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Linköping, Sweden

Dasu A.,County Council of Ostergotland | Dasu A.,Linkoping University | Toma-Dasu I.,University of Stockholm
Medical Physics | Year: 2013

Purpose: To explore the impact of variable proton relative biological effectiveness (RBE) on dose fractionation for clinically relevant situations. A generic RBE = 1.1 is generally used for isoeffect calculations, while experimental studies showed that proton RBE varies with tissue type, dose, and linear energy transfer (LET). Methods: An analytical expression for the LET and α/β dependence of the linear-quadratic (LQ) model has been used for proton simulations in parallel with the assumption of a generic RBE = 1.1. Calculations have been performed for ranges of LET values and fractionation sensitivities to describe clinically relevant cases, such as the treatment of head and neck and prostate tumors. Isoeffect calculations were compared with predictions from a generic RBE value and reported clinical results. Results: The generic RBE = 1.1 appears to be a reasonable estimate for the proton RBE of rapidly growing tissues irradiated with low LET radiation. However, the use of a variable RBE predicts larger differences for tissues with low α/β (both tumor and normal) and at low doses per fraction. In some situations these differences may appear in contrast to the findings from photon studies highlighting the importance of accurate accounting for the radiobiological effectiveness of protons. Furthermore, the use of variable RBE leads to closer predictions to clinical results. Conclusions: The LET dependence of the RBE has a strong impact on the predicted effectiveness of fractionated proton radiotherapy. The magnitude of the effect is modulated by the fractionation sensitivity and the fractional dose indicating the need for accurate analyses both in the target and around it. Care should therefore be employed for changing clinical fractionation patterns or when analyzing results from clinical studies for this type of radiation. © 2013 American Association of Physicists in Medicine.

Welander J.,County Council of Ostergotland | Andreasson A.,Karolinska University Hospital | Juhlin C.C.,Karolinska University Hospital | Wiseman R.W.,University of Wisconsin - Madison | And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: Pheochromocytomas and paragangliomas have a highly diverse genetic background, with a third of the cases carrying a germline mutation in 1 of 14 identified genes. Objective: This study aimed to evaluate next-generation sequencing for more efficient genetic testing of pheochromocytoma and paraganglioma and to establish germline and somatic mutation frequencies for all known susceptibility genes. Design: A targeted next-generation sequencing approach on an Illumina MiSeq instrument was used for a mutation analysis in 86 unselected pheochromocytoma and paraganglioma tumor samples. The study included the genes EGLN1, EPAS1, KIF1Bβ, MAX, MEN1, NF1, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and VHL. Results were verified in tumor and constitutional DNA with Sanger sequencing. Results: In all cases with clinical syndromes or known germline mutations, a mutation was detected in the expected gene. Among 68 nonfamilial tumors, 32 mutations were identified in 28 of the samples (41%), including germline mutations in EGLN1, KIF1Bβ, SDHA, SDHB, and TMEM127 and somatic mutations in EPAS1, KIF1Bβ, MAX, NF1, RET, and VHL, including one double monoallelic EPAS1 mutation. Conclusions: Targeted next-generation sequencing proved to be fast and cost effective for the genetic analysis of pheochromocytoma and paraganglioma. More than half of the tumors harbored mutations in the investigated genes. Notably, 7% of the apparently sporadic cases carried germline mutations, highlighting the importance of comprehensive genetic testing. KIF1Bβ, which previously has not been investigated in a large cohort, appears to be an equally important tumor suppressor as MAX and TMEM127 and could be considered for genetic testing of these patients. Copyright © 2014 by the Endocrine Society.

Eriksson P.,Linkoping University | Sandell C.,County Council of Ostergotland | Backteman K.,Linkoping University | Ernerudh J.,Linkoping University
Journal of Rheumatology | Year: 2012

Objective. T helper cells lacking CD28 (CD4+CD28-) have been implicated in the pathogenesis of granulomatosis with polyangiitis (Wegener; GPA) and microscopic polyangiitis (MPA). Expansions of CD4+CD28- and CD8+CD28- T cells have also been associated with latent cytomegalovirus (CMV) infection. We assessed these T cells with and without coexpression of CD56 and CD57 in relation to vasculitis as well as CMV status. Methods. Blood from 16 patients in remission (12 GPA, 4 MPA), 18 patients with active vasculitis (12 GPA, 6 MPA), and 20 healthy controls was examined by flow cytometry for expression of CD4, CD8, CD56, CD57, and CD28 on T cells. The influence of age, CMV status, presence of disease, and disease activity on T cell subpopulations was tested with multiple regression analyses. Results. In active vasculitis, the total numbers and proportion of lymphocytes were decreased. Total numbers of CD4+, CD8+, CD4+CD28-, CD8+CD28-, CD4+CD57+, and CD8+CD57+ T subpopulations were decreased to the same extent, implying unchanged proportions. Multivariate analyses showed no associations between vasculitis and CD28- or CD57+ T subpopulations, whereas immunoglobulin G antibodies to CMV were associated with expanded proportions of CD28- and CD57+ T cells, in both the CD4+ and the CD8+ compartments. Conclusion. CD28- and CD57+ T cells were associated with latent CMV infection and not with a diagnosis of GPA or MPA. Vasculitis assessment should include CMV status. The Journal of Rheumatology Copyright © 2012. All rights reserved.

Ohrn A.,Linkoping University | Olai A.,Linkoping University | Rutberg H.,County Council of Ostergotland | Nilsen P.,Linkoping University | Tropp H.,Linkoping University
Acta Orthopaedica | Year: 2011

Background and purpose: Our knowledge of complications and adverse events in spinal surgery is limited, especially concerning incidence and consequences. We therefore investigated adverse events in spine surgery in Sweden by comparing patient claims data from the County Councils' Mutual Insurance Company register with data from the National Swedish Spine Register (Swespine). Methods: We analyzed patient claims (n = 182) to the insurance company after spine surgery performed between 2003 and 2005. The medical records of the patients filing these claims were reviewed and compared with Swespine data for the same period. Results: Two-thirds (119/182, 65%) of patients who claimed economic compensation from the insurance company were registered in Swespine. Of the 210 complications associated with these 182 claims, only 74 were listed in Swespine. The most common causes of compensated injuries (n = 139) were dural lesions (n = 40) and wound infections (n = 30). Clinical outcome based on global assessment, leg pain, disability, and quality of health was worse for patients who claimed economic compensation than for the total group of Swespine patients. Interpretation: We found considerable under-reporting of complications in Swespine. Dural lesions and infections were not well recorded, although they were important reasons for problems and contributed to high levels of disability. By analyzing data from more than one source, we obtained a better understanding of the patterns of adverse events and outcomes after spine surgery. Copyright: © Nordic Orthopaedic Federation.

Wallstrom A.,County Council of Ostergotland | Frisman G.H.,Operations and Speciality Surgery Center
Journal of Clinical Nursing | Year: 2014

Aims and objectives: To determine how restored gastrointestinal motility can be accelerated after colorectal surgery. Background: Regaining normal bowel functions after surgery is described as unexpectedly problematic. Postoperative ileus is expected after all surgery where the peritoneum is entered, and the length of surgery has little or no impact in terms of the duration of Postoperative ileus. There is some speculation about the best way to facilitate bowel motility after colorectal surgery. Design: A systematic review. Method: The computerised databases Medline, Scopus and CINAHL were searched to locate randomised, controlled trials by using the following keywords: colorectal surgery, postoperative ileus, recovery of function and gastrointestinal motility. The systematic search was limited to studies published between January 2002-January 2012. Reference lists were also searched manually. Results: A total of 34 randomised, controlled trials were included in the review. Recovery of gastrointestinal motility was accelerated when one of the following forms of treatment was administered: probiotics, early feeding in combination with multimodal regimens, pentoxifylline, flurbiprofen, valdecoxib, ketorolac, clonidine, ropivacaine, lidocaine or spinal analgesia. Gum chewing, preoperative carbohydrate loading, bisacodyl and Doppler-guided fluid management have an uncertain effect on bowel motility. The use of nonpharmacological interventions, intrathecal morphine, restricted fluid therapy and choline citrate yielded no significant acceleration in bowel motility. Conclusions: A multimodal treatment, where the use of morphine is restricted, seems to be the best way to accelerate the recovery of gastrointestinal bowel motility. However, more studies are required to optimise the multimodal protocol. Relevance to clinical practice: The early return of bowel functions leads to quicker overall postoperative recovery, which may ease patient discomfort and decrease hospitalisation costs. © 2013 John Wiley & Sons Ltd.

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