Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans

Background: Despite the good prognosis of erythema migrans (EM), some patients have persisting symptoms of various character and duration post-treatment. Several factors may affect the clinical outcome of EM, e. g. the early interaction between Borrelia (B.) burgdorferi and the host immune response, the B. burgdorferi genotype, antibiotic treatment as well as other clinical circumstances. Our study was designed to determine whether early cytokine expression in the skin and in peripheral blood in patients with EM is associated with the clinical outcome. Methods: A prospective follow-up study of 109 patients with EM was conducted at the A land Islands, Finland. Symptoms were evaluated at 3, 6, 12 and 24 months post-treatment. Skin biopsies from the EM and healthy skin were immunohistochemically analysed for expression of interleukin (IL)-4, IL-10, IL-12p70 and interferon (IFN)-gamma, as well as for B. burgdorferi DNA. Blood samples were analysed for B. burgdorferi antibodies, allergic predisposition and levels of systemic cytokines. Findings: None of the patients developed late manifestations of Lyme borreliosis. However, at the 6-month follow-up, 7 of 88 patients reported persisting symptoms of diverse character. Compared to asymptomatic patients, these 7 patients showed decreased expression of the Th1-associated cytokine IFN-gamma in the EM biopsies (p = 0.003). B. afzelii DNA was found in 48%, B. garinii in 15% and B. burgdorferi sensu stricto in 1% of the EM biopsies, and species distribution was the same in patients with and without post-treatment symptoms. The two groups did not differ regarding baseline patient characteristics, B. burgdorferi antibodies, allergic predisposition or systemic cytokine levels. Conclusion: Patients with persisting symptoms following an EM show a decreased Th1-type inflammatory response in infected skin early during the infection, which might reflect a dysregulation of the early immune response. This finding supports the importance of an early, local Th1-type response for optimal resolution of LB.Original Publication: Johanna Sjöwall, Linda Fryland, Marika Nordberg, Florence Sjögren, Ulf Garpmo, Christian Jansson, Sten-Anders Carlsson, Sven Bergstrom, Jan Ernerudh, Dag Nyman, Pia Forsberg and Christina Ekerfelt, Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans, 2011, PLOS ONE, (6), 3, 0018220. http://dx.doi.org/10.1371/journal.pone.0018220 Copyright: Public Library of Science (PLoS) http://www.plos.org

Medical proton dosimetry using radioluminescence from aluminium oxide crystals attached to optical-fiber cables

The prime objective of this study is to investigate if radioluminescence (RL) from carbon-doped aluminum oxide (Al2O3:C) crystals potentially can be used for absorbed dose-rate measurements during proton radiotherapy. The RL from two separate (2 mg) Al2O3:C crystals attached to optical-fiber cables were recorded during irradiations in water in a 175 MeV clinical proton beam. The RL response for low-LET protons in the plateau region of the Bragg curve was found to closely resemble that observed for a clinical 6 MV X-ray beam. An identical response was found in the Bragg peak (where the dose-averaged LET is about 4 keV/mu m) for absorbed doses less than 0.3 Gy. For doses in the range of 0.3-3Gy, we observed a significant decrease in luminescence efficiency with LET. At 3 Gy, the luminescence efficiency was about 60% in the Bragg-peak region. The study implies that the RL-signal from Al2O3:C could potentially be suitable for medical proton dosimetry in the 0-0.3 Gy range even without any LET-dependent correction factors. (C) 2007 Elsevier B.V. All rights reserved

Ferrous sulphate gel dosimetry and MRI for proton beam dose measurements

Ferrous sulphate gel dosimetry has the potential for measurement of absorbed dose distributions in proton therapy. The chemical properties of the gel are altered according to the radiation dose and these changes can be evaluated in three dimensions using MRI. The purpose of this work was to investigate the properties of a ferrous gel used with clinical proton beams. The gel was irradiated with both monoenergetic and range-modulated proton beams. It was then evaluated using MRI. The depth dose by means of the 1/T1 distribution was studied and compared with data from a plane-parallel plate ionization chamber. 1/T1 was shown to be proportional to the dose at a mean proton energy of approximately 90 MeV. The dose response was no different from that obtained using photon beams. However, on normalization at the entrance, the relative 1/T1 at the Bragg peak was 15-20% lower than the corresponding ionization chamber data for the monoenergetic proton beam. Better agreement was found for the modulated beam, but with significant differences close to the distal edge of the 1/T1 distribution. The change in sensitivity with depth was explained by means of a linear energy transfer dependence. This property was further studied using Monte Carlo methods

The influence of RBE variations in a clinical proton treatment plan for a hypopharynx cancer

Currently, most clinical range-modulated proton beams are assumed to have a fixed overall relative biological effectiveness (RBE) of 1.1. However, it is well known that the RBE increases with depth in the spread-out Bragg peak (SOBP) and becomes about 10% higher than mid-SOBP RBE at 2 mm from the distal edge (Paganetti 2003 Technol. Cancer Res. Treat. 2 413-26) and can reach values of 1.3-1.4 in vitro at the distal edge (Robertson et al 1975 Cancer 35 1664-77, Courdi et al 1994 Br. J. Radiol. 67 800-4). We present a fast method for applying a variable RBE correction with linear energy transfer (LET) dependent tissue-specific parameters based on the alpha(ref)/beta(ref) ratios suitable for implementation in a treatment planning system. The influence of applying this variable RBE correction on a clinical multiple beam proton dose plan is presented here. The treatment plan is evaluated by RBE weighted dose volume histograms (DVHs) and the calculation of tumour control probability (TCP) and normal tissue complication probability (NTCP) values. The variable RBE correction yields DVHs for the clinical target volumes (CTVs), a primary advanced hypopharynx cancer and subclinical disease in the lymph nodes, that are slightly higher than those achieved by multiplying the absorbed dose with RBE = 1.1. Although, more importantly, the RBE weighted DVH for an organ at risk, the spinal cord is considerably increased for the variable RBE. As the spinal cord in this particular case is located 8 mm behind the planning target volume (PTV) and hence receives only low total doses, the NTCP values are zero in spite of the significant increase in the RBE weighted DVHs for the variable RBE. However, high NTCP values for the non-target normal tissue were obtained when applying the variable RBE correction. As RBE variations tend to be smaller for in vivo systems, this study-based on in vitro data since human tissue RBE values are scarce and have large uncertainties-can be interpreted as showing the upper limits of the possible effects of utilizing a variable RBE correction. In conclusion, the results obtained here still indicate a significant difference in introducing a variable RBE compared to applying a generic RBE of 1.1, suggesting it is worth considering such a correction in clinical proton therapy planning, especially when risk organs are located immediately behind the target volume