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Sökning: WFRF:(Nittby Henrietta)

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1.
  • AHLSTEDT, JONATAN, et al. (författare)
  • Effect of Blockade of Indoleamine 2, 3-dioxygenase in Conjunction with Single Fraction Irradiation in Rat Glioma
  • 2015
  • Ingår i: Jacobs journal of radiation oncology. - 2376-9424. ; 2:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Glioblastoma (GBM), or WHO Astrocytoma grade IV, is the most common primary brain tumour in adults. GBM is shown to escape host immune surveillance through many paths, of which expression of indoleamine 2,3-dioxygenase (IDO), leading to induction and accumulation of regulatory T-cells in the tumour microenvironment, has been shown to be of importance. 1-Methyl tryptophan (1-MT) is an inhibitor of IDO that has been shown to have a positive effect on survival in experimental models of GBM. In this study, we evaluate the effect of combined single-fraction irradiation of 8 Gy with 1-MT treatment in Fischer rats carrying the RG2 glioma model. We also investigate expression of IDO in the RG2 model before and after irradiation. Thirty-three Fischer 344 rats received intracranial inoculations of RG2 tumour cells, and were treated with either intraperito-neal 1-MT, 8 Gy single-fraction radiotherapy, or a combination of the two. Survival in the combined treatment group (29 days ± 0.75) was significantly better than controls (20 ± 0.99, p=0.015) and radiation only (17 ± 2.75, p=0.014). Survival was also better with combined treatment compared to 1-MT only but the difference was non-significant (18 ± 0.28, p=0.215).Our results add to the growing base of evidence suggesting 1-methyl-tryptophan is an attractive candidate for clinical investi-gation in patients carrying highly malignant astrocytoma, especially in combination with radiation treatment, even in singular fraction settings.
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2.
  • Ahlstedt, Jonatan, et al. (författare)
  • Evaluating vacquinol-1 in rats carrying glioblastoma models RG2 and NS1
  • 2018
  • Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:9, s. 8391-8399
  • Tidskriftsartikel (refereegranskat)abstract
    • Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, and available experimental and routine therapies result in limited survival benefits. A vulnerability of GBM cells to catastrophic vacuolization and cell death, a process termed methuosis, induced by Vacquinol-1 (VQ-1) has been described earlier. In the present study, we investigate the efficacy of VQ-1 treatment in two syngeneic rat GBM models, RG2 and NS1. VQ-1 treatment affected growth of both RG2 and NS1 cells in vitro. Intracranially, significant reduction in RG2 tumor size was observed, although no effect was seen on overall survival. No survival advantage or effect on tumor size was seen in animals carrying the NS1 models compared to untreated controls. Furthermore, immunological staining of FOXP3, CD4 and CD8 showed no marked difference in immune cell infiltrate in tumor environment following treatment. Taken together, a survival advantage of VQ-1 treatment alone could not be demonstrated here, even though some effect upon tumor size was seen. Staining for immune cell markers did not indicate that VQ-1 either reduced or increased host anti-tumor immune response.
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3.
  • Ahlstedt, Jonatan, et al. (författare)
  • Growth pattern of experimental glioblastoma
  • 2020
  • Ingår i: Histology and Histopathology. - 1699-5848. ; 35:8, s. 871-886
  • Tidskriftsartikel (refereegranskat)abstract
    • Glioblastoma multiforme (GBM) is an aggressive primary brain malignancy with a very poor prognosis. Researchers employ animal models to develop potential therapies. It is important that these models have clinical relevance. This means that old models, propagated for decades in cultures, should be questioned. Parameters to be evaluated include whether animals are immune competent or not, the infiltrative growth pattern of the tumor, tumor volume resulting in symptoms and growth rate.We here describe the growth pattern of an experimental glioblastoma model in detail with GFP positive glioblastoma cells in fully immune competent animalsand study tumor growth rate and tumor mass as a function of time from inoculation.We were able to correlate findings made with classical immunohistochemistry and MR findings. The tumor growth rate was fitted by a Gompertz function. The model predicted the time until onset of symptoms for 5000 inoculated cells to 18.7±0.4 days, and the tumor mass at days 10 and 14, which are commonly used as the start of treatment in therapeutic studies, were 5.97±0.62 mg and 29.1±3.0 mg, respectively.We want to raise the question regarding the clinical relevance of the outline of glioblastoma experiments, where treatment is ofteninitiated at a very early stage. The approach presented here could potentially be modified to gain information also from other tumor models.
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4.
  • Ahlstedt, Jonatan, et al. (författare)
  • Increased effect of two-fraction radiotherapy in conjunction with IDO1 inhibition in experimental glioblastoma
  • 2020
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives The aim of the study was to investigate therapeutic efficacy of single-or two-fraction radiotherapy in conjunction with IDO1-inhibition in a syngeneic rat glioblastoma model. IDO is known to cause immunosuppression through breakdown of tryptophan in the tumor microenvironment. Methods Gene expression analyses of IDO in glioblastoma were performed with data from publicly available datasets. Fractionation studies were done on animals to evaluate tumor size, immune cell infiltration of tumors and serum profile on day 18 after tumor inoculation. Survival analyses were done with animals carrying intracranial glioblastomas comparing twofraction radiotherapy+IDO1-inhibition to controls. IDO inhibition was achieved by administration of 1-methyl tryptophan (1-MT), and radiotherapy (RT) was delivered in doses of 8Gy. Results The expression of IDO1 was increased on gene level in glioblastoma stem cells. Tumor size was significantly reduced in animals treated with 1-MT+RTx 2 (both long and short intervals, i.e. 7 and 4 days between the treatments) as compared to control animals, animals treated with only 1-MT or animals treated with 1-MT+RTx1. Serum levels of IL-1A were significantly altered in all treated animals as compared to control animals. Survival was significantly increased in the animals treated with 1-MT+RTx2 (7-day interval) compared to control animals. Conclusions Addition of two-fraction RT to IDO1 inhibition with 1-MT significantly reduced tumor size in animals with glioblastoma. Survival was significantly increased in animals treated with twofractioned RT+1-MT as compared to untreated controls increased significantly. Advances in knowledge The currently used combination of only two fractions of radiotherapy and immune therapy is a promising area of research, increasing efficacy compared to single fraction irradiation, while potentially lowering radiation side effects compared to radiation in current clinical practice.
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5.
  • Bartek, Jiri, Jr., et al. (författare)
  • Scandinavian Multicenter Acute Subdural Hematoma (SMASH) Study : Study Protocol for a Multinational Population-Based Consecutive Cohort
  • 2019
  • Ingår i: Neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 0148-396X .- 1524-4040. ; 84:3, s. 799-803
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUNDTraumatic acute subdural hematomas (ASDHs) are associated with high rate of morbidity and mortality, especially in elderly individuals. However, recent reports indicate that the morbidity and mortality rates might have improved.OBJECTIVETo evaluate postoperative (30-d) mortality in younger vs elderly (70 yr) patients with ASDH. Comparing younger and elderly patients, the secondary objectives are morbidity patterns of care and 6 mo outcome according to Glasgow outcome scale (GOS). Finally, in patients with traumatic ASDH, we aim to provide prognostic variables.METHODS This is a large-scale population-based Scandinavian study including all neurosurgical departments in Denmark and Sweden. All adult (18 yr) patients surgically treated between 2010 and 2014 for a traumatic ASDH in Denmark and Sweden will be included. Identification at clinicaltrials.gov is NCT03284190.EXPECTED OUTCOMESWe expect to provide data on potential differences between younger vs elderly patients in terms of mortality and morbidity. We hypothesize that elderly patients selected for surgery have a similar pattern of care as compared with younger patients. We will provide functional outcome in terms of GOS at 6 mo in younger vs elderly patients undergoing ASDH evacuation. Finally, clinical useful prognostic factors for favorable (GOS 4-5) vs unfavorable (GOS 1-3) will be identified.DISCUSSION An improved understanding of the clinical outcome, treatment and resource allocation, clinical course, and the prognostic factors of traumatic ASDH will allow neurosurgeons to make better treatment decisions.
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6.
  • Bartek, Jiri, Jr, et al. (författare)
  • Neurokirurgin alltjämt kärnan i behandlingen av hjärntumörer : [Neurosurgery still pivotal in the diagnostics and treatment of brain tumor patients]
  • 2023
  • Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 120
  • Tidskriftsartikel (refereegranskat)abstract
    • Behandling av hjärntumörer görs i samverkan mellan flera medicinska discipliner: neurokirurgi, onkologi, neurologi, neuropatologi, neuroradiologi och rehabiliteringsmedicin.Symtom som talar för förhöjt intrakraniellt tryck, såsom kraftig huvudvärk, illamående, kräkningar och papillödem, bör leda till snabb utredning och kontakt med neurokirurg. Förbättrad preoperativ kartläggning av tumören samt angränsande anatomiska och funktionella hjärnområden tillsammans med avancerad mikrokirurgisk teknik, intraoperativ monitorering och visualisering samt nya minimalinvasiva tekniker gör operationer säkrare, och det är i dag möjligt att utföra ingrepp som tidigare ansågs omöjliga eller alltför riskabla.
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7.
  • Bartek, Jiri, et al. (författare)
  • Neurosurgery still pivotal in the diagnostics and treatment of brain tumor patients
  • 2023
  • Ingår i: Läkartidningen. - 0023-7205. ; 120
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Treatment of adult patients with brain tumors is a multi-disciplinary effort involving several medical disciplines: neurosurgery, oncology, neurology, neuropathology, neuroradiology, and rehabilitation medicine. While the brain tumor field has gone through vast diagnostical changes during the last decade, the hopes of similar achievements in the systemic treatment of these patients with new methods have so far not been fulfilled. As such, neurosurgery still has a pivotal role in the diagnostics and treatment of brain tumor patients. Improved preoperative evaluation of the tumor and adjacent anatomical and functional brain areas, together with advanced microsurgical techniques, intraoperative mapping and monitoring, as well as new minimally invasive techniques, makes brain tumor surgery safer. Indeed, it is now possible to safely operate patients previously considered to have too unfavorable risk-benefit ratio. This article aims at presenting an overview of current neurosurgical treatments of brain tumors.
