163 research outputs found
Comparison of N-terminal pro-atrial natriuretic peptide and atrial natriuretic peptide in human plasma as measured with commercially available radioimmunoassay kits
Atrial natriuretic peptide (ANP) has become an important parameter for assessing the condition of patients with cardia disease. Recently, attention has also focused on N-terminal pro-atrial natriuretic peptide (NtproANP) in this context. NtproANP circulates in plasma in higher concentration, is more stable ex vivo, and may be a better parameter for cardiac function over time. We have evaluated a new commercially available radioimmunoassay kit for NtproANP and compared results and method withthose of ANP measurements. The NtproANP kit was found to be reliable and easy to use (no plasma extraction step is necessary), with good reproducibility (coefficients of variation 7-15%). Normal values in 15 healthy laboratory workers, 25 healthy elderly subjects and 25 patients with heart failure were 207 ± 70, 368 ± 134 and 1206 ± 860 pmol/l, respectively, 8.3, 11.8 and 13.0 times higher, respectively, than corresponding ANP concentrations. NtproANP correlated well with ANP (r 0.64-0.78). We conclude that plasma NtproANP measurement may be a good alternative to plasma ANP measurement: technically, it is easier to perform, and NtproANP is more stable in plasma. Whether NtproANP is a better diagnostic and prognostic parameter than ANP remains to be further established
A Duality Based 2-Approximation Algorithm for Maximum Agreement Forest
We give a 2-approximation algorithm for the Maximum Agreement Forest problem on two rooted binary trees. This NP-hard problem has been studied extensively in the past two decades, since it can be used to compute the rooted Subtree Prune-and-Regraft (rSPR) distance between two phylogenetic trees. Our algorithm is combinatorial and its running time is quadratic in the input size. To prove the approximation guarantee, we construct a feasible dual solution for a novel linear programming formulation. In addition, we show this linear program is stronger than previously known formulations, and we give a compact formulation, showing that it can be solved in polynomial tim
Human renal and systemic hemodynamic, natriuretic, and neurohumoral responses to different doses of L-NAME
Experimental evidence indicates that the renal circulation is more
sensitive to the effects of nitric oxide (NO) synthesis inhibition than
other vascular beds. To explore whether in men the NO-mediated vasodilator
tone is greater in the renal than in the systemic circulation, the effects
of three different intravenous infusions of NG-nitro-L-arginine methyl
ester (L-NAME; 1, 5, and 25 microg. kg-1. min-1 for 30 min) or placebo on
mean arterial pressure (MAP), systemic vascular resistance (SVR), renal
blood flow (RBF), renal vascular resistance (RVR), glomerular filtration
rate (GFR), and fractional sodium and lithium excretion (FENa and FELi)
were studied in 12 healthy subjects, each receiving randomly two of the
four treatments on two different occasions. MAP was measured continuously
by means of the Finapres device, and stroke volume was calculated by a
model flow method. GFR and RBF were estimated from the clearances of
radiolabeled thalamate and hippuran. Systemic and renal hemodynamics were
followed for 2 h after start of infusions. During placebo, renal and
systemic hemodynamics and FENa and FELi remained stable. With the low and
intermediate L-NAME doses, maximal increments in SVR and RVR were similar:
20.4 +/- 19.6 and 23.5 +/- 16.0%, respectively, with the low dose and 31.4
+/- 26.7 and 31.2 +/- 14.4%, respectively, with the intermediate dose
(means +/- SD). With the high L-NAME dose, the increment in RVR was
greater than the increment in SVR. Despite a decrease in RBF, FENa and
FELi did not change with the low L-NAME dose, but they decreased by 31.2
+/- 11.0 and 20.2 +/- 6.3%, respectively, with the intermediate dose and
by 70.8 +/- 8.1 and 31.5 +/- 15.9% with the high L-NAME dose,
respectively. It is concluded that in men the renal circulation is not
more sensitive to the effects of NO synthesis inhibition than the systemic
circulation and that the threshold for NO synthesis inhibition to produce
antinatriuresis is higher than the threshold level to cause renal
vasoconstriction
Split scheduling with uniform setup times
We study a scheduling problem in which jobs
may be split into parts, where the parts of a split job may be
processed simultaneously on more than one machine. Each
part of a job requires a setup time, however, on the machine
where the job part is processed. During setup, a machine
cannot process or set up any other job. We concentrate on
the basic case in which setup times are job-, machine- and
sequence-independent. Problems of this kind were encountered
when modelling practical problems in planning dis-
aster relief operations. Our main algorithmic result is a
polynomial-time algorithm for minimising total completion
time on two parallel identical machines. We argue, why the
same problem with threemachines is not an easy extension of
the two-machine case, leaving the complexity of this case as a
tantalising open problem. We give a constant-factor approximation
algorithm for the general case with any number of
machines and a polynomial-time approximation scheme for
a fixed number of machines. For the version with the objective
to minimise total weighted completion time, we prove
NP-hardness. Finally, we conclude with an overview of the
state of the art for other split scheduling problems with job-,
machine- and sequence-independent setup times
Angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade prevent cardiac remodeling in pigs after myocardial infarction: role of tissue angiotensin II
BACKGROUND: The mechanisms behind the beneficial effects of
renin-angiotensin system blockade after myocardial infarction (MI) are not
fully elucidated but may include interference with tissue angiotensin II
(Ang II). METHODS AND RESULTS: Forty-nine pigs underwent coronary artery
ligation or sham operation and were studied up to 6 weeks. To determine
coronary angiotensin I (Ang I) to Ang II conversion and to distinguish
plasma-derived Ang II from locally synthesized Ang II, (125)I-labeled and
endogenous Ang I and II were measured in plasma and in infarcted and
noninfarcted left ventricle (LV) during (125)I-Ang I infusion. Ang II type
1 (AT(1)) receptor-mediated uptake of circulating (125)I-Ang II was
increased at 1 and 3 weeks in noninfarcted LV, and this uptake was the
main cause of the transient elevation in Ang II levels in the noninfarcted
LV at 1 week. Ang II levels and AT(1) receptor-mediated uptake of
circulating Ang II were reduced in the infarct area at all time points.
