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.
Full Text Available Abstract Background While acute effects of stress on pain are well described, those produced by chronic stress are still a matter of dispute. Previously we demonstrated that chronic unpredictable stress results in antinociception in the tail-flick test, an effect that is mediated by increased levels of corticosteroids. In the present study, we evaluated nociception in rats after chronic treatment with corticosterone (CORT and dexamethasone (DEX in order to discriminate the role of each type of corticosteroid receptors in antinociception. Results Both experimental groups exhibited a pronounced antinociceptive effect after three weeks of treatment when compared to controls (CONT; however, at four weeks the pain threshold in CORT-treated animals returned to basal levels whereas in DEX-treated rats antinociception was maintained. In order to assess if these differences are associated with altered expression of neuropeptides involved in nociceptive transmission we evaluated the density of substance P (SP, calcitonin gene-related peptide (CGRP, somatostatin (SS and B2-γ-aminobutiric acid receptors (GABAB2 expression in the spinal dorsal horn using light density measurements and stereological techniques. After three weeks of treatment the expression of CGRP in the superficial dorsal horn was significantly decreased in both CORT and DEX groups, while GABAB2 was significantly increased; the levels of SP for both experimental groups remained unchanged at this point. At 4 weeks, CGRP and SP are reduced in DEX-treated animals and GABAB2 unchanged, but all changes were restored to CONT levels in CORT-treated animals. The expression of SS remained unaltered throughout the experimental period. Conclusion These data indicate that corticosteroids modulate nociception since chronic corticosteroid treatment alters the expression of neuropeptides involved in nociceptive transmission at the spinal cord level. As previously observed in some supraspinal areas, the
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. Giv
Voorn, B. van der; Pal, S.M. van der; Rotteveel, J.; Finken, M.J.
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 miner
Full Text Available Glucocorticoid-induced myopathy is the most common type of drug-induced myopathy. Nearly 60% of patients with Cushing′s syndrome have muscle weakness. Glucocorticoid-induced muscle atrophy affects mainly fast-twitch glycolytic muscle fibers (type IIb fibers. This brief review will discuss the pathophysiology behind glucocorticoid-induced myopathy, along with diagnostic features and treatment.
JI Hong; GUO Wei-zao; YAN Zhi-hong; LI Di; LU Cui-lian
Background Glucocorticoid signaling exerts major roles in inflammation, metabolism and depression, which are three crucial factors accompanying or underlying coronary heart disease. Although accumulating evidence indicates the influence of glucocorticoids on the pathology and treatment of coronary heart disease, there is still a dearth of pharmaceutical mechanisms for this relationship. This study aimed to investigate the influence of drug treatment on glucocorticoid receptor levels in coronary heart disease.Methods Eighty hospitalized patients (average age (59.0 7.5) years, 46 male and 34 female) with coronary heart disease were categorized into four groups with 20 members in each according to one of the four drugs they were treated with. The four drugs were: nitrated derivative isosorbide dinitrate, the beta-adrenergic receptor blocker metoprolol, the calcium antagonist nifedipine, and the HMG-CoA reductase inhibitor lovastatin. Glucocorticoid receptor protein levels of peripheral blood lymphocytes were tested using immunoblotting analysis before and after one month of treatment. Results Immunoblotting analysis showed increased glucocorticoid receptor levels after treatment with metoprolol and nifedipine. There were no statistically significant changes of glucocorticoid receptor levels after treatment with isosorbide dinitrate or lovastatin, although there were trends of up-regulation of glucocorticoid receptor expression after both treatments.Conclusions Both the beta-blocker and the calcium blocker can increase glucocorticoid receptor levels after chronic administration. This effect suggests a mechanism for their anti-inflammatory and other therapeutic roles for coronary heart disease and comorbid disorders.
Full Text Available Stress and stress hormones, glucocorticoids (GCs, exert widespread actions in central nervous system, ranging from the regulation of gene transcription, cellular signaling, modulation of synaptic structure, and transmission and glial function to behavior. Their actions are mediated by glucocorticoid and mineralocorticoid receptors which are nuclear receptors/transcription factors. While GCs primarily act to maintain homeostasis by inducing physiological and behavioral adaptation, prolonged exposure to stress and elevated GC levels may result in neuro- and psychopathology. There is now ample evidence for cause-effect relationships between prolonged stress, elevated GC levels, and cognitive and mood disorders while the evidence for a link between chronic stress/GC and neurodegenerative disorders such as Alzheimer’s (AD and Parkinson’s (PD diseases is growing. This brief review considers some of the cellular mechanisms through which stress and GC may contribute to the pathogenesis of AD and PD.
Bruce Montgomery; Heather H Cheng; James Drechsler; Elahe A Mostaghel
Glucocorticoids have been used in the treatment of prostate cancer to slow disease progression, improve pain control and offset side effects of chemo-and hormonal therapy. However, they may also have the potential to drive prostate cancer growth via mutated androgen receptors or glucocorticoid receptors (GRs). In this review we examine historical and contemporary use of glucocorticoids in the treatment of prostate cancer, review potential mechanisms by which they may inhibit or drive prostate cancer growth, and describe potential means of deifning their contribution to the biology of prostate cancer.
The peculiarities of adrenal glucocorticoid function and membrane potential (MP) of zona fasciculata adrenocorticocyte (ACC) in rats after chronic x-ray exposure was studied. The changes of adrenal glucocorticoid function caused by chronic x-ray exposure within a relatively small period of irradiation (1.5 months) are obscure and manifest themselves only at physiological load. With the prolongation of the period (8 and 15 months), more considerable inhibition of the adrenal glucocorticoid function and disturbances in the membrane mechanisms of ACC MP level regulation are revealed
N. Teeninga (Nynke)
textabstractUnderstanding which factors influence relapse patterns in childhood nephrotic syndrome is clinically very relevant and could aid in developing new treatment strategies. Clinicians are continuously challenged to reduce relapse rates and at the same time to avoid glucocorticoid toxicity. B
Full Text Available Hypothalamus-pituitary-adrenal (HPA hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR - neuronal nitric oxide synthesis enzyme (nNOS - nitric oxide (NO pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.
Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis, yet few patients receive proper measures to prevent its development. We retrospectively searched prescription records to determine if patients receiving oral prednisolone were receiving prophylaxis or treatment for osteopenia and osteoporosis. Patients who were prescribed greater or equal to 7.5 milligrams of prednisolone for 6 months or longer during a 6- month period were identified through the prescription monitoring system. Demographic and clinical data were extracted from the patient records, and dual energy x-ray absorptiometry (DEXA) scans were retrieved, when available. Use of oral calcium, vitamin D and anti-resorptives was recorded. One hundred males and 65 females were receiving oral prednisolone for a mean (SD) duration of 40.4 (29.9) months in males and 41.2 (36.4) months in females. Twenty-one females (12.7%) and 5 (3%) males had bone mineral density measured by DEXA. Of those, 10 (47.6%) females and 3 (50%) males were osteoporotic and 11(52.4%) females and 2 (40%) males were osteopenic. Calcium and vitamin D were prescribed to the majority of patients (60% to 80%), but none were prescribed antiresorptive/anabolic therapy. Patients in this study were neither investigated properly nor treated according to the minimum recommendations for the management of GIOP. Physician awareness about the prevention and treatment of GIOP should be a priority for the local health care system. (author)
Stress is an important risk factor for mood disorders. Stress also stimulates the secretion of glucocorticoids, which have been found to influence mood. To determine the role of forebrain glucocorticoid receptors (GR) in behavioral responses to chronic stress, the present experiments compared behavioral effects of repeated social defeat in mice with forebrain GR deletion and in floxed GR littermate controls. Repeated defeat produced alterations in forced swim and tail suspension immobility in...
Full Text Available The aims of this study were to investigate the influence of serotonin (5-HT on the effects of intra-articular injections of glucocorticoid on pain of the temporomandibular joint (TMJ in patients with inflammatory disorders of the TMJ. The pretreatment synovial fluid 5-HT was negatively, and plasma 5-HT positively, correlated to change in TMJ pain after treatment. The pretreatment plasma 5-HT was positively correlated to change in pressure-pain threshold after treatment. In conclusion, this study shows that local and systemic serotonergic mechanisms partly determine the effect of intra-articular glucocorticoid treatment on TMJ pain in patients with chronic TMJ arthritis of systemic nature, while change in pressure-pain threshold over the TMJ is influenced by systemic serotonergic mechanisms.
Michaud, Kathy; Forget, Helene; Cohen, Henri
Cumulative exposure to glucocorticoid hormones (GC) over the lifespan has been associated with cognitive impairment and may contribute to physical and cognitive degeneration in aging. The objective of the present study was to examine whether the pattern of cognitive deficits in patients with Cushing's syndrome (CS), a disorder characterized by…
Keenan, Christine R; Radojicic, Danica; Li, Meina; Radwan, Asmaa; Stewart, Alastair G
Glucocorticoids (GCs) have impressive anti-inflammatory and immunosuppressive effects and show a diversity of actions across a variety of cell phenotypes. Implicit in efforts to optimize GCs as anti-inflammatory agents for any or all indications is the notion that the relevant mechanism(s) of action of GCs are fully elucidated. However, recent advances in understanding GC signalling mechanisms have revealed remarkable complexity and contextual dependence, calling into question whether the mechanisms of action are sufficiently well-described to embark on optimization. In the current review, we address evidence for differences in the mechanism of action in different cell types and contexts, and discuss contrasts in mechanisms of glucocorticoid insensitivity, with a focus on asthma and Chronic Obstructive Pulmonary Disease (COPD). Given this complexity, we consider the potential breadth of impact and selectivity of strategies directed to reversing the glucocorticoid insensitivity. PMID:25596317
Kuhnke, A; Burmester, G.; Krauss, S.; Buttgereit, F
Objective: To investigate whether activity and glucocorticoid treatment of rheumatic diseases are reflected by selected parameters of cellular energy metabolism of peripheral blood mononuclear cells (PBMC).
Trijau, Sophie; de Lamotte, Gaëlle; Pradel, Vincent; Natali, François; Allaria-Lapierre, Véronique; Coudert, Hervé; Pham, Thao; Sciortino, Vincent; Lafforgue, Pierre
Introduction Long-term glucocorticoid therapy is the leading cause of secondary osteoporosis. The management of glucocorticoid-induced osteoporosis (GIOP) seems to be inadequate in many European countries. Objective To evaluate the rate of screening and treatment of GIOP. Design Information was collected from a national public health-insurance database in our geographic area of Provence-Alpes-Côte-d'Azur and in Corsica, from September 2009 through August 2011. Patients We identified participants aged 15 years and over starting glucocorticoid therapy (≥7.5 mg of prednisone equivalent per day during at least 90 days consecutive). This cohort was compared with an age-matched and sex-matched population that did not receive glucocorticoids. Main outcome measures Bone mass, prescription of bone antiresorptive medication and use of calcium and/or vitamin D treatment. Results We identified 32 812 patients who were prescribed glucocorticoid therapy, yielding 1% prevalence. Incidence of glucocorticoid therapy was 2.8/1000 inhabitants/year. Males represented 44%, the mean age was 58 years. The median prednisone-equivalent dose was 11 mg/day (IQR 9–18 mg/day). 8% underwent bone mass measurement. Calcium and/or vitamin D, and bisphosphonates were prescribed in 18% and 12%, respectively. Results were lower for the control population: 3% underwent bone mass measurement and 3% received bisphosphonate therapy. The rates of osteodensitometry and treatments were higher in women over 55 years of age than in men and women 55 years of age and younger, and also when glucocorticoid therapy was initiated by a rheumatologist versus other physician specialty. Conclusions The management of GIOP remains very inadequate, despite the availability of a statutory health insurance system. Targeted interventions are needed to improve the management of GIOP. PMID:27486526
Rennard, Stephen I
Chronic obstructive pulmonary disease (COPD) is a readily diagnosable disorder that responds to treatment. Smoking cessation can reduce symptoms and prevent progression of disease. Bronchodilator therapy is key in improvement of lung function. Three classes of bronchodilators-beta agonists, anticholinergics, and theophylline-are available and can be used individually or in combination. Inhaled glucocorticoids can also improve airflow and can be combined with bronchodilators. Inhaled glucocorticoids, in addition, might reduce exacerbation frequency and severity as might some bronchodilators. Effective use of pharmacotherapy in COPD needs integration with a rehabilitation programme and successful treatment of co-morbidities, including depression and anxiety. Treatment for stable COPD can improve the function and quality of life of many patients, could reduce admissions to hospital, and has been suggested to improve survival. PMID:15337408
Klopot, Anna; Baida, Gleb; Bhalla, Pankaj; Haegeman, Guy; Budunova, Irina
Background: Glucocorticoids are effective anti-inflammatory drugs widely used in dermatology and for the treatment of blood cancer patients. Unfortunately, chronic treatment with glucocorticoids results in serious metabolic and atrophogenic adverse effects including skin atrophy. Glucocorticoids act via the glucocorticoid receptor (GR), a transcription factor that causes either gene transactivation (TA) or transrepression (TR). Compound A (CpdA), a novel non-steroidal GR ligand, does not prom...
Full Text Available Glucocorticoid-induced osteoporosis (GIO is the most common cause of secondary osteoporosis (OP and a main cause of drug-induced OP. Fractures of the skeleton are registered in 30–50% of patients who have taken oral glucocorticoids (GCs for a long time, during which the frac- tures develop with the use of any daily GC dose and with higher bone mineral density (BMD than in postmenopausal OP. In patients who have taken oral GCs long or in high daily doses, decrease of BMD and low bone tissue quality leading to fractures are largely associated with the reduction of bone formation. This gives proof to the administration of antiosteoporotic agents that enhance the formation of bone during its remodeling. Teriparatide, a recombinant human parathyroid hormone, enhances osteoblast function, decreases the apoptosis of osteoblasts and osteocytes, increases the differentiation of osteoblast precursors, and can prevent the negative effect of exogenous GCs on bone. According to clinical trials results, teriparatide treatment increases BMD and reduces the risk of vertebral fractures in patients who have taken oral GCs long. In accordance of the clinical recommendations for the diagnosis, prevention, and treatment of GIO, which have been developed by the Russian Osteoporosis Association jointly with the Association of Rheumatologists of Russia and the Russian Respiratory Society, teriparatide is the drug of first choice for the treatment of GIO in men and women at high risk for fractures (with the history of fragility fractures or having high FRAX 10-year absolute fracture risk. Teriparatide may be prescribed in case of previous antiosteoporotic treatment failure (new fractures occurring during treatment and/or continuing to decrease BMD, as well as when other drugs to treat OP are intolerable or when there are contraindications to their use.
We define chronic migraine as that clinical situation in which migraine attacks appear 15 or more days per month. Until recently, and in spite of its negative impact, patients with chronic migraine were excluded of the clinical trials. This manuscript revises the current treatment of chronic migraine. The first step should include the avoidance of potential precipitating/aggravating factors for chronic migraine, mainly analgesic overuse and the treatment of comorbid disorders, such as anxiety and depression. The symptomatic treatment should be based on the use of nonsteroidal anti-inflammatory agents and triptans (in this case ergotamine-containing medications. Preventive treatment includes a 'transitional' treatment with nonsteroidal anti-inflammatory agents or steroids, while preventive treatment exerts its actions. Even though those medications efficacious in episodic migraine prevention are used, the only drugs with demonstrated efficacy in the preventive treatment of chronic migraine are topiramate and pericranial infiltrations of Onabotulinumtoxin A. PMID:22532241
Lu, Huaixiu; Xu, Minguang; Wang, Feng; Liu, Shisen; Gu, Jing; Lin, Songshan; Zhao, Lisheng
Periodontitis is a common chronic inflammatory disease. Recent studies have shown that chronic stress (CS) might modulate periodontal disease, but there are few models of CS-induced periodontitis, and the underlying mechanisms are unclear. The present study established a rat model of periodontitis associated with CS induced by nylon thread ligatures. The severity of periodontitis was evaluated in this model by radiographic and pathological examination. The inflammatory reaction indicated by the elevated serum levels of interleukin (IL)-1β, IL-6 and IL-8 was assessed by enzyme-linked immunosorbent assay. Toll-like receptor-4 (TLR4) and glucocorticoid receptor-α (GR-α) expressions were detected by reverse transcriptase-PCR and western blotting. Open-field tests and serum corticosterone were used to evaluate CS. The results showed that CS induced behavioral changes and increased corticosterone levels of the animals with periodontitis. CS stimulation markedly increased alveolar bone loss, periodontal pocket depth and the number of plaques. It also enhanced the inflammatory reaction. These results suggest that CS accelerated the ligature-induced pathological changes associated with periodontitis. Further analysis of the mechanisms involved showed that GR-α expression was significantly downregulated in periodontal tissues of the animals undergoing CS. Blocking GR-α signaling in lipopolysaccharide and corticosteroid-treated human periodontal ligament fibroblast cells in vitro significantly upregulated the expression of p-Akt (protein kinase B) and TLR4, promoted nuclear factor-κB activity and increased levels of IL-1β, IL-6 and IL-8. This research suggests that CS might accelerate the pathological progression of periodontitis by a GR-α signaling-mediated inflammatory response and that this may be a potential therapeutic target for the treatment of periodontal disease, particularly in patients with CS. PMID:27012709
... in the treatment. Treatment With chronic pain, the goal of treatment is to reduce pain and improve ... some treatments used for chronic pain. Less invasive psychotherapy, relaxation therapies, biofeedback, and behavior modification may also ...
Mathiesen, Elisabeth R; Christensen, Ann-Birgitte L; Hellmuth, Ellinor;
Poor glycemic control is often a serious clinical problem during glucocorticoid treatment for fetal lung maturation in pregnant women with diabetes. An algorithm for improved subcutaneous insulin treatment during glucocorticoid treatment in insulin-dependent diabetic women was developed and tested....
Full Text Available Abstract Objective As chronic obstructive pulmonary disease (COPD is known for poor glucocorticoid (GC response, we hypothesized that polymorphic variants of the glucocorticoid receptor (GR gene might predispose for COPD and/or disease severity. Materials and methods Three out of about 50 of the most abundant receptor GR gene polymorphisms were investigated in a case-control study which included 207 patients with chronic bronchitis or COPD (mean FEV1 50.5% predicted, GOLD I-IV and 106 age matched healthy subjects (mean FEV1 101.8% predicted. These were genotyped: a for the N363S (Exon 2; 1220 A > G (I; b the BCLI restriction fragment length polymorphism (Intron 2; 647 C > G (II; and c the ER2223EK (Exon 2; 198, 200 G > A (III, using RT-PCR and PCR-RFLP method on genomic DNA isolated from EDTA blood. Results Genotype distribution between COPD and healthy subjects were alike in all of these three polymorphisms. N363S was found in 0.94% of the healthy and 0% of the COPD subjects. BCLI was detected in 11.3% of the controls and 15.5% of the COPD patients whereas heterozygote frequency was less in the COPD (44.4% group (controls 60.4%. ER2223EK lacks in any of the study subjects. Further, SNPs did not correlate with COPD severity stage (GOLD, exacerbation rates, and clinical course. Conclusion COPD is not linked to gene polymorphisms N363S, BCLI-RFLP, and ER2223EK. Since we analyzed only these 3 receptor gene polymorphisms, this study cannot rule out that other GR gene variants and linkages may be of influence.
Mitić, Žarko J.; Najman, Stevo J.; Cakić, Milorad D.; Ajduković, Zorica R.; Ignjatović, Nenad L.; Nikolić, Ružica S.; Nikolić, Goran M.; Stojanović, Sanja T.; Vukelić, Marija Đ.; Trajanović, Miroslav D.
The influence of glucocorticoids on the composition and mineral/organic content of the mandible in tested animals after recovery and healing phase was investigated in this work. The results of FTIR analysis demonstrated that bone tissue composition was changed after glucocorticoid treatment. The increase of calcium, magnesium, phosphorus content and mineral part of bones was statistically significant in recovery phase and in treatment phase that included calcitonin and thymus extract. Some changes also happened in the organic part of the matrix, as indicated by intensity changes for already present IR bands and the appearance of new IR bands in the region 3500-1300 cm-1.
Gathercole, LL; Morgan, SA; Bujalska, IJ; Stewart, PM; Tomlinson, JW
Background: Endogenous or exogenous glucocorticoid (GC) excess (Cushing's syndrome) is characterized by increased adiposity and insulin resistance. Although GCs cause global insulin resistance in vivo, we have previously shown that GCs are able to augment insulin action in human adipose tissue, contrasting with their action in skeletal muscle. Cushing's syndrome develops following chronic GC exposure and, in addition, is a state of hyperinsulinemia. Objectives: We have therefore compared the ...
The ability of dexamethasone(dex) to induce alkaline phosphatase activity was found to decrease with chronic hormone exposure. In order to better understand this adaptive resistance, the structure of the receptor from control cells and cells under long term dex (10-6M) treatment was analyzed. Native isoelectric focusing showed that receptor from dex treated cells focused at more basic pI than receptor from control cells. Denaturing two-dimensional gel analysis resulted in the characteristic 4-5 spots of [3H]dexamethasone mesylate (DM) binding of receptor from control cells, but no [3H]DM binding could be seen for receptor from dex treated cells. In order to study DNA-binding characteristics, gels were renatured, transferred to nitrocellulose and probed with [32P]MMTV-GRE. Receptor from control cells showed 5 spots of DNA-binding at 101 kDa molecular weight and a pI range of 7.42 to 7.32. However, receptor from dex treated cells showed less intense DNA-binding which occurred only at the more basic range of pIs (7.42 to 7.39). Furthermore, no nuclear receptor sites could be measured in the dex treated cells, whereas 20,000 sites were measured in control cells. Even after being taken off hormone treatment for 12 days, cells could regenerate only 50% of their receptors. In conclusion, this system is conducive to studying the mechanism of receptor regulation
de Quervain, Dominique J-F; Margraf, Jürgen
Post-traumatic stress disorder (PTSD) and phobias belong to the most common anxiety disorders and to the most common psychiatric illnesses in general. In both disorders, aversive memories are thought to play an important role in the pathogenesis and symptomatology. Previously, we have reported that elevated glucocorticoid levels inhibit memory retrieval in animals and healthy humans. We therefore hypothesized that the administration of glucocorticoids might also inhibit the retrieval of aversive memory, thereby reducing symptoms in patients with PTSD and phobias. In recent clinical studies, we found first evidence to support this hypothesis. In patients with PTSD, low-dose cortisol treatment for one month reduced symptoms of traumatic memories without causing adverse side effects. Furthermore, we found evidence for a prolonged effect of the cortisol treatment. Persistent retrieval and reconsolidation of traumatic memories is a process that keeps these memories vivid and thereby the disorder alive. By inhibiting memory retrieval, cortisol may weaken the traumatic memory trace, and thus reduce symptoms even beyond the treatment period. In patients with social phobia, we found that a single oral administration of cortisone 1 h before a socio-evaluative stressor significantly reduced self-reported fear during the anticipation-, exposure-, and recovery phase of the stressor. In subjects with spider phobia, repeated oral administration of cortisol 1 h before exposure to a spider photograph induced a progressive reduction of stimulus-induced fear. This effect was maintained when subjects were exposed to the stimulus again two days after the last cortisol administration, indicating that cortisol facilitated the extinction of phobic fear. In conclusion, by a common mechanism of reducing the retrieval of aversive memories, glucocorticoids may be suited for the treatment of PTSD as well as phobias. More studies are needed to further evaluate the therapeutic efficacy of
Fernández-Bertolín, Laura; Mullol, Joaquim; Fuentes-Prado, Mireya; Roca-Ferrer, Jordi; Alobid, Isam; Picado, César; Pujols, Laura
Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the upper airways frequently associated with asthma. Bacterial infection is a feature of CRSwNP that can aggravate the disease and the response to glucocorticoid treatment. Objective We examined whether the bacterial product lipopolysaccharide (LPS) reduces glucocorticoid receptor (GR) function in control nasal mucosa (NM) fibroblasts and in nasal polyp (NP) fibroblasts from patients with CRSwNP and asthma. Methods NP (n = 12) and NM fibroblasts (n = 10) were in vitro pre-incubated with LPS (24 hours) prior to the addition of dexamethasone. Cytokine/chemokine secretion was measured by ELISA and Cytometric Bead Array. GRα, GRβ, mitogen-activated protein-kinase phosphatase-1 (MKP-1) and glucocorticoid-induced leucine zipper (GILZ) expression was measured by RT-PCR and immunoblotting, GRα nuclear translocation by immunocytochemistry, and GRβ localization by immunoblotting. The role of MKP-1 and GILZ on dexamethasone-mediated cytokine inhibition was analyzed by small interfering RNA silencing. Results Pre-incubation of nasal fibroblasts with LPS enhanced the secretion of IL-6, CXCL8, RANTES, and GM-CSF induced by FBS. FBS-induced CXCL8 secretion was higher in NP than in NM fibroblasts. LPS effects on IL-6 and CXCL8 were mediated via activation of p38α/β MAPK and IKK/NF-κB pathways. Additionally, LPS pre-incubation: 1) reduced dexamethasone’s capacity to inhibit FBS-induced IL-6, CXCL8 and RANTES, 2) reduced dexamethasone-induced GRα nuclear translocation (only in NM fibroblasts), 3) did not alter GRα/GRβ expression, 4) decreased GILZ expression, and 5) did not affect dexamethasone’s capacity to induce MKP-1 and GILZ expression. MKP-1 knockdown reduced dexamethasone’s capacity to suppress FBS-induced CXCL8 release. Conclusion The bacterial product LPS negatively affects GR function in control NM and NP fibroblasts by interfering with the capacity of the
Brereton, Daniel; Plochocki, Jeffrey; An, Daniel; Costas, Jeffrey; Simons, Erin
The development of spinal curvature deformities is a hallmark of muscular dystrophy. While glucocorticoid treatment has been shown to prolong muscle function in dystrophic mice, its effects on the development of dystrophinopathic spinal deformation are poorly understood. In this study, we test the effects of glucocorticoid treatment on the onset of thoracolumbar kyphosis in the dystrophin-deficient mdx mouse using voluntary running exercise to exacerbate muscle fibrosis. We measure the kyphot...