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8.
  • Ceberg, Crister, et al. (författare)
  • Photon activation therapy of RG2 glioma carrying Fischer rats using stable thallium and monochromatic synchrotron radiation.
  • 2012
  • Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 57:24, s. 8377-8391
  • Tidskriftsartikel (refereegranskat)abstract
    • 75 RG2 glioma-carrying Fischer rats were treated by photon activation therapy (PAT) with monochromatic synchrotron radiation and stable thallium. Three groups were treated with thallium in combination with radiation at different energy; immediately below and above the thallium K-edge, and at 50 keV. Three control groups were given irradiation only, thallium only, or no treatment at all. For animals receiving thallium in combination with radiation to 15 Gy at 50 keV, the median survival time was 30 days, which was 67% longer than for the untreated controls (p = 0.0020) and 36% longer than for the group treated with radiation alone (not significant). Treatment with thallium and radiation at the higher energy levels were not effective at the given absorbed dose and thallium concentration. In the groups treated at 50 keV and above the K-edge, several animals exhibited extensive and sometimes contra-lateral edema, neuronal death and frank tissue necrosis. No such marked changes were seen in the other groups. The results were discussed with reference to Monte Carlo calculated electron energy spectra and dose enhancement factors.
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9.
  • Cederberg, David, et al. (författare)
  • Extreme intracranial pressure elevation > 90 mmHg in an awake patient with primary CNS lymphoma—case report
  • 2020
  • Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 162:8, s. 1819-1823
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe a patient with primary CNS lymphomas, awake despite an extreme ICP elevation. A 48-year-old woman presented with headache since 1 month, and bilateral papillary edema was observed. Magnetic resonance imaging revealed diffuse infiltration around the petrous bone. Following external ventricular drainage (EVD) placement, ICP levels of > 90 mmHg were recorded while the patient was fully awake. Cytology revealed an aggressive primary CNS lymphoma. Cerebrospinal fluid (CSF) drainage at high opening pressure levels was required. We conclude that extreme ICP elevations, treatable by CSF drainage, can be observed without a reduced level of consciousness.
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10.
  • Chakwizira, Arthur, et al. (författare)
  • Mathematical modelling of the synergistic combination of radiotherapy and indoleamine-2,3-dioxygenase (IDO) inhibitory immunotherapy against glioblastoma
  • 2018
  • Ingår i: British Journal of Radiology. - : British Institute of Radiology. - 0007-1285 .- 1748-880X. ; 91:1087
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Recent research has shown that combining radiotherapy and immunotherapy can counteract the ability of cancer to evade and suppress the native immune system. To optimise the synergy of the combined therapies, factors such as radiation dose and fractionation must be considered, alongside numerous parameters resulting from the complexity of cancer-immune system interactions. It is instructive to use mathematical models to tackle this problem. Methods: In this work, we adapted a model primarily to describe the synergistic effect between single-fraction radiotherapy and immunotherapy (1-methyl tryptophan) observed in previous experiments with glioblastoma-carrying rats. We also showed how the model can be used to generate hypotheses on the outcome of other treatment fractionation schemes. Results: The model successfully reproduced the results of the experiments. Moreover, it provided support for the hypothesis that, for a given biologically effective dose, the efficacy of the combination therapy and the synergy between the two therapies are favoured by the administration of radiotherapy in a hypofractionated regime. Furthermore, for a double-fraction irradiation regimen, the synergy is favoured by a short time interval between the treatment fractions. Conclusion: It was concluded that the model could be fitted to reproduce the experimental data well within its uncertainties. It was also demonstrated that the fitted model can be used to form hypotheses to be validated by further pre-clinical experiments. Advances in knowledge: The results of this work support the hypothesis that the synergetic action of combined radiotherapy and immunotherapy is favoured by using a hypofractionated radiation treatment regimen, given over a short time interval.
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11.
  • Drake, Mattias, et al. (författare)
  • Swedish trial on embolization of middle meningeal artery versus surgical evacuation in chronic subdural hematoma (SWEMMA)—a national 12-month multi-center randomized controlled superiority trial with parallel group assignment, open treatment allocation and blinded clinical outcome assessment
  • 2022
  • Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Chronic subdural hematoma (cSDH) is one of the most common neurosurgical disorders and the incidence is rising. The routine treatment is neurosurgical hematoma evacuation, which is associated with recurrence rates up to 10–25%. In recent years, endovascular embolization of the middle meningeal artery (eMMA) has garnered much attention due to recurrence rates as low as < 5%. Several randomized controlled trials are planned or ongoing. In most of these trials, conventional neurosurgical treatment with or without adjunctive endovascular embolization is compared. The proposed trial aims to conduct a head-to-head comparison between neurosurgical and endovascular treatment as stand-alone treatments. Methods: The trial is academically driven and funded within existing public healthcare systems and infrastructure. Patients with uni- or bilateral cSDH, presenting with mild-to moderate symptoms, and admitted to neurosurgery on clinical grounds will be offered participation. Subjects are randomized 1:1 between conventional neurosurgical treatment (control) and endovascular embolization of the middle meningeal artery (intervention). Primary endpoint is reoperation due to clinically and/or radiologically significant recurrence within 3 months. Secondary endpoints include safety, technical success rate, neurological disability, and quality of life. Discussion: There are mounting retrospective data suggesting eMMA, as sole treatment or as an adjunctive to neurosurgery for cSDH, is safe and effective with a reoperation rate lower than neurosurgical hematoma evacuation alone. If randomized controlled trials confirm these findings, there is a potential for a paradigm shift in the treatment of cSDH where a minimally invasive procedure can replace open surgery in a large and oftentimes old and fragile patient cohort. Trial registration: ClinicalTrials.gov, ClinicalTrials.gov Identifier NCT05267184. Registered March 4, 2022.
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12.
  • Fahlström, Andreas, et al. (författare)
  • A grading scale for surgically treated patients with spontaneous supratentorial intracerebral hemorrhage : The Surgical Swedish ICH Score
  • 2020
  • Ingår i: Journal of Neurosurgery. - Rolling Meadows, IL United States : American Association of Neurological Surgeons. - 0022-3085 .- 1933-0693. ; 133:3, s. 800-807
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE The authors aimed to develop the first clinical grading scale for patients with surgically treated spontaneous supratentorial intracerebral hemorrhage (ICH). METHODS A nationwide multicenter study including 401 ICH patients surgically treated by craniotomy and evacuation of a spontaneous supratentorial ICH was conducted between January 1, 2011, and December 31, 2015. All neurosurgical centers in Sweden were included. All medical records and neuroimaging studies were retrospectively reviewed. Independent predictors of 30-day mortality were identified by logistic regression. A risk stratification scale (the Surgical Swedish ICH [SwICH] Score) was developed using weighting of independent predictors based on strength of association. RESULTS Factors independently associated with 30-day mortality were Glasgow Coma Scale (GCS) score (p = 0.00015), ICH volume ≥ 50 mL (p = 0.031), patient age ≥ 75 years (p = 0.0056), prior myocardial infarction (MI) (p = 0.00081), and type 2 diabetes (p = 0.0093). The Surgical SwICH Score was the sum of individual points assigned as follows: GCS score 15–13 (0 points), 12–5 (1 point), 4–3 (2 points); age ≥ 75 years (1 point); ICH volume ≥ 50 mL (1 point); type 2 diabetes (1 point); prior MI (1 point). Each increase in the Surgical SwICH Score was associated with a progressively increased 30-day mortality (p = 0.0002). No patient with a Surgical SwICH Score of 0 died, whereas the 30-day mortality rates for patients with Surgical SwICH Scores of 1, 2, 3, and 4 were 5%, 12%, 31%, and 58%, respectively. CONCLUSIONS The Surgical SwICH Score is a predictor of 30-day mortality in patients treated surgically for spontaneous supratentorial ICH. External validation is needed to assess the predictive value as well as the generalizability of the Surgical SwICH Score.
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13.
  • Fahlström, Andreas, et al. (författare)
  • Differences in neurosurgical treatment of intracerebral haemorrhage: a nation-wide observational study of 578 consecutive patients
  • 2019
  • Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 161:5, s. 955-965
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundSupratentorial intracerebral haemorrhage (ICH) carries an excessive mortality and morbidity. Although surgical ICH treatment can be life-saving, the indications for surgery in larger cohorts of ICH patients are controversial and not well defined. We hypothesised that surgical indications vary substantially among neurosurgical centres in Sweden.ObjectiveIn this nation-wide retrospective observational study, differences in treatment strategies among all neurosurgical departments in Sweden were evaluated.MethodsPatient records, neuroimaging and clinical outcome focused on 30-day mortality were collected on each operated ICH patient treated at any of the six neurosurgical centres in Sweden from 1 January 2011 to 31 December 2015.ResultsIn total, 578 consecutive surgically treated ICH patients were evaluated. There was a similar incidence of surgical treatment among different neurosurgical catchment areas. Patient selection for surgery was similar among the centres in terms of patient age, pre-operative level of consciousness and co-morbidities, but differed in ICH volume, proportion of deep-seated vs. lobar ICH and pre-operative signs of herniation (p<.05). Post-operative patient management strategies, including the use of ICP-monitoring, CSF-drainage and mechanical ventilation, varied among centres (p<.05). The 30-day mortality ranged between 10 and 28%.ConclusionsAlthough indications for surgical treatment of ICH in the six Swedish neurosurgical centres were homogenous with regard to age and pre-operative level of consciousness, important differences in ICH volume, proportion of deep-seated haemorrhages and pre-operative signs of herniation were observed, and there was a substantial variability in post-operative management. The present results reflect the need for refined evidence-based guidelines for surgical management of ICH.
