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  • Petridou, Eleni Th., et al. (författare)
  • In vitro fertilization and risk of childhood leukemia in Greece and Sweden
  • 2012
  • Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 58:6, s. 930-936
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Cancer risk in children born after in vitro fertilization (IVF) remains largely unknown. We aimed to investigate risk of leukemia and lymphoma following IVF using two nationwide datasets. Methods. The hospital-based case-control study in Greece derived from the National Registry for Childhood Hematological Malignancies (1996-2008, 814 leukemia and 277 lymphoma incident cases with their 1: 1 matched controls). The Swedish casecontrol study was nested in the Swedish Medical Birth Register (MBR) (1995-2007, 520 leukemia and 71 lymphoma cases with their 5,200 and 710 matched controls) with ascertainment of incident cancer cases in the National Cancer Register. Study-specific and combined odds ratios (OR) were estimated using conditional logistic regression, with adjustment for possible risk factors. Results. Nationwide studies pointed to similar size excess risk of leukemia following IVF, but to a null association between IVF and lymphoma. The proportion of leukemia cases conceived through IVF was 3% in Greece and 2.7% in Sweden; prevalence of IVF in matched controls was 1.8% and 1.6%, respectively. In combined multivariable analyses, the increased risk of leukemia was confined to age below 3.8 years (OR 2.21; 95% confidence interval, CI: 1.27-3.85) and to acute lymphoblastic leukemia (ALL) (OR 1.77; 95% CI: 1.062.95) with no sufficient evidence of excess risk for other leukemias (OR 1.34; 95% CI: 0.38-4.69). Following IVF, OR for ALL was 2.58 (95% CI: 1.37-4.84) before age 3.8 and 4.29 (95% CI: 1.4912.37) before age 2 years. Conclusions. IVF seems to be associated with increased risk of early onset ALL in the offspring. 
  • 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.
  • Sundgren, P, et al. (författare)
  • Paragangliomas of the spinal canal
  • 1999
  • Ingår i: Neuroradiology. - : Springer Science and Business Media LLC. - 1432-1920 .- 0028-3940. ; 41:10, s. 788-794
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the clinical MRI and histopathological features of five consecutive cases of spinal paraganglioma. Three intradural tumours were found in the typical location (two at the L4, one at the S2 level); one intradural extramedullary tumour arose at an unusual level, from the ventral C2 root, and one extradural tumour growing along the L5 nerve root sheath had an aggressive growth pattern with early, local paraspinal recurrence and, eventually, intradural metastatic spread. This type of growth pattern has not been described previously. Paragangliomas of the spinal canal are more common than previously thought and can be located anywhere along the spine, although the lumbosacral level is the most common. Their appearance on MRI can not distinguish them from other tumours in the spinal canal. Even though paragangliomas in general are benign and slowly growing their growth pattern can vary and be more aggressive, to the point of metastatic spread.
  • Söderquist, Fanny (författare)
  • Melatonin in the gastrointestinal tract
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Melatonin is recognised as the pineal hormone regulating sleep and circadian rhythm. It has also been identified in peripheral tissues (mainly in animals) and thought to display a variety of actions, including anti-inflammatory properties, regulation of gastrointestinal (GI) functions, glucose homeostasis and beneficial effects in different tumour types. Patients with irritable bowel disorder commonly exhibit psychiatric co-morbidity and disturbances of the gut-brain axis have been proposed to play a role in these disorders. The focus of this thesis was to study melatonin and melatonin receptors in the normal human GI tract, the pancreas and small intestinal neuroendocrine tumours. The thesis also explores the complex relationship between GI symptoms and underlying psychiatric traits in the context of elevated levels of peripheral melatonin during waking hours.In paper I-II, tissue samples from the normal human GI tract and pancreas and tumour tissue from small intestinal neuroendocrine tumours were analysed for expression of melatonin and melatonin receptors using immunohistochemistry. For tumour patients, melatonin was also analysed in plasma and set in relation to symptoms and outcome. In paper III-IV, a cohort of young adults (18-25 years) seeking psychiatric care was examined for GI symptoms, melatonin levels in saliva, depressive symptoms and anxiety traits. Psychiatric assessments were performed using structured or semi structured interviews. Depressive symptoms were measured using the self-rating version of the Montgomery-Åsberg Depression Rating Scale; GI symptoms were measured using the Gastrointestinal Symptoms Rating Scale for Irritable Bowel Syndrome; and personality traits were evaluated using the Swedish Universities Scales of Personality.Melatonin and melatonin receptors were widely expressed in the normal human gut and pancreas (paper I) but even in small intestinal neuroendocrine tumours known to produce serotonin (paper II). The intensity of the melatonin immunoreactivity in tumour tissue was found to correlate with lower proliferation index. After treatment, plasma levels of melatonin were reduced in tumour patients. Young adult patients seeking psychiatric care reported more GI symptoms than healthy controls, regardless of the currently active psychotropic medication. The level of GI symptoms was associated with severity of depressive symptoms and trait anxiety (paper III). Higher postprandial levels of melatonin were associated with the GI symptoms of bloating and pain (paper IV).In summary, these findings demonstrate the widespread presence of melatonin in the human gut and confirm a link between melatonin, psychiatric health and GI symptoms.
