamic study including endomyocardial biopsy were carried out at 12, 24 and 52 weeks of therapy. Arterial lesions were also assessed by digital subtraction angiography at 0 and 52 weeks of immunosuppressive therapy. At the end of a year of treatment all patients with congestive heart failure (10/13) showed symptomatic improvement by at least one New York Heart Association (NYHA) class. There was a significant fall in erythrocyte sedimentation rate (48 +/- 12 mm/1st h to 31 +/- 12 mm/1st h, P < 0.05), pulmonary artery pressure (32 +/- 14 mmHg to 20 +/- 9 mmHg, P < 0.05), left ventricular filling pressure (20 +/- 11 mmHg to 11 +/- 7 mmHg, P < 0.05) and increase in left ventricle ejection fraction (39 +/- 16% to 51 +/- 14%, P < 0.05) associated with resolution of morphological changes on endomyocardial biopsy. Arterial lesions remained static with neither progression nor appearance of new lesions. No significant complications of therapy were noticed in any patient. Our uncontrolled observations suggest that immunosuppressive therapy is safe and results in clinical, hemodynamic and myocardial morphological improvement in a subset of patients with non-specific aortoarteritis and associated myocarditis.

  11. The effects of glucocorticoid on microarchitecture, collagen, mineral and mechanical properties of sheep femur cortical bone

    DEFF Research Database (Denmark)

    Ding, Ming; Danielsen, Carl Christian; Overgaard, Søren

    2011-01-01

    In this study, 18 female skeletally mature sheep were randomly allocated into three groups of six each. Group 1 (glucocorticoid-1) received prednisolone treatment (0.60 mg/kg/day, five times weekly) for 7 months. Group 2 (glucocorticoid-2) received the same treatment regime followed by observation...... months after glucocorticoid cessation, suggesting a delayed effect of glucocorticoid on cortical bone. Thus, changes in cortical bone beyond cancellous bone might further increase fracture risk in patients treated with glucocorticoids. This model might be used as a glucocorticoid-induced osteoporotic...

  12. The effectiveness of group reminiscence therapy for loneliness, anxiety and depression in older adults in long-term care: a systematic review.

    Science.gov (United States)

    Syed Elias, Sharifah Munirah; Neville, Christine; Scott, Theresa

    2015-01-01

    Loneliness, anxiety and depression are common problems for older adults in long-term care. Reminiscence therapy is a non-pharmacological intervention that may be of some benefit. In comparison to individual reminiscence therapy, group reminiscence therapy is a preferred option when dealing with the resource constraints of long-term care. The aim of this paper was to systematically review the literature in order to explore the effectiveness of group reminiscence therapy for older adults with loneliness, anxiety and depression in long-term care. Results indicated that group reminiscence therapy is an effective treatment for depression in older adults, however to date, there is limited research support for its effectiveness to treat loneliness and anxiety. Further research and an improvement in methodological quality, such as using qualitative and mixed methods approaches, is recommended to help establish an evidence base and provide better understanding of the effectiveness of group reminiscence therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Medical therapy and subthalamic deep brain stimulation in advanced Parkinson's disease: a different long-term outcome?

    Science.gov (United States)

    Merola, Aristide; Rizzi, Laura; Zibetti, Maurizio; Artusi, Carlo Alberto; Montanaro, Elisa; Angrisano, Serena; Lanotte, Michele; Rizzone, Mario Giorgio; Lopiano, Leonardo

    2014-05-01

    Few clinical trials reported the comparative short-term efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) versus medical therapy in advanced Parkinson's disease (PD). However, the comparative efficacy, safety and the potential disease-modifying effect of these treatments have not been investigated over a longer follow-up period. In this study, we organised a 'retrospective control group' to compare medical and surgical therapies over a long-term period. We assessed a group of PD patients suitable for STN-DBS but successively treated with medical therapies for reasons not related to PD, and a group of similar consecutive STN-DBS patients. We thus obtained two groups comparable at baseline, which were re-evaluated after an average follow-up of 6 years (range 4-11). Patients treated with STN-DBS showed a long-lasting superior clinical efficacy on motor fluctuations, with a significant reduction in the average percentage of the waking day spent in 'OFF' and in the duration and disability of dyskinesia. Moreover, operated patients showed a better outcome in the activities of daily living in 'Medication-OFF' condition. On the other hand, a similar progression of motor score and cognitive/behavioural alterations was observed between the two groups, apart from phonemic verbal fluency, which significantly worsened in STN-DBS patients. To our knowledge, this is the first long-term comparison between medical and surgical therapies; a superior efficacy of STN-DBS was observed on motor disability, while no significant differences were observed in the progression of motor symptoms and, apart from phonemic verbal fluency, of neuropsychological alterations.

  14. Relevance of bisphosphonate long-term therapy in radiation therapy of endosteal jaw metastases; Zur Relevanz einer Bisphosphonat-Langzeittherapie bei der Strahlentherapie enossaler Kiefermetastasen

    Energy Technology Data Exchange (ETDEWEB)

    Groetz, K.A. [HSK Dr. Horst-Schmidt-Kliniken, Wiesbaden (Germany). Akademisches Lehrkrankenhaus, Klinik fuer Mund-Kiefer-Gesichtschirurgie; Mainz Univ. (Germany). Klinik und Poliklinik fuer Mund-, Kiefer- und Gesichtschirurgie; Walter, C.; Al-Nawas, B. [Mainz Univ. (Germany). Klinik und Poliklinik fuer Mund-, Kiefer- und Gesichtschirurgie; Kuettner, C. [HSK Dr. Horst-Schmidt-Kliniken, Wiesbaden (Germany). Akademisches Lehrkrankenhaus, Klinik fuer Mund-Kiefer-Gesichtschirurgie