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14.
  • Förnvik, Karolina, et al. (författare)
  • Anti-C1-inactivator treatment of glioblastoma
  • 2018
  • Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:100, s. 37421-37428
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Glioblastoma multiforme (GBM) or astrocytoma grade IV is the most common type of primary brain tumor in adults. In the present study, we investigate the role of the complement system in the glioblastoma situation in an experimental model, since we have previously been able to show a blockade of this system in the glioblastoma setting. Technique and results: A GFP-positive glioblastoma cell line was used to induce glioblastomas subcutaneously in rats (n=42). Antibodies against C1-Inactivator (C1-IA) were used to try to re-activate the complement system. We were able to demonstrate an increased survival in rats treated with anti-C1-IA with an intratumoral route, and we could establish the same the results in a second series. Serum analyses revealed decreased levels of IL-1b and GM-CSF in animals 24 days after tumor cell inoculation in the anti-C1-IA group when compared to controls. Immunohistochemistry revealed decreased expression of C1-IA following treatment. Interpretation: These results are in line with our previous work showing an upregulation of C1-IA, which is able to block the classical complement pathway, in glioblastomas. Treatment with antibodies against C1-IA seems to be beneficial in the glioblastoma situation, and no side effects could be seen in our experiments.
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15.
  • Förnvik, Karolina, et al. (författare)
  • C1-inactivator is upregulated in glioblastoma
  • 2017
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Glioblastoma is the most common and aggressive type of primary brain tumor in adults. A key problem is the capacity of glioma cells to inactivate the body’s immune response. The complement system acts as a functional bridge between the innate and adaptive immune response. Still, the role of the complement system has almost been forgotten in glioma research. In our present study, we hypothesize that C1 inactivator (C1-IA) is upregulated in astrocytoma grade IV, and that its inhibition of the complement system has beneficial effects upon survival. Methods and results: We have explored this hypothesis both on gene and protein levels and found an upregulation of C1-IA in human glioblastoma cells using data from a publicly available database and our own mRNA material from glioblastoma patients. Furthermore, we demonstrated the presence of C1-IA by using immunohistochemistry on glioma cells from both humans and rats in vitro. Finally, we could demonstrate a significantly increased survival in vivo in animals inoculated intracerebrally with glioma cells pre-coated with C1-IA antibodies as compared to control animals. Conclusions: Our findings indicate that overexpression of C1-IA is present in glioblastomas. This could be demonstrated both at the gene level from patients with glioblastoma, on mRNA level and with immunohistochemistry. Treatment with antibodies against C1-IA had beneficial effects on survival when tested in vivo.
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16.
  • Förnvik, Karolina, et al. (författare)
  • ITPP treatment of RG2 glioblastoma in a rat model
  • 2016
  • Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 36:11, s. 5751-5755
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Inositol trispyrophosphate (ITPP) has been shown to reduce tumour growth in different animal cancer models, as well as of human U87 glioma cells grafted onto chick chorioallantoic membrane (CAM). The aim of this study was to establish whether ITPP crosses the blood-brain barrier and whether it halts the growth of RG2 glioblastoma tumour. Materials and Methods: A model comprising of Fischer 344 rats was chosen and RG2 cells were implanted either intracranially, or subcutaneously on the left hind leg, and the animals were treated with ITPP either intraperitoneally, intravenously or both routes combined. Overall survival was then calculated. Results: No prolonged survival was seen in animals treated with ITPP. The route of ITPP administration did not affect outcome. Conclusion: ITPP had no favourable effect upon survival in our animal model with RG2 glioblastoma tumours in Fischer 344 rats.
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17.
  • Förnvik, Karolina, et al. (författare)
  • What is the role of CRP in glioblastoma?
  • 2021
  • Ingår i: Cancer Treatment and Research Communications. - : Elsevier BV. - 2468-2942. ; 26
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Glioblastoma is the most common primary malignant brain tumor in adults. Previous studies have suggested that CRP (C-reactive protein) could serve as a biomarker candidate as well as a prognostic factor in glioblastoma patients, and we here further investigate its potential role. Materials and methods: Publicly available datasets were used to compare gene expression between brain samples from glioblastoma patients and non-tumor tissue. The structure of CRP was compared between humans and rats. Glioblastoma cells from humans and rats were stained with anti-CRP. Fischer 344 rats were inoculated with syngeneic glioblastoma cells pre-coated with anti-CRP, and survival was monitored. CRP concentration in rats carrying glioblastoma was followed. Results: CRP was upregulated on one locus on gene level in glioblastoma tissue as compared to non-tumor brain tissue, but not in glioma stem cells as compared to neural stem cells. The structure of the CRP protein was a characteristic pentamer in both humans and rats. Both human and rat glioblastoma cells were clearly positive for anti-CRP staining. Pre-coating of glioblastoma cells with anti-CRP antibodies did not affect survival in rats with intracranial tumors. Serum levels of CRP increased during tumor progression but did not reach significantly different levels. Conclusions: Both human and rat glioblastoma cells could be stained with anti-CRP antibodies in vitro. In a syngeneic glioblastoma rat model we could see an increase in serum CRP during tumor progression, but coating glioblastoma cells with anti-CRP antibodies did not provide any survival change for the animals.
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18.
  • Grafström, Gustav, et al. (författare)
  • Histopathological examinations of rat brains after long-term exposure to GSM-900 mobile phone radiation.
  • 2008
  • Ingår i: Brain Research Bulletin. - : Elsevier BV. - 0361-9230. ; 77, s. 257-263
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to mimic the real life situation, with often life-long exposure to the electromagnetic fields emitted by mobile phones, we have investigated in a rat model the effects of repeated exposures under a long period to Global System for Mobile Communication-900MHz (GSM-900) radiation. Out of a total of 56 rats, 32 were exposed once weekly in a 2-h period, for totally 55 weeks, at different average whole-body specific absorption rates (SAR) (of in average 0.6 and 60mW/kg at the initiation of the experimental period). The animals were exposed in a transverse electromagnetic transmission line chamber (TEM-cell) to radiation emitted by a GSM-900 test phone. Sixteen animals were sham exposed and eight animals were cage controls, which never left the animal house. After behavioural tests, 5-7 weeks after the last exposure, the brains were evaluated for histopathological alterations such as albumin extravasation, dark neurons, lipofuscin aggregation and signs of cytoskeletal and neuritic neuronal changes of the type seen in human ageing. In this study, no significant alteration of any these histopathological parameters was found, when comparing the GSM exposed animals to the sham exposed controls.
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19.
  • Jakobsson, Johan, et al. (författare)
  • Long-Term Functional Outcome and Quality of Life After Surgical Evacuation of Spontaneous Supratentorial Intracerebral Hemorrhage: Results from a Swedish Nationwide Cohort
  • 2022
  • Ingår i: World Neurosurgery. - : Elsevier BV. - 1878-8750 .- 1878-8769. ; 70
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate long-term survival, neurologic outcome, and quality of life in patients with spontaneous supratentorial intracerebral hemorrhage (ICH) treated with craniotomy and hematoma evacuation. Methods: A nationwide multicenter retrospective analysis of 341 patients who underwent craniotomy and evacuation of supratentorial ICH between January 1, 2011, and December 31, 2015, was performed. Baseline characteristics associated with 6-month mortality and long-term mortality were investigated. Survivors received a questionnaire about their state of health from which EuroQol 5D (EQ-5D) and modified Rankin scale (mRS) were obtained. Predictors of mortality, unfavorable outcome, and life quality were analyzed. Results: The mean follow-up time was 55.2 months. Predictors of 6-month mortality in multiple regression analysis were age ≥75 years, previous myocardial infarction, lower level of consciousness, and mechanical ventilation. Predictors of long-term mortality were higher age and mechanical ventilation. At follow-up, 49.5% of survivors had a favorable neurologic outcome (mRS ≤3). Predictors of an unfavorable functional outcome were higher age and ICH volume ≥50 mL. The mean EQ-5D health index was 0.719, and the mean EQ-5D visual analog scale score was 53.9. In multiple regression, only a higher mRS score was significantly associated with worse life quality. Conclusions: Knowledge about survival, functional outcome, and life quality as well as their predictors in this specific patient group is previously primarily described in short-term follow-up. This multicenter study provides novel information in the long-term perspective, which is important for improved surgical decision-making and prognostication.
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20.
  • Konradsson, Elise, et al. (författare)
  • Comparable Long-Term Tumor Control for Hypofractionated FLASH Versus Conventional Radiation Therapy in an Immunocompetent Rat Glioma Model
  • 2022
  • Ingår i: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 7:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To ensure a clinical translation of FLASH radiation therapy (FLASH-RT) for a specific tumor type, studies on tumor control and toxicity within the same biological system are needed. In this study, our objective was to evaluate tumor control and toxicity for hypofractionated FLASH-RT and conventional radiation therapy (CONV-RT) in an immunocompetent rat glioma model. Methods and Materials: Fisher 344 rats (N = 68) were inoculated subcutaneously with NS1 glioma cells and randomized into groups (n = 9-10 per group). CONV-RT (∼8 Gy/min) or FLASH-RT (70-90 Gy/s) was administered in 3 fractions of either 8 Gy, 12.5 Gy, or 15 Gy using a 10-MeV electron beam. The maximum tumor diameter was measured weekly, and overall survival was determined until day 100. Long-term tumor control was defined as no evident tumor on day 100. Animals were evaluated for acute dermal side effects at 2 to 5 weeks after completed RT and for late dermal side effects at 3 months after initiation of treatment. Results: Survival was significantly increased in all irradiated groups compared with control animals (P <.001). In general, irradiated tumors started to shrink at 1 week post–completed RT. In 40% (23 of 58) of the irradiated animals, long-term tumor control was achieved. Radiation-induced skin toxic effects were mild and consisted of hair loss, erythema, and dry desquamation. No severe toxic effect was observed. There was no significant difference between FLASH-RT and CONV-RT in overall survival, acute side effects, or late side effects for any of the dose levels. Conclusions: This study shows that hypofractionated FLASH-RT results in long-term tumor control rates similar to those of CONV-RT for the treatment of large subcutaneous glioblastomas in immunocompetent rats. Neither treatment technique induced severe skin toxic effects. Consequently, no significant difference in toxicity could be resolved, suggesting that higher doses may be required to detect a FLASH sparing of skin.
