SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Hellman Per) srt2:(2005-2009)"

Sökning: WFRF:(Hellman Per) > (2005-2009)

  • Resultat 1-50 av 50
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Hellman, Per, et al. (författare)
  • Ligand surface density is important for efficient capture of immunoglobulin and phosphatidylcholine coated particles by human peripheral dendritic cells
  • 2009
  • Ingår i: Cellular Immunology. - : Elsevier BV. - 0008-8749 .- 1090-2163. ; 258:2, s. 123-30
  • Tidskriftsartikel (refereegranskat)abstract
    • A unique property of dealuminated zeolite particles is the exceptional ability to bind both hydrophilic and hydrophobic biomolecules without any covalent linkages. By adsorbing phospholipids onto the particle surface, capture of particles by human peripheral myeloid dendritic cells (mDCs) was observed. Capture of zeolite particles was only seen when a low density of phosphatidylcholine was present on the particles, indicating a specific recognition of the structural features realised by phosphatidylcholine after adsorption on the particle. Adsorbing IgG on the particles revealed capture by mDCs that was dependent upon the density of the IgG molecules. To obtain a smaller particle exposing a high density of IgG molecules, immune complexes (ICs) were formed and both mDCs and pDCs (peripheral plasmacytoid DCs) captured immune complexes, although the mDCs showed a more efficient capture of ICs. As expected, mDCs captured and internalized ICs, whereas pDCs captured ICs but showed no internalization of ICs.
  •  
2.
  • Ahlström, Tommy, et al. (författare)
  • Correlation between plasma calcium, parathyroid hormone (PTH) and the metabolic syndrome (MetS) in a community-based cohort of men and women
  • 2009
  • Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 71:5, s. 673-678
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: In recent years, an association has been noted between several abnormalities that characterize the metabolic syndrome (MetS) and primary hyperparathyroidism (pHPT). These abnormalities include dyslipidaemia, obesity, insulin resistance and hypertension. The correlations between plasma calcium, parathyroid hormone (PTH) and the variables in the MetS in a normal population are still unclear.OBJECTIVE: To describe correlations between plasma calcium and PTH and the various abnormalities present in the MetS in a healthy population.DESIGN: We studied 1016 healthy individuals from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) population of 70 years old, by means of plasma analyses of calcium, PTH, creatinine, lipids, insulin and glucose, as well as by standardized blood pressure measurements. Further, body mass index (BMI) and waist circumference were determined.RESULTS: The more National Cholesterol Education Program (NCEP) criteria for the MetS that were met, the higher the s-PTH and albumin-corrected s-calcium. Further, positive correlations between plasma calcium and BMI (P = 0.0003), waist circumference (P = 0.0009) and insulin resistance (P = 0.079) were found. PTH and BMI (P < 0.0001), waist circumference (P < 0.0001), systolic blood pressure (P = 0.0034), diastolic blood pressure (P = 0.0008), serum triglycerides (P = 0.0003) and insulin resistance (P = 0.0003) were positively correlated, whereas serum high density lipoproteins (HDL) (P = 0.036) and PTH were negatively correlated.CONCLUSIONS: We conclude that PTH correlates with several of the metabolic factors included in the MetS within a normocalcaemic population. In addition, individuals with mild pHPT present significantly more NCEP criteria for MetS. We postulate that increased levels of PTH in pHPT may be associated with the increased cardiovascular morbidity and mortality seen in pHPT.
  •  
3.
  • Andersson, Maria, et al. (författare)
  • Interindividual differences in initial DNA repair capacity when evaluating H2O2-induced DNA damage in extended-term cultures of human lymphocytes using the comet assay
  • 2007
  • Ingår i: Cell Biology and Toxicology. - : Springer Science and Business Media LLC. - 0742-2091 .- 1573-6822. ; 23:6, s. 401-411
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been suggested that extended-term cultures of human lymphocytes could be used as a complement to cell lines based on transformed cells when testing the genotoxicity of chemicals. To investigate whether the pattern of induced DNA damage and its subsequent repair differs significantly between cultures based on different blood donors, hydrogen peroxide (H2O2)-induced DNA damage was measured in cultures from four different subjects using the comet assay. The DNA damage was significantly increased in all cultures after 10 min exposure to 0.25 mmol/L H2O2, and there was a significant decrease in the H2O2-induced DNA damage in all cultures after 30 min of DNA repair. The level of damage varied between the different donors, especially after the repair. Using PCR and DNA sequencing, exon 5 of the p53 gene was sequenced in the lymphocytes from the donors with the lowest and highest residual damage. No such mutation was found. Mouse lymphoma L5178Y cells carrying the p53 mutation in exon 5 were included as a reference. These cells were found to be less sensitive toward the H2O2-induced DNA damage, and they were also found to have a rather low DNA repair capacity. The demonstrated variation in H2O2-induced DNA damage and DNA repair capacity between the cultures from the different subjects may be important from a risk assessment perspective, but is obviously not of decisive importance when it comes to the development of a routine assay for genotoxicity.
  •  
4.
  • Andersson, Mattias K., 1978- (författare)
  • Cleavage Specificity of Mast Cell Chymases
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Mast cells (MC) are potent inflammatory cells that are known primarily for their prominent role in IgE mediated allergies. However, they also provide beneficial functions to the host, e.g. in bacterial and parasitic defence. MCs react rapidly upon stimulation by releasing potent granule-stored mediators, and serine proteases of the chymase or tryptase families are such major granule constituents. As a first step towards a better understanding of the biological function of these proteases, we have determined the extended cleavage specificities of four mammalian mast cell chymases, by utilizing a substrate phage display approach. The specificities of these enzymes have then been used to compare their functional characteristics.The major mucosal MC chymase in mice, mMCP-1, was found to possess a strict preference in four amino acid positions of the peptide substrate. Using this sequence to search the mouse proteome for potential in vivo substrates led to the identification of several very interesting potential novel substrates. Some of them may explain the increased epithelial permeability provided by this enzyme.Human MCs, express only one single α-chymase, and the rodent α-chymases have secondarily gained elastase-like primary cleavage specificity. However, rodents express additional chymases, the β-chymases, and rodent β-chymases may have adopted the function of the α-chymases. The cleavage specificities of the human chymase and two rodent β-chymases were therefore determined (rat rMCP-1 and mouse mMCP-4). N-terminal of the cleaved bond the three chymases showed similar preferences, but C-terminal the human chymase and mMCP-4 shared a high preference for acidic amino acids in the P2´ position and therefore seem to be functional homologues. The molecular interactions mediating the preference for acidic amino acids in position P2´ were further investigated. By site-directed mutagenesis of the human chymase, amino acids Arg143 and Lys192 were concluded to synergistically mediate this preference.Our data show that chymases, of different MC subpopulations, display quite different extended cleavage specificities. However mouse do possess a MC chymase with almost identical cleavage specificity as the human MC chymase indicating a strong evolutionary pressure to maintain this enzyme specificity.
  •  
5.
  •  
6.
  •  
7.
  •  
8.
