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  • 1
    Keywords: DISEASE ; kidney ; TRIAL ; HEALTH ; OUTCOMES ; METAANALYSIS ; RENIN-ANGIOTENSIN SYSTEM ; GENOME-WIDE ASSOCIATION ; GENETIC-VARIANTS ; D SUPPLEMENTATION
    Abstract: Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49 363), increased 25(OH) D concentration was associated with decreased systolic blood pressure (beta per 10% increase, -0.12 mm Hg, 95% CI -0.20.to -0.04; p=0.003) and reduced odds of hypertension (odds ratio [OR] 0.98, 95% CI 0.97-0.99; p=0.0003), but not with decreased diastolic blood pressure (beta per 10% increase, -0.02 mm Hg, -0.08 to 0.03; p=0.37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0.10 mm Hg in systolic blood pressure (-0.21 to -0.0001; p=0.0498) and a change of -0.08 mm Hg in diastolic blood pressure (-0.15 to -0.02; p=0.01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0.98, 0.96-0.99; p=0.001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH) D concentration was associated with a change of -0.29 mm Hg in diastolic blood pressure (-0.52 to -0.07; p=0.01), a change of -0.37 mm Hg in systolic blood pressure (-0.73 to 0.003; p=0.052), and an 8 1% decreased odds of hypertension (OR 0.92, 0.87-0.97; p=0.002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
    Type of Publication: Journal article published
    PubMed ID: 24974252
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  • 2
    ISSN: 0168-9002
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0168-9002
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0304-4165
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: nimodipine ; subarachnoid haemorrhage ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Patients with a ruptured supratentorial aneurysm undergoing early surgery after the subarachnoid haemorrhage were treated postoperatively with nimodipine to prevent delayed ischaemic dysfunction. It was given first as a continuous intravenous infusion 2 mg/h (mean dose 0.5 µg/kg/min) for at least 7 days, and then orally (45 mg × 6) for at least a further 7 days. During the i.v. infusion, the mean plasma concentration was 26.6±1.8 ng/ml. The plasma clearance ranged from 0.57 to 1.77 l/kg/h and was negatively correlated with the age of the patient. Immediately prior to successive oral doses, the mean plasma concentration was 13.2 ng/ml (range〈3–38.8 ng/ml). The peak level was usually found after 1 h; it ranged from 7.0–96.0 ng/ml. Mean bioavailability was 15.9%. The nitropyridine metabolite was found in measurable concentrations only after oral treatment with nimodipine. In some cases, the concentration of metabolite exceeded that of the parent compound. The three patients investigated who developed delayed ischaemic dysfunction had plasma concentrations well within the range in patients who did not, so it seems unlikely that the therapeutic failure could be attributed to individual deviations in the pharmacokinetics of the drug.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Theoretical chemistry accounts 19 (1970), S. 326-334 
    ISSN: 1432-2234
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Zusammenfassung Die Gleichgewichtskonformation von trans- und cis-Stilben und die Rotationsbarriere zwischen zwei Isomeren wurde nach der CNDO/2-Methode berechnet. Die Ergebnisse in bezug auf die Geometrie stimmen mit experimentellen Daten gut überein, die Rotationsbarriere für die Drehung der Phenylringe dagegen ist praktisch Null.
    Abstract: Résumé La méthode CNDO/2 a été employée pour calculer les conformations d'équilibre du trans- et du cis-stilbène ainsi que la barrière de rotation entre ces deux isomères. Angles d'équilibre et distances calculés sont en bon accord avec les données expérimentales. Cependant les calculs indiquent que les cycles phényles devraient posséder une rotation libre soumise seulement à l'empêchement stérique. Ce résultat s'écarte de l'opinion courante. Les résultats sont discutés en relation avec les données théoriques et expérimentales antérieures.
