| 1. |
- Alonderis, A, et al.
(författare)
-
Medico-legal implications of sleep apnoea syndrome: Driving license regulations in Europe.
- 2008
-
Ingår i: Sleep medicine. - : Elsevier BV. - 1389-9457 .- 1878-5506. ; 9:4, s. 362-75
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sleep apnoea syndrome (SAS), one of the main medical causes of excessive daytime sleepiness, has been shown to be a risk factor for traffic accidents. Treating SAS results in a normalized rate of traffic accidents. As part of the COST Action B-26, we looked at driving license regulations, and especially at its medical aspects in the European region. METHODS: We obtained data from Transport Authorities in 25 countries (Austria, AT; Belgium, BE; Czech Republic, CZ; Denmark, DK; Estonia, EE; Finland, FI; France, FR; Germany, DE; Greece, GR; Hungary, HU; Ireland, IE; Italy, IT; Lithuania, LT; Luxembourg, LU; Malta, MT; Netherlands, NL; Norway, EC; Poland, PL; Portugal, PT; Slovakia, SK; Slovenia, SI; Spain, ES; Sweden, SE; Switzerland, CH; United Kingdom, UK). RESULTS: Driving license regulations date from 1997 onwards. Excessive daytime sleepiness is mentioned in nine, whereas sleep apnoea syndrome is mentioned in 10 countries. A patient with untreated sleep apnoea is always considered unfit to drive. To recover the driving capacity, seven countries rely on a physician's medical certificate based on symptom control and compliance with therapy, whereas in two countries it is up to the patient to decide (on his doctor's advice) to drive again. Only FR requires a normalized electroencephalography (EEG)-based Maintenance of Wakefulness Test for professional drivers. Rare conditions (e.g., narcolepsy) are considered a driving safety risk more frequently than sleep apnoea syndrome. CONCLUSION: Despite the available scientific evidence, most countries in Europe do not include sleep apnoea syndrome or excessive daytime sleepiness among the specific medical conditions to be considered when judging whether or not a person is fit to drive. A unified European Directive seems desirable.
|
|
| 2. |
- He, S, et al.
(författare)
-
The effect of platelets on fibrin gel structure formed in the presence of recombinant factor VIIa in hemophilia plasma and in plasma from a patient with Glanzmann thrombasthenia
- 2005
-
Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 3:2, s. 272-279
-
Tidskriftsartikel (refereegranskat)abstract
- Fibrin gel structure has been shown to be dependent on the thrombin concentration as well as the rate of thrombin generation. Accordingly, factor VIII (FVIII)and FIX-deficient plasma (hemophilia A and B) form loose fibrin clots with high permeability constants. By adding rFVIIa in vitro to FVIII-deficient plasma containing platelets (frozen and thawed), the fibrin gel permeability constant normalized, indicating that extra rFVIIa (1.2 mug mL(-1) or higher) induced a tight fibrin structure. Thrombin generation is highly dependent on the number of platelets, and in this study it was demonstrated that the addition of rFVIIa (5 mug mL(-1)) normalizes the fibrin gel permeability in samples containing platelets (frozen-thawed) in numbers of at least down to 20 x 106 mL(-1). The effect of rFVIIa was not observed when unfrozen platelets instead of frozen-thawed platelets were added. Neither was any effect on the fibrin permeability seen, in the presence of annexin V, known to block the effect of phospholipids on the platelet surface. This indicates an important role of platelet phospholipids for the effect of rFVIIa. A similar effect on the fibrin permeability of rFVIIa was observed when added to platelet-rich plasma from a patient with Glanzinarm thrombasthenia. Recombinant FVIIa has been found to induce hemostasis in patients with hemophilia and inhibitors against FVIII/FIX as well as in patients with Glanzmann thrombasthenia, indicating the importance of the formation of a tight fibrin gel structure, more resistant against premature proteolysis, for maintaining hemostasis. In conclusion, the addition of rFVIIa (5 mug mL(-1)) also substantially decreased the permeability constant of fibrin gels formed in FVIII-deficient plasma in the presence of low numbers of frozen-thawed platelets (down to 20 x 10(6) mL(-1)). A similar pattern was obtained in plasma from a Glanzmann patient. No effect was found in the presence of unfrozen instead of frozen-thawed platelets. Annexin V blocked any effect of rFVIIa. A normalization of the overall fibrinolysis potential (OFP) during the same condition supports the effect of rFVIIa on the fibrin permeability in the presence of a limited number of platelets.
|
|
| 3. |
- Johansson, Magnus C, 1954, et al.
(författare)
-
The influence of patent foramen ovale on oxygen desaturation in obstructive sleep apnoea
- 2007
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 0903-1936 .- 0903-1936 .- 1399-3003. ; 29:1, s. 149-55
-
Tidskriftsartikel (refereegranskat)abstract
- Obstructive sleep apnoea (OSA) is associated with oxygen desaturation to a varying degree. A patent foramen ovale (PFO) may allow interatrial right-to-left shunting. The hypothesis of the current study was that oxygen desaturation will occur more often, in proportion to the frequency of respiratory disturbances, in OSA subjects with PFO than in those without. In a group of 209 subjects diagnosed with OSA, the proportion of desaturation to respiratory events was calculated as the ratio of oxygen desaturation index (ODI)/apnoea-hypopnoea index (AHI). A total of 15 cases with high proportional desaturation (ODI/AHI >or=0.66) were individually matched with 15 controls with low proportional desaturation (ODI/AHI or=20 bubbles passed over from the right to the left atrium after a single injection. The prevalence of large PFO was nine out of 15 (60%) in the high proportional desaturation group versus two out of 15 (13%) in the low proportional desaturation group. The median number of passing bubbles was positively correlated to minimum oxygen saturation among those with PFO. In conclusion, oxygen desaturation occurs more often, in proportion to the frequency of respiratory disturbances, in obstructive sleep apnoea subjects with a patent foramen ovale than in those without.
|
|
| 4. |
- Kathiresan, Sekar, et al.
(författare)
-
Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.
- 2008
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 189-97
-
Tidskriftsartikel (refereegranskat)abstract
- Blood concentrations of lipoproteins and lipids are heritable risk factors for cardiovascular disease. Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue) and targeted replication association analyses in up to 18,554 independent participants, we show that common SNPs at 18 loci are reproducibly associated with concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and/or triglycerides. Six of these loci are new (P < 5 x 10(-8) for each new locus). Of the six newly identified chromosomal regions, two were associated with LDL cholesterol (1p13 near CELSR2, PSRC1 and SORT1 and 19p13 near CILP2 and PBX4), one with HDL cholesterol (1q42 in GALNT2) and five with triglycerides (7q11 near TBL2 and MLXIPL, 8q24 near TRIB1, 1q42 in GALNT2, 19p13 near CILP2 and PBX4 and 1p31 near ANGPTL3). At 1p13, the LDL-associated SNP was also strongly correlated with CELSR2, PSRC1, and SORT1 transcript levels in human liver, and a proxy for this SNP was recently shown to affect risk for coronary artery disease. Understanding the molecular, cellular and clinical consequences of the newly identified loci may inform therapy and clinical care.
|
|
| 5. |
- Orho-Melander, Marju, et al.
(författare)
-
Common Missense Variant in the Glucokinase Regulatory Protein Gene Is Associated With Increased Plasma Triglyceride and C-Reactive Protein but Lower Fasting Glucose Concentrations
- 2008
-
Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 57:11, s. 3112-3121
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Using the genome-wide association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metabolic phenotypes, including measures of glucose homeostasis, to evaluate the GCYR locus in samples of non-European ancestry and to fine-map across the associated genomic interval. RESEARCH DESIGN AND METHODS-We performed association studies in 12 independent cohorts comprising >45,000 individuals representing several ancestral groups (whites from Northern and Southern Europe, whites from the U.S., African Americans from the U.S., Hispanics of Caribbean origin, and Chinese, Malays, and Asian Indians from Singapore). We conducted genetic fine-mapping across the similar to 417-kb region of linkage disequilibrium. spanning GCKR and 16 other genes on chromosome 2p23 by imputing untyped HapMap single nucleotide polymorphisms (SNPs) and genotyping 104 SNPs across the associated genomic interval. RESULTS-We provide comprehensive evidence that GCYR rs780094 is associated with opposite effects on fasting plasma triglyceride (P-meta = 3 x 10(-56)) and glucose (P-meta = 1 x 10(-13)) concentrations. In addition, we confirmed recent reports that the same SNP is associated with C-reactive protein (CRP) level (P = 5 x 10(-5)). Both fine-mapping approaches revealed a common missense GCKR variant (rs1260326, Pro446Leu, 34% frequency, r(2) = 0.93 with rs780094) as the strongest association signal in the region. CONCLUSIONS-These findings point to a molecular mechanism in humans by which higher triglycerides and CRP can be coupled with lower plasma glucose concentrations and position GCKR in central pathways regulating both hepatic triglyceride and glucose metabolism. Diabetes 57:3112-3121, 2008
|
|
| 6. |
- Phillips, C. L., et al.
(författare)
-
The effect of short-term withdrawal from continuous positive airway pressure therapy on sympathetic activity and markers of vascular inflammation in subjects with obstructive sleep apnoea
- 2007
-
Ingår i: J Sleep Res. - 0962-1105. ; 16:2, s. 217-25
-
Tidskriftsartikel (refereegranskat)abstract
- Obstructive sleep apnoea (OSA) is commonly associated with cardiovascular disease and sympathetic activation. However, it is unclear whether this association is independent of obesity and to what extent treatment with nasal continuous positive airway pressure (CPAP) alleviates the vascular inflammation that underpins cardiovascular disease. We therefore evaluated whether short-term withdrawal from CPAP therapy in subjects with moderate-severe OSA would result in increased levels of sympathetic activity and circulating inflammatory cytokines independent of weight. Vascular inflammatory markers (hsCRP, hsIL-6 and hsTNF-alpha) were assessed in 20 subjects after one and seven nights of withdrawal from CPAP together with the hypoxia-responsive angiogenic marker VEGF and urinary catecholamines. Compared with baseline on CPAP, withdrawal from therapy resulted in an immediate return of OSA with an increase in RDI to 26.7 +/- 5.2 and 39.0 +/- 5.9 events per hour after one and seven nights without CPAP, respectively (both P < 0.0001). This was accompanied by a concomitant rise in daytime urinary noradrenaline (P < 0.0001) after seven nights CPAP withdrawal that was positively associated with the severity of hypoxaemia. In contrast, withdrawal from CPAP therapy was not accompanied by any change in measured cytokines or VEGF (all P > 0.1). In conclusion, 1 week of CPAP withdrawal was associated with a return of OSA and a marked increase in sympathetic activity without a concomitant elevation of vascular inflammatory markers.
|
|
| 7. |
- Sjögren, M., et al.
(författare)
-
Antifouling activity of synthesized peptide analogs of the sponge metabolite barettin
- 2006
-
Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 27:9, s. 2058-2064
-
Tidskriftsartikel (refereegranskat)abstract
- Barettin (cyclo [(6-bromo-8-en-tryptophan) arginine]), a diketopiperazine isolated from the marine sponge Geodia barretti, is a potent inhibitor of barnacle larvae settlement with an EC50-value of 0.9 mu M. In the present study, 14 analogs of barettin and its structural congener dipodazine were synthezised and tested for their ability to inhibit larval settlement. Two of the analogs have an intact barettin skeleton. The remaining analogs have a dipodazine skeleton (a diketopiperazine where arginine is replaced with glycine). Six of the tested synthetic analogs displayed significant settlement inhibition with the most potent inhibitor being benzo[g]dipodazine, which displayed even stronger activity than barettin (EC50-value 0.034 mu M). The effect of benzo[g]dipodazine was also shown to be readily reversible, when cyprids were transferred to filtered seawater (FSW). (c) 2006 Elsevier Inc. All rights reserved.
|
|
| 8. |
- Vedam, Hima, et al.
(författare)
-
Short-term hypoxia reduces arterial stiffness in healthy men.
- 2009
-
Ingår i: European journal of applied physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 105:1, s. 19-25
-
Tidskriftsartikel (refereegranskat)abstract
- This study examined the effects of hypoxia (80% arterial oxyhaemoglobin saturation for 20 min) and the accompanying changes in heart rate and blood pressure on two components of arterial stiffness in healthy men. Augmentation index (AIx) and time to reflection (Tr) representing measures of muscular artery and aortic stiffness, respectively, were continuously measured. At first, subjects were exposed to either hypoxia (n = 12) or room air (n = 5). During early hypoxia AIx increased by 6% before decreasing to baseline. After hypoxia AIx decreased by a further 6%. In contrast there was no change in Tr. Six subjects were then exposed to hypoxia following infusion with the nitric oxide (NO) synthase inhibitor NG-mono-methyl-L: -arginine (L-NMMA) or saline. During hypoxia AIx decreased by 12% following saline but increased by 14% after L-NMMA and Tr did not change. These findings suggest that hypoxia may induce NO-mediated vasodilatation of small muscular arteries but not the aorta.
|
|
| 9. |
- Yee, B. J., et al.
(författare)
-
The effect of sibutramine-assisted weight loss in men with obstructive sleep apnoea
- 2007
-
Ingår i: Int J Obes (Lond). - : Springer Science and Business Media LLC. - 0307-0565. ; 31:1, s. 161-168
-
Tidskriftsartikel (refereegranskat)abstract
- Objective:Obstructive sleep apnoea (OSA) occurs frequently in obese patients and may be reversible with weight loss. Obstructive sleep apnoea and obesity are both independent risk factors for hypertension and increased sympathetic activity. Sibutramine has been increasingly used in the management of obesity, but is relatively contraindicated in patients with hypertension. No studies have investigated the effect of sibutramine on OSA, blood pressure and heart rate. We aimed to assess the changes in OSA and cardiovascular parameters in obese men with OSA enrolled in a sibutramine-assisted weight loss programme (SIB-WL).Design:Open uncontrolled cohort study of obese male subjects with OSA in an SIB-WL.Subjects:Eighty-seven obese (body mass index =34.2+/-2.8 kg/m(2)) middle-aged (46.3+/-9.3 years) male subjects with symptomatic OSA (Epworth score 13.4+/-3.6; respiratory disturbance index (RDI) 46.0+/-23.1 events/h) completed the study.Results:At 6 months, there was significant weight loss (8.3+/-4.7 kg, P<0.0001), as well as a reduction in waist and neck circumference and sagittal height (all P<0.0001). These changes were accompanied by a reduction in OSA severity (RDI fell by 16.3+/-19.4 events/h and Epworth score by 4.5+/-4.6), both P<0.0001). There was no significant change to systolic (P=0.07) or diastolic blood pressure (P=0.87); however, there was a mild rise in resting heart rate (P<0.0001).Conclusion:Moderate ( approximately 10%) weight loss with SIB-WL results in improvement in OSA severity without increase in blood pressure in closely monitored OSA subjects.International Journal of Obesity (2007) 31, 161-168. doi:10.1038/sj.ijo.0803363; published online 2 May 2006.
|
|