  • Enberg, U., et al. (författare)
  • Increased ratio of mRNA expression of the genes CYP17 and CYP11B1 indicates autonomous cortisol production in adrenocortical tumors
  • 2009
  • Ingår i: Journal of Endocrinological Investigation. - 0391-4097 .- 1720-8386. ; 32:10, s. 810-815
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Due to increased use of imaging techniques, adrenal incidentalomas are frequently detected. The majority are non-hyperfunctioning adrenocortical tumors. We have previously shown that expression of the gene CYP17, coding for the enzyme in the cortisol pathway, correlates with cortisol release from adrenocortical tumors in vitro. The aim of this study was to compare clinical data with mRNA expression of CYP17 and CYP11B1 in adrenocortical tumors from patients with and without Cushing's syndrome and to identify adrenal tumors that may cause subclinical Cushing's syndrome. DESIGN: A retrospective study of 34 patients undergoing adrenalectomy due to an adrenal tumor. METHODS: Clinical data were collected. In the adrenal gland the mRNA expression of the genes CYP17 and CYP11B1 was studied with in situ hybridisation technique. RESULTS: The median ratio of CYP17/CYP11B1 expression in tumors from patients with Cushing's syndrome was significantly higher than the median ratio in the non-hyperfunctioning tumors. Tumors from 2 patients with subclinical Cushing's syndrome had ratios within the upper range for non-hyperfunctioning tumors. CONCLUSIONS: The ratio between the expression of the genes CYP17 and CYP11B1 in tumors from patients with Cushing's syndrome is significantly higher than in the non-hyperfunctioning tumors. This indicates that 17alpha-hydroxylase is a major determinant of cortisol overproduction. The patients with subclinical Cushing's syndrome in this study are too few to draw any firm conclusions although the results suggest that subclinical Cushing's syndrome may be identified post-operatively with this method.
  •  
9.
  • Enqvist, Stina, et al. (författare)
  • Germ Line Origin and Somatic Mutations Determine the Target Tissues in Systemic AL-Amyloidosis
  • 2007
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 2:10, s. e981-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Amyloid is insoluble aggregated proteins deposited in the extra cellular space. About 25 different proteins are known to form amyloid in vivo and are associated with severe diseases such as Alzheimeŕs disease, prion diseases and type-2 diabetes. Light chain (AL) -amyloidosis is unique among amyloid diseases in that the fibril protein, a monoclonal immunoglobulin light chain, varies between individuals and that no two AL-proteins with identical primary structures have been described to date. The variability in tissue distribution of amyloid deposits is considerably larger in systemic AL-amyloidosis than in any other form of amyloidosis. The reason for this variation is believed to be based on the differences in properties of the amyloidogenic immunoglobulin light chain. However, there is presently no known relationship between the structure of an AL-protein and tissue distribution. METHODOLOGY/PRINCIPAL FINDINGS: We compared the pattern of amyloid deposition in four individuals with amyloid protein derived from variable light chain gene O18-O8, the source of a high proportion of amyloidogenic light chains, and in whom all or most of the fibril protein had been determined by amino acid sequencing. In spite of great similarities between the structures of the proteins, there was a pronounced variability in deposition pattern. We also compared the tissue distribution in these four individuals with that of four other patients with AL-amyloid derived from the L2-L16 gene. Although the interindividual variations were pronounced, liver and kidney involvement was much more evident in the latter four. CONCLUSIONS/SIGNIFICANCE: We conclude that although the use of a specific gene influences the tissue distribution of amyloid, each light chain exhibits one or more determinants of organ-specificity, which originate from somatic mutations and post-translational modifications. Eventual identification of such determinants could lead to improved treatment of patients with AL amyloidosis.
  •  
10.
  • Eriksson, John, et al. (författare)
  • Surgery and radiofrequency ablation for treatment of liver metastases from midgut and foregut carcinoids and endocrine pancreatic tumors
  • 2008
  • Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 32:5, s. 930-938
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Many neuroendocrine tumors (NETs) have a tendency to metastasize to the liver. In case of limited number of metastases, liver surgery or radiofrequency ablation (RFA) may result in apparently total clearance of metastases. However, it is not clear whether such therapy will provide symptom reduction or increased survival.METHODS: Seventy-three patients with foregut (n=6) or midgut carcinoids (n=37) or endocrine pancreatic tumors (n=28), and two patients with NETs without discernable origin were studied. Symptoms were evaluated using a Symptom Severity Score. Liver surgery was performed in 42 operations and RFA on 205 lesions.RESULTS:Apparently total clearance of liver metastases was attained in 1 of 6 patients with foregut carcinoids, 15 of 37 with midgut carcinoids, and 13 of 28 with EPT. Symptom improvement was noted in 12 of 17 (70.6%) patients with carcinoid syndrome, and 75% also reduced their 5-HIAA and P-CgA by at least 50%. Patients with nonfunctioning EPT generally had no improvement of symptoms after surgical/RFA liver treatment, but eight patients had functioning EPT, and four of these reduced their biochemical markers by at least 50%. NETs with higher Ki67 index tended to recur more often. Complications occurred in 9 of 45 open surgery procedures, and in 8 of 203 RFA procedures.CONCLUSIONS:Treatment of liver metastases is successful in midgut carcinoid patients with limited liver metastases. Patients with foregut carcinoid and EPTs recur more often, possibly related to higher Ki67 index, and treatment of liver lesions less often reduces symptoms. Liver resections and RFA may be safely performed, and RFA is associated with few complications.
  •  
11.
  • Hagström, Emil, et al. (författare)
  • Metabolic abnormalities in patients with normocalcemic hyperparathyroidism detected at a population-based screening
  • 2006
  • Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 155:1, s. 33-39
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Dyslipidemia, hypertension, diabetes mellitus and also primary hyperparathyroidism (pHPT)are associated with an increased risk of cardiovascular diseases. Metabolic abnormalities in mild pHPThave been reported, but never in cases with normal calcium and high parathyroid hormone (PTH)levels, i.e. suffering from ‘normocalcemic pHPT’. Our aim was to explore the occurrence of thesemetabolic abnormalities in individuals with normocalcemic pHPT identified in a population-basedscreening, and the effects of parathyroidectomy vs conservative treatment on metabolic variables.Design and methods: A population-based screening of 5202 post-menopausal women identified 30patients with normal calcium, inappropriately high PTH and normal creatinine. A 5-year follow-upincluded 15 parathyroidectomized (PTx) and nine conservatively followed cases, in a non-randomizedsetting, together with age-matched controls. Biochemical variables and body mass index (BMI) wereinvestigated.Results: At study entry, cases had higher calcium, PTH, glucose, low-density lipoprotein (LDL)/highdensitylipoprotein (HDL)-cholesterol, very low-density lipoprotein (VLDL)-cholesterol, total triglycerides,and BMI compared to controls (PZ!0.0001–0.035). The cases had a lower HDL-cholesterolvalue (PZ0.013) and one third of the cases had hypertriglyceridemia. During follow-up, the PTx casesdecreased in calcium, PTH, LDL/HDL-cholesterol, total and LDL-cholesterol (PZ0.0076–0.022).Investigated biochemical variables remained adverse in conservatively followed cases during follow-upexcept a decreased LDL-cholesterol value. All surgically treated patients had parathyroid adenoma.Conclusions: Cases with normocalcemic pHPT have increased proatherogenic lipoprotein levels, BMIand glucose levels compared to age-matched controls. Parathyroidectomy has positive effects on someof these variables and reverses them to the same level as the controls, while conservative treatmentfails to normalize the investigated metabolic variables.
  •  
12.