    Notes: Abstract The equilibrium conformations of trans- and cis-stilbene and the rotational barrier between the two isomers were calculated using the CNDO/2 method. The results for the equilibrium angles and distances are in good agreement with experimental data. However, according to the calculations the phenyl rings would have a nearly free rotation which is only limited by steric hindrance. This result obviously deviates from the current view. The results are discussed in relation to previous theoretical and experimental evidence.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-8798
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human antibodies to HIV antigens expressed on the surface of infected cells may inhibit cell fusion with uninfected CD 4-positive cells and mediate killing of the infected cells by effector cells bearing the Fc receptor. Sequential sera from ten HIV-antibody seroconverted men, of which five progressed to ARC or AIDS (CDC stage IV) during the follow-up period of two years, were tested for the ability to inhibit CD 4-dependent cell fusion, (CFI) and to mediate antibody-dependent cellular cytotoxicity (ADCC). Nine patients developed HIV-specific ADCC and seven CFI-antibodies using the HIV strain HTLV-IIIB as target antigen. These antibodies appeared approximately at the same time 2–12 months after primary infection, defined as antibody seroconversion or antigenaemia. ADCC antibodies were detectable at higher titers as compared to CFI-antibodies. All sera of asymptomatic individuals (CDC stage II and III) were CFI antibody positive and had a higher mean ADCC titer as compared to sera from patients progressing to AIDS or ARC. ADCC and CFI antibodies coincided in some cases in the complete absence of core antibodies. Because the relationship between ADCC and CFI was not exclusive it is concluded that distinct domains of the HIV envelope induce natural antibodies mediating ADCC and CFI.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0942-0940
    Keywords: Traditional lumbar disc surgery ; dural tear ; outcome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of this study was to evaluate whether wide surgical exposures result in poorer outcome of lumbar disc surgery compared to smaller traditional exposures. The aim was also to assess if a dural tear has any impact on the postoperative clinical outcome. One hundred and twenty-two patients (56 women and 66 men, mean age 40.8 years) with herniated intervertebral lumbar disc and no previous back surgery, were included. Postoperatively they were grouped according to surgery as follows: surgery on one vs. two herniated discs (106 vs. 16 patients), partial vs. full laminectomy (93 vs. 29 patients), and the occurrence or not of a dural rent (8 vs. 114 patients). The outcome of surgery was evaluated one year postoperatively mainly by a composite clinical overall score (COS) and by its separate elements, which were: pain intensity in the lower-back or leg (VAS), neurological and clinical examination, functional capacity (Oswestry), and the need for analgesics. The results of the statistical regression analyses did not reveal significant differences in the postoperative outcome scores in the various groups of patients. The groups were comparable; no significant differences were seen in the pre-operative clinical overall scores.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 0942-0940
    Keywords: Ruptured cerebral aneurysms ; subarachnoid haemorrhage ; early operation ; delayed ischaemic deficit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A prospective open multicenter study on the preventive effect of nimodipine on symptomatic vascular spasm was performed in 120 (consecutive) patients with aneurysmal subarachnoid haemorrhage (SAH). All patients underwent early surgery (i.e. within 72 hours post SAH) and were in neurological grades I–III in Hunt and Hess. Grade IV and V as well as patients with significant intracerebral haematoma are not included. On preoperative CT, SAH was mild in 28 cases, moderate in 56 and severe in 36 cases. 25 patients (21%) were in grade I, 63 patients (53%) in grade II and 32 patients (26%) in grade III. The ruptured aneurysm was located on the anterior cerebral artery complex in 57 patients, on the internal carotid artery complex in 35, on the middle cerebral artery in 24 patients and on the basilar artery in 4 patients. After occlusion of the ruptured aneurysm, the lipophilic calcium channel blocker nimodipine was administered in the following manner: 1. Intraoperative, topical irrigation of the exposed arteries. 2. Intravenous infusion until day 7–14 after SAH followed by peroral medication for another week. Nimodipine was well tolerated and neither significant hypotension nor any other adverse reaction attributable to the drug was observed. Ischaemic cerebral dysfunction of delayed onset with permanent neurological deficit occurred in 2 patients (2%). Another 8 patients showed transient ischaemic symptoms. At 6 months follow-up, 93 % of the patients were classified as having made a full recovery, 16% as being minimally disabled, 5% as being moderately disabled and 3% as being severely disabled. Three patients had died. The present study supports the concept that preventive nimodipine treatment may reduce delayed ischaemic deficit in early aneurysm surgery.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0942-0940
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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