  • Thurin, Erik, et al. (författare)
  • Depression and ability to work after vestibular schwannoma surgery : a nationwide registry-based matched cohort study on antidepressants, sedatives, and sick leave
  • 2021
  • Ingår i: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 163:8, s. 2225-2235
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundIn patients with vestibular schwannomas (VS), tumor control is often achieved, and life expectancy is relatively good. The main risks of surgical treatment are hearing loss and facial nerve function. The occurrence of mood and sleeping disorders in relation to surgery is an important aspect of health that has rarely been studied. Similarly, only limited data exist on the rate of sick leave for patients with VS. In this nationwide registry-based study, we define the use of antidepressants and sedatives and the sick leave pattern before and after VS surgery.MethodsAdult patients with histopathologically verified VS were identified in the Swedish Brain Tumor Registry (SBTR) and clinical data were linked to relevant national registries after assigning five matched controls to each patient. We studied patterns of dispensed antidepressants and sedative drugs as well as patterns of sick leave compared to respective controls at 2 years before and 2 years following surgery.ResultsWe identified 333 patients and 1662 matched controls. The rate of antidepressant use was similar between patients and controls 2 years before surgery (6.0% vs 6.3%) and 2 years after surgery (10.1% vs 7.5%). The rate of sedative use was also similar 2 years before surgery (3.9% vs 4.3%) and 2 years after surgery (4.8% vs 5.3%). The rate of sick leave was similar at baseline between patients and controls, but at 2 years after surgery, 75% of patients vs 88% of controls (p < 0.01) had no registered sick leave. Long-term sick leave after surgery was predicted by use of sedatives (OR 0.60, 95% CI 0.38–0.94, p = 0.03), more preoperative sick leave (OR 0.91, 95% CI 0.89–0.93, p < 0.001), and new-onset neurological deficits after surgery (OR 0.42, 95% CI 0.24–0.76, p = 0.004).ConclusionThis nationwide study shows no significant differences in the use of antidepressants and sedatives between patients and controls, while the rate of postoperative sick leave was higher in patients than in controls after VS surgery. Our findings underpin the importance of avoiding surgical sequelae and facilitating return to normal professional life.
  • Toporski, Jacek, et al. (författare)
  • High-dose iodine-131-metaiodobenzylguanidine with haploidentical stem cell transplantation and posttransplant immunotherapy in children with relapsed/refractory neuroblastoma.
  • 2009
  • Ingår i: Biology of Blood and Marrow Transplantation. - : Elsevier BV. - 1083-8791. ; 15:9, s. 1077-1085
  • Tidskriftsartikel (refereegranskat)abstract
    • We evaluated the feasibility and efficacy of using high-dose iodine-131-metaiodobenzylguanidine ((131)I-MIBG) followed by reduced-intensity conditioning (RIC) and transplantation of T cell-depleted haploidentical peripheral blood stem cells (designated haplo-SCT) to treat relapsing/refractory neuroblastoma (RRNB). Five RRNB patients were enrolled: 4 with relapse (3 after autologous SCT) and 1 with induction therapy failure. The preparative regimen included high-dose (131)I-MIBG on day -20, followed by fludarabine (Flu), thiotepa, and melphalan (Mel) from day -8 to -1. Granulocyte-colony stimulating factor (G-CSF)-mobilized, T cell-depleted haploidentical paternal stem cells were infused on day 0 together with cultured donor mesenchymal stem cells. A single dose of rituximab was given on day +1. After cessation of short immunosuppression (mycophenolate, OKT3), 4 children received donor lymphocyte infusion (DLI). (131)I-MIBG infusion and RIC were well tolerated. All patients engrafted. No primary acute graft-versus-host disease (aGVHD) was observed. Four children developed aGVHD after DLI and were successfully treated. Analysis of immunologic recovery showed fast reappearance of potentially immunocompetent natural killer (NK) and T cells, which might have acted as effector cells responsible for the graft-versus-tumor (GVT) effect. Two children are alive and well, with no evidence of disease 40 and 42 months after transplantation. One patient experienced late progression with new bone lesions (sternum) 38 months after haplo-SCT, and is being treated with local irradiation and reinstituted DLI. One patient rejected the graft, was rescued with autologous backup, and died of progressive disease 5 months after transplantation. Another child relapsed 7 months after transplantation and died 5 months later. High-dose (131)I-MIBG followed by RIC and haplo-SCT for RRNB is feasible and promising, because 2 of 5 children on that regimen achieved long-lasting remission. Further studies are needed to evaluate targeted therapy and immune-mediated tumor control in high-risk neuroblastoma.
  • Wisniewski, Karol, et al. (författare)
  • H3 K27M-Altered Diffuse Midline Gliomas : A Review
  • 2023
  • Ingår i: Indian Journal of Neurosurgery. - : Georg Thieme Verlag KG. - 2277-954X .- 2277-9167. ; 12:02, s. 104-115
  • Forskningsöversikt (refereegranskat)abstract
    • Diffuse midline glioma H3 K27M-altered is a recently renamed high-grade glioma in the 2021 World Health Organization (WHO) Classification of Central Nervous System Tumors, previously being labelled diffuse midline glioma H3 K27M-mutant in the 2016 update and diffuse intrinsic pontine glioma prior to 2016. After identification of multiple alterations causing H3 K27 hypomethylation, the definition of this tumor subtype was changed. To further characterize this new entity in both the pediatric and adult population, we conducted a review of the current literature, investigating genetic, epidemiological, clinical, radiological, histopathological, treatment and prognostic characteristics, particularly highlighting the differences between adults and children. This tumor is more common in children, and has a poorer prognosis. Additionally, childhood H3 K27-altered gliomas are more common in the brainstem, but more common in the thalamus in adults. Sadly, limited treatment options exist for these tumors, with radiotherapy the only treatment shown to improve overall survival.
  • Wängberg, Bo, 1953, et al. (författare)
  • Intraoperative detection of somatostatin-receptor-positive neuroendocrine tumours using indium-111-labelled DTPA-D-Phe1-octreotide.
  • 1996
  • Ingår i: British journal of cancer. - 0007-0920. ; 73:6, s. 770-5
  • Tidskriftsartikel (refereegranskat)abstract
    • After injection of 111In-labelled DTPA-D-Phe1-octreotide, intraoperative tumour localisation was performed using a scintillation detector in 23 patients with neuroendocrine tumours. Count rates from suspect tumour lesions and adjacent normal tissue were expressed as a ratio before (Rin situ) and after (Rex vivo) excision. 111In activity concentration ratios of tumour tissue to blood (T/B) were determined in a gamma counter. In patients with midgut carcinoids, (all scintigraphy positive), false Rin situ recordings were found in 4/29 macroscopically identified tumours. T/B ratios were all high (27-650). In patients with medullary thyroid carcinomas (eight out of ten scintigraphy positive), misleading Rin situ results were found in 4/37 macroscopically identified tumours. T/B ratios were lower (3-39) than those seen in midgut carcinoids. Two out of four patients with endocrine pancreatic tumours had positive scintigraphy, reliable intraoperative measurements and very high T/B ratios (910-1500). One patient with a gastric carcinoid had correct measurements in situ and ex vivo with high T/B ratios (71-210). In situ measurements added little information to preoperative scintigraphy and surgical findings using the present detection system. Rex vivo measurements were more reliable. The very high T/B ratios seen in midgut carcinoids and some endocrine pancreatic tumours would be favourable for future radiation therapy via somatostatin receptors.
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