  • Hagström, Emil, 1975- (författare)
  • Metabolic Disturbances in Relation to Serum Calcium and Primary Hyperparathyroidism
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Primary hyperparathyroidism (pHPT), characterized by elevated serum levels of calcium and parathyroid hormone (PTH), is associated with a number of metabolic derangements causing secondary manifestations. These include osteoporosis and increased risk of fractures, but also risk factors for cardiovascular morbidity and mortality. These risk factors include impaired glucose tolerance (IGT), dyslipidemia, increased body mass index and hypertension. While the skeletal abnormalities are mainly due to elevated PTH, the latter disturbances are still unexplained. Non-insulin dependent diabetes mellitus (NIDDM), IGT, dyslipidemia and hypertension are all included in the metabolic syndrome, also associated with morbidity and mortality in cardiovascular diseases.In this thesis, decreased bone mineral density (BMD) and variables of the metabolic syndrome are explored in patients with mild and normocalcemic pHPT before and after parathyroidectomy. To further investigate the relationship between insulin sensitivity and calcium, a community-based cohort was investigated.In two different patient cohorts of pHPT, lipoprotein alterations with decreased levels of HDL-cholesterol and elevated triglycerides were found in association with a high frequency of IGT, NIDDM and decreased insulin sensitivity. Parathyroidectomy had effects on the dyslipidemia and in part on the glucose metabolism. The disturbed glucose metabolism in pHPT was substantiated by results from the general population by a negative association between insulin sensitivity, measured by hyperinsulinemic clamp, and serum calcium.In conclusion, normocalcemic, mild and overt pHPT are associated with a range of risk factors for cardiovascular diseases, development of NIDDM and decreased BMD in cortical as well as trabecular bone. These findings explain, at least in part, the elevated morbidity and mortality from cardiovascular disease as well as fractures, reported in pHPT patients. Moreover, in the general population, serum calcium is associated with decreased insulin sensitivity. Parathyroidectomy has positive effects on several, but not all, of the investigated metabolic parameters.
  •  
13.
  • Hagström, Emil, et al. (författare)
  • Plasma parathyroid hormone and the risk of cardiovascular mortality in the community
  • 2009
  • Ingår i: Circulation. - : American Heart Association. - 0009-7322 .- 1524-4539. ; 119:21, s. 2765-2771
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Diseases with elevated levels of parathyroid hormone (PTH) such as primary and secondary hyperparathyroidism are associated with increased incidence of cardiovascular disease and death. However, data on the prospective association between circulating PTH levels and cardiovascular mortality in the community are lacking. METHODS AND RESULTS: The Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (mean age, 71 years; n=958), was used to investigate the association between plasma PTH and cardiovascular mortality. During follow-up (median, 9.7 years), 117 participants died of cardiovascular causes. In Cox proportional-hazards models adjusted for established cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease), higher plasma PTH was associated with higher risk for cardiovascular mortality (hazard ratio for 1-SD increase in PTH, 1.38; 95% confidence interval, 1.18 to 1.60; P<0.001). This association remained essentially unaltered in participants without previous cardiovascular disease and in participants with normal PTH (<6.8 pmol/L) with no other signs of a disturbed mineral metabolism (normal serum calcium, 2.2 to 2.6 mmol/L; normal glomerular filtration rate, >50 mL . min(-1) . 1.73 m(-2) and without vitamin D deficiency, plasma 25-OH vitamin D >37.5 nmol/L). Interestingly, elevated plasma PTH (>5.27 pmol/L) accounted for 20% (95% confidence interval, 10 to 26) of the population-attributable risk proportion for cardiovascular mortality. CONCLUSIONS: Plasma PTH levels predict cardiovascular mortality in the community, even in individuals with PTH within the normal range. Further studies are warranted to evaluate the clinical implications of measuring PTH in cardiovascular risk prediction and to elucidate whether PTH is a modifiable risk factor.
  •  
14.
  •  
15.
  • Hagström, Emil, et al. (författare)
  • Serum calcium is independently associated with insulin sensitivity measured with euglycaemic-hyperinsulinaemic clamp in a community-based cohort
  • 2007
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 50:2, s. 317-324
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS/HYPOTHESIS: Diabetes mellitus type 2 is associated with altered calcium metabolism. Moreover, in diseases with supranormal serum calcium levels, such as primary hyperparathyroidism, the prevalence of diabetes is increased. Relatively little is known about the relationship between serum calcium concentration and the underlying causes of diabetes-insulin resistance and defective insulin secretion-in the normocalcaemic general population. MATERIALS AND METHODS: We investigated associations between serum calcium concentration and insulin sensitivity and secretion in a population-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men, n = 961). Insulin sensitivity index (M/I; glucose disposal rate [M] divided by mean insulin concentration [I]) was assessed using euglycaemic-hyperinsulinaemic clamp, and insulin secretion was estimated from the early insulin response (EIR) during an OGTT. RESULTS: In a multivariable linear regression model adjusting for BMI, physical activity, smoking, consumption of tea, alcohol, coffee and dietary calcium, serum phosphate and serum creatinine, 1 SD increase in serum calcium was associated with 0.17 mg kg(-1) min(-1) (mU/l)(-1) x 100 (0.024 mg kg(-1) min(-1) [pmol/l](-1) x 100) decrease in M/I (p = 0.01). The results remained robust in individuals with normal fasting glucose, normal glucose tolerance and serum calcium within the normal range (n = 413, regression coefficient for 1 SD increase -0.45, p = 0.001). Serum calcium was not associated with EIR. Dietary intake of calcium was not independently associated with insulin sensitivity or EIR. CONCLUSION/INTERPRETATION: Our data support the notion that endogenous calcium may be involved early in the development of diabetes and that this effect is mediated mainly through effects on insulin sensitivity rather than defective insulin secretion. Dietary intake of calcium does not seem to influence insulin sensitivity.
  •  
16.
  •  
17.
  • Hellman, Per (författare)
  • Culture of parathyroid cells
  • 2005
  • Ingår i: Human Cell Culture. - New Jersey : Humana Press. - 1592598617 ; , s. 291-301
  • Bokkapitel (refereegranskat)
  •  
18.
  • Hellman, Per (författare)
  • Endokrina tumörer - ett folkhälsoproblem?
  • 2009
  • Ingår i: Svensk kirurgi. - 0346-847X. ; 67:2, s. 69-71
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Kan endokrina tumörer vara en av de större bakomliggande orsakerna till hjärtkärlsjukdom i Sverige och skall endokrinkirugin drastiskt öka för att motverka detta? En fråga som Per Hellman, professor i kirurgi vid Akademiska sjukhuset i Uppsala och tillika kirurgföreningens vetenskaplige sekreterare, väcker.
  •  
19.
  •  
20.
