| 1. |
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| 2. |
- Radecka, Eva, et al.
(författare)
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An unusual case of tumor thrombus in the inferior vena cava : A case report
- 2003
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Ingår i: Acta Radiologica. - 0284-1851 .- 1600-0455. ; 44:2, s. 160-161
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Tidskriftsartikel (refereegranskat)abstract
- Adrenal cortical carcinoma (ACC) is a rare malignancy. Patients present either with a functional tumor or secondary to mass effect. In non-functioning tumors, the tumor size often exceeds 5 cm by the time of diagnosis, and tumor thrombus can occur. We report on a case of a small non-functioning ACC causing a large tumor thrombus in the inferior vena cava.
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| 3. |
- Ask, Karl, 1978, et al.
(författare)
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Intending or pretending? Automatic evaluations of goal cues discriminate true and false intentions
- 2013
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Ingår i: Applied Cognitive Psychology. - : Wiley. - 0888-4080 .- 1099-0720. ; 27:2, s. 173-177
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Tidskriftsartikel (refereegranskat)abstract
- This research presents a novel approach to discriminating between true and deceptive statements about intended future behavior. Arguing that true intentions are goal-directed, we predict that people who genuinely intend to pursue a reported goal will implicitly evaluate goal-relevant cues positively, whereas people who do not intend to pursue the goal will not. Participants in an experiment were instructed to tell the truth about a planned future behavior (true intention) or to falsely report that same behavior to mask their actual mock-criminal intention (false intention). As predicted, an evaluative priming task showed that participants with true intention exhibited implicit positive evaluations of cues relevant to the reported goal, whereas participants with false intention did not. Subsequent analyses showed that implicit positivity significantly discriminated between true and false intentions. The findings are discussed in terms of theoretical contributions and implications for the development of future detection tools.
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| 4. |
- Backman, Samuel, et al.
(författare)
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The Evolutionary History of Metastatic Pancreatic Neuroendocrine Tumours Reveals a Therapy Driven Route to High-Grade Transformation.
- 2024
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Ingår i: medRxiv : the preprint server for health sciences.
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Tidskriftsartikel (refereegranskat)abstract
- Tumour evolution with acquisition of more aggressive disease characteristics is a hallmark of disseminated cancer. Metastatic pancreatic neuroendocrine tumours (PanNETs) in particular, show frequent progression from a low/intermediate to a high-grade disease. To understand the molecular mechanisms underlying this phenomenon, we performed multi-omics analysis of 32 longitudinal samples from six metastatic PanNET patients. Following MEN1 inactivation, PanNETs exhibit genetic heterogeneity on both spatial and temporal dimensions with parallel and convergent tumuor evolution involving the ATRX/DAXX and mTOR pathways. Following alkylating chemotherapy treatment, some PanNETs develop mismatch repair deficiency and acquire a hypermutator phenotype. This DNA hypermutation phenotype was only found in cases that also showed transformation into a high-grade PanNET. Overall, our findings contribute to broaden the understanding of metastatic PanNET, and suggests that therapy driven disease evolution is an important hallmark of this disease.
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| 5. |
- Bergström, Mats, et al.
(författare)
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PET imaging of adrenal cortical tumors with the 11beta-hydroxylase tracer 11C-metomidate
- 2000
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Ingår i: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 41:2, s. 275-282
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to evaluate PET with the tracer 11C-metomidate as a method to identify adrenal cortical lesions.METHODS:PET with 11C-metomidate was performed in 15 patients with unilateral adrenal mass confirmed by CT. All patients subsequently underwent surgery, except 2 who underwent biopsy only. The lesions were histopathologically examined and diagnosed as adrenal cortical adenoma (n = 6; 3 nonfunctioning), adrenocortical carcinoma (n = 2), and nodular hyperplasia (n = 1). The remaining were noncortical lesions, including 1 pheochromocytoma, 1 myelolipoma, 2 adrenal cysts, and 2 metastases.RESULTS:All cortical lesions were easily identified because of exceedingly high uptake of 11C-metomidate, whereas the noncortical lesions showed very low uptake. High uptake was also seen in normal adrenal glands and in the stomach. The uptake was intermediate in the liver and low in other abdominal organs. Images obtained immediately after tracer injection displayed high uptake in the renal cortex and spleen. The tracer uptake in the cortical lesions increased throughout the examination. For quantitative evaluation of tracer binding in individual lesions, a model with the splenic radioactivity concentration assigned to represent nonspecific uptake was applied. Values derived with this method, however, did show the same specificity as the simpler standardized uptake value concept, with similar difference observed for cortical versus noncortical lesions.CONCLUSION:PET with 11C-metomidate has the potential to be an attractive method for the characterization of adrenal masses with the ability to discriminate lesions of adrenal cortical origin from noncortical lesions.
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| 6. |
- Bergström, Mats, et al.
(författare)
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PET with [11C]-Metomidate for the Visualization of Adrenocortical Tumors and Discrimination from Other Lesions
- 1999
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Ingår i: Clinical Positron Imaging. - 1095-0397 .- 1878-5751. ; 2:6, s. 339-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:The purpose of the study was to evaluate the potential role of PET with the adrenocortical-specific tracer 11C-metomidate in the characterization of incidentally found adrenal cortical lesions and in adrenocortical carcinomas.Methods:PET with 11C-metomidate was performed in 15 patients with unilateral adrenal mass confirmed by CT (incidentalomas) and in 9 additional patients with adrenocortical cancer. All incidentalomas subsequently underwent surgery, except 2 subjected to biopsy only. These lesions were histopathologically examined and diagnosed as adrenal cortical adenoma (n = 6; 3 nonfunctioning), adrenocortical carcinoma (n = 2) and nodular hyperplasia (n = 1). The remaining were non-cortical lesions including 1 pheochromocytoma, 1 myelolipoma, 2 adrenal cysts, and 2 metastases.Results:All lesions, except 1, with an adrenocortical origin were easily identified due to exceedingly high uptake of 11C-metomidate, whereas the non-cortical lesions showed very low uptake. The 1 false negative was a cancer that at surgery was found to be extensively necrotic. High uptake was also seen in normal adrenal glands. The tracer uptake kinetics indicated trapping of the tracer in the cortical lesions. For quantitative evaluation of tracer binding in individual lesions, the simple SUV concept was found to be equally accurate as more elaborate kinetic analyses.Conclusion:The patients presented and altogether over 40 PET investigations have demonstrated 11C-metomidate to be an attractive tracer for the characterization of adrenal masses with the ability to discriminate lesions of adrenal cortical origin from non-cortical lesions. Additionally the method allows the assessment of metastases from adrenocortical cancers, and the very high contrast has allowed partial whole-body examinations.
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| 7. |
- Calissendorff, Jan, et al.
(författare)
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Adrenal cysts : an emerging condition.
- 2023
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Ingår i: Nature Reviews Endocrinology. - : Springer Nature. - 1759-5029 .- 1759-5037. ; 19, s. 398-406
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Tidskriftsartikel (refereegranskat)abstract
- Adrenal cysts are rare lesions representing approximately 1-2% of adrenal incidentalomas. The majority of these rare lesions are benign. Rarely, phaeochromocytomas and adrenal malignant masses can present as cystic lesions and can occasionally be difficult to distinguish from benign cysts. Histologically, adrenal cysts are subdivided into pseudocysts, endothelial cysts, epithelial cysts and parasitic cysts. The radiological appearance of an adrenal cyst is generally similar to that of cysts in the kidney. They are thus well demarcated, usually rounded, with a thin wall and homogenous internal structure, low attenuating (<20 Hounsfield Units) on CT, low signalling on T1-weighted MRI sequences and high signalling on T2-weighted MRI sequences, and anechoic or hypoechoic on ultrasonography. Benign adrenal cysts have a slight female predominance and are usually diagnosed between the ages of 40 and 60. Most adrenal cysts are asymptomatic and are detected incidentally, although very large adrenal cysts can lead to mass effect symptoms, with surgery required to alleviate the symptoms. Thus, conservative management is usually recommended for asymptomatic cysts. However, when uncertainty exists regarding the benign nature of the cyst, additional work-up or follow-up is needed. The management of an adrenal cyst should preferably be discussed at an adrenal multidisciplinary team meeting.
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| 8. |
- Calissendorff, Jan, et al.
(författare)
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Adrenal myelolipomas
- 2021
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Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 9:11, s. 767-776
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Forskningsöversikt (refereegranskat)abstract
- Adrenal myelolipomas are benign, lipomatous tumours with elements of myeloid cells, most of which present as adrenal incidentalomas and comprise 3·3-6·5% of all adrenal masses. Adrenal myelolipomas are usually unilateral (in 95% of cases), variable in size, most often found during midlife, and affect both sexes almost equally. On imaging, adrenal myelolipomas show pathognomonic imaging features consistent with the presence of macroscopic fat. Large adrenal myelolipomas can cause symptoms of mass effect, and can occasionally be complicated by haemorrhage. In the event of a concomitant adrenal cortical adenoma or hyperplasia, adrenal hormone excess might be detected in patients with adrenal myelolipoma. Patients with congenital adrenal hyperplasia exhibit a higher prevalence of adrenal myelolipomas than other patient groups, and are at risk of developing large and bilateral lesions. This Review discusses the pathogenesis, clinical presentation, and management of adrenal myelolipomas.
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| 9. |
- Cano-Viktorsson, Carlos, 1977-
(författare)
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From Vision to Transition : Exploring the Potential for Public Information Services to Facilitate Sustainable Urban Transport
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Policy initiatives to promote sustainable travel through the use of Internet based public information systems have increased during the last decade. Stockholm, in being one of the first cities in Europe to implement an Internet based service for facilitating sustainable travel is believed to be a good candidate for an analysis of key issues for developing sustainable travel planning services to the public.Aim: This thesis investigates the past development of two Stockholm based public information systems and their services in order to draw lessons on how to better provide for a public information service geared towards facilitating environmentally sustainable travel planning through information and communications technology. The overall goal of the thesis is to contribute to an understanding on how to better design and manage current and future attempts at facilitating sustainable travel planning services based on historical case studies.Approach: The thesis draws ideas from the concept of organizational responsiveness – an organization’s ability to listen, understand and respond to demands put to it by its internal and external stakeholders – in order to depict how well or not the two public information systems and their owners have adapted to established norms and values of their surroundings.Results: Overall, the findings from the historical case studies suggest that organizations attempting to provide sustainable travel planning to the public need to design and manage their systems in such a way that it responds to shifting demands on how to provide for information. Implementing and embedding new technologies involves complex processes of change both at the micro level – for users and practitioners of the service – and at the meso level for the involved public service organizations themselves. This condition requires a contextualist framework to analyze and understand organizational, contextual and cultural issues involved in the adoption of new technologies and procedures.Conclusions: The thesis concludes with a discussion on how the findings from the historical case studies may provide lessons for both current and future attempts at providing public information systems geared towards facilitating environmentally sustainable travel planning to the public. Historical examples and issues concerning collective intelligence and peer to peer based forms of designing, producing and supervising public information services identified throughout the study are looked upon and discussed in terms of their possible role in increasing the potential for public information services to facilitate sustainable urban transport.
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| 10. |
- Carling, Tobias, et al.
(författare)
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Hyperparathyroidism of multiple endocrine neoplasia type 1 : candidate gene and parathyroid calcium sensing protein expression
- 1995
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Ingår i: Surgery. - 0039-6060 .- 1532-7361. ; 118:6, s. 924-931
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Hyperparathyroidism affects most patients with multiple endocrine neoplasia type 1 (MEN 1). This study investigates expression of the candidate MEN1 gene phospholipase C beta 3 (PLC beta 3) and expression and function of a putative calcium sensing protein (CAS) in hyperparathyroidism of MEN 1.METHODS:In 31 parathyroid glands from 17 patients with MEN 1, CAS distribution was studied immunohistochemically and parallel sections were explored for PLC beta 3 mRNA expression by in situ hybridization. Enzymatically dispersed parathyroid cells were analyzed for cytoplasmic calcium concentrations [Ca2+]i and parathyroid hormone (PTH) release.RESULTS:All glands exhibited a heterogeneously reduced CAS immunoreactivity, especially meager in nodularly assembled parathyroid cells. Calcium regulated [Ca2+]i and PTH release tended to be more deranged in the glands possessing the lowest immunostaining. Parathyroid PLC beta 3 invariably was homogeneously expressed, and this included even MEN 1 patients with reduced PLC beta 3 expression in endocrine pancreatic tumors.CONCLUSIONS:The findings support variable calcium insensitivity of [Ca2+]i and PTH release in hyperparathyroidism of MEN 1, apparently coupled to heterogeneously reduced CAS expression. For clarification of the role of PLC beta 3 in MEN 1 parathyroid tumorigenesis further study of this protein is required.
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| 11. |
- Carlsson, Axel C, et al.
(författare)
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Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes : findings from two community based cohorts of elderly
- 2014
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 237:1, s. 236-242
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatingsTNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.
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| 12. |
- Dogra, Prerna, et al.
(författare)
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Rare benign adrenal lesions
- 2023
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Ingår i: European Journal of Endocrinology. - : Oxford University Press. - 0804-4643 .- 1479-683X. ; 188:4, s. 407-420
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Tidskriftsartikel (refereegranskat)abstract
- While most benign lesions of the adrenal glands represent either an adrenocortical adenoma or a myelolipoma, the advent and frequent use of high-resolution radiological investigations have led to relatively increased incidental discovery of rare adrenal lesions, specifically benign adrenal cysts, adrenal ganglioneuromas, adrenal schwannomas, adrenal hemorrhage, and adrenal calcifications. Radiological characteristics of the different rare benign adrenal lesions could vary from distinct to indeterminate. Though typically nonfunctional, these rare lesions require evaluation for adrenal hormone excess, as they may phenotypically appear similar to pheochromocytoma or adrenocortical carcinoma and could sometimes be associated with or conceal an underlying functional adrenal tumor. In this review, we discuss the various rare benign adrenal lesions, emphasizing a practical perspective.
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| 13. |
- Eriksson, Barbro, et al.
(författare)
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The role of PET in localization of neuroendocrine and adrenocortical tumors
- 2002
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 970, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Positron emission tomography (PET) supplies a range of labeled compounds to be used for the characterization of tumor biochemistry. Some of these have proved to be of value for clinical diagnosis, treatment follow up, and clinical research. The first routinely used PET tracer in oncology, 18F-labeled deoxyglucose (FDG), was successfully used for diagnosis of cancer, reflecting increased expression of glucose transporter in cancerous tissue. This tracer, however, usually does not show sufficient uptake in well-differentiated tumors such as neuroendocrine tumors. We developed a tracer more specific to neuroendocrine tumors—the serotonin precursor 5-hydroxytryptophan (5-HTP) labeled with 11C—and demonstrated increased uptake and irreversible trapping of this tracer in carcinoid tumors. The uptake was so selective and the resolution was so high that we could detect more liver and lymph node metastases with PET than with CT or octreotide scintigraphy. To further improve the method, especially to reduce the high renal excretion of the tracer producing streaky artifacts in the area of interest, we introduced premedication by the decarboxylase inhibitor carbidopa, leading to a six-fold decreased renal excretion while the tumor uptake increased three-fold, hence improving the visualization of the tumors.11C-labeled l-DOPA was evaluated as an alternative tracer, especially for endocrine pancreatic tumors, which usually do not demonstrate enhanced urinary serotonin metabolites. However, only half of the EPTs, mainly functioning tumors, could be detected with l-DOPA. Instead 5-HTP seems to be a universal tracer for EPT and foregut carcinoids. With new, more sensitive PET cameras, larger field of view and procedures for whole-body coverage, the PET examination with 5-HTP is now routinely performed as reduced whole-body PET examinations with coverage of the thorax and abdomen. With this method we have been able to visualize small neuroendocrine lesions in the pancreas and thorax (e.g., ACTH-producing bronchial carcinoids) not detectable by any other method, including octreotide scintigraphy, MRI, and CT. Another tracer, the 11β-hydroxylase inhibitor, metomidate labeled with 11C, was developed to simplify diagnosis and follow-up of patients with incidentalomas. A large series of patients with incidentally found adrenal masses have been investigated and so far all lesions of adrenocortical origin have been easily identified because of exceedingly high uptake of 11C-metomidate, whereas noncortical lesions showed very low uptake. In addition, adrenocortical cancer shows high uptake, suggesting that this PET tracer can be used for staging purposes.
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| 14. |
- Fotouhi, Omid, et al.
(författare)
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Regional differences in somatostatin receptor 2 (SSTR2) immunoreactivity is coupled to level of bowel invasion in small intestinal neuroendocrine tumors
- 2018
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Ingår i: Neuro - endocrinology letters. - Stockholm, Sweden : Maghira & Maas Publications. - 0172-780X. ; 39:4, s. 305-309
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Somatostatin receptor (SSTR) expression constitutes a pivotal cornerstone for accurate radiological detection and medical treatment of small intestinal neuroendocrine tumors (SI-NETs), and the development of somatostatin analogues for these purposes have revolutionized the clinical work-up. Previous assessments of SSTR isoform expression in SI-NETs have found correlations to overall prognosis and treatment response, however these analyses usually report overall tumoral immunoreactivity, and little is reported regarding histo-regional differences in expressional patterns.METHODS: Thirty-seven primary SI-NETs (WHO grade I, n=32 and WHO grade II, n=5) were collected and assessed for SSTR2 immunohistochemistry. Samples were stratified with regards to histological level of bowel infiltration and spread (mucosal region, muscularis propria region, subserosal region) and each of these tumoral regions was separately scored by SSTR2 staining localization (membrane, cytoplasmic), overall staining intensity and local staining differences within each region.RESULTS: SSTR2 immunoreactivity was progressively weaker as the tumor cells advanced through the small intestinal layers. This was exemplified by a reduction in the amount of tumor samples with strong SSTR2 expression in the deeper histological levels of the section; 56% of tumors displayed strong SSTR2 expression in the mucosal region, as compared to 29% and 30% of tumors within muscularis propria and subserosal layers, respectively.CONCLUSIONS: This observation indicates a down-regulation of SSTR2 expression as the tumors progress through the intestinal wall, which might signify underlying biological processes of importance for SI-NET invasion behavior.
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| 15. |
- Gimm, Oliver, et al.
(författare)
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Dual-Energy Computed Tomography Localizes Ectopic Parathyroid Adenoma
- 2010
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Ingår i: The Journal of Clinical Endocrinology & Metabolism. - Chevy Chase, MD, United States : The Endocrine Society. - 0021-972X .- 1945-7197. ; 95:7, s. 3092-3093
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Tidskriftsartikel (refereegranskat)abstract
- Dual-energy computed tomography (DECT) can acquire two datasets showing different attenuation levels allowing collectionof additional information about the elementary chemical compositionof the scanned material. Color can then be assigned accordingto the 80- and 140-kV computed tomography (CT) values to obtaina color-mapped, dual-energy image. DECT has been used extensivelyin our department in postmortem CT with excellent results (1).One of the advantages of DECT is that iodine contrast uptakein soft tissue can be quantified. We were wondering about itsability to localize parathyroid adenomas (PAs).
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| 16. |
- Haglund, Felix, et al.
(författare)
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Detailed Lymph Node Sectioning of Papillary Thyroid Carcinoma Specimen Increases the Number of pN1a Patients
- 2016
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Ingår i: Endocrine pathology. - : HUMANA PRESS INC. - 1046-3976 .- 1559-0097. ; 27:4, s. 346-351
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Tidskriftsartikel (refereegranskat)abstract
- Papillary thyroid carcinoma (PTC) is a common endocrine malignancy, frequently presenting with lymph node metastasis at the time of diagnosis. Lymph node staging (N) partly determines treatment, follow-up, and prognosis. Since 2011, our institution has employed a more comprehensive histopathological work-up of lymph nodes in patients with PTC. We sought to retrospectively determine the value of serial lymph node level sectioning in PTCs with negative preoperative lymph node status (pN0) as a method to increase the sensitivity of detecting metastatic disease. We included all patients that underwent thyroidectomy and central neck dissection and subsequent comprehensive lymph node level sectioning due to PTC with an initial pN0 status between the years 2011 and 2015 at our institution. Sixty-seven cases of PTC with a median of 10 metastatic free lymph nodes identified per case were included. After serial lymph node sectioning of the central compartment, 11 cases (16 %) revealed lymph node metastasis, six of which (55 %) presented with a small primary tumor (amp;lt; 20 mm, T1). Of all T1 tumors with initial pN0 status, 18 % (T1a) and 9 % (T1b) reached a pN1 stage after comprehensive lymph node sectioning. Cases with altered lymph node status had a median of 15 identified lymph nodes as compared to ten in cases that remained negative. We conclude that comprehensive lymph node sectioning increased the sensitivity of detecting metastases in PTC and altered the pathological TNM staging (pTNM) for a significant number of patients. Although of limited prognostic significance, the method should be considered as an adjunct tool when assessing lymph node status of PTC as a part of the routine histological work-up to ensure an accurate cancer staging.
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| 17. |
- Haglund, Felix, et al.
(författare)
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Inflammatory infiltrates in parathyroid tumors
- 2017
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 177:6, s. 445-453
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Tidskriftsartikel (refereegranskat)abstract
- Context: Inflammatory infiltrates are sometimes present in solid tumors and may be coupled to clinical behavior or etiology. Infectious viruses contribute to tumorigenesis in a significant fraction of human neoplasias. Objective: Characterize inflammatory infiltrates and possible viral transcription in primary hyperparathyroidism. Design: From the period 2007 to 2016, a total of 55 parathyroid tumors (51 adenomas and 4 hyperplasias) with prominent inflammatory infiltrates were identified from more than 2000 parathyroid tumors in the pathology archives, and investigated by immunohistochemistry for CD4, CD8, CD20 and CD45 and scored as +0, +1 or +2. Clinicopathological data were compared to 142 parathyroid adenomas without histological evidence of inflammation. Transcriptome sequencing was performed for 13 parathyroid tumors (four inflammatory, 9 non-inflammatory) to identify potential viral transcripts. Results: Tumors had prominent germinal center-like nodular (+2) lymphocytic infiltrates consisting of T and B lymphocytes (31%) and/or diffuse (+1-2) infiltrates of predominantly CD8+T lymphocytes (84%). In the majority of cases with adjacent normal parathyroid tissue, the normal rim was unaffected by the inflammatory infiltrates (96%). Presence of inflammatory infiltrates was associated with higher levels of serum-PTH (P = 0.007) and oxyphilic differentiation (P = 0.002). Co-existent autoimmune disease was observed in 27% of patients with inflammatory infiltrates, which in turn was associated with oxyphilic differentiation (P = 0.041). Additionally, prescription of anti-inflammatory drugs was associated with lower serum ionized calcium (P = 0.037). Conclusions: No evidence of virus-like sequences in the parathyroid tumors could be found by transcriptome sequencing, suggesting that other factors may contribute to attract the immune system to the parathyroid tumor tissue.
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| 18. |
- Hellman, Per, et al.
(författare)
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Positron emission tomography with 11C-methionine in hyperparathyroidism
- 1994
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Ingår i: Surgery. - 0039-6060 .- 1532-7361. ; 116:6, s. 974-981
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Positron emission tomography (PET) has not been evaluated for preoperative localization and functional characterization of the parathyroid tissue in hyperparathyroidism. METHODS: Images of the neck and upper mediastinum of 23 patients with hyperparathyroidism were obtained by PET after intravenous administration of 400 to 800 MBq L-[methyl-11C]-methionine. The investigation was repeated in six patients after Na2-ethylenediamine tetraacetic acid infusion, whereby stable 65% to 157% rise in intact serum parathyroid hormone values was attained. RESULTS: Parathyroid surgical procedure revealed single (21 patients) or two enlarged parathyroid glands (two patients) that were characterized as chief cell adenoma (n = 13), hyperplasia (n = 10), or carcinoma (n = 2) and weighed 80 to 6000 mg. Twenty (80%) of these glands were localized by PET. The remaining examinations (20%) were false negative and mainly encompassed small parathyroids in juxtathyroid position. Among 15 patients undergoing parathyroid reoperation true-positive localizations were obtained for 87% of the glands. The images displayed lower tracer uptake in residual thyroid lobes (n = 40), esophagus, and cervical vertebrae. Na2-ethylenediamine tetraacetic acid infusion failed to enhance parathyroid uptake values. Ultrasonography, computed tomography, technetium-thallium scintigraphy, and venous sampling revealed 25% to 53% of the pathologic parathyroid tissues of the patients undergoing reoperation and was largely complementary to PET. CONCLUSIONS: The results suggest that PET may provide novel possibilities for the imaging of pathologic parathyroid glands in hyperparathyroidism.
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| 19. |
- Holmberg, Lina, et al.
(författare)
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Trauma triage criteria as predictors of severe injury-a Swedish multicenter cohort study
- 2022
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Ingår i: BMC Emergency Medicine. - : Springer Nature. - 1471-227X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Adequate performance of trauma team activation (TTA) criteria is important in order to accurately triage trauma patients. The Swedish National Trauma Triage Criteria (SNTTC) consists of 29 criteria that trigger either a Trauma Alert, the highest level of TTA, or a Trauma Response. This study aimed to evaluate the SNTTC and its accuracy in predicting a severely injured patient in a multicenter setting. Methods A cohort study in Sweden involving six trauma receiving hospitals. Data was collected from the Swedish Trauma Registry. Some 626 patients were analyzed with regard to the specific criteria used to initiate the TTA, injury severity with New Injury Severity Score (NISS) and emergency interventions. Sensitivity, specificity, positive predictive value (PPV) and positive likelihood ratio (LR+) of the criteria were calculated, as well as undertriage and overtriage. Results All 29 criteria of SNTTC had a sensitivity > 80% for identifying a severely injured patient. The 16 Trauma Alert Criteria had a lower sensitivity of 62.6% but higher LR+ (3.5 vs all criteria 1.4), specificity (82.3 vs 39.1%) and PPV (55.4 vs 37.6%) and the highest accuracy (AUC 0.724). When using only the six physiological criteria, sensitivity (44.8%) and accuracy (AUC 0.690) decreased while LR+ (6.7), specificity (93.3%) and PPV (70.2%) improved. Conclusion SNTTC is efficient in identifying severely injured patients. The current set of criteria exhibits the best sensitivity compared to other examined combinations and no additional criterion was found to improve the protocol enough to promote a change.
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| 20. |
- Höög, Anders, et al.
(författare)
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Somatostatin Receptor Expression in Renal Cell Carcinoma-A New Front in the Diagnostics and Treatment of Renal Cell Carcinoma
- 2018
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Ingår i: Clinical Genitourinary Cancer. - : CIG MEDIA GROUP, LP. - 1558-7673 .- 1938-0682. ; 16:3, s. E517-E520
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Tidskriftsartikel (refereegranskat)abstract
- Clinical Practice PointsRenal cell carcinoma (RCC) has a poor prognosis and is difficult to treat because of its ability to spread asymptomatically and its resistance to chemotherapy.In this patient series, we report that RCC metastases can be identified using gallium-68 (68Ga)-edotreotide (DOTATOC) positron emission tomography/computed tomography (PET/CT).Immunostaining of tumor tissue from primary RCC tumors and their matched adrenal, pancreatic, and thyroid metastases showed that RCC cells express membranous somatostatin receptor 2.These findings indicate that 68Ga-DOTATOC PET/CT can be used as a new imaging modality in management of metastatic RCC and might contribute to the development of new somatostatin analogue-based methods for the treatment of metastatic RCC.
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| 21. |
- Johnson, Linda S.B., et al.
(författare)
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Irregularity and lack of p waves in short tachycardia episodes predict atrial fibrillation and ischemic stroke
- 2018
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Ingår i: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 15:6, s. 805-811
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Tidskriftsartikel (refereegranskat)abstract
- Background: Atrial fibrillation (AF) is defined as an irregular supraventricular tachycardia (SVT) without p waves, with duration >30 seconds. Whether AF characteristics during short SVT episodes predict AF and stroke is not known. Objective: The purpose of this study was to determine whether irregularity and lack of p waves, alone or in combination, during short SVT episodes increase the risk of incident AF and ischemic stroke. Methods: The population-based Malmö Diet and Cancer study includes 24-hour ECG screening of 377 AF-free individuals (mean age 64.5 years; 43% men) who were prospectively followed for >13 years. There were 65 AF events and 25 ischemic stroke events during follow-up. Subjects with an SVT episode ≥5 beats were identified, and the longest SVT episode was assessed for irregularity and lack of p waves. The association between SVT classification and AF and stroke was assessed using multivariable adjusted Cox regression. Results: The incidence of AF increased with increasing abnormality of the SVTs. The risk-factor adjusted hazard ratio for AF was 4.95 (95% confidence interval 2.06–11.9; P <.0001) for those with short irregular SVTs (<70 beats) without p waves. The incidence of ischemic stroke was highest in the group with regular SVT episodes without p waves (hazard ratio 14.2; 95% confidence interval 3.76–57.6; P <.0001, adjusted for age and sex). Conclusion: Characteristics of short SVT episodes detected at 24-hour ECG screening are associated with incident AF and ischemic stroke. Short irregular SVTs without p waves likely represent early stages of AF or atrial myopathy. Twenty-four–hour ECG could identify subjects suitable for primary prevention efforts.
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| 22. |
- Juhlin, C, et al.
(författare)
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[Differential diagnosis in adrenal gland tumors using PET and 11C-metomidate]
- 1998
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Ingår i: Nordisk Medicin. - 0029-1420. ; 113:9, s. 306-307
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated 13 patients with incidentaloma using PET with 11C-metomidate. The patients included six adrenocortical adenomas, one adrenal cancer, two pheochromocytomas, one myelolipoma, one benign cyst and two metastases. A very high tracer uptake was observed in all tumors originating from the adrenal cortex, allowing excellent visualisation, whereas all other processes were negative. PET with 11C-metomidate is a very promising method for the characterisation of incidentalomas and is suggested to be included very early in the evaluation of these patients.
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| 23. |
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| 24. |
- Juhlin, Oskar, et al.
(författare)
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Fashionable Services for Wearables : Inventing and Investigating a New Design Path for Smart Watches
- 2016
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Ingår i: Proceedings of the 9th Nordic Conference on Human-Computer Interaction. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450347631
-
Konferensbidrag (refereegranskat)abstract
- With the advent of wearable devices equipped with publicly visible screens, we argue for the need to apply fashion thinking in designing their visual expression. The screen provides endless variations of visual expression, beyond traditional clothing. The topic motivates us to investigate the potential of assembling “fashion thinking” with services generation, to create new forms of use that wearers will adore, as they do with clothes. Disregarding fashion thinking in wearable design might lead to user dissatisfaction and missed opportunities. In an explorative design study we triangulate three methods i.e. a small study on the use of smart watches in dressing practices; an invention and design of a service called “Watch for Figuracy”, with a watch face contextually dependent on the wearer’s dressed ensemble, and finally an initial user feedback study. Altogether they indicate the potential of fashion wearable hybrids and shortcomings in utilizing color theory for matching the watch face to the outfit.
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| 25. |
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| 26. |
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| 27. |
- Khan, Tanweera Shaheena, et al.
(författare)
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Vincristine, Cisplatin, Teniposide and Cyclophosphamide Combination in the Treatment of Recurrent or Metastatic Adrenocortical Cancer
- 2004
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Ingår i: Medical Oncology. - 1357-0560 .- 1559-131X. ; 21:2, s. 167-177
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy and tolerability of a combination of vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) in 11 patients (median age, 45 yr) with recurrent and/or metastatic adrenocortical cancer (ACC) (seven functional and four nonfunctional) were evaluated. All patients received this regimen after the failure of streptozocin and o,p'-DDD (SO) combination therapy. The regimen comprised cyclophosphamide, 600 mg/m2, and vincristine, 1.5 mg/m2, maximum dose 2.0 mg (d 1); cisplatin, 100 mg/m2 (d 2) and teniposide, 150 mg/m2 (d 4). Cycles were repeated every 4 wk. One to eight cycles (median, six cycles) of OPEC were administered to each patient. The median duration of treatment was 6 mo. The overall 2-yr survival rate was 82% and the median survival since diagnosis was 44 mo while it was 21 mo since start of OPEC therapy. Responses were obtained in nine patients: partial response in two patients, and stable disease in seven patients. The median duration of response was 6.75 mo. A total of 60 cycles of chemotherapy were given to all patients; grade 1-2 toxicity occurred in 57 cycles, while grade 3 toxicity was observed only in two cycles, according to NCI's Common Toxicity Criteria. We conclude that the OPEC regimen may be considered in recurrent or metastatic ACC as a second-line medical treatment. However, the combination is accompanied by considerable side effects and dose modifications are necessary in order to be able to recommend the treatment. This regimen needs further evaluation compared with SO therapy preferably in a randomized multicenter trial.
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| 28. |
- Laurell, Cecilia, et al.
(författare)
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Transcriptional profiling enables molecular classification of adrenocortical tumours
- 2009
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 161:1, s. 141-152
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Tumours in the adrenocortex are common human tumours. Malignancy is however, rare, the yearly incidence being 0.5-2 per million inhabitants, but associated with a very aggressive behaviour. Adrenocortical tumours are often associated with altered hormone production with a variety of clinical symptoms. The aggressiveness of carcinomas together with the high frequency of adenomas calls for a deeper understanding of the underlying biological mechanisms and an improvement of the diagnostic possibilities. Methods: Microarray gene expression analysis was performed in tumours of adrenocortex with emphasis on malignancy as well as hormonal activity. The sample set consisted of 17 adenomas, 11 carcinomas and 4 histological normal adrenocortexes. RNA from these was hybridised according to a reference design on microarrays harbouring 29 760 human cDNA clones. Confirmation was performed with quantitative real time-PCR and western blot analysis. Results: Unsupervised clustering to reveal relationships between samples based on the entire gene expression profile resulted in two subclusters; carcinomas and non-cancer specimens. A large number of genes were accordingly found to be differentially expressed comparing carcinomas to adenomas. Among these were IGF2, FGFR1 and FGFR4 in growth factor signalling the most predominant and also the USP4, UBE2C and UFD1L in the ubiquitin-proteasome pathway. Moreover, two subgroups of carcinomas were identified with different survival outcome, suggesting that survival prediction can be made on the basis of gene expression profiles. Regarding adenomas with aldosterone overproduction, OSBP and VEGFB were among the most up-regulated genes compared with the other samples. Conclusions: Adrenocortical carcinomas are associated with a distinct molecular signature apparent in their gene expression profiles. Differentially expressed genes were identified associated with malignancy, survival as well as hormonal activity providing a resource of candidate genes for an exploration of possible drug targets and diagnostic and prognostic markers.
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| 29. |
- Mochalina, Natalia, et al.
(författare)
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Antithrombotic therapy in patientswith non-valvular atrial fibrillation in Southern Sweden : A population-based cohort study
- 2016
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 140, s. 94-99
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Oral anticoagulants in patients with atrial fibrillation (AF) with moderate-to-high stroke risk are strongly recommended by the current guidelines.Materials and methods: Population-based register study of all 13,837 patients with incident non-valvular AF diagnosed during 2011-2014 in primary and secondary care (including all in-and outpatient visits) in Skane County, Sweden. The outcome was the prescription of direct-acting oral anticoagulants (DOAC), warfarin or acetylsalicylic acid (ASA).Results and conclusion: Guideline adherence increased from 47.6% in 2011 to 66.1% in 2014, mostly due to decrease in undertreatment. In patients with CHA(2)DS(2)-VASc score >= 2, ASA uptake decreased from 29.9% to 14.7% and DOAC uptake increased from 2.1% to 25.1%. The use of ASA was more common among elderly and with increasing stroke-and bleeding risk. Overall, 47.4% of patients with CHA(2)DS(2)-VASc score >= 2 did not receive oral anticoagulants. Undertreatment was particularly common in women < 65 years (55.8%) and in patients >84 years (65.3% in women and 62% in men). Overtreatment of patients at low stroke risk was 35.9% in men and 36.4% in women. Provider speciality affected the choice of treatment only to a minor degree. Despite increasing guideline adherence, there is a suboptimal use of antithrombotic therapy in a large proportion of AF patients diagnosed in different clinical settings. Efforts to further improve guideline adherence should particularly be targeted on women < 65 years, elderly > 84 years and patients at low stroke risk.
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| 30. |
- Mochalina, Natalia, et al.
(författare)
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Ischemic stroke rates decline in patients with atrial fibrillation as anticoagulants uptake improves : A Swedish cohort study
- 2017
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Ingår i: Thrombosis Research. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0049-3848 .- 1879-2472. ; 158, s. 44-48
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The impact of the increased anticoagulants uptake on incidence rate of ischemic stroke is largely unknown. We assessed time trends in rates of ischemic stroke in patients with incident atrial fibrillation (AF) diagnosed between 2011 and 2013.Materials and methods: Population-based retrospective registry study of all 11,500 adults diagnosed with incident non-valvular atrial fibrillation in 2011-2013 in primary and secondary care and receiving oral anticoagulants (n = 4847), aspirin (n = 2850) or no treatment (n = 3766) in Skane County, Sweden. The primary outcome was the rate of ischemic stroke within 365 days after AF diagnosis.Results and conclusion: Cumulative incidence of ischemic stroke decreased from 2.87% (95% confidence interval (CI) 2.37-3.45%) to 1.93% (95% CI 1.54-2.41%) while the uptake of oral anticoagulants increased from 36.6% to 48.4% between 2011 and 2013 (regression coefficient - 0.08; 95% CI, - 0.09 to - 0.07, p < 0.001). The increased uptake of oral anticoagulants in the community is associated with decreased incidence of ischemic stroke in AF patients.
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| 31. |
- Måneheim, Alexandra, et al.
(författare)
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Diagnostic reliability of monitoring for premature atrial and ventricular complexes
- 2024
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Ingår i: Europace. - 1099-5129. ; 26:8
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Tidskriftsartikel (refereegranskat)abstract
- Aims Short-term ambulatory electrocardiogram (ECG) monitoring is often used to assess premature atrial complex (PAC) and premature ventricular complex (PVC) frequency, but the diagnostic reliability is unknown. The objective of this study was to study the day-to-day variability of PAC and PVC frequency. Methods We used 14-day full-disclosure mobile cardiac telemetry recordings without atrial fibrillation in 8245 US patients aged and results 17-103 years to calculate the diagnostic reliability of shorter ambulatory ECG recordings compared with 14-day averages. Over 14 days, 1853 patients had ≥500 PACs/day, 410 patients had ≥5000 PACs/day, and 197 patients had ≥10 000 PACs/day; 1640 patients had ≥500 PVCs/day, 354 patients had ≥5000 PVCs/day, and 175 patients had ≥10 000 PVCs/day. After 3 days, the estimated daily PAC frequency differed by ≥50% from the 14-day mean in 25% of patients; for PVCs, the corresponding duration was 7 days. Ten days of monitoring were needed to estimate PAC and PVC frequency within ±20% of the overall 14-day frequency in 80% of patients. For daily PAC and PVC frequencies ≥10 000, single-day estimation had a specificity of 99.3% [95% confidence interval (CI) 99.1-99.5] at a sensitivity of 76.6 (95% CI 70.1-80.4%) for PACs and a 99.6% (95% CI 99.4-99.7%) specificity at 79.4 (95% CI 72.7-85.2) sensitivity for PVCs. After 7 days, the sensitivity increased to 88.8% (95% CI 83.6-92.9) for PACs and 86.9% (95% CI 80.9-91.5%) for PVCs. Conclusion While there is substantial daily variability across most PAC and PVC levels, findings of ≥10 000 PACs or PVCs are highly specific and do not need to be confirmed with longer recordings.
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| 32. |
- Måneheim, Alexandra, et al.
(författare)
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Elevated premature ventricular complex counts on 24-hour electrocardiogram predict incident atrial fibrillation and heart failure—A prospective population-based cohort study
- 2022
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Ingår i: Heart Rhythm O2. - : Elsevier BV. - 2666-5018. ; 3:4, s. 344-350
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPremature ventricular complexes (PVCs) are known to predict heart failure (HF) and premature atrial contractions (PACs) are known to predict atrial fibrillation (AF) and stroke. PVCs and PACs share pathophysiological mechanisms; however, the combined effects of PVCs and PACs on HF, AF, and stroke risk have not been studied.ObjectivesTo study elevated PVC counts on 24-hour electrocardiogram monitoring (24hECG) in relation to incidence of AF, HF, and stroke, and whether this effect is altered by PAC frequency.MethodsThe prospective population-based Malmö Diet and Cancer study includes 24hECG registrations in 375 AF- and HF-free subjects (mean age 65 years, 55% women). During 17 years of follow-up there were 28 HF, 89 AF, and 28 stroke events. The hazard ratios (HR) of elevated PVC counts (defined as the top quartile, ≥77/24 hours) vs lower quartiles were assessed using multivariable adjusted Cox regression models.ResultsElevated PVC counts predicted incident AF (HR 1.9, 95% confidence interval [CI] 1.2–3.0) and HF (HR 3.1, 95% CI 1.4–7.0). Results were similar after adjustment for NT-proBNP and PACs. Multiform PVCs were associated with even higher risks (HR 2.8, 95% CI: 1.7–4.6 for AF; HR 5.0, 95% CI 2.2–11.7 for HF), as was the presence of both elevated PACs and PVCs (9% of the population, HR 4.1, 95% CI 2.4–6.8 for AF and HR 4.3, 95% CI 1.7–11.4 for HF). No significant association was found between elevated PVC counts and incident stroke.ConclusionElevated PVC counts predict incident AF and HF, particularly if PVCs are multiform or occur in combination with elevated PAC counts.
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| 33. |
- Skogseid, Britt, et al.
(författare)
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Adrenal lesions in multiple endocrine neoplasia type 1
- 1995
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Ingår i: Surgery. - 0039-6060 .- 1532-7361. ; 118:6, s. 1077-1082
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Multiple endocrine neoplasia (MEN) type 1 is accompanied by adrenal involvement, but characteristics and clinical handling of this lesion have been insufficiently explored. METHODS: Patients with MEN 1 (n = 43) were monitored (mean, 6.3 years) with annual biochemical and radiologic adrenal evaluation. Adrenal specimens were examined by in situ RNA-RNA hybridization for expression of the MEN1 candidate gene phospholipase C beta 3 (PLC beta 3) and immunostaining for insulin-like growth factor-1 receptor. RESULTS: Altogether 17 patients (40%) displayed adrenal enlargement, which was limited to the adrenal cortex and showed signs of progression, marked atypia, and cancer development in three of them. Only the carcinoma exhibited adrenocortical hormone excess. PLC beta 3 was expressed in the hyperplastic and adenomatous proliferation but not the carcinoma. Pancreatic endocrine tumors with insulin-proinsulin excess were overrepresented in the patients with adrenocortical involvement, but significant insulin-like growth factor-1 receptor immunoreactivity was restricted to the carcinoma. CONCLUSIONS: The prevalent adrenocortical lesion associated with MEN 1 requires regular attention because of malignant potential. It was unrelated to loss of constitution heterozygosity for the MEN1 locus (11q13) and PLC beta 3 expression, except for the cortical carcinoma exhibiting allelic losses involving also the Wiedemann-Beckwith gene at 11p15. Mechanisms for mitogenic relationships between the pancreatic and adrenal lesions of MEN 1 demand further clarification.
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| 34. |
- Skogseid, Britt, et al.
(författare)
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Limited tumor involvement found at multiple endocrine neoplasia type I pancreatic exploration : can it be predicted by preoperative tumor localization?
- 1998
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 22:7, s. 673-677; discussion 667-668
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Tidskriftsartikel (refereegranskat)abstract
- Radiologically demonstrable pancreatic endocrine tumors are a frequent requirement for exploration in patients with multiple endocrine neoplasia type I (MEN-I). Such delayed intervention is accompanied by a 30% to 50% incidence of pancreatic endocrine metastases. This study explores biochemical tumor markers and operative findings in relation to preoperative pancreatic radiology in 25 MEN-I patients. They underwent pancreatic surgery with (n = 19) or without (n = 6) radiologic signs of primary tumor and absence of metastases upon conventional examination, including OctreoScan testing (n = 10). Biochemical diagnosis required an increasing elevation of at least two independent pancreatic tumor markers. Tumor diameters averaged 1.1 cm (0-5 cm) and 0.9 cm (0.2-1.5 cm) in the patients with and without positive preoperative radiology, respectively. These investigations never displayed more than one of the consistently multiple tumors, and the results were falsely positive in 26%. Preoperatively unidentified regional or hepatic metastases were found at surgical exploration in 26% of patients with radiologic localization and in none of the others. Limited pancreatic tumor involvement necessitated intraoperative absence of metastases and pancreatic lesions /= 7 mm in diameter. Conventional pancreatic imaging is insensitive and nonspecific for recognizing even substantial pancreatic tumors associated with MEN-I.
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| 35. |
- Subramaniam, Raja, et al.
(författare)
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An isomer-specific high-energy collision-induced dissociation MS/MS database for forensic applications : a proof-of-concept on chemical warfare agent markers
- 2011
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Ingår i: Journal of Mass Spectrometry. - : Wiley. - 1076-5174 .- 1096-9888. ; 46:9, s. 917-924
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Tidskriftsartikel (refereegranskat)abstract
- Spectra database search has become the most popular technique for the identification of unknown chemicals, minimizing the need for authentic reference chemicals. In the present study, an isomer-specific high-energy collision-induced dissociation (CID) MS/MS spectra database of 12 isomeric O-hexyl methylphosphonic acids (degradation markers of nerve agents) was created. Phosphonate anions were produced by the electrospray ionization of phosphonic acids or negative-ion chemical ionization of their fluorinated derivatives and were analysed in a hybrid magnetic-sector–time-of-flight tandem massspectrometer. A centre-of-mass energy (Ecom) of 65eV led to an optimal sequential carbon–carbon bond breakage, which was interpreted in terms of charge remote fragmentation. The proposed mechanism is discussed in comparison with the routinely used low-energy CID MS/MS. Even-mass (odd-electron) charge remote fragmentation ion series were diagnostic of the O-alkyl chain structure and can be used to interpret unknown spectra. Together with the odd-mass ion series, they formed highly reproducible, isomer-specific spectra that gave significantly higher database matches and probability factors (by 1.5 times) than did the EI MS spectra of the trimethylsilyl derivatives of the same isomers. In addition, ionization by negative-ion chemical ionization and electrospray ionization resulted in similar spectra, which further highlights the general potential of the high-energy CID MS/MS technique.
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| 36. |
- Subramaniam, Raja, et al.
(författare)
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Determination of S-2-(N,N-diisopropylaminoethyl)- and S-2-(N,N-diethylaminoethyl) methylphosphonothiolate, nerve agent markers, in water samples using strong anion-exchange disk extraction, in vial trimethylsilylation, and gas chromatography-mass spectrometry analysis
- 2012
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Ingår i: Journal of Chromatography A. - Amsterdam : Elsevier. - 0021-9673 .- 1873-3778. ; 1229, s. 86-94
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Tidskriftsartikel (refereegranskat)abstract
- Since the establishment of the Chemical Weapons Convention in 1997, the development of analytical methods for unambiguous identification of large numbers of chemicals related to chemical warfare agents has attracted increased interest. The analytically challenging, zwitterionic S-2-(N,N-diisopropylaminoethyl) methylphosphonothiolate (EA-2192), a highly toxic degradation marker of the nerve agent VX, has been reported to resist trimethylsilylation or to result in an unacceptably high limit of detection in GC-MS analysis. In the present study, the problem is demonstrated to be associated with the presence of salt, which hinders trimethysilylation. EA-2192 was extracted from aqueous samples by use of a strong anion-exchange disk, derivatized as a trimethylsilyl derivative via in vial solid-phase trimethylsilylation and identified by GC-MS. The limits of detection were 10ng/mL and 100ng/mL (in a water sample) for SIM and SCAN mode respectively. The analytical method was found to be repeatable with relative standard deviation <10%. The performance of the method was evaluated using a proficiency test sample and environmental samples (spiked river water and Baltic Bay water) and compared with the commonly used evaporation-silylation method. The disk method displayed good tolerance to the presence of salt and the spiked EA-2192 was conclusively identified in all matrices. In addition, the applicability of the method was further demonstrated for other selected hydrolysis products of VX and Russian VX, namely S-2-(N,N-diethylaminoethyl) methylphosphonothiolate, ethyl methylphosphonic acid, methylphosphonic acid, and isobutyl methylphosphonic acid. For the synthesis of reference compounds, EA-2192 and its analog from degradation of the Russian VX isomer, the present methods were improved by using a polymer-bound base, resulting in >90% purity based on (1)H NMR. Based on the current results and earlier work on alkylphosphonic acids using the same method, we conclude that the method is a viable choice for the simultaneous determination of a wide range of degradation products of nerve agents - zwitterionic, monoacid, diacid, and monothioacid chemicals - with excellent performance.
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| 37. |
- Subramaniam, Raja, et al.
(författare)
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Direct derivatization and rapid GC-MS screening of nerve agent markers in aqueous samples
- 2010
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 82:17, s. 7452-7459
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Tidskriftsartikel (refereegranskat)abstract
- A rapid screening and identification method based on derivatization and gas chromatography mass spectrometry (GC-MS) has been developed for the detection of alkylphosphonic acids (APAs), the degradation products of organophosphorus nerve agents. The novel method described involves rapid (5 min) and direct derivatization of 25 muL aqueous sample using highly fluorinated phenyldiazomethane reagents (e.g., 1-(diazomethyl)-3,5-bis(trifluoromethyl)benzene). The APA derivatives are then screened by GC-MS negative ion chemical ionization (NICI) and identified by electron ionization (EI) mode. The conditions for the derivatization were optimized using statistical experimental design and multivariate data analysis. Method robustness was evaluated using aqueous samples from an official OPCW Proficiency Test and all APAs present in the sample were conclusively identified. Limits of detection for rapid screening using SIM NICI were between 5 and 10 ng/mL APA in aqueous sample, and for identification using full scan EI 100 ng/mL.
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| 38. |
- Welander, Jenny, et al.
(författare)
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Rare Germline Mutations Identified by Targeted Next-Generation Sequencing of Susceptibility Genes in Pheochromocytoma and Paraganglioma
- 2014
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 99:7, s. E1352-E1360
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Tidskriftsartikel (refereegranskat)abstract
- Context: Pheochromocytomas and paragangliomas have a highly diverse genetic background, with a third of the cases carrying a germline mutation in 1 of 14 identified genes. Objective: This study aimed to evaluate next-generation sequencing for more efficient genetic testing of pheochromocytoma and paraganglioma and to establish germline and somatic mutation frequencies for all known susceptibility genes. Design: A targeted next-generation sequencing approach on an Illumina MiSeq instrument was used for a mutation analysis in 86 unselected pheochromocytoma and paraganglioma tumor samples. The study included the genes EGLN1, EPAS1, KIF1B beta, MAX, MEN1, NF1, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and VHL. Results were verified in tumor and constitutional DNA with Sanger sequencing. Results: In all cases with clinical syndromes or known germline mutations, a mutation was detected in the expected gene. Among 68 nonfamilial tumors, 32 mutations were identified in 28 of the samples (41%), including germline mutations in EGLN1, KIF1B beta, SDHA, SDHB, and TMEM127 and somatic mutations in EPAS1, KIF1B beta, MAX, NF1, RET, and VHL, including one double monoallelic EPAS1 mutation. Conclusions: Targeted next-generation sequencing proved to be fast and cost effective for the genetic analysis of pheochromocytoma and paraganglioma. More than half of the tumors harbored mutations in the investigated genes. Notably, 7% of the apparently sporadic cases carried germline mutations, highlighting the importance of comprehensive genetic testing. KIF1B beta, which previously has not been investigated in a large cohort, appears to be an equally important tumor suppressor as MAX and TMEM127 and could be considered for genetic testing of these patients.
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| 39. |
- Wennerberg, Erik, et al.
(författare)
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Human anaplastic thyroid carcinoma cells are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract NK cells
- 2014
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 20:22, s. 5733-5744
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive forms of cancer with no curative therapies available. To date, strategies to target ATC by immunotherapy have not been evaluated. We investigated whether ATC would be a suitable target for natural killer (NK) cell-based immunotherapy.EXPERIMENTAL DESIGN: We first established seven new cell lines from ATC tumors, three from papillary thyroid carcinoma tumors and analyzed them together with eight additional ATC cell lines. Cells were analyzed for sensitivity to lysis by NK cells and their ability to chemoattract and regulate the activity of NK cells. In addition, fresh tumor samples and peripheral blood from six patients with ATC were analyzed for NK cell infiltration and phenotype.RESULTS: We observed that ATC cell lines are sensitive to lysis by ex vivo expanded NK cells and that the lysis was abrogated upon blockade of NKG2D. Sensitivity of thyroid cancer cell lines to NK cell-mediated lysis correlated with surface expression of UL16-binding protein 2 on tumor cells. Moreover, ATC cell lines produced high levels of CXCL10 and stimulated migration of expanded NK cells and ATC tumors were enriched for NK cells expressing the cognate chemokine receptor CXCR3. However, compared with NK cells in peripheral blood, ATC tumor-derived NK cells displayed a suppressed phenotype with a downregulated expression of NKG2D. In vitro, suppression of NK cell-mediated lysis and NKG2D expression by ATC cells was restored upon neutralization of prostaglandin-E2.CONCLUSIONS: ATC cell lines are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract CXCR3-positive NK cells. Patients with ATC may benefit from NK cell-based immunotherapy.
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| 40. |
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| 41. |
- Örlefors, Håkan, et al.
(författare)
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Whole-body 11C-5-hydroxytryptophan positron emission tomography as a universal imaging technique for neuroendocrine tumors : Comparison with somatostatin receptor scintigraphy and computed tomography
- 2005
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 90:6, s. 3392-3400
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Tidskriftsartikel (refereegranskat)abstract
- Neuroendocrine tumors (NETs) can be small and situated almost anywhere throughout the body. Our objective was to investigate whether whole-body (WB) positron emission tomography (PET) with 11C-5-hydroxytryptophan (5-HTP) can be used as a universal imaging technique for NETs and to compare this technique with established imaging methods. Forty-two consecutive patients with evidence of NET and a detected lesion on any conventional imaging (six bronchial, two foregut, 16 midgut, and two thymic carcinoids; one ectopic Cushing’s syndrome; four gastrinomas; one insulinoma; six nonfunctioning endocrine pancreatic tumors; one gastric carcinoid, one paraganglioma; and two endocrine-differentiated pancreatic carcinomas) were studied. The WB-11C-5-HTP-PET examinations were compared with WB-computed tomography (CT) and somatostatin receptor scintigraphy (SRS). Tumor lesions were imaged with PET in 95% of the patients. In 58% of the patients, PET could detect more lesions than SRS and CT and equal numbers in 34%, whereas in three cases, SRS or CT showed more lesions. In 84% (16 of 19 patients), PET could visualize the primary tumor compared with 47 and 42% for SRS and CT, respectively. The surgically removed PET-positive primary tumor sizes were 6–30 mm. To conclude, this study indicates that WB-11C-5-HTP-PET can be used as a universal imaging method for detection of NETs. This study also shows that WB-11C-HTP-PET is sensitive in imaging small NET lesions, such as primary tumors, and can in a majority of cases image significantly more tumor lesions than SRS and CT.
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