| 1. |
- Brophy, D F, et al.
(author)
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Monitoring rFVIIa 90 μg kg(-1) dosing in haemophiliacs: comparing laboratory response using various whole blood assays over 6 h.
- 2011
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In: Haemophilia. - : Wiley. - 1351-8216. ; 17:5, s. 949-957
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Journal article (peer-reviewed)abstract
- Summary. Recombinant FVIIa is a haemostatic agent administered to patients with severe FVIII or FIX deficiency with inhibitors. Although rFVIIa is effective at stopping bleeding, a reliable assay to monitor its effect is lacking. To characterize the pharmacokinetics and global coagulation effects of rFVIIa for 6 h following a IV dose of 90 μg kg(-1) . Ten non-bleeding subjects with severe FVIII or FIX deficiency were infused with a single-dose of rFVIIa 90 μg kg(-1) body weight and blood was collected before and at 0.5, 1, 2, 4 and 6 h postdose. Global haemostasis was characterized throughout the study utilizing whole blood analyses (Hemodyne HAS, TEG, ROTEM). The clearance and half-life of factor FVII:C was estimated as 39.0 ± 8.8 mL h(-1) kg(-1) and 2.1 ± 0.2 h respectively. There was good inter-assay agreement with respect to clot initiation parameters (R, CT and FOT) and these parameters all fell to a mean of approximately 9 min following rFVIIa dosing. The platelet contractile force (PCF) and clot elastic modulus (CEM) were positively correlated to FVII:C (P < 0.0001), and these parameters were dynamic throughout the 6-h period. The MA and MCF did not correlate to FVII:C nor did they significantly change during the study. Prothrombin F1 + 2 significantly increased following rFVIIa dosing (P < 0.001), but remained steady throughout the study. There was no change in D-dimer concentrations over time. The FOT, R and CT characterized clot initiation following rFVIIa dosing. The PCF and CEM were correlated to FVII:C and characterized the dynamics of platelet function and clot strength over the rFVIIa dosing interval. The clinical significance of these findings needs additional study.
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| 2. |
- Arnardottir, E. S., et al.
(author)
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The Sleep Revolution project: the concept and objectives
- 2022
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In: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 31:4
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Journal article (peer-reviewed)abstract
- Obstructive sleep apnea is linked to severe health consequences such as hypertension, daytime sleepiness, and cardiovascular disease. Nearly a billion people are estimated to have obstructive sleep apnea with a substantial economic burden. However, the current diagnostic parameter of obstructive sleep apnea, the apnea-hypopnea index, correlates poorly with related comorbidities and symptoms. Obstructive sleep apnea severity is measured by counting respiratory events, while other physiologically relevant consequences are ignored. Furthermore, as the clinical methods for analysing polysomnographic signals are outdated, laborious, and expensive, most patients with obstructive sleep apnea remain undiagnosed. Therefore, more personalised diagnostic approaches are urgently needed. The Sleep Revolution, funded by the European Union's Horizon 2020 Research and Innovation Programme, aims to tackle these shortcomings by developing machine learning tools to better estimate obstructive sleep apnea severity and phenotypes. This allows for improved personalised treatment options, including increased patient participation. Also, implementing these tools will alleviate the costs and increase the availability of sleep studies by decreasing manual scoring labour. Finally, the project aims to design a digital platform that functions as a bridge between researchers, patients, and clinicians, with an electronic sleep diary, objective cognitive tests, and questionnaires in a mobile application. These ambitious goals will be achieved through extensive collaboration between 39 centres, including expertise from sleep medicine, computer science, and industry and by utilising tens of thousands of retrospectively and prospectively collected sleep recordings. With the commitment of the European Sleep Research Society and Assembly of National Sleep Societies, the Sleep Revolution has the unique possibility to create new standardised guidelines for sleep medicine.
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| 3. |
- Dyrehag, L E, et al.
(author)
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Relations between self-rated musculoskeletal symptoms and signs and psychological distress in chronic neck and shoulder pain.
- 1998
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In: Scandinavian journal of rehabilitation medicine. - 0036-5505. ; 30:4, s. 235-42
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Journal article (peer-reviewed)abstract
- The purposes of the present study were to describe physical and psychological characteristics of 55 chronic pain patients with predominantly nociceptive neck and shoulder complaints, and to explore relationships between physical assessment methods, self-reported pain and psychological distress. The physical measures included cervical and shoulder mobility and muscle tenderness. The Pain Severity and Interference subscales from the Multidimensional Pain Inventory (MPI), Becks Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI-Y), and a pain drawing assessed self-reports of pain and psychological distress. The number of tender points (TP score) correlated significantly with pain severity, (p < 0.01) Interference (p < 0.05), pain drawing score (p < 0.05), BDI (p < 0.05) and state anxiety (p < 0.05). No significant correlation was seen between TP score and age, pain duration or trait anxiety. The results suggest that there are relationships between observers' ratings of muscle tenderness (TP score) and self-reports of pain severity, interference of pain and psychological distress in patients with chronic cervico-brachial pain.
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| 4. |
- Gunduz, C., et al.
(author)
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Hyperlipidaemia prevalence and cholesterol control in obstructive sleep apnoea: Data from the European sleep apnea database (ESADA)
- 2019
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 676-688
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Journal article (peer-reviewed)abstract
- Background and objective Obstructive sleep apnoea (OSA) and hyperlipidaemia are independent risk factors for cardiovascular disease. This study investigates the association between OSA and prevalence of hyperlipidaemia in patients of the European Sleep Apnea Database (ESADA) cohort. Methods The cross-sectional analysis included 11 892 patients (age 51.9 +/- 12.5 years, 70% male, body mass index (BMI) 31.3 +/- 6.6 kg/m(2), mean oxygen desaturation index (ODI) 23.7 +/- 25.5 events/h) investigated for OSA. The independent odds ratio (OR) for hyperlipidaemia in relation to measures of OSA (ODI, apnoea-hypopnoea index, mean and lowest oxygen saturation) was determined by means of general linear model analysis with adjustment for important confounders such as age, BMI, comorbidities and study site. Results Hyperlipidaemia prevalence increased from 15.1% in subjects without OSA to 26.1% in those with severe OSA, P < 0.001. Corresponding numbers in patients with diabetes were 8.5% and 41.5%, P < 0.001. Compared with ODI quartile I, patients in ODI quartiles II-IV had an adjusted OR (95% CI) of 1.33 (1.15-1.55), 1.37 (1.17-1.61) and 1.33 (1.12-1.58) (P < 0.001), respectively, for hyperlipidaemia. Obesity was defined as a significant risk factor for hyperlipidaemia. Subgroups of OSA patients with cardio-metabolic comorbidities demonstrated higher prevalence of HL. In addition, differences in hyperlipidaemia prevalence were reported in European geographical regions with the highest prevalence in Central Europe. Conclusion Obstructive sleep apnoea, in particular intermittent hypoxia, was independently associated with the prevalence of hyperlipidaemia diagnosis.
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| 5. |
- Hedner, E, et al.
(author)
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Reactivated herpes simplex virus infection as a possible cause of dry socket after tooth extraction
- 1993
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In: Journal of oral and maxillofacial surgery (Print). - 0278-2391 .- 1531-5053. ; 51:4, s. 370-376; discussion 377
-
Journal article (peer-reviewed)abstract
- This study was designed to evaluate a possible association between reactivated herpes simplex virus type 1 (HSV-1) infection after lower third molar extraction and development of dry socket (DS). The HSV-1 antibody response was analyzed before and after tooth removal by enzyme-linked immunosorbent assay and immunoblotting in 208 patients. History of previous possible oral herpes reactivation was evaluated by a questionnaire that was based on self-rated frequency of oral cold sores. Tobacco users were identified. The anatomic proximity of the root apex to the mandibular nerve canal was classified radiographically before extraction. Fifteen patients (7%) developed DS after tooth extraction. Eleven of the 15 DS patients (73%) were HSV seropositive as compared with 7 of 15 (47%) in the matched control group. Seven of the 11 seropositive DS patients have shown HSV-1 reactivation by an increase of specific polypeptides, predominantly gB, gC, gD and ICP 4 and 6, in the immunoblot test. No change in HSV-1 reactivity was observed in control sera. DS patients reported a high frequency of oral cold sores (64%) compared with the controls (33%). Tobacco use was not found to influence the frequency of cold sores or the development of DS. A close radiographic proximity between the mandibular canal and root apex was more common (P < .05) in DS patients. The results indicate that extraction of a mandibular third molar could be a possible cause of reactivation and recurrence of an HSV-1 infection. The serum antibody response, the anatomical nerve/root proximity, and the history of oral cold sores reflect an association between HSV-1 and DS after tooth extraction.
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| 6. |
- Johnson, Toby, et al.
(author)
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Blood Pressure Loci Identified with a Gene-Centric Array.
- 2011
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In: American Journal of Human Genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 89:6, s. 688-700
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Journal article (peer-reviewed)abstract
- Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56× 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56× 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
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| 7. |
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| 8. |
- Lombardi, C., et al.
(author)
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Periodic limb movements during sleep and blood pressure changes in sleep apnoea: Data from the European Sleep Apnoea Database
- 2020
-
In: Respirology. - : Wiley. - 1323-7799 .- 1440-1843. ; 25:8, s. 872-879
-
Journal article (peer-reviewed)abstract
- Background and objective OSA and PLMS are known to induce acute BP swings during sleep. Our current study aimed to address the independent effect of PLMS on BP in an unselected OSA patient cohort. Methods This cross‐sectional analysis included 1487 patients (1110 males, no previous hypertension diagnosis or treatment, mean age: 52.5years, mean BMI: 30.5kg/m2) with significant OSA (defined as AHI≥10) recruited from the European Sleep Apnoea Cohort. Patients underwent overnight PSG. Patients were stratified into two groups: patients with significant PLMS (PLMSI>25 events/hour of sleep) and patients without significant PLMS (PLMSI<25 events/hour of sleep). SBP, DBP and PP were the variables of interest. For each of these, a multivariate regression linear model was fitted to evaluate the relationship between PLMS and outcome adjusting for sociodemographic and clinical covariates (gender, age, BMI, AHI, ESS, diabetes, smoking and sleep efficiency). Results The univariate analysis of SBP showed an increment of BP equal to 4.70mm Hg (P<0.001) in patients with significant PLMS compared to patients without significant PLMS. This increment remained significant after implementing a multivariate regression model (2.64mm Hg, P = 0.044). No significant increment of BP was observed for DBP and PP. Conclusion PLMS is associated with a rise in SBP regardless of AHI, independent of clinical and sociodemographic confounders. A PLMS phenotype may carry an increased risk for cardiovascular disease in OSA patients.
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| 9. |
- Orho-Melander, Marju, et al.
(author)
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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
-
In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 57:11, s. 3112-3121
-
Journal article (peer-reviewed)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
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| 10. |
- Rodriguez-Merchan, E. C., et al.
(author)
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Joint protection in haemophilia
- 2011
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In: Haemophilia. - : Wiley. - 1351-8216. ; 17, s. 1-23
-
Journal article (peer-reviewed)abstract
- Haemarthroses (intra-articular haemorrhages) are a frequent finding typically observed in patients with haemophilia. Diagnosis and treatment of these bleeding episodes must be delivered as early as possible. Additionally, treatment should ideally be administered intensively (enhanced on-demand treatment) until the resolution of symptoms. Joint aspiration plays an important role in acute and profuse haemarthroses as the presence of blood in the joint leads to chondrocyte apoptosis and chronic synovitis, which will eventually result in joint degeneration (haemophilic arthropathy). Ultrasonography (US) is an appropriate diagnostic technique to assess the evolution of acute haemarthrosis in haemophilia, although magnetic resonance imaging remains the gold standard as far as imaging techniques are concerned. Some patients experience subclinical haemarthroses, which eventually tend to result in some degree of arthropathy, especially in the ankles. Nowadays, the most effective way of protecting these patients is primary prophylaxis, which in practice changes severe haemophilia into moderate haemophilia, preventing or at least minimizing the occurrence of haemarthrosis. If primary prophylaxis is, for whatever reason not an option, secondary prophylaxis and enhanced on demand treatment should be considered. Two alternatives are available for inhibitor patients: (i) control of haemostasis using by-passing agents (rFVIIa or aPCCs) either as enhanced on demand treatment or secondary prophylaxis, as appropriate, following the same basic principles used for non-inhibitor patients and (ii) immune tolerance induction (ITI) to eradicate the inhibitor.
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| 11. |
- Rodriguez-Merchan, E. C., et al.
(author)
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Prevention of haemophilic arthropathy during childhood. May common orthopaedic management be extrapolated from patients without inhibitors to patients with inhibitors?
- 2008
-
In: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 14:Suppl. 6, s. 68-81
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Journal article (peer-reviewed)abstract
- We recommend prophylaxis in haemophilic children with an inhibitor as a way of preventing the musculoskeletal impairment that is likely to affect them. This approach has been used for children without inhibitors with excellent results. If prophylaxis is not feasible, we suggest that intensive on-demand treatment should be given. Two agents, recombinant activated FVII (rFVIIa) and activated prothrombin complex concentrates (aPCC), are currently used to control haemostasis either for prophylaxis or intensive on-demand treatment. As it is recombinant, rFVIIa would seem more appropriate to be employed in children. aPCC could be used in adults, or in the event of an unsatisfactory response to rFVIIa. We recommend prophylaxis or, at least, intensive on-demand treatment in haemophilia children with inhibitors. Both rFVIIa and aPCC are being used for this purpose. It would seem that rFVIIa might be more appropriate for children as it is a recombinant product. Nevertheless, after skeletal maturity (in adults), both agents could be used indistinctively (taking into consideration that FEIBA is a plasma-derived product). We still need more well-designed comparative studies in order to be able to assert that our consensus-based conclusion is evidence based. In orthopaedic surgery, both aPCC and rFVIIa have been reported to be effective in controlling perioperative haemostasis, although in practice most centres have so far used rFVIIa for their orthopaedic procedures. We recommend rehabilitation programmes for all patients with inhibitors in order to mitigate the disabling and handicapping impact of their condition and thereby enable them to achieve social integration. Programmes for haemophilic children without inhibitors can be applied to children with inhibitors but should be individually tailored.
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| 12. |
- Torén, Kjell, 1952, et al.
(author)
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Vital capacity and COPD: the Swedish CArdioPulmonary bioImage Study (SCAPIS)
- 2016
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In: International Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1178-2005. ; 11:1, s. 927-933
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Journal article (peer-reviewed)abstract
- Background: Spirometric diagnosis of chronic obstructive pulmonary disease (COPD) is based on the ratio of forced expiratory volume in 1 second (FEV1)/vital capacity (VC), either as a fixed value <0.7 or below the lower limit of normal (LLN). Forced vital capacity (FVC) is a proxy for VC. The first aim was to compare the use of FVC and VC, assessed as the highest value of FVC or slow vital capacity (SVC), when assessing the FEV1/VC ratio in a general population setting. The second aim was to evaluate the characteristics of subjects with COPD who obtained a higher SVC than FVC. Methods: Subjects (n=1,050) aged 50-64 years were investigated with FEV1, FVC, and SVC after bronchodilation. Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPDFVC was defined as FEV1/FVC <0.7, GOLDCOPD(VC) as FEV1/VC <0.7 using the maximum value of FVC or SVC, LLNCOPDFVC as FEV1/FVC below the LLN, and LLNCOPDVC as FEV1/VC below the LLN using the maximum value of FVC or SVC. Results: Prevalence of GOLDCOPD(FVC) was 10.0% (95% confidence interval [CI] 8.2-12.0) and the prevalence of LLNCOPDFVC was 9.5% (95% CI 7.8-11.4). When estimates were based on VC, the prevalence became higher; 16.4% (95% CI 14.3-18.9) and 15.6% (95% CI 13.5-17.9) for GOLDCOPD(VC) and LLNCOPDVC, respectively. The group of additional subjects classified as having COPD based on VC, had lower FEV1, more wheeze and higher residual volume compared to subjects without any COPD. Conclusion: The prevalence of COPD was significantly higher when the ratio FEV1/VC was calculated using the highest value of SVC or FVC compared with using FVC only. Subjects classified as having COPD when using the VC concept were more obstructive and with indications of air trapping. Hence, the use of only FVC when assessing airflow limitation may result in a considerable under diagnosis of subjects with mild COPD.
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| 13. |
- Agersø, H, et al.
(author)
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Recombinant human factor VIIa (rFVIIa) cleared principally by antithrombin following IV administration in haemophilia patients.
- 2011
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In: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 9:2, s. 333-338
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Journal article (peer-reviewed)abstract
- Objective: The objective of the present study was to evaluate the pharmacokinetics and the clearance pathways of rFVIIa after intravenous administration to haemophilia patients. Methods: Ten severe haemophilia patients were included in the study; all patients were intravenously administered a clinical relevant dose of 90 μg/kg (1.8 nmol/kg) rFVIIa. Blood samples were collected consecutively to describe the pharmacokinetics of rFVIIa. All samples were analysed using three different assays: a clot assay to measure the activity (FVIIa:C), an enzyme immunoassay (EIA) to measure the antigen levels (FVII:Ag), and a EIA (FVIIa-AT) to measure the FVIIa antithrombin III (AT) complex. Pharmacokinetic parameters were evaluated both by use of standard non-compartmental methods and by use of mixed effects methods. A population pharmacokinetic model was used to simultaneously model all three datasets. The total body clearance of rFVIIa:C was estimated to be 38 mL/h/kg. The rFVII:AT complex formation was responsible for 65% of the total rFVIIa:C clearance. The initial and the terminal half-life of rFVIIa:C was estimated to be 0.6 and 2.6 hours, respectively. The formation of rFVII-AT complex were able to explain the difference observed between the rFVIIa:C and the rFVII:Ag concentration. The non-compartmental analysis resulted in almost identical parameters.
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| 14. |
- Alonderis, A, et al.
(author)
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Medico-legal implications of sleep apnoea syndrome: Driving license regulations in Europe.
- 2008
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In: Sleep medicine. - : Elsevier BV. - 1389-9457 .- 1878-5506. ; 9:4, s. 362-75
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Journal article (peer-reviewed)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.
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| 15. |
- Alvarez-Madrazo, S., et al.
(author)
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Common Polymorphisms in the CYP11B1 and CYP11B2 Genes: Evidence for a Digenic Influence on Hypertension
- 2013
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In: Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0194-911X .- 1524-4563. ; 61:1, s. 232-239
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Journal article (peer-reviewed)abstract
- The locus encompassing the corticosteroidogenic genes CYP11B2 and CYP11B1 is of potential importance in essential hypertension. We analyzed the association of polymorphisms at this locus with risk of essential hypertension, using 2 white case-control collections for discovery (n = 3340) and confirmation (n = 2929). Single-marker and haplotype analyses were performed, with the CYP11B2 Intron 2 Conversion polymorphism showing strongest association with hypertension in both cohorts and in combined analysis (odds ratio = 1.16, P = 8.54x10(-5)). The CYP11B1 ACA haplotype associated with increased risk of hypertension relative to the alternative, GTC (odds ratio = 1.11; P = 7.4x10(-3)), whereas the CYP11B2 TWtC haplotype seemed protective relative to the contrasting CConvT (odds ratio = 0.88, P = 2.2x10(-3)). Analysis spanning the whole CYP11B1/CYP11B2 locus showed that haplotypes associated with raised risk of hypertension tend to coexist. Functional analysis of heterozygous human adrenal tissue demonstrated decreased CYP11B2 expression and increased CYP11B1 expression for those alleles associating with reduced risk of hypertension. These results confirm the hypertensive influence of this locus, with data suggesting a complex digenic mechanism whereby altered relative CYP11B1 and CYP11B2 gene expression could have a chronic effect on enzyme activity and corticosteroid synthesis.
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| 16. |
- Andrén, Lennart, 1946, et al.
(author)
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Circulatory effects of noise.
- 1983
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In: Acta medica Scandinavica. - : Wiley. - 0001-6101. ; 213:1, s. 31-5
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Journal article (peer-reviewed)abstract
- Thirteen patients with mild essential hypertension, mean age 44 years (range 21-59), were studied during "stress" before and after postsynaptic alpha-adrenoceptor blockade and combined postsynaptic alpha- and non-selective beta-adrenoceptor blockade. Loud broad band noise (100 dBA for 10 min) was used as the stress stimulus. Exposure to noise caused a significant increase in systolic (7%, p less than 0.05), diastolic (9%, p less than 0.01) and mean arterial pressure (6%, p less than 0.01). The blood pressure elevation was caused by an increase in total peripheral resistance (12%, p less than 0.05). There was no significant change in heart rate, stroke volume or cardiac output. The blood pressure response during noise stimulation was not affected by postsynaptic alpha-adrenoceptor blockade (prazosin, 2 mg orally). The hemodynamic reaction pattern, however, was totally reversed. Thus, the cardiac output increased significantly (9%, p less than 0.05), while the total peripheral resistance tended to decrease. Combined postsynaptic alpha- and non-selective beta-adrenoceptor blockade (labetalol, 200 mg orally) inhibited the increase in systolic blood pressure caused by noise, while the diastolic and mean arterial pressures still increased significantly (5%, p less than 0.01). Labetalol effectively blocked the stress-induced increase in total peripheral resistance and there was no significant increase in cardiac output after combined alpha- and beta-adrenoceptor blockade. Exposure to noise caused a significant increase in circulating noradrenaline (20%, p less than 0.05). Plasma adrenaline and plasma renin activity were not affected by noise stimulation. These results suggest that blood pressure elevation is essential during "stress" but that the hemodynamic pattern causing blood pressure elevation may vary and may be affected by pharmacological blockade of various parts of the sympathetic nervous system.
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| 17. |
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| 18. |
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| 19. |
- Bonsignore, M. R., et al.
(author)
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Clinical presentation of patients with suspected obstructive sleep apnea and self-reported physician-diagnosed asthma in the ESADA cohort
- 2018
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In: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 27:6
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Journal article (peer-reviewed)abstract
- Obstructive sleep apnea (OSA) and asthma are often associated and several studies suggest a bidirectional relationship between asthma and OSA. This study analyzed the characteristics of patients with suspected OSA from the European Sleep Apnea Database according to presence/absence of physician-diagnosed asthma. Cross-sectional data in 16,236 patients (29.1% female) referred for suspected OSA were analyzed according to occurrence of physician-diagnosed asthma for anthropometrics, OSA severity and sleepiness. Sleep structure was assessed in patients studied by polysomnography (i.e. 48% of the sample). The prevalence of physician-diagnosed asthma in the entire cohort was 4.8% (7.9% in women, 3.7% in men, p < 0.0001), and decreased from subjects without OSA to patients with mild-moderate and severe OSA (p = 0.02). Obesity was highly prevalent in asthmatic women, whereas BMI distribution was similar in men with and without physician-diagnosed asthma. Distribution of OSA severity was similar in patients with and without physician-diagnosed asthma, and unaffected by treatment for asthma or gastroesophageal reflux. Asthma was associated with poor sleep quality and sleepiness. Physician-diagnosed asthma was less common in a sleep clinic population than expected from the results of studies in the general population. Obesity appears as the major factor raising suspicion of OSA in asthmatic women, whereas complaints of poor sleep quality were the likely reason for referral in asthmatic men.
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| 20. |
- Bouloukaki, I., et al.
(author)
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Mild obstructive sleep apnea increases hypertension risk, challenging traditional severity classification
- 2020
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In: Journal of Clinical Sleep Medicine. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 16:6, s. 889-898
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Journal article (peer-reviewed)abstract
- Study Objectives: The association of mild obstructive sleep apnea (OSA) with important clinical outcomes remains unclear. We aimed to investigate the association between mild OSA and systemic arterial hypertension (SAH) in the European Sleep Apnea Database cohort. Methods: In a multicenter sample of 4,732 participants, we analyzed the risk of mild OSA (subclassified into 2 groups: mild(AHI) (5-<)(11)(/h) (apnea-hypopnea index [AHI], 5 to <11 events/h) and mild(AHI) (1)(1-<15/h) (AHI, >= 11 to <15 events/h) compared with nonapneic snorers for prevalent SAH after adjustment for relevant confounding factors including sex, age, smoking, obesity, daytime sleepiness, dyslipidemia, chronic obstructive pulmonary disease, type 2 diabetes, and sleep test methodology (polygraphy or polysomnography). Results: SAH prevalence was higher in the mild(AHI) (11-<15/h) OSA group compared with the mild(AHI 5-<11/h) group and nonapneic snorers (52% vs 45% vs 30%; P < .001). Corresponding adjusted odds ratios for SAH were 1.789 (mild(AHI) (11-<15/h); 95% confidence interval [CI], 1.49-2.15) and 1.558 (mild 1.34-1.82), respectively (P < .001). In sensitivity analysis, mild(AHI) (11-<15/h) OSA remained a significant predictor for SAH both in the polygraphy (odds ratio, 1.779; 95% CI, 1.403-2.256; P < .001) and polysomnography groups (odds ratio, 1.424; 95% CI, 1.047-1.939; P = .025). Conclusions: Our data suggest a dose-response relationship between mild OSA and SAH risk, starting from 5 events/h in polygraphy recordings and continuing with a further risk increase in the 11- to <150-events/h range. These findings potentially introduce a challenge to traditional thresholds of OSA severity and may help to stratify participants with OSA according to cardiovascular risk.
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| 21. |
- Brophy, Donald F, et al.
(author)
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Overcoming delayed in-vitro response to rFVIIa: effects of rFVIIa and rFVIIa analogue (vatreptacog alfa) concentration escalation in whole blood assays.
- 2011
-
In: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 22, s. 541-546
-
Journal article (peer-reviewed)abstract
- In a previous pharmacokinetic/pharmacodynamic study in nonbleeding hemophilia patients, variability in laboratory response to recombinant factor VIIa (rFVIIa) 90 μg/kg was noted, and the patients were described as delayed or rapid laboratory responders based on time to clot formation. The current study determined whether in-vitro experiments could reproduce previous in-vivo findings; whether the delayed laboratory response to rFVIIa 90 μg/kg is improved by spiking with high-dose rFVIIa or rFVIIa analogue (vatreptacog alfa); whether a dose-response is observed with our method. In-vitro experiments were conducted in our previous patient cohort using rFVIIa 1.28 and 3.84 μg/ml and vatreptacog alfa 0.28 and 0.56 μg/ml. Whole blood studies were conducted using the Hemodyne Hemostasis Analysis System (platelet contractile force, clot elastic modulus, force onset time) and rotational thromboelastometry (clotting time, maximum clot firmness). Spiking with rFVIIa 1.28 μg/ml showed the same distribution of delayed and rapid laboratory response as observed previously. Increasing in-vitro rFVIIa concentrations improved the coagulation parameters; however, there remained delayed and rapid responders. Vatreptacog alfa improved the coagulation parameters at all concentrations tested, and the 0.56 μg/ml concentration normalized the force onset time, platelet contractile force, clot elastic modulus and clotting time parameters. A dose-response was observed with both assays. There was good agreement between the laboratory responses obtained after intravenous administration of rFVIIa 90 μg/kg and in-vitro spiking studies. Escalating rFVIIa and vatreptacog alfa concentrations improved coagulation parameters in all patients compared to rFVIIa 1.28 μg/ml. Vatreptacog alfa produced more pronounced coagulation effects at lower concentrations than rFVIIa; and the 0.56 μg/ml concentration completely normalized responses in all patients.
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| 22. |
- Buschard, Karsten, et al.
(author)
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Low serum concentration of sulfatide and presence of sulfated lactosylceramid are associated with Type 2 diabetes. The Skaraborg Project
- 2005
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In: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 22:9, s. 1190-8
-
Journal article (peer-reviewed)abstract
- AIMS: The glycosphingolipid sulfatide (sulfated galactosyl-ceramide) increases exocytosis of beta-cell secretory granules, activates K(ATP)-channels and is thereby able to influence insulin secretion through its presence in the islets. A closely related compound, sulfated lactosylceramide (sulf-lac-cer), is present in the islets during fetal and neonatal life when, as in Type 2 diabetes, insulin is secreted autonomically without the usual first phase response to glucose. The aim was to examine whether serum concentrations of these glycolipids are associated with Type 2 diabetes. METHODS: A case-control study, comprising 286 women and 283 men, was designed using a population-based sample of patients with Type 2 diabetes and a population survey. RESULTS: Low serum concentrations of sulfatide were associated with Type 2 diabetes, independent of traditional risk factors for diabetes in a sex-specific analysis: odds ratio (OR) 2.1 (95% confidence interval 1.1, 3.9) in men, and 2.3 (1.2, 4.3) in women, comparing the lowest and the highest tertiles. Type 2 diabetes was also associated with detectable amounts of sulf-lac-cer in serum: OR 1.7 (0.9, 3.4) in men, and 7.6 (3.8, 15.2) in women. After adjustment for confounding from other diabetes risk factors, these associations remained basically unchanged. The connections between sulfatide and Type 2 diabetes, and sulf-lac-cer and Type 2 diabetes were independent of each other. Insulin resistance (HOMA-IR) was negatively correlated with sulfatide concentration and positively correlated with sulf-lac-cer (both P < 0.0001, independently). CONCLUSIONS: We report a new, robust and highly significant independent association between Type 2 diabetes and serum concentrations of sulfatide in both sexes, and sulf-lac-cer in females. The associations were also independent of other known diabetes risk factors.
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| 23. |
- Eliasson, T, et al.
(author)
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Myocardial turnover of endogenous opioids and calcitonin-gene-related peptide in the human heart and the effects of spinal cord stimulation on pacing-induced angina pectoris.
- 1998
-
In: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 89:3, s. 170-7
-
Journal article (peer-reviewed)abstract
- Earlier studies have shown that spinal cord stimulation (SCS) has antianginal and anti-ischemic effects in severe coronary artery disease. In the present study, 14 patients were subjected to right-sided atrial catheterization and atrial pacing. The patients were paced to angina during a control session and during spinal cord stimulation. Myocardial extraction of beta-endorphin (BE) during control pacing (8 +/- 22%) changed to release at the maximum pacing rate during treatment (-21 +/- 47%, a negative value representing release). Furthermore, the results indicate local myocardial turnover of leuenkephalin, BE and calcitonin-gene-related peptide. In addition, it is implied that SCS may induce myocardial release of BE which could explain the beneficial effects in myocardial ischemia.
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| 24. |
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| 25. |
- Elmasry, A., et al.
(author)
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Obstructive sleep apnoea and urine catecholamines in hypertensive males: a population-based study
- 2002
-
In: Eur Respir J. ; 19:3
-
Journal article (peer-reviewed)abstract
- Studies addressing the relationship between obstructive sleep apnoea (OSA) and sympathoadrenal activity have been criticized for poor control of factors known to confound sympathetic function, including hypertension. The aim of this study was to investigate the relationship between OSA and urinary catecholamines in a population-based sample of hypertensive males. In 1994, 2,668 males aged 40-79 yrs answered a questionnaire regarding sleep disorders and somatic diseases. Of those who reported hypertension, an age-stratified sample of 116 was selected for monitoring of breathing during sleep and overnight urine analysis. Subjects with OSA, defined as apnoea-hypopnoea index > or = 10 x h(-1), had higher concentrations of urinary normetanephrine (182+/-57 versus 141+/-45 micromol x mol(-1) creatinine, p<0.001) and metanephrine (70+/-28 versus 61+/-28 micromol mol(-1) creatinine, p<0.05) in comparison to subjects without OSA. In a multiple regression analysis, there was an association between variables of sleep-disordered breathing and normetanephrine and metanephrine concentrations, independent of major confounding factors. The authors concluded that, in a population-based sample of hypertensive males, obstructive sleep apnoea is associated with increased urinary concentrations of extraneuronal metabolites of catecholamines independent of major confounding factors, suggesting increased sympathoadrenal activity. Elevated sympathoadrenal activity may explain the increased cardiovascular morbidity associated with obstructive sleep apnoea.
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| 26. |
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| 27. |
- Erfurth, E M, et al.
(author)
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Suppressed plasma prolactin response to thyrotropin-releasing hormone in hyperthyroidism reproduced by thyroxine but not by triiodothyronine administration to normal subjects
- 1988
-
In: Acta Endocrinologica. - : Oxford University Press (OUP). - 0001-5598 .- 0804-4643 .- 1479-683X. ; 117:2, s. 8-241
-
Journal article (peer-reviewed)abstract
- In 10 hyperthyroid women studied in the follicular phase of the menstrual cycle, basal plasma PRL was normal, but PRL release after TRH was significantly suppressed compared with that in 11 control women. The suppressed PRL response to TRH was not explained by changes in serum estradiol or sex hormone-binding globulin. It recovered after treatment of hyperthyroidism. When normal women were treated with T4 (0.5 mg daily for 6 to 10 days), their mean serum free T4 level increased to about 70% of that in the hyperthyroid patients, whereas their serum free T3 levels increased to a lesser degree. During T4 administration, these women had PRL changes similar to those of the hyperthyroid patients. When the normal women took T3 (60-120 micrograms for 6 to 8 days), their serum free T3 increased to almost the level of the hyperthyroid patients, but the TRH stimulated PRL release remained close to the control level. The PRL increase after dopaminergic blockade with metoclopramide was significantly suppressed in hyperthyroid patients, and they had no PRL response to TRH after pretreatment with metoclopramide. In conclusion, the PRL changes in hyperthyroidism were reproduced by administration of T4, but not by administration of T3 to healthy women. The site of action is suggested to be pituitary, but additional hypothalamic effects cannot be excluded.
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| 28. |
- Fietze, I, et al.
(author)
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Management of obstructive sleep apnea in Europe
- 2011
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In: Sleep Medicine. - : Elsevier. - 1389-9457 .- 1878-5506. ; 12:2, s. 190-197
-
Journal article (peer-reviewed)abstract
- Objectives: In Europe, the services provided for the investigation and management of obstructive sleep apnoea (OSA) varies from country to country. The aim of this questionnaire-based study was to investigate the current status of diagnostic pathways and therapeutic approaches applied in the treatment of OSA in Europe, qualification requirements of physicians involved in diagnosis and treatment of OSA, and reimbursement of these services. Methods: Two questionnaires were sent to 39 physicians in 22 countries in Europe. In order to standardize the responses, the questionnaire was accompanied by an example. Results: Sleep centers from 21 countries (38 physicians) participated. A broad consistency among countries with respect to the following was found: pathways included referral to sleep physicians/sleep laboratories, necessity for objective diagnosis (primarily by polysomnography), use of polygraphic methods, analysis of polysomnography (PSG), indications for positive airway pressure (PAP) therapy, application of standard continuous PAP (CPAP) therapy (100% with an CPAP/APAP ratio of 2.24:1), and the need (90.5%) and management of follow-up. Differences were apparent in reimbursement of the diagnostic procedures and follow-up, in the procedures for PAP titration from home APAP titration with portable sleep apnea monitoring (38.1%) up to hospital monitoring with PSG and APAP (85.7%), and in the qualification requirements of sleep physicians. Conclusions: Management of OSA in different European countries is similar except for reimbursement rules, qualification of sleep specialists and procedures for titration of the CPAP treatment. A European network (such as the one accomplished by the European Cooperation in Science and Technology [COST] B26 Action) could be helpful for implementing these findings into health-service research in order to standardize management in a cost effective perspective.
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| 29. |
- Fridriksson, Benedikt, 1987, et al.
(author)
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Beneficial Effects of Early Intervention Telemedicine-based Follow-Up in Sleep Apnea A Randomized Controlled Multicenter Trial
- 2023
-
In: Annals of the American Thoracic Society. - 1546-3222. ; 20:10, s. 1499-1507
-
Journal article (peer-reviewed)abstract
- Rationale: Positive airway pressure (PAP) is standard treatment for obstructive sleep apnea. Telemedicine has been introduced for improved PAP follow-up. Objectives: Our study aim was to evaluate the clinical utility of and patient satisfaction with PAP follow-up with an early intervention telemedical protocol. Methods: A randomized controlled trial was conducted at four sleep clinics of the same county. Treatment-naive patients with obstructive sleep apnea were randomized to standard PAP follow-up (203 patients, fixed follow-up procedures) or early intervention telemedical follow-up (AirView, ResMed; 206 patients, continuous follow-up) for 3 months. Evaluated variables included PAP adherence at 3 months, patient-reported outcome measures (Epworth Sleepiness Scale, 36-item Short Form Health Survey, Insomnia Severity Index, Hospital Anxiety and Depression Scale), and staff time. Group differences were analyzed with linear mixed regression models adjusted for age, body mass index, apnea-hypopnea index, and study center. Results: The study groups were comparable at baseline (N= 409; mean age, 59 +/- 12 yr; body mass index, 31.9 +/- 6 kg/m(2), apnea-hypopnea index, 41.5 +/- 21 events/h). PAP adherence was higher in the proactive telemedicine group than in the control group (4.3 +/- 2.4 and 4.1 +/- 2.6 h/night; P = 0.01, respectively), and mean mask pressure at follow-up was significantly lower in the telemedicine group than in the control group (8.7 +/- 2.1 cm H2O vs. 9.2 +/- 2.5 cm H2O; P = 0.028). In post hoc analysis, the difference in PAP adherence between groups was most pronounced in patients with depression (4.8 +/- 2.6 h/night vs. 2.7 +/- 2.3 h/night; P = 0.03). Relevant mask leakage (>24 L/min) was lower in the telemedicine group (5.4% vs. 12.1%, P = 0.024). Improvement of patient-reported outcome measures and patient satisfaction was equivalent between groups. Conclusions: Proactive telemedical management of the initial follow-up of PAP treatment compared favorably with conventional follow-up in terms of adherence, pressure level, and mask leakage. Patients with depression may particularly benefit from telemedical follow-up. Specific clinical routines are required to establish this practice in sleep clinics.
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| 30. |
- Fu, Michael, 1963, et al.
(author)
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Functional autoimmune epitope on alpha 1-adrenergic receptors in patients with malignant hypertension.
- 1994
-
In: Lancet. - 0140-6736. ; 344:8938, s. 1660-3
-
Journal article (peer-reviewed)abstract
- Because of the growing evidence that hypertensive disease is accompanied by immunological dysfunction, we have investigated autoimmunity in patients with malignant hypertension. Peptides corresponding to the sequence of the second extracellular loops of the human alpha 1-adrenergic receptor and the M2-muscarinic receptor were used as antigens in an ELISA. Serum from 4 (12%) of 33 healthy controls, 3 (20%) of 15 patients with malignant essential hypertension, and 7 (64%) of 11 with secondary hypertension showed positive responses in the ELISA for the alpha 1-adrenergic receptor peptide. Positive responses were significantly more common among the patients with secondary hypertension than in the other two groups (p < 0.01). By contrast, no autoantibodies against the M2-muscarinic receptor peptide were detected in either hypertensive group. Autoantibodies against the alpha 1-adrenergic receptor, affinity-purified from patients with positive responses, specifically recognised bands with molecular masses of 68, 40, and 37 kDa on immunoblotted membrane proteins of rat ventricles. The patients' autoantibodies caused a decrease in tritiated prazosin binding sites and an increase in heart beating frequency of neonatal cultured rat cardiomyocytes; antibodies purified from the controls had no effect. Circulating autoantibodies against the alpha 1-adrenergic receptor are present in a subgroup of patients with malignant hypertension. These autoantibodies have pharmacological activity in vitro, which suggests that they may be involved in the pathogenesis of malignant hypertension.
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| 31. |
- Gunduz, C., et al.
(author)
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Long-term positive airway pressure therapy is associated with reduced total cholesterol levels in patients with obstructive sleep apnea: data from the European Sleep Apnea Database (ESADA)
- 2020
-
In: Sleep Medicine. - : Elsevier BV. - 1389-9457. ; 75, s. 201-209
-
Journal article (peer-reviewed)abstract
- Background and aim: Obstructive sleep apnea (OSA) is an independent risk factor for dyslipidemia. The current study examined the effects of positive airway pressure (PAP) treatment on lipid status in the European Sleep Apnea Database (ESADA). Methods: The prospective cohort study enrolled 1564 OSA subjects (74% male, mean age 54 ± 11y, body mass index (BMI) 32.7 ± 6.6 kg/m2 and apnea-hypopnea index (AHI) 40.3 ± 24.4 n/h) undergoing PAP therapy for at least three months (mean 377.6 ± 419.5 days). Baseline and follow-up total cholesterol (TC) from nine centers were analyzed. Repeated measures and logistic regression tests (adjusted for age, sex, weight changes, lipid lowering medication, PAP compliance, and treatment duration) were used to compare changes in TC concentration. Incident risk for a coronary heart disease event (CHD) was used to compute a Framingham CHD risk score (estimated from age, BMI, blood pressure, and TC). Results: Adjusted means of TC decreased from 194.2 mg/dl to 189.3 mg/dl during follow-up (p = 0.019). A clinically significant (10%) reduction of TC at PAP follow-up was observed in 422 patients (27%). Duration of PAP therapy was identified as independent predictor for TC reduction, which implies an approximately 10% risk reduction for incident CHD events (from 26.7% to 24.1% in men and from 11.2% to 10.1% in women, p < 0.001 respectively). Conclusion: This observational study demonstrates a reduction of TC after long-term PAP treatment. The close association between TC concentration and cardiovascular (CV) mortality suggests that identification and treatment of OSA may have a beneficial effect on overall CV risk due to this mechanism. This possibility needs to be evaluated in prospective randomized studies. © 2020 Elsevier B.V.
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| 32. |
- Hansson, D., et al.
(author)
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Clinical impact of routine sleep assessment by peripheral arterial tonometry in patients with COPD
- 2023
-
In: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 9:2
-
Journal article (peer-reviewed)abstract
- Background Coexisting obstructive sleep apnoea (OSA) in patients with COPD, defined as overlap syndrome (OVS), is prevalent and underdiagnosed. Routine assessment of OSA is not common practice in COPD care. Our study assessed the clinical impact of sleep assessment by peripheral arterial tonometry (PAT) in COPD patients. Methods 105 COPD patients (mean age 68.1 +/- 9 years, body mass index (BMI) 28.3 +/- 6.0 kg center dot m(-2), 44% males, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I to IV in 2%, 40%, 42% and 16%, respectively) underwent assessment at an outpatient COPD clinic including anthropometrics, arterial blood gas (ABG) and spirometry in this clinical cohort study. PAT-based sleep studies were performed. Predictors of OVS and ABG were determined. Rapid eye movement (REM) sleep-related OSA (REM-OSA) was analysed in OVS. Results 49 COPD patients (47%) suffered from moderate to severe OSA (OVS group, mean apnoea-hypopnoea index 30.8 +/- 18 events center dot h(-)1, REM-oxygen desaturation index (REM-ODI) 26.9 +/- 17 events center dot h(-)1). OVS was more prevalent in males compared to females (59% and 37%, p=0.029, respectively). Age (70.1 +/- 8 versus 66.3 +/- 10 years), BMI (30.0 +/- 6 versus 26.4 +/- 7 kg center dot m(-2)) and hypertension prevalence (71% versus 45%) were elevated (all p<0.03, respectively), while deep sleep (12.7 +/- 7% and 15.4 +/- 6%, p=0.029) and mean overnight oxygenation (90.6 +/- 3% and 92.3 +/- 2%, p=0.003) were lower in OVS compared to COPD alone. REM-ODI was independently associated with daytime arterial carbon dioxide tension (P-aCO2) (beta=0.022, p<0.001). REM-OSA was associated with an elevated prevalence of atrial fibrillation compared to no REM-OSA (25% and 3%, p=0.022). Conclusions OVS was highly prevalent, specifically in obese males. REM-related OSA showed strong association with elevated daytime P-aCO2 and prevalent cardiovascular disease. PAT was feasible for sleep assessment in COPD.
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| 33. |
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| 34. |
- Hedner, E., et al.
(author)
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Brominated cyclodipeptides from the marine sponge Geodia barretti as selective 5-HT ligands
- 2006
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In: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 69:10, s. 1421-1424
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Journal article (peer-reviewed)abstract
- The brominated cyclodipeptides barettin(cyclo[(6-bromo-8-entryptophan) arginine]) and 8,9-dihydrobarettin ( cyclo[(6-bromotryptophan) arginine]) isolated from the marine sponge Geodia barretti have previously been shown to inhibit settlement of barnacle larvae in a dose-dependent manner in concentrations ranging from 0.5 to 25 mu M. To further establish the molecular target and mode of action of these compounds, we investigated their affinity to human serotonin receptors. The tryptophan residue in the barettins resembles that of endogenous serotonin [5-hydroxytryptamine]. A selection of human serotonin receptors, including representatives from all subfamilies (1-7), were transfected into HEK-293 cells. Barettin selectively interacted with the serotonin receptors 5-HT2A, 5-HT2C, and 5-HT4 at concentrations close to that of endogenous serotonin, with the corresponding K-i values being 1.93, 0.34, and 1.91 mu M, respectively. 8,9-Dihydrobarettin interacted exclusively with the 5-HT2C receptor with a K-i value of 4.63 mu M; it failed to show affinity to 5-HT2A and 5-HT4, indicating that the double bond between the tryptophan and arginine residue plays an important role in the interaction with the receptor proteins.
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| 35. |
- Hedner, E, et al.
(author)
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Primary herpes simplex virus (type 1) infection delays healing of oral excisional and extraction wounds in the rat
- 1990
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In: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 19:10, s. 471-476
-
Journal article (peer-reviewed)abstract
- The effect of acute herpes simplex virus type 1 (HSV-1) infection on the healing process of intraoral wounds and tooth extraction sockets in the rat was studied. A standardized size of the buccal mucosa was excised and molars were extracted and a HSV-1 suspension was topically applied. The virus infected wounds were clinically characterized by erythema and swelling and histologically by heavy inflammation cell infiltrate and abscesses during the first week. The acute HSV-1 infection was found to significantly delay healing of both types of wounds by 3 days. Antiviral treatment with acyclovir (ACV) decreased the degree of inflammation and improved healing of the infected wounds. The present results indicate a delayed and disturbed healing of wounds in the oral cavity in the presence of HSV-1. The findings may have a clinical significance for primary or latent HSV-1 infections in conjunction with surgical intervention in the oral cavity.
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| 36. |
- Hedner, E, et al.
(author)
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Recrudescence of herpes simplex virus type 1 in latently infected rats after trauma to oral tissues
- 1993
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In: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 22:5, s. 214-220
-
Journal article (peer-reviewed)abstract
- Tooth extraction in rats was used to trigger a latent HSV-1 infection. HSV-1 was inoculated unilaterally in the rat palates. Eight weeks later two molars were removed bilaterally. The trigeminal ganglia were co-cultivated and HSV-1 was isolated from 63% of the ganglia on the infected sides but from only 11% on control sides. The immune response pattern was analysed by immunoblotting of rat serum, and strong reactivity to HSV-1 specific cell polypeptides and glycoproteins (ICP6, gC, pgC, gD) was seen after reactivation. The extraction sockets were histopathologically evaluated and showed healing on the infected side in 26% compared to 63% in contralateral control sockets. The effect of acyclovir (ACV) treatment was elucidated and was found to influence the subsequent development of antibodies and to promote healing of the sockets. Vesiculation in intra- and subepithelial tissue was present on the infected side in 58% but in only 12% of ACV-treated animals. The present study in rats has shown that a latent HSV-1 infection can be established and reactivated by tooth extraction. Reactivation resulted in delayed healing of sockets on the latently infected side but not on the contralateral control side. HSV-1 reactivation was demonstrated serologically by immunoblotting. Healing was significantly promoted by administration of ACV, which also supports the contention that HSV-1 interferes with the healing process.
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| 37. |
- Hedner, Thomas, 1949, et al.
(author)
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Achieving better blood pressure control.
- 2008
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In: Blood pressure. - Stockholm : Informa Healthcare. - 1651-1999 .- 0803-7051. ; 17 Suppl 1, s. 3-4
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Other publication (other academic/artistic)
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| 38. |
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| 39. |
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| 40. |
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| 41. |
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| 42. |
- Hedner, Thomas, 1949, et al.
(author)
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Hypertension control - a global challenge.
- 2005
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In: Blood pressure. - Stockholm : Taylor & Francis. - 1651-1999 .- 0803-7051. ; 14 Suppl 1, s. 4-5
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Other publication (other academic/artistic)
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| 43. |
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| 44. |
- Hedner, Thomas, 1949, et al.
(author)
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Management of older hypertensive patients.
- 2008
-
In: Blood pressure. - Stockholm : Informa Healthcare. - 1651-1999 .- 0803-7051. ; 17:4, s. 184-5
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Other publication (other academic/artistic)
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| 45. |
- Hedner, Thomas, 1949, et al.
(author)
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Medical decision making in hypertension.
- 2006
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In: Blood pressure. - Stockholm : Taylor & Francis. - 0803-7051 .- 1651-1999. ; 15:4, s. 196-7
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Other publication (other academic/artistic)
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| 46. |
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| 47. |
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| 48. |
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| 49. |
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| 50. |
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