Meduri, Gianfranco Umberto; Schwingshackl, Andreas; Hermans, Greet
Systemic inflammation and duration of immobilization are strong independent risk factors for the 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 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 reanalysis 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. PMID:27532030
This thesis focuses on the efficacy of existing and alternative treatments in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) and explores predictors of treatment response in patients with CIDP treated with corticosteroids. The efficacy of intra
A A Fedorova
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.
... ALL Treatment Childhood AML Treatment Research Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Lymphocytic Leukemia Go to Health Professional Version Key Points Chronic ...
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... Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic Cancer Recurrent Cancer Research NCI’s Role in ... on the hands and feet. Muscle pain. Itching. Diarrhea . Stages of Chronic Myeloproliferative Neoplasms Key Points There is no standard staging system ...
Brask-Lindemann, Dorthe; Eiken, P; Eskildsen, P; Abrahamsen, B
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...... 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 < 0.001). Further, a diagnosis of COPD was associated with an increasing tendency of initiating alendronate treatment in the study period (OR 1.3 (95 % CI 1...
Schydlowsky, Pierre; Szkudlarek, Marcin; Madsen, Ole Rintek
We compared the effect of subcutaneous adalimumab injections with intraarticular glucocorticoid injections on frozen shoulder of 18 patients with unilateral joint involvement. Ten patients were randomised to subcutaneous injections with adalimumab and eight to intraarticular glucocorticoid inject...
Full Text Available Prolonged and excessive glucocorticoids (GC exposure resulted from Cushing's syndrome or GC therapy develops central obesity. Moreover, mitochondria are crucial in adipose energy homeostasis. Thus, we tested the hypothesis that mitochondrial dysfunction may contribute to chronic GC exposure-induced epididymal adiposity in the present study. A total of thirty-six 5-week-old male C57BL/6J mice (∼20 g were administrated with 100 µg/ml corticosterone (CORT or vehicle through drinking water for 4 weeks. Chronic CORT exposure mildly decreased body weight without altering food and water intake in mice. The epididymal fat accumulation was increased, but adipocyte size was decreased by CORT. CORT also increased plasma CORT, insulin, leptin, and fibroblast growth factor 21 concentrations as measured by RIA or ELISA. Interestingly, CORT increased plasma levels of triacylglycerols and nonesterified fatty acids, and up-regulated the expression of both lipolytic and lipogenic genes as determined by real-time RT-PCR. Furthermore, CORT impaired mitochondrial biogenesis and oxidative function in epididymal WAT. The reactive oxygen species production was increased and the activities of anti-oxidative enzymes were reduced by CORT treatment as well. Taken together, these findings reveal that chronic CORT administration-induced epididymal adiposity is, at least in part, associated with mitochondrial dysfunction in mouse epididymal white adipose tissue.
Objective To explore the effect and its clinical significance of different dose of glucocorticoids on inflammation mediators in patients with acute exacerbation of chronic obstructive pulmonary diseases.Methods 45 patients admitted to our hospitals from March 2007 to March 2011were randomly divided into 3 groups:methylprednisolone40 mg group(methylprednisolone 40mg,iv,qd),meth-
RUAN Jing-wen; WANG Chu-huai; LIAO Xin-xue; YAN Ying-shuo; HU Yue-hua; RAO Zhong-dong; WEN Ming; ZENG Xiao-xiang; LAI Xin-sheng
Background Due to the quick rhythm of life and work pressure, more and more people suffer from sleep quality problems. In this study, we investigated the effect of electroacupuncture on sleep quality of chronic insomniacs and the safety of electroacupuncture therapy.Methods Four courses of electroacupuncture treatment were applied to 47 patients. With pre-treatment and post-treatment self-control statistical method, Pittsburgh sleep quality index (PSQI) scores were used for evaluating sleep quality. Polysomnogram was used for detecting insomniacs' changes in sleep architecture. The safety of electroacupuncture was evaluated by monitoring the self-designed adverse events and side effects during treatment and post-treatment.Results Electroacupuncture considerably improved insomniacs' sleep quality and social function during the daytime.Electroacupuncture had certain repairing effect on the disruption in sleep architecture. At the same time,electroacupuncture prolonged slow wave sleep (SWS) time and relatively rapid eye movement sleep (REM sleep) time.There was no hangover, addiction or decrements in vigilance during the daytime (incidence rate was 0). However,insomnia rebound rate was about 23% within one month.Conclusions These results suggest that electroacupuncture has beneficial effect on sleep quality improvement in the patients with chronic insomnia, which may be associated with repairing sleep architecture, reconstructing sleep continuity,as well as prolonging SWS time and REM sleep time. Electroacupuncture treatment for chronic insomnia is safe.Therefore, electroacupuncture therapy could be a promising avenue of treatment for chronic insomnia.
Oller do Nascimento Cláudia
Full Text Available Abstract Background Adiponectin is the most abundant plasma protein synthesized for the most part in adipose tissue, and it is an insulin-sensitive hormone, playing a central role in glucose and lipid metabolism. In addition, it increases fatty acid oxidation in the muscle and potentiates insulin inhibition of hepatic gluconeogenesis. Two adiponectin receptors have been identified: AdipoR1 is the major receptor expressed in skeletal muscle, whereas AdipoR2 is mainly expressed in liver. Consumption of high levels of dietary fat is thought to be a major factor in the promotion of obesity and insulin resistance. Excessive levels of cortisol are characterized by the symptoms of abdominal obesity, hypertension, glucose intolerance or diabetes and dyslipidemia; of note, all of these features are shared by the condition of insulin resistance. Although it has been shown that glucocorticoids inhibit adiponectin expression in vitro and in vivo, little is known about the regulation of adiponectin receptors. The link between glucocorticoids and insulin resistance may involve the adiponectin receptors and adrenalectomy might play a role not only in regulate expression and secretion of adiponectin, as well regulate the respective receptors in several tissues. Results Feeding of a high-fat diet increased serum glucose levels and decreased adiponectin and adipoR2 mRNA expression in subcutaneous and retroperitoneal adipose tissues, respectively. Moreover, it increased both adipoR1 and adipoR2 mRNA levels in muscle and adipoR2 protein levels in liver. Adrenalectomy combined with the synthetic glucocorticoid dexamethasone treatment resulted in increased glucose and insulin levels, decreased serum adiponectin levels, reduced adiponectin mRNA in epididymal adipose tissue, reduction of adipoR2 mRNA by 7-fold in muscle and reduced adipoR1 and adipoR2 protein levels in muscle. Adrenalectomy alone increased adiponectin mRNA expression 3-fold in subcutaneous adipose
麦乃铿; 杨晨; 孙瑞佼; 吕艳; 赵津京; 潘树义
Objective To explore the effects of hyperbaric oxygen treatment on chronic stress and glucocorticoid receptor (GR) expression in the hippocampus.Methods A total of 60 male Wistar rats were randomly divided into a restraint group,an HBO (hyperbaric oxygen) group,an HBO-restraint group and a control group using a random number table,each group with 15 animals.All the rats in the restraint and HBO groups were constrained by immobilizing their fore-and hind-limbs on a self-made frame for 3h daily for 21 days,and those in the HBO group received HBO treatment once daily for the same 21 days.The HBO-restraint group was immobilized in the morning and treated with HBO in the afternoon.The control group was reared without any special intervention.On the 1st,11th and 21st day of treatment,rats from the different groups were assessed using the open field test.On the 21st day,all the animals were sacrificed and their brains were harvested to detect GR expression.Results In the open field test on the 11 th day,the restraint group scored (131.0 ± 20.6) in terms of motor level and (26.5 ± 4.6) for exploratory behavior,both significantly higher than before restraint and significantly higher than those in the HBO-restraint group at the same time point.Immunofluorescence assay showed that GR expression in the hippocampus of the restraint group was significantly decreased compared with the control group.There was no significant difference,however,between the HBO-restraint group and the control group.Conclusion Chronic restraint stress induces changes in behavior and GR expression in rats which can be alleviated by hypbaric oxygen treatment.%目的 观察高压氧(HBO)处理和慢性束缚对大鼠行为学及海马区糖皮质激素受体(GR)表达水平的影响,探讨HBO对慢性束缚大鼠的干预作用.方法 将60只雄性Wistar大鼠按随机数字表法分成单纯束缚组、单纯HBO组、HBO联合束缚组和空白对照组,每组15只.单纯束缚组给予行为限制3
Cronin, C C
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.
Fontaine, D; Blond, S; Mertens, P; Lanteri-Minet, M
Neurosurgical treatment of pain used two kind of techniques: 1) Lesional techniques interrupt the transmission of nociceptive neural input by lesionning the nociceptive pathways (drezotomy, cordotomy, tractotomy…). They are indicated to treat morphine-resistant cancer pain and few cases of selected neuropathic pain. 2) Neuromodulation techniques try to decrease pain by reinforcing inhibitory and/or to limit activatory mechanisms. Chronic electrical stimulation of the nervous system (peripheral nerve stimulation, spinal cord stimulation, motor cortex stimulation…) is used to treat chronic neuropathic pain. Intrathecal infusion of analgesics (morphine, ziconotide…), using implantable pumps, allows to increase their efficacy and to reduce their side effects. These techniques can improve, sometimes dramatically, selected patients with severe and chronic pain, refractory to all other treatments. The quality of the analgesic outcome depends on the relevance of the indications. PMID:25681114
Schaik, van, I.N.; Eftimov, F.
This thesis focuses on the efficacy of existing and alternative treatments in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) and explores predictors of treatment response in patients with CIDP treated with corticosteroids. The efficacy of intravenous immunoglobulin (IVIg) in CIDP and MMN was confirmed in meta-analyses. In CIDP, IVIg efficacy was similar to the efficacy of plasma exchange, prednisolone and intravenous methylprednisolone. ...
KÖKSAL, Cengiz; Alsalehi, Saleh; Kocamaz, Özgür; Sunar, Hasan
Chronic venous insufficiency (CVI), with its high prevalence, high cost of diagnosis and treatment, substantial loss in manpower and negative effects on quality of life, is an important health issue. A comprehensive knowledge of the anatomy and functions of venous system is a must to understand the pathophysiology of CVI. The diagnosis of CVI is made by history, physical examination and noninvasive tests. The traditional surgical strategy for CVI treatment is high ligation of saphenofemoral v...
Cengiz Köksal; Saleh Alsalehi; Özgür Kocamaz; Hasan Sunar
Chronic venous insufficiency (CVI), with its high prevalence, high cost of diagnosis and treatment, substantial loss in manpower and negative effects on quality of life, is an important health issue. A comprehensive knowledge of the anatomy and functions of venous system is a must to understand the pathophysiology of CVI. The iagnosis of CVI is made by history, physical examination and noninvasive tests. The traditional surgical strategy for CVI treatment is high ligation of saphenofemoral ve...
Full Text Available Glucocorticoids are currently the only drug treatment recognized to benefit Duchenne muscular dystrophy (DMD patients. The nature of the mechanisms underlying the beneficial effects remains incompletely understood but may involve an increase in the expression of utrophin. Here, we show that treatment of myotubes with 6alpha-methylprednisolone-21 sodium succinate (PDN results in enhanced expression of utrophin A without concomitant increases in mRNA levels thereby suggesting that translational regulation contributes to the increase. In agreement with this, we show that PDN treatment of cells transfected with monocistronic reporter constructs harbouring the utrophin A 5'UTR, causes an increase in reporter protein expression while leaving levels of reporter mRNAs unchanged. Using bicistronic reporter assays, we further demonstrate that PDN enhances activity of an Internal Ribosome Entry Site (IRES located within the utrophin A 5'UTR. Analysis of polysomes demonstrate that PDN causes an overall reduction in polysome-associated mRNAs indicating that global translation rates are depressed under these conditions. Importantly, PDN causes an increase in the polysome association of endogenous utrophin A mRNAs and reporter mRNAs harbouring the utrophin A 5'UTR. Additional experiments identified a distinct region within the utrophin A 5'UTR that contains the inducible IRES activity. Together, these studies demonstrate that a translational regulatory mechanism involving increased IRES activation mediates, at least partially, the enhanced expression of utrophin A in muscle cells treated with glucocorticoids. Targeting the utrophin A IRES may thus offer an important and novel therapeutic avenue for developing drugs appropriate for DMD patients.
Olivarius, Niels de Fine; Siersma, Volkert; Dyring-Andersen, Beatrice; Drivsholm, Thomas Bo; Hansen, Lars J; Henriksen, Jan Erik
sex and to 1.39 (0.92-2.11, p = 0.12, n = 1086) when risk factors, complications and cancer were added to the model. Apart from differences in age and overweight, patients in this relatively small sample of those diagnosed with clinical type 2 diabetes during GC treatment were comparable at diagnosis...... Chronic exposure to glucocorticoids (GCs) has many side effects including glucose intolerance and diabetes and may accelerate the occurrence of cardiovascular disease and increase mortality. We studied the 14-year clinical development of diabetes in patients diagnosed with diabetes during GC...... treatment. A population-based sample of 1369 people newly diagnosed with clinical type 2 diabetes underwent a clinical examination at diagnosis, and surviving patients were followed up 6 and 14 years later. Patients receiving oral GC treatment at diagnosis were compared with the other patients. Of 1369...
Olivarius, Niels de Fine; Siersma, Volkert Dirk; Dyring-Andersen, B.; Drivsholm, Thomas Bo; Hansen, L.J.; Henriksen, J.E.
sex and to 1.39 (0.92-2.11, p = 0.12, n = 1086) when risk factors, complications and cancer were added to the model. Apart from differences in age and overweight, patients in this relatively small sample of those diagnosed with clinical type 2 diabetes during GC treatment were comparable at diagnosis......Chronic exposure to glucocorticoids (GCs) has many side effects including glucose intolerance and diabetes and may accelerate the occurrence of cardiovascular disease and increase mortality. We studied the 14-year clinical development of diabetes in patients diagnosed with diabetes during GC...... treatment. A population-based sample of 1369 people newly diagnosed with clinical type 2 diabetes underwent a clinical examination at diagnosis, and surviving patients were followed up 6 and 14 years later. Patients receiving oral GC treatment at diagnosis were compared with the other patients. Of 1369...
曾平; 陶建瓴; 李雪梅
Glucocorticoids have remained important anti-inflammatory agents in the treatment of chronic kidney disease (CKD).However,the use of glucocorticoids can invoke or enhance insulin resistance,which is closely associated with renal injury and serves as an independent risk of the occurrence and progression of CKD.On the other hand,CKD patients may have insulin resistance,which hampers the use of glucocorticoids in these patients.%糖皮质激素作为一种抗炎介质在慢性肾脏病的治疗中有重要地位,而糖皮质激素的使用可使患者发生胰岛素抵抗或使原有胰岛素抵抗加重.胰岛素抵抗与肾脏病变关系密切,可作为慢性肾脏病发生发展的独立危险因素,并加重肾脏病变.慢性肾脏病患者亦可有胰岛素抵抗表现,这给慢性肾脏病患者的糖皮质激素治疗造成了困难,本文就这一问题进行综述.
Adachi, Yoshiko; Yamagami, Toshiko
The efficacy of non-pharmacological intervention for chronic insomnia has been proven by several meta-analytic reviews, an NIH report, an American Academy of Sleep Medicine review, and numerous clinical trials. Behavior therapy for chronic insomnia consists of relaxation, stimulus control, sleep restriction, cognitive restructuring and sleep hygiene education, which has produced reliable and durable changes in total sleep time, sleep onset latency, number and duration of awakening. These studies also showed that the post-treatment effect of behavior therapy is equal to that of hypnotic therapy, and that these effects were maintained for 6 months on follow-up assessment. Elderly insomniac patients would gain considerable benefit from behavioral treatments because there are no adverse physical effects as there are from pharmacological therapy. The authors present the basic theory, techniques of behavior therapy for insomnia, and the results of two important key meta-analytic reviews. Any behavioral approach such as convenient education, self-care enhancement by bibliotherapy, and individual face-to-face counseling, seem to be fruitful not only for American but also Japanese insomnia patients. Nonetheless, there are no currently actual intervention studies using behavior therapy in Japan. We have discussed the methodology of intervention study and published a behavioral self-help manual for people with sleep problems. Development of a behavioral approach to chronic insomnia seemed to be very beneficial and a useful contribution to mental health services. PMID:12373807
Full Text Available Chronic venous insufficiency (CVI, with its high prevalence, high cost of diagnosis and treatment, substantial loss in manpower and negative effects on quality of life, is an important health issue. A comprehensive knowledge of the anatomy and functions of venous system is a must to understand the pathophysiology of CVI. The iagnosis of CVI is made by history, physical examination and noninvasive tests. The traditional surgical strategy for CVI treatment is high ligation of saphenofemoral vein and saphenous vein stripping. In recent years, novel minimally invasive techniques such as ultrasound-guided foam sclerotherapy, endovenous laser and radiofrequency ablation have been more widely applied. Here, we have reviewed the various treatment strategies used in CVI.
ObjectiveTo observe the effect of antibiotics combined with glucocorticoid in the treatment of elderly patients with chronic obstructive pulmonary emphysema effect.Methods A total of 110 elderly patients with chronic obstructive pulmonary emphysema patients were given conventional treatment with antibiotics and glucocorticoid treatment.ResultsThe total efficiency of the observation group after treatment,arterial partial pressure of oxygen, carbon dioxide partial pressure were better than the control group. ConclusionIn elderly patients with chronic obstructive pulmonary emphysema and effect of antibiotics and glucocorticoid treatment was significantly.%目的：观察抗生素联合糖皮质激素治疗中老年慢性阻塞性肺气肿的效果。方法110例慢性阻塞性肺气肿老年患者分别给予常规治疗与抗生素联合糖皮质激素治疗。结果观察组治疗总有效率、治疗后血氧分压、二氧化碳分压均优于对照组。结论抗生素联合糖皮质激素治疗中老年慢性阻塞性肺气肿效果显著。
S.W. Paugh (Steven); E.J. Bonten (Erik J.); D. Savic (Daniel); L.B. Ramsey (Laura B.); W.E. Thierfelder (William E.); P. Gurung (Prajwal); R.K.S. Malireddi (R. K. Subbarao); M. Actis (Marcelo); A. Mayasundari (Anand); J. Min (Jaeki); D.R. Coss (David R.); L.T. Laudermilk (Lucas T.); J.C. Panetta (John); J.R. McCorkle (J. Robert); Y. Fan (Yiping); K.R. Crews (Kristine R.); G. Stocco (Gabriele); M.R. Wilkinson (Mark R.); A.M. Ferreira (Antonio M.); C. Cheng (Cheng); W. Yang (Wenjian); S.E. Karol (Seth E.); C.A. Fernandez (Christian A.); B. Diouf (Barthelemy); C. Smith (Colton); J.K. Hicks (J Kevin); A. Zanut (Alessandra); A. Giordanengo (Audrey); D.J. Crona; J.J. Bianchi (Joy J.); L. Holmfeldt (Linda); C.G. Mullighan (Charles); M.L. den Boer (Monique); R. Pieters (Rob); S. Jeha (Sima); T.L. Dunwell (Thomas L.); F. Latif (Farida); D. Bhojwani (Deepa); W.L. Carroll (William L.); C.-H. Pui (Ching-Hon); R.M. Myers (Richard M.); R.K. Guy (R Kiplin); T.-D. Kanneganti (Thirumala-Devi); M.V. Relling (Mary); W.E. Evans (William)
textabstractGlucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and resistance to glucocorticoids in leukemia cells confers poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the prednisolone sensitivity of primary leukemia ce
Arp, J Marit; Ter Horst, Judith P; Loi, Manila; den Blaauwen, Jan; Bangert, Eline; Fernández, Guillén; Joëls, Marian; Oitzl, Melly S; Krugers, Harm J
Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated (i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal day 2 to 9 - affects conditioned fear in adult mice and (ii) whether these effects can be prevented by blocking glucocorticoid receptors (GRs) at adolescent age. In adult male and female mice, ELS did not affect freezing behavior to the first tone 24h after training in an auditory fear-conditioning paradigm. Exposure to repeated tones 24h after training also resulted in comparable freezing behavior in ELS and control mice, both in males and females. However, male (but not female) ELS compared to control mice showed significantly more freezing behavior between the tone-exposures, i.e. during the cue-off periods. Intraperitoneal administration of the GR antagonist RU38486 during adolescence (on postnatal days 28-30) fully prevented enhanced freezing behavior during the cue-off period in adult ELS males. Western blot analysis revealed no effects of ELS on hippocampal expression of glucocorticoid receptors, neither at postnatal day 28 nor at adult age, when mice were behaviorally tested. We conclude that ELS enhances freezing behavior in adult mice in a potentially safe context after cue-exposure, which can be normalized by brief blockade of glucocorticoid receptors during the critical developmental window of adolescence. PMID:27246249
Tempfer, Herbert; Gehwolf, Renate; Lehner, Christine; Wagner, Andrea; Mtsariashvili, Maia; Bauer, Hans-Christian; Resch, Herbert; Tauber, Mark
Background Rotator cuff tears are a common cause of shoulder pain and impairment. Subacromial glucocorticoid injections are widely used for treatment of epiphenomenons of chronic impingement syndrome with the possible side effects of tendon rupture and impaired tendon healing. Methods Using qRT-PCR, western blot, immunoflourescence, and measurement of 3H-thymidine uptake we investigated the effects of the crystalline glucocorticoid triamcinolone acetonide (TAA) when added to the culture mediu...
Magnussen, Helgo; Disse, Bernd; Rodriguez-Roisin, Roberto;
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 bronchod......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...... fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric...
May, Arne; Schulte, Laura H
Chronic migraine has a great detrimental influence on a patient's life, with a severe impact on socioeconomic functioning and quality of life. Chronic migraine affects 1-2% of the general population, and about 8% of patients with migraine; it usually develops from episodic migraine at an annual conversion rate of about 3%. The chronification is reversible: about 26% of patients with chronic migraine go into remission within 2 years of chronification. The most important modifiable risk factors for chronic migraine include overuse of acute migraine medication, ineffective acute treatment, obesity, depression and stressful life events. Moreover, age, female sex and low educational status increase the risk of chronic migraine. The pathophysiology of migraine chronification can be understood as a threshold problem: certain predisposing factors, combined with frequent headache pain, lower the threshold of migraine attacks, thereby increasing the risk of chronic migraine. Treatment options include oral medications, nerve blockade with local anaesthetics or corticoids, and neuromodulation. Well-defined diagnostic criteria are crucial for the identification of chronic migraine. The International Headache Society classification of chronic migraine was recently updated, and now allows co-diagnosis of chronic migraine and medication overuse headache. This Review provides an up-to-date overview of the classification of chronic migraine, basic mechanisms and risk factors of migraine chronification, and the currently established treatment options. PMID:27389092
Scaroni, C; Favia, G; Lumachi, F; Opocher, G; Bonanni, G; Mantero, F; Armanini, D
In untreated congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHDS) the presence of adrenal and testicular tumors had been described; however little is known about the effect of the enzymatic defect on fertility in males. We studied a male adult patient affected by 21OHDS for infertility, after a long period of discontinuation of glucocorticoid therapy and then during resumption of treatment and 8 months after monoadrenalectomy. The initial spermatic count revealed azoospermia and testicular needle aspiration showed a cytological picture consistent with prepuberty. The morphofunctional study revealed a right adrenal mass with reduced uptake at radioscan. Treatment was resumed with onset of impotency, which improved after reduction of the dose of glucocorticoids. The patient was monoadrenalectomised and his spermatic count increased. The patient shows that corticosteroid therapy in 21OHDS should be continued lifelong to avoid adrenal hyperplasia with possible areas of autonomy and to allow regular fertility. Impotence during treatment is probably due to a decrease of excessive adrenal androgens while testicular androgen production is still suppressed. PMID:12605349
Sadowska, Grazyna B.; Stonestreet, Barbara S
Gap junctions facilitate intercellular communication and are important in brain development. Connexins (Cx) comprise a transmembrane protein family that forms gap junctions. Cx-32 is expressed in oligodendrocytes and neurons, Cx-36 in neurons, and Cx-43 in astrocytes. Although single antenatal steroid courses are recommended for fetal lung maturation, multiple courses can be given to women at recurrent risk for premature delivery. We examined the effects of single and multiple glucocorticoid ...
Michele Baccarani; Fausto Castagnetti; Gabriele Gugliotta; Francesca Palandri; Gianantonio Rosti
The first treatment of chronic myeloid leukemia (CML) included spleen x-radiation and conventional drugs, mainly Busulfan and Hydroxyurea. This therapy improved the quality of life during the chronic phase of the disease, without preventing nor significantly delaying the progression towards advanced phases. The introduction of allogeneic stem cell transplantation (alloSCT) marked the first important breakthrough in the evolution of CML treatment, because about 50% of the eligible patients wer...
Baccarani, Michele; Castagnetti, Fausto; Gugliotta, Gabriele; Palandri, Francesca; Rosti, Gianantonio
The first treatment of chronic myeloid leukemia (CML) included spleen x-radiation and conventional drugs, mainly Busulfan and Hydroxyurea. This therapy improved the quality of life during the chronic phase of the disease, without preventing nor significantly delaying the progression towards advanced phases. The introduction of allogeneic stem cell transplantation (alloSCT) marked the first important breakthrough in the evolution of CML treatment, because about 50% of the eligible patients wer...