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21.
  • Liljedahl, Emma, et al. (författare)
  • Combined anti-C1-INH and radiotherapy against glioblastoma
  • 2023
  • Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A more effective immune response against glioblastoma is needed in order to achieve better tumor control. Radiotherapy can induce anti-tumor mediated immune reactions, in addition to its dose response effects. The complement system can function as a bridge between innate and adaptive immune responses. Combining radiotherapy and complement activating therapy is theoretically interesting. Methods: Radiotherapy at 8 Gy × 2 was combined with treatment against C1-inhibitor (C1-INH), a potent inhibitor of activation of the classical pathway of the complement system. Anti-C1-INH was delivered as intratumoral injections. Fully immunocompetent Fischer 344 rats with NS1 glioblastoma tumors were treated. Survival was monitored as primary outcome. Models with either intracranial or subcutaneous tumors were evaluated separately. Results: In the intracranial setting, irradiation could prolong survival, but there was no additional survival gain as a result of anti-C1-INH treatment. In animals with subcutaneous tumors, combined radio-immunotherapy with anti-C1-INH and irradiation at 8 Gy × 2 significantly prolonged survival compared to control animals, whereas irradiation or anti-C1-INH treatment as single therapies did not lead to significantly increased survival compared to control animals. Conclusions: Anti-C1-INH treatment could improve the efficacy of irradiation delivered at sub-therapeutic doses and delay tumor growth in the subcutaneous tumor microenvironment. In the intracranial setting, the doses of anti-C1-INH were not enough to achieve any survival effect in the present setting.
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22.
  • Liljedahl, Emma, et al. (författare)
  • Comparable survival in rats with intracranial glioblastoma irradiated with single-fraction conventional radiotherapy or FLASH radiotherapy
  • 2023
  • Ingår i: Frontiers in Oncology. - 2234-943X. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Radiotherapy increases survival in patients with glioblastoma. However, the prescribed dose is limited by unwanted side effects on normal tissue. Previous experimental studies have shown that FLASH radiotherapy (FLASH-RT) can reduce these side effects. Still, it is important to establish an equal anti-tumor efficacy comparing FLASH-RT to conventional radiotherapy (CONV-RT). Methods: Fully immunocompetent Fischer 344 rats with the GFP-positive NS1 intracranial glioblastoma model were irradiated with CONV-RT or FLASH-RT in one fraction of 20 Gy, 25 Gy or 30 Gy. Animals were monitored for survival and acute dermal side effects. The brains were harvested upon euthanasia and tumors were examined post mortem. Results: Survival was significantly increased in animals irradiated with CONV-RT and FLASH-RT at 20 Gy and 25 Gy compared to control animals. The longest survival was reached in animals irradiated with FLASH-RT and CONV-RT at 25 Gy. Irradiation at 30 Gy did not lead to increased survival, despite smaller tumors. Tumor size correlated inversely with irradiation dose, both in animals treated with CONV-RT and FLASH-RT. Acute dermal side effects were mild, but only a small proportion of the animals were alive for evaluation of those side effects. Conclusion: The dose response was similar for CONV-RT and FLASH-RT in the present model. Tumor size upon the time of euthanasia correlated inversely with the irradiation dose.
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23.
  • Liljedahl, Emma, et al. (författare)
  • Long-term anti-tumor effects following both conventional radiotherapy and FLASH in fully immunocompetent animals with glioblastoma
  • 2022
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 12285-12285
  • Tidskriftsartikel (refereegranskat)abstract
    • Radiotherapy can induce an immunological response. One limiting factor is side effects on normal tissue. Using FLASH radiotherapy, side effects could possibly be reduced. The efficacy of FLASH in relation to conventional radiotherapy (CONV-RT) has not been extensively explored in fully immunocompetent animals. Fully immunocompetent Fischer 344 rats were inoculated with NS1 glioblastoma cells subcutaneously or intracranially. Radiotherapy was delivered with FLASH or CONV-RT at 8 Gy × 2 (subcutaneous tumors) and 12.5 Gy × 2 (intracranial tumors). Cured animals were re-challenged in order to explore long-term anti-tumor immunity. Serum analytes and gene expression were explored. The majority of animals with subcutaneous tumors were cured when treated with FLASH or CONV-RT at 8 Gy × 2. Cured animals could reject tumor re-challenge. TIMP-1 in serum was reduced in animals treated with FLASH 8 Gy × 2 compared to control animals. Animals with intracranial tumors survived longer when treated with FLASH or CONV-RT at 12.5 Gy × 2, but cure was not reached. CONV-RT and FLASH were equally effective in fully immunocompetent animals with glioblastoma. Radiotherapy was highly efficient in the subcutaneous setting, leading to cure and long-term immunity in the majority of the animals.
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24.
  • Munkvold, Bodil Karoline Ravn, et al. (författare)
  • Variations in the management of diffuse low-grade gliomas : A Scandinavian multicenter study
  • 2021
  • Ingår i: Neuro-Oncology Practice. - : Oxford University Press. - 2054-2577 .- 2054-2585. ; 8:6, s. 706-717
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Early extensive surgery is a cornerstone in treatment of diffuse low-grade gliomas (DLGGs), and an additional survival benefit has been demonstrated from early radiochemotherapy in selected "high-risk" patients. Still, there are a number of controversies related to DLGG management. The objective of this multicenter population-based cohort study was to explore potential variations in diagnostic work-up and treatment between treating centers in 2 Scandinavian countries with similar public health care systems.Methods. Patients screened for inclusion underwent primary surgery of a histopathologically verified diffuse WHO grade II glioma in the time period 2012 through 2017. Clinical and radiological data were collected from medical records and locally conducted research projects, whereupon differences between countries and inter-hospital variations were explored.Results. A total of 642 patients were included (male:female ratio 1:4), and annual age-standardized incidence rates were 0.9 and 0.8 per 100 000 in Norway and Sweden, respectively. Considerable inter-hospital variations were observed in preoperative work-up, tumor diagnostics, surgical strategies, techniques for intraoperative guidance, as well as choice and timing of adjuvant therapy.Conclusions. Despite geographical population-based case selection, similar health care organizations, and existing guidelines, there were considerable variations in DLGG management. While some can be attributed to differences in clinical implementation of current scientific knowledge, some of the observed inter-hospital variations reflect controversies related to diagnostics and treatment. Quantification of these disparities renders possible identification of treatment patterns associated with better or worse outcomes and may thus represent a step toward more uniform evidence-based care.
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25.
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26.
  • Nittby, Henrietta, et al. (författare)
  • Analgetic effects of non-thermal GSM-1900 radiofrequency electromagnetic fields in the land snail Helix pomatia
  • 2012
  • Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 88:3, s. 245-252
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose : To investigate whether mobile phone radiation might affect snail nociception, employing radiofrequency (RF) electromagnetic fields (EMF) which, to our knowledge, have hitherto not been studied in a snail model. Exposure to extremely low frequency (ELF) magnetic fields has however been shown to significantly affect nociceptive responses. Materials and methods : In the present study, we exposed 29 land snails of the strain Helix pomatia to global system for mobile communications (GSM) EMF at 1900 MHz at the non-thermal level 48 mW/kg for 1 hour each and 29 snails were sham controls. The experiments took place during the onset of summer, with all snails being well out of hibernation. Before and after GSM or sham exposure, the snails were subjected to thermal pain by being placed on a hot plate. The reaction time for retraction from the hot plate was measured by two blinded observers. Results : Comparing the reaction pattern of each snail before and after exposure, the GSM-exposed snails were less sensitive to thermal pain as compared to the sham controls, indicating that RF exposure induces a significant analgesia (Mann-Whitney p < 0.001). Conclusion : This study might support earlier findings, describing beneficial effects of EMF exposure upon nociception.
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27.
  • Nittby, Henrietta, et al. (författare)
  • Cognitive impairment in rats after long-term exposure to GSM-900 mobile phone radiation
  • 2008
  • Ingår i: Bioelectromagnetics. - : Wiley. - 0197-8462 .- 1521-186X. ; 29:3, s. 219-232
  • Tidskriftsartikel (refereegranskat)abstract
    • Considering the frequent use of mobile phones, we have directed attention to possible implications on cognitive functions. In this study we investigated in a rat model the long-term effects of protracted exposure to Global System for Mobile Communication-900 MHz (GSM-900) radiation. Out of a total of 56 rats, 32 were exposed for 2 h each week for 55 weeks to radio-frequency electromagnetic radiation at different SAR levels (0.6 and 60 mW/kg at the initiation of the experimental period) emitted by a (GSM-900) test phone. Sixteen animals were sham exposed and eight animals were cage controls, which never left the animal house. After this protracted exposure, GSM-900 exposed rats were compared to sham exposed controls. Effects on exploratory behaviour were evaluated in the open-field test, in which no difference was seen. Effects on cognitive functions were evaluated in the episodic-like memory test. In our study, GSM exposed rats had impaired memory for objects and their temporal order of presentation, compared to sham exposed controls (P = 0.02). Detecting the place in which an object was presented was not affected by GSM exposure. Our results suggest significantly reduced memory functions in rats after GSM microwave exposure (P = 0.02).
