| 41. |
- Forssell-Aronsson, Eva, 1961, et al.
(författare)
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Indium-111 activity concentration in tissue samples after intravenous injection of indium-111-DTPA-D-Phe-1-octreotide.
- 1995
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 36:1, s. 7-12
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Tidskriftsartikel (refereegranskat)abstract
- Indium-111 activity concentrations in human tumor and normal tissue samples were determined at 24, 48 and 120 hr after i.v. injection of 111In-DTPA-D-Phe-1-octreotide. Fourteen patients were included in the study. Seven patients had medullary thyroid carcinoma, four had midgut carcinoid tumors, two had endocrine pancreatic tumors and one had chronic pancreatitis.
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| 42. |
- Glimelius, Bengt, et al.
(författare)
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Persistent prevention of oxaliplatin-induced peripheral neuropathy using calmangafodipir (PledOx®) : a placebo-controlled randomised phase II study (PLIANT)
- 2018
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 57:3, s. 393-402
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Oxaliplatin causes disabling acute and chronic peripheral neuropathy. We explored the preventive effects of calmangafodipir, mimicking the mitochondrial enzyme manganese superoxide dismutase, thereby protecting cells from oxidative stress, in a placebo-controlled, double-blinded randomised phase II study (ClinicalTrials.gov.NCT01619423) in patients with metastatic colorectal cancer (mCRC).Patient and methods: mCRC patients treated with modified FOLFOX-6 (folinic acid 200 mg/m2, 5-fluorouracil bolus 400 mg/m2, oxaliplatin 85 mg/m2 and 5-fluorouracil 2400 mg/m2 continuous infusion for 46 h) every fortnight for 8 cycles in first or second line were eligible. Calmangafodipir was given in a phase I dose-finding and in a phase II placebo-controlled study, as a 5-min infusion 10 min prior to oxaliplatin. Neurotoxicity was evaluated by the physician using the Oxaliplatin Sanofi Specific Scale and by the patient using the cold allodynia test and the Leonard scale.Results: Eleven patients were included in phase I without any detectable toxicity to calmangafodipir. In the phase II study, 173 patients were randomised to placebo (n = 60), calmangafodipir 2 µmol/kg (n = 57) and calmangafodipir 5 µmol/kg (n = 45, initially 10 µmol/kg, n = 11). Calmangafodipir-treated patients (all three doses pooled) had less physician graded neurotoxicity (odds ratio (90% confidence interval one-sided upper level) 0.62(1.15), p = .16), significantly less problems with cold allodynia (mean 1.6 versus 2.3, p < .05) and significantly fewer sensory symptoms in the Leonard scale (cycle 1–8 mean 1.9 versus 3.0, p < .05 and during follow-up after 3 and 6 months, mean 3.5 versus 7.3, p < .01). Response rate, progression-free and overall survival did not differ among groups.Conclusions: Calmangafodipir at a dose of 5 µmol/kg appears to prevent the development of oxaliplatin-induced acute and delayed CIPN without apparent influence on tumour outcomes.
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| 43. |
- Hartel, Bas P., et al.
(författare)
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A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa
- 2016
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Ingår i: Hearing Research. - Amsterdam, Netherlands : Elsevier. - 0378-5955 .- 1878-5891. ; 339, s. 60-68
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Usher syndrome is an inherited disorder that is characterized by hearing impairment (HI), retinitis pigmentosa, and in some cases vestibular dysfunction. Usher syndrome type IIa is caused by mutations in USH2A. HI in these patients is highly heterogeneous and the present study evaluates the effects of different types of USH2A mutations on the audiometric phenotype. Data from two large centres of expertise on Usher Syndrome in the Netherlands and Sweden were combined in order to create a large combined sample of patients to identify possible genotype-phenotype correlations.Design: A retrospective study on HI in 110 patients (65 Dutch and 45 Swedish) genetically diagnosed with Usher syndrome type IIa. We used methods especially designed for characterizing and testing differences in audiological phenotype between patient subgroups. These methods included Age Related Typical Audiograms (ARTA) and a method to evaluate the difference in the degree of HI developed throughout life between subgroups.Results: Cross-sectional linear regression analysis of last-visit audiograms for the best hearing ear demonstrated a gradual decline of hearing over decades. The congenital level of HI was in the range of 16-33 dB at 0.25-0.5 kHz, and in the range of 51-60 dB at 1-8 kHz. The annual threshold deterioration was in the range of 0.4-0.5 dB/year at 0.25-2 kHz and in the range of 0.7-0.8 dB/year at 4-8 kHz. Patients with two truncating mutations, including homozygotes for the common c.2299delG mutation, developed significantly more severe HI throughout life than patients with one truncating mutation combined with one nontruncating mutation, and patients with two nontruncating mutations.Conclusions: The results have direct implications for patient counselling in terms of prognosis of hearing and may serve as baseline measures for future (genetic) therapeutic interventions.
