Dyb G.,Norwegian Center for Violence |
Jensen T.K.,Norwegian Center for Violence and Traumatic Stress Studies |
Nygaard E.,Norwegian Center for Violence and Traumatic Stress Studies |
Ekeberg O.,University of Oslo |
And 3 more authors.
British Journal of Psychiatry | Year: 2014
Survivor characteristics that can be assessed in the early aftermath of a terrorist attack strongly predict the subsequent mental health problems of exposed youths. The highly elevated symptoms observed were largely attributable to the traumatic experience and reflect the mental health costs of the terrorist attack.
Hagensen M.K.,Institute of Clinical Medicine |
Vanhoutte P.M.,Chonbuk National University |
Bentzon J.F.,Institute of Clinical Medicine
Cardiovascular Research | Year: 2012
For more than a decade, a prevailing hypothesis in research related to arterial disease has been that circulating endothelial progenitor cells (EPCs) provide protection by their innate ability to replace dysfunctional or damaged endothelium. This paradigm has led to extensive investigation of EPCs in the hope of finding therapeutic targets to control their homing and differentiation. However, from the very beginning, the nomenclature and the phenotype of EPCs have been subject to controversy and there are currently no specific markers that can unambiguously identify these cells. Moreover, many of the initial observations that EPCs differentiate to endothelial cells in the course of arterial disease have been criticized for methodological problems. The present review discusses the contrasting experimental evidence as to the role of EPCs in contributing to relining of the endothelium and highlights some of the methodological pitfalls and terminological ambiguities that confuse the field. © The Author 2012.
News Article | February 15, 2017
Sophia Antipolis, Feb. 15, 2017: Statin side effects are the strongest predictor of failure to meet low-density lipoprotein (LDL) cholesterol targets, according to research published today in the European Journal of Preventive Cardiology.1 Other predictors were statin non-adherence and use of weaker statins. "The beneficial effect of reducing LDL cholesterol on slowing the progression of coronary heart disease is overwhelmingly documented today in epidemiologic and randomised controlled studies," said lead author Dr John Munkhaugen, a cardiology trainee and post-doctoral researcher at Drammen Hospital, Norway. "European guidelines2 recommend a blood LDL cholesterol goal of less than 1.8 mmol/l but just one in five cardiac patients taking lipid-lowering drugs achieve this,"3 he added. The NORwegian COR (NOR-COR) prevention project originates from the Department of Medicine at Drammen Hospital and is a collaboration between Drammen and Vestfold hospitals, and the Department of Behavioural Sciences in Medicine and Institute of Clinical Medicine, University of Oslo. It is investigating why patients fail to control risk factors including lipids and blood pressure after they have a cardiovascular event. This analysis examined the reasons why cardiac patients do not achieve the LDL cholesterol target. The study included 1,095 patients hospitalised with a first or recurrent coronary event or treatment (heart attack, coronary artery bypass graft, or coronary stent) who were identified from medical records at two Norwegian hospitals (Drammen and Vestfold). Sociodemographic, medical and psychosocial information was collected from medical records, an interdisciplinary self-report questionnaire, clinical examinations, and blood samples while patients were in hospital and at follow-up after two to 36 months. The impact of potential barriers on achieving the LDL cholesterol target was calculated with LDL as a dichotomous (above or below 1.8 mmol/l) and continuous variable. The researchers found that 57% of patients were not meeting the LDL target of 1.8 mmol/l at follow-up. Statin specific side effects (mainly muscle complaints), low statin adherence, and moderate- or low-intensity statin therapy were the main reasons for failing to meet the target. Patients with side effects were more than three times more likely to miss the cholesterol target than those without side effects. Those who did not take their statins were three times more likely to miss the target than patients who did take them. Patients prescribed moderate- or low-intensity statins were 62% more likely to miss the target than those prescribed high-intensity statins. "We found the same three reasons for not meeting the target when LDL was analysed as a dichotomous or continous variable which confirms the strength of the associations," said Dr Munkhaugen. "Surprisingly, low socioeconomic status and psychosocial factors did not predict failure to control LDL cholesterol." "The findings show that the focus for interventions to improve LDL cholesterol control are statin side effects, and adherence to and prescription of sufficiently potent statins," he continued. Dr Munkhaugen said more research was needed on why side effects of statins had such a big effect on meeting cholesterol goals. "Patients who experience side effects are probably more likely to reduce or terminate statin use, or their doctor may prescribe a weaker drug or take them off statins altogether," he said. "Individual variations in how the body reacts to and uses the drug may also play a role." The links between non-adherence and intensity of statin therapy on LDL cholesterol are likely explained by the pharmacological effects of the drug. "Not taking the prescribed amount of statins or being prescribed a weaker statin means there is less drug in the body to act and lower LDL," said Dr Munkhaugen. "The reasons for statin non-adherence are a complex interaction between factors related to the patient and the healthcare system," he added. "Interventions aiming to improve statin adherence have been a priority in recent years, but the success has been modest and short-lived." The study found that the use of high-intensity statins was significantly more frequent in patients who achieved the cholesterol target. But Dr Munkhaugen said: "The relationship with adherence and side effects needs to be clarified before advice can be given about the potency of statins that should be prescribed. Our findings point to the need for more research on ways to ensure adherence and prescription of sufficiently potent statins, while at the same time addressing side effects."
Takigawa T.,Toranomon Hospital |
Matsumaru Y.,Toranomon Hospital |
Hayakawa M.,Toranomon Hospital |
Nemoto S.,Jichi Medical University |
Matsumura A.,Institute of Clinical Medicine
Journal of Vascular Surgery | Year: 2010
Background: Although carotid artery stenting (CAS) has been proposed as an alternative to carotid endarterectomy in cerebral revascularization, restenosis remains an unsolved issue. Cilostazol is a unique antiplatelet drug that has vasodilatory effects and inhibits smooth muscle cell proliferation. We investigated whether cilostazol reduces restenosis after CAS. Methods: A database of 113 consecutive CAS procedures between April 2002 and December 2007 was assessed retrospectively. All patients received aspirin (100 mg/d) and another antiplatelet drug such as cilostazol (200 mg/d), ticlopidine (200 mg/d), or clopidogrel (75 mg/d) at least 3 days before CAS. Two antiplatelet drugs were continued for 2 to 3 months after CAS and reduced to one thereafter. Patients were evaluated at 3 and 6 months and at 6-month intervals thereafter with duplex ultrasound (DUS) imaging. Angiography was used for confirmation when stenosis was suspected as >50% with DUS imaging. Results: We were able to monitor 97 patients for a 12-month period. The overall combined rate of stroke, myocardial infarction, and death was 3.1% at 30 days and 4.1% at 1 year. In-stent recurrent stenosis was documented in 11 patients (11%); in 10 patients (9.7%), this occurred ≤12 months of CAS. In-stent restenosis was significantly reduced in the cilostazol (+) group (0% vs 15.7% [11 of 70], P = .03). Patient characteristics were similar between the cilostazol (+) and cilostazol (-) groups. Conclusions: Although this study was retrospective and nonrandomized, the results suggest that cilostazol administration improves long-term patency after CAS due to its inhibitory effect on smooth muscle cell growth. © 2010 Society for Vascular Surgery.
Gallo J.,Palacky University |
Goodman S.B.,Stanford University |
Konttinen Y.T.,Institute of Clinical Medicine |
Konttinen Y.T.,ORTON Orthopaedic Hospital of the Invalid Foundation |
And 3 more authors.
Acta Biomaterialia | Year: 2013
Aseptic loosening and other wear-related complications are some of the most frequent late reasons for revision of total knee arthroplasty (TKA). Periprosthetic osteolysis (PPOL) pre-dates aseptic loosening in many cases, indicating the clinical significance of this pathogenic mechanism. A variety of implant-, surgery- and host-related factors have been delineated to explain the development of PPOL. These factors influence the development of PPOL because of changes in mechanical stresses within the vicinity of the prosthetic device, excessive wear of the polyethylene liner, and joint fluid pressure and flow acting on the peri-implant bone. The process of aseptic loosening is initially governed by factors such as implant/limb alignment, device fixation quality and muscle coordination/strength. Later, large numbers of wear particles detached from TKA trigger and perpetuate particle disease, as highlighted by progressive growth of inflammatory/granulomatous tissue around the joint cavity. An increased accumulation of osteoclasts at the bone-implant interface, impairment of osteoblast function, mechanical stresses and increased production of joint fluid contribute to bone resorption and subsequent loosening of the implant. In addition, hypersensitivity and adverse reactions to metal debris may contribute to aseptic TKA failure, but should be determined more precisely. Patient activity level appears to be the most important factor when the long-term development of PPOL is considered. Surgical technique, implant design and material factors are the most important preventative factors, because they influence both the generation of wear debris and excessive mechanical stresses. New generations of bearing surfaces and designs for TKA should carefully address these important issues in extensive preclinical studies. Currently, there is little evidence that PPOL can be prevented by pharmacological intervention. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Sakon M.,Nishinomiya Municipal Central Hospital |
Kobayashi T.,Hamamatsu Medical Center |
Shimazui T.,Institute of Clinical Medicine
Thrombosis Research | Year: 2010
Background: Enoxaparin sodium (enoxaparin) is used worldwide for the prevention of venous thromboembolism (VTE). Registration trials of enoxaparin have been conducted primarily in Caucasian populations, and its preventive use in Japanese patients has yet to be established. To address this, we evaluated the efficacy and safety of postoperative enoxaparin in Japanese patients undergoing surgery for abdominal cancer. Methods: This multicenter, open-label study randomized 151 Japanese patients undergoing curative surgery for abdominal cancer to enoxaparin 20 mg twice daily for 14 days, started 24-36 hours after surgery (n = 113) or intermittent pneumatic compression (IPC) as a reference (n = 38). IPC was performed at least once in both groups between randomization and surgery. The primary efficacy endpoint was the incidence of VTE in the modified intention-to-treat (mITT) population. The primary safety outcome was the incidence of any bleeding during treatment and follow-up. Results: Incidence of VTE was 1.2% (95% CI, 0.03-6.53%) (1/83 patients) in the enoxaparin group and 19.4% (95% CI, 7.45-37.47%) (6/31 patients) in the IPC group. In the safety population, 10/109 patients in the enoxaparin group (9.2%; 95% CI, 4.49-16.23%) and 3/38 patients in the IPC group (7.9%; 95% CI, 1.66-21.38%) experienced a bleeding event. There were no cases of fatal bleeding or bleeding into any critical organ. Conclusions: These favorable efficacy and safety data support the use of enoxaparin (20 mg twice daily for 14 days started 24-36 hours after surgery) in Japanese patients undergoing abdominal or pelvic cancer surgery. © 2009 Elsevier Ltd. All rights reserved.
Braekkan S.K.,Institute of Clinical Medicine |
Mathiesen E.B.,Institute of Clinical Medicine |
NjoLstad I.,University of Tromsø |
Wilsgaard T.,University of Tromsø |
And 2 more authors.
Journal of Thrombosis and Haemostasis | Year: 2010
Background: Platelet size, measured as mean platelet volume (MPV), is associated with platelet reactivity. MPV is increased in acute myocardial infarction, and has been identified as an independent risk factor for future myocardial infarction and stroke. Objectives: The purpose of the study was to determine the impact of platelet count and MPV on the incidence of venous thromboembolism (VTE) in a prospective, population-based study. Methods: Platelet count, MPV and baseline characteristics were registered in 25 923 subjects aged 25-96 years who participated in the Tromsø Study in 1994-1995. Incident VTE events were registered to the end of follow-up (1 September 2007). Results: There were 445 validated incident VTE events (1.6 per 1000 person-years), of which 186 (42%) were unprovoked, during a mean of 10.8 years of follow-up. Subjects with MPV ≥ 9.5 fL had a 1.3-fold [95% confidence interval (CI) 1.0-1.7] higher risk of total VTE and a 1.5-fold (95% CI 1.1-2.3) higher risk of unprovoked VTE than subjects with MPV < 8.5 fL in analyses adjusted for age, sex, smoking, body mass index, and platelet count. Increasing MPV was associated with increased risk of total VTE (P for trend = 0.09) and unprovoked VTE (P for trend = 0.03) in analyses adjusted for age and sex. There was no significant association between increasing platelet count and risk of VTE. Conclusions: An increasing MPV was identified as a predictor for VTE, in particular VTE of unprovoked origin. The present findings support the concept that platelet reactivity is important in the pathogenesis of VTE. © 2009 International Society on Thrombosis and Haemostasis.
Ratsep T.,University of Tartu |
Minajeva A.,University of Tartu |
Minajeva A.,Institute of Clinical Medicine |
Asser T.,University of Tartu
European Spine Journal | Year: 2013
Purpose: Lumbar disc degeneration may be associated with intensity of neovascularization in disc herniations. Our study was designed to evaluate how much the severity of histodegeneration is related to the development of neovascularization and to the level of pleiotrophin in the herniated lumbar discs. Methods: Surgically excised lumbar disc specimens were obtained from 29 patients with noncontained (i.e., extruding through the posterior longitudinal ligament) and 21 patients with contained disc herniations. The histodegeneration scores and levels of neovascularization were estimated according to semiquantitative analysis in lumbar disc and endplate samples. Immunohistochemical staining were performed to identify the newly formed blood vessels and to detect the presence of pleiotrophin in the specimens. Results: Higher levels of disc and endplate neovascularity were registered in noncontained herniations. The level of neovascularization was significantly related to the score of histodegeneration in the herniated disc tissues but not in the endplate specimens. Both contained and noncontained herniations had the highest values of histodegeneration in conjunction with the highest level of neovascularization but the relations between neovascularity and degenerative changes remained to be significant only in the group of noncontained herniations. Registration or frequency of pleiotrophin positive cells did not correlate significantly with histodegeneration or level of neovascularization in the disc samples. Conclusion: Severe histodegeneration of the lumbar disc herniations is associated with enhanced neovascularization and potentially also spontaneous regression of the herniated tissue. © 2013 Springer-Verlag Berlin Heidelberg.
Torsvik I.,University of Bergen |
Ueland P.M.,University of Bergen |
Markestad T.,Institute of Clinical Medicine |
Bjorke-Monsen A.-L.,University of Bergen
American Journal of Clinical Nutrition | Year: 2013
Background: During infancy, minor developmental delays and gastrointestinal complaints are common, as is a biochemical profile indicative of impaired cobalamin status. Objective: We investigated whether cobalamin supplementation can improve development or symptoms in infants with biochemical signs of impaired cobalamin function and developmental delay or feeding difficulties. Design: Infants <8 mo of age (n = 105) who were referred for feeding difficulties, subtle neurologic symptoms, or delayed psychomotor development were assessed for cobalamin status [by the measurement of serum cobalamin, plasma total homocysteine (tHcy), and plasma methylmalonic acid (MMA)]. Infants with biochemical signs of impaired cobalamin function, defined as a plasma tHcy concentration 6.5 mmol/L (n = 79), were enrolled in a double-blind, randomized controlled trial to receive 400 mg hydroxycobalamin intramuscularly (n = 42) or a sham injection (n = 37). Motor function [Alberta Infants Motor Scale (AIMS)] and clinical symptoms (parental questionnaire) were recorded at entry and after 1 mo. Results: During follow-up, cobalamin supplementation changed all markers of impaired cobalamin status (ie, plasma tHcy decreased by 54%, and MMA decreased by 84%), whereas no significant changes were seen in the placebo group (P < 0.001). The median (IQR) increase in the AIMS score was higher in the cobalamin group than in the placebo group [7.0 (5.0, 9.0) compared with 4.5 (3.3, 6.0); P = 0.003], and a higher proportion showed improvements in regurgitations (69% compared with 29%, respectively; P = 0.003). Conclusions: In infants with biochemical signs of impaired cobalamin function, 1 intramuscular injection of cobalamin resulted in biochemical evidence of cobalamin repletion and improvement in motor function and regurgitations, which suggest that an adequate cobalamin status is important for a rapidly developing nervous system. This trial was registered at clinicaltrials.gov as NCT00710359 and NCT00710138. © 2013 American Society for Nutrition.
Salminen A.,Institute of Clinical Medicine |
Salminen A.,Kuopio University Hospital |
Kaarniranta K.,Institute of Clinical Medicine |
Kaarniranta K.,Kuopio University Hospital
Ageing Research Reviews | Year: 2010
An ability to mount a stress resistance under pressure is a major host defence mechanism and has been a fundamental force during evolution. However, the adaptation capacity clearly declines during aging and this loss of stress resistance accelerates the aging process exposing the organism to degenerative diseases. The effect of stress on organisms seems to be a dose-dependent response, i.e. mild stress induces a stress tolerance and extends the lifespan whereas excessive stress accentuates the aging process. This paradox is known as hormesis in aging research. It is essential to distinguish the intensity of cellular stress and thus mount an appropriate host defence. The endoplasmic reticulum (ER) contains three branches of stress transducers, i.e. IRE1, PERK, and ATF6 pathways, all of which recognize stress-related disturbances in the function of ER. These transducers trigger a complex signaling network which activates an unfolded protein response (UPR). Interestingly, ER stress transducers can distinguish the intensity of ER stress and induce a dose-dependent UPR, either adaptive response to stress or apoptotic cell death. The efficiency of the stress recognition system and UPR signaling declines during aging. We will discuss the role of ER stress in hormetic regulation of aging process and longevity. © 2010 Elsevier Ireland Ltd. All rights reserved.