Diener, Hans-Christoph; Dodick, David W; Goadsby, Peter J;
According to the revised 2nd Edition of the International Classification of Headache Disorders, primary headaches can be categorized as chronic or episodic; chronic migraine is defined as headaches in the absence of medication overuse, occurring on =15 days per month for =3 months, of which...... headaches on =8 days must fulfill the criteria for migraine without aura. Prevalence and incidence data for chronic migraine are still uncertain, owing to the heterogeneous definitions used to identify the condition in population-based studies over the past two decades. Chronic migraine is severely...... disabling and difficult to manage, as affected patients experience substantially more-frequent headaches, comorbid pain and affective disorders, and fewer pain-free intervals, than do those with episodic migraine. Data on the treatment of chronic migraine are scarce because most migraine-prevention trials...
Mahrle, G; Schulze, H J
In a randomized open study we compared the effect of conventional dithranol therapy (CSV-therapy, 7 patients) with a combination regimen, in which patients were pretreated with a 0.064% betametason dipropionate ointment (Diprosis) for 1 week before the onset of dithranol therapy (B + CSV-therapy). Clinical evaluation was performed by grading 4 representative lesions per patient for erythema, plaque thickness and scaling every week (EPS-score). After one week of therapy glucocorticoid was superior to dithranol (reduction of EPS-scores 68% vs. 35%). Thereafter the benefit of CSV-therapy surpassed that of B + CSV-therapy. 33 days after onset of therapy there was a 95% reduction of skin lesions in the CSV-group compared to a 75% reduction in the B + CSV-group. In terms of a 95% reduction the CSV-group required 32.9 +/- 5.5 days versus 45.1 +/- 19.7 days of the B + CSV-group. During the 6 months follow-up relapses occurred in 3 of 7 patients of the CSV-group 15.32 and 34 days after discontinuation of therapy and in 2 of 7 patients of the B + CSV-group 64 and 82 days after discontinuation of therapy. The present findings reveal that a pretreatment of psoriasis with topical glucocorticoids reduces the response to dithranol and the duration of remission. PMID:2187310
Yoon, Na Young; Jung, Min young; Kim, Dong Hye; Lee, Hae Jin; Choi, Eung Ho
Congenitally or early impaired skin barrier as the first event starting the 'atopic march' in atopic dermatitis (AD) patients can increase allergen penetration that results in sensitization, even in the airways, followed by asthma and allergic rhinitis. Thymic stromal lymphopoietin (TSLP) is a cytokine existing in high levels in AD skin and is considered as a novel therapeutic target for atopic disease. We generated oxazolone (Ox)-induced AD-like (Ox-AD) hairless mice and divided them into four groups according to the therapeutic challenges: topical glucocorticoid, pimecrolimus, emollient, and control (acetone-only treated). We assessed the functional studies of skin barrier, epidermal expressions of differentiation markers, IL-1α, TNF-α, proteinase-activated receptor-2 (PAR-2), TSLP and antimicrobial peptides (AMP), and serum IgE in each group. Topical glucocorticoid or pimecrolimus treatment improved AD-like skin lesions and barrier functions, and restored the epidermal expression of differentiation markers, IL-1α, TNF-α, PAR-2, and TSLP, in Ox-AD mice. The improvement was relatively better with the glucocorticoid than pimecrolimus. Epidermal AMP expression was restored by topical glucocorticoid, but not pimecrolimus. Our result showed that topical glucocorticoid or pimecrolimus improved the AD-like skin lesions and barrier impairment by suppressing TSLP-related allergic inflammation. PMID:25786383
Kaplan, Allen P
Chronic spontaneous urticaria is defined as persistent symptoms of urticaria for 6 weeks or more. It is associated with autoimmunity in approximately 45 percent of patients. Therapy is often difficult however the initial approach should employ high-dose non-sedating antihistamines; 4-6 tablets/day may be necessary. It has been shown that the response to 4 tablets/day exceeds 3, and exceeds 2, which exceeds 1. However the dose that corresponds to the maximal dose of first generation antihistam...
Full Text Available Chronic spontaneous urticaria is a distressing disease encountered frequently in clinical practice. The current mainstay of therapy is the use of second-generation, non-sedating antihistamines. However, in patients who do not respond satisfactorily to these agents, a variety of other drugs are used. This article examines the available literature for frequently used agents including systemic corticosteroids, leukotriene receptor antagonists, dapsone, sulfasalazine, hydroxychloroquine, H2 antagonists, methotrexate, cyclosporine A, omalizumab, autologous serum therapy, and mycophenolate mofetil, with an additional focus on publications in Indian literature.
Andersen, E.S.; Weis, Nina
Worldwide, 350 million people are infected with chronic hepatitis B. Over the last few years, it has been possible to treat chronic hepatitis B. Treatment very often consists of nucleos(t)ide analogs and in a few cases of pegylated alpha-interferon. In 2007, a new nucleoside analog, Telbivudine......, was approved to treat chronic hepatitis B. In phase II and ongoing phase III studies, Telbivudine has proven more effective than the nucleoside analog, Lamivudine, which was very often used up until recently Udgivelsesdato: 2008/11/24...
The current mainstay of management of chronic beryllium disease involves cessation of beryllium exposure and use of systemic corticosteroids. However, there are no randomized controlled trials to assess the effect of these interventions on the natural history of this disease. Despite this limitation, it is prudent to remove patients with chronic beryllium disease from further exposure and consider treating progressive disease early with long-term corticosteroids. The effect of treatment shoul...
Naschitz, J; Dreyfuss, D; Yeshurun, D.; Rosner, I
The long term results of midodrine treatment in a patient having debilitating chronic fatigue syndrome (CFS) are reported. Midodrine treatment, directed at the autonomic nervous system, resulted in correction of the dysautonomia followed by improvement of fatigue. This finding is consistent with the hypothesis that dysautonomia plays a major part in the pathophysiology of CFS and that therapies directed at the autonomic nervous system may be effective in the treatment of CFS.
Sobue, Kenji; Fukumoto, Kentaro
The glucocorticoids (GCs), the most downstream effectors of the hypothalamic-pituitary-adrenal (HPA) axis, are the main mediators of stress response. Stress-triggered GCs as well as acute and chronic GC treatment can impair the structural plasticity and function of the brain. The exposure of perinatal animals and humans to excess stress or GCs can affect the brain development, resulting in altered behaviors in the adult offspring of animals and an increased risk of psychiatric disorders in hu...
Yamaguti, A; Trevisanello, C; Lobo, I M; Carvalho, M C; Bortoletto, M L; Silva, M L; Brasil Filho, R; Levi, G C; Mendonça, J S
Seventeen adult patients with chronic osteomyelitis were treated with oral ciprofloxacin, 750 mg twice daily. Treatment ranged from 28 to 254 days. Efficacy was considered to be good, based upon clinical resolution observed in 13 patients (76%). Clinical and microbiological failure was observed in 3 patients (18%), and there was one case of reinfection. Tolerance was very satisfactory, since the adverse reactions were mild and transitory; these occurred in 7 patients (41%), being cutaneous rash in 4 patients and diarrhoea in 3 patients. No patient had to discontinue treatment. Thus, oral ciprofloxacin may be useful option for the prolonged treatment of chronic osteomyelitis, provided that it is always associated with surgical debridement. Due to the probable development of ciprofloxacin resistance in the S. aureus multiresistant strain, already observed in two patients in the present investigation, it is suggested that for the treatment of such infections another drug with antistaphylococcal activity should be associated with the ciprofloxacin. PMID:8354592
Moriarty, Maureen; Mallick-Searle, Theresa
Migraine is a debilitating headache disorder that is underdiagnosed and undertreated worldwide, partially attributable to misdiagnosis and expectations of poor treatment outcomes. This article provides a review of chronic migraine, including pathophysiology, burden, diagnosis, and management, with special emphasis on the role of NPs. PMID:27203455
Kalager, T; Bøe, E; Digranes, A; Høisaether, P; Solberg, C O
Twenty-eight patients with chronic urinary tract infections were treated with 400 mg pivmecillinam orally three times daily for 10 to 15 days. The diagnosis was confirmed by a history of cystitis or cystopyelitis four to six times annually, microscopy of urine sediment, and growth of pathogens in urine specimens obtained by suprapubic bladder puncture. Three days, three and six weeks after completion of therapy the success rates were 24/28, 20/28 and 19/28 respectively. Pivmecillinam was well tolerated. Two patients developed nausea and vomiting. Other side-effects were not observed. Pivmecillinam is a useful drug in the treatment of chronic urinary tract infections. PMID:204581
Naaman, Sandra; Sussman, Gordon
Chronic idiopathic urticaria (CIU) is a common autoimmune skin condition characterized by spontaneously recurring hives for 6 weeks or longer. The new terminology used for CIU in most countries including Canada is chronic spontaneous urticaria (CSU). CSU is associated with significant psychosocial morbidity with a markedly negative impact on overall quality of life. Conventional approaches with antihistamines, even at high doses, is effective in about 50% of patients suffering from CSU. A new treatment option, omalizumab, a humanized monoclonal antibody against the Fc domain of IgE, has undergone the scrutiny of randomized research studies evaluating the efficacy in CSU. This editorial reviews mechanisms of action of omalizumab, efficacy, cost and potential side effect profile. Omalizumab has emerged as a very promising treatment option for patients with CSU. Future research is necessary to establish standardized protocols related to dosing as well as monitoring possible adverse effects of long-term treatment. PMID:25807072
. Corticoid-induced osteoporosis is the main adverse event deriving from their systemic and long-term administration, being the most frequent cause of secondary osteoporosis. This implies an important health and socio-economic repercussion due to the complications it causes, such as fragility fractures, above all of vertebral origin, and the resultant functional incapacity. The bone loss is produced early, being greatest in the first few months of glucocorticoid use, in relation fundamentally to daily dose. The pathogenesis of this type of osteoporosis is multifactorial, but the inhibitory effect of corticoids on bone formation can be emphasised. The adequate management of this serious health problem requires an active attitude that is currently suboptimal. It involves similar diagnostic, preventive and therapeutic recommendations available for other, different causes of bone loss, but with certain particularities, especially including those referring to the self-management of corticosteroids. A multidisciplinary strategy is advisable, which has shown its effectiveness, mainly if it is carried out early, from the start of glucocorticoid therapy. Nevertheless, there are many questions to be clarified about aspects relating to therapy with corticosteroids in general, and to the osteoporosis caused by them in particular. What is needed is the evaluation and investigation of new treatments that will improve the effectiveness obtained with those in current use, in order to minimize the adverse consequences that glucocorticoid use has for the health of patients.
Sánchez-Quijano, Armando; Lissen-Otero, Eduardo
Hepatitis C virus infection is the principal cause of chronic liver disease, cirrhosis and hepatocellular carcinoma in the Western World. Chronic hepatitis C is often silent, most of the times discovered only by routine serologic or biochemical testing and the interval between infection and the development of cirrhosis exceed 30 years. Interestingly the complications of chronic hepatitis C virus infection can be prevented by antiviral therapy. At present, the combination of pegylated interferon-alfa and ribavirina has become the standard treatment of chronic hepatitis C. The management of HCV infection in "special populations" (HIV coinfection and HCV therapy-experienced patient) has improved significantly over the past few years, through a better knowledge of the disease and the publication of several clinical trials performed in these patients. At presents, a number of new anti-HCV therapies are in development. Future drugs for HCV infection might make possible to eradicate HCV in future. PMID:16987471
Abdel Kawy, Hala S
Airway inflammation in chronic obstructive pulmonary disease (COPD) is refractory to corticosteroids and hence COPD treatment is hindered and insufficient. This study assessed the effects of oral treatment with Montelukast (10 and 30 mg/kg) or dexamethasone (20 mg/kg) for 20 days on COPD model induced by chronic exposure to lipopolysaccharide (LPS). Six groups of male guinea pigs were studied. Group 1: naïve group, group 2: exposed to saline nebulization. Groups 3, 4, 5, and 6: exposed to 9 nebulizations of LPS (30 μg/ml) for 1 hour, 48 hours apart with or without treatment with Montelukast or dexamethasone. Airway hyperreactivity (AHR) to methacholine (MCh), histopathological study and bronchoalveolar lavage fluid (BALF) as well as lung tissue analyses were performed 48 hours after the final exposure to LPS (day 20). LPS-induced pulmonary dysfunction was associated with increased neutrophil count, leukotriene (LT) B4, and tumor necrosis factor (TNF)-α in BALF. Moreover, there was an increase in malondialdehyde (MDA) level and a decrease in histone deacetylases(HDAC) activity in the lung tissue. Both Montelukast (10 or 30 mg /kg) and dexamethasone significantly reduced neutrophil count in BALF and inflammatory cells in lung parenchyma as well as TNF-α, and MDA levels. However, dexamethasone was more effective (p dexamethasone. These results suggest that treatment with Montelukast can be useful in chronic airway inflammatory diseases including COPD poorly responsive to glucocorticoids. PMID:26751767
Walsh, Michael; Merkel, Peter A.; Peh, Chen Au; Szpirt, Wladimir; Guillevin, Loïc; Charles D. Pusey; deZoysa, Janak; Ives, Natalie; Clark, William F.; Quillen, Karen; Winters, Jeffrey L.; Wheatley, Keith; Jayne, David
Background Granulomatosis with polyangiitis (GPA, Wegener’s) and microscopic polyangiitis (MPA) are small vessel vasculitides collectively referred to as anti-neutrophil cytoplasm antibody-associated vasculitis (AAV). AAV is associated with high rates of morbidity and mortality due to uncontrolled disease and treatment toxicity. Small randomized trials suggest adjunctive plasma exchange may improve disease control, while observational evidence suggests that current oral glucocorticoid doses a...
Full Text Available Despite of extensive blood product screening and national immunization programs, chronic hepatitis B and C infections continues to be a global problem with high mortality, morbidity and economic impact. Even though acquisition of these infections mostly occurs in childhood, major problems appear in adulthood. Cirrhosis and HCC are two major expected late events related to chronic hepatitis B and C infections. Rarely, children may also face these complications. To avoid these complications and increase the life expectancy in adults treatment of these two type infections should be started in childhood with appropriate patient selection. In contrast to children, adults are luckier in terms of treatment alternatives. They have the chance to use more potent antivirals with higher genetic barrier and pegylated form of interferons. Recently, the use of pegylated interferon and ribavirin combinations has been approved in children in Chronic HCV infection. However, chronic hepatitis B treatment in children is still dependent on the use of one type antiviral drug and conventional interferon. Treatment in early ages with an antiviral agent that has limited genetic barrier may block the chance of treatment or reduce the response rate in adulthood in chronic hepatitis B infection. This burden indicates the necessity of new therapeutic modalities in children. In this term pegylated interferons may be one of the optiones. In this article we aimed to reviewe the efficacy and safety of conventional and pegylated interferons, for the treatment of Hepatitis C and B infections in children.
A A Fedorova
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
Tan, Gabriel; Fukui, Tenley; Jensen, Mark P; Thornby, John; Waldman, Karen L
Chronic low back pain (CLBP) is a significant healthcare problem, and many individuals with CLBP remain unresponsive to available interventions. Previous research suggests that hypnosis is effective for many chronic pain conditions; however, data to support its efficacy for CLBP are outdated and have been limited primarily to case studies. This pilot study indicated that a brief, 4-session standardized self-hypnosis protocol, combined with psycho-education, significantly and substantially reduced pain intensity and pain interference. Significant session-to-session improvements were also noted on pain ratings and mood states; however, follow-up data suggest that these benefits may not have been maintained across time in this sample. These findings need to be replicated and confirmed in a larger clinical trial, which could also assess the long-term effects of this treatment. PMID:20183738
Full Text Available The first treatment of chronic myeloid leukemia (CML included spleen x-radiation and conventional drugs, mainly Busulfan and Hydroxyurea. This therapy improved the quality of life during the chronic phase of the disease, without preventing nor significantly delaying the progression towards advanced phases. The introduction of allogeneic stem cell transplantation (alloSCT marked the first important breakthrough in the evolution of CML treatment, because about 50% of the eligible patients were cured. The second breakthrough was the introduction of human recombinant interferon-alfa, able to achieve a complete cytogenetic remission in 15% to 30% of patients, with a significant survival advantage over conventional chemotherapy. At the end of the last century, about 15 years ago, all these treatments were quickly replaced by a class of small molecules targeting the tyrosine kinases (TK, which were able to induce a major molecular remission in most of the patients, without remarkable side effects, and a very prolonged life-span. The first approved TK inhibitor (TKI was Imatinib Mesylate (Glivec or Gleevec, Novartis. Rapidly, other TKIs were developed tested and commercialized, namely Dasatinib (Sprycel, Bristol-Myers Squibb, Nilotinib (Tasigna, Novartis, Bosutinib (Busulif, Pfizer and Ponatinib (Iclusig, Ariad. Not all these compounds are available worldwide; some of them are approved only for second line treatment, and the high prices are a problem that can limit their use. A frequent update of treatment recommendations is necessary. The current treatment goals include not only the prevention of the transformation to the advanced phases and the prolongation of survival, but also a length of survival and of a quality of life comparable to that of non-leukemic individuals. In some patient the next ambitious step is to move towards a treatment-free remission. The CML therapy, the role of alloSCT and the promising experimental strategies are reviewed in
van de Veerdonk, Frank L; Netea, Mihai G
Autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) is a rare and severe primary immunodeficiency that is characterized by mucocutaneous fungal infection, autoimmunity, cerebral aneurysms, and oropharyngeal and esophageal cancer. Recently, it was discovered that STAT1 mutations are responsible for AD-CMC. These mutations lead to the inability of STAT1 to be dephosphorylated, resulting in hyperphosphorylation, increased binding to the DNA, and gain of function (GOF) effects on STAT1 signaling. Furthermore, a characteristic feature of AD-CMC patients is deficiency in the T-helper 17 (Th17) responses, which is believed to be the immunological cause of the mucocutaneous fungal infection. No targeted treatment other than lifelong antifungal prophylaxis exists for AD-CMC. However, the discovery of the genetic and immunological defects makes it now possible to explore new treatment strategies. This review will discuss immunomodulatory treatment options that can be explored in patients with STAT1 GOF mutations. PMID:27161991
Occurrence of glucocorticoids discharged from a sewage treatment plant in Japan and the effects of clobetasol propionate exposure on the immune responses of common carp (Cyprinus carpio) to bacterial infection.
Nakayama, Kei; Sato, Kentaro; Shibano, Takazumi; Isobe, Tomohiko; Suzuki, Go; Kitamura, Shin-Ichi
The present study evaluated the environmental risks to common carp (Cyprinus carpio) posed by glucocorticoids present in sewage treatment plant (STP) effluent. To gather information on the seasonal variations in glucocorticoid concentration, the authors sampled the effluent of a Japanese STP every other week for 12 mo. Six of 9 selected glucocorticoids were detected in the effluent, with clobetasol propionate and betamethasone 17-valerate detected at the highest concentrations and frequencies. The present study's results indicated that effluent glucocorticoid concentration may depend on water temperature, which is closely related to the removal efficiency of the STP or to seasonal variations in the public's use of glucocorticoids. In a separate experiment, to clarify whether glucocorticoids in environmental water increase susceptibility to bacterial infection in fish, the authors examined the responses to bacterial infection (Aeromonas veronii) of common carp exposed to clobetasol propionate. Clobetasol propionate exposure did not affect bacterial infection-associated mortality. In fish infected with A. veronii but not exposed to clobetasol propionate, head kidney weight and number of leukocytes in the head kidney were significantly increased (p < 0.05), whereas these effects were not observed in infected fish exposed to clobetasol. This suggests that clobetasol propionate alleviated bacterial infection-associated inflammation. Together, these results indicate that susceptibility to bacterial infection in common carp is not affected by exposure to glucocorticoids at environmentally relevant concentrations. Environ Toxicol Chem 2016;35:946-952. © 2015 SETAC. PMID:26126539
Full Text Available The yeast named Candida normally colonizes the gut and vagina without causing any sign of its presence. It is a commensal and opportune fungus but in certain conditions it turns to be pathogenic, causing chronic disturbances in any part of the body. The pathogenesis is complex, signs and symptoms are non-specific. The colonisation is difficult to distinguish from invasive disease. The current diagnostic methods do not always allow a definitive diagnosis to be made. Treatment is complex, individual and no protocol can be created. The author tries to give an overview of the Candida related problem.
Since the introduction of imatinib just over a decade ago, there has been a dramatic change in the treatment and prognosis of early chronic phase chronic myeloid Leukaemia (CML). This review article focuses on recent advances, culminating in the approval of nilotinib by the US Food and Drug Administration for the treatment of adult patients with newly diagnosed CML in the chronic phase.
Full Text Available INTRODUCTION: The principal indication for surgical intervention in chronic pancreatitis is intractable pain. Depending upon the presence of dilated pancreatic ductal system, pancreatic duct drainage procedures and different kinds of pancreatic resections are applied. OBJECTIVE: The objective of the study was to show the most appropriate procedure to gain the most possible benefits in dependence of type of pathohistological process in chronic pancreatitis. METHOD: Our study included 58 patients with intractable pain caused by chronic pancreatitis of alcoholic genesis. The first group consisted of 30 patients with dilated pancreatic ductal system more than 10 mm. The second group involved 28 patients without dilated pancreatic ductal system. Pain relief, weight gain and glucose tolerance were monitored. RESULTS: All patients of Group I (30 underwent latero-lateral pancreaticojejunal - Puestow operation. 80% of patients had no pain after 6 month, 13.6% had rare pain and 2 patients, i.e. 6.4%, who continued to consume alcohol, had strong pain. Group II consisting of 28 patients was without dilated pancreatic ductal system. This group was subjected to various types of pancreatic resections. Whipple procedure (W was done in 6 patients, pylorus preserving Whipple (PPW in 7 cases, and duodenum preserving cephalic pancreatectomy (DPCP was performed in 15 patients. Generally, 89.2% of patients had no pain 6 month after the operation. An average weight gain was 1.9 kg in W group, 2.8 kg in PPW group and 4.1 kg in DPCP group. Insulin-dependent diabetes was recorded in 66.6% in W group, 57.1% in PPW group and 0% in DPCP group. CONCLUSION: According to our opinion, DPCP may be considered the procedure of choice for surgical treatment of pain in chronic pancreatitis in patients without dilatation of pancreas ductal system because of no serious postoperative metabolic consequences.
Atucha, Erika; Zalachoras, Ioannis; van den Heuvel, José K; van Weert, Lisa T C M; Melchers, Diana; Mol, Isabel M; Belanoff, Joseph K; Houtman, René; Hunt, Hazel; Roozendaal, Benno; Meijer, Onno C
Adrenal glucocorticoid hormones are potent modulators of brain function in the context of acute and chronic stress. Both mineralocorticoid (MRs) and glucocorticoid receptors (GRs) can mediate these effects. We studied the brain effects of a novel ligand, C118335, with high affinity for GRs and modest affinity for MRs. In vitro profiling of receptor-coregulator interactions suggested that the compound is a "selective modulator" type compound for GRs that can have both agonistic and antagonistic effects. Its molecular profile for MRs was highly similar to those of the full antagonists spironolactone and eplerenone. C118335 showed predominantly antagonistic effects on hippocampal mRNA regulation of known glucocorticoid target genes. Likewise, systemic administration of C118335 blocked the GR-mediated posttraining corticosterone-induced enhancement of memory consolidation in an inhibitory avoidance task. Posttraining administration of C118335, however, gave a strong and dose-dependent impairment of memory consolidation that, surprisingly, reflected involvement of MRs and not GRs. Finally, C118335 treatment acutely suppressed the hypothalamus-pituitary-adrenal axis as measured by plasma corticosterone levels. Mixed GR/MR ligands, such as C118335, can be used to unravel the mechanisms of glucocorticoid signaling. The compound is also a prototype of mixed GR/MR ligands that might alleviate the harmful effects of chronic overexposure to endogenous glucocorticoids. PMID:26305887
Holm, Jens-Christian; Gamborg, Michael; Bille, Dorthe S;
Clinically-relevant protocols for the treatment of childhood obesity are lacking. This study report results for a clinic-based structured treatment program for chronic childhood obesity.......Clinically-relevant protocols for the treatment of childhood obesity are lacking. This study report results for a clinic-based structured treatment program for chronic childhood obesity....
Full Text Available Abstract Background Synthetic glucocorticoids such as dexamethasone (DEX are commonly used to promote fetal lung maturation in at-risk preterm births, but there is emerging evidence of subsequent neurobehavioral abnormalities in these children e.g. problems with inattention/hyperactivity. However, molecular pathways mediating effects of glucocorticoid overexposure on motor and cognitive development are poorly understood. Methods In this study with common marmoset monkeys, we investigated for neonatal and adulthood effects of antenatal DEX treatment on the expression of the corticosteroid receptors and also calcyon, a risk gene for attention-deficit/hyperactivity disorder, in the prefrontal cortex (PFC. Pregnant marmosets were exposed to DEX (5 mg/kg body weight or vehicle during early (days 42-48 or late (days 90-96 stages of the 144-day pregnancy. Results In neonates, relative to controls, glucocorticoid receptor (GR mRNA levels were significantly reduced after the late DEX treatment in the medial, orbital and dorsal PFC and after the early DEX treatment in the dorsal PFC. The early DEX exposure, specifically, resulted in significant reduction in calcyon mRNA expression in the medial, orbital, dorsal and lateral PFC relative to controls. Mineralocorticoid receptor (MR mRNA levels were not significantly affected by DEX treatment. In adults, PFC GR, calcyon, and MR mRNA levels were not significantly affected by early or late prenatal DEX treatment. Conclusion These findings indicate that antenatal DEX treatment could lead to short-term alterations in PFC expression of the GR and calcyon genes, with possible neurodevelopmental functional consequences.
