bluuebunny/crossref_metadata_2025 huggingface dataset:
The Stereochemical Activity of the Lone Pair in [Bi(NO3)3{(iPrO)2(O)PCH2P(O)(OiPr)2}2] — Comparison of Bismuth, Lanthanum and Praseodymium Nitrate Complexes
Authors: Mehring Michael , Mansfeld Dirk , Schürmann Markus
Published: February 2004

Five coordination compounds of bismuth, lanthanum and praseodymium nitrate with the oxygen‐coordinating chelate ligand (iPrO)2(O)PCH2P(O)(OiPr)2 (L) are reported: [Bi(NO3)3(L)2] (1), [La(NO3)3(L)2] (2), [Pr(NO3)3(L)2] (3), [La(NO3)3(L)(H2O)] (4) and [Pr(NO3)3(L)(H2O)] (5). The compounds were characterized by means of single crystal X‐ray crystallography, 1H and 31P NMR spectroscopy in solution, solid‐state 31P NMR spectroscopy, IR spectroscopy, DTA‐TG measurements (1, 2 and 4), conductometry and electrospray ionization mass spectrometry (ESI‐MS). In addition, DFT calculations for model compounds of 1 and 2 support our experimental work. In the solid state mononuclear coordination compounds were observed for 1—3, whereas compounds 4 and 5 gave one‐dimensional hydrogen‐bonded polymers via water‐nitrate coordination. Despite of the similar ionic radii of bismuth(III), lanthanum(III) and praseodymium(III) for a given coordination number the bismuth and lanthanide compounds 1—3 are not isostructural. The bismuth compound 1 shows a 9‐coordinate bismuth atom whereas lanthanum(III) and praseodymium(III) atoms are 10‐coordinate in the lanthanide complexes 2—5. The general LnO10 coordination motif in compounds 2—5 is best described as a distorted bi‐capped square antiprism. The BiO9 polyhedron might be deduced from the LnO10 polyhedron by replacing one oxygen ligand with a stereochemically active lone pair. The one‐to‐one complexes 4 and 5 dissociate in solution to give the corresponding one‐to‐two complexes 2 and 3, respectively, and solvated Ln(NO3)3. In contrast to the lanthanides, the one‐to‐two bismuth complex 1 is less stable in CH3CN solution and partially dissociates to give solvated Bi(NO3)3 and (iPrO)2(O)PCH2P(O)(OiPr)2.
Aminotroponiminate and a Related Diimine as Ligands for Tungsten Complexes
Authors: Kirin Vladimir , Roesky Peter W.
Published: February 2004

Reaction of N‐isopropyl‐2‐(isopropylamino)troponimine, {(i‐Pr)2ATI}H, with fac‐[W(CO)3(NCMe)3] yield the complex tungsten‐tetracarbonyl‐N, N'‐diisopropyl‐1, 2‐diimino‐3, 5‐cycloheptadiene (1), in which the ligand is tautomerized from the enamino to the imino isomer. As a result of the rearrangement the conjugate 10 π electron system of the ligand is destroyed. Further, treatment of compound 1 with an excess of KH in THF leads to the ionic complex [K(THF)2][{(i‐Pr)2ATI}W(CO)4] (2). In the presence of diglyme the corresponding complex [K(diglyme)2][{(i‐Pr)2ATI}W(CO)4] (3) is obtained. All compounds have been characterized by spectroscopic methods. Complex 1 has also been investigated by single crystal X‐ray diffraction.
Synthesis and Structure of the Clusters [Hg2(μ—SePh)2(SePh)2(PPh3)2] and [Hg3Br3(μ—SePh)3] · 2 DMSO
Authors: Schulz Lang Ernesto , Müller Dias Marcelo , Santos dos Santos Sailer , Vázquez‐López Ezequiel M. , Abram Ulrich
Published: February 2004

The compounds [Hg2(μ—SePh)2(SePh)2(PPh3)2] (I) and [Hg3Br3(μ—SePh)3] · 2 DMSO (II) are formed by reactions of [Hg(SePh)2] with PPh3 in THF(I) or with HgBr2 in DMSO (II) at room temperature. X—ray crystallography reveals that the cluster I consists of a distorted square built by each two Hg and Se atoms. The Hg atoms have almost tetrahedral co‐ordination environments formed by selenium atoms of two (μ‐—SePh) ligands and Se and P atoms of terminal —SePh and PPh3 ligands. The compound II is a six‐membered ring with alternating Hg and Se atoms in the chair conformation. Two DMSO molecules occupy positions below and above the [Hg3Se3] ring with the oxygen atoms directed to the centre of the ring.
Stabilization of Discrete [Cu(C2O4)2(H2O)2]2— Dianions in the Solid State by an Extensive Hydrogen Bonded Network
Authors: Keene Tony D. , Hursthouse Michael B. , Price Daniel J.
Published: February 2004

