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| 2. |
- Palmblad, Jan, et al.
(författare)
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TPO, but not soluble-IL-6 receptor, levels increase after anagrelide treatment of thrombocythemia in chronic myeloproliferative disorders
- 2008
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Ingår i: International Journal of Medical Sciences. - Lake Haven : Ivyspring international publishers. - 1449-1907. ; 5:2, s. 87-91
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Tidskriftsartikel (refereegranskat)abstract
- Anagrelide is often used in the treatment of thrombocythemia in myeloproliferative disease (MPD), but information concerning effects of treatment on cytokines involved in regulation of blood platelet levels is limited. Here, we investigated serum levels of thrombopoietin (TPO) and soluble IL-6 receptor (sIL-6R) in relation to response to treatment with and plasma concentrations of anagrelide. Samples from 45 patients with thrombocythemia due to MPD (ET=31, PV=14), being treated with anagrelide for 6 months, were analyzed for TPO, sIL-6R and anagrelide levels. The mean baseline platelet count was 983x10(9)/L. A reduction of platelets to <600 in asymptomatic or <400 x 10(9)/L in symptomatic patients was defined as a complete remission (CR), a reduction with >50% of baseline as partial remission, and <50% reduction as failure. At 6 months, 35 patients were in CR, 1 had a partial remission and 9 were treatment failures. For all patients, there was an increase in TPO of 44% from baseline; this change was more pronounced for patients with partial remission and failure. sIL-6R levels did not change significantly. There was no correlation between levels of anagrelide and cytokine levels at 6 months, and changes of cytokine levels did not relate to changes of platelet counts. Thus, a pronounced increase of TPO levels after 6 months of anagrelide treatment indicated that this treatment affected a major regulatory mechanism for megakaryocyte and platelet formation in MPD.
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| 3. |
- Broman, Lars Mikael, et al.
(författare)
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Pressure and flow properties of cannulae for extracorporeal membrane oxygenation II : drainage (venous) cannulae
- 2019
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Ingår i: Perfusion. - : SAGE PUBLICATIONS LTD. - 0267-6591 .- 1477-111X. ; 34, s. 65-73
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Tidskriftsartikel (refereegranskat)abstract
- The use of extracorporeal life support devices such as extracorporeal membrane oxygenation in adults requires cannulation of the patient's vessels with comparatively large diameter cannulae to allow circulation of large volumes of blood (>5 L/min). The cannula diameter and length are the major determinants for extracorporeal membrane oxygenation flow. Manufacturing companies present pressure-flow charts for the cannulae; however, these tests are performed with water. Aims of this study were 1. to investigate the specified pressure-flow charts obtained when using human blood as the circulating medium and 2. to support extracorporeal membrane oxygenation providers with pressure-flow data for correct choice of the cannula to reach an optimal flow with optimal hydrodynamic performance. Eighteen extracorporeal membrane oxygenation drainage cannulae, donated by the manufacturers (n = 6), were studied in a centrifugal pump driven mock loop. Pressure-flow properties and cannula features were described. The results showed that when blood with a hematocrit of 27% was used, the drainage pressure was consistently higher for a given flow (range 10%-350%) than when water was used (data from each respective manufacturer's product information). It is concluded that the information provided by manufacturers in line with regulatory guidelines does not correspond to clinical performance and therefore may not provide the best guidance for clinicians.
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| 5. |
- Sandgren, Johanna, et al.
(författare)
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Integrative epigenomic and genomic analysis of malignant pheochromocytoma
- 2010
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Ingår i: Experimental and Molecular Medicine. - : Springer Science and Business Media LLC. - 1226-3613 .- 2092-6413. ; 42:7, s. 484-502
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Tidskriftsartikel (refereegranskat)abstract
- Epigenomic and genomic changes affect gene expression and contribute to tumor development. The histone modifications trimethylated histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) are epigenetic regulators associated to active and silenced genes, respectively and alterations of these modifications have been observed in cancer. Furthermore, genomic aberrations such as DNA copy number changes are common events in tumors. Pheochromocytoma is a rare endocrine tumor of the adrenal gland that mostly occurs sporadic with unknown epigenetic/genetic cause. The majority of cases are benign. Here we aimed to combine the genome-wide profiling of H3K4me3 and H3K27me3, obtained by the ChIP-chip methodology, and DNA copy number data with global gene expression examination in a malignant pheochromocytoma sample. The integrated analysis of the tumor expression levels, in relation to normal adrenal medulla, indicated that either histone modifications or chromosomal alterations, or both, have great impact on the expression of a substantial fraction of the genes in the investigated sample. Candidate tumor suppressor genes identified with decreased expression, a H3K27me3 mark and/or in regions of deletion were for instance TGIF1, DSC3, TNFRSF10B, RASSF2, HOXA9, PTPRE and CDH11. More genes were found with increased expression, a H3K4me3 mark, and/or in regions of gain. Potential oncogenes detected among those were GNAS, INSM1, DOK5, ETV1, RET, NTRK1, IGF2, and the H3K27 trimethylase gene EZH2. Our approach to associate histone methylations and DNA copy number changes to gene expression revealed apparent impact on global gene transcription, and enabled the identification of candidate tumor genes for further exploration.
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| 6. |
- Sandgren, Johanna, et al.
(författare)
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Recurrent genomic alterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis
- 2010
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 17:3, s. 561-579
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Tidskriftsartikel (refereegranskat)abstract
- Pheochromocytomas and abdominal paragangliomas are adrenal and extra-adrenal catecholamine-producing tumours. They arise due to heritable cancer syndromes, or more frequently occur sporadically due to an unknown genetic cause. The majority of cases are benign, but malignant tumours are observed. Previous comparative genomic hybridization (CGH) and loss of heterozygosity studies have shown frequent deletions of chromosome arms 1p, 3q and 22q in pheochromocytomas. We applied high-resolution whole-genome array CGH on 53 benign and malignant pheochromocytomas and paragangliomas to narrow down candidate regions as well as to identify chromosomal alterations more specific to malignant tumours. Minimal overlapping regions (MORs) were identified on 16 chromosomes, with the most frequent MORs of deletion (> or = 32%) occurring on chromosome arms 1p, 3q, 11p/q, 17p and 22q, while the chromosome arms 1q, 7p, 12q and 19p harboured the most common MORs of gain (> or = 14%). The most frequent MORs (61-75%) in the pheochromocytomas were identified at 1p, and the four regions of common losses encompassed 1p36, 1p32-31, 1p22-21 and 1p13. Tumours that did not show 1p loss generally demonstrated aberrations on chromosome 11. Gain of chromosomal material was significantly more frequent among the malignant cases. Moreover, gain at 19q, trisomy 12 and loss at 11q were positively associated with malignant pheochromocytomas, while 1q gain was commonly observed in the malignant paragangliomas. Our study revealed novel and narrow recurrent chromosomal regions of loss and gain at several autosomes, a prerequisite for identifying candidate tumour suppressor genes and oncogenes involved in the development of adrenal and extra-adrenal catecholamine-producing tumours.
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| 7. |
- Alimohammadi, Mohammad, et al.
(författare)
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Autoimmune Polyendocrine Syndrome Type 1 : NALP5 in Autoimmune Polyendocrine Syndrome Type 1
- 2006
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Ingår i: The New England Journal of Medicine. ; 358:10, s. 1018-28
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Tidskriftsartikel (refereegranskat)abstract
- Background Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disorder caused by mutations in AIRE, the autoimmune regulator gene. Though recent studies concerning AIRE deficiency have begun to elucidate the molecular pathogenesis of organ-specific autoimmunity in patients with APS-1, the autoantigen responsible for hypoparathyroidism, a hallmark of APS-1 and its most common autoimmune endocrinopathy, has not yet been identified. Methods We performed immunoscreening of a human parathyroid complementary DNA library, using serum samples from patients with APS-1 and hypoparathyroidism, to identify patients with reactivity to the NACHT leucine-rich-repeat protein 5 (NALP5). Subsequently, serum samples from 87 patients with APS-1 and 293 controls, including patients with other autoimmune disorders, were used to determine the frequency and specificity of autoantibodies against NALP5. In addition, the expression of NALP5 was investigated in various tissues. Results NALP5-specific autoantibodies were detected in 49% of the patients with APS-1 and hypoparathyroidism but were absent in all patients with APS-1 but without hypoparathyroidism, in all patients with other autoimmune endocrine disorders, and in all healthy controls. NALP5 was predominantly expressed in the cytoplasm of parathyroid chief cells. Conclusions NALP5 appears to be a tissue-specific autoantigen involved in hypoparathyroidism in patients with APS-1. Autoantibodies against NALP5 appear to be highly specific and may be diagnostic for this prominent component of APS-1.
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| 8. |
- Alimohammadi, Mohammad, et al.
(författare)
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Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen
- 2008
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 358:10, s. 1018-1028
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disorder caused by mutations in AIRE, the autoimmune regulator gene. Though recent studies concerning AIRE deficiency have begun to elucidate the molecular pathogenesis of organ-specific autoimmunity in patients with APS-1, the autoantigen responsible for hypoparathyroidism, a hallmark of APS-1 and its most common autoimmune endocrinopathy, has not yet been identified. METHODS: We performed immunoscreening of a human parathyroid complementary DNA library, using serum samples from patients with APS-1 and hypoparathyroidism, to identify patients with reactivity to the NACHT leucine-rich-repeat protein 5 (NALP5). Subsequently, serum samples from 87 patients with APS-1 and 293 controls, including patients with other autoimmune disorders, were used to determine the frequency and specificity of autoantibodies against NALP5. In addition, the expression of NALP5 was investigated in various tissues. RESULTS: NALP5-specific autoantibodies were detected in 49% of the patients with APS-1 and hypoparathyroidism but were absent in all patients with APS-1 but without hypoparathyroidism, in all patients with other autoimmune endocrine disorders, and in all healthy controls. NALP5 was predominantly expressed in the cytoplasm of parathyroid chief cells. CONCLUSIONS: NALP5 appears to be a tissue-specific autoantigen involved in hypoparathyroidism in patients with APS-1. Autoantibodies against NALP5 appear to be highly specific and may be diagnostic for this prominent component of APS-1.
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| 9. |
- Andreasson, B, et al.
(författare)
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Management of patients with polycythaemia vera: results of a survey among Swedish haematologists
- 2005
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Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 74:6, s. 489-495
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Tidskriftsartikel (refereegranskat)abstract
- The prevailing attitudes regarding diagnostic and therapeutic procedures in patients with polycythaemia vera (PV) among Swedish haematologists were surveyed by way of a mailed questionnaire in August 2002. Among diagnostic procedures frequent use is reported for arterial O-2 saturation, spleen size determination, bone marrow histology, serum erythropoietin, serum cobalamins and leukocyte alkaline phosphatase score, while direct determination of the red blood cell mass is used infrequently (seldom or never by 82%). Among therapeutic modalities hydroxyurea and phlebotomy alone were most frequently used. The P-32 therapy was used at least sometimes by 57% of the physicians, and more widely in the university clinics. Anagrelide and alfa-interferon was used in a minority of patients only. The use of prophylactic acetylsalicylic acid was very variable. The majority of the physicians had an aim for their phlebotomy treatment at a level of 0.45 or less, but 21% used a level of 0.46-0.49 and 8% a level of 0.55-0.60 (in younger patients). The platelet level, at which myelosuppressive therapy was initiated, also varied, from 400 x 10(9)/L to > 1500 x 10(9)/L. It can be concluded that in practical clinical work in Sweden the diagnosis of PV is established by frequent use of serum erythropoietin, bone marrow examination and spleen size determination. The use of different therapeutic modalities is very variable. Many physicians carry out their phlebotomy treatment with less intensity compared with national and international recommendations.
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