Menguy, R; Chey, W
We review current experience with surgical treatment of severe constipation due to primary inertia of the colon. Over the last 10 years, we have operated 18 patients (14 females and 4 males) with severe constipation. The surgical procedure was either nearly total colonectomy with ascending colon/rectum anastomosis (8 cases) or total colonectomy with ileorectal anastomosis (9 cases). In one patient, coloproctectomy was performed with an ileoanal anastomosi. Indications for surgery were based on results of barium emena and functional evaluation of defecation. Results were satisfactory in all patients. In several patients however, we noted that the motility of other levels of the digestive tract was also impaired. Colonectomy was introduced as a treatment for chronic constipation nearly a century ago and although very few indications have been retained in the recent this procedure has now become an acceptable surgical approach in a limited number of well-though-out cases. PMID:7729199
Bernardo Barcellos Terra
Full Text Available ABSTRACTOBJECTIVE: To report the clinical and functional results from arthroscopic release of the short radial extensor of the carpus (SREC in patients with chronic lateral epicondylitis that was refractory to conservative treatment. METHODS: Over the period from January 2012 to November 2013, 15 patients underwent arthroscopic treatment. The surgical technique used was the one described by Romeo and Cohen, based on anatomical studies on cadavers. The inclusion criteria were that the patients needed to present lateral epicondylitis and that conservative treatment (analgesics, anti-inflammatory agents, corticoid infiltration or physiotherapy had failed over a period of more than six months. The patients were evaluated based on the elbow functional score of the Mayo Clinic, Nirschl's staging system and a visual analog scale (VAS for pain. RESULTS: A total of 15 patients (9 men and 6 women were included. The mean Mayo elbow functional score after the operation was 95 (ranging from 90 to 100. The pain VAS improved from a mean of 9.2 before the operation to 0.64 after the operation. On Nirschl's scale, the patients presented an improvement from a mean of 6.5 before the operation to approximately one. There were significant differences from before to after the surgery for the three functional scores used ( p 0.05. CONCLUSION: Arthroscopic treatment for lateral epicondylitis was shown to be a safe and effective therapeutic option when appropriately indicated and performed, in refractory cases of chronic lateral epicondylitis. It also allowed excellent viewing of the joint space for diagnosing and treating associated pathological conditions, with a minimally invasive procedure.
Paugh, Steven W.; Bonten, Erik J.; Savic, Daniel; Ramsey, Laura B.; Thierfelder, William E.; Gurung, Prajwal; Malireddi, R. K. Subbarao; Actis, Marcelo; Mayasundari, Anand; Min, Jaeki; Coss, David R.; Laudermilk, Lucas T.; Panetta, John C.; McCorkle, J. Robert; Fan, Yiping; Crews, Kristine R.; Stocco, Gabriele; Wilkinson, Mark R.; Ferreira, Antonio M.; Cheng, Cheng; Yang, Wenjian; Karol, Seth E.; Fernandez, Christian A.; Diouf, Barthelemy; Smith, Colton; Hicks, J. Kevin; Zanut, Alessandra; Giordanengo, Audrey; Crona, Daniel; Bianchi, Joy J.; Holmfeldt, Linda; Mullighan, Charles G.; den Boer, Monique L.; Pieters, Rob; Jeha, Sima; Dunwell, Thomas L.; Latif, Farida; Bhojwani, Deepa; Carroll, William L.; Pui, Ching-Hon; Myers, Richard M.; Guy, R. Kiplin; Kanneganti, Thirumala-Devi; Relling, Mary V.; Evans, William E.
Glucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and leukemia cell resistant to glucocorticoids confers a poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the sensitivity to prednisolone of primary leukemia cells from 444 newly diagnosed ALL patients, revealing significantly higher expression of caspase 1 (CASP1) and its activator NLRP3 in glucocorticoid resistant leukemia cells, due to significantly lower somatic methylation of CASP1 and NLRP3 promoters. Over-expression of CASP1 resulted in cleavage of the glucocorticoid receptor, diminished glucocorticoid-induced transcriptional response and increased glucocorticoid resistance. Knockdown or inhibition of CASP1 significantly increased glucocorticoid receptor levels and mitigated glucocorticoid resistance in CASP1 overexpressing ALL. Our findings establish a new mechanism by which the NLRP3/CASP1 inflammasome modulates cellular levels of the glucocorticoid receptor and diminishes cell sensitivity to glucocorticoids. The broad impact on glucocorticoid transcriptional response suggests this mechanism could also modify glucocorticoid effects in other diseases. PMID:25938942
Quinn, Matthew; Ramamoorthy, Sivapriya; Cidlowski, John A
Sexual dimorphism is a well-documented phenomenon that is observed at all levels of the animal kingdom. Historically, sex hormones (testosterone and estrogen) have been implicated as key players in a wide array of pathologies displaying sexual dimorphism in their etiology and progression. While these hormones clearly contribute to sexually dimorphic diseases, other factors may be involved in this phenomenon as well. In particular, the stress hormone cortisol exerts differential effects in both males and females. The underlying molecular basis for the sexually dimorphic actions of glucocorticoids is unknown but clearly important to understand, since synthetic glucocorticoids are the most widely prescribed medication for the treatment of chronic inflammatory diseases and hematological cancers in humans. PMID:24739020
B.S. Nagoba,; B.J. Wadher and S.P. Selkar
Chronic wound infections in animals not responding to conventional treatment modality are the important cause of morbidity. Infection is responsible for delayed wound healing. In the present study, an attempt was made to develop simple and effective treatment modality by using citric acid as a sole antimicrobial agent to control chronic wound infections in animals. Thirty eight cases of chronic wounds not responding to conventional treatment modalities were divided into two groups. Each group...
Full Text Available Abstract Background To test the hypothesis of down-regulating the increased immune system activation/destruction process associated with chronic HIV infection, we focused our interest on prednisolone (PDN, because we had showed that, in vitro, PDN had a strong anti-apoptotic activity on activated T cells of HIV-infected patients and no effect on viral replication. We thus designed in 1992 a pilot study to evaluate the clinical, immunologic and virologic effects of PDN. The drug was given to a group of 44 patients with CD4 T cells over 200/μl. After one year, no patient had developed clinical AIDS and the mean CD4 T cell count of the group had increased from 441 ± 21 cells/μl to 553 ± 43 cells/μl. Moreover, markers of immune activation had dropped back to normal levels while the mean viral load of the group had remained unchanged. Here we explore the long-term clinical, immunologic, and virologic impact of prednisolone on the chronic phase of HIV infection. Methods Retrospective study over 10 years starting between July 1992 and February 1993. A total of 44 patients with CD4 cells/μl ranging from 207 to 775 were treated with prednisolone, 0.5 mg/kg/d, over 6 months and 0.3 mg/kg/d thereafter. Results No clinical AIDS developed under prednisolone; side effects of the drug were mild. CD4 cells which increased from 421 cells/μl at entry to 625 cells/μl at day 15, slowly decreased to reach 426 cells/μl after two years; T cell apoptosis and activation markers dropped within 15 days to normal levels and reincreased slowly thereafter. Serum viral loads remained stable. The percentage of patients maintaining CD4 cells over entry was 43.2% at two years, 11.4% at five years and 4.6% at 10 years. Initial viral load was highly predictive of the rate of CD4 decrease under prednisolone. Conclusions Prednisolone postponed CD4 cell decrease in a viral load dependent manner for a median of two years and for up to 10 years in a fraction of the patients
Full Text Available Aisha Masood1, Taimur Sher2, Aneel Paulus2, Kena C Miller2, Kasyapa S Chitta3, Asher Chanan-Khan4 1The Tisch Cancer Institute, Bone Marrow Transplant Unit, Mount Sinai School of Medicine, 2Department of Medicine, Roswell Park Cancer Institute, 3Department of Molecular Targets and Experimental Therapeutics, Roswell Park Cancer Institute, New York, NY, 4Division of Hematology/Oncology, Mayo Clinic, Jacksonville, FL, USA Abstract: The treatment of chronic lymphocytic leukemia (CLL has evolved over the last few decades. Recognition has increased of several key components of CLL biology currently manipulated for therapeutics. A milestone in the treatment of CLL was reached with the incorporation of immunotherapy with conventional chemotherapy. The fludarabine/cyclophosphamide/rituximab combination has demonstrated survival advantage for the first time in the treatment of CLL. Several other biological compounds are being explored with the hope of improving responses, impacting survival, and ultimately curing CLL. Important agents being tested are targeted on CLL surface molecules and their ligands, signal transduction protein and oncogenes. This review provides a brief summary of the recent advances made in preclinical and clinical investigation of selected promising therapeutic agents, which lead the target-directed therapeutic approach. Keywords: CLL, Akt inhibitors, Bcl-2 inhibitors, cyclin d kinase inhibitors, heat shock protein inhibitors, immunomodulatory drugs, monoclonal antibodies
Olsson, A.; Oturai, D B; Sørensen, P S;
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 the...... 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...
Olesen, Søren Schou; Bowense, S; Wilder-Smith, Oliver; van Goor, H; Drewes, Asbjørn Mohr
Intractable pain usually dominates the clinical presentation of chronic pancreatitis (CP). Slowing of electroencephalogram (EEG) rhythmicity has been associated with abnormal cortical pain processing in other chronic pain disorders. The aim of this study was to investigate the spectral distribution...
Hae-Yeon Lee; Jung-Han Park; Hyun-Seok Cho; Jung-Chul Kim; Tae-Hyun Baik; Jong-Seong Wi
Chronic acalculous cholecystitis gets possession of about 12 to 13 percent of patients with chronic cholecystitis. Pathologically it is characterised by chronic inflammation and thickening of the gallbladder wall but doesn't come across stones. Clinical symptoms are vague and include abdominal discomfort and distension, nausea, flatulence and intolerance of fatty foods. A patient on chronic acalculous cholecystitis diagnosed from his clinical symtoms and abdominal ultrasonogram was treated by...
Przybilla, B; Kaudewitz, P
In a comparative study, 20 ambulatory patients suffering from chronic psoriasis vulgaris with plaques were treated with preparations containing either dithranol (0.1/0.2%) plus urea (17%) or desoximetasone (0.25%). In the two groups, 7 and 8 courses, resp., could be evaluated. Both modalities led to significant improvement of the skin lesions. During the course of treatment, there were no significant differences between the two regimens with regard to both the area of skin involvement and the scores of semiquantitative evaluation of infiltration, erythema, and scaling. PMID:3281386
Reul, Johannes M.H.M.; Collins, Andrew; Saliba, Richard S.; Mifsud, Karen R.; Carter, Sylvia D.; Gutierrez-Mecinas, Maria; Qian, Xiaoxiao; Linthorst, Astrid C.E.
Glucocorticoid hormones play a pivotal role in the response to stressful challenges. The surge in glucocorticoid hormone secretion after stress needs to be tightly controlled with characteristics like peak height, curvature and duration depending on the nature and severity of the challenge. This is important as chronic hyper- or hypo-responses are detrimental to health due to increasing the risk for developing a stress-related mental disorder. Proper glucocorticoid responses to stress are critical for adaptation. Therefore, the tight control of baseline and stress-evoked glucocorticoid secretion are important constituents of an organism's resilience. Here, we address a number of mechanisms that illustrate the multitude and complexity of measures safeguarding the control of glucocorticoid function. These mechanisms include the control of mineralocorticoid (MR) and glucocorticoid receptor (GR) occupancy and concentration, the dynamic control of free glucocorticoid hormone availability by corticosteroid-binding globulin (CBG), and the control exerted by glucocorticoids at the signaling, epigenetic and genomic level on gene transcriptional responses to stress. We review the beneficial effects of regular exercise on HPA axis and sleep physiology, and cognitive and anxiety-related behavior. Furthermore, we describe that, possibly through changes in the GABAergic system, exercise reduces the impact of stress on a signaling pathway specifically in the dentate gyrus that is strongly implicated in the behavioral response to that stressor. These observations underline the impact of life style on stress resilience. Finally, we address how single nucleotide polymorphisms (SNPs) affecting glucocorticoid action can compromise stress resilience, which becomes most apparent under conditions of childhood abuse.
Jensen, Tonny Joran; Hansen, M; Madsen, J C;
OBJECTIVE: To evaluate the influence of inflammatory activity and glucocorticoid (GC) treatment on serum parathyroid hormone (s-PTH) and bone metabolism in patients with rheumatoid arthritis (RA). Furthermore, in patients with active RA, to examine the PTH secretion and Ca2+ set point before and...... after treatment with GC. METHODS: A range of biochemical markers of bone metabolism and calcium homeostasis were measured in 95 patients with definite RA stratified into groups according to disease activity and GC treatment. In a subgroup of 12 patients with active disease, initiating slow......-acting-anti-rheumatic-drugs (SAARDs) +/- GC, the PTH secretion and calcium set point were evaluated by use of the Cica clamp technique before and after 1 month of treatment. RESULTS: S-osteocalcin, s-total alkaline phosphatase (s-TAP) and s-carboxyterminal cross-linked telopeptide of type I collagen (s-ICTP) were elevated in all...
A radioimmunoassay was developed to measure calmodulin in striatum from rats treated with one dose or repeated injections of amphetamine. Chronic, but not acute, amphetamine treatment resulted in a significant increase in total calmodulin levels in striatal homogenates. This effect may be linked to the behavioral sensitization which develops after chronic amphetamine treatments. (Auth.)
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.
Damsker, Jesse M; Dillingham, Blythe C; Rose, Mary C; Balsley, Molly A; Heier, Christopher R; Watson, Alan M; Stemmy, Erik J; Jurjus, Roslyn A; Huynh, Tony; Tatem, Kathleen; Uaesoontrachoon, Kitipong; Berry, Dana M; Benton, Angela S; Freishtat, Robert J; Hoffman, Eric P; McCall, John M; Gordish-Dressman, Heather; Constant, Stephanie L; Reeves, Erica K M; Nagaraju, Kanneboyina
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. PMID:23667681
Exercício físico previne alterações cardiometabólicas induzidas pelo uso crônico de glicocorticóides Ejercicio físico previene alteraciones cardiometabólicas inducidas por el uso crónico de glucocorticoides Exercise prevents cardiometabolic alterations induced by chronic use of glucocorticoids
Carlos Hermano da Justa Pinheiro
exercise on cardiometabolic alterations induced by chronic administration of dexamethasone (Dex - 0.5 mg/kg/day ip in rats. METHODS: Male Wistar rats (n = 24 were divided in four groups: Control group; Trained group; Treated with Dex group and Treated with Dex and trained group. The exercise training (initiated 72 hours after the first dose of Dex was carried out three times a week until the end of the treatment. At the end of this period, the following biochemical assessments were performed: fasting glycemia, oral glucose tolerance test and analysis of the blood lipid profile that included total cholesterol (TC, LDL-c, HDL-c, VLDL-c and triglycerides (TG. The weight of the gastrocnemius muscle, the histopathological analysis of the liver and cardiometabolic indices (TC/HDL-c, LDL-c/HDL-c and TG/HDL-c were also performed. RESULTS: Hyperglycemia, lower glucose tolerance, increased TC, LDL-c, VLDL-c, TG, CT/HDL-c, LDL-c/HDL-c and TG/HDL-c, decreased HDL-c, presence of liver steatosis and muscular hypotrophy were observed in the animals treated with Dex. The exercise training reduced hyperglycemia, improved glucose tolerance, decreased dyslipidemia and prevented liver steatosis, muscular hypotrophy and reduced CT/HDL-c, LDL-c/HDL-c and TG/HDL-c ratios. However, there was no significant effect on HDL-c. CONCLUSION: The aerobic exercise training have a protective effect against the cardiometabolic alterations induced by the chronic use of glucocorticoids.
Full Text Available Chronic acalculous cholecystitis gets possession of about 12 to 13 percent of patients with chronic cholecystitis. Pathologically it is characterised by chronic inflammation and thickening of the gallbladder wall but doesn't come across stones. Clinical symptoms are vague and include abdominal discomfort and distension, nausea, flatulence and intolerance of fatty foods. A patient on chronic acalculous cholecystitis diagnosed from his clinical symtoms and abdominal ultrasonogram was treated by Geonbihwan, acupuncture and herbal acupuncture. Satisfactory symptomatic improvement was achieved and findings of abdominal ultrasonogram came also normal.
Maher, C G
It is now feasible to adopt an evidence-based approach when providing physical treatment for patients with chronic LBP. A summary of the efficacy of a range of physical treatments is provided in Table 1. The evidence-based primary care options are exercise, laser, massage, and spinal manipulation; however, the latter three have small or transient effects that limit their value as therapies for chronic LBP. In contrast, exercise produces large reductions in pain and disability, a feature that suggests that exercise should play a major role in the management of chronic LBP. Physical treatments, such as acupuncture, backschool, hydrotherapy, lumbar supports, magnets, TENS, traction, ultrasound, Pilates therapy, Feldenkrais therapy, Alexander technique, and craniosacral therapy are either of unknown value or ineffective and so should not be considered. Outside of primary care, multidisciplinary treatment or functional restoration is effective; however, the high cost probably means that these programs should be reserved for patients who do not respond to cheaper treatment options for chronic LBP. Although there are now effective treatment options for chronic LBP, it needs to be acknowledged that the problem of chronic LBP is far from solved. Though treatments can provide marked improvements in the patient's condition, the available evidence suggests that the typical chronic LBP patient is left with some residual pain and disability. Developing new, more powerful treatments and refining the current group of known effective treatments is the challenge for the future. PMID:15062718
Chronic obstructive pulmonary disease (COPD) is defined by fixed airflow limitation associated with an abnormal pulmonary and systemic inflammatory response of the lungs to cigarette smoke. COPD represents an increasing burden worldwide, reported to be the sixth leading cause of death in 1990 and the fourth in 2000. Discouragingly, it is projected to jump to third place by the year 2020.There is increasing evidence that COPD is a more complex systemic disease than an airway and lung disease. In particular, cachexia, skeletal muscle abnormalities, diabetes, coronary artery disease, heart failure, cancer and pulmonary vascular disease are the most common comorbidities. It is associated with a wide variety of systemic consequences, most notably systemic inflammation. Because COPD patients have in general ahigher cardiovascular risk than the average population, cardiovascular safety in a COPD medication is of critical importance.SINGH et al performed a systematic review and recta-analysis of 17 clinical trials enrolling 14 783 patients treated with inhaled anticholinergic drugs used for the treatment of COPD. Inhaled anticholinergics significantly increased the risk of cardiovascular death, MI, or stroke ( 1.8 % vs 1.2 % for control; RR, 1.58 (95 % CI,1.21 - 2.06); P < 0.001 ). However, UPLIIFT (Understanding the Potential Long-Term Impacts on Function with Tiotropium) , a large, 4-year, placebo controlled clinical trial with tiotropium in approximately 6 000 patients with COPD. The preliminary results of UPLIFT showed that there was no increased risk of stroke with tiotropium bromide compared to placebo.A meta-analysis is always considered less convincing than a large prospective trial designed to assess the outcome of interest. However, COPD is a systemic disease. COPD management needs to focus on four major areas: smoking cessation, pharmacologic therapy, exercise training, and pulmonary rehabilitation. Clinicians and patients should always carefully consider any
Damsted, Sara K.; Born, A P; Paulson, Olaf B;
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...... reduces neurogenesis and cerebral volume, impairs memory and increases the incidence of cerebral palsy. Cerebral effects of glucocorticoids in later childhood have been less thoroughly studied, but apparent brain atrophy, reduced size of limbic structures and neuropsychiatric symptoms have been reported......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...
Daniel L Marks
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
A chronic anal fissure is a common perianal condition. This review aims to evaluate both existing and new therapies in the treatment of chronic fissures. Pharmacological therapies such as glyceryl trinitrate (GTN), Diltiazem ointment and Botulinum toxin provide a relatively non-invasive option, but with higher recurrence rates. Lateral sphincterotomy remains the gold standard for treatment. Anal dilatation has no role in treatment. New therapies include perineal support devices, Gonyautoxin i...
Spiga, Francesca; Knight, David M; Droste, Susanne K; Conway-Campbell, Becky; Kershaw, Yvonne; MacSweeney, Cliona P; Thomson, Fiona J; Craighead, Mark; Peeters, Bernard WMM; Lightman, Stafford L
The effects of RU486 and S-P, a more selective glucocorticoid receptor antagonist from Schering-Plough, were investigated on glucocorticoid receptor nuclear translocation and DNA binding. In the in vitro study, AtT20 cells were treated with vehicle or with RU486, S-P or corticosterone (3–300 nM) or co-treated with vehicle or glucocorticoid receptor antagonists (3–300 nM) and 30 nM corticosterone. Both glucocorticoid receptor antagonists induced glucocorticoid receptor nuclear translocation but only RU486 induced DNA binding. RU486 potentiated the effect of corticosterone on glucocorticoid receptor nuclear translocation and DNA binding, S-P inhibited corticosterone-induced glucocorticoid receptor nuclear translocation, but not glucocorticoid receptor-DNA binding. In the in vivo study, adrenalectomized rats were treated with vehicle, RU486 (20 mg/kg) and S-P (50 mg/kg) alone or in combination with corticosterone (3 mg/kg). RU486 induced glucocorticoid receptor nuclear translocation in the pituitary, hippocampus and prefrontal cortex and glucocorticoid receptor-DNA binding in the hippocampus, whereas no effect of S-P on glucocorticoid receptor nuclear translocation or DNA binding was observed in any of the areas analysed. These findings reveal differential effects of RU486 and S-P on areas involved in regulation of hypothalamic–pituitary–adrenal axis activity in vivo and they are important in light of the potential use of this class of compounds in the treatment of disorders associated with hyperactivity of the hypothalamic–pituitary–adrenal axis. PMID:20093322
Rosa Maria Rodrigues Pereira
Full Text Available Os glicocorticoides (GC são prescritos por praticamente todas as especialidades médicas, e cerca de 0,5% da população geral do Reino Unido utiliza esses medicamentos. Com o aumento da sobrevida dos pacientes com doenças reumatológicas, a morbidade secundária ao uso dessa medicação representa um aspecto importante que deve ser considerado no manejo de nossos pacientes. As incidências de fraturas vertebrais e não vertebrais são elevadas, variando de 30%-50% em pessoas que usam GC por mais de três meses. Assim, a osteoporose e as fraturas por fragilidade devem ser prevenidas e tratadas em todos os pacientes que iniciarão ou que já estejam em uso desses esteroides. Diversas recomendações elaboradas por várias sociedades internacionais têm sido descritas na literatura, porém não há consenso entre elas. Recentemente, o Americam College of Rheumatology publicou novas recomendações, porém elas são fundamentadas na FRAX (WHO Fracture Risk Assessment Tool para analisar o risco de cada indivíduo e, dessa maneira, não podem ser completamente utilizadas pela população brasileira. Dessa forma, a Comissão de Osteoporose e Doenças Osteometabólicas da Sociedade Brasileira de Reumatologia, em conjunto com a Associação Médica Brasileira e a Associação Brasileira de Medicina Física e Reabilitação, implementou as diretrizes brasileiras de osteoporose induzida por glicocorticoide (OPIG, baseando-se na melhor evidência científica disponível e/ou experiência de experts. DESCRIÇÃO DO MÉTODO DE COLETA DE EVIDÊNCIA: A revisão bibliográfica de artigos científicos desta diretriz foi realizada na base de dados MEDLINE. A busca de evidência partiu de cenários clínicos reais, e utilizou as seguintes palavras-chave (MeSH terms: Osteoporosis, Osteoporosis/chemically induced*= (Glucocorticoids= Adrenal Cortex Hormones, Steroids, Glucocorticoids, Glucocorticoids/administration and dosage, Glucocorticoids/therapeutic use
Grossi, O; Généreau, T
The risk of infection is increased in patients treated with glucocorticoids, especially in those taking long-term and high dosage treatment. However, there is little valid practice for the prevention of infections in this patient population. The risk of reactivation or worsening of a latent infection (e.g., hepatitis B, tuberculosis, strongyloidiasis) is proved and individual reflection should be conducted in at-risk patients. Preventions of Pneumocystis jiroveci or upper urinary tract infections are considered differently according to practitioners' habits and their specialties. Adequate prevention should be prescribed in glucocorticoid-treated patients who have been in contact with varicella zoster or measles virus. Many vaccines could be prescribed in those people but live vaccines should be avoided. A consultation of travel medicine should be systematically proposed before a travel in intertropical zone. Anti-inflammatory and stimulant properties of glucocorticoids are frequently misused in order to improve sport performances. All glucocorticoids are considered as performance-enhancing drugs. Their prescription should therefore be adapted to the laws in force in the sport. By reducing vomiting and pain, glucocorticoids may be beneficial in patients undergoing surgery. However, in people prescribed long-term glucocorticoid therapy, the risk of postoperative adrenal insufficiency has to be considered, even though very few data are available on this topic. Oral contraceptives or intra-uterine devices are effective contraceptives methods in patients treated with systemic glucocorticoids. PMID:23415059
Mitić, M.; Simić, I.; Djordjević, J.; Radojčić, M. B.; Adžić, M.
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and stress disorders. Glucocorticoids, key regulators of the stress response, exert diverse effects on cellular processes in the hippocampus. Beside non-genomic pathways, glucocorticoid effects are mediated through activation of the glucocorticoid receptor (GR), a ligand activated transcriptional factor that belongs to the nuclear hormone receptor superfamily. We analysed the GR protein levels both in the cytoplasmic and nuclear compartments of the hippocampus of Wistar rats exposed to chronic psychosocial isolation stress upon chronic fluoxetine (FLU) treatment. Under chronic stress, corticosterone levels (CORT) were decreased compared to the control, and treatment with FLU did not change its level in the stressed rats. At the molecular level, FLU normalized the level of nuclear GR protein in the hippocampus of the stressed rats. Discrepancy between normalization of nuclear GR in the hippocampus and lack of normalization of HPA axis activity judged by CORT, suggests that other brain structures such as the amygdale and prefrontal cortex that also regulate HPA axis activity, seem not to be normalized by the FLU treatment used in our study.
Sullivan, P B; Marsh, M N; Phillips, M B; Dewit, O; Neale, G; Cevallos, A M; Yamson, P; Farthing, M J
To determine the prevalence of giardiasis in Gambian children with chronic diarrhoea and to assess their response to treatment, 31 children with chronic diarrhoea and malnutrition were investigated for giardiasis using a combination of serology (specific antigiardia IgM antibody) and microscopy of faeces and jejunal biopsy specimens. Fourteen of 31 children with chronic diarrhoea had giardiasis compared with only four of 33 healthy age and sex matched control children. Four of 15 malnourished...