  • Hennings, Joakim, et al. (författare)
  • [11C]metomidate positron emission tomography of adrenocortical tumors in correlation with histopathological findings
  • 2006
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:4, s. 1410-4
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Adrenal incidentalomas are common findings necessitating extensive laboratory work-up and repetitive radiological examinations. Positron emission tomography (PET) using (11)C-labeled metomidate (MTO) has previously been described as a tool for specific adrenocortical imaging. OBJECTIVE: We evaluated 212 MTO-PET examinations in 173 patients to identify its role in the management of adrenal tumors. DESIGN: Seventy-five histopathological examinations from 73 patients were retrospectively analyzed. SETTING: All examinations were performed at a referral center. PATIENTS: Patients who were operated or biopsied due to adrenal tumors had histopathological diagnoses of adrenocortical adenoma (n = 26), adrenocortical cancer (ACC; n = 13), adrenocortical hyperplasia (n = 8), pheochromocytoma (n = 6), metastasis (n = 3), and tumors of nonadrenal origin (n = 19). MAIN OUTCOME MEASURES: The main outcome measures were statistical analyses and findings while scrutinizing images. The hypothesis that MTO-PET is of value in the management of adrenal tumors, especially incidentaloma, was stated before data collection. RESULTS: Sensitivity was 0.89 and specificity was 0.96 for MTO-PET in proving adrenocortical origin of the lesions. Pheochromocytomas, metastases to the adrenal gland, and nonadrenal masses were all MTO negative. PET measurements using standardized uptake values (SUV) in pathological adrenocortical tissue could differentiate lesions larger than 1-1.5 cm from normal adrenocortical tissue. SUV was higher in aldosterone-hypersecreting adenomas, and the SUV ratio between the tumor and the contralateral gland was significantly higher in all hormonally hypersecreting adenomas as well as in ACC. CONCLUSION: MTO-PET is a specific and sensitive method for diagnosing adrenocortical tumors. MTO-PET is useful in the imaging work-up of adrenal incidentalomas and may be beneficial for the examination of patients with primary aldosteronism or ACC.
  •  
21.
  • Hennings, Joakim, 1969- (författare)
  • Clinical Studies on Adrenocortical Tumours using  [11C]-metomidate Positron Emission Tomography
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Adrenal tumours, discovered en passant in patients undergoing radiological examinations for non-adrenal disease, so-called adrenal incidentalomas, have increased dramatically in the recent era of more sophisticated diagnostic modalities such as high resolution multidetector computed tomography (CT) and magnetic resonance imaging (MRI). Furthermore, primary aldosteronism (PA) has been documented in several screening studies as being far more common than previously believed among hypertensive patients. In this thesis, a long-term follow-up cohort of patients who had undergone surgery for PA revealed that there was an excellent effect on blood-pressure, reduction of anti-hypertensive medication and hypokalaemia after surgery, even though the majority of these patients still required some anti-hypertensive medication. This was also true, in the higher than expected number of dominant nodular hyperplasia (nIHA) found in the study, but was slightly less pronounced than in aldosterone producing adenomas (APA).  Surgery was thus effective in lateralized PA. Metomidate positron emission tomography (MTO-PET) was explored in relation to histopathology in post-operative patients and found to be highly specific and sensitive in categorizing adrenocortical disease. Also, a higher standardized uptake value (SUV) ratio between tumours and normal adrenal cortex was found in hormonally hypersecreting adenomas as well as in adrenocortical cancer (ACC). The resolution limited the diagnosis of small tumours (<1-1.5 cm). MTO-PET was compared to standard radiological modalities (CT and MRI) in the diagnostic work-up of adrenal incidentalomas. All three modalities categorized and characterized the lesions well, with MTO-PET showing the highest sensitivity and specificity.  However this method is currently recommended to be used as complementary to the others in unclear cases, due to high costs and less availability. The resolution of MTO-PET was improved with respect to less noise and better delineation of small tumours when applying masked volume-wise principal component analysis (MVW-PCA), which will possibly enable future detection of small tumours in PA patients. Dexamethasone suppression treatment prior to MTO-PET examinations in PA patients decreased SUV in normal adrenal cortex but could not be shown to increase the SUV ratio between adenoma and normal cortex enabling better detection of small tumours, even though all the tumours were readily categorized in the study. Heterogenic SUV reactions to dexamethasone treatment indicate a need for further studies and refinement of the suppression method. In conclusion, long-term results of surgery for lateralized PA are good. MTO-PET is a highly sensitive and specific method for categorizing adrenocortical disease. Modulation of the method, e.g. by using MVW-PCA and refined dexamethasone suppression treatment, may improve the resolution of the method in delineating small tumours in PA, thus making MTO-PET a non-invasive and non-operator dependent future alternative to the currently recommended adrenal venous sampling (AVS) for lateralization diagnosis prior to surgery for PA.
  •  
22.
  • Hennings, Joakim, et al. (författare)
  • Computed tomography, magnetic resonance imaging and 11C-metomidate positron emission tomography for evaluation of adrenal incidentalomas
  • 2009
  • Ingår i: European Journal of Radiology. - : Elsevier BV. - 0720-048X .- 1872-7727. ; 69:2, s. 314-23
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Given the higher sensitivity of modern computed tomography (CT) scanners, adrenal incidentalomas are being discovered increasingly often. This implies a growing quantitative diagnostic and clinical problem. CT and/or magnetic resonance imaging (MRI) and usually thorough hormonal testing are routinely used to determine the origin of these lesions. Recently, positron emission tomography (PET) using the tracer (11)C-metomidate (MTO) has been established as an alternative diagnostic method with high sensitivity for identifying adrenocortical lesions. The aim of this study was to evaluate the clinical use and value of MTO-PET compared to CT and MRI in the characterisation and work-up of adrenal incidentalomas. METHODS: Initially, we retrospectively evaluated 20 adrenal incidentalomas in patients who had undergone CT, MRI and MTO-PET and from whom we had either histopathological diagnosis or clinical follow-up data. After this analysis we conducted a prospective study in order to compare the imaging modalities. In the latter study, 24 incidentalomas were imaged by CT, MRI and MTO-PET and the results were correlated to those from histopathology (n=8) and clinical diagnosis after follow-up (n=16). RESULTS: In the retrospective analysis, MRI and especially MTO-PET, correlated well to histopathology and clinical diagnosis after follow-up, whereas specificity with CT was low. This was possibly due to the presence of several haematomas/fibrosis which were misdiagnosed as adrenocortical adenomas. In the prospective cohort, sensitivity and specificity with CT were 0.71 and 1.0, respectively, and further characterisation by MRI increased these values to 0.86 and 1.0, whereas maximum sensitivity and specificity were reached when MTO-PET was added. CONCLUSION: The diagnosis of an adrenocortical adenoma may be established by CT in most patients and by MRI in an additional number. For the few remaining patients needing further characterisation, MTO-PET is advantageous as an additional imaging modality.
  •  
23.
  •  
24.
  • Hessman, Ola, et al. (författare)
  • High success rate of parathyroid reoperation may be achieved with improved localization diagnosis
  • 2008
  • Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 32:5, s. 774-81; discussion 782
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Because of the difficulty of reoperative parathyroid surgery, preoperative imaging studies have been increasingly adopted. We report the use of consistently applied localization diagnosis to yield high success rates in parathyroid reoperations. METHODS: Parathyroid reoperation was performed after previous parathyroid surgery in 144 patients with nonmalignant hyperparathyroidism (HPT) between 1962 and 2007. From the year 2000, 46 patients who underwent parathyroid reoperation and 14 patients who were subjected to thyroid surgery before primary parathyroid operation were investigated with sestamibi scintigraphy (MIBI), 11C-methionine PET/CT (met-PET), surgeon-performed ultrasound (US), US-guided fine-needle aspiration biopsy (US-FNA), and selective venous sampling (SVS) with rapid PTH (Q-PTH) analyses. When imaging was considered adequate, additional studies were generally not obtained. RESULTS: Reversal of hypercalcemia was achieved by reoperation in 134 of 144 (93%) of all patients with previous parathyroid surgery. In patients operated from year 2000, MIBI had 90% sensitivity and 88% predictive value, met-PET 79% sensitivity and 87% predictive value, and US 72% sensitivity and 93% predictive value. SVS with Q-PTH analyses provided accurate localization or regionalization in 11 of 11 recently selected patients. Q-PTH analyses in fine-needle aspirations verified parathyroid origin of excised specimens, and intraoperative Q-PTH helped decide when operations could be terminated. In patients subjected to the algorithm of imaging procedures, reversal of hypercalcemia and apparent cure was obtained after the reoperation in 45 of 46 patients with previous parathyroid surgery, implying a success rate of 98%, and in all patients with previous thyroid surgery. CONCLUSIONS: Reoperative parathyroid surgery is challenging. Results can be improved by consistently applied sensitive methods of preoperative imaging, and reoperative procedures may then achieve nearly the same success rates as primary operations.