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28.
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29.
  • Nittby, Henrietta (författare)
  • Effects of Mobile Phone Radiation upon the Mammalian Brain
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • oday about half of the world's population owns the microwave producing mobile phones. The blood-brain barrier (BBB) protects the mammalian brain from potentially harmful substances circulating in the blood. The permeability of the BBB has been shown to be increased after exposure to electromagnetic fields (EMFs) of the kind emitted by mobile phones and neuronal damage has been found several weeks after the exposure. The aim of this thesis was to further investigate the effects of exposure to global system for mobile communications (GSM) radiation upon the rat brain. In Paper I, rats were exposed to GSM radiation for two hours, followed by a seven-day recovery period after which the animals were sacrificed. The GSM exposed rats had a significantly increased BBB permeability as compared to the sham exposed control rats, seen as increased amount of albumin extravasation. In Paper II, we examined the effects of long-term exposure of rats for totally 55 weeks, 2 hours weekly, to GSM radiation. After this protracted exposure, an open-field test demonstrated no behavioural changes. On the other hand, the episodic memory was impaired after GSM exposure, as demonstrated in the episodic-like memory test. In Paper III histopathological light microscopial examinations of the long-term GSM exposed animals were presented. Albumin extravasation, neuronal damage and signs of accelerated ageing were investigated. No significant difference between the GSM exposed and sham control rats was seen. In Paper IV, microarray analysis of the gene expression in cortex and hippocampus of mobile phone exposed rats was performed. 31, 099 rat genes, including splicing variants, were analyzed. At the single gene level, no statistically significant alterations could be seen. However, with Gene Ontology (GO) analysis, 25 predefined GO categories had significantly altered gene expression in cortex and 20 GO categories had significantly altered gene expression in hippocampus. Four GO categories were among the ten most significantly altered groups in both cortex and hippocampus after GSM exposure; that is, extracellular region, signal transducer activity, intrinsic to membrane and integral to membrane. Considering the vast number of mobile phone users today, the non-thermal effects of mobile phoning and the mechanisms behind them, must indeed continue to be investigated.
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30.
  • Nittby, Henrietta, et al. (författare)
  • Exposure to radiation from global system for mobile communications at 1,800 MHz significantly changes gene expression in rat hippocampus and cortex
  • 2008
  • Ingår i: The Environmentalist. - : Springer Science and Business Media LLC. - 0251-1088 .- 1573-2991. ; 28:4, s. 458-465
  • Tidskriftsartikel (refereegranskat)abstract
    • We have earlier shown that radio frequency electromagnetic fields can cause significant leakage of albumin through the blood-brain barrier of exposed rats as compared to non-exposed rats, and also significant neuronal damage in rat brains several weeks after a 2 h exposure to a mobile phone, at 915 MHz with a global system for mobile communications (GSM) frequency modulation, at whole-body specific absorption rate values (SAR) of 200, 20, 2, and 0.2 mW/kg. We have now studied whether 6 h of exposure to the radiation from a GSM mobile test phone at 1,800 MHz (at a whole-body SAR-value of 13 mW/kg, corresponding to a brain SAR-value of 30 mW/kg) has an effect upon the gene expression pattern in rat brain cortex and hippocampus-areas where we have observed albumin leakage from capillaries into neurons and neuronal damage. Microarray analysis of 31,099 rat genes, including splicing variants, was performed in cortex and hippocampus of 8 Fischer 344 rats, 4 animals exposed to global system for mobile communications electromagnetic fields for 6 h in an anechoic chamber, one rat at a time, and 4 controls kept as long in the same anechoic chamber without exposure, also in this case one rat at a time. Gene ontology analysis (using the gene ontology categories biological processes, molecular functions, and cell components) of the differentially expressed genes of the exposed animals versus the control group revealed the following highly significant altered gene categories in both cortex and hippocampus: extracellular region, signal transducer activity, intrinsic to membrane, and integral to membrane. The fact that most of these categories are connected with membrane functions may have a relation to our earlier observation of albumin transport through brain capillaries.
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31.
  • Nittby, Henrietta, et al. (författare)
  • Increased blood-brain barrier permeability in mammalian brain 7 days after exposure to the radiation from a GSM-900 mobile phone.
  • 2009
  • Ingår i: Pathophysiology. - : Elsevier BV. - 1873-149X .- 0928-4680.
  • Tidskriftsartikel (refereegranskat)abstract
    • Microwaves were for the first time produced by humans in 1886 when radio waves were broadcasted and received. Until then microwaves had only existed as a part of the cosmic background radiation since the birth of universe. By the following utilization of microwaves in telegraph communication, radars, television and above all, in the modern mobile phone technology, mankind is today exposed to microwaves at a level up to 10(20) times the original background radiation since the birth of universe. Our group has earlier shown that the electromagnetic radiation emitted by mobile phones alters the permeability of the blood-brain barrier (BBB), resulting in albumin extravasation immediately and 14 days after 2h of exposure. In the background section of this report, we present a thorough review of the literature on the demonstrated effects (or lack of effects) of microwave exposure upon the BBB. Furthermore, we have continued our own studies by investigating the effects of GSM mobile phone radiation upon the blood-brain barrier permeability of rats 7 days after one occasion of 2h of exposure. Forty-eight rats were exposed in TEM-cells for 2h at non-thermal specific absorption rates (SARs) of 0mW/kg, 0.12mW/kg, 1.2mW/kg, 12mW/kg and 120mW/kg. Albumin extravasation over the BBB, neuronal albumin uptake and neuronal damage were assessed. Albumin extravasation was enhanced in the mobile phone exposed rats as compared to sham controls after this 7-day recovery period (Fisher's exact probability test, p=0.04 and Kruskal-Wallis, p=0.012), at the SAR-value of 12mW/kg (Mann-Whitney, p=0.007) and with a trend of increased albumin extravasation also at the SAR-values of 0.12mW/kg and 120mW/kg. There was a low, but significant correlation between the exposure level (SAR-value) and occurrence of focal albumin extravasation (r(s)=0.33; p=0.04). The present findings are in agreement with our earlier studies where we have seen increased BBB permeability immediately and 14 days after exposure. We here discuss the present findings as well as the previous results of altered BBB permeability from our and other laboratories.
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32.
  • Nittby, Henrietta, et al. (författare)
  • Nonthermal GSM RF and ELF EMF effects upon rat BBB permeability
  • 2011
  • Ingår i: The Environmentalist. - : Springer Science and Business Media LLC. - 0251-1088 .- 1573-2991. ; 31:2, s. 140-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Since the late 1980s, our group has examined the effects of radiofrequency electromagnetic fields (RF-EMF), including pulse-modulated waves of the type emitted by mobile phones, upon the blood-brain barrier. In more than 2,000 rats, we have repeatedly demonstrated a passage of the rats' own albumin from the blood through the brain capillaries into the surrounding brain parenchyma at SAR values down to 0.1mW/kg. In most of these experiments, the animals were exposed in TEM-cells, ventilated by an external electrical fan at 50 Hz. In the present study, we examined whether the extremely low frequency (ELF) magnetic fields from the fan (50 Hz, 0.3-1.5 μT) might add to the RF effect. Sixty-four rats were divided into 4 groups: RF only, ELF only and RF + ELF exposure plus a sham group. The GSM-900 MHz RF exposure was at the very low, nonthermal, average whole-body SAR level 0.4 mW/kg. Demonstration of the normally occurring albumin extravasation in the basal hypothalamus is our inbuilt control proving that the staining is reliable. Two full series of staining of the whole material gave negative results for hypothalamus. Not until we changed to avidin, biotin, and antibodies from a third supplier, we received an acceptable staining. Twenty-five percent of the RF animals had a pathological albumin leakage, while the ELF and RF + ELF groups with three and two pathological findings, respectively, were not significantly different from the control group. We conclude that the use of external fans has had no major influence upon the result.
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33.
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34.
  • Nittby, Henrietta Redebrandt, et al. (författare)
  • A Subgaleal Hematoma That Turned Out to Be a B-Cell Lymphoma
  • 2016
  • Ingår i: World Neurosurgery. - : Elsevier BV. - 1878-8750. ; 93, s. 489-489
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Subgaleal masses are relatively common in the clinical praxis, and after a trauma to the head, a subgaleal hematoma is usually suspected. However, other differential diagnoses, such as malignant tumors, should be kept in mind despite a history of a previous trauma. Case description and Conclusions We report a case of a subgaleal mass that was clinically and radiologically diagnosed as a subgaleal hematoma in a patient on antiplatelet therapy. The patient had a history of trauma to her head, but pathologic examination after surgery unexpectedly showed a malignant B-cell lymphoma. A review of the literature is also presented.
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35.
  • Nittby, Henrietta Redebrandt, et al. (författare)
  • Early postoperative haematomas in neurosurgery
  • 2016
  • Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 158:5, s. 837-846
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A postoperative haematoma can be a very serious complication following a neurosurgical procedure. Patients should be informed about the risks of such an event prior to surgery. From a practical point of view, it would be important to know when the patient is most likely to deteriorate and to require surgery because of a postoperative haematoma and when it might be safe to transfer the patient to the regular ward. The up-to-date studies regarding this topic are few. Methods: We therefore undertook the present retrospective study, including a cohort of all patients operated on at the Department of Neurosurgery in Lund during the years 2011–2014, with the aim to define the time windows for clinical deterioration and reoperation, and whether risk factors such as anticoagulant agents/antiplatelet therapy, emergency versus elective surgery and abnormal coagulation blood values were present. We also defined the type of surgery resulting in postoperative haematoma and tried to find the clinical state of the patients when they deteriorated, as well as the outcome at 3 months postoperatively. Results: During the time period from June 2011 to November 2014, a total of 7,055 surgical procedures of all kinds were registered at our department. By the search for the diagnosis codes AWE00 and AWD00 (reoperation for deep haemorrhage and for superficial haemorrhage respectively), we identified 93 reoperations, meaning a percentage of 1.3 %. Thirty-four of the reoperations were done within the first 24 h. Twenty-four patients were reoperated on >24 h but ≤72 h after the first operation. Only four patients who were initially doing well postoperatively showed a delayed clinical deterioration within the time frame from >6 h and ≤24 h postoperatively. This means that 0.06 % of the patients who were operated upon were doing well initially, being completely awake and with no new neurological deficit and no deterioration within the first 6 h postoperatively, and then deteriorated from a postoperative haematoma within the time frame of >6 h and ≤24 h postoperatively. Conclusions: We could conclude that no exact time window distinguished very early from somewhat later postoperative haematomas in our material. However, all but two patients deteriorating between 6 and 24 h after the operation had at least one of the following risk factors defined for post-operative haematoma: meningioma surgery, anticoagulant agents/antiplatelet therapy prior to surgery (including Dalteparin [Fragmin®], Enoxaparinnatrium [Klexane®], Warfarin [Waran®], ASA [Trombyl®] or ASA and caffeine [Treo®]), emergency operation, posterior fossa surgery or chronic subdural haematoma in a patient with a shunt. This material is too small to make any definitive conclusions, but a suggestion could be to include these factors when considering the transfer of a patient from the postoperative intensive care unit to the regular ward.
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36.
  • Nittby, Henrietta, et al. (författare)
  • Radiofrequency and extremely low-frequency electromagnetic field effects on the blood-brain barrier.
  • 2008
  • Ingår i: Electromagnetic Biology and Medicine. - : Informa UK Limited. - 1536-8386 .- 1536-8378. ; 27:2, s. 103-126
  • Tidskriftsartikel (refereegranskat)abstract
    • During the last century, mankind has introduced electricity and during the very last decades, the microwaves of the modern communication society have spread a totally new entity--the radiofrequency fields--around the world. How does this affect biology on Earth? The mammalian brain is protected by the blood-brain barrier, which prevents harmful substances from reaching the brain tissue. There is evidence that exposure to electromagnetic fields at non thermal levels disrupts this barrier. In this review, the scientific findings in this field are presented. The result is a complex picture, where some studies show effects on the blood-brain barrier, whereas others do not. Possible mechanisms for the interactions between electromagnetic fields and the living organisms are discussed. Demonstrated effects on the blood-brain barrier, as well as a series of other effects upon biology, have caused societal anxiety. Continued research is needed to come to an understanding of how these possible effects can be neutralized, or at least reduced. Furthermore, it should be kept in mind that proven effects on biology also should have positive potentials, e.g., for medical use.
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37.
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38.
  • Nittby, Henrietta, et al. (författare)
  • Zebularine induces long-term survival of pancreatic islet allotransplants in streptozotocin treated diabetic rats.
  • 2013
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Coping with the immune rejection of allotransplants or autologous cells in patients with an active sensitization towards their autoantigens and autoimmunity presently necessitates life-long immune suppressive therapy acting on the immune system as a whole, which makes the patients vulnerable to infections and increases their risk of developing cancer. New technologies to induce antigen selective long-lasting immunosuppression or immune tolerance are therefore much needed.
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39.
  • Osther, Kurt, et al. (författare)
  • Upregulation of C1-inhibitor in pancreatic cancer
  • 2019
  • Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 10:55, s. 5703-5712
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The complement system has recently sparked more interest in cancer research. The classical pathway is initiated by activation of the C1 complex, which irreversibly can be bound to and inhibited by C1-INH. We have previously shown that C1-INH is upregulated in human glioblastoma (astrocytoma grade IV) on both gene and protein level. We here examine whether the complement system seems to play a role also in pancreatic cancer.Technique and results: We performed an expression analysis of complement associated genes in 36 pancreatic ductal adenocarcinoma tumors and matching normal pancreatic tissue samples from pancreatic cancer patients (data from the publicly available database GSE15471). C1-INH was significantly upregulated in the pancreatic cancer tissue. None of the downstream components of the cascade were significantly upregulated in the cancer samples as compared to the control samples, which is the same pattern as we found in glioblastoma. GO analysis showed that membrane attack complex came up as the second most significantly associated cellular component. Analyzing gene expression of C1-INH in the pancreatic cancer cell lines from primary tumors versus metastatic tumor revealed no difference for the two mRNA transcripts (GSE59357).Interpretation: Analysis of gene expression of complement related genes shows an upregulation of C1-INH and a downregulation of downstream components. This could suggest that C1-INH plays a role also in pancreatic cancer.
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40.
  • Parikh, Hemang, et al. (författare)
  • Molecular correlates for maximal oxygen uptake (VO2max) and type 1 fibers.
  • 2008
  • Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; Apr 29, s. 1152-1159
  • Tidskriftsartikel (refereegranskat)abstract
    • Maximal oxygen uptake (VO2max) and the amount of type 1 fibers are interrelated but the underlying unifying molecular mechanisms are poorly understood. To explore these mechanisms we related gene expression profiles in skeletal muscle biopsies of 43 age-matched men from published datasets with VO2max and amount of type 1 fibers and replicated some of the findings in muscle biopsies from 154 young and elderly individuals using real-time PCR. We identified 66 probesets (genes or ESTs) positively and 83 probesets inversely correlated with VO2max and 171 probesets positively and 217 probesets inversely correlated with percentage of type 1 fibers in human skeletal muscle. Genes involved in oxidative phosphorylation (OXPHOS) showed high expression in individuals with high VO2max whereas the opposite was not the case in individuals with low VO2max. Instead, genes like AHNAK and BCL6 were associated with low VO2max. Also, expression of the OXPHOS genes NDUFB5 and ATP5C1 increased with exercise training and decreased with aging. In contrast, expression of AHNAK in skeletal muscle decreased with exercise training and increased with aging. Eleven genes (NDUFB4, COX5A, UQCRB, ATP5C1, ATP5G3, ETHE1, FABP3, ISCA1, MYST4, C9orf3 and PKIA) were positively correlated with both VO2max and percentage of type 1 fibers. VO2max closely reflects expression of OXPHOS genes, particularly of NDUFB5 and ATP5C1 in skeletal muscle suggesting good muscle fitness. In contrast, a high expression of AHNAK was associated with a low VO2max and poor muscle fitness. Key words: VO2max, Type 1 fibers, Aging.
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41.
  • Persson, Bertil R, et al. (författare)
  • “Abscopal” Effect of Radiation Therapy Combined with Immune-Therapy Using IFN-γ Gene Transfected Syngeneic Tumor Cells, in Rats with Bilateral Implanted N29 Tumors
  • 2011
  • Ingår i: ISRN Immunology. - : Hindawi Limited. - 2090-5645 .- 2090-5653. ; 2011
  • Tidskriftsartikel (refereegranskat)abstract
    • The tumor growth rate response was studied on N29 rat glioma tumor cells subcutaneously implanted on both hind legs of Fischer-344 rats. At around 30 days after inoculation, RT was given with 60Co gamma radiation with 4 daily fractions of 5 Gy only to the right-lateral tumors. At days 26, 42, and 54 after inoculation, immunization was performed with irradiated syngeneic IFNγ-gene transfected cells. Tumor growth rate (TGR % per day) of the right-lateral irradiated tumor was significantly decreased (P<0.01) after RT alone and with the combination of RT and immunization. But immunization alone gave no significant decrease of the TGR but significantly increased time of survival. The TGR of the unirradiated left-lateral tumors was significantly decreased (P<0.02) only in the group of rats treated with RT alone. It is apparent that tumor cells killed by the radiation mediate suppression of tumor cells outside the target area. This effect is called the abscopal effect.
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42.