The dominant species in aqueous copper(II) solutions containing a high concentration of oxalate (ox) is trans‐[Cu(ox)2(H2O)2]2—, yet the ability of the oxalate anion to bridge metal ions means that very few examples of this isolated anion are seen in solid state structures. The structure of [pipH2]2+[Cu(ox)2(H2O)2]2— · 2H2O (pip = piperazine) (1) comprises discrete ions held in a complex 3‐dimensional hydrogen bonded network.
Hydrothermal Synthesis of Rare Earth Iodates from the Corresponding Periodates: II1). Synthesis and Structures of Ln(IO3)3 (Ln = Pr, Nd, Sm, Eu, Gd, Tb, Ho, Er) and Ln(IO3)3 · 2H2O (Ln = Eu, Gd, Dy, Er, Tm, Yb)
Authors: Douglas Paul , Hector Andrew L. , Levason William , Light Mark E. , Matthews Melissa L. , Webster Michael
Published: February 2004

Single crystals of lanthanide iodates have been quickly grown by decomposition of the corresponding periodates under hydrothermal conditions. Single crystal X‐ray diffraction showed that two structure types form with the elements from Pr‐Yb, an anhydrous form for Pr, Nd, Sm, Eu, Gd, Tb, Ho, Er and a dihydrate for Eu, Gd, Dy, Er, Tm, Yb. A detailed structure study is presented for one representative of each of these types, along with structure type and lattice parameters for the other materials.

Tb(IO3)3: Space group P21/c, Z = 4, lattice dimensions at 120 K: a = 7.102(1), b = 8.468(1), c = 13.355(2)Å, β = 99.67(1)°; R1 = 0.034.

Yb(IO3)3 · 2H2O: Space group P1¯, Z = 2, lattice dimensions at 120 K: a = 7.013(1), b = 7.370(1), c = 10.458(2)Å, α = 95.250(5), β = 105.096(5), γ = 109.910(10)°; R1 = 0.024.
The System LiSO3CF3/RbSO3CF3: Phase Diagram, Solid State NMR Investigations, and Ionic Conductivity
Authors: Pompetzki M. , van Wüllen L. , Jansen M.
Published: February 2004

In the system LiSO3CF3/RbSO3CF3 four different quasi‐ternary phases occur: Li0.7Rb0.3SO3CF3, Li0.55Rb0.45SO3CF3, LiRb2(SO3CF3)3, and Li0.2Rb0.8SO3CF3. These have been identified, and characterized by means of X‐ray powder diffractometry and DSC. LiSO3CF3 is trimorphic, LiRb2(SO3CF3)3 is dimorphic and RbSO3CF3 exists in four different modifications. The cation dynamics has been studied using 7Li‐NMR line shape analysis and 7Li‐spin lattice relaxation (T1) measurements. The pure and mixed trifluoromethylsulfonates in the system LiSO3CF3/RbSO3CF3 are solid electrolytes. Their ionic conductivities below 475 K increase with the rubidium content. Above this temperature, the conductivity of β‐LiRb2(SO3CF3)3 exceeds the one of δ‐RbSO3CF3.
Novel Layered Structures Formed by Iodocuprate Clusters Stabilized by Dialkylsulphide Ligands
Authors: Paulsson Heléne , Berggrund Malin , Fischer Andreas , Kloo Lars
Published: February 2004

From solutions of copper iodide and dodecyldimethylsulphonium iodide in acetonitrile, single crystals of [Cu4I4(DodecylMeS)4] (1) and [Cu3I4(DodecylMeS)3](DodecylMe2S) (2) could be obtained. Both compounds crystallize in the triclinic crystal system, space group P1¯ (1: a = 957.23(1), b = 967.25(2), c = 3818.38(6) pm, α = 90.3837(6)°, β = 86.4687(7)°, γ = 75.0996(7)°, 2: a = 874.23(1), b = 979.29(1), c = 4388.75(4) pm, α = 90.4472(3)°, ß = 94.7088(3)°, γ = 116.1162(3)°). 1 consists of tetrahedral Cu4 clusters, which are capped by four iodide ions over the tetrahedral faces. 2 contains trigonal Cu3 clusters, which are coordinated by four iodide ions, one centered over the plane, three bridging over the edges of the Cu3 triangle. In both compounds, the S atoms of (DodecylMeS) ligands coordinate to the Cu atoms. In 2, a (DodecylMe2S) cation is also present.
[PbAsSiiPr3]6 — the First Structurally Characterized Compound with Chemical Bonds between Lead and Arsenic
Authors: von Hänisch Carsten , Nikolova Donna
Published: February 2004