  •  
25.
  •  
26.
  • Hultin, Hella, et al. (författare)
  • Association of parathyroid adenoma and pregnancy with preeclampsia
  • 2009
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 94:9, s. 3394-3399
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Case reports have described associations between calcium metabolism disturbances and primary hyperparathyroidism with preeclampsia, suggesting parathyroid involvement in preeclampsia etiology. This study examines whether parathyroid adenoma, the main cause of hyperparathyroidism, diagnosed and treated before pregnancy is associated with preeclampsia. DESIGN: We conducted a register-based study to assess the association between parathyroid adenoma and subsequent preeclampsia. SETTING: Births among Sweden's general population were studied. POPULATION: The study population included 52 women with a diagnosis of parathyroid adenoma and 519 without, all of whom had a subsequent singleton pregnancy between 1973 and 1997. METHODS: We performed a conditional logistic regression investigating the association of parathyroid adenoma with subsequent preeclampsia in the first singleton pregnancy with adjustment for potential confounding factors. MAIN OUTCOME MEASURE: The main outcome was a diagnosis of preeclampsia that does not include women with prior chronic hypertension. To ensure that treatment of parathyroid adenoma was completed before pregnancy, those with a diagnosis of parathyroid adenoma made less than 2 yr before delivery (and the matched comparison women) were excluded. RESULTS: Statistically, parathyroid adenoma prior to delivery is significantly (P < 0.001) associated with preeclampsia, producing an adjusted odds ratio of 6.89 (95% confidence interval, 2.30, 20.58). CONCLUSION: A history of parathyroid adenoma should be viewed as a risk for preeclampsia.
  •  
27.
  • Ihse, Elisabet, et al. (författare)
  • Proportion between wild-type and mutant protein in truncated compared to full-length ATTR : an analysis on transplanted transthyretin T60A amyloidosis patients
  • 2009
  • Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 379:4, s. 846-850
  • Tidskriftsartikel (refereegranskat)abstract
    • Familial ATTR amyloidosis is caused by point mutations in the transthyretin gene. The clinical manifestations are highly varied but polyneuropathy and/or cardiomyopathy are generally the main symptoms. The amyloid fibrils can either be composed of only intact ATTR molecules or intact together with fragmented ATTR species. As plasma TTR is almost exclusively synthesized in the liver, liver transplantation is performed in order to eliminate the mutant plasma TTR. The procedure has shown best results among patients with the V30M mutation, while a rapid continued cardiac deposition of wild-type (wt) TTR has been seen for many other mutations. In this paper we investigated the proportion of wtATTR in two TTRT60A patients that underwent liver transplantation; one patient died 3 weeks after surgery, the other patient survived for 12 months. As the role of fragmented TTR species in the pathogenesis is far from understood, we investigated the proportion of wt in these species separately to the full-length molecules, which has not been done before in transplanted patients. The results show a higher proportion of wtTTR in the 12-months-surviving patient than the 3-weeks-surviving patient, but interestingly this difference in wt proportion is mainly seen among the full-length, and not the fragmented, molecules.
  •  
28.
  •  
29.
  • Mihai, Radu, et al. (författare)
  • Imaging for primary hyperparathyroidism : an evidence-based analysis
  • 2009
  • Ingår i: Langenbeck's archives of surgery (Print). - : Springer Science and Business Media LLC. - 1435-2443 .- 1435-2451. ; 394:5, s. 765-784
  • Forskningsöversikt (refereegranskat)abstract
    • OBJECTIVE: Imaging in patients with primary hyperparathyroidism has been proven difficult. During the last decade, sestamibi scintigraphy and ultrasound (US) have been used with various success. The importance of these procedures has risen since minimal invasive parathyroid (MIP) surgery also has developed, and it is claimed that preoperative localization usually is needed before embarking on such a procedure. METHODS: We have scanned the most recent literature in this matter in order to identify evidence, using commonly accepted grading, and also concluded a number of recommendations. RESULTS AND CONCLUSIONS: We found evidence at level III leading to recommendations at grade B, that sestamibi scintigraphy is a recommended first test, but that US by an experienced investigator may be an alternative. MIP may be performed when both tests are concordant, and in case of only one test being positive, unilateral exploration and use of intraoperative PTH measurements are recommended. Bilateral neck exploration is used when both tests are negative. For reoperative procedures, repeat investigations are recommended, but also to use US-guided fine needle aspiration and PTH measurements as well as venous sampling. However, for reoperative procedures, the level of evidence is weaker-level IV, but recommendations still at grade B.
  •  
30.
  • Rask, Eva, 1958-, et al. (författare)
  • Adrenocorticotropin-independent Cushing's syndrome in pregnancy related to overexpression of adrenal luteinizing hormone/human chorionic gonadotropin receptors
  • 2009
  • Ingår i: Journal of Endocrinological Investigation. - : Editrice kurtis. - 0391-4097 .- 1720-8386. ; 32:4, s. 313-316
  • Tidskriftsartikel (refereegranskat)abstract
    • Cushing's syndrome during pregnancy is rare, and rather than being of pituitary origin most patients exhibit ACTH-independent adrenal hypercortisolism. In some cases the syndrome has spontaneously resolved post partum, suggesting the presence of a pregnancy-associated stimulatory factor(s). We describe a case with aberrant adrenal LH/hCG receptors in a large adrenal tumor as a possible explanation for cortisol hypersecretion and tumor growth in Cushing s syndrome during pregnancy. A 27-yr-old woman presented with hypertension and diabetes mellitus in early pregnancy. Investigations revealed hypercortisolemia, suppressed ACTH-levels, and a 6.4- cm right adrenal tumor. The tumor was successfully removed by laparoscopy at 26th week of pregnancy. Hypercortisolism and hypertension resolved post-operatively. The tumor displayed higher LH/hCG receptor mRNA and protein positivity than adjacent normal adrenal tissue as examined by in situ hybridization and immunocytochemistry. High physiological levels of hCG, in conjunction with aberrant adrenal LH/hCG receptor overexpression, may have contributed to the development of Cushing's syndrome in pregnancy.
  •  
31.
