| 1. |
- Brunner, Sandra, et al.
(author)
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Overexpression of RPGR leads to male infertility in mice due to defects in flagellar assembly
- 2008
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In: Biology of Reproduction. - : Oxford University Press (OUP). - 0006-3363 .- 1529-7268. ; 79:4, s. 608-617
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Journal article (peer-reviewed)abstract
- Male infertility is one possible consequence of a group of disorders arising from dysfunction of cilia. Ciliopathies include primary ciliary dyskinesia, polycystic kidney disease, Usher syndrome, nephronophthisis, Bardet-Biedl syndrome, Alstrom syndrome, and Meckel-Gruber syndrome as well as some forms of retinal degenerations. Mutations in the retinitis pigmentosa GTPase regulator gene (RPGR) are best known for leading to retinal degeneration but have also been associated with ciliary dysfunctions affecting other tissues. To further study the involvement of RPGR in ciliopathies, transgenic mouse lines overexpressing RPGR were generated. Animals carrying the transgene in varying copy numbers were investigated. We found that infertility due to aberrant spermatozoa correlated with increased copy numbers. In animals with moderately increased gene copies of Rpgr, structural disorganization in the flagellar midpiece, outer dense fibers, and fibrous sheath was apparent. In contrast, in animals with high copy numbers, condensed sperm heads were present, but the flagellum was absent in the vast majority of spermatozoa, although early steps of flagellar biogenesis were observed. This complexity of defects in flagellar assembly suggests a role of RPGR in intraflagellar transport processes.
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| 2. |
- Lippert, Barbara, et al.
(author)
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Cost effectiveness of haemophilia treatment: a cross-national assessment.
- 2005
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In: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 16:7, s. 477-485
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Journal article (peer-reviewed)abstract
- The aim of this study was to assess the incremental cost effectiveness of on-demand versus prophylactic haemophilia therapy in Germany, Sweden, the United Kingdom and The Netherlands from the third-party payers' perspective. Using a decision tree model, the cost effectiveness of on-demand versus prophylactic therapy was analysed by extrapolating data from the European Haemophilia Economic Study to a 1-year analytic time horizon. Five hundred and six patients with severe haemophilia A and B, without inhibitors and at least 14 years of age, were enrolled in this study. Patients treated prophylactically had fewer bleeds than patients treated on-demand. With prophylactic treatment, the incremental cost per avoided bleeding ranged from [Euro sign]6650 for patients 30 years of age or younger in Germany to [Euro sign]14 140 for patients over 30 years old in Sweden. If quality of life was taken into account, patients receiving prophylactic treatment had higher mean utilities than patients on on-demand therapy. The incremental effectiveness ratios in Germany were [Euro sign]1.2 million per quality-adjusted life year gained for patients 30 years or younger and HIV-positive and [Euro sign]2.2 million for patients 30 years or younger and HIV-negative. In the group aged over 30 years and HIV-positive the on-demand treatment strategy was dominant, whereas in the over 30 years/HIV-negative group the incremental cost-utility ratio was [Euro sign]4.7 million per quality-adjusted life year. Based on our decision analysis, the use of prophylactic treatment was overall more effective than on-demand therapy in young haemophiliacs, but at extremely high cost.
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