| 1. |
- Antonarakis, S. E., et al.
(författare)
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Factor VIII gene inversions in severe hemophilia A : Results of an international consortium study
- 1995
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 86:6, s. 2206-2212
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Tidskriftsartikel (refereegranskat)abstract
- Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells ware observed among 225 cases (≃ 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).
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| 2. |
- Halldén, Christer, 1957-, et al.
(författare)
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Investigation of disease-associated factors in haemophilia A patients without detectable mutations
- 2012
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Ingår i: Haemophilia. - : Blackwell. - 1351-8216 .- 1365-2516. ; 18:3, s. e132-e137
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Tidskriftsartikel (refereegranskat)abstract
- To investigate disease causing mechanism in haemophilia A patients without detectable mutation. Screening for F8 mutations in 307 haemophilia A patients using: re-sequencing and inversion PCR, reverse transcription (RT-PCR) of mRNA, MLPA analysis, haplotyping using SNP and microsatellite markers. No F8 mutations were detected in 9 of the 307 patients (2.9%) using re-sequencing and inversion PCR. MLPA analysis detected duplication in exon 6 in one patient and RT-PCR showed no products for different regions of mRNA in four other patients, indicating failed transcription. No obvious associations were observed between the phenotypes of the nine patients, their F8 haplotypes and the putative mutations detected. The mutation-positive patients carrying the same haplotypes as the mutation-negative patients show a multitude of different mutations, emphasizing the lack of associations at the haplotype level. VWF mutation screening and factor V measurements ruled out type 2N VWD and combined factor V and VIII deficiency respectively. To further investigate a possible role for FVIII interacting factors the haplotypes/diplotypes of F2, F9, F10 and VWF were compared. The nine patients had no specific haplotype/diplotype combination in common that can explain disease. Duplications and faulty transcription contribute to the mutational spectrum of haemophilia A patients where conventional mutation screening fail to identify mutations.
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| 3. |
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| 4. |
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| 5. |
- Clausen, Niels, et al.
(författare)
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Similar bleeding phenotype in young children with haemophilia A or B : A cohort study
- 2014
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 20:6, s. 747-755
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Tidskriftsartikel (refereegranskat)abstract
- The bleeding phenotype has been suggested to differ between haemophilia A and B. More knowledge on the bleeding phenotype at initiation of treatment is important to optimize patient care. The aim of this study was to investigate the severity of the bleeding phenotype and the variation in bleeding in children with severe or moderate haemophilia A and B. Consecutive, previously untreated patients with severe or moderate haemophilia A and B (factor VIII or IX activity <0.01 or 0.01-0.05 IU mL-1 respectively) born between January 1st 2000 and January 1st 2010 were included. Primary outcome was severity of bleeding tendency. Secondary outcome was variation in bleeding pattern. A total of 582 patients with severe haemophilia A and 76 with severe haemophilia B did not differ in age at first exposure to clotting factor (0.81 vs. 0.88 years, P = 0.20), age at first bleed (0.82 vs. 0.88 years, P = 0.36), and age at first joint bleed (1.18 vs. 1.20 years, P = 0.59). Patients with moderate haemophilia were older compared to patients with severe haemophilia. In patients with moderate haemophilia there were no clear differences between haemophilia A and B. Severity and variation in bleeding phenotype are similar during the early stage of treatment in patients with severe and moderate haemophilia A and B respectively. The findings imply that children with haemophilia B should be observed and treated as vigilantly as those with haemophilia A.
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| 6. |
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| 7. |
- Peake, I R, et al.
(författare)
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Haemophilia : strategies for carrier detection and prenatal diagnosis
- 1993
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Ingår i: Bulletin of the World Health Organization. - 0042-9686. ; 71:3-4, s. 58-429
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Tidskriftsartikel (refereegranskat)abstract
- In 1977 WHO published in the Bulletin a Memorandum on Methods for the Detection of Haemophilia Carriers. This was produced following a WHO/WFH (World Federation of Haemophilia) Meeting of Investigators in Geneva in November 1976, and has served as a valuable reference article on the genetics of haemophilia. The analyses discussed were based on phenotypic assessment, which, at that time, was the only procedure available. The molecular biology revolution in genetics during the 1980s made enormous contributions to our understanding of the molecular basis of the haemophilias and now permits precise carrier detection and prenatal diagnosis. WHO and WFH held a joint meeting on this subject in February 1992 in Geneva. This article is the result of these discussions.