Coronary Ang I to Ang II conversion was unaffected by MI. Captopril and
the AT(1) receptor antagonist eprosartan attenuated postinfarct
remodeling, although both drugs increased cardiac Ang II production.
Captopril blocked coronary conversion by >80% and normalized Ang II uptake
in the noninfarcted LV. Eprosartan did not affect coronary conversion and
blocked cardiac Ang II uptake by >90%. CONCLUSIONS: Both circulating and
locally generated Ang II contribute to remodeling after MI. The rise in
tissue Ang II production during angiotensin-converting enzyme inhibition
and AT(1) receptor blockade suggests that the antihypertrophic effects of
these drugs result not only from diminished AT(1) receptor stimulation but
also from increased stimulation of growth-inhibitory Ang II type 2
receptors
Caries experience among children born after a complicated pregnancy
Objectives: Behavioural and lifestyle factors, as oral hygiene and diet, are well-established risk factors in the pathogenesis of dental caries, though displaying large differences in susceptibility across individuals. Since enamel formation already starts in utero, pregnancy course and outcome may eventually play a role in enamel strength and caries susceptibility. Therefore, we studied the association between history of pregnancy complications and the caries experience in their six-year-old children. The pregnancy complications included small for gestational age (SGA), spontaneous preterm birth (sPTB), gestational hypertension (GH), pre-eclampsia (PE), individually, and a combination of those, designated as placental syndrome. Methods: This study was embedded in Generation R, a prospective longitudinal Dutch multiethnic pregnancy cohort study. Information about pregnancy complications was obtained from questionnaires completed by midwives and obstetricians with cross-validation in medical records. These included SGA, sPTB, GH and PE. Caries experience was assessed with the decayed, missing and filled teeth (dmft) index at a mean age of six years. The association between dental caries experience and a history of pregnancy complications was studied by using hurdle negative binomial (HNB) models. Results: We were able to assess the dmft index in 5323 six-year-old children (mean age 6.2Â years, SD 0.5). We did not find an association between the different pregnancy complications and dental caries experience in childhood, whether for SGA, sPTB, GH, PE, or for the combined outcome placental syndrome (HNB estimates: OR 1.02, 95%CI 0.87 - 1.19; RR 0.90, 95%CI 0.78 - 1.04). Further adjustment of the models with different confounders did not alter the outcome. Conclusions: Although it is expected that prenatal stress can be a risk factor for caries development later in life, our findings do not support this hypothesis. Therefore, we believe disparities in caries experience between children are probably not explained by early life events during a critical intrauterine period of development
Design and overview of the Origins of Alzheimer’s Disease Across the Life course (ORACLE) study
Brain development and deterioration across the lifespan are integral to the etiology of late-life neurodegenerative disease. Factors that influence the health of the adult brain remain to be elucidated and include risk factors, protective factors, and factors related to cognitive and brain reserve. To address this knowledge gap we designed a life-course study on brain health, which received funding through the EU ERC Programme under the name Origins of Alzheimer’s Disease Across the Life course (ORACLE) Study. The ORACLE Study is embedded within Generation R, a prospective population-based cohort study of children and their parents, and links this with the Rotterdam Study, a population-based study in middle-aged and elderly persons. The studies are based in Rotterdam, the Netherlands. Generation R focuses on child health from fetal life until adolescence with repeated in-person examinations, but has also included data collection on the children’s parents. The ORACLE Study aims to extend the parental data collection in nearly 2000 parents with extensive measures on brain health, including neuroimaging, cognitive testing and motor testing. Additionally, questionnaires on migraine, depressive symptoms, sleep, and neurological family history were completed. These data allow for the investigation of longitudinal influences on adult brain health as well as intergenerational designs involving children and parents. As a secondary focus, the sampling is enriched by mothers (n = 356) that suffered from hypertensive disorders during pregnancy in order to study brain health in this high-risk population. This article provides an overview of the rationale and the design of the ORACLE Study
A Novel, Single Algorithm Approach to Predict Acenocoumarol Dose Based on CYP2C9 and VKORC1 Allele Variants
The identification of CYP2C9 and VKORC1 genes has strongly stimulated the research on pharmacogenetics of coumarins in the last decade. We assessed the combined influence of CYP2C9 *2 and *3, and VKORC1 c.-1639G>A, 497C>G, and 1173C>T variants, on acenocoumarol dosage using a novel algorithm approach, in 193 outpatients who had achieved stable anticoagulation. We constructed an “acenocoumarol-dose genotype score” (AGS, maximum score = 100) based on the number of alleles associated with higher acenocoumarol dosage carried by each subject for each polymorphism. The mean AGS was higher in the high-dose (>28mg/week) compared with the low-dose (<7mg/week) group (mean(SEM) of 84.1±3.4 vs. 62.2±4.8, P = 0.008). An AGS>70 was associated with an increased odds ratio (OR) of requiring high acenocoumarol dosage (OR: 3.347; 95%CI: 1.112–10.075; P = 0.032). In summary, although more research is necessary in other patient cohorts, and this algorithm should be replicated in an independent sample, our data suggest that the AGS algorithm could be used to help discriminating patients requiring high acenocoumarol doses to achieve stable anti-coagulation
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