Christensen, E; Gluud, C
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...
The most common chronic bloodborne infection in the United States, hepatitis C virus (HCV) is the most frequent reason for liver transplantation. Unfortunately, most infected individuals don't realize they're HCV positive and only discover the disease after severe liver damage has occurred. Here, update your knowledge on the epidemiology, transmission and risk factors, diagnosis, clinical presentation, and management of chronic HCV. Insight on counseling and quality of life issues for infected patients is also included. PMID:11984417
This thesis describes the treatment, epidemiology and clinical features of the adolescent chronic fatigue syndrome (CFS). Fatigue is a common complaint among adolescents, with a reported incidence of up to 20% in girls. This fatigue however is not chronic, does not debilitate and has an identifiable
Objective:To explore the clinical effect of glucocorticoid in the treatment of endocrine disorders.Methods:106 patients with endocrine diseases were selected.They were randomly divided into the experimental group and the control group with 54 cases in each.The control group were given conventional treatment,and the experimental group were given glucocorticoids on the basis of the control group,then we observed the therapeutic effect in the two groups.Results:In the experimental group,the total efficiency(98.1%) was significantly higher than that of the control group(79.6%);the satisfaction(98.1%) was significantly higher than that of the control group(79.6%);the adverse reaction rate(3.7%) was significantly lower than that of the control group(14.8%), P<0.05.Conclusion:Glucocorticoid treatment of endocrine disorders can significantly improve the patient's symptoms and improve patient satisfaction,and the safety was good.%目的：探讨糖皮质激素治疗内分泌疾病的临床效果。方法：收治内分泌疾病患者106例，随机分为试验组和对照组各54例，对照组采用常规方法治疗，试验组在对照组的基础上加入糖皮质激素治疗，观察两组的治疗效果。结果：在试验组总有效率(98.1%)明显高于对照组(79.6%)，满意度(98.1%)明显高于对照组(79.6%)，不良反应率(3.7%)明显低于对照组(14.8%)，P＜0.05。结论：采用糖皮质激素治疗内分泌疾病可以明显改善患者的症状，提高患者的满意度，安全性好。
Full Text Available Chronic wound infections in animals not responding to conventional treatment modality are the important cause of morbidity. Infection is responsible for delayed wound healing. In the present study, an attempt was made to develop simple and effective treatment modality by using citric acid as a sole antimicrobial agent to control chronic wound infections in animals. Thirty eight cases of chronic wounds not responding to conventional treatment modalities were divided into two groups. Each group included 19 cases. In group 1, 3% citric acid solution and in group 2, 5% citric acid solution was used for local application to find out its efficacy in the treatment of chronic wound infections in animals. Citric acid was found effective in the control of all 38 cases in 7 to 20 applications. In group 1, the wounds healed in 10-20 applications. In group 2, the wounds healed in 7-15 applications. Citric acid treatment was found most effective and economical approach for the successful treatment of chronic infected wounds in animals not responding to conventional antibiotic treatment and local wound care. These results suggest that when healing of chronic wounds in animals is a matter of great concern, the value of topical agents like citric acid should not be forgotten.
Gibney, Virgil P.
This Classic article is a reprint of the original work by Virgil P. Gibney, Chapter XVIII. Operative Treatment in Chronic Articular Ostitis. An accompanying biographical sketch of Virgil P. Gibney, MD, is available at DOI 10.1007/s11999-009-1166-2. The Classic Article is ©1884 and is abridged from Gibney VP. Operative treatment in chronic articular ostitis. In: The Hip and Its Diseases. New York, NY, London, UK: Bermingham & Co; 1884:388–402.
Clark, Glenn T; Padilla, Mariela; Dionne, Raymond
Chronic pain in the orofacial region has always been a vexing problem for dentists to diagnose and treat effectively. For trigeminal neuropathic pain, there are 3 medications (gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors) to use plus topical anesthetics that have therapeutic efficacy. For chronic daily headaches (often migraine in origin), 3 prophylactic medications have reasonable therapeutic efficacy (β-blockers, tricyclic antidepressants, and antiepileptic drugs). The 3 Food and Drug Administration-approved drugs for fibromyalgia (pregabalin, duloxetine, and milnacipran) are not robust, with poor efficacy. For osteroarthritis, nonsteroidal anti-inflammatory drugs have therapeutic efficacy and when gastritis contraindicates them, corticosteriod injections are helpful. PMID:27475515
Hudgens, Alletta Jervey
Describes the outcome of a short-term, family-centered, behavioral approach to chronic pain at the University of Minnesota Hospitals. Family members were taught operant conditioning techniques which rewarded nonpain-oriented behavior in patients. By treating the total family, 75 percent of the patients and families were able to lead satisfactory…
... Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic Cancer Recurrent Cancer Research NCI’s Role in ... on the hands and feet. Muscle pain. Itching. Diarrhea . Stages of Chronic Myeloproliferative Neoplasms Key Points There is no standard staging system ...
... Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic Cancer Recurrent Cancer Research NCI’s Role in ... on the hands and feet. Muscle pain. Itching. Diarrhea . Stages of Chronic Myeloproliferative Neoplasms Key Points There is no standard staging system ...
Tsujimoto, Tatsuhiro; Kawaratani, Hideto; Yoshiji, Hitoshi; Uemura, Masahito; Fukui, Hiroshi
Chronic pancreatitis is a progressive inflammatory condition characterized by repeated attacks of abdominal pain, and the destruction and fibrosis of the pancreatic parenchyma which causes to reduced exocrine and endocrine functions. Alcohol is the most common cause of chronic pancreatitis. Although abstinence is usually considered a prerequisite for successful treatment of alcoholic chronic pancreatitis, we often encounter patients who have repeated attacks from the compensated stage through the transitional stage. In alcoholic chronic pancreatitis, continued alcohol consumption causes changes in the digestive hormones and vagal nerve function that induce the pancreatic acinar cells to oversecrete protein, increasing the protein concentration and viscosity of the pancreatic juice. This induces protein sedimentation from the pancreatic juice and formation of protein plugs within the pancreatic duct, triggering repeated attacks of acute pancreatitis. The treatment of alcoholic chronic pancreatitis includes alleviation of symptoms, particularly abdominal pain, elimination of trigger factors, prevention of recurrence and disease progression, adjuvant therapies for pancreatic exocrine and endocrine failure. Recently, the main constituent proteins in these protein plugs have been identified, enabling trials of several therapies, such as the administration of secretin formulations and endoscopic removal. Bromhexine hydrochloride, a bronchial mucolytic, has an affinity for the pancreatic acinar cells, inducing them to secrete pancreatic juice of low viscosity. In this review, we summarize the most recent thoughts about alcoholic chronic pancreatitis, and the new treatments, and in particular, we present our findings concerning the efficacy of bromhexine hydrochloride in the treatment of this disease. PMID:19630718
Full Text Available Migraine is a disabling neurologic condition with a spontaneous clinical evolution into a chronic form. Migraine progression from an episodic into a chronic form is realized through a period of time involving several months or years, during which an increase attack frequency occurs. .According to the International Classification of Headache Disorders (ICHD-3 chronic migraine is a type of primary headache occurring on 15 or more days per month for more than 3 months, in which more than 8 days per month headache meet criteria for migraine with or without aura or respond to specific migraine treatment. The prevalence of chronic migraine is estimated between 1- 3% of general population. Persons with chronic migraine are more likely to suffer from severe disability; chronic migraine has an important socio-economic impact. Diagnostic approach in chronic migraine includes exclusion of a secondary headache disorder and confirmation of a primary episodic headache. When a patient is found to overuse pain medication, diagnosis of both chronic migraine and MOH should be considered. Treating episodic migraine early and managing attack frequency using preventive medication and behavioural interventions will be benefic in reducing the risk of chronicisation. Lifestyle changes are important for avoiding triggers for migraine attacks; treatment of comorbidities is equally important because these conditions exacerbate patient’s tendency to have headaches. The initial relief step for drug abusers always relies in drug withdrawal. For migraine attacks treatment begins with non-pharmacologic interventions (staying in a quiet, dark room, pressure on painful areas, applying cold compresses , simple OTC analgetics (NSAIDs, paracetamol, aspirin, acetaminophen. If these are not effective, triptans are the drugs of choice. Preventive treatment is always recommended in patients with chronic migraine because the high frequency of headache attacks. Treatment should be
Huynh, Tony; Uaesoontrachoon, Kitipong; Quinn, James L; Tatem, Kathleen S; Heier, Christopher R; Van Der Meulen, Jack H; Yu, Qing; Harris, Mark; Nolan, Christopher J; Haegeman, Guy; Grounds, Miranda D; Nagaraju, Kanneboyina
The over-expression of NF-κB signalling in both muscle and immune cells contribute to the pathology in dystrophic muscle. The anti-inflammatory properties of glucocorticoids, mediated predominantly through monomeric glucocorticoid receptor inhibition of transcription factors such as NF-κB (transrepression), are postulated to be an important mechanism for their beneficial effects in Duchenne muscular dystrophy. Chronic glucocorticoid therapy is associated with adverse effects on metabolism, growth, bone mineral density and the maintenance of muscle mass. These detrimental effects result from direct glucocorticoid receptor homodimer interactions with glucocorticoid response elements of the relevant genes. Compound A, a non-steroidal selective glucocorticoid receptor modulator, is capable of transrepression without transactivation. We confirm the in vitro NF-κB inhibitory activity of compound A in H-2K(b) -tsA58 mdx myoblasts and myotubes, and demonstrate improvements in disease phenotype of dystrophin deficient mdx mice. Compound A treatment in mdx mice from 18 days of post-natal age to 8 weeks of age increased the absolute and normalized forelimb and hindlimb grip strength, attenuated cathepsin-B enzyme activity (a surrogate marker for inflammation) in forelimb and hindlimb muscles, decreased serum creatine kinase levels and reduced IL-6, CCL2, IFNγ, TNF and IL-12p70 cytokine levels in gastrocnemius (GA) muscles. Compared with compound A, treatment with prednisolone, a classical glucocorticoid, in both wild-type and mdx mice was associated with reduced body weight, reduced GA, tibialis anterior and extensor digitorum longus muscle mass and shorter tibial lengths. Prednisolone increased osteopontin (Spp1) gene expression and osteopontin protein levels in the GA muscles of mdx mice and had less favourable effects on the expression of Foxo1, Foxo3, Fbxo32, Trim63, Mstn and Igf1 in GA muscles, as well as hepatic Igf1 in wild-type mice. In conclusion, selective
Iakhontova, O I; Dudanova, O P
Chronic liver diseases are marked by a well-defined relationship between the intensity of the cytolytic syndrome and the level of circulating immune complexes (CIC). The highest damaging action on hepatocytes is produced by medium-sized CIC because of their penetrating and complement fixing effects. The level of thrombocytopenia and, to a less measure, of leukopenia also depends on the concentration and size of CIC in CAH and liver cirrhosis (LC), which may provide indirect evidence of the lytic action of CIC on hepatocytes, leading in turn to the impairment of microcirculation and aggravation of hepatocyte hypoxia. The data obtained attest to the role CIC of varying size play in the pathogenesis of CAH and LC. The changes in the properties of immune complexes induced by the derangement of cellular membranes also influence the course of immune responses, favouring an increase of antibody formation. As a result of an appreciable suppression of antibody and medium-sized CIC formation enhancing the cytolytic syndrome, the preference during glucocorticoid treatment should be given to the use of the medium doses of prednisolone which ensure less intensity and less duration of cytolysis as compared to the application of large drug doses. PMID:1509358
Metz, M; Ständer, S
Chronic pruritus is a major symptom in numerous dermatological and systemic diseases. Similar to chronic pain, chronic pruritus can have a dramatic impact on the quality of life and can worsen the general condition of the patient considerably. The pathogenesis of itch is diverse and involves a complex network of cutaneous and neuronal cells. In recent years, more and more itch-specific mediators and receptors, such as interleukin-31, gastrin-releasing peptide receptor or histamine H4 receptor have been identified and the concept of itch-specific neurons has been further characterized. Understanding of the basic principles is important for development of target-specific treatment of patients with chronic pruritus. In this review, we summarize the current knowledge about the pathophysiological principles of itch and provide an overview about current and future treatment options. PMID:20846147
Unal, Vuslat Sema; Dayican, Avni; Demirel, Murat; Portakal, Suleyman; Ozkan, Guray; Ucaner, Ahmet
Objectives: We evaluated clinical and follow-up findings and treatment methods of pediatric patients with chronic osteomyelitis. Methods: The study included 22 children (14 boys, 8 girls; mean age 8±7 years) who were treated for chronic osteomyelitis. Infection sites were the femur, tibia, ulna, and radius in 11, 8, 1, and 2 patients, respectively. Sixteen patients had a history of trauma. Fourteen patients had fractures, nine of which were associated with segmentary bone defects. All the ...
Tsao, Jennie C. I.; Marcia Meldrum; Kim, Su C.; Jacob, Margaret C.; Zeltzer, Lonnie K
CAM therapies have become increasingly popular in pediatric populations. Yet, little is known about children's preferences for CAM. This study examined treatment preferences in chronic pediatric pain patients offered a choice of CAM therapies for their pain. Participants were 129 children (94 girls) (mean age = 14.5 years ± 2.4; range = 8–18 years) presenting at a multidisciplinary, tertiary clinic specializing in pediatric chronic pain. Bivariate and multivariate analyses were used to examin...
Alex Rodrigo Espinoza Giacomozzi; Alexander Parajeles Vindas; Ariovaldo Alberto da Silva Junior; Carlos Alberto Bordini; Carlos Federico Buonanotte; Celia Aparecida de Paula Roesler; Claudio Manoel Brito; Cristina Perez; Deusvenir de Souza Carvalho; Djacir Dantas Pereira de Macedo; Elcio Juliato Piovesan; Elder Machado Sarmento; Eliana Meire Melhado; Fabiola Dach Eckeli; Fernando Kowacs
Chronic migraine is a condition with significant prevalence all around the world and high socioeconomic impact, and its handling has been challenging neurologists. Developments for understanding its mechanisms and associated conditions, as well as that of new therapies, have been quick and important, a fact which has motivated the Latin American and Brazilian Headache Societies to prepare the present consensus. The treatment of chronic migraine should always be preceded by a careful diagnosis...
The decision to have children is often coupled with varying degrees of apprehension. Women with chronic disease often worry about how the disease itself or its treatment will affect pregnancy and the fetus. The aim of this thesis was to add to the current knowledge concerning pregnancy and birth outcomes in chronic inflammatory disease. First, we studied pregnancy and delivery complications in women with Crohn’s disease and ulcerative colitis, the main types of inflammatory bowel diseas...
Three hundred and fifty million people worldwide are estimated to be chronically infected with hepatitis B virus. 15%-40% of these subjects will develop cirrhosis,liver failure or hepatocellular carcinoma during their life. The treatment of chronic hepatitis B has improved dramatically over the last decade merits to the advent of nucleoside/nucleotide analogues and the use of pegylated interferons. Approved drugs for chronic hepatitis B treatment include: standard interferonalpha 2b, pegylated interferon-alpha 2a, lamivudine,adefovir dipivoxil, and entecavir. Unfortunately, these agents are not effective in all patients and are associated with distinct side effects. Interferons have numerous side effects and nucleoside or nucleotide analogues,which are well tolerated, need to be used for prolonged periods, even indefinitely. However, prolonged treatment with nucleoside or nucleotide analogues is associated with a high rate of resistance. Telbivudine is a novel,orally administered nucleoside analogue for use in the treatment of chronic hepatitis B. In contrast to other nucleoside analogues, Telbivudine has not been associated with inhibition of mammalian DNA polymerase with mitochondrial toxicity. Telbivudine has demonstrated potent activity against hepatitis B with a significantly higher rate of response and superior viral suppression compared with lamivudine, the standard treatment.Telbivudine has been generally well tolerated, with a low adverse effect profile, and at its effective dose, no doselimiting toxicity has been observed. Telbivudine is one of the most potent antiviral agents for chronic hepatitis B virus and was approved by the FDA in late 2006.
Daan R van der Veen
Full Text Available Circadian rhythms in cardiac function are apparent in e.g., blood pressure, heart rate, and acute adverse cardiac events. A circadian clock in heart tissue has been identified, but entrainment pathways of this clock are still unclear. We cultured tissues of mice carrying bioluminescence reporters of the core clock genes, period 1 or 2 (per1(luc or PER2(LUC and compared in vitro responses of atrium to treatment with medium and a synthetic glucocorticoid (dexamethasone [DEX] to that of the suprachiasmatic nucleus (SCN and liver. We observed that PER2(LUC, but not per1(luc is rhythmic in atrial tissue, while both per1(luc and PER2(LUC exhibit rhythmicity in other cultured tissues. In contrast to the SCN and liver, both per1(luc and PER2(LUC bioluminescence amplitudes were increased in response to DEX treatment, and the PER2(LUC amplitude response was dependent on the time of treatment. Large phase-shift responses to both medium and DEX treatments were observed in the atrium, and phase responses to medium treatment were not attributed to serum content but the treatment procedure itself. The phase-response curves of atrium to both DEX and medium treatments were found to be different to the liver. Moreover, the time of day of the culturing procedure itself influenced the phase of the circadian clock in each of the cultured tissues, but the magnitude of this response was uniquely large in atrial tissue. The current data describe novel entrainment signals for the atrial circadian clock and specifically highlight entrainment by mechanical treatment, an intriguing observation considering the mechanical nature of cardiac tissue.
Xi, Yang; Li, Lei; Duffield, Giles E.
Circadian rhythms in cardiac function are apparent in e.g., blood pressure, heart rate, and acute adverse cardiac events. A circadian clock in heart tissue has been identified, but entrainment pathways of this clock are still unclear. We cultured tissues of mice carrying bioluminescence reporters of the core clock genes, period 1 or 2 (per1luc or PER2LUC) and compared in vitro responses of atrium to treatment with medium and a synthetic glucocorticoid (dexamethasone [DEX]) to that of the suprachiasmatic nucleus (SCN) and liver. We observed that PER2LUC, but not per1luc is rhythmic in atrial tissue, while both per1luc and PER2LUC exhibit rhythmicity in other cultured tissues. In contrast to the SCN and liver, both per1luc and PER2LUC bioluminescence amplitudes were increased in response to DEX treatment, and the PER2LUC amplitude response was dependent on the time of treatment. Large phase-shift responses to both medium and DEX treatments were observed in the atrium, and phase responses to medium treatment were not attributed to serum content but the treatment procedure itself. The phase-response curves of atrium to both DEX and medium treatments were found to be different to the liver. Moreover, the time of day of the culturing procedure itself influenced the phase of the circadian clock in each of the cultured tissues, but the magnitude of this response was uniquely large in atrial tissue. The current data describe novel entrainment signals for the atrial circadian clock and specifically highlight entrainment by mechanical treatment, an intriguing observation considering the mechanical nature of cardiac tissue. PMID:23110090
Chronic hepatitis is a common disorder in dogs seen by general practitioners. Several new drugs have been marketed for treating this disease. Unfortunately, there are few controlled studies that examine the efficacy of these medications for the treatment of canine chronic hepatitis. A rational therapeutic approach can be implemented based on histopathologic findings of a liver biopsy. A liver biopsy is essential for establishing a definitive diagnosis and guiding the optimal therapy. The biopsy allows characterizing the inflammatory process, quantitating hepatic copper concentrations, and determining if fibrosis is present. Copper associated hepatopathy is treated with zinc and copper chelators. Idiopathic chronic hepatitis is thought to be immune mediated. The treatment of idiopathic chronic hepatitis consists of controlling inflammation (prednisone, azathioprine), reversing fibrosis (colchicine), and protecting against oxidant damage (vitamin E, ursodeoxycholic acid, S-adenosylmethionine). The prognosis for chronic hepatitis is quite variable. Dogs with end-stage disease have a poor prognosis, while dogs diagnosed earlier can have a mean survival of years. Early diagnosis and intervention are key to the successful treatment of dogs with chronic hepatitis. PMID:14738204
Keith Bruce D
Full Text Available Abstract Background Glucocorticoids are often used in the treatment of nonhematologic malignancy. This review summarizes the clinical evidence of the effect of glucocorticoid therapy on nonhematologic malignancy. Methods A systematic review of clinical studies of glucocorticoid therapy in patients with nonhematologic malignancy was undertaken. Only studies having endpoints of tumor response or tumor control or survival were included. PubMed, EMBASE, the Cochrane Register/Databases, conference proceedings (ASCO, AACR, ASTRO/ASTR, ESMO, ECCO and other resources were used. Data was extracted using a standard form. There was quality assessment of each study. There was a narrative synthesis of information, with presentation of results in tables. Where appropriate, meta-analyses were performed using data from published reports and a fixed effect model. Results Fifty four randomized controlled trials (RCTs, one meta-analysis, four phase l/ll trials and four case series met the eligibility criteria. Clinical trials of glucocorticoid monotherapy in breast and prostate cancer showed modest response rates. In advanced breast cancer meta-analyses, the addition of glucocorticoids to either chemotherapy or other endocrine therapy resulted in increased response rate, but not increased survival. In GI cancer, there was one RCT each of glucocorticoids vs. supportive care and chemotherapy +/- glucocorticoids; glucocorticoid effect was neutral. The only RCT found of chemotherapy +/- glucocorticoids, in which the glucocorticoid arm did worse, was in lung cancer. In glucocorticoid monotherapy, meta-analysis found that continuous high dose glucocorticoids had a detrimental effect on survival. The only other evidence, for a detrimental effect of glucocorticoid monotherapy, was in one of the two trials in lung cancer. Conclusion Glucocorticoid monotherapy has some benefit in breast and prostate cancer. In advanced breast cancer, the addition of glucocorticoids to other
Mahattanakul, W; Crawford, T O; Griffin, J. W.; Goldstein, J. M.; Cornblath, D. R.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune mediated polyneuropathy for which there are effective therapies. However, not all patients improve with these treatments. Eight patients with CIDP, two with IgG monoclonal gammopathies, were treated with cyclosporin-A (3 to 5 mg/kg/day). In three, this treatment was successful. It was unsuccessful in four patients who were resistant to other treatments and in one who had initially received cyclosporin-A. There were no serio...
Haller, Heidemarie; Lauche, Romy; Cramer, Holger; Rampp, Thomas; Saha, Felix J.; Ostermann, Thomas; Dobos, Gustav
Objectives: With growing evidence for the effectiveness of craniosacral therapy (CST) for pain management, the efficacy of CST remains unclear. This study therefore aimed at investigating CST in comparison with sham treatment in chronic nonspecific neck pain patients. Materials and Methods: A total of 54 blinded patients were randomized into either 8 weekly units of CST or light-touch sham treatment. Outcomes were assessed before and after treatment (week 8) and again 3 months later (week 20)...
Full Text Available Kuen Yeow Chin, Suresh M Anandan,* Karan Koshal,* Prashant Gujadhur* Department of Plastic Surgery, Wexham Park Hospital, Slough, United Kingdom *These authors contributed equally to this work Abstract: Chronic wounds are common and their incidence has been on the increase. They place an enormous burden on health care services and have a major impact on several aspects of patients' wellbeing. It is vital for clinicians to recognize the complexity of the underlying processes leading to the development of a chronic wound. With this knowledge, the key factors that led to their development in each patient can be identified and appropriate steps taken to address modifiable factors. There is currently a wide range of treatments available for treatment of chronic wounds, with a range of exciting new treatments being developed. This paper aims to give an overview of the common etiology and pathophysiology of chronic wounds followed by a discussion of a range of current and future developments in their treatment. Keywords: chronic wound, wound healing, cutaneous
Giuseppe Chiarioni; Corrado Asteria; William E Whitehead
This systematic review addresses the pathophysiology, diagnostic evaluation, and treatment of several chronic pain syndromes affecting the pelvic organs: chronic proctalgia, coccygodynia, pudendal neuralgia, and chronic pelvic pain. Chronic or recurrent pain in the anal canal, rectum, or other pelvic organs occurs in 7% to 24% of the population and is associated with impaired quality of life and high health care costs. However, these pain syndromes are poorly understood, with little research evidence available to guide their diagnosis and treatment. This situation appears to be changing: A recently published large randomized, controlled trial by our group comparing biofeedback, electrogalvanic stimulation, and massage for the treatment of chronic proctalgia has shown success rates of 85% for biofeedback when patients are selected based on physical examination evidence of tenderness in response to traction on the levator ani muscle-a physical sign suggestive of striated muscle tension. Excessive tension (spasm) in the striated muscles of the pelvic floor appears to be common to most of the pelvic pain syndromes. This suggests the possibility that similar approaches to diagnostic assessment and treatment may improve outcomes in other pelvic pain disorders.
Januário, Virginia; de Ávila, Dione Augusto; Penetra, Maria Alice; Sampaio, Ana Luisa Bittencourt; Noronha Neta, Maria Isabel; Cassia, Flavia de Freire; Carneiro, Sueli
BACKGROUND: Among the chronic leg ulcers, venous ulcers are the most common and constitute a major burden to public health. Despite all technology available, some patients do not respond to established treatments. In our study, carboxymethylcellulose was tested in the treatment of refractory chronic venous ulcers. OBJECTIVE: To evaluate the efficacy of carboxymethylcellulose 20% on the healing of chronic venous ulcers refractory to conventional treatments. METHODS: This is an analytical, pre-experimental study. Thirty patients were included with refractory venous ulcers, and applied dressings with carboxymethylcellulose 20% for 20 weeks. The analysis was based on measurement of the area of ulcers, performed at the first visit and after the end of the treatment. RESULTS: There was a reduction of 3.9 cm2 of lesion area (p=0.0001), corresponding to 38.8% (p=0.0001). There was no interruption of treatment and no increase in lesion area in any patient. CONCLUSIONS: Carboxymethylcellulose 20% represents a low cost and effective therapeutic alternative for the treatment of refractory chronic venous ulcers. However, controlled studies are necessary to prove its efficacy. PMID:26982773
Choi, Jae-Sung; Jang, An-Soo; Lee, June-Hyuk; Park, Jong-Sook; Park, Sung Woo; Kim, Do-Jin; Park, Choon-Sik
Asthma is a chronic disorder that can place considerable restrictions on the physical, emotional, and social aspects of the lives of patients. Inhaled glucocorticoids (GCs) are the most effective controller therapy. The purpose of this study was to evaluate the effect of inhaled GCs on quality of life in patients with moderate to severe asthma. Patients completed the asthma quality of life questionnaire (AQLQ) and pulmonary function test at baseline and after 4 wks treatment of GCs. We enroll...
Rheumatoid arthritis (RA) is a common chronic inflammatory disease that affects about 1% of the Western population. Glucocorticoids (GC) are widely used for the treatment of RA and other immune-mediated diseases, such as asthma, but their use is associated with adverse effects on bone metabolism. Because of that, new selective GC receptor (GR) agonists (SEGRAs) with the potential for an improved risk/benefit profile have been developed. Compound A (CpdA) is a novel SEGRA, which showed an impr...
Full Text Available Chronic pleural empyema with aspergillus is a rare complication that usually presents after lung resection operations. Etiologic factors of pleural aspergillus includes healed or presence pulmonary tuberculosis, bronchopleural fistula, pleural catheterisation or drainage, lung resection, complex antibiotic uses. Medical and surgical treatments of chronic pleural empyema with aspergillus were examined in this study. Antifungal agents is used as medical treatment. Surgical therapy has a widely spectrum which includes tube tho-racostomy, open drainage, (Eleosser flap, Clagett Procedures, thoracostoma, decortication, omentum and/or extrathoracic or abdominal muscles transpo-sition to intrathoracic space.
Purpose To review the efficacy and safety of pegylated interferons (peginterferons) in the treatment of chronic hepatitis C.Data sources An English language literature search (MEDLINE 1988-2001) was performed and a total of 19 original articles related to the issue were selected.Data extraction After careful review of the selected papers, the meaningful results and conclusions were extracted using scientific criteria. The papers reviewed pertained mainly to the efficacy and safety profiles of peginterferons in the treatment of chronic hepatitis C.
... and relieve stress. Psychological methods These include counseling, hypnosis, and cognitive-behavioral therapy—a treatment that involves a wide variety of coping skills and relaxation methods to help prepare for and cope with pain. Surgery Although not always an option, surgery may ...
Patel, P; Mandal, B.; Greenway, M
A 76 year old woman presented with a quadriparesis associated with hyperkalaemia. She had a 10 month history of treatment with oral diclofenac sodium. On admission she had hyperkalaemic metabolic acidosis with a normal anion gap and mild renal impairment. Her weakness resolved after withdrawal of diclofenac and medical correction of her hyperkalaemia. Non-steroidal anti-inflammatory drugs are known to cause hyperkalaemic acidosis and should be used with caution, especially in the presence of ...
Alex Rodrigo Espinoza Giacomozzi
Full Text Available Chronic migraine is a condition with significant prevalence all around the world and high socioeconomic impact, and its handling has been challenging neurologists. Developments for understanding its mechanisms and associated conditions, as well as that of new therapies, have been quick and important, a fact which has motivated the Latin American and Brazilian Headache Societies to prepare the present consensus. The treatment of chronic migraine should always be preceded by a careful diagnosis review; the detection of possible worsening factors and associated conditions; the stratification of seriousness/impossibility to treat; and monitoring establishment, with a pain diary. The present consensus deals with pharmacological and nonpharmacological forms of treatment to be used in chronic migraine.
Matsuda, Kazuki M; Sharma, Divya; Schonfeld, Ariel R; Kwatra, Shawn G
Chronic pruritus is a distressing symptom that is often refractory to treatment. Patients frequently fail topical therapies and oral over-the-counter antihistamines, prompting the clinician to consider alternative therapies such as neuroactive agents. Herein, the use of gabapentin and pregabalin, 2 medications well known for treating neuropathic pain and epilepsy that are occasionally used for relieving chronic pruritus is explored. The findings from original sources published to date to evaluate the use of gabapentin and pregabalin as antipruritic agents are explored. They are found to be promising alternative treatments for the relief of several forms of chronic pruritus, particularly uremic pruritus and neuropathic or neurogenic itch, in patients who fail conservative therapies. PMID:27206757
Diaz Heijtz, R; Fuchs, E.; Feldon, J.; Pryce, C. R.; Forssberg, H.
BACKGROUND: Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to promote fetal lung maturation in at-risk preterm births, but there is emerging evidence of subsequent neurobehavioral abnormalities in these children e.g. problems with inattention/hyperactivity. However, molecular pathways mediating effects of glucocorticoid overexposure on motor and cognitive development are poorly understood. METHODS: In this study with common marmoset monkeys, we investigated for neonat...
Feldon Joram; Fuchs Eberhard; Diaz Heijtz Rochellys; Pryce Christopher R; Forssberg Hans
Abstract Background Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to promote fetal lung maturation in at-risk preterm births, but there is emerging evidence of subsequent neurobehavioral abnormalities in these children e.g. problems with inattention/hyperactivity. However, molecular pathways mediating effects of glucocorticoid overexposure on motor and cognitive development are poorly understood. Methods In this study with common marmoset monkeys, we investigated for...
QIN Huimin; LI Hongtao; XING Mingyou; WU Chunming; LI Guojun; SONG Jianxin
The therapeutic effectiveness of nutritional support in the treatment of severe chronic hepatitis and posthepatitic cirrhosis was evaluated. 143 patients with severe chronic hepatitis and 83 with posthepatitic cirrhosis were evaluated with SGA for assessing the nutritional status before the treatment. Patients with severe chronic hepatitis were divided into three groups: group A subject to enteral nutrition (EN) and parenteral nutrition (PN), group B subject to comprehensive treatment (CT) +PN; group C subject to CT+ EN. The patients with posthepatitic cirrhosis were divided into two groups: group D receiving CT and group E receiving CT+PN+EN. The function of liver and kidney and nutritional status were monitored to assess the therapy in 6 weeks. The results showed before treatment, over 90 % patients had moderate to severe malnutrition. After nutritional support, the liver function (ALT, T-biil) and nutritional status (TP, TC) in group A was improved significantly as compared with that in groups B and C (P＜0.05). Compared with group D,the values of TP and Alb were increased significantly in group E (P＜0.05), but the levels of ALT, AST and T-bil had no obvious change. It was suggested that most patients with severe chronic hepatitis or posthepatitic cirrhosis had malnutrition to varying degrees. The nutritional support treatment could obviously improve the nutritional status of these patients, and was helpful to ameliorate the liver function of the patients with severe chronic hepatitis. Among the methods of nutritional support treatment, PN combined with EN had the best effectiveness.
Guerino, M. R.; Baranauskas, V.; Guerino, A. C.; Parizotto, N.
In this work, we investigated the effects of He-Ne laser irradiation on the inflammatory process induced in the articular cartilage of the right knee of guinea pigs. Through electron microscopy analysis it was possible to identify the induced arthritis in the articular cartilage and its modification after the laser treatment. The laser radiation promoted a reduction in the proliferation of the inflammatory cells in the damaged tissue and also induced the formation of cartilage bridges that tied the destroyed parts favoring the formation of a repaired tissue in the injured cartilage.
P.A. van Doorn (Pieter)
textabstractPatients with a chronic inflammatory demyelinating polyneuropathy (CIDP) may respond to treatment with corticosteroids and to plasmapheresis, which was demonstrated in controlled clinical studies. In an uncontrolled study it was found that 13/17 CIDP patients had a rapid and clinical imp
Chantal Frigon; Joëlle Desparmet
The case of a seven-year-old boy with chronic pruritus secondary to a giant congenital melanocytic nevus is presented. The pruritus did not respond to conventional antipruritic drug treatment, but responded to ondansetron, a selective antagonist of 5-hydroxytryptamine type 3 receptors.
Full Text Available The case of a seven-year-old boy with chronic pruritus secondary to a giant congenital melanocytic nevus is presented. The pruritus did not respond to conventional antipruritic drug treatment, but responded to ondansetron, a selective antagonist of 5-hydroxytryptamine type 3 receptors.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition in which organised thrombi obstruct the pulmonary vessels, causing increased pulmonary vascular resistance, progressive pulmonary hypertension (PH) and right heart failure. The treatment of choice is pulmonary endarterectomy, which restores pulmonary haemodynamics with acceptable periprocedural mortality rates in the majority of suitable patients. However, CTEPH may be inoperable owing to surgically inaccess...
Andrews, R.; Lynch, M
Objective: To determine if breathing helium oxygen mixtures in addition to conventional therapy in non-intubated adult chronic obstructive airways disease (COPD) patients reduces the arterial partial pressure of carbon dioxide (PaCO2) more than conventional treatment alone, and confers an advantage in terms of the odds of intubation in the acute setting.
J Gordon Millichap
Full Text Available The safety and efficacy of immediate-release methylphenidate (MPH-IR for the treatment of attention deficit hyperactivity disorder (ADHD in children (ages 6-12 years with Tourette's syndrome (96% or chronic motor tic disorder (4% were evaluated at State University of New York, Stony Brook.
Carter Bryan D; Threlkeld Brooke M
Abstract Chronic pain in children and adolescents is associated with major disruption to developmental experiences crucial to personal adjustment, quality of life, academic, vocational and social success. Caring for these patients involves understanding cognitive, affective, social and family dynamic factors associated with persistent pain syndromes. Evaluation and treatment necessitate a comprehensive multimodal approach including psychological and behavioral interventions that maximize retu...
Advantages of metoprolol succinate in patients with chronic heart failure (CHF) are covered. Results of MERIT-HF study are taken as the main evidences. Patterns of the metoprolol succinate use in the treatment of different categories of patients with CHF (women, the elderly , severe CHF forms, CHF with concomitant hypertension or diabetes) are considered.
O. D. Ostroumova
Full Text Available Advantages of metoprolol succinate in patients with chronic heart failure (CHF are covered. Results of MERIT-HF study are taken as the main evidences. Patterns of the metoprolol succinate use in the treatment of different categories of patients with CHF (women, the elderly , severe CHF forms, CHF with concomitant hypertension or diabetes are considered.
Daniels, J. M. A.; Vonk-Noordegraaf, A.; Janssen, J. J. W. M.; Postmus, P. E.; van Altena, R.
Although imatinib is not considered a predisposing factor for tuberculosis (TB), the present case report describes three patients in whom imatinib treatment for chronic myeloid leukaemia was complicated by TB. This raises the question of whether imatinib increases susceptibility to TB. There are sev
Simonsson, Bengt; Hjorth-Hansen, Henrik; Bjerrum, Ole Weis;
Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-α) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-α compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions...
Simonsson, Bengt; Hjorth-Hansen, Henrik; Bjerrum, Ole Weis;
Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-a) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-a compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions...
Full Text Available Chronic pain related to PCOA is a clinical condition which affects more than 5 percent of the population. This article presents two clinical cases of severe pain related to the disease treated with opioids and epidural SCS with inadequate results. Treatment by intrathecal ziconotide showed, in both cases, a good reduction of pain. These clinical cases represent the first experience of ischemic pain treatment with ziconotide.
Sabrina Giusto; Domenico Quattrone; Placido Calì
Chronic pain related to PCOA is a clinical condition which affects more than 5 percent of the population. This article presents two clinical cases of severe pain related to the disease treated with opioids and epidural SCS with inadequate results. Treatment by intrathecal ziconotide showed, in both cases, a good reduction of pain. These clinical cases represent the first experience of ischemic pain treatment with ziconotide.
Yoon, Min-Suk; Chan, Andrew; Gold, Ralf
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired, immune-mediated polyradiculoneuritis that is progressive or relapsing over a period of at least 8 weeks. Although the exact pathogenesis is unclear, it is thought to be mediated by both cellular and humoral immune reactions directed against the peripheral nerve myelin or axon. CIDP also involves spinal nerve roots. Early medical treatment of CIDP is important to prevent axonal loss. Only three treatment regimens for CIDP...
van Doorn, P. A.
Intravenous immunoglobulin (IVIg) treatment is shown to be effective in a selected group of patients with a chronic inflammatory demyelinating polyneuropathy (CIDP). The proportion of patients that improve after IVIg treatment varies between studies. Because 40% of a group of IVIg treated CIDP patients needed intermittent IVIg infusions to maintain their improved clinical condition, it is expected that IVIg is effective, at least in this subgroup of patients. However, the proportion of patien...
textabstractPatients with a chronic inflammatory demyelinating polyneuropathy (CIDP) may respond to treatment with corticosteroids and to plasmapheresis, which was demonstrated in controlled clinical studies. In an uncontrolled study it was found that 13/17 CIDP patients had a rapid and clinical important improvement after infusion of Fresh Frozen Plasma (FFP). A beneficial response was also seen after-mtravenous rmmunoglobulin (Mg) treatment. The aims of this study were: - to evaluate the cl...
Olsen, P C; Kitoko, J Z; Ferreira, T P; de-Azevedo, C T; Arantes, A C; Martins, Μ A
Glucocorticoids have been the hallmark anti-inflammatory drug used to treat asthma. It has been shown that glucocorticoids ameliorate asthma by increasing numbers and activity of Tregs, in contrast recent data show that glucocorticoid might have an opposite effect on Treg cells from normal mice. Since Tregs are target cells that act on the resolution of asthma, the aim of this study was to elucidate the effect of glucocorticoid treatment on lung Tregs in mouse models of asthma. Allergen challenged mice were treated with either oral dexamethasone or nebulized budesonide. Broncoalveolar lavage and airway hyperresponsiveness were evaluated after allergenic challenge. Lung, thymic and lymph node cells were phenotyped on Treg through flow cytometry. Lung cytokine secretion was detected by ELISA. Although dexamethasone inhibited airway inflammation and hyperresponsiveness, improving resolution, we have found that both dexamethasone and budesonide induce a reduction of Treg numbers on lungs and lymphoid organs of allergen challenged mice. The reduction of lung Treg levels was independent of mice strain or type of allergen challenge. Our study also indicates that both glucocorticoids do not increase Treg activity through production of IL-10. Glucocorticoid systemic or localized treatment induced thymic atrophy. Taken together, our results demonstrate that glucocorticoids decrease Treg numbers and activity in different asthma mouse models, probably by reducing thymic production of T cells. Therefore, it is possible that glucocorticoids do not have beneficial effects on lung populations of Treg cells from asthmatic patients. PMID:25499819
Leda M.F. Lucinda
Full Text Available Evaluate the effect of the extract of Ginkgo biloba L., Ginkgoaceae (EGb in the Bcl-2 expression by osteoblasts in the femoral trabecular bone of Wistar rats with glucocorticoid-induced osteoporosis. Rats were divided into five groups: osteoporosis; EGb1 (28 mg/kg; EGb2 (56 mg/kg; alendronate (0.2 mg/animal and control. The treatments were conducted for 20 or 30 days. The Bcl-2 expression by osteoblasts cells was evaluated in the femoral trabecular bone. The control group was compared with the osteoporosis-induced group (Student's t-test. The other groups were analyzed by ANOVA test followed by Tukey's test (p < 0.05. The percentage of Bcl-2 expression was reduced, when the control group (17.95 ± 3.45 20 days; 21.11 ± 3.43 30 days was compared with the osteoporosis group (10.64 ± 3.30 20 days; 9.72 ± 2.84 30 days. Nevertheless, this percentage increased in the EGb2 group (18.58 ± 3.41 20 days; 16.51 ± 1.80 30 days when compared to the osteoporosis group. The EGb increased the expression of the anti-apoptotic protein, suggesting a decrease in osteoblast apoptosis.
D Festi; L Sandri; G Mazzella; E Roda; T Sacco; T Staniscia; S Capodicasa; A Vestito; A Colecchia
Hepatitis C is a major cause of liver-related morbidity and mortality worldwide, In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicate infection and prevent progression of the disease. The treatment has evolved from the use of α-interferon (TFNα)alone to the combination of IFNα plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin.Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjects are not suitable owing to intolerance toward drugs. IFNβ represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety of IFNβ treatment in HCV-related chronic hepatitis.The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNβ are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNβ treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported.A more recent study, performed to compare IFNβ alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event
Huynh, Tony; Uaesoontrachoon, Kitipong; Quinn, James L; Tatem, Kathleen S; Heier, Christopher R; Jack H. Van der Meulen; Yu, Qing; Harris, Mark; Nolan, Christopher J.; Haegeman, Guy; Grounds, Miranda D.; Nagaraju, Kanneboyina
The over-expression of NF-κB signalling in both muscle and immune cells contribute to the pathology in dystrophic muscle. The anti-inflammatory properties of glucocorticoids, mediated predominantly through monomeric glucocorticoid receptor inhibition of transcription factors such as NF-κB (transrepression), are postulated to be an important mechanism for their beneficial effects in Duchenne muscular dystrophy. Chronic glucocorticoid therapy is associated with adverse effects on metabolism, gr...
Wu, I; Shin, S C; Cao, Y; Bender, I K; Jafari, N; Feng, G; Lin, S; Cidlowski, J A; Schleimer, R P; Lu, N Z
Induction of T-cell apoptosis contributes to the anti-inflammatory and antineoplastic benefits of glucocorticoids. The glucocorticoid receptor (GR) translational isoforms have distinct proapoptotic activities in osteosarcoma cells. Here we determined whether GR isoforms selectively induce apoptosis in Jurkat T lymphoblastic leukemia cells. Jurkat cells stably expressing individual GR isoforms were generated and treated with vehicle or dexamethasone (DEX). DEX induced apoptosis in cells expressing the GR-A, -B, or -C, but not the GR-D, isoform. cDNA microarray analyses of cells sensitive (GR-C3) and insensitive (GR-D3) to DEX revealed glucocorticoid-induced proapoptotic transcriptomes. Genes that were regulated by the proapoptotic GR-C3, but not by the GR-D3, isoform likely contributed to glucocorticoid-induced apoptosis. The identified genes include those that are directly involved in apoptosis and those that facilitate cell killing. Chromatin immunoprecipitation assays demonstrated that distinct chromatin modification abilities may underlie the distinct functions of GR isoforms. Interestingly, all GR isoforms, including the GR-D3 isoform, suppressed mitogen-stimulated cytokines. Furthermore, the GR-C isoforms were selectively upregulated in mitogen-activated primary T cells and DEX treatment induced GR-C target genes in activated T cells. Cell-specific expressions and functions of GR isoforms may help to explain the tissue- and individual-selective actions of glucocorticoids and may provide a basis for developing improved glucocorticoids. PMID:23303127
K. Dejakum; Piegger, J.; C. Plewka; A. Gunkel; Thumfart, W.; S. Kudaibergenova; Goebel, G.; Kral, F.; Freysinger, W
The purpose of this study was to evaluate the effect of medium-level laser therapy in chronic tinnitus treatment. In a prospective double-blind placebo-controlled trial, either active laser (450 mW, 830 nm combined Ga-Al-As diode laser) or placebo irradiation was applied through the external acoustic meatus of the affected ear towards the cochlea. Fourty-eight patients with chronic tinnitus were studied. The main outcome was measured using the Goebel tinnitus questionnaire, visual analogue sc...
Pereira, Eduardo Guimarães; Guimarães, Tais Ferreira; Bottino, Caroline Bertolini; D'Acri, Antonio Macedo; Lima, Ricardo Barbosa; Martins, Carlos José
Sarcoidosis is a disease which still has uncertain etiology. Possible environmental causes are cited in the literature, like organic and inorganic particles and infectious agents. Recent studies have demonstrated the occurrence of sarcoidosis in patients with chronic C hepatitis; however, this association remains without statistical or causal evidence. In this report a case of sarcoidosis associated with chronic hepatitis C will be described, with subcutaneous lesions, considered rare, and good response to treatment with colchicine and prednisone. The hepatitis C virus was isolated in sarcoid tissue and the association between the two diseases will be discussed. PMID:27192527
Riario-Sforza, Gian Galeazzo; Ridolo, Erminia; Riario-Sforza, Edoardo; Incorvaia, Cristoforo
Glycopyrronium bromide is a new long-acting muscarinic antagonist to be used once-daily, which is approved as a bronchodilator for the symptomatic maintenance treatment of adult patients with chronic obstructive pulmonary disease (COPD). In the Glycopyrronium bromide in chronic Obstructive pulmonary disease airWays trials, treatment with inhaled glycopyrronium bromide at 50 μg once daily achieved a significantly better lung function than placebo, as measured by the trough forced expiratory volume in 1 s in patients with moderate-to-severe COPD. The lung function improvement was maintained for up to 52 weeks. Other improved indexes were dyspnea scores, health status, exacerbation rates and time of exercise endurance. Studies comparing the efficacy of glycopyrronium versus tiotropium bromide found substantial equivalence of the two drugs. Glycopyrronium was generally well tolerated. These data add inhaled glycopyrronium bromide to the treatment of patients with moderate to severe COPD as an effective once-daily LAMA. PMID:25547422
Strehl, Cindy; Bijlsma, Johannes W J; de Wit, Maarten; Boers, Maarten; Caeyers, Nele; Cutolo, Maurizio; Dasgupta, Bhaskar; Dixon, William G; Geenen, Rinie; Huizinga, Tom W J; Kent, Alison; de Thurah, Annette Ladefoged; Listing, Joachim; Mariette, Xavier; Ray, David W; Scherer, Hans U; Seror, Raphaèle; Spies, Cornelia M; Tarp, Simon; Wiek, Dieter; Winthrop, Kevin L; Buttgereit, Frank
There is convincing evidence for the known and unambiguously accepted beneficial effects of glucocorticoids at low dosages. However, the implementation of existing recommendations and guidelines on the management of glucocorticoid therapy in rheumatic diseases is lagging behind. As a first step to improve implementation, we aimed at defining conditions under which long-term glucocorticoid therapy may have an acceptably low level of harm. A multidisciplinary European League Against Rheumatism task force group of experts including patients with rheumatic diseases was assembled. After a systematic literature search, breakout groups critically reviewed the evidence on the four most worrisome adverse effects of glucocorticoid therapy (osteoporosis, hyperglycaemia/diabetes mellitus, cardiovascular diseases and infections) and presented their results to the other group members following a structured questionnaire for final discussion and consensus finding. Robust evidence on the risk of harm of long-term glucocorticoid therapy was often lacking since relevant study results were often either missing, contradictory or carried a high risk of bias. The group agreed that the risk of harm is low for the majority of patients at long-term dosages of ≤5 mg prednisone equivalent per day, whereas at dosages of >10 mg/day the risk of harm is elevated. At dosages between >5 and ≤10 mg/day, patient-specific characteristics (protective and risk factors) determine the risk of harm. The level of harm of glucocorticoids depends on both dose and patient-specific parameters. General and glucocorticoid-associated risk factors and protective factors such as a healthy lifestyle should be taken into account when evaluating the actual and future risk. PMID:26933146
Kowal, John; Wilson, Keith G.; Henderson, Peter R.; McWilliams, Lachlan A.
Objectives To examine suicidal ideation in individuals with chronic pain, especially change in suicidal thinking following interdisciplinary treatment. Methods Consecutive patients (n = 250) admitted to a 4-week, group-based chronic pain management program completed measures of pain intensity, functional limitations, depressive symptoms, overall distress, pain catastrophizing, self-perceived burden, and suicidal ideation at pre- and post-treatment. Results Before treatment, 30 (12.0%) participants were classified as having a high level of suicidal ideation, 56 (22.4%) had a low level of suicidal ideation, and 164 (65.6%) reported none. Following treatment, there was a significant reduction in suicidal ideation and improvements in all other outcomes, but there were still some individuals with high (n = 22, 8.8%) or low (n = 28, 11.2%) levels at discharge. Patients with high suicidal ideation at baseline differed from those with no suicidal thinking on pre- and post-treatment measures of depression, distress, catastrophizing, and self-perceived burden, but not on pain intensity or functional limitations. Patients high in suicidal ideation endorsed greater pain catastrophizing and self-perceived burden than those low in suicidal thinking. Sustained suicidal ideation after treatment was associated with higher baseline levels of suicidal thinking and self-perceived burden to others, as well as a more limited overall response to treatment. Discussion Suicidal ideation was common in individuals with chronic pain, although mostly at a low level. Interdisciplinary treatment may result in reduced suicidal thinking; however, some patients continue to express thoughts of self-harm. Future studies could examine processes of change and interventions for treatment-resistant suicidal concerns. PMID:24281291
Fidanaza, A; Floridi, S; Lenti, L
Urinary metabolites of glucocorticoids have been measured in man before and after administration of panthenol in high doses. The quantitative assay was performed according to the technique of Porter and Silber which measures only cortisol and some of its metabolites. In all panthenol treated subjects a significant increase in the urinary excretion of 17-alpha-21-dihydroxy-20-keto steroids has been observed and it appeared to be higher in male ageing between 18 and 25. The results obtained confirm that a statistically significant increase in glucocorticoid production after panthenol administration in high doses is present also in man. PMID:7317179
Full Text Available Yaoyu Chen,1 Shaoguang Li2 1Department of Oncology, Novartis Institutes for Biomedical Research, Cambridge, 2Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA Abstract: In a significant proportion of patients with chronic myeloid leukemia, resistance to BCR-ABL tyrosine kinase inhibitors develops due to acquisition of BCR-ABL kinase domain mutations and insensitivity of leukemia stem cells to tyrosine kinase inhibitors. Omacetaxine mepesuccinate (formerly called homoharringtonine is a natural alkaloid that inhibits protein synthesis and induces cell death. Omacetaxine mepesuccinate has been recently approved by the US Food and Drug Administration to treat patients with chronic myeloid leukemia who failed to respond to multiple tyrosine kinase inhibitors and/or acquired the BCR-ABL-T315I mutation. In this review, we discuss the use and effectiveness of omacetaxine mepesuccinate in the treatment of chronic myeloid leukemia, with coverage of its pharmacology, mode of action, and pharmacokinetics. We believe that omacetaxine mepesuccinate will be beneficial to many patients with chronic myeloid leukemia who do not respond well to tyrosine kinase inhibitors. Keywords: BCR-ABL, leukemic stem cells, chronic myeloid leukemia, biomarker, hematopoietic stem cells, cancer stem cells
Full Text Available ABSTRACT: Nearly 60 to 70 crores of people all over the world are suffering from various types of chronic headache. This is one of the commonest medical problems. To get relief from headache various medical treatments are used with little success. The aim of our study is to give permanent treatment to chronic headache patients by using infrared diode laser selective retinal photocoagulati on. NIDEK infrared diode laser with NIDEK SL40 slit - lamp and NIDEK digital fundus camera for retinal evaluation, MAINSTER 135D lens for laser beam focusing and retinal examination and TOPCON non - contact tonometer for intra ocular pressure measurements are used. Diode laser is chosen because of its deep penetration into all the layers of retina and choroid. 500 cases of chronic headache were studied. Laser photocoagulation was given in selective areas of retina in 2 to 3 sessions with 15 days interval. 10 to 60 years age group were studied. 90% of patients who got laser treatment are relieved from their headache in severity and in frequency. 80% of patients needed 2 sittings and 20% of patients needed 3 sittings. 70% of patients got relief from headache by fi rst sitting itself. 50% of patients are not only relieved from their headaches but also noticed visual clarity improvement. Retinal ischaemia is one of the main cause for ocular pain and headache. Laser treatment will improve circulation by reducing ischae mia thereby relieves ocular pain and headache
Monti, S; Caporali, R
Musculoskeletal conditions are the most frequent cause of chronic pain and affect around 1 in 5 adults in Europe. When chronic pain occurs, it becomes disease itself, with substantial clinical, social and economic impact. Efficacy and tolerability problems are encountered with all therapeutic strategies available to treat musculoskeletal pain. This often limits effective analgesia and patients' long term compliance, with the result that chronic pain is persistently underestimated and undertreated. Tapentadol is a novel, centrally acting analgesic that has been recently commercialized for the treatment of chronic pain. This new molecule, by combining two distinct mechanisms of action, μ-opioid receptor agonism (MOR) and noradrenaline reuptake inhibition (NRI), introduces a new pharmacological class called MOR-NRI. Several studies demonstrated promising results in the management of both nociceptive and neuropathic pain and good tolerability profile, particularly concerning side effects, compared to traditional opioids. This novel analgesic represents a possible therapeutic option also in the rheumatologic field, particularly in the treatment of osteoarthritis and low back pain. PMID:26492961
Full Text Available Musculoskeletal conditions are the most frequent cause of chronic pain and affect around 1 in 5 adults in Europe. When chronic pain occurs, it becomes disease itself, with substantial clinical, social and economic impact. Effi cacy and tolerability problems are encountered with all therapeutic strategies available to treat musculoskeletal pain. This often limits effective analgesia and patients’ long term compliance, with the result that chronic pain is persistently underestimated and undertreated. Tapentadol is a novel, centrally acting analgesic that has been recently commercialized for the treatment of chronic pain. This new molecule, by combining two distinct mechanisms of action, μ-opioid receptor agonism (MOR and noradrenaline reuptake inhibition (NRI, introduces a new pharmacological class called MOR-NRI. Several studies demonstrated promising results in the management of both nociceptive and neuropathic pain and good tolerability profi le, particularly concerning side effects, compared to traditional opioids. This novel analgesic represents a possible therapeutic option also in the rheumatologic fi eld, particularly in the treatment of osteoarthritis and low back pain.
Hidalgo, Alejandro A.; Trump, Donald L.; Johnson, Candace S.
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
Atucha, E.; Zalachoras, I.; Heuvel, J.K. van den; Weert, L.T.C.M. van; Melchers, D.; Mol, I.M.; Belanoff, J.K.; Houtman, R.; Hunt, H.; Roozendaal, B.; Meijer, O.C.
Adrenal glucocorticoid hormones are potent modulators of brain function in the context of acute and chronic stress. Both mineralocorticoid (MRs) and glucocorticoid receptors (GRs) can mediate these effects. We studied the brain effects of a novel ligand, C118335, with high affinity for GRs and modes
Fialho, D; Chan, Y‐C; Allen, D C; Reilly, M.M.; Hughes, R A C
We discovered many reports of other immunosuppressive drugs being used in adults with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but none of methotrexate. As weekly low dose oral methotrexate is safe, effective, and well tolerated in other diseases, we treated 10 patients with otherwise treatment resistant CIDP. Seven showed improvement in strength by at least two points on the MRC sum score and three worsened. Only two showed an improvement in disability and both were a...
Agostino Cortelezzi; Mariarita Sciumè; Gianluigi Reda
The application of nucleoside analogue-based chemotherapy and immunotherapy with rituximab or alemtuzumab has increased both response rate and survival in patients with Chronic Lymphocytic Leukemia (CLL). However, because none of these therapies is curative, sequential therapeutic regimens are required. The majority of patients with relapsed or refractory CLL carry poor prognostic factors and show shorter overall survival and resistance to standard treatment. Numerous drugs have recently be...
Lukinykh L.M.; Kruglova N.V.
To optimize a therapeutic process due to technological development in dentistry there have appeared new progressive technologies that allow improving life quality of patients with periodontal inflammatory diseases. Modern techniques of a complex etiopathogenic treatment of periodontal inflammatory diseases including conservative, orthopedic, orthodontic and surgical measures have been presented. There has been proved the use of preparations of systemic and local effect to treat chronic ge...
Irina Yuryevna Suvorova
Full Text Available Recently there has been a considerable increase in the number of patients with lingering recurrent and chronic pain syndromes of various origin. Forty-one patients with dorsopathies were examined. Two types of pain were identified; these were vertebrogenic and nonvertebrogenic pains. The appropriateness of this identification was confirmed by instrumental studies. Treatment was performed using a selective nonsteroidal antiinflammatory drug (Amelotex. Pain syndrome relief was noted during the therapy
Irina Yuryevna Suvorova
Full Text Available Recently there has been a considerable increase in the number of patients with lingering recurrent and chronic pain syndromes of various origin. Forty-one patients with dorsopathies were examined. Two types of pain were identified; these were vertebrogenic and nonvertebrogenic pains. The appropriateness of this identification was confirmed by instrumental studies. Treatment was performed using a selective nonsteroidal antiinflammatory drug (Amelotex. Pain syndrome relief was noted during the therapy
Bertino, Gaetano; Ardiri, Annalisa; Proiti, Maria; Rigano, Giuseppe; Frazzetto, Evelise; Demma, Shirin; Ruggeri, Maria Irene; Scuderi, Laura; Malaguarnera, Giulia; Bertino, Nicoletta; Rapisarda, Venerando; Di Carlo, Isidoro; Toro, Adriana; Salomone, Federico; Malaguarnera, Mariano; Bertino, Emanuele; Malaguarnera, Michele
Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects. PMID:26807205
Peter Rohon; Jana Vondrakova; Anna Jonasova; Milena Holzerova; Marie Jarosova; Karel Indrak
Epigenetic therapy with hypomethylating agent (5-azacytidine; AZA) is common in the management of specific subtypes of myelodysplastic syndrome (MDS), but there are only few studies in chronic myelomonocytic leukemia (CMML) patients. In this paper our experience with 3 CMML patients treated with AZA is described. In one patient transfusion independency was observed after 4 treatment cycles; in one case a partial response was recorded, but a progression to acute myeloid leukemia (AML) after 13...
V. V. Bryuzgin
Noninvasive treatments for chronic pain syndrome benefit in 80-90% of cancer patients. Invasive, intervention procedures for analgesia should be used in other cases. These include neuroablative and neuromodulatory measures. Neuroablation is defined as the physical suspension of painful impulse transmission pathways by a surgical, chemical, or thermal method and comprises lytic and other blocks. Neuromodulation is the dynamic and functional suppression of pain impulse pathways by the intraspin...
Murphy Daniel R
Full Text Available Abstract Background This paper presents the model and results to evaluate the use of teriparatide as a first-line treatment of severe postmenopausal osteoporosis (PMO and Glucocorticoid-induced osteoporosis (GIOP. The study’s objective was to determine if teriparatide is cost effective against oral bisphosphonates for two large and high risk cohorts. Methods A computer simulation model was created to model treatment, osteoporosis related fractures, and the remaining life of PMO and GIOP patients. Natural mortality and additional mortality from osteoporosis related fractures were included in the model. Costs for treatment with both teriparatide and oral bisphosphonates were included. Drug efficacy was modeled as a reduction to the relative fracture risk for subsequent osteoporosis related fractures. Patient health utilities associated with age, gender, and osteoporosis related fractures were included in the model. Patient costs and utilities were summarized and incremental cost-effectiveness ratios (ICERs for teriparatide versus oral bisphosphonates and teriparatide versus no treatment were estimated. For each of the PMO and GIOP populations, two cohorts differentiated by fracture history were simulated. The first contained patients with both a historical vertebral fracture and an incident vertebral fracture. The second contained patients with only an incident vertebral fracture. The PMO cohorts simulated had an initial Bone Mineral Density (BMD T-Score of −3.0. The GIOP cohorts simulated had an initial BMD T-Score of −2.5. Results The ICERs for teriparatide versus bisphosphonate use for the one and two fracture PMO cohorts were €36,995 per QALY and €19,371 per QALY. The ICERs for teriparatide versus bisphosphonate use for the one and two fracture GIOP cohorts were €20,826 per QALY and €15,155 per QALY, respectively. Conclusions The selection of teriparatide versus oral bisphosphonates as a first-line treatment for the high risk PMO
Aghdassi, Ali; Mayerle, Julia; Kraft, Matthias; Sielenkämper, Andreas W; Heidecke, Claus-Dieter; Lerch, Markus M
Pancreatic pseudocysts are a well-known complication of acute or chronic pancreatitis, with a higher incidence in the latter. Diagnosis is accomplished most often by computed tomographic scanning, by endoscopic retrograde cholangiopancreatography, or by ultrasound, and a rapid progress in the improvement of diagnostic tools enables detection with high sensitivity and specificity. Different strategies contribute to the treatment of pancreatic pseudocysts: endoscopic transpapillary or transmural drainage, percutaneous catheter drainage, or open surgery. The feasibility of endoscopic drainage is highly dependent on the anatomy and topography of the pseudocyst, but provides high success and low complication rates. Percutaneous drainage is used for infected pseudocysts. However, its usefulness in chronic pancreatitis-associated pseudocysts is questionable. Internal drainage and pseudocyst resection are frequently used as surgical approaches with a good overall outcome, but a somewhat higher morbidity and mortality compared with endoscopic intervention. We therefore conclude that pseudocyst treatment in chronic pancreatitis can be effectively achieved by both endoscopic and surgical means. This review entails publications referring to the classification of pancreatic pseudocysts, epidemiology, diagnostic tools, and therapeutic options for pancreatic pseudocysts. Only full articles were considered for the review. Based on a search in PubMed, the MeSH terms "pancreatic pseudocysts and classification," "diagnosis," and "endoscopic, percutaneous, and surgical treatment" were used either alone or in combination. PMID:18376299
K. V. Zhdanov
Full Text Available Purpose of the present research studying dynamics of the parameters describing a metabolism of iron at chronic hepatitis С patients on a combined antiviral therapy peg-interferon-2а and ribavirin. Has served 50 patients chronic hepatitis C (anti-HCV “+”, РНК HCV “+”, 1b genotype in the age from 18 till 59 years, on the average 33±1,5years, at various stages of disease and stages of monitoring antiviral treatments. To patients the parameters describing a metabolism of iron (serum iron, transferrin, ferritin, haptoglobin, ceruplasmin, total iron binding capacity, transferrin saturation by iron were defined. The sustain virology response (SVR was estimated - definition RNA HCV in half a year after end of treatment (72 week. It was carried out liver biopsy with the subsequent estimation of a degree of inflammatory activity and fibrosis on system METAVIR. Therapy peg-interferon-2а and ribavirin was accompanied by decrease serum iron, transferrin, ferritin, ceruplasmin, haptoglobin, transferrin saturation by iron irrespective of the answer to treatment. Thus, SVR directly correlated with higher level of iron and ceruplasmin of blood before therapy, on its background and during supervision. Normalization of biochemical activity chronic hepatitis C and positive morphological dynamics correspond with the parameters describing changes in a metabolism of iron at its patients, possibly, were compensatory-adaptive and to some extent endogen antiviral reaction of an organism of the person on HCV - infection.
Full Text Available Recommended treatment of severe hypotonic hyponatremia is based on the infusion of 3% sodium chloride solution, with a daily correction rate below 10 mEq/L of sodium concentration, according to the Adrogué and Madias formula that includes the current desired change in sodium concentrations. However, such treatment needs close monitoring of the rate of infusion and does not take into account the body weight or age of the patient. This may result in hypercorrection and neurological damage. We made an inverse calculation using the same algorithms of the Adrogué and Madias formula to estimate the number of vials of sodium chloride needed to reach a correction rate of the serum sodium concentration below 0.4 mEq/h, taking into account the body weight and age of the patient. Three tables have been produced, each containing the number of vials to be infused, according to the patient’s age and body weight, the serum sodium concentration, and the rate of correction over 24 h to avoid the risk of brain damage. We propose a new practical model to calculate the need of sodium chloride infusate to safely correct the hyponatremia. The tables make treatment easier to manage in daily clinical practice in a wide range of patient ages and body weights.
Giselle Soares Passos
Full Text Available The purposes of this systematic/critical review are: 1 to identify studies on the effects of exercise on chronic insomnia and sleep complaints in middle-aged and older adults and to compare the results of exercise with those obtained with hypnotic medications and 2 to discuss potential mechanisms by which exercise could promote sleep in insomniac patients. We identified studies from 1983 through 2011 using MEDLINE, SCOPUS and Web of Science. For systematic analyses, only studies assessing the chronic effects of exercise on sleep in people with sleep complaints or chronic insomnia were considered. We used the following keywords when searching for articles: insomnia, sleep, sleep complaints, exercise and physical activity. For a critical review, studies were selected on the effects of exercise and possible mechanisms that may explain the effects of exercise on insomnia. We identified five studies that met our inclusion criteria for systematic review. Exercise training is effective at decreasing sleep complaints and insomnia. Aerobic exercise has been more extensively studied, and its effects are similar to those observed after hypnotic medication use. Mechanisms are proposed to explain the effects of exercise on insomnia. There is additional documented evidence on the antidepressant and anti-anxiety effects of exercise. Exercise is effective to decrease sleep complaints and to treat chronic insomnia. Exercise presented similar results when compared with hypnotics; however, prospective studies comparing the effects of exercise with medical and non-medical treatments are warranted before including exercise as a first-line treatment for chronic insomnia are necessary.
... for Treatment of Chronic Plaque Psoriasis AGENCY: Agency for Healthcare Research and Quality (AHRQ... Phototherapy medical devices for treatment of chronic plaque psoriasis. Scientific information is being... Phototherapy for Treatment of Chronic Plaque Psoriasis, which is currently being conducted by the...
Full Text Available Chronic stress can affect skin function, and some skin diseases might be triggered or aggravated by stress. Stress can activate the central hypothalamic-pituitary-adrenocortical (HPA axis, which causes glucocorticoid levels to increase. The skin has HPA axis elements that react to environmental stressors to regulate skin functions, such as melanogenesis. This study explores the mechanism whereby chronic stress affects skin pigmentation, focusing on the HPA axis, and investigates the role of glucocorticoids in this pathway. We exposed C57BL/6 male mice to two types of chronic stress, chronic restraint stress (CRS and chronic unpredictable mild stress (CUMS. Mice subjected to either stress condition showed reduced melanogenesis. Interestingly, CRS and CUMS triggered reductions in the mRNA expression levels of key factors involved in the HPA axis in the skin. In mice administered corticosterone, decreased melanin synthesis and reduced expression of HPA axis elements were observed. The reduced expression of HPA axis elements and melanogenesis in the skin of stressed mice were reversed by RU486 (a glucocorticoid receptor antagonist treatment. Glucocorticoids had no significant inhibitory effect on melanogenesis in vitro. These results suggest that, high levels of serum corticosterone induced by chronic stress can reduce the expression of elements of the skin HPA axis by glucocorticoid-dependent negative feedback. These activities can eventually result in decreased skin pigmentation. Our findings raise the possibility that chronic stress could be a risk factor for depigmentation by disrupting the cutaneous HPA axis and should prompt dermatologists to exercise more caution when using glucocorticoids for treatment.
Sara M. Schaefer
Full Text Available Migraine is the most common neurological disorder, and contributes to disability and large healthcare costs in the United States and the world. The treatment of migraine until recently has focused on medications, both abortive and prophylactic, but treatment of chronic migraine has been revolutionized with the introduction of botulinum toxin injection therapy. In this review, we explore the current understanding of migraine pathophysiology, and the evolution of the use of botulinum toxin therapy including proposed pathophysiological mechanisms through animal data. We also discuss the similarities and differences between three injection techniques.
Lee, Kun Song; Kang, Dong Soo; Yu, Jeesuk; Chang, Young Pyo; Park, Woo Sung
Chronic diarrhea is defined as passing watery stools that lasts for more than 2 weeks. Persistent diarrhea belongs to chronic diarrhea and is a chronic episode of diarrhea of infectious etiology. The etiology of chronic diarrhea is varied. It is important to consider the child's age and clinical manifestations with alarm signals for an application of proper treatments to children with chronic diarrhea. Vicious cycle is present in chronic diarrhea and nutritional rehabilitation can break the v...
Marit Arp, J; Ter Horst, Judith P; Loi, Manila; den Blaauwen, Jan; Bangert, Eline; Fernández, Guillén; Joëls, Marian; Oitzl, Melly S; Krugers, Harm
Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal d
LU Wei-ju; LI Bin; BAO Ni-rong; QIAN Hong-bo; ZENG Xiao-feng; XU Bin; CHEN Yong; ZHAO Jian-ning
Objective: To avoid disadvantages of two-stage cancellus bone autograft, we investigated the feasibility of one-stage allograft for reconstructing the bone defect resulting from debridement of chronic osteomyelitis in limbs.Methods: Between Feb. 1999 and Apr. 2004, 35 cases of chronic osteomyelitis (8 cases of nonunion )underwent one-stage allograft after debridement in our hospital.Results: Thirty-five cases were followed up for an average period of 28 months (range, 13 to 55 months), in which 32 cases (91.43%) were found no infection, and 3cases (8.57 %) were confirmed recurrence of infection.Four out of 8 cases of bone nonunion healed in 9.5 months on average (range, 3 to 12 months), and another case also acquired union after redebridement and autograft of ilium due to infection recurrence 35 days after surgery.Renonunion occurred in 3 cases, 2 out of whom healed after secondary operation with autograft. One case of renonunion and 2 cases of infection recurrence refused further treatment.Conclusions: A high rate of infection arrest can be attained when one-stage allograft is used to reconstruct the bone defect of chronic osteomyelitis after debridement in limbs. Therefore, chronic osteomyelitis should not be regarded as a contraindication to one-stage allogeneic bone grafting. Renonuion, however, achieves a relatively high rate, especially in cases of segmental bone defect.
The purpose of this study was to clarify the effect of (-)-nicotine on cerebral benzodiazepine receptors (BzR) with radiotracer methods. The effect of (-)-nicotine on BzR was examined in in vitro studies using chronic (-)-nicotine-treated rats using 3H-diazepam. The in vitro radioreceptor assay showed a 14% increase in the maximum number of binding sites of BzR in chronic (-)-nicotine-treated rats in comparison with the control rats. Moreover, a convenient in vivo uptake index of 125I-iomazenil was calculated and a higher uptake of the radioactivity was observed in the chronic (-)-nicotine-treated group than in the control group. Although further studies of the mechanism of (-)-nicotine on such BzR changes are required, an increase in the amount of BzR in the cerebral cortex was found in rats that underwent chronic (-)-nicotine treatment, and this result contributed to the understanding of the effects of (-)-nicotine and smoking on neural functions
Nogués, Martín A; Varela, Francisco J; Seminario, Gisela; Insúa, María C; Bezrodnik, Liliana
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired disease that may affect nerve roots and peripheral nerves. Despite its low incidence, diagnosis is particularly important because there are different effective treatments. Human immunoglobulin is one of the mainstays of the treatment. Although there are few studies up to date, subcutaneous immunoglobulin (IgSC) has been proposed as an alternative to intravenous administration with similar efficacy. We present three cases with definite CIDP, classified according to the European Federation of Neurological Societies / Peripheral Nerve, Society (EFNS /PNS) criteria in which was used SCIgG as a treatment after success with the intravenous route. The Overall Neuropathy Limitations Scale (ONLS) was used to estimate the changes in the muscular strength before and after treatment. PMID:26826992
Jennifer L Mozeiko
•\tIncreased activation in S2’s bilateral inferior frontal gyrus following the second treatment session indicates that a second Treatment Period can influence continued neuroplastic change in severe, chronic aphasia. •\tS1 appears to show the most activation following Treatment Period I. It is possible that his greater lesion volume or site did not allow for benefit from a second dose to the same degree as S2. •\tActivation changes (or lack thereof in both cases corresponded with performance on the naming task in the scanner, reflecting the effect of treatment. •\tFor S2, neuroimaging supported the behavioral results which favor a second dose of ILAT. For S1, behavioral results, particularly in his consistent increases on the BNT, are not supported by either the behavioral results in the scanner or the BOLD response.
Fashler, Samantha R; Cooper, Lynn K; Oosenbrug, Eric D; Burns, Lindsay C; Razavi, Shima; Goldberg, Lauren; Katz, Joel
This study reviewed the published literature evaluating multidisciplinary chronic pain treatment facilities to provide an overview of their availability, caseload, wait times, and facility characteristics. A systematic literature review was conducted using PRISMA guidelines following a search of MEDLINE, PsycINFO, and CINAHL databases. Inclusion criteria stipulated that studies be original research, survey more than one pain treatment facility directly, and describe a range of available treatments. Fourteen articles satisfied inclusion criteria. Results showed little consistency in the research design used to describe pain treatment facilities. Availability of pain treatment facilities was scarce and the reported caseloads and wait times were generally high. A wide range of medical, physical, and psychological pain treatments were available. Most studies reported findings on the percentage of practitioners in different health care professions employed. Future studies should consider using more comprehensive search strategies to survey facilities, improving clarity on what is considered to be a pain treatment facility, and reporting on a consistent set of variables to provide a clear summary of the status of pain treatment facilities. This review highlights important information for policymakers on the scope, demand, and accessibility of pain treatment facilities. PMID:27445618
Holden, Neil S; Bell, Matthew J; Rider, Christopher F; King, Elizabeth M; Gaunt, David D; Leigh, Richard; Johnson, Malcolm; Siderovski, David P; Heximer, Scott P; Giembycz, Mark A; Newton, Robert
In asthma and chronic obstructive pulmonary disease, activation of G(q)-protein-coupled receptors causes bronchoconstriction. In each case, the management of moderate-to-severe disease uses inhaled corticosteroid (glucocorticoid)/long-acting β(2)-adrenoceptor agonist (LABA) combination therapies, which are more efficacious than either monotherapy alone. In primary human airway smooth muscle cells, glucocorticoid/LABA combinations synergistically induce the expression of regulator of G-protein signaling 2 (RGS2), a GTPase-activating protein that attenuates G(q) signaling. Functionally, RGS2 reduced intracellular free calcium flux elicited by histamine, methacholine, leukotrienes, and other spasmogens. Furthermore, protection against spasmogen-increased intracellular free calcium, following treatment for 6 h with LABA plus corticosteroid, was dependent on RGS2. Finally, Rgs2-deficient mice revealed enhanced bronchoconstriction to spasmogens and an absence of LABA-induced bronchoprotection. These data identify RGS2 gene expression as a genomic mechanism of bronchoprotection that is induced by glucocorticoids plus LABAs in human airway smooth muscle and provide a rational explanation for the clinical efficacy of inhaled corticosteroid (glucocorticoid)/LABA combinations in obstructive airways diseases. PMID:22080612
It is evident that the morning symptoms of rheumatoid arthritis (RA) are linked to the circadian abnormal increase in night inflammation, favoured by inadequate cortisol secretion under conditions of active disease. Therefore, exogenous glucocorticoid treatment is recommended in RA at low doses since it may partially act like a 'replacement therapy'. The prevention/treatment of the night upregulation of the immune/inflammatory reaction (and related flare of cytokine synthesis) has been shown to be more effective when exogenous glucocorticoid administration is obtained with a night-time-release formulation. Large-scale trials documented that modified-release prednisone has greater efficacy then morning prednisone for long-term low-dose glucocorticoid treatment in patients with RA, showing at least a more significant reduction in morning joint stiffness. Interestingly, despite a considerably higher cost than conventional prednisone, chronotherapy with night-time-release prednisone was recognised as a cost-effective option for patients with RA not on glucocorticoids who are eligible for therapy with biological disease-modifying antirheumatic drugs (DMARDs). Moreover, since different cell populations involved in the inflammatory process are particularly activated during the night, other therapeutical approaches used in RA, for example, conventional DMARDs and non-steroidal anti-inflammatory drugs (NSAIDs), should follow the same concepts of glucocorticoid chronotherapy. Indeed, bedtime methotrexate chronotherapy was found to improve RA symptoms compared to the current standard dosing methods, and several available NSAIDs (ie, indomethacin, aceclofenac, ketoprofen, flurbiporfen, lornoxicam) have been very recently modified in their formulation, in order to obtain chronotherapeutical effects in RA. PMID:27042335
Full Text Available Overproduction of oxidants (reactive oxygen species and reactive nitrogen species in the human body is responsible for the pathogenesis of some diseases. The scavenging of these oxidants is thought to be an effective measure to depress the level of oxidative stress of organisms. It has been reported that intake of vegetables and fruits is inversely associated with the risk of many chronic diseases, and antioxidant phytochemicals in vegetables and fruits are considered to be responsible for these health benefits. Antioxidant phytochemicals can be found in many foods and medicinal plants, and play an important role in the prevention and treatment of chronic diseases caused by oxidative stress. They often possess strong antioxidant and free radical scavenging abilities, as well as anti-inflammatory action, which are also the basis of other bioactivities and health benefits, such as anticancer, anti-aging, and protective action for cardiovascular diseases, diabetes mellitus, obesity and neurodegenerative diseases. This review summarizes recent progress on the health benefits of antioxidant phytochemicals, and discusses their potential mechanisms in the prevention and treatment of chronic diseases.
Full Text Available The purpose of this study was to evaluate the effect of medium-level laser therapy in chronic tinnitus treatment. In a prospective double-blind placebo-controlled trial, either active laser (450 mW, 830 nm combined Ga-Al-As diode laser or placebo irradiation was applied through the external acoustic meatus of the affected ear towards the cochlea. Fourty-eight patients with chronic tinnitus were studied. The main outcome was measured using the Goebel tinnitus questionnaire, visual analogue scales measuring the perceived loudness of tinnitus, the annoyance associated with tinnitus, and the degree of attention paid to tinnitus as well as psycho-acoustical matches of tinnitus pitch and loudness. The results did show only very moderate temporary improvement of tinnitus. Moreover, no statistically relevant differences between laser and placebo group could be found. We conclude that medium-level laser therapy cannot be regarded as an effective treatment of chronic tinnitus in our therapy regime considering the limited number of patients included in our study.
Riemann, Dieter; Nissen, Christoph; Palagini, Laura; Otte, Andreas; Perlis, Michael L; Spiegelhalder, Kai
Chronic insomnia is defined by difficulties in falling asleep, maintaining sleep, and early morning awakening, and is coupled with daytime consequences such as fatigue, attention deficits, and mood instability. These symptoms persist over a period of at least 3 months (Diagnostic and Statistical Manual 5 criteria). Chronic insomnia can be a symptom of many medical, neurological, and mental disorders. As a disorder, it incurs substantial health-care and occupational costs, and poses substantial risks for the development of cardiovascular and mental disorders, including cognitive deficits. Family and twin studies confirm that chronic insomnia can have a genetic component (heritability coefficients between 42% and 57%), whereas the investigation of autonomous and central nervous system parameters has identified hyperarousal as a final common pathway of the pathophysiology, implicating an imbalance of sleep-wake regulation consisting of either overactivity of the arousal systems, hypoactivity of the sleep-inducing systems, or both. Insomnia treatments include benzodiazepines, benzodiazepine-receptor agonists, and cognitive behavioural therapy. Treatments currently under investigation include transcranial magnetic or electrical brain stimulation, and novel methods to deliver psychological interventions. PMID:25895933
I. M. Lang
Full Text Available Chronic thromboembolic pulmonary hypertension (CTEPH is a life-threatening condition in which organised thrombi obstruct the pulmonary vessels, causing increased pulmonary vascular resistance, progressive pulmonary hypertension (PH and right heart failure. The treatment of choice is pulmonary endarterectomy, which restores pulmonary haemodynamics with acceptable periprocedural mortality rates in the majority of suitable patients. However, CTEPH may be inoperable owing to surgically inaccessible thrombi or comorbid diseases that confer an unacceptably high risk. Pharmacotherapies, although not yet approved, may be useful in this situation or for treating residual or recurrent PH following surgery. Vasodilator drugs for PH are attracting growing interest as potential treatments for CTEPH because this disease has recently been labelled as a "dual" pulmonary vascular disorder: major vessel obstruction and remodelling is combined with a small vessel arteriopathy that is histologically indistinguishable from the classical pulmonary arteriopathy observed in pulmonary arterial hypertension. Of three completed randomised controlled trials in patients with CTEPH, only one was powered to detect a treatment effect. The BENEFIT trial employed the dual endothelin-receptor antagonist bosentan. Although haemodynamics improved significantly, the second component of the primary end-point, exercise capacity, was not met. More evidence is required to resolve whether vasodilator treatments are beneficial for inoperable chronic thromboembolic pulmonary hypertension.
Full Text Available Lukáš Smolej 4th Department of Internal Medicine – Hematology, University Hospital Hradec Králové and Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic Abstract: Introduction of targeted agents revolutionized the treatment of chronic lymphocytic leukemia (CLL in the past decade. Addition of chimeric monoclonal anti-CD20 antibody rituximab to chemotherapy significantly improved efficacy including overall survival (OS in untreated fit patients; humanized anti-CD52 antibody alemtuzumab and fully human anti-CD20 antibody ofatumumab lead to improvement in refractory disease. Novel small molecule inhibitors such as ibrutinib and idelalisib demonstrated excellent activity and were very recently licensed in relapsed/refractory CLL. Obinutuzumab (GA101 is the newest monoclonal antibody approved for the treatment of CLL. This novel, glycoengineered, type II humanized anti-CD20 antibody is characterized by enhanced antibody-dependent cellular cytotoxicity and direct induction of cell death compared to type I antibodies. Combination of obinutuzumab and chlorambucil yielded significantly better OS in comparison to chlorambucil monotherapy in untreated comorbid patients. These results led to approval of obinuzutumab for the treatment of CLL. Numerous clinical trials combining obinutuzumab with other cytotoxic drugs and novel small molecules are currently under way. This review focuses on the role of obinutuzumab in the treatment of CLL. Keywords: chronic lymphocytic leukemia, anti-CD20 antibodies, chlorambucil, rituximab, ofatumumab, obinutuzumab, overall survival
Schut, Christina; Mollanazar, Nicholas K; Kupfer, Jörg; Gieler, Uwe; Yosipovitch, Gil
Patients with chronic itch suffer from higher levels of depression and anxiety than their healthy counterparts. Furthermore, psychological factors, such as stress, are known to aggravate itch. The mere act of thinking about itching can induce the sensation. Interventions like habit reversal training and arousal reduction have been shown to have positive effects on itch relief. Yet, there is still limited data on the psychological management to control the itch scratch cycle and a description of methods suitable to address itch. In this review, we describe different psychological interventions shown to be effective in the treatment of chronic itch. We also provide suggestions based on our experience of suitable interventions for patients with different types of itch. PMID:26073701
Galmiche, Jean-Paul; Hatlebakk, Jan; Attwood, Stephen;
Context Gastroesophageal reflux disease (GERD) is a chronic, relapsing disease with symptoms that have negative effects on daily life. Two treatment options are long-term medication or surgery. Objective To evaluate optimized esomeprazole therapy vs standardized laparoscopic antireflux surgery...... (LARS) in patients with GERD. Design, Setting, and Participants The LOTUS trial, a 5-year exploratory randomized, open, parallel-group trial conducted in academic hospitals in 11 European countries between October 2001 and April 2009 among 554 patients with well-established chronic GERD who initially.......6%). Conclusion This multicenter clinical trial demonstrated that with contemporary antireflux therapy for GERD, either by drug-induced acid suppression with esomeprazole or by LARS, most patients achieve and remain in remission at 5 years....
Burns, J W
This study examined whether repression predicts outcome following multidisciplinary treatment for chronic pain and whether links between anxiety and outcome are obscured by repressors. Ninety-three chronic pain patients completed a 4-week pain program. Lifting capacity, walking endurance, depression, pain severity, and activity were measured at pre- and posttreatment. Low-anxious, repressor, high-anxious, and defensive/high-anxious groups were formed from median splits of Anxiety Content (ACS) and Lie scales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). Significant ACS x Lie interactions were found for lifting capacity, depression, and pain severity changes. Planned comparisons showed that both repressors and high-anxious patients performed poorly on lifting capacity; repressors alone recovered poorly on depression and pain severity. Results imply that repression may interfere with the process and outcome of pain programs. PMID:10711590
Osteoporosis is defined as a condition of impairment in bone strength and predisposes individuals to an increased risk of fractures. The risk of fragility fracture is shown to be high in patients with chronic kidney disease (CKD). Osteoporosis treatment for patients with CKD G1-3 should not differ from treatment for patients without CKD, as long as there are no accompanying hyperparathyroidism and hyperphosphatemia that indicate the co-existence of CKD -mineral and bone disorder. However, there are few published data on osteoporosis treatment for patients with CKD G4, 5. So, considerations for current pharmacologic therapy (such as bisphosphonate, denosumab, teriparatide, and raloxifene) should be a thoughtful and open discussion with these patients. PMID:26529937
Duque, Erica de Almeida; Munhoz, Carolina Demarchi
Glucocorticoids are a class of steroid hormones derived from cholesterol. Their actions are mediated by the glucocorticoid and mineralocorticoid receptors, members of the superfamily of nuclear receptors, which, once bound to their ligands, act as transcription factors that can directly modulate gene expression. Through protein-protein interactions with other transcription factors, they can also regulate the activity of many genes in a composite or tethering way. Rapid non-genomic signaling was also demonstrated since glucocorticoids can act through membrane receptors and activate signal transduction pathways, such as protein kinases cascades, to modulate other transcriptions factors and activate or repress various target genes. By all these different mechanisms, glucocorticoids regulate numerous important functions in a large variety of cells, not only in the peripheral organs but also in the central nervous system during development and adulthood. In general, glucocorticoids are considered anti-inflammatory and protective agents due to their ability to inhibit gene expression of pro-inflammatory mediators and other possible damaging molecules. Nonetheless, recent studies have uncovered situations in which these hormones can act as pro-inflammatory agents depending on the dose, chronicity of exposure, and the structure/organ analyzed. In this review, we will provide an overview of the conditions under which these phenomena occur, a discussion that will serve as a basis for exploring the mechanistic foundation of glucocorticoids pro-inflammatory gene regulation in the brain. PMID:27445981
Lin, Sien; Huang, Jianping; Zheng, Liang; Liu, Yanzhi; Liu, Guihua; Li, Nan; Wang, Kuixing; Zou, Liyi; Wu, Tie; Qin, Ling; Cui, Liao; Li, Gang
This study evaluated whether growing rats were appropriate animal models of glucocorticoid-induced osteoporosis. The 3-month-old male rats were treated with either vehicle or prednisone acetate at 1.5, 3.0, and 6.0 mg/kg/day by oral gavage, respectively. All rats were injected with tetracycline and calcein before sacrificed for the purpose of double in vivo labeling. Biochemistry, histomorphometry, mechanical test, densitometry, micro-CT, histology, and component analysis were performed. We found that prednisone treatments dose dependently decreased body weight, serum biomarkers, biomechanical markers, bone formation, and bone resorption parameters in both tibial and femoral trabecular bone without trabecular bone loss. We also found that significant bone loss happened in femoral cortical bone in the glucocorticoid-treated rats. The results suggested that prednisone not only inhibited bone formation, but also inhibited bone resorption which resulted in poor bone strength but with no cancellous bone loss in growing rats. These data also suggested that the effects of glucocorticoid on bone metabolism were different between cortical bone and trabecular bone, and different between tibia and femur. Growing rats may be a glucocorticoid-induced osteoporosis animal model when evaluated the effects of drugs upon juvenile patients exposed to GC for a long time. PMID:25086673
Full Text Available Ila Tamascar, Jeyanthi RamanarayananDepartment of Medical Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, USAAbstract: Chronic myeloid leukemia (CML is a myeloproliferative disorder characterized by clonal expansion of pleuripotent hematopoetic stem cells. The incidence of CML is 1 to 2 cases per 100,000 people per year; in the Western Hemisphere, CML accounts for 15% of leukemias in adults. Discovery of the specific karyotypic abnormality of the Philadelphia (Ph chromosome in the pathogenesis of CML has led to a better understanding of the disease and hence to an advancement of targeted therapeutics. Availability of imatinib as an accepted targeted therapy in newly diagnosed patients has changed the treatment paradigm in CML. The majority of CML patients in chronic phase achieve excellent and durable responses with standard-dose imatinib. Mechanisms of primary and secondary resistance to imatinib in CML have been extensively studied and newer tyrosine kinase inhibitors are now being evaluated for clinical use. It is important that at any time the CML treatment and response remain optimal and thus patients on imatinib require continuous monitoring for early detection of resistance. This review will discuss the treatment and guidelines for monitoring CML patients in the imatinib era.Keywords: BCR-ABL, imatinib, tyrosine kinase inhibitors, leukemia, CML
Tsao, Jennie C I; Meldrum, Marcia; Kim, Su C; Jacob, Margaret C; Zeltzer, Lonnie K
CAM therapies have become increasingly popular in pediatric populations. Yet, little is known about children's preferences for CAM. This study examined treatment preferences in chronic pediatric pain patients offered a choice of CAM therapies for their pain. Participants were 129 children (94 girls) (mean age = 14.5 years +/- 2.4; range = 8-18 years) presenting at a multidisciplinary, tertiary clinic specializing in pediatric chronic pain. Bivariate and multivariate analyses were used to examine the relationships between CAM treatment preferences and patient's sociodemographic and clinical characteristics, as well as their self-reported level of functioning. Over 60% of patients elected to try at least one CAM approach for pain. The most popular CAM therapies were biofeedback, yoga and hypnosis; the least popular were art therapy and energy healing, with craniosacral, acupuncture and massage being intermediate. Patients with a diagnosis of fibromyalgia (80%) were the most likely to try CAM versus those with other pain diagnoses. In multivariate analyses, pain duration emerged as a significant predictor of CAM preferences. For mind-based approaches (i.e. hypnosis, biofeedback and art therapy), pain duration and limitations in family activities were both significant predictors. When given a choice of CAM therapies, this sample of children with chronic pain, irrespective of pain diagnosis, preferred non-invasive approaches that enhanced relaxation and increased somatic control. Longer duration of pain and greater impairment in functioning, particularly during family activities increased the likelihood that such patients agreed to engage in CAM treatments, especially those that were categorized as mind-based modalities. PMID:17965769
Jennie C. I. Tsao
Full Text Available CAM therapies have become increasingly popular in pediatric populations. Yet, little is known about children's preferences for CAM. This study examined treatment preferences in chronic pediatric pain patients offered a choice of CAM therapies for their pain. Participants were 129 children (94 girls (mean age = 14.5 years ± 2.4; range = 8–18 years presenting at a multidisciplinary, tertiary clinic specializing in pediatric chronic pain. Bivariate and multivariate analyses were used to examine the relationships between CAM treatment preferences and patient's sociodemographic and clinical characteristics, as well as their self-reported level of functioning. Over 60% of patients elected to try at least one CAM approach for pain. The most popular CAM therapies were biofeedback, yoga and hypnosis; the least popular were art therapy and energy healing, with craniosacral, acupuncture and massage being intermediate. Patients with a diagnosis of fibromyalgia (80% were the most likely to try CAM versus those with other pain diagnoses. In multivariate analyses, pain duration emerged as a significant predictor of CAM preferences. For mind-based approaches (i.e. hypnosis, biofeedback and art therapy, pain duration and limitations in family activities were both significant predictors. When given a choice of CAM therapies, this sample of children with chronic pain, irrespective of pain diagnosis, preferred non-invasive approaches that enhanced relaxation and increased somatic control. Longer duration of pain and greater impairment in functioning, particularly during family activities increased the likelihood that such patients agreed to engage in CAM treatments, especially those that were categorized as mind-based modalities.
鞠建伟; 郭亚玲; 梁延平; 孙世宁; 杨建华; 杨素云
The therapeutic effects of Shenshuailing Kou Fu Ye (SKFY肾衰灵口服液, the Oral Liquid for Renal Failure) and Shenshuailing Guan Chang Ye (SGCY肾衰灵灌肠液, the Enema for Renal Failure) were evaluated in treatment of chronic renal failure, with coateg aldehyde oxystarch as the controls. The changes in the clinical symptoms, serum creatinine, blood urea nitrogen and creatinine clearance rate were observed. The total effective rate in the former was 90.46%, and the latter 60.43%.
AIM: To assess the efficacy and safety profile of adalimumab in patients with severe, recalcitrant chronic plaque psoriasis, and to assess short-term overlapping of other systemic treatment with adalimumab to prevent flaring of disease. METHODS: This was a retrospective study comprising 39 patients with chronic plaque psoriasis treated with adalimumab between October 2005 and January 2008. All had failed treatment with other systemic agents, including biological therapies in 59% of patients. Patients were started on adalimumab 40 mg weekly or fortnightly, as clinically indicated. Severity of psoriasis was assessed by the Psoriasis Area and Severity Index (PASI). Therapeutic response was assessed by 75% improvement on PASI (PASI 75). All adverse events were recorded. RESULTS: Results were analysed separately for those treated with adalimumab only and those on combination treatment. PASI 75 was achieved in 38% (8 of 21 patients at week 16), 62% (13 of 21 patients) at week 24, 69% (9 of 13 patients) at week 48% and 71% (5 of 7 patients) at week 72 in the adalimumab-only group, compared with 56% (5 of 9 patients) at week 16, 50% (4 of 8 patients) at week 24, 80% (4 of 5 patients) at week 48% and 67% (2 of 3 patients) at week 72 in the combined group. Of the 39 patients, 15 (38%) achieved a PASI of 0 at some point in their treatment. Adalimumab was well tolerated; 38% of patients experienced side-effects, which were generally mild. CONCLUSION: Adalimumab was effective in a group of patients with psoriasis refractory to other systemic therapies, including biological treatments, and was well tolerated.
Young, D.A.; Nicholson, M.L.; Guyette, W.A.; Giddings, S.J.; Mendelsohn, S.L.; Nordeen, S.K.; Lyons, R.T.
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.
Full Text Available Roxanne Ferdinand,1 Stephen A Mitchell,2 Sarah Batson,2 Indra Tumur11Pfizer, Tadworth, UK; 2Abacus International, Bicester, UKBackground: Chronic myeloid leukemia (CML is a myeloproliferative disorder of blood stem cells. The tyrosine kinase inhibitor (TKI imatinib was the first targeted therapy licensed for patients with chronic-phase CML, and its introduction was associated with substantial improvements in response and survival compared with previous therapies. Clinical trial data are now available for the second-generation TKIs (nilotinib, dasatinib, and bosutinib in the first-, second-, and third-line settings. A qualitative systematic review was conducted to qualitatively compare the clinical effectiveness, safety, and effect on quality of life of TKIs for the management of chronic-, accelerated-, or blast-phase CML patients.Methods: Included studies were identified through a search of electronic databases in September 2011, relevant conference proceedings and the grey literature.Results: In the first-line setting, the long-term efficacy (up to 8 years of imatinib has been confirmed in a single randomized controlled trial (International Randomized Study of Interferon [IRIS]. All second-generation TKIs reported lower rates of transformation, and comparable or superior complete cytogenetic response (CCyR, major molecular response (MMR, and complete molecular response rates compared with imatinib by 2-year follow-up. Each of the second-generation TKIs was associated with a distinct adverse-event profile. Bosutinib was the only second-generation TKI to report quality-of-life data (no significant difference compared with imatinib treatment. Data in the second- and third-line setting confirmed the efficacy of the second-generation TKIs in either imatinib-resistant or -intolerant patients, as measured by CCyR and MMR rates.Conclusion: Data from first-line randomized controlled trials reporting up to 2-year follow-up indicate superior response
Hebert, Elizabeth A; Vincent, Norah; Lewycky, Samantha; Walsh, Kaitlyn
This study examined the ability of the Theory of Planned Behavior (TPB; Ajzen, 1985) and the Transtheoretical Model of Behavior Change (TTM; Prochaska & DiClemente, 1983) to explain adherence and attrition in an online treatment program for chronic insomnia. Responses to questionnaire measures of the TPB and TTM were used to predict adherence and dropout over the subsequent 5 weeks of treatment. Results showed that there was a 17% dropout rate and that perceived behavioral control, social support, and intention to complete the program were significantly associated with adherence to sleep hygiene homework. Attrition was predicted only by symptom severity and psychiatric comorbidity. Implications are that these models should be considered to maximize adherence. PMID:20582757
Full Text Available Epigenetic therapy with hypomethylating agent (5-azacytidine; AZA is common in the management of specific subtypes of myelodysplastic syndrome (MDS, but there are only few studies in chronic myelomonocytic leukemia (CMML patients. In this paper our experience with 3 CMML patients treated with AZA is described. In one patient transfusion independency was observed after 4 treatment cycles; in one case a partial response was recorded, but a progression to acute myeloid leukemia (AML after 13 AZA cycles has appeared. In one patient, AZA in reduced dosage was administered as a bridging treatment before allogeneic stem cell transplantation (ASCT, but in the control bone marrow aspirate (before ASCT a progression to AML was recorded. Future studies are mandatory for evaluation of new molecular and clinical features which could predict the efficiency of hypomethylating agents in CMML therapy with respect to overall survival, event-free survival, quality-adjusted life year, and pharmacoeconomy.
Rohon, Peter; Vondrakova, Jana; Jonasova, Anna; Holzerova, Milena; Jarosova, Marie; Indrak, Karel
Epigenetic therapy with hypomethylating agent (5-azacytidine; AZA) is common in the management of specific subtypes of myelodysplastic syndrome (MDS), but there are only few studies in chronic myelomonocytic leukemia (CMML) patients. In this paper our experience with 3 CMML patients treated with AZA is described. In one patient transfusion independency was observed after 4 treatment cycles; in one case a partial response was recorded, but a progression to acute myeloid leukemia (AML) after 13 AZA cycles has appeared. In one patient, AZA in reduced dosage was administered as a bridging treatment before allogeneic stem cell transplantation (ASCT), but in the control bone marrow aspirate (before ASCT) a progression to AML was recorded. Future studies are mandatory for evaluation of new molecular and clinical features which could predict the efficiency of hypomethylating agents in CMML therapy with respect to overall survival, event-free survival, quality-adjusted life year, and pharmacoeconomy. PMID:22937326
Carter Bryan D
Full Text Available Abstract Chronic pain in children and adolescents is associated with major disruption to developmental experiences crucial to personal adjustment, quality of life, academic, vocational and social success. Caring for these patients involves understanding cognitive, affective, social and family dynamic factors associated with persistent pain syndromes. Evaluation and treatment necessitate a comprehensive multimodal approach including psychological and behavioral interventions that maximize return to more developmentally appropriate physical, academic and social activities. This article will provide an overview of major psychosocial factors impacting on pediatric pain and disability, propose an explanatory model for conceptualizing the development and maintenance of pain and functional disability in medically difficult-to-explain pain syndromes, and review representative evidence-based cognitive behavioral and systemic treatment approaches for improving functioning in this pediatric population.
Carter, Bryan D; Threlkeld, Brooke M
Chronic pain in children and adolescents is associated with major disruption to developmental experiences crucial to personal adjustment, quality of life, academic, vocational and social success. Caring for these patients involves understanding cognitive, affective, social and family dynamic factors associated with persistent pain syndromes. Evaluation and treatment necessitate a comprehensive multimodal approach including psychological and behavioral interventions that maximize return to more developmentally appropriate physical, academic and social activities. This article will provide an overview of major psychosocial factors impacting on pediatric pain and disability, propose an explanatory model for conceptualizing the development and maintenance of pain and functional disability in medically difficult-to-explain pain syndromes, and review representative evidence-based cognitive behavioral and systemic treatment approaches for improving functioning in this pediatric population. PMID:22676345
Dejgard, A; Kastrup, J; Petersen, P
Sixteen of nineteen patients completed a randomised double-blind crossover trial to assess the effect of oral mexiletine (10 mg/kg bodyweight daily) on the symptoms and signs of chronic painful diabetic neuropathy. The median age of the sixteen patients was 50 years (range 30-64). Assessment with...... threshold levels, beat-to-beat variation in heart rate during deep breathing, and postural blood pressure response. Mild side-effects were seen in three of the sixteen patients during mexiletine treatment....... with a five-item clinical symptom scale showed significant improvement during the mexiletine phase compared with the placebo phase. Pain was reduced during mexiletine but not during placebo, as assessed by a visual analogue rating scale. Mexiletine treatment had no effect on tendon reflexes, vibration...
Full Text Available M Gentile, E Vigna, C Mazzone, E Lucia, AG Recchia, L Morabito2, MG Bisconte, C Gentile, F Morabito1UOC di Ematologia, Azienda Ospedaliera di Cosenza, Italy; 2Servicio de Hematología y Hemoterapia, Hospital Universitario de Canarias, La Laguna, Tenerife, SpainAbstract: Chronic lymphocytic leukemia (CLL is a lymphoproliferative disorder that originates from antigen-experienced B lymphocytes that do not die and hence accumulate due to external survival signals or undergo apoptosis and are replenished by proliferating precursors. These neoplastic lymphocytes exhibit a characteristic immunophenotype of CD5+/CD19+/CD20+/HLA-DR+/CD23+/sIgdim. Thus, the CD20 antigen has been an appealing target for therapy. The introduction of the monoclonal antibody rituximab (anti-CD20 enabled an outstanding advance in CLL treatment. The introduction of this monoclonal antibody into chemotherapy regimens has dramatically improved complete response rates and progression-free survival in patients with both untreated and relapsed CLL. Although only preliminary data from phase III confirmatory trials have been reported, the FCR regimen, which combines fludarabine and cyclophosphamide with rituximab, is currently the most effective treatment regimen for CLL patients, and has also been demonstrated to significantly improve overall survival . The success of rituximab and the identification of other CLL lymphocyte surface antigens have spurred the development of a multitude of monoclonal antibodies targeting distinct proteins and epitopes in an attempt to target CLL cells more effectively.Keywords: rituximab, chronic lymphocytic leukemia, chemotherapy