The compound [PbAsSiiPr3]6 (1) could be obtained by the reaction of PbCl2 with iPr3SiAs(SiMe3)2 in THF at 0 °C. Central structural motif is a hexagonal prism built by six lead and six arsenic atoms. The average Pb—As bond length is 281 pm. The cluster crystallizes in the monoclinic space group C2/c, the lattice constants are: a = 4460.8(9) b = 2296.6(5), c = 2734.4(6) pm, β = 117.57(3)°. The thermogravimetric analysis in vacuum shows the tendecy of 1 to decompose under formation of elementary lead and volatile arsenic compounds.
Ein Metaarsenat(V) Anion neuartiger Konstitution in AgAsO3
Authors: Curda J. , Peters E.‐M. , Jansen M.
Published: February 2004

AgAsO3 wurde durch Festkörperreaktion zwischen Ag2O und As2O3 oder As unter erhöhtem Sauerstoffdruck erstmals dargestellt (T = 500 °C, p(O2) = 2 kbar, 1—2 Tage). Nach den Ergebnissen der Einkristallröntgenstrukturanalyse (Pca21; a = 1948.8(3), b = 660.0(1), c = 1266.1(3) pm; Z = 24; 4741 unabh. Reflexe; R1 = 0.044) liegt gemäß [(AsO6/2)(AsO2/1O2/2)2] ein neuartiges Polyanion vor, das Arsen nebeneinander in oktaedrischer und tetraedrischer Koordination enthält. Es weist damit Struktureinheiten wie As2O5 auf, die darüber hinaus in ähnlicher Weise verknüpft sind.
Azidoberyllate mit Adamantanstruktur: Synthese, IR‐Spektren und Kristallstrukturen von (Ph4P)2[Be4X4(μ‐N3)6] (X = Cl, Br)
Authors: Neumüller Bernhard , Dehnicke Kurt
Published: February 2004

Azido Beryllates with Adamantan‐like Structures: Synthesis, IR Spectra, and Crystal Structures of (Ph4P)2[Be4X4(μ‐N3)6] (X = Cl, Br)

The azido beryllates (Ph4P)2[Be4X4(μ‐N3)6] (X = Cl 1a, X = Br 1b) have been prepared by the reaction of Me3SiN3 with the halogeno beryllates (Ph4P)2[Be2Cl6] and (Ph4P)2[Be2Br6], respectively, in CH2Cl2 and CH2Br2 solution, respectively. Both complexes form moisture sensitive, colourless crystals, which are nonexplosive with respect to mechanical or thermal stress. They are characterized by IR spectroscopy and by crystal structure determinations. 1a and 1b crystallize isotypically in the space group C2/c with 12 formula units per unit cell. Whereas 1a was only refined to R1 = 0.13, which is caused by disordering, 1b could be refined to R1 = 0.066. The structures contain adamantanlike dianions [Be4X4(μ‐N3)6]2— with two symmetry nonequivalent individuals which differ only slightly from one another. The Be4N6 core is formed by bridging function of the α‐nitrogen atoms of the azide groups with BeN bond lengths of 172.5 and bond lengths Nα—Nβ = 123.2 pm and Nβ—Nγ = 113.1 pm on average in the structure of 1b.
On damping in two‐layer elastic‐viscoelastic media
Authors: Renardy M.
Published: February 2004

We consider one‐dimensional wave propagation through two layers consisting, respectively, of an elastic and a viscoelastic medium. We show that, if the instantaneous elastic modulus of the viscoelastic medium is infinite, then there exists a family of modes with frequencies going to infinity, but damping rates going to zero. Hence the overall rate of damping is not exponential. On the other hand, there is a possibility of faster than exponential damping (i.e., the damping rate goes to infinity with frequency) if the elastic moduli of the two media are matched and the derivative G′(0) of the relaxation modulus of the viscoelastic medium is ‐∞.
A computer‐assisted instability proof for the Orr‐Sommerfeld equation with Blasius profile
Authors: Lahmann J.‐R. , Plum M.
Published: February 2004