  • Razifar, Pasha, et al. (författare)
  • Masked volume wise Principal Component Analysis of small adrenocortical tumours in dynamic [11C]-metomidate Positron Emission Tomography
  • 2009
  • Ingår i: BMC Medical Imaging. - : Springer Science and Business Media LLC. - 1471-2342. ; 9:6
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In previous clinical Positron Emission Tomography (PET) studies novel approaches for application of Principal Component Analysis (PCA) on dynamic PET images such as Masked Volume Wise PCA (MVW-PCA) have been introduced. MVW-PCA was shown to be a feasible multivariate analysis technique, which, without modeling assumptions, could extract and separate organs and tissues with different kinetic behaviors into different principal components (MVW-PCs) and improve the image quality. METHODS: In this study, MVW-PCA was applied to 14 dynamic 11C-metomidate-PET (MTO-PET) examinations of 7 patients with small adrenocortical tumours. MTO-PET was performed before and 3 days after starting per oral cortisone treatment. The whole dataset, reconstructed by filtered back projection (FBP) 0-45 minutes after the tracer injection, was used to study the tracer pharmacokinetics. RESULTS: Early, intermediate and late pharmacokinetic phases could be isolated in this manner. The MVW-PC1 images correlated well to the conventionally summed image data (15-45 minutes) but the image noise in the former was considerably lower. PET measurements performed by defining "hot spot" regions of interest (ROIs) comprising 4 contiguous pixels with the highest radioactivity concentration showed a trend towards higher SUVs when the ROIs were outlined in the MVW-PC1 component than in the summed images. Time activity curves derived from "50% cut-off" ROIs based on an isocontour function whereby the pixels with SUVs between 50 to 100% of the highest radioactivity concentration were delineated, showed a significant decrease of the SUVs in normal adrenal glands and in adrenocortical adenomas after cortisone treatment. CONCLUSION: In addition to the clear decrease in image noise and the improved contrast between different structures with MVW-PCA, the results indicate that the definition of ROIs may be more accurate and precise in MVW-PC1 images than in conventional summed images. This might improve the precision of PET measurements, for instance in therapy monitoring as well as for delineation of the tumour in radiation therapy planning.
  •  
32.
  • Segersten, Ulrika, et al. (författare)
  • 25-hydroxyvitamin D3 1alpha-hydroxylase expression in breast cancer and use of non-hydroxylated vitamin D analogue
  • 2005
  • Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 7, s. R980-R986
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION:The cytochrome P450 mitochondrial enzyme 25-hydroxyvitamin D3 1alpha-hydroxylase (1alpha-hydroxylase) of renal tubule cells hydroxylates the major circulating form of vitamin D (25(OH)D3) to the active systemic hormone 1,25(OH)2D3. Local production of 1,25(OH)2D3 appears to occur also at other sites where 1alpha-hydroxylase is expressed for autocrine/paracrine regulation. To reduce risks of hypercalcemia during treatment with vitamin D, we have previously suggested use of non-1alpha-hydroxylated vitamin D analogues to target tissues where 1alpha-hydroxylase is expressed, including the parathyroid glands in secondary hyperparathyroidism. The present study was undertaken to examine expression of 1alpha-hydroxylase in breast cancer and to investigate whether a non-1alpha-hydroxylated vitamin D analogue displayed biological function. In addition, expression of the 25-hydroxyvitamin D3 24-hydroxylase (24-hydroxylase) and the vitamin D receptor (VDR) was investigated.METHODS:The expression of 1alpha-hydroxylase, 24-hydroxylase and VDR was investigated in breast cancer specimens (n = 19) and normal breast tissues (n = 10) by immunohistochemistry and/or RT-PCR. Consecutive cryosections of 6 mum essentially free of immune cells were used in the analyses. The effect of vitamin D analogues on transcriptional activation was analyzed in transiently transfected MCF-7 breast cancer cells.RESULTS:1alpha-hydroxylase protein was demonstrated in 79% and 100% of breast cancer specimens and normal breast, respectively. The overall relative mRNA levels of 1alpha-hydroxylase and 24-hydroxylase in normal breast compared to breast tumors were: 1alpha-hydroxylase, 1 +/- 0.07 versus 0.7 +/- 0.05, respectively (p < 0.001); 24-hydroxylase, 1 +/- 0.08 verus 2.1 +/- 0.2, respectively (p < 0.001). The VDR was expressed in 95% of the tumors as expected, with mRNA levels of 1 +/- 0.09 and 1.4 +/- 0.12 (p < 0.05) in breast cancer and normal breast, respectively. The ketoconazole-sensitive transcription activation potential of the non-1alpha-hydroxylated vitamin D analogue prodrug of EB1089 (EB1285) was demonstrated in MCF-7 cells, which express 1alpha-hydroxylase. The activity of EB1285 was about 20% of 1,25(OH)2D3.CONCLUSION:These results demonstrate nearly normal expression levels of 1alpha-hydroxylase, 24-hydroxylase and VDR in the majority of investigated breast cancer specimens. A non-1alpha-hydroxylated vitamin D analogue displayed activity in breast cancer cells. Such analogues may present future therapeutic options for proliferative disorders where 1alpha-hydroxylase is expressed.
  •  
33.
  • Segersten, Ulrika, et al. (författare)
  • Potentiating effects of non-active/active vitamin D analogues and ketoconazole in parathyroid cells
  • 2007
  • Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 66:3, s. 399-404
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and objective: 1,25-dihydroxyvitamin D3 [1α,25(OH)2D3, calcitriol], and its less calcaemic synthetic analogues have therapeutic potential in several diseases, including hyperparathyroidism (HPT). We have suggested that non-1α-hydroxylated (nonactive) vitamin D analogues may present an alternative in tumour cells expressing 25-hydroxyvitamin D3 1α-hydroxylase (1α-hydroxylase). The aim of this study was to investigate biological effects of a non-1α-hydroxylated vitamin D analogue in normal and tumour parathyroid cells. Patients and methods: Effects of vitamin D analogues and ketoconazole on parathyroid hormone (PTH) secretion (radioimmunoassay) and PTH mRNA expression (reverse transcription-polymerase chain reaction) were studied in primary bovine parathyroid cells. Proliferation of tumour cells isolated from HPT patients was determined by thymidine incorporation Results: EB1285, non-1α-hydroxylated precursor of the vitamin D analogue EB1089, suppressed PTH secretion and PTH mRNA level as well as increased expression of 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase) in bovine parathyroid cells. EB1285 also inhibited cell proliferation of parathyroid tumour cells from primary (pHPT) and secondary HPT (sHPT) patients. Combined treatment with the cytochrome P450-dependent enzyme inhibitor ketoconazole and EB1285 or with active vitamin D compounds potentiated the suppressive effect on PTH secretion from bovine parathyroid cells. Ketaconazole alone displayed PTH suppression and increased 24-hydroxylase expression. Conclusion: The results support the idea that a non-1α-hydroxylated vitamin D analogue may elicit vitamin D receptor (VDR) effects in 1α-hydroxylase expressing parathyroid tumour cells. Further studies are warranted to elucidate whether precursor vitamin D analogues as well as inhibitors of 24-hydroxylase present therapeutic alternatives in patients suffering from HPT.
  •  
34.
