Terminal Differentiation of Human Fibroblasts is Induced by Radiation

In order to analyze the effect of various kinds of radiation on the terminal differentiation processes of fibroblasts in culture, both human skin and lung fibroblasts were irradiated with electromagnetic non ionizing as well as ionizing radiation in clonal and sparse mass culture systems. As analyzed by cell biological (cell type frequencies), biochemical (collagen synthesis) and molecular markers (expression of protein PIVa) human skin and lung fibroblasts are induced to differentiate prematurely into terminal postmitotic cells. Thus, both electromagnetic and ionizing radiation induce terminal differentiation in cultured cells. These data add some new aspects for the interpretation of radiation effects on cells, e.g., in clinical therapy, as well as for the development of normal tissue responses during early and late effects after radiotherapy

Effects of 3 Weeks of Oral Low-Dose Cobalt on Hemoglobin Mass and Aerobic Performance

Introduction: Cobalt ions (Co2+) stabilize HIFa and increase endogenous erythropoietin (EPO) production creating the possibility that Co2+ supplements (CoSupp) may be used as performance enhancing substances. The aim of this study was to determine the effects of a small oral dosage of CoSupp on hemoglobin mass (Hbmass) and performance with the objective of providing the basis for establishing upper threshold limits of urine [Co2+] to detect CoSupp misuse in sport. Methods: Twenty-four male subjects participated in a double-blind placebo-controlled study. Sixteen received an oral dose of 5mg of ionized Co2+ per day for 3 weeks, and eight served as controls. Blood and urine samples were taken before the study, during the study and up to 3 weeks after CoSupp. Hbmass was determined by the CO-rebreathing method at regular time intervals, and VO2max was determined before and after the CoSupp administration period. Results: In the Co2+ group, Hbmass increased by 2.0 +/- 2.1% (p < 0.001) while all the other analyzed hematological parameters did not show signi fi cant interactions of time and treatment. Hemoglobin concentration ([Hb]) and hematocrit (Hct) tended to increase (p = 0.16, p = 0.1) and also [EPO] showed a similar trend (baseline: 9.5 +/- 3.0, after 2 weeks: 12.4 +/- 5.2 mU/ml). While mean VO2max did not change, there was a trend for a positive relationship between changes in Hbmass and changes in VO2max immediately after CoSupp (r = 0.40, p = 0.11). Urine [Co2+] increased from 0.4 +/- 0.3 to 471.4 +/- 384.1 ng/ml (p < 0.01) and remained signi fi cantly elevated until 2 weeks after cessation. Conclusion: An oral Co2+ dosage of 5 mg/day for 3 weeks effectively increases Hbmass with a tendency to increase hemoglobin concentration ([Hb]) and hematocrit (Hct). Because urine Co2+ concentration remains increased for 2 weeks after cessation, upper limit threshold values for monitoring CoSupp can be established

Psychometric properties of the Patient Assessment of Chronic Illness Care measure (PACIC-5A) among patients with obesity

Abstract Background The Patient Assessment of Chronic Illness Care (PACIC-5A) was developed to assess the satisfaction with patient-provider interaction based on the Chronic Care Model. The additional 5A approach (assess, advise, agree, assist, arrange) allows to score behavioral counseling. The aim of the study was to assess the psychometric properties of the German adaptation of the PACIC-5A questionnaire in a sample of general practitioners (GP) patients with obesity. Methods Analyses were based on data from the study “Five A’s counseling in weight management of obese patients in primary care: a cluster randomized controlled trial (INTERACT)”. Data were collected via standardized questionnaires containing the 26-item version of the PACIC-5A questionnaire. A total of 117 patients with obesity were included in the analyses. Statistical procedures comprised descriptive analyses, the calculation of Cronbach’s alpha, test-retest analyses and factor analyses in order to assess the psychometric properties including reliability and validity of the PACIC-5A. Results The patient’s mean age was 43.4 years and the sample was mostly female (59%). Middle educational level was found for the majority (78%) and the mean Body Mass Index was 38.9 kg/m2. Descriptive analyses revealed a mean PACIC score of 2.33 and 5A sum score of 2.29. Notable floor effects were found. PACIC-5A showed high level of internal consistency (Cronbach’s alphas > 0.9) and exploratory factor analyses resulted in a unidimensional structure. Conclusion The results of this study provide evidence regarding the psychometric properties of the German version of the PACIC-5A used in a sample of GP patients with obesity and make an important contribution to the reliable and valid assessment of the patient-GP interaction with regard to obesity counseling in primary care

Indocyanine green enhanced fluorescence optical imaging in early and very early arthritis patients: a comparative study with magnetic resonance imaging. Arthritis Rheum 2013;65:3036–44