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| 8. |
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| 9. |
- Björck, Svante, et al.
(författare)
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A South Atlantic island record uncovers shifts in westerlies and hydroclimate during the last glacial
- 2019
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 15:6, s. 1939-1958
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Tidskriftsartikel (refereegranskat)abstract
- Changes in the latitudinal position and strength of the Southern Hemisphere westerlies (SHW) are thought to be tightly coupled to important climate processes, such as cross-equatorial heat fluxes, Atlantic Meridional Overturning Circulation (AMOC), the bipolar seesaw, Southern Ocean ventilation and atmospheric CO2 levels. However, many uncertainties regarding magnitude, direction, and causes and effects of past SHW shifts still exist due to lack of suitable sites and scarcity of information on SHW dynamics, especially from the last glacial. Here we present a detailed hydroclimate multiproxy record from a 36.4-18.6 kyr old lake sediment sequence on Nightingale Island (NI). It is strategically located at 37ĝF S in the central South Atlantic (SA) within the SHW belt and situated just north of the marine Subtropical Front (SF). This has enabled us to assess hydroclimate changes and their link to the regional climate development as well as to large-scale climate events in polar ice cores. The NI record exhibits a continuous impact of the SHW, recording shifts in both position and strength, and between 36 and 31 ka the westerlies show high latitudinal and strength-wise variability possibly linked to the bipolar seesaw. This was followed by 4 kyr of slightly falling temperatures, decreasing humidity and fairly southerly westerlies. After 27 ka temperatures decreased 3-4 ĝC, marking the largest hydroclimate change with drier conditions and a variable SHW position. We note that periods with more intense and southerly-positioned SHW seem to be related to periods of increased CO2 outgassing from the ocean, while changes in the cross-equatorial gradient during large northern temperature changes appear as the driving mechanism for the SHW shifts. Together with coeval shifts of the South Pacific westerlies, our results show that most of the Southern Hemisphere experienced simultaneous atmospheric circulation changes during the latter part of the last glacial. Finally we can conclude that multiproxy lake records from oceanic islands have the potential to record atmospheric variability coupled to large-scale climate shifts over vast oceanic areas..
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| 10. |
- Björkenstam, E., et al.
(författare)
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Multi-Exposure and Clustering of Adverse Childhood Experiences, Socioeconomic Differences and Psychotropic Medication in Young Adults
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1, s. e53551-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Stressful childhood experiences have negative long-term health consequences. The present study examines the association between adverse childhood experiences, socioeconomic position, and risk of psychotropic medication in young adulthood. Methods: This register-based cohort study comprises the birth cohorts between 1985 and 1988 in Sweden. We followed 362 663 individuals for use of psychotropic medication from January 2006 until December 2008. Adverse childhood experiences were severe criminality among parents, parental alcohol or drug abuse, social assistance recipiency, parental separation or single household, child welfare intervention before the age of 12, mentally ill or suicidal parents, familial death, and number of changes in place of residency. Estimates of risk of psychotropic medication were calculated as odds ratio (OR) with 95% confidence intervals (CIs) using logistic regression analysis. Results: Adverse childhood experiences were associated with increased risks of psychotropic medication. The OR for more than three adverse childhood experiences and risk of psychotropic medication was for women 2.4 (95% CI 2.3-2.5) and for men 3.1 (95% CI 2.9-3.2). The risk of psychotropic medication increased with a higher rate of adverse childhood experiences, a relationship similar in all socioeconomic groups. Conclusions: Accumulation of adverse childhood experiences increases the risk of psychotropic medication in young adults. Parental educational level is of less importance when adjusting for adverse childhood experiences. The higher risk for future mental health problems among children from lower socioeconomic groups, compared to peers from more advantaged backgrounds, seems to be linked to a higher rate of exposure to adverse childhood experiences.
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