  • Segersten, Ulrika, 1973- (författare)
  • Vitamin D Hydroxylating Enzymes and Analogues in Parathyroid Tumors and Breast Cancer
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In hyperparathyroidism (HPT) raised serum concentrations of ionized calcium is caused by increased secretion of parathyroid hormone (PTH) by parathyroid tumors. Active vitamin D, 1α,25-dihydroxyvitamin D3, is known to suppress PTH secretion and to reduce proliferation of parathyroid tumor cells.The aim of this thesis was to examine expression of vitamin D hydroxylating enzymes, regulating the activation and inactivation of vitamin D and to study effects of vitamin D analogues, in parathyroid tumors and breast cancer.The vitamin D activating enzyme, CYP27B1/25-hydroxyvitamin D3 1α-hydroxylase (1α-hydroxylase) and the vitamin D inactivating enzyme CYP24A1/25-hydroxyvitamin D3 24-hydroxylase (24-hydroxylase) were expressed in parathyroid tumors and breast cancer. The parathyroid tumors had raised expression levels of 1α-hydroxylase and reduced levels of 24-hydroxylase in comparison to normal parathyroid glands, indicating ability for endogenous activation of vitamin D. The expression of 1α-hydroxylase may be of therapeutic advantage for local activation of non-1α-hydroxylated vitamin D analogues in tumor cells, thereby reducing unwanted hypercalcemic effects. Three of five selected low calcemic vitamin D analogues had as efficient PTH suppressing effect, in bovine parathyroid cells, as three vitamin D analogues used clinically for treatment of secondary HPT.The non-1α-hydroxylated vitamin D analogue EB1285 showed antiproliferative and PTH suppressive effects as well as transcriptional activity in parathyroid and breast tumor cells, respectively.Ketoconazole, an inhibitor of vitamin D hydroxylating enzymes, suppressed PTH secretion and potentiated the effect of vitamin D analogues. Combined treatment with vitamin D analogues and specific 24-hydroxylase inhibitors may be important for future therapy.
  •  
35.
  • Stålberg, Peter, et al. (författare)
  • Surgical treatment of Graves' disease : evidence-based approach.
  • 2008
  • Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 32:7, s. 1269-77
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The optimal treatment of Graves disease (GD) is still controversial. Surgery is one treatment option along with radioactive iodine (RAI) and antithyroid medication. In this evidence-based review, we examine four issues: (1) Is surgery better than RAI or long-term antithyroid medication? (2) What is the recommended surgical approach? (3) How does the presence of Graves' ophthalmopathy (GO) influence the role of surgery? (4) What is the role of surgery in children with GD? METHODS: We conducted a systematic review of the literature using evidence-based criteria regarding these four issues. RESULTS: (1) There are no recommendations reaching any grade of evidence for which treatment to choose for adults with GD. (2) Total thyroidectomy has complication rates equal to those seen with lesser resections but it has higher cure rates and negligible recurrence rates (Level I-IV data leading to a grade A recommendation). (3) Data support surgery when severe GO is present, but RAI combined with glucocorticoids may be equally safe (Level II-IV data, grade B recommendation). The extent of thyroid resection does not influence the outcome of GO (Level II data, grade B recommendation). (4) Based on the available data, definitive treatment can be advocated for children (Level IV data, grade C recommendation) using either RAI or surgery. No recommendation can be given as to whether RAI or surgery is preferred owing to the lack of studies addressing this issue. Increased cancer risk with RAI in children below the age of 5 years supports surgery in this setting (Level I data, grade A recommendation). CONCLUSION: If surgery is considered for definitive management, evidence-based criteria support total thyroidectomy as the surgical technique of choice for GD. Available evidence also supports surgery in the presence of severe endocrine GO. Children with GD should be treated with an ablative strategy. Whether this is achieved by total thyroidectomy or RAI may still be debatable. Data on long-term cancer risk are missing or conflicting; and until RAI has proven harmless in children, we continue to recommend surgery in this group.
  •  
36.
  • Zar, Niklas, 1967- (författare)
  • Epidemiological Studies of Small Intestinal Tumours
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Malignant tumours of the small intestine are rare. Age-standardised incidence in Europe is between 0.5-1.5 per 100 000. As the small intestine represents more than 90 % of the gastrointestinal mucosal surface, it is surprising that it gives rise to less than 2 % of gastrointestinal malignancies. The dominating histological subtypes are carcinoids and adenocarcinomas. We used three population-based registries in Sweden to study survival, second malignant tumours, causes of death, and Crohn’s disease as a risk factor for small intestinal adenocarcinoma and carcinoid.We evaluated tumour site, sex, age, and year of diagnosis as prognostic factors. For adenocarcinomas there was no difference in survival between duodenal and jejunal/ileal tumours. Women with jejunal/ileal adenocarcinomas showed higher probabilities of survival than men, while no such relation was found for duodenal tumours. Old age correlated with poor survival for duodenal tumours, and prognosis has improved in later years. For carcinoids, duodenal tumours had a more favourable prognosis than jejunal/ileal tumours. There was no difference in survival between sexes. Old age correlated with poor survival, and survival has improved in recent years.Female patients with adenocarcinoma had increased risk of acquiring cancer in the genital organs and breasts, and both sexes had increased risks of second tumours in the gastrointestinal tract and skin. Men with carcinoid tumours had increased risk of prostate cancer. Both sexes had increased risk of malignant melanoma and malignancies of endocrine organs.Patients with adenocarcinoma had increased risk of dying from malignant diseases other than the primary small intestinal cancer and from gastrointestinal disease. The cohort with carcinoid had higher than expected risk of dying from malignant disease, gastrointestinal disease, and cardiovascular disease.Patients with Crohn’s disease had increased risk of small intestinal adenocarcinoma and carcinoid, and the risk has increased for patients diagnosed in recent years.
  •  
37.
  • Zar, Niklas, et al. (författare)
  • Risk of second primary malignancies and causes of death in patients with adenocarcinoma and carcinoid of the small intestine
  • 2008
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 44:5, s. 718-25
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied risk of second malignancies and causes of death in 1829 cases of adenocarcinoma and 3055 cases of carcinoid tumours in the small bowel reported to the Swedish Cancer Registry from 1960 through to 2000. Data on causes of death were analysed as from 1966 whereas data on second tumours was available during the whole registry-period. Follow-up was available until 2001. Standard mortality ratio (SMR) and standard incidence ratio (SIR) were calculated. Female patients with adenocarcinoma had increased risk of acquiring cancer in the female genital organs (SIR 3.2; 95% confidence intervals (CI) 1.9–5.0) and breasts (SIR 2.7; 95% CI 1.1–5.4). Both sexes combined had increased risk of second tumours in the gastrointestinal tract (SIR 1.5; 95% CI 1.1–2.1) and skin (SIR 4.6; 95% CI 1.2–12). Men with carcinoid tumour had increased risk of prostate cancer (SIR 2.8; 95% CI 1.6–4.6). Increased risk was seen for both sexes with carcinoid for malignant melanoma (SIR 6.3; 95% CI 2.7–12), malignant skin tumours (SIR 3.6; 95% CI 1.7–6.7) and malignancies of endocrine organs (SIR 2.3 95% CI 1.3–3.8). Patients with adenocarcinoma had increased risk of dying from malignant diseases other than the primary cancer (SMR 9.5; 95% CI 8.6–10) and gastrointestinal disease (SMR 2.6 95% CI 1.6–4.2). The cohort with carcinoid had higher than expected risk of dying from malignant disease (SMR 4.3; 95% CI 4.0–4.6), gastrointestinal disease (SMR 2.8; 95% CI 2.1–3.6) and cardiovascular disease (SMR 1.1; 95% CI 1.0–1.3). The increased risk of second malignant tumours is an indication of common aetiology, or possibly, a general vulnerability to malignant disease for these patients. A detailed analysis of causes of death in a population-based cohort of small intestinal malignancies has not been presented before in the literature.
  •  
38.