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| 44. |
- Karlsson, Markus, et al.
(författare)
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Increased bile excretion of Gd-EOB-DTPA in diffuse liver disease : mechanistic modeling of qDCE-MRI in patients with severe fibro-sis
- 2016
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Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer. - 0968-5243 .- 1352-8661. ; 29:1, s. S272-S273
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionOver the past decades, several different non-invasive methods for staging hepatic fibrosis have been proposed. One such method is dynamic contrast enhanced MRI (DCE-MRI) using the contrast agent (CA) Gd-EOB-DTPA. Gd-EOB-DTPA is liver specific, which means that it is taken up specifically by the hepatocytes via the OATP3B1/B3 transporters and excreted into the bile via the MRP2 transporter. Several studies have shown that DCE-MRI and Gd-EOBDTPA can separate patients with advanced (F3-F4) from mild (F0-F2) hepatic fibrosis by measuring the signal intensity, where patients with advanced fibrosis have a lower signal intensity than the mild fibrosis cases.1 However, none of the studies up to date have been able to differentiate if the reduced signal intensity in the liver is because of an decreased uptake of CA or an increased excretion. Analyzing the DCE-MRI data with mechanistic mathematical modelling has the possibility of investigating such a differentiation.Subjects and methods88 patients with diffuse liver disease were examined using DCE-MRI (1.5 T Philips Achieva, two-point Dixon, TR=6.5 ms, TE=2.3/4.6 ms, FA=13) after a bolus injection of Gd-EOB-DTPA, followed by a liver biopsy. Regions of interest were placed within the liver, spleen and veins and a whole-body mechanistic pharmacokinetic model2 was fitted to the data. The fitted parameters in the model correspond to the rate of CA transport between different compartments, e.g. hepatocytes, blood plasma, and bile (Fig. 1).ResultsAs can be seen in Fig. 2, the parameter corresponding to the transport of CA from the blood plasma to the hepatocytes, kph, is lower for patients with advanced fibrosis (p=0.01). Fig. 3 shows that the parameter corresponding to the CA excretion into the bile, khb, is higher for patients with advanced fibrosis (p<0.01).Discussion/ConclusionThis work shows that the decreased signal intensity in DCE-MRI images in patients with advanced fibrosis depends on both a decreased uptake of CA in the hepatocytes and an increased excretion into the bile. Similar results have also been observed in a rat study3. In that study, rats with induced cirrhosis had a higher MRP2-activity than the healthy control rats.References1Norén et al: Eur. Radiol, 23(1), 174-181, 2013.2Forsgren et al: PloS One, 9(4): e95700, 2014.3Tsuda & Matsui: Radiol, 256(3): 767-773, 2010.
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| 45. |
- Lönnbro-Widgren, Jennie, et al.
(författare)
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Treatment pattern in patients with idiopathic membranous nephropathy-practices in Sweden at the start of the millennium
- 2016
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 9:2, s. 227-233
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Tidskriftsartikel (refereegranskat)abstract
- Background Idiopathic membranous nephropathy (MN) is one of the leading causes of nephrotic syndrome in adults and may result in end-stage renal disease (ESRD). In this retrospective study, we describe the outcomes and treatment patterns of patients with idiopathic MN in six nephrology clinics in the western part of Sweden. Methods Seventy-three consecutive patients with biopsy-proven MN in the years 2000-12 were classified as idiopathic, i.e. secondary forms were excluded. The patients were followed retrospectively for a mean period of 83 months and clinical data were collected through the medical files. Results A high proportion (88%) of the patients received supportive treatment with angiotensin-converting enzyme inhibition, angiotensin receptor blockade and/or statins. At the end of follow-up, 43 patients were in complete remission, 12 in partial remission, 10 patients had developed ESRD and 8 patients had on-going proteinuria. Fifty-one per cent of the patients received immunosuppressive therapy and the choice of therapy varied between and within the clinics. There was a tendency to initiate specific treatment at an early point instead of awaiting a possible spontaneous remission (21% of the patients), and non-recommended therapy such as corticosteroids only was used in a high proportion of these cases (47%). Conclusions Even though the treatment recommendations in idiopathic MN have not changed the last decade, the question of whom and when to treat seems to lead to uncertainty. Recent studies have presented promising results supporting the PLA2R antibody the predictive marker needed for this patient group. The diverse treatment approach presented in this study might have resulted in a worse outcome than expected. Hopefully, unnecessary exposure to immunosuppressive therapy or delayed treatment can be avoided through better support, education and treatment forums, and thus result in an improved outcome. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.
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| 46. |
- Morgell, Ann, et al.
(författare)
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Metabolic Characterization of Plasma and Cyst Fluid from Cystic Precursors to Pancreatic Cancer Patients Reveal Metabolic Signatures of Bacterial Infection
- 2021
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3907 .- 1535-3893. ; 20:5, s. 2725-2738
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer is the seventh leading cause of cancer-related death worldwide, with a 5 year survival rate as low as 9%. One factor complicating the management of pancreatic cancer is the lack of reliable tools for early diagnosis. While up to 50% of the adult population has been shown to develop precancerous pancreatic cysts, limited and insufficient approaches are currently available to determine whether a cyst is going to progress into pancreatic cancer. Recently, we used metabolomics approaches to identify candidate markers of disease progression in patients diagnosed with intraductal papillary mucinous neoplasms (IPMNs) undergoing pancreatic resection. Here, we enrolled an independent cohort to verify the candidate markers from our previous study with orthogonal quantitative methods in plasma and cyst fluid from serous cystic neoplasm and IPMN (either low- or high-grade dysplasia or pancreatic ductal adenocarcinoma). We thus validated these markers with absolute quantitative methods through the auxilium of stable isotope-labeled internal standards in a new independent cohort. Finally, we identified novel markers of IPMN status and disease progression - including amino acids, carboxylic acids, conjugated bile acids, free and carnitine-conjugated fatty acids, purine oxidation products, and trimethylamine-oxide. We show that the levels of these metabolites of potential bacterial origin correlated with the degree of bacterial enrichment in the cyst, as determined by 16S RNA. Overall, our findings are interesting per se, owing to the validation of previous markers and identification of novel small molecule signatures of IPMN and disease progression. In addition, our findings further fuel the provoking debate as to whether bacterial infections may represent an etiological contributor to the development and severity of the disease in pancreatic cancer, in like fashion to other cancers (e.g., Helicobacter pylori and gastric cancer).
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| 47. |
- Ohlsson, Bodil, et al.
(författare)
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Patients with irritable bowel syndrome and dysmotility express antibodies against gonadotropin-releasing hormone in serum.
- 2011
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 23, s. 459-1000
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Tidskriftsartikel (refereegranskat)abstract
- Background The etiology of irritable bowel syndrome (IBS) and dysmotility is in most cases unknown. Organic, pathognomonic changes have not been described. We have previously demonstrated sporadic expressions of antibodies against gonadotropin-releasing hormone (GnRH) in serum from these patients. The aim of this study was to screen for the presence of GnRH antibodies in healthy subjects and patients with gastrointestinal (GI) diseases. Methods Consecutive patients suffering from either IBS, idiopathic dysmotility, GI complaints secondary to diabetes mellitus, celiac disease or inflammatory bowel disease (IBD) were included. Healthy blood donors served as controls. Blood samples were taken for analyzing IgM and IgG antibodies against GnRH using an ELISA method. Medical records were scrutinized with respect to duration of symptoms, co-existing diseases, drug treatments, hereditary factors, and laboratory analyses. Key Results Healthy controls expressed low levels of GnRH IgM antibodies in a prevalence of 23%. The prevalence of GnRH IgM antibodies in IBS and dysmotility patients was 42% (P = 0.008), and the levels were higher (P = 0.000). Patients with diabetes mellitus expressed GnRH IgM antibodies in the same prevalence as controls (25%), but in higher levels (P = 0.02). Patients with celiac disease or IBD had the same or lower levels of antibodies. There were no associations between antibodies, other co-existing diseases or laboratory analyses. Conclusions & Inferences Higher levels of GnRH IgM antibodies were detected in patients with IBS and dysmotility, but not organic GI diseases, compared with healthy controls. These findings suggest that IBS and dysmotility to some extent may be of an autoimmune origin.
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| 48. |
- Stråvik, Mia, 1994, et al.
(författare)
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Maternal Intake of Cow's Milk during Lactation Is Associated with Lower Prevalence of Food Allergy in Offspring
- 2020
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 12:12, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- Maternal diet during pregnancy and lactation may affect the propensity of the child to develop an allergy. The aim was to assess and compare the dietary intake of pregnant and lactating women, validate it with biomarkers, and to relate these data to physician-diagnosed allergy in the offspring at 12 months of age. Maternal diet during pregnancy and lactation was assessed by repeated semi-quantitative food frequency questionnaires in a prospective Swedish birth cohort (n = 508). Fatty acid proportions were measured in maternal breast milk and erythrocytes. Allergy was diagnosed at 12 months of age by a pediatrician specialized in allergy. An increased maternal intake of cow's milk during lactation, confirmed with biomarkers (fatty acids C15:0 and C17:0) in the maternal blood and breast milk, was associated with a lower prevalence of physician-diagnosed food allergy by 12 months of age. Intake of fruit and berries during lactation was associated with a higher prevalence of atopic eczema at 12 months of age. Our results suggest that maternal diet modulates the infant's immune system, thereby influencing subsequent allergy development.
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| 49. |
- Söderquist, Fanny
(författare)
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Melatonin in the gastrointestinal tract
- 2019
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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.
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