    2007-04-15

    Background and Purpose: Bisphosphonates are used in the treatment of bone metastasis and malignant myeloma. They have been associated with osteonecrosis of the jaw (ONJ) since the year 2003. Etiology and pathogenesis of this clinical problem are not clear. The high rate of newly diagnosed cases is alarming. Based on the collective of two departments of oral and maxillofacial surgery, the results of therapy in the coincidence of systemic bisphosphonate treatment and local radiotherapy (RT) are analyzed. Patients and Methods: In the course of 33 months (01/2003-09/2005), 63 synchronic or metachronic ONJs were seen in 42 patients as newly diagnosed episodes. Three of the 42 patients had an RT of jaw metastasis. Results: Only one patient was followed over the whole treatment period. Under RT she developed a therapy-refractory ONJ similar to osteoradionecrosis at a dose of 40 Gy. She required a wide segmental osteotomy of the mandible resulting in a total loss of masticatory function. In 39 patients with 60 ONJs without RT not a single segmental resection of the mandible was necessary. Conclusion: Local RT in bisphosphonate long-term therapy seems to be a high risk constellation. As long as the pathogenesis of bisphosphonate-associated ONJ is unclear, patients subjected to RT of the head-and-neck area should be treated.

  15. [Animal assisted therapy in a long-term care nursing home].

    Science.gov (United States)

    Mudzyk, Agnés; Bourque, Monique; Guilbert, Héléne; Seguin, Anne Dahaba; Savoye, Marie-Jo

    2011-01-01

    Animal assisted therapy sessions have been set up at the Bellevaux nursing home in Besançon. The project has required a number of specific procedures and training courses to be put in place as well as the involvement of different departments. The sessions give real pleasure to the residents and produce interesting results.

  16. Internet-based therapy for adolescents with chronic fatigue syndrome: long-term follow-up

    NARCIS (Netherlands)

    Nijhof, S.L.; Priesterbach, L.P.; Uiterwaal, C.S.; Bleijenberg, G.; Kimpen, J.L.L.; Putte, E.M. van de

    2013-01-01

    OBJECTIVE: Cognitive behavioral therapy (CBT) is known to be an effective treatment of adolescents with chronic fatigue syndrome (CFS), but its availability is limited. Fatigue in Teenagers on the Internet (FITNET), an Internet-based CBT program for adolescents with CFS, has been developed as an

  17. The Creative Journey: A Model for Short-Term Group Art Therapy with Posttreatment Cancer Patients.

    Science.gov (United States)

    Luzzatto, Paola; Gabriel, Bonnie

    2000-01-01

    Cancer patients who have completed medical treatment are often left with unresolved psychological issues. Memorial Sloan-Kettering Cancer Center in New York offers a group art therapy program for cancer patients to help them regain their self-confidence and readjust their self-identity. The response of 70 participants has been positive and has…

  18. Long-Term Effects of Brief Acceptance and Commitment Therapy for Psychosis

    Science.gov (United States)

    Bach, Patricia; Hayes, Steven C.; Gallop, Robert

    2012-01-01

    A previous report explored the impact of a brief (four session) acceptance and commitment therapy (ACT) intervention as compared with treatment as usual (TAU) on rehospitalization over 4 months in a sample of 80 inpatients with psychosis. The present study extended the follow-up period to 1 year and used a more sophisticated survival analysis to…

  19. A rat model of early stage osteonecrosis induced by glucocorticoids

    Directory of Open Access Journals (Sweden)

    Kerachian Mohammad

    2011-12-01

    Full Text Available Abstract Background Glucocorticoid (GC-induced osteonecrosis (ON is an important complication of medical therapy. The exact pathomechanisms of ON has not been clearly elucidated. There is a need for a reproducible animal model that better approximates the clinical scenario. Methods To determine the genetic susceptibility of rats to develop GC-induced femoral head ON, we evaluated 5 different inbred strains of rats (Spontaneous Hypertensive Rat, Wistar Kyoto, Wistar Furth, SASCO Fisher and Lewis. Prednisone pellets (dosage of 1.82-2.56 mg/kg/day were implanted subcutaneously for 90. After 90 days, the femurs were resected and examined histologically and radiographically. Pathological and histological examination was performed. Hematoxylin and eosin (H & E staining was used to delineate the femoral head osteonecrosis lesions as well as abnormalities of articular cartilage and growth plate. Results The greatest differences in H & E staining were seen in the Wistar Kyoto and Wistar Furth groups. In these groups 4 out of 5 and 3 out of 5, respectively, steroid-induced rats revealed growth plate disruption with acellular areas. The TUNEL apoptosis staining assay for apoptosis revealed that 4 out of 5 of Wistar Kyoto rats, 5 out of 5 of Wistar Furth, 2 out of 4 of surviving Lewis and 2 out of 2 of the surviving spontaneous hypertensive rats had apoptotic osteocytes in trabeculae, whereas none of the Fisher rats showed apoptotic osteocytes. Conclusions We postulate that Wistar Kyoto, Wistar Furth and spontaneous hypertensive rats may be strains of rats more susceptible to develop ON of the femoral head while Fisher rats were the most resistant.

  20. Time trends for alendronate prescription practices in women with chronic obstructive pulmonary disease and women exposed to systemic glucocorticoids

    DEFF Research Database (Denmark)

    Brask-Lindemann, Dorthe; Eiken, P; Eskildsen, P

    2013-01-01

    aims to evaluate alendronate prescription practices related to COPD and/or to exposure to systemic glucocorticoids among Danish women. Methods A total of 388,314 female subjects >50 years old, 64,719 of whom initiated treatment with alendronate, and 323,595 age- and gender-matched controls were...... retrospectively identified between 1996 and 2008 from national health registers. Multivariate logistic regression was used for examining prescription practices, specifically if these risk factors (COPD or glucocorticoid exposure) increased or decreased the likelihood of beginning alendronate therapy. Results...... A diagnosis of COPD was associated with an increased likelihood of using alendronate (odds ratio (OR) 1.4, 95 % confidence interval (CI) 1.4–1.5, p 

  1. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy

    NARCIS (Netherlands)

    Pakker, NG; Otto, SA; Hall, D; Wit, FWNM; Hamann, D; van der Ende, Marchina E.; Claessen, FAP; Kauffmann, RH; Koopmans, PP; Sprenger, HG; Weigel, HM; Montaner, JSG; Lange, JMA; Reiss, P; Schellekens, PTA; Miedema, F; Ten Napel, Chris H. H.

    1999-01-01

    Background: Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. Objectives: In this study, long-term immune reconstitution was investigated during highly active antiretroviral

  2. Long-term results of forward intensity-modulated radiation therapy for patients with early-stage breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Boram; Suh, Hyun Suk; Lee, Ji Hae; Lee, Kyung Ja; Lee, Rena; Moon, Byung In [Ewha Womans University College of Medicine, Seoul (Korea, Republic of)

    2013-12-15

    To observe long-term clinical outcomes for patients with early-stage breast cancer treated with forward intensity-modulated radiation therapy (IMRT), including local control and clinical toxicities. We retrospectively analyzed a total of 214 patients with stage I-II breast cancer who were treated with breast conserving surgery followed by adjuvant breast radiation therapy between 2001 and 2008. All patients were treated using forward IMRT. The whole breast was irradiated to a dose of 50 to 50.4 Gy followed by an 8 to 12 Gy electron boost to the surgical bed. The median age was 46 years (range, 21 to 82 years) and the medial follow-up time was 7.3 years (range, 2.4 to 11.7 years). Stage T1 was 139 (65%) and T2 was 75 (35%), respectively. Ipsilateral breast recurrence was observed in 3 patients. The 5- and 10-year local control rates were 99.1% and 97.8%, respectively. The cosmetic outcome was evaluated according to the Harvard scale and 89.4% of patients were scored as excellent or good. The whole breast radiation therapy as an adjuvant treatment using a forward IMRT technique showed excellent long-term local control as well as favorable outcomes of toxicity and cosmesis.

  3. Different metabolic responses induced by long-term interdisciplinary therapy in obese adolescents related to ACE I/D polymorphism

    Directory of Open Access Journals (Sweden)

    Sandro S Almeida

    2017-04-01

    Full Text Available Introduction: The main purpose of the present study was to investigate whether I/D polymorphism of the ACE gene might affect metabolic changes related to the metabolic syndrome through a long-term interdisciplinary therapy in obese adolescents. Methods: In total, 125 obese adolescents who entered the interdisciplinary obesity programme were assigned to the following two subgroups: metabolic syndrome or non-metabolic syndrome. They were evaluated at baseline and after 1 year. Genomic DNA was extracted from circulating leukocytes. Results: Subjects with the II genotype in the non-metabolic syndrome group were only to increase their fat-free mass after therapy. Regarding lipid profile, subjects with ID and DD genotypes from both groups reduced their low-density lipoprotein cholesterol levels significantly. The metabolic parameters from the ID and DD genotypes of the non-metabolic syndrome group showed a significantly improved insulin response. Conclusion: In the present study, we showed that the ACE polymorphism was able to influence the fat-free mass in the I-carry allele in the non-metabolic syndrome group positively. In addition, the I-carry allele was able to improve the insulin resistance of the metabolic syndrome group significantly. These results suggest that the ACE I/D genotypes can influence, in different ways, the specific parameters of metabolism among obese adolescents submitted for long-term interdisciplinary therapy.

  4. Outpatient Long-term Intensive Therapy for Alcoholics (OLITA): a successful biopsychosocial approach to the treatment of alcoholism

    Science.gov (United States)

    Krampe, Henning; Stawicki, Sabina; Hoehe, Margret R.; Ehrenreich, Hannelore

    2007-01-01

    Alcohol dependence is a frequent, chronic, relapsing, and incurable disease with enormous societal costs. Thus, alcoholism therapy and research into its outcome are of major importance for public health. The present article will: (i) give a brief overview of the epidemiology, pathogenesis, and treatment outcomes of alcohol dependence; (ii) introduce the basic principles of outpatient long-term therapy of alcohol-dependent patients; and (iii) discuss in detail process-outcome research on Outpatient Long-term intensive Therapy for Alcoholics (OLITA). This successful biopsychosocial approach to the treatment of alcoholisms shows a 9-year abstinence rate of over 50%, a re-employment rate of 60%, and a dramatic recovery from comorbid depression, anxiety disorders, and physical sequelae. The outcome data are empirically based on treatment processes that have proven high predictive validity and give concrete information about where to focus the therapeutic efforts. Thus, process-outcome research on OLITA can serve for the development of new therapeutic guidelines on adapting individual relapse prevention strategies. PMID:18286800

  5. The heterogeneity of patients with epilepsy in terms of psychological characteristics, quality of life, and a response to anticonvulsant therapy

    Directory of Open Access Journals (Sweden)

    R. A. Zorin

    2017-01-01

    Full Text Available The complex characterization of patients with epilepsy involves a description of their psychological sphere, quality of life, and a response to ongoing anticonvulsant therapy.Objective: to study the heterogeneity of a group of patients with epilepsy in terms of the indicators of emotional and cognitive disorders, social adaptation, and a response to ongoing anticonvulsant therapy in order to identify criteria for rating these spheres.Patients and methods. 110 patients with epilepsy were examined. The levels of anxiety and depression, cognitive functions, and quality of life were assessed using the SF-36 and QOLIE-31 questionnaires, as well as the number of seizures and that of taken anticonvulsants were estimated. Multivariate statistical methods were used to divide the patients into subgroups.Results. Based on the examined characteristics, the investigators identified patient subgroups differing in the level of anxiety and depression, the characteristics of cognitive functions, quality of life, and a response to ongoing therapy with anticonvulsants, established a relationship between these characteristics and the form of epilepsy, and proposed criteria for rating these disorders. The heterogeneity of a group of patients with epilepsy was established using the examined characteristics; the higher level of cognitive impairment, the low efficiency of anticonvulsant therapy and the level of social adaptation were described in patients with symptomatic epilepsy. 