  • Åberg, Ola, 1978-, et al. (författare)
  • Synthesis and Biological Evaluation of [Carboxyl-11C]eprosartan
  • 2009
  • Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 52:8, s. 295-303
  • Tidskriftsartikel (refereegranskat)abstract
    • Essential hypertension occurs in approximately 25% of the adult population and one cause of hypertension is primary aldosteronism. Targeting the angiotensin II AT1 receptor using PET and an appropriate tracer may offer a diagnostic method for adrenocortical tissue. This report describes the synthesis of the selective AT1 receptor antagonist [carboxyl-11C]eprosartan 10, 4-[2-butyl-5-((E)-2-carboxy-3-thiophen-2-yl-propenyl)-imidazol-1-ylmethyl]-[carboxyl-11C]benzoic acid, and its precursor (E)-3-[2-butyl-3-(4-iodo-benzyl)-3H-imidazol-4-yl]-2-thiophen-2-ylmethyl-acrylic acid 9. 11C-carboxylation of the iodobenzyl moiety was performed using a palladium-mediated reaction with [11C]carbon monoxide in the presence of tetra-n-butyl-ammonium hydroxide in a micro-autoclave using a temperature gradient from 25 to 140°C over 5 min. After purification by semipreparative HPLC, [carboxyl-11C]eprosartan 10 was obtained in 37–54% decay-corrected radiochemical yield (from [11C]carbon monoxide) with a radiochemical purity >95% within 35 min of the end of bombardment (EOB). A 5-µAh bombardment gave 2.04 GBq of 10 (50% rcy from [11C]carbon monoxide) with a specific activity of 160 GBq µmol−1 at 34 min after EOB. Frozen-section autoradiography shows specific binding in kidney, lung and adrenal cortex. In vivo experiments in rats demonstrate a high accumulation in kidney, liver and intestinal wall.
  •  
39.
  • Åkerström, Göran, et al. (författare)
  • Carcinoid neoplasms
  • 2009. - 2
  • Ingår i: General surgery. - London : Springer. - 9781846288333 ; , s. 1709-1718
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
  •  
40.
  •  
41.
  • Åkerström, Göran, et al. (författare)
  • Carcinoid tumors
  • 2006
  • Ingår i: General Surgery. - : Springer 2006.
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
  •  
42.
  • Åkerström, Göran, et al. (författare)
  • Gastrointestinal carcinoids
  • 2009
  • Ingår i: Endocrine surgery. - London : Saunders. - 9780702030161 ; , s. 163-169
  • Bokkapitel (populärvet., debatt m.m.)
  •  
43.
  • Åkerström, Göran, et al. (författare)
  • Gastrointestinal carcinoids
  • 2005
  • Ingår i: Endocrine Surgery. - : Elsevier Ltd Edinburgh. ; , s. 163-197
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
  •  
44.
  • Åkerström, Göran, et al. (författare)
  • Management of midgut carcinoids
  • 2005
  • Ingår i: J Surg Oncol. ; 89:3, s. 161-169
  • Tidskriftsartikel (populärvet., debatt m.m.)
  •  
45.
  •  
46.
  • Åkerström, Göran, et al. (författare)
  • Pancreatic tumours as part of the MEN-1 syndrome.
  • 2005
  • Ingår i: Best Practice & Research Clinical Endocrinology & Metabolism. - : Elsevier. - 1521-6918.
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
  •  
47.
  • Åkerström, Göran, et al. (författare)
  • Parathyroid carcinoma
  • 2009. - 2
  • Ingår i: Clinical endocrine oncology. - Malden : Blackwell Publishing. - 9781405145848 ; , s. 180-184
  • Bokkapitel (populärvet., debatt m.m.)
  •  
48.
  •  
49.
  • Åkerström, Göran, et al. (författare)
  • Surgery on neuroendocrine tumours
  • 2007
  • Ingår i: Baillière's Best Practice & Research. Clinical Endocrinology & Metabolism. - : Elsevier BV. - 1521-690X .- 1532-1908. ; 21:1, s. 87-109
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuroendocrine tumours of the gastrointestinal tract and pancreas present a major challenge to physicians in their recognition and treatment requirements, and surgical treatment of these tumours has become increasingly important for symptom palliation and survival. For some carcinoid tumours the extent of surgery may depend on tumour size. Midgut carcinoid is the most common cause of the carcinoid syndrome, requiring surgery for primary and mesenteric tumours to minimize the risk for abdominal complications but also for removal of liver metastases to palliate hormonal symptoms. Among endocrine pancreatic tumours, insulinoma and gastrinoma often cause severe symptoms of hormone excess despite their inconspicuous size, but they can be successfully removed with improved pre- and intraoperative localization. Other tumours--glucagonoma, VIPoma, and non-functioning endocrine pancreatic tumours--are often large or metastasizing, but generally require surgical debulking to alleviate hormonal symptoms and have favourable survival.
  •  
50.
  • Åkerström, Göran, et al. (författare)
  • Surgical aspects of neuroendocrine tumours
  • 2009
  • Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 45:Suppl 1, s. 237-50
  • Tidskriftsartikel (refereegranskat)
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-50 av 50
Typ av publikation
tidskriftsartikel (35)
bokkapitel (8)
doktorsavhandling (5)
forskningsöversikt (2)
Typ av innehåll
refereegranskat (34)
övrigt vetenskapligt/konstnärligt (12)
populärvet., debatt m.m. (4)
Författare/redaktör
Hellman, Per (43)
Åkerström, Göran (19)
Hagström, Emil (5)
Westin, Gunnar (5)
Sundin, Anders (4)
Westermark, Per (4)
visa fler...
Lind, Lars (3)
Hellman, Ulf (3)
Björklund, Peyman (3)
Segersten, Ulrika (3)
Holmberg, Lars (2)
Eriksson, Barbro (2)
Långström, Bengt (2)
Rudberg, Claes (2)
Skogseid, Britt (2)
Sletten, Knut (2)
Ärnlöv, Johan (2)
Hall, Håkan (1)
Hamberger, B (1)
Berglund, Lars (1)
Larsson, Anders (1)
Ahlström, Håkan (1)
Ekbom, Anders (1)
Hellman, Lars (1)
Held, Claes, 1956- (1)
Pejler, Gunnar (1)
Mallmin, Hans (1)
Suhr, Ole B. (1)
Andersson, Linda (1)
Garmo, Hans (1)
Hultin, Hella (1)
Andersson, Maria (1)
Buchwald, Pamela (1)
Enberg, U (1)
Ahlström, Tommy (1)
Ingelsson, Erik (1)
Nordgren, Hans (1)
Elvin, A. (1)
Hellman, Björn (1)
Melhus, Håkan (1)
Sundström, Johan (1)
Bergenfelz, Anders (1)
Larsson, Tobias E (1)
Eriksson, Håkan (1)
Montgomery, Scott M. (1)
Bergström, Joakim (1)
Karlsson, F. A. (1)
Rask, Eva, 1958- (1)
Eriksson, Lars-Gunna ... (1)
Michaëlsson, Karl (1)
visa färre...
Lärosäte
Uppsala universitet (50)
Karolinska Institutet (5)
Umeå universitet (2)
Örebro universitet (2)
Lunds universitet (1)
Malmö universitet (1)
visa fler...
Högskolan Dalarna (1)
visa färre...
Språk
Engelska (48)
Svenska (2)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (10)
Naturvetenskap (1)
Teknik (1)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy