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Gallo J.,Palacky University | Vaculova J.,University of Ostrava | Goodman S.B.,Stanford University | Konttinen Y.T.,Institute of Clinical Medicine | Thyssen J.P.,Copenhagen University
Acta Biomaterialia | Year: 2014

Aseptic loosening and osteolysis are the most frequent late complications of total hip arthroplasty (THA) leading to revision of the prosthesis. This review aims to demonstrate how histopathological studies contribute to our understanding of the mechanisms of aseptic loosening/osteolysis development. Only studies analysing periprosthetic tissues retrieved from failed implants in humans were included. Data from 101 studies (5532 patients with failure of THA implants) published in English or German between 1974 and 2013 were included. "Control" samples were reported in 45 of the 101 studies. The most frequently examined tissues were the bone-implant interface membrane and pseudosynovial tissues. Histopathological studies contribute importantly to determination of key cell populations underlying the biological mechanisms of aseptic loosening and osteolysis. The studies demonstrated the key molecules of the host response at the protein level (chemokines, cytokines, nitric oxide metabolites, metalloproteinases). However, these studies also have important limitations. Tissues harvested at revision surgery reflect specifically end-stage failure and may not adequately reveal the evolution of pathophysiological events that lead to prosthetic loosening and osteolysis. One possible solution is to examine tissues harvested from stable total hip arthroplasties that have been revised at various time periods due to dislocation or periprosthetic fracture in multicenter studies. © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. Source

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. Source

Kuo M.T.,University of Houston | Fu S.,University of Houston | Savaraj N.,Veterans Affairs Medical Center | Chen H.H.W.,Institute of Clinical Medicine | Chen H.H.W.,National Cheng Kung University
Cancer Research | Year: 2012

The high-affinity copper transporter (Ctr1; SCLC31A1) plays an important role in regulating copper homeostasis because copper is an essential micronutrient and copper deficiency is detrimental to many important cellular functions, but excess copper is toxic. Recent research has revealed that human copper homeostasis is tightly controlled by interregulatory circuitry involving copper, Sp1, and human (hCtr1). This circuitry uses Sp1 transcription factor as a copper sensor in modulating hCtr1 expression, which in turn controls cellular copper and Sp1 levels in a 3-way mutual regulatory loop. Posttranslational regulation of hCtr1 expression by copper stresses has also been described in the literature. Because hCtr1 can also transport platinum drugs, this finding underscores the important role of hCtr1 in platinum-drug sensitivity in cancer chemotherapy. Consistent with this notion is the finding that elevated hCtr1 expression was associated with favorable treatment outcomes in cisplatin-based cancer chemotherapy. Moreover, cultured cell studies showed that elevated hCtr1 expression can be induced by depleting cellular copper levels, resulting in enhanced cisplatin uptake and its cell-killing activity. A phase I clinical trial using a combination of trientine (a copper chelator) and carboplatin has been carried out with encouraging results. This review discusses new insights into the role of hCtr1 in regulating copper homeostasis and explains how modulating cellular copper availability could influence treatment efficacy in platinum-based cancer chemotherapy through hCtr1 regulation. © 2012 AACR. Source

The nation-wide electronic health record database acts as an interoperable repository of health data obtained throughout citizen contacts with health care providers. This system improves accessibility for citizens and researchers to health data with the ability to assign context to disease development. In that system, individual patients who are members of the large population-based health database can be assessed as individuals or as a population in prospective studies of prospective diseases. © 2011 American Chemical Society. Source

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. Source

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