The Orr‐Sommerfeld equation is one of the governing equations of hydrodynamic stability. Mathematically, it constitutes a non‐selfadjoint eigenvalue problem. Depending on its spectrum being contained in the right complex half‐plane or not, the underlying flow is stable or unstable under some given perturbation. Here, we focus on the Blasius profile modelling a flow along a wall. We present a computer‐assisted method for computing eigenvalue enclosures for such non‐selfadjoint problems. As a specific result, for a particular parameter constellation in the Orr‐Sommerfeld equation (often used as test example in the engineering literature), we enclose an eigenvalue in a circle which is completely contained in the left half‐plane. This constitutes the first rigorous proof of instability for the Orr‐Sommerfeld equation with Blasius profile.
Second order methods for boundary control of the instationary Navier‐Stokes system
Authors: Hinze M. , Kunisch K.
Published: February 2004

Second order methods for open loop optimal boundary control problems governed by the instationary Navier‐Stokes system are investigated. A general analytic framework is developed which allows an elegant representation of first and second order derivatives of the objective functional and of the state equations. Moreover a second order sufficient optimality condition is proved which guarantees local quadratic convergence of Newton's method.
Asymptotics of self‐intersecting loop solutions of the pendant drop equations
Authors: O'Brien S.B.G.
Published: February 2004

We construct asymptotic solutions for loop‐like self intersecting mathematical solutions of the Laplace‐Young capillary equation which was originally derived to model liquid rise in capillary tubes. We show that each successive loop has a complicated asymptotic structure which is resolved using the method of matched asymptotic expansions.
On the convergence of the Newton iteration
Authors: Veselić K.
Published: February 2004

We give a new class of convergence criteria for the classical Newton method for the equation f(x) = 0. We prove the global convergence, if the function f is the gradient of a uniformly convex function, while the convergence in the general case is still open. Our convergence condition consists of only one bound with a constant, which is shown to be sharp. We apply our result to a generic variational problem as well as to uniformly diagonally dominant Hessians. The convergence result is extended to the cases where the derivative is defined merely as a distribution.
A new relationship for the experimental‐analytical solution of the axisymmetric thermoelasticity problem
Authors: Ainola L. , Aben H.
Published: February 2004

The following inverse problem of axisymmetric thermoelasticity is considered: stresses σz and σrz are determined experimentally but the temperature distribution is not known; the stresses σr and σθ are to be determined. By eliminating temperature from the compatibility equations and using the equilibrium equations, a new relationship between the stress components for the axisymmetric thermoelasticity problem has been derived. Using this relationship, a closed form solution of the problem has been obtained.
Specialist care of heart failure improves appropriate pharmacotherapy at the expense of greater polypharmacy and drug‐interactions
Authors: Ledwidge Mark , Travers Bronagh , Ryder Mary , Ryan Enda , McDonald Kenneth
Published: February 2004

Background:

There is growing concern at the nature and extent of polypharmacy in heart failure (HF), which may be associated with increased drug interactions, adverse drug effects and a poor understanding of and compliance with therapy.

Aims:

This study evaluates polypharmacy in a relatively unselected community heart failure population following emergency admission and determines the impact of an in‐hospital, specialist heart failure care programme on appropriate pharmacotherapy, polypharmacy and drug interactions.

Methods:

We analysed the medication profiles of 91 consecutive patients with an emergency admission for HF to our institution on admission and discharge. The numbers of inappropriate medicines, inappropriate dosages and omitted medicines according to guidelines were recorded. Medication profiles were analysed for potential drug–drug, drug–liver and drug–kidney interactions using standard criteria.

Results:

In the study population, average age 71.1±10.4 years, 65.9% were male, 68.1% had left ventricular systolic dysfunction and the average ejection fraction on transfer to the specialist HF service was 38±13%. A total of 66 inappropriate medicines, 107 omitted medicines and 37 inappropriate dosage regimens were identified in the cohort on admission. These figures had dropped to 31, 33 and 19, respectively, on discharge, with per patient averages decreasing significantly (all P<0.0001). However, polypharmacy and potential drug interactions increased by 33% and 62%, respectively, from admission to discharge (P<0.0001) as did drug–kidney interactions and drug–liver interactions. Only ischemic aetiology and hypercholesterolaemia predicted polypharmacy in this cohort on discharge, whereas age, sex, renal function and heart failure type did not.