  • Persson, Bertil R, et al. (författare)
  • Mörka Neuron och Mobiltelefoner : Dedicerad till en 90-årig man, Arne Brun i Lund
  • 2021
  • Ingår i: Acta Scientiarum Lundensia. - 1651-5013. ; 2021:001, s. 1-23
  • Tidskriftsartikel (refereegranskat)abstract
    • Med denna svenska översikt av våra egna och andra forskares observationer av mörka neuron vid mikrovågs exponering från mobiltelefoner, som lite senkommet tillägnas Arne Brun på hans 90 års-dag, vill vi att hans insatser blir uppmärksammade och inte faller i glömska.Kring 2000 millennium skiftet pågick ett intensivt arbete i Lund med att sammanfatta och bekräfta effekterna av exponering med GSM-900 MHz mikrovågor på blod-hjärna barriären och hjärnans neuroner. Leif G. Salford, Arne Brun och medarbetare presenterade år 2003 i tidskriften Environmental Health Perspectives resultaten från en undersökning av skador på nervcellerna i råtthjärna efter exponering för mikrovågor från GSM Mobiltelefoner. Kontroller och testdjur visade alla tecken på närvao av albumin i hypotalamus, vilket år normalt och indikerar att albumin infärgningen av BBB läckaget också fungerar. Cresylviolettfärgningen avslöjade förekomst av spridda och grupperade mörka nervceller, som ofta var skrumpna och mörkt homogent färgade utan urskiljbara interna cellstrukturer. Några av dessa mörka nervceller var också albuminpositiva eller visade cytoplasmatiska mikrovakuoler som indikerar en aktiv patologisk process. År 2008 presenterades resultaten av ytterligare undersökningar av blod-hjärn barriärens permeabilitet och nervcellsskador i råtthjärnan efter en återhämtningstid på antingen 14 och 28 dagar efter 2 timmas exponering för mikrovågor från GSM-mobiltelefoner i 900 MHz-bandet. Efter 14 dagars återhämtningstid observerades albumin-läckage i BBB och albumin upptag i neuroner. Mörka neuron observerades endast hos råttor som exponerats med det lägsta SAR-värdet, 0,12 mW/kg. Efter 28 dagars återhämtnings period observerades läckage av albumin endast hos råttor som exponerats med det högsta SAR-värdet, 100 mW/kg. Däremot observerades efter 28 dagar förekomst av mörka neuron i råtthjärnor hos alla grupperna vilket korrelerade väl med neuronernas albumin upptag.I studien observeras neuro-patologiska förändringar redan vid SAR-värden så låga som 0,12 mW/kg vilket överensstämmer med våra tidigare resultat. Speciellt iögonfallande är att det högsta albumin upptaget i neuroner observeras vid den lägsta SAR nivån på 0,12 mW/kg. Frekvensen hos förekomsten av mörka nervceller ökade, jämfört med kontrollerna både efter 14 och 28 dagars återhämtning, men var endast signifikant vid 28 dagar efter exponering. Inga signifikanta tecken på förekomsten av mörka neuron observerades emellertid efter 7 dagars återhämtning.I en Fransk studie redovisad av Poulletier de Gannes och medarbetare 2009 exponerades enbart huvudet hos 16 st. Fischer 344-råttor (14 veckor gamla) för GSM-900 under 2 timmar vid SAR värden 0,14 och 2,0 W/kg. Fjorton alternatvt 50 dagar efter GSM-900 exponeringen kunde varken BBB-läckage eller förekomst av mörka nervceller upptäckas i rått hjärnorna. Deras resultat indikerar att det föreligger en väsentlig skillnad i resultaten vid helkropp exponering jämfört med exponering av endast huvudet.År 2015 presenterades en studie, stödd av Nationella Vetenskaps Akademin i Kina (NSFC), avseende albumin-läckage i blod-hjärnbarriären efter exponering med kontinuerliga mikrovågor på 900 MHz med SARvärden mellan 0,016 (hela kroppen) och 2 W/kg (lokalt i huvudet). Hos råttor som exponerats under 28 dagar observerades cellulärt ödem och neuronal cellorganell degeneration hos råttorna. Dessutom observerades med immun-färgning BBB-läckage av albumin i hippocampus och cortex. Efter exponering för 900 MHz mikrovågor under 14 respektive 28 dagar hade serum albumin diffunderat in i neuropilen mellan cellkropparna, som omger neuronerna. Upptag av Albumin i hippocampus neuron hos råttor exponerade under 28 dagar, visar förekomst av mörka neuron. Deras resultat är i linje med Lunda-resultaten som publicerades 2003 och 2008.
  •  
43.
  • Persson, Bertil R, et al. (författare)
  • Non-thermal" Effects on the Blood-Brain Barrier in Fischer rats by exposure to microwaves
  • 2012
  • Ingår i: Acta Scientiarum Lundensia. - 1651-5013. ; 2012-006:006, s. 1-39
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Effect of 915 MHz electromagnetic fields (EMF) on the blood brain-barrier (BBB) permeability has been studied in Fischer 344 rats of both sexes. Male and female Fischer 344 rats were exposed in a Transverse Electromagnetic Transmission line chamber to microwaves of 915 MHz as continuous wave (CW) and pulse-modulated with different pulse power and at various time intervals. The CW-pulse power varied from 0.001W to 10 W and the exposure time from 2 min. to 960 min. In each experiment we randomly placed 4 rats in excited and 4 control rats in non-excited TEM-cells respectively. The rats were not anaesthetised during the exposure. The rats were exposed to 915 MHz microwaves, either continuous wave (CW) or pulse modulated at 4,8,16 or 217 Hz with 0.57 ms pulse width, or pulse modulated at 50 Hz with 6.6 ms pulse width as well as from a real GSM-900 telephone. All animals were sacrificed by perfusion-fixation of the brains under chloralhydrate anaesthesia after the exposure. The brains were then perfused, first with saline for 3-4 minutes, and then with 4% formaldehyde for 5-6 minutes. Whole coronal sections of the brains were dehydrated and embedded in paraffin and sectioned at 5 μm. The degree of albumin leakage was demonstrated immune-histo-chemically and classified in order of increased number of albumin extravasations by a rank number: 0 - 0.5 - 1.0 - 1.5 - 2 - 3. Pathological albumin leakage was judged as albumin extravasations equal to or larger than 1. The frequency of pathological rats in all control groups was about 17%. Among rats exposed to pulse modulated microwaves the ratio of pathological rats was 170/481(0.35±0.03) and among rats exposed to continuous wave exposure (CW) it was 74/149 (0.50±0.07). These results are both highly significantly different to their corresponding controls (p<0.0001). The rats were exposed to SAR various values: 0.2; 2; (20-40); (100-500); (1000-3000) mW/kg. In the 217 Hz modulated group (GSM simulated) we found the most increased ratio of albumin extravasations OR= 4 at 0.2 mW/kg. But no significant increased ratio at SAR 2000 mW/kg. The response curve of OR versus log(SAR) had the shape of a bathtub, with a minimum at a100 mW/kg. A similar curve was recorded for OR versus Specific Absorbed Energy (SAE Joule / kg) with a minimum at 100 J/kg. Similar response curves were recorded for the various modulation frequencies 4; 8; 16; 50 Hz. We found no pronounced difference between the various modulation frequencies other than the effect of CW exposure seems to be more effective than pulse modulated exposure in opening the BBB at high SAR values 100-2000 mW/kg. Conclusion: The opening of the BBB is most effective at SAR values in the range of 0.1-0.5 mW.kg-1 and less effective in the range of 50-500 mW.kg-1. In this low SAR range thermal effects are unlikely. Thus there seems to be a non-thermal mechanism involved triggering the opening of the BBB.
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44.
  • Persson, Bertil R, et al. (författare)
  • Radiation immunomodulatory gene tumor therapy of rats with intracerebral glioma tumors.
  • 2010
  • Ingår i: Radiation Research. - 0033-7587. ; 173:4, s. 433-440
  • Tidskriftsartikel (refereegranskat)abstract
    • Single-fraction radiation therapy with 5 or 15 Gy (60)Co gamma radiation was combined with intraperitoneal injections of syngeneic interferon gamma (IFN-gamma)-transfected cells in rats with intracerebral N29 or N32 glioma tumors at days 7, 21 and 35 after inoculation. For intracerebral N29 tumors, single-fraction radiation therapy with 5 or 15 Gy had no significant effect on the survival time. Immunization with IFN-gamma-transfected N29 cells significantly increased the survival time by 61%. Single-fraction radiation therapy with 5 Gy combined with immunization increased the survival time significantly by 87% and complete remissions by 75% while with 15 Gy the survival time increased 45% with 38% complete remissions. For intracerebral N32 tumors, single-fraction radiation therapy with 15 Gy increased the survival time significantly by 20%. Immunization by itself had no significant effect with IFN-gamma-transfected N32 cells, but combined with 15 Gy single-fraction radiation therapy it increased survival time significantly by 40%, although there were no complete remissions. Based on these findings, we suggest a new therapeutic regimen for malignant glioma using single-fraction radiation therapy with a target absorbed dose of the order of 5-10 Gy combined with clinically verified immunotherapy.
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45.
  • Persson, Bertil R, et al. (författare)
  • S-100 protein levels in the blood of Fischer rats exposed to 915 MHz CW-microwaves and magnetic fields.
  • 2020
  • Ingår i: Acta Scientiarum Lundensia. - 1651-5013. ; 2020:005, s. 1-9
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • EnglishPersson, B. R. R., Nittby Redenbrant, H., Malmgren, L., Brun, A., and Salford, L. G. (2020). S-100 protein levels in the blood of Fischer rats exposed to 915 MHz CW-microwaves and magnetic fields. Acta Scientiarum Lundensia, Vol. 2020-005, pp. 1-9, ISSN 1651-5013Abstrakt.Syftet var att studera nivån av S-100 i blodprover som tagits från Fischer-344-råttor efter exponering för 915 MHz CW-mikrovågor och ELF-magnetfält i TEM-celler. Magnetfältsexponering ägde rum med TEM-cellen i ett Helmholtz-spolarrangemang med antingen 50 Hz sinusformat magnetfält på 5 µT eller inkoherent magnetfältbrus IMF med en maximal amplitud på 50 µT.Det verkar inte finnas någon signifikant förändring i S-100-koncentrationen i blod hos råttor som exponerats under 6 timmar för höga nivåer (4W) av kontinuerlig våg (CW) 915MHz mikrovågor, 50Hz sinusformade magnetfält (5µT) och osammanhängande magnetfält (IMF) vid 50µT. Däremot indikerar resultaten av den kombinerade exponeringen CW + IMF en minskad koncentration av S100 i blod.Minskningen överensstämmer med resultaten av en undersökning under 2010 att de extremt lågfrekventa (ELF) magnetfälten från fläktmotorn (50Hz AC, 0,3-1,5 T) minskade det förväntade BBB-läckaget av albumin på grund av mikrovågsexponering .Resultaten från andra studier indikerar också att bioeffekter orsakade av exponering för mikrovågor reduceras genom överläggning med extremt lågfrekventa magnetfält ELF. Det är därför av yttersta vikt när man undersöker bioeffekter från mikrovågor för att också kontrollera nivåer och frekvenser av lågfrekventa magnetfält i omgivningen, vilket kan vara en av anledningarna till den breda spridningen i de rapporterade resultaten.
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46.
  • Robertson, John A, et al. (författare)
  • Simultaneous fMRI and EEG during the Multi-Source Interference Task
  • 2014
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12
  • Tidskriftsartikel (refereegranskat)abstract
    • fMRI and EEG are two non-invasive functional imaging techniques within cognitive neuroscience that have complementary advantages to obtain both temporal and spatial information. The multi-source interference task (MSIT) has been shown to generate robust activations of the dorsal anterior cingulate cortex (dACC) on both a single-subject level and in group averages, in fMRI studies. We have now simultaneously acquired fMRI and EEG during a cognitive interference task.
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47.
  • Salford, Leif G., et al. (författare)
  • Non-thermal effects of EMF upon the mammalian brain : The Lund experience
  • 2007
  • Ingår i: The Environmentalist. - : Springer Science and Business Media LLC. - 0251-1088 .- 1573-2991. ; 27:4, s. 493-500
  • Tidskriftsartikel (refereegranskat)abstract
    • The environment in which biology exists has dramatically changed during the last decades. Life was formed during billions of years, exposed to, and shaped by the original physical forces such as gravitation, cosmic irradiation and the terrestrial magnetism. The existing organisms are created to function in harmony with these forces. However, in the late 19th century mankind introduced the use of electricity and during the very last decades, microwaves of the modern communication society spread around the world. Today one third of the world's population is owner of the microwave-producing mobile phones. The question is: to what extent are living organisms affected by these ubiquitous radio frequency fields? Since 1988 our group has studied the effects upon the mammalian blood-brain barrier (BBB) by non-thermal radio frequency electromagnetic fields (RF-EMF). These have been revealed to cause significantly increased leakage of albumin through the BBB of exposed rats as compared to non-exposed animals-in a total series of about two thousand animals. One remarkable observation is the fact that the lowest energy levels give rise to the most pronounced albumin leakage. If mobile communication, even at extremely low energy levels, causes the users' own albumin to leak out through the BBB, also other unwanted and toxic molecules in the blood, may leak into the brain tissue and concentrate in and damage the neurons and glial cells of the brain. In later studies we have shown that a 2-h exposure to GSM 915 MHz at non-thermal levels, gives rise to significant neuronal damage, seen 28 and 50 days after the exposure. In our continued research, the non-thermal effects (histology, memory functions) of long-term exposure for 13 months are studied as well as the effects of short term GSM 1,800 MHz upon gene expression. Most of our findings support that living organisms are affected by the non-thermal radio frequency fields. Studies from other laboratories in some cases find effects, while in other cases effects are not seen. Our conclusion is that all researchers involved in this field have the obligation to intensify this research in order to reduce, or avoid, the possible negative effects of the man made microwaves!
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48.
  • Salford, Leif, et al. (författare)
  • The mammalian brain in the electromagnetic fields designed by man with special reference to blood-brain barrier function, neuronal damage and possible physical mechanisms
  • 2008
  • Ingår i: PROGRESS OF THEORETICAL PHYSICS SUPPLEMENT. - 0375-9687. ; :173, s. 283-309
  • Konferensbidrag (refereegranskat)abstract
    • Life oil earth was formed during billions of years, exposed to, and shaped by the original physical forces such as gravitation, cosmic irradiation, atmospheric electric fields and the terrestrial magnetism. The Schumann resonances at 7.4 Hz are all example of oscillations possibly important for life.(1)) The existing organisms are created to function in harmony with these forces. However, in the late 19th century mankind introduced the use of electricity, in the early 20th century long-wave radio and in the 1940-ies short-wave radio. High frequency RF was introduced in the 50-ies as FM and television and during the very last decades, microwaves of the modern communication society spread around the world. Today, however, one third of the world's population is owner of the microwave-producing mobile phones and an even larger number is exposed to the cordless RF emitting systems. To what; extent are all living organisms affected by these, almost everywhere present radio frequency fields? And what will be the effects of many years of continuing exposure? Since 1989 Our group has studied the effects upon the mammalian blood-brain barrier (BBB) in rats by non-thermal radio frequency electromagnetic fields (RF-EMF). These have been shown to cause significantly increased leak-age of the rats' own blood albumin through the BBB of exposed rats, at energy levels of 1W/kg and below, as compared to non-exposed animals in a total series of about two thousand animals.(2)-6)) One remarkable observation is the fact that the lowest energy levels, with whole-body average power densities below 10mW/kg, give rise to the most pronounced albumin leakage. If mobile communication, even at extremely low energy levels, causes the users' own albumin to leak out through the BBB, also other unwanted and toxic molecules in the blood, may leak into the brain tissue and concentrate in and damage the neurons and glial cells of the brain. In later studies we have shown that a 2-h exposure to GSM 915 MHz, at non-thermal SAB-values of 0.2, 2 and 200 mW/kg, gives rise to significant neuronal damage, seen not only 50 days after the exposure 7) but also after 28 days but not after 14 days. Albumin extravasations and uptake into neurons was enhanced after 14 clays, but not after 28.(8)) in our continued research, also the non-thermal effects oil tissue structure and memory function of long-term exposure for 13 months are studied.(9)) We have also performed microarray analysis of brains from rats exposed to short term GSM both at 1,800 MHz and at 900MHz and have found significant effects upon gene expression of membrane associated genes as compared to control animals.(10),11)) Most of our findings support that living organisms are affected by the non-thermal radio frequency fields. Some other Studies agree while others find no effects. The mechanisms by which the EMFs may alter BBB permeability are not Well Understood. At low field strengths, the effects on body temperature are negligible and thus heating effects are not involved. A change in the physicochemical characteristics of membranes has been suggested as a cause.(12)) We have performed experiments to verify a quantum mechanical model for interaction with protein-bound ions. Our results show that controlled frequency and amplitude of ELF EM fields upon spinach plasma vesicles can steer transport over the membrane.(13)) This may be a first proof of a resonance phenomenon where appropriate levels of frequency and amplitude in the right combination have the potency to communicate with the biology of membranes and transport systems. Our study has prompted Lis to elaborate on magnetic resonance models; the Ion Cyclotron Resonance (ICR) model and the Ion Parametric Resonance (IPR) Model in an attempt to explain the occurrence of resonance frequencies. This is extensively described here under the heading: Mechanisms behind the effects of electromagnetical fields upon biology. We also bring forward the concept of solitons being active in membranes and DNA/RNA-transcription as a, possible mean to understand and prove the biological effects of EMF. The Nishinomiya-Yukawa International and Interdisciplinary Symposium 2007 raised the question: What is Life? An obvious and simple answer could be: It is DNA! The DNA strand can be looked upon as an antenna resonating in the microwave band 6GHz with its harmonics and subharmonics.(14)-18)) If this holds true, the dramatic situation might exist, that all living organisms have a receptor for the newly constructed and world-wide man-made microvaves, leading to a direct effect upon the function of DNA - in concordance with our experimental findings! Our generation invented the microwave emitters. We now have in imperative obligation to further investigate the links between EMF and biology in order to prevent possible detrimental effects of the microwaves.
  •  
49.
  • Sun, Wenjun J., et al. (författare)
  • Calcium efflux of plasma membrane vesicles exposed to ELF magnetic fieldsutest of a nuclear magnetic resonance interaction model
  • 2012
  • Ingår i: Bioelectromagnetics. - : Wiley. - 0197-8462. ; 33:7, s. 535-542
  • Tidskriftsartikel (refereegranskat)abstract
    • The question whether very weak, low frequency magnetic fields can affect biological matter is still under debate. The theoretical possibility of such an interaction is often questioned and the site of interaction in the cell is unknown. In the present study, the influence of extremely weak 60?Hz magnetic fields on the transport of Ca2+ was studied in a biological system consisting of highly purified plasma membrane vesicles. We tested a newly proposed quantum mechanical model postulates that polarization of hydrogen nuclei can elicit a biological effect. Vesicles were exposed for half an hour at 32?degrees C and the calcium efflux was studied using radioactive 45Ca2+ as a tracer. A static magnetic field of 26?mu T and time-varying magnetic fields with a frequency of 60?Hz and amplitudes between 0.6 and 6.3?mu T were used. The predictions of the model, proposed by Lednev, that at a frequency of 60?Hz the biological effect under investigation would significantly be altered at the amplitudes of 1.3 and 3.9?mu T could not be confirmed. Bioelectromagnetics 33:535542, 2012. (c) 2012 Wiley Periodicals, Inc.
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50.
  • Tefre, Sondre, et al. (författare)
  • Endoscopic third ventriculostomy for adults with hydrocephalus: creating a prognostic model for success: protocol for a retrospective multicentre study (Nordic ETV)
  • 2022
  • Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Endoscopic third ventriculostomy (ETV) is becoming an increasingly widespread treatment for hydrocephalus, but research is primarily based on paediatric populations. In 2009, Kulkarni et al created the ETV Success score to predict the outcome of ETV in children. The purpose of this study is to create a prognostic model to predict the success of ETV for adult patients with hydrocephalus. The ability to predict who will benefit from an ETV will allow better primary patient selection both for EN and shunting. This would reduce additional second procedures due to primary treatment failure. A success score specific for adults could also be used as a communication tool to provide better information and guidance to patients. Methods and analysis The study will adhere to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis reporting guidelines and conducted as a retrospective chart review of all patients >= 18 years of age treated with EN at the participating centres between 1 January 2010 and 31 December 2018. Data collection is conducted locally in a standardised database. Univariate analysis will be used to identify several strong predictors to be included in a multivariate logistic regression model. The model will be validated using K-fold cross validation. Discrimination will be assessed using area under the receiver operating characteristic curve (AUROC) and calibration with calibration belt plots. Ethics and dissemination The study is approved by appropriate ethics or patient safety boards in all participating countries.
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