  6. The comparative effects of long-term carvedilol versus bisoprolol therapy on QT dispersion in patients with chronic heart failure.

    Science.gov (United States)

    Aygul, Nazif; Ozdemir, Kurtulus; Duzenli, Mehmet Akif; Aygul, Meryem Ulku

    2009-01-01

    Carvedilol and bisoprolol reduce QT dispersion (QTD) in chronic heart failure (CHF). However, it is unclear whether there is a difference between the effects of the two drugs. The aim of the present study was to compare the long-term effects of carvedilol and bisoprolol on QTD in patients with CHF. Eighty-one patients with CHF with no previous beta-blocker therapy were included in this prospective study. The patients were randomly allocated to carvedilol or bisoprolol therapy. Left ventricular ejection fraction (LVEF), heart rate (HR), QTD, and corrected QTD (QTcD) were calculated at baseline and at the 6th month of therapy. In comparison to baseline values in both therapy groups, LVEF was significantly improved, and a statistically significant decrease was found in HR (carvedilol from 76 +/- 12 to 65 +/- 10 beats/min, p < 0.001; bisoprolol from 78 +/- 13 to 65 +/- 8 beats/min, p < 0.001) and QTcD (carvedilol from 85 +/- 28 to 65 +/- 22 ms, p < 0.001; bisoprolol from 83 +/- 22 to 61 +/- 20 ms, p < 0.001). In our study, carvedilol and bisoprolol were found to have similar effects on LVEF, HR, and QTcD. Carvedilol and bisoprolol decrease HR and QTcD in patients with CHF, and there is no meaningful difference between the two beta-blockers as regards their effects on these parameters. Copyright 2008 S. Karger AG, Basel.

  7. Moderate- to long-term periodontal outcomes of subjects failing to complete a course of periodontal therapy.

    Science.gov (United States)

    Goh, V; Hackmack, P P; Corbet, E F; Leung, W K

    2017-06-01

    The current retrospective cross-sectional study investigated 5-18-year treatment outcomes in subjects who did not complete a recommended course of periodontal therapy. Sixty-five subjects who voluntarily discontinued therapy were recalled. The subjects' demographic data and dental history since discontinuation of periodontal treatment were collected via questionnaires. The subjects' periodontal condition, radiographic data and individual tooth-based prognosis at pre-discontinuation and recall were compared. A total of 229 teeth had been lost over time, mainly due to periodontal reasons. Upper and lower molars were most frequently lost. Rate of tooth loss (0.38/patient per year) was comparable to untreated patients. Deterioration in periodontal health in terms of increased percentage of sites with bleeding on probing (BOP) and sites with probing pocket depths (PPD) of 6 mm or more at re-examination was observed. Positive correlations were found between tooth loss and: (i) years since therapy discontinued; (ii) percentage of sites with PPD of 6 mm or more at pre-discontinuation; and (iii) at re-examination. Percentage of sites with PPD of 6 mm or more at recall was positively correlated with periodontal tooth loss and negatively correlated with percentage of sites without BOP. Patients not completing a course of periodontal therapy are at risk of further tooth loss and deterioration in periodontal conditions over time. © 2016 Australian Dental Association.

  8. Glucocorticoid Receptor Polymorphisms and Outcomes in Pediatric Septic Shock.

    Science.gov (United States)

    Cvijanovich, Natalie Z; Anas, Nick; Allen, Geoffrey L; Thomas, Neal J; Bigham, Michael T; Weiss, Scott L; Fitzgerald, Julie; Checchia, Paul A; Meyer, Keith; Quasney, Michael; Gedeit, Rainer; Freishtat, Robert J; Nowak, Jeffrey; Raj, Shekhar S; Gertz, Shira; Grunwell, Jocelyn R; Opoka, Amy; Wong, Hector R

    2017-04-01

    Polymorphisms of the glucocorticoid receptor gene are associated with outcome and corticosteroid responsiveness among patients with inflammatory disorders. We conducted a candidate gene association study to test the hypothesis that these polymorphisms are associated with outcome and corticosteroid responsiveness among children with septic shock. We genotyped 482 children with septic shock for the presence of two glucocorticoid receptor polymorphisms (rs56149945 and rs41423247) associated with increased sensitivity and one glucocorticoid receptor polymorphism (rs6198) associated with decreased sensitivity to corticosteroids. The primary outcome variable was complicated course, defined as 28-day mortality or the persistence of two or more organ failures 7 days after a septic shock diagnosis. We used logistic regression to test for an association between corticosteroid exposure and outcome, within genotype group, and adjusted for illness severity. Multiple PICUs in the United States. Standard care. There were no differences in outcome when comparing the various genotype groups. Among patients homozygous for the wild-type glucocorticoid receptor allele, corticosteroids were independently associated with increased odds of complicated course (odds ratio, 2.30; 95% CI, 1.01-5.21; p = 0.047). Based on these glucocorticoid receptor polymorphisms, we could not detect a beneficial effect of corticosteroids among any genotype group. Among children homozygous for the wild-type allele, corticosteroids were independently associated with increased odds of poor outcome.

  9. Long-term efficacy of single-dose radiofrequency-induced heat therapy vs. intralesional antimonials for cutaneous leishmaniasis in India

    NARCIS (Netherlands)

    Bumb, R.A.; Prasad, N.; Khandelwal, K.; Aara, N.; Mehta, R.D.; Ghiya, B.C.; Salotra, P.; Wei, L.; Peters, S.; Satoskar, A.R.

    2013-01-01

    Background Radiofrequency-induced heat therapy (RFHT) has been found to be safe and effective against cutaneous leishmaniasis (CL) in the short term, but its long-term efficacy is unclear. Objectives To compare the long-term efficacy of RFHT vs. intralesional sodium stibogluconate (SSG) injections

  10. Emerging pharmaceutical therapies for COPD.

    Science.gov (United States)

    Lakshmi, Sowmya P; Reddy, Aravind T; Reddy, Raju C

    2017-01-01

    COPD, for which cigarette smoking is the major risk factor, remains a worldwide burden. Current therapies provide only limited short-term benefit and fail to halt progression. A variety of potential therapeutic targets are currently being investigated, including COPD-related proinflammatory mediators and signaling pathways. Other investigational compounds target specific aspects or complications of COPD such as mucus hypersecretion and pulmonary hypertension. Although many candidate therapies have shown no significant effects, other emerging therapies have improved lung function, pulmonary hypertension, glucocorticoid sensitivity, and/or the frequency of exacerbations. Among these are compounds that inhibit the CXCR2 receptor, mitogen-activated protein kinase/Src kinase, myristoylated alanine-rich C kinase substrate, selectins, and the endothelin receptor. Activation of certain transcription factors may also be relevant, as a large retrospective cohort study of COPD patients with diabetes found that the peroxisome proliferator-activated receptor γ (PPARγ) agonists rosiglitazone and pioglitazone were associated with reduced COPD exacerbation rate. Notably, several therapies have shown efficacy only in identifiable subgroups of COPD patients, suggesting that subgroup identification may become more important in future treatment strategies. This review summarizes the status of emerging therapeutic pharmaceuticals for COPD and highlights those that appear most promising.

  11. [Acupuncture therapy for regaining consciousness in terms of acupoint location, needle insertion and needle manipulation].

    Science.gov (United States)

    Meng, Xianggang; Gu, Wenlong; Ma, Fen; Du, Yuzheng; Zhao, Qi

    2015-03-01

    Acupuncture therapy for regaining consciousness activates soreness, numbness, distention, heaviness, radiating and moving, electric shock and ant climbing sensations at the specific acupoints in the stroke patients. Radiating and moving sensations are the summary of needling sensations such as soreness, numbness and twitching presenting during lifting and thrusting manipulation. These sensations are the essential factors of the therapeutic effect of regaining consciousness. Radiating sensation refers to the conduction along meridians and radiation of soreness and numbness. Moving sensation refers to the local muscular twitching at acupoints and the involuntary movement of limbs, joints and the distal. Acupuncture at the specific acupoints achieves radiating and moving sensations for promoting the circulation in meridians, regulating qi and mind and balancing yin and yang in stroke patients. This therapy was introduced in the paper in view of acupoint location, needle insertion and manipulation.

  12. Bilateral Osteonecrosis of the Femoral and Humeral Heads after Short Term Corticosteroid Therapy. A Case Study.

    Science.gov (United States)

    El Gamal, Tarek Ahmed; El-Bakoury, Ahmed; Hawkins, Amanda; Ed AlTayeb Mussa, Moham; Er Ahmed Sweed, Tam; Eh Samir Ansara, Sam

    2016-03-23

    Steroid induced osteonecrosis is a devastating injury that usually requires rebuild of the joint, with the femoral and the humeral head being most commonly affected. Steroid therapy is the most common reported cause of atraumatic osteonecrosis. The Collaborative Osteonecrosis Group Study confirmed that steroids are the primary cause of multi-focal osteonecrosis in 91% of the cases. Osteonecrosis is considered multifocal when three or more joints are involved. We report a rare case of bilateral steroid-induced osteonecrosis of the proximal femora and humeri nine months after a short course of intravenous methylprednisolone for treatment of multiple myeloma. The relationship between development of osteonecrosis and corticosteroid treatment has been extensively investigated. Steroid therapy is the most common reported cause of atraumatic osteonecrosis. Multi-focal osteonecrosis should be highly suspected and thoroughly investigated in patients with persistent pain at typical sites after commencement of steroids.

  13. SCL-90-R Symptom Profiles and Outcome of Short-Term Psychodynamic Group Therapy

    OpenAIRE

    Jensen, Hans Henrik; Mortensen, Erik L.; Lotz, Martin

    2013-01-01

    Background. Psychodynamic group psychotherapy may not be an optimal treatment for anxiety and agoraphobic symptoms. We explore remission of SCL-90-R Global Severity Index (GSI) and target symptoms in 39 sessions of psychodynamic group therapy. Methods. SCL-90-R ?target symptom? profile and GSI remission according to Danish norms were identified in 239 patients and evaluated according to reliable and clinical significant change. Results. Four major groups of target symptom cases (depression, i...

  14. House sparrows mitigate growth effects of post-natal glucocorticoid exposure at the expense of longevity.

    Science.gov (United States)

    Grace, Jacquelyn K; Froud, Louise; Meillère, Alizée; Angelier, Frédéric

    2017-11-01

    Acute, short-term effects of early-life stress and associated glucocorticoid upregulation on physiology and survival are widely documented across vertebrates. However, the persistence and severity of these effects are largely unknown, especially through the adult stage and for natural systems. Here, we investigate physiological, morphological, and survival effects of post-natal glucocorticoid upregulation across the nestling, juvenile, and adult life stages in house sparrows (Passer domesticus). We manipulate circulating corticosterone concentration in wild, free-living house sparrow nestlings and monitor body size, size-corrected mass, two measures of health (hematocrit and phytohemagglutinin-induced skin swelling), and survival in a captive environment until adulthood. We find that early-life corticosterone exposure depresses nestling size-corrected mass in both sexes, with no strong effect of the treatment on body size or our two measures of health. Birds are able to compensate for negative effects of high early-life corticosterone exposure in the long-term and this effect largely disappears by the juvenile and adult stages. However, treatment has a negative effect on survival through one year of age, suggesting that long-term compensation comes at a price. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. [Long-term effects of combined therapy in patients with beta-thalassemia major].

    Science.gov (United States)

    Bagnulo, S; Giannini, A M; Moscatelli, F; Stragapede, L; Acquafredda, A; Dammacco, A

    1998-01-01

    We evaluated therapy complications in 19 beta-thalassemia major patients (mean age from 3 years/5 months and 1 years/6 months) who were followed at II Pediatric Department-University of Bari. 3 out of 19 patients underwent allogenic BMT from matched related donor; 2 out of 19 underwent splenectomy. All of them were receiving hypertransfusion therapy and continuous chelation with DFO. In all patients we performed physical examination, laboratory assays, cardiac and endocrinologic function tests, serum HBV-HCV-HIV antibodies, otoscopy and audiometric test, fundus oculi, skeletal x-ray. 1 out of 19 patients, who was under 15, had a slight dilatation of left ventricle and arythmia. All patients were HBsAb positive. 4/19 patients were HCV Ab positive (ELISA test) with an increase in ALT-AST serum levels since at least 6 months. In 3 of them we assessed RIBA test, always positive. 3 of them underwent liver biopsy (1 iron overload 2 chronic active hepatitis). All patients were HIV Ab negative. 4/15 patients revealed low GH levels after Arginina test. 13 pre-pubescent patients had normal results with GNRH test but lower results after FSH test. 1 pubescent patient had gonadotropic hypophyseal deficit. 4 patients had subclinic hypothiroidism. We couldn't find any sequelas in bone-eyes-ears. Hypertransfusion therapy, chelation, profilaxis of infections improved length and quality of life in thalassemic patients. Hypogonadotropic hypogonadism remains a serious sequela and we think it needs to be treated.

  16. Mortality risk of long-term amiodarone therapy for atrial fibrillation patients without structural heart disease.

    Science.gov (United States)

    Qin, Dingxin; Leef, George; Alam, Mian Bilal; Rattan, Rohit; Munir, Mohamad Bilal; Patel, Divyang; Khattak, Furqan; Adelstein, Evan; Jain, Sandeep K; Saba, Samir

    2015-01-01

    Amiodarone is often prescribed in the management of atrial fibrillation (AF) but is known to cause significant end-organ toxicities. In this study, we examined the impact of amiodarone on all-cause mortality in AF patients with structurally normal hearts. We performed a retrospective cohort analysis of all AF patients with structurally normal hearts who were prescribed antiarrhythmic drugs (AAD) for rhythm control of AF at our institution from 2006 to 2013 (n = 2,077). Baseline differences between the amiodarone (AMIO: n = 403) and other AADs (NON-AMIO: n = 1,674) groups were corrected for using propensity score matching. Amiodarone use as first-line therapy decreased significantly with a higher degree of prescriber specialization in arrhythmia management (31%, 22%, and 9% for primary care physicians, general cardiologists and cardiac electrophysiologists, respectively, p amiodarone was associated with increased all-cause (HR 2.41, p = 0.012) and non-cardiac (HR 3.55, p = 0.008) mortality, but not cardiac mortality. AF recurrence and cardiac hospitalizations were similar between the two study groups. Amiodarone treatment of AF is associated with increased mortality in patients without structural heart disease and therefore should be avoided or only used as a second-line therapy, when other AF therapies fail. Adherence to guideline recommendations in the management of AF patients impacts clinical outcome.

  17. Short-Term Group Therapy for Complicated Grief: The Relationship Between Patients' In-Session Reflection and Outcome.

    Science.gov (United States)

    Kealy, David; Sierra-Hernandez, Carlos A; Piper, William E; Joyce, Anthony S; Weideman, Rene; Ogrodniczuk, John S

    2017-01-01

    The objective of the present study was to examine the nature of patients' work in two types of short-term group psychotherapy. The study sought to investigate the relationship between patients' psychodynamic work versus supportive work in group psychotherapy and treatment outcome at termination and at 6-month follow-up. Psychodynamic work refers to reflection regarding intrapsychic motivations, defenses, and relational patterns, and supportive work refers to practical problem solving. Participants were 110 patients who completed two forms of group therapy for complicated grief: interpretive therapy and supportive therapy. Two types of patients' in-session activity-psychodynamic work and supportive work-were rated by group therapists in both treatments. Pre-post and follow-up outcome domains included general symptoms, grief symptoms, and life dissatisfaction/severity of target objectives. There was no significant difference in the nature of patients' therapeutic work between interpretive and supportive groups. Psychodynamic work was associated with pre-post improvement in grief symptoms. Psychodynamic work was also associated with further improvement in grief symptoms at 6-month follow-up, along with improvement in broader symptom domains. Supportive work was not associated with any pre-post or follow-up benefit. The findings provide evidence that psychodynamic work-focused on the development of insight and self-reflection-in group psychotherapy can contribute to further benefit after the completion of treatment. This finding cut across two approaches to short-term group therapy for complicated grief, suggesting that it may reflect a general curative mechanism of group treatments.

  18. Long-Term Effects of AposTherapy in Patients with Osteoarthritis of the Knee: A Two-Year Followup

    Directory of Open Access Journals (Sweden)

    Yaron Bar-Ziv

    2013-01-01

    Full Text Available Several biomechanics treatments for knee osteoarthritis (OA have emerged with the goal of reducing pain and improving function. Through this, researchers have hoped to achieve a transition from the pathological gait patterns to coordinated motor responses. The purpose of the study was to determine the long-term effects of a therapy using a biomechanical device in patients with knee OA. Patients with knee OA were enrolled to active and control groups. The biomechanical device used in therapy (AposTherapy was individually calibrated to each patient in the active group. Patients in the control group received standard treatment. Outcomes were the Western Ontario and McMaster Osteoarthritis Index (WOMAC, Aggregated Locomotor Function (ALF, Short Form 36 (SF-36, and Knee Society Score assessments. The active and control groups were similar at the baseline (group difference in all scores . The active group showed a larger improvement over time between groups in all three WOMAC categories (, 21.7, and 18.1 for pain, stiffness, and function; all , SF-36 Physical Scale (; , Knee Society Knee Score (; , and Knee Society Function Score (; . At the two-year endpoint, the active group showed significantly better results (all . The groups showed a difference of 4.9, 5.6, and 4.7 for the WOMAC pain, stiffness, and function scores, respectively, 10.8 s in ALF score, 30.5 in SF-36 Physical Scale, 16.9 in SF-36 Mental Scale, 17.8 in Knee Society Knee Score, and 25.2 in Knee Society Function Score. The biomechanical therapy examined was shown to significantly reduce pain and improve function and quality of life of patients with knee OA over the long term.

  19. Bladder Function Preservation With Brachytherapy, External Beam Radiation Therapy, and Limited Surger in Bladder Cancer Patients: Long-Term Results

    Energy Technology Data Exchange (ETDEWEB)

    Aluwini, Shafak, E-mail: s.aluwini@erasmusmc.nl [Department of Radiation Oncology, Erasmus MC Cancer Institution, Rotterdam (Netherlands); Rooij, Peter H.E. van [Department of Radiation Oncology, Erasmus MC Cancer Institution, Rotterdam (Netherlands); Kirkels, Wim J.; Boormans, Joost L. [Department of Urology, Erasmus MC Cancer Institution, Rotterdam (Netherlands); Kolkman-Deurloo, Inger-Karina K.; Wijnmaalen, Arendjan [Department of Radiation Oncology, Erasmus MC Cancer Institution, Rotterdam (Netherlands)

    2014-03-01

    Purpose: To report long-term results of a bladder preservation strategy for muscle-invasive bladder cancer (MIBC) using external beam radiation therapy and brachytherapy/interstitial radiation therapy (IRT). Methods and Materials: Between May 1989 and October 2011, 192 selected patients with MIBC were treated with a combined regimen of preoperative external beam radiation therapy and subsequent surgical exploration with or without partial cystectomy and insertion of source carrier tubes for afterloading IRT using low dose rate and pulsed dose rate. Data for oncologic and functional outcomes were prospectively collected. The primary endpoints were local recurrence-free survival (LRFS), bladder function preservation survival, and salvage cystectomy-free survival. The endpoints were constructed according to the Kaplan-Meier method. Results: The mean follow-up period was 105.5 months. The LRFS rate was 80% and 73% at 5 and 10 years, respectively. Salvage cystectomy-free survival at 5 and 10 years was 93% and 85%. The 5- and 10-year overall survival rates were 65% and 46%, whereas cancer-specific survival at 5 and 10 years was 75% and 67%. The distant metastases-free survival rate was 76% and 69% at 5 and 10 years. Multivariate analysis revealed no independent predictors of LRFS. Radiation Therapy Oncology Group grade ≥3 late bladder and rectum toxicity were recorded in 11 patients (5.7%) and 2 patients (1%), respectively. Conclusions: A multimodality bladder-sparing regimen using IRT offers excellent long-term oncologic outcome in selected patients with MIBC. The late toxicity rate is low, and the majority of patients preserve their functional bladder.

  20. Metastatic lung cancer in the age of targeted therapy: improving long-term survival

    OpenAIRE

    Del Rivero, Jaydira; Enewold, Lindsey; Thomas, Anish

    2016-01-01

    Epidermal growth factor receptor (EGFR) mutations are the most frequent targetable genetic abnormality observed in non-small cell lung cancer (NSCLC). More than a decade after EGFR mutations were shown to predict sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKI), retrospective cohort studies are now identifying and characterizing 5-year survivors. While these studies indicate subsets of patients achieving long-term survival, there is paucity of data pertaining to the long-term surviva...

  1. ROLE OF THE ENDOCANNABINOID SYSTEM IN REGULATING GLUCOCORTICOID EFFECTS ON MEMORY FOR EMOTIONAL EXPERIENCES

    NARCIS (Netherlands)

    Atsak, P.; Roozendaal, B.; Campolongo, P.

    2012-01-01

    Glucocorticoids, stress hormones released from the adrenal cortex, have potent modulatory effects on emotional memory. Whereas early studies focused mostly on the detrimental effects of chronic stress and glucocorticoid exposure on cognitive performance and the classic genomic pathways that mediate

  2. Lymphocyte glucocorticoid receptor resistance and depressive symptoms severity : A preliminary report

    NARCIS (Netherlands)

    Tanke, M. A. C.; Bosker, F. J.; Gladkevich, An.; Medema, H. M.; den Boer, J. A.; Korf, J.

    2008-01-01

    Objective: Assessment of the temporal interrelationship of neuropsychiatric parameters requires technologies allowing frequent biological measurements. We propose glucocorticoid receptor (GR) function of lymphocytes to assess the temporal relationship between glucocorticoid resistance and the course

  3. Adrenal Insufficiency Caused by Locally Applied Glucocorticoids-Myth or Fact?

    DEFF Research Database (Denmark)

    Dinsen, Stina; Klose, Marianne; Rasmussen, Åse Krogh

    2015-01-01

    Case-reports have made it evident that both inhaled, percutaneous, intranasal, intraarticular and ophthalmic administered glucocorticoids have the potential to cause life threatening adrenal insufficiency. With few and sometimes conflicting data and study methodology the prevalence of adrenal...... insufficiency secondary to locally applied glucocorticoids is not clear. Adrenal insufficiency can only be correctly evaluated by a stimulation test, and has by this procedure been reported in up to 40-50% of patients treated with high-dose inhaled glucocorticoids. Medium- to low-dose inhaled glucocorticoids...... have been shown to cause adrenal suppression in 0-16% of patients. Glucocorticoid creams and nasal glucocorticoids can cause adrenal insufficiency, also when used within prescribed doses, but the frequency seems to be less than with inhaled glucocorticoids. Intraarticularly administered glucocorticoids...

  4. Antimicrobial Therapy in Long-Term Care: Controversy, Colonization, and Criteria.

    Science.gov (United States)

    Backus, Danielle

    2015-09-01

    To empower pharmacists to improve the outcomes of residents in long-term care facilities with urinary tract (UTIs) and skin and soft-tissue infections (SSTIs). Relevant articles published since 1990 to date were found via PubMed regarding: long-term care, urinary tract infection, skin and soft-tissue infection, antimicrobials, multi-drug-resistant organisms, antimicrobial resistance, and dementia. Two additional Web sites were included for pharmacists' resources. A total of 28 sources were used (studies, Web sites, and review articles). Sixteen studies were included regarding treatment of suspected infections, antimicrobial resistance of organisms present in long-term care facilities, and interventions previously attempted toward antimicrobial stewardship. The types of infection seen in long-term care facilities were narrowed to UTIs and SSTIs. Data were extracted regarding the type/resistance of bacteria and treatment outcomes. The review demonstrates growing antimicrobial resistance in long-term care for pathogens causing UTIs and SSTIs. The review outlines guidelines for the treatment of such infections, and the incidence of asymptomatic bacteriuria, and subsequent overtreatment. Also included is a discussion of antimicrobial usage in dementia and resources for antimicrobial stewardship. Pharmacists can aid with antimicrobial stewardship in long-term care by educating providers on the need for changes in prescribing habits and the criteria for treating UTIs and SSTIs.

  5. Adherence to depot versus oral antipsychotic medication in schizophrenic patients during the long-term therapy

    Directory of Open Access Journals (Sweden)

    Stanković Žana

    2013-01-01

    Full Text Available Background/Aim. There is a high rate of schizophrenic patients who do not adhere to their prescribed therapy, despite the implementation of antipsychotic long-acting injections and the introduction of atypical antipsychotics. The aim of this study was to investigate the differences in sociodemographic, clinical and medication adherence variables between the two groups of schizophrenic patients on maintenance therapy with depot antipsychotic fluphenazine decanoate and oral antipsychotics only as well as a correlation between the medication adherence and other examined variables. Methods. A total of 56 patients of both genders, aged < 60 years, with the diagnosis of schizophrenia (F20 (ICD-10, 1992 clinically stable for at least 6 months were introduced in this cross-sectional study. The patients from the depot group (n = 19 were on classical depot antipsychotic fluphenazine decanoate administering intramuscularly every 4 weeks (with or without oral antipsychotic augmentation and the patients from the oral group (n = 37 were on oral therapy alone with classical or atypical antipsychotics, either as monotherapy or combined. The Positive and Negative Syndrome Scale (PANSS was used to assess symptom severity. Item G12 of the PANSS was used to assess insight into the illness. The patients completed the Medical Adherence Rating Scale (MARS was used to assess adherence to the therapy. A higher MARS score indicates behavior [Medical Adherence Questionnaire (MAQ subscale] and attitudes toward medication [Drug Attitude Inventory (DAI subscale] that are more consistent with treatment adherence. The exclusion criteria were determined. The Pearson's χ2 test was used to compare categorical variables, Student's t-test to compare continuous variables and Pearson's correlation to test the correlation significance; p = 0.05. Results. Significant betweengroup differences in age, illness duration, chlorpromazine equivalents, PANSS score and DAI subscore were found

  6. The effect of perinatal hormonal imprinting with 13-cis-retinoic acid (isotretinoin) on the thymic glucocorticoid receptors of female and testosterone level of male adult rats.

    Science.gov (United States)

    Csaba, G; Gaál, A; Inczefi-Gonda, A

    1999-09-01

    In earlier experiments, the long-term effect of perinatal treatment (hormonal imprinting) with all-trans-retinol and all-trans-retinoic acid on the thymic glucocorticoid and uterine estrogen receptors was studied and was found effective. In the present experiments, the imprinting effect of four retinoids (13-cis-retinaldehyde, 13-cis-retinoic acid, 9-cis-retinaldehyde and 9-cis-retinoic acid) was investigated, using receptor kinetic analysis and sexual hormone (testosterone and progesterone) level determinations. Exclusively 13-cis-retinoic acid (isotretinoin) had an effect, significantly decreasing glucocorticoid receptor affinity and increasing serum testosterone level. Relationships with RAR-RXR receptor binding and teratogenicity is discussed.

  7. Fluorescence-guided laser therapy for penile carcinoma and precancerous lesions: long-term follow-up.

    Science.gov (United States)

    Schlenker, Boris; Gratzke, Christian; Seitz, Michael; Bader, Markus J; Reich, Oliver; Schneede, Peter; Hungerhuber, Edwin; Stief, Christian G; Tilki, Derya

    2011-01-01

    Laser therapy for penile carcinoma is commonly used despite high recurrence rates of up to 48%. The aim of our study was to investigate the long-term recurrence rate of patients treated by fluorescence-guided laser therapy for penile carcinoma and its impact on oncologic outcome. Between 1999 and 2005, a total of 26 patients with premalignant carcinoma in situ (Tis) (n = 11) or invasive penile carcinoma (n = 15) were treated by fluorescence-guided laser therapy in our center. The mean follow-up was 71.1 months (range 41-104 months). Recurrence rate, time to recurrence, and impact on survival was investigated for Tis patients and penile carcinoma patients separately. No patient died tumor-associated recurrence during follow-up. No local progression of T stage was observed in patients with Tis tumor. In the group with invasive penile cancer, there were 4 (15.4%) local recurrences. However, 3 of them occurred after more than 3 years and, therefore, are more likely to be considered as "de novo" carcinoma. No intra- or perioperative side effects of photodynamic diagnosis (PDD) were observed. Local recurrence rate of laser therapy can be reduced by fluorescence guidance without impairing cosmetic or functional results. The necessary equipment is available in many centers that perform PDD for urothelial bladder cancer. PDD, therefore, can be considered to be cost-effective and easy to perform. Prospective multi-center studies to directly compare recurrence rates between white light and fluorescence-guided laser therapy for penile carcinoma are required. Copyright © 201