Objective. Indocyanine green-enhanced fluorescence optical imaging (FOI) is a novel diagnostic tool for the assessment of inflammation in arthritis. We undertook this study to compare FOI with magnetic resonance imaging (MRI) in 32 patients with early and very early untreated arthritis (mean disease duration 7.1 months). Methods. FOI images were acquired with the commercially available Xiralite system. Image interpretation was done for an early phase (phase 1), an intermediate phase (phase 2), and a late phase (phase 3), and for an electronically generated composite image. The results were compared with those of clinical examination (960 joints) and contrast (gadolinium)-enhanced 1.5T MRI (382 joints) of the clinically more affected hand. Additionally, we evaluated FOI in a control group of 46 subjects without any signs of inflammatory joint disease Results. With MRI as the reference method, the sensitivity of FOI was 86% and the specificity was 63%, while the composite image, phase 1, and phase 3 reached high specificities (87%, 90%, and 88%, respectively). The results differed considerably between the composite image and the phases. FOI did not detect inflammation in 11 joint regions that showed palmar tenosynovitis on MRI. Intrareader and interreader agreements were moderate to substantial ( ‫؍‬ 0.55-0.73). In the control group, FOI showed positive findings in 5% of normal joints in phase 2. Conclusion. Further multicenter studies will address the question of whether FOI allows sensitive and reliable detection of inflammatory changes in early arthritis, as suggested by our initial findings. If this is confirmed, FOI has the potential to be a sensitive and valuable tool for monitoring disease activity on site in clinical settings and for serving as an outcome parameter in clinical trials

Interleukin 17F Level and Interferon Beta Response in Patients With Multiple Sclerosis

ImportanceHigh serum levels of interleukin 17F (IL-17F) at baseline have been associated with suboptimal response to interferon beta in patients with relapsing-remitting multiple sclerosis.ObjectiveTo further investigate the role of IL-17F in predicting treatment response to interferon beta-1b in patients with relapsing-remitting multiple sclerosis using the Singulex Erenna IL-17F immunoassay.Design, setting, and patientsSerum samples were analyzed from 239 randomly selected patients treated with interferon beta-1b, 250 μg, for at least 2 years in the Betaferon Efficacy Yielding Outcomes of a New Dose Study.ExposureTreatment with interferon beta-1b, 250 μg, for at least 2 years.Main outcome measuresLevels of IL-17F at baseline and month 6 as well as the difference between the IL-17F levels at month 6 and baseline were compared between the following: (1) patients with less disease activity vs more disease activity; (2) patients with no disease activity vs some disease activity; and (3) responders vs nonresponders.ResultsLevels of IL-17F measured at baseline and month 6 did not correlate with lack of response to treatment after 2 years using clinical and magnetic resonance imaging criteria. Relapses and new lesions on magnetic resonance imaging were not associated with pretreatment serum IL-17F levels. When patients with neutralizing antibodies were excluded, the results did not change. All patients with levels of IL-17F greater than 200 pg/mL were associated with poor response with some clinical or radiological activity.Conclusions and relevanceAn increase of IL-17F before and early after treatment with interferon beta-1b was not associated with poor response. These data do not support the value of IL-17F as a treatment response indicator for therapy of patients with multiple sclerosis with interferon beta, although high levels of IL-17F greater than 200 pg/mL may predict nonresponsiveness

Interleukin 17F Level and Interferon Beta Response in Patients With Multiple Sclerosis

IMPORTANCE: High serum levels of interleukin 17F (IL-17F) at baseline have been associated with suboptimal response to interferon beta in patients with relapsing-remitting multiple sclerosis. OBJECTIVE: To further investigate the role of IL-17F in predicting treatment response to interferon beta-1b in patients with relapsing-remitting multiple sclerosis using the Singulex Erenna IL-17F immunoassay. DESIGN, SETTING, AND PATIENTS: Serum samples were analyzed from 239 randomly selected patients treated with interferon beta-1b, 250 µg, for at least 2 years in the Betaferon Efficacy Yielding Outcomes of a New Dose Study. EXPOSURE: Treatment with interferon beta-1b, 250 µg, for at least 2 years. MAIN OUTCOME MEASURES: Levels of IL-17F at baseline and month 6 as well as the difference between the IL-17F levels at month 6 and baseline were compared between the following: (1) patients with less disease activity vs more disease activity; (2) patients with no disease activity vs some disease activity; and (3) responders vs nonresponders. RESULTS: Levels of IL-17F measured at baseline and month 6 did not correlate with lack of response to treatment after 2 years using clinical and magnetic resonance imaging criteria. Relapses and new lesions on magnetic resonance imaging were not associated with pretreatment serum IL-17F levels. When patients with neutralizing antibodies were excluded, the results did not change. All patients with levels of IL-17F greater than 200 pg/mL were associated with poor response with some clinical or radiological activity. CONCLUSIONS AND RELEVANCE: An increase of IL-17F before and early after treatment with interferon beta-1b was not associated with poor response. These data do not support the value of IL-17F as a treatment response indicator for therapy of patients with multiple sclerosis with interferon beta, although high levels of IL-17F greater than 200 pg/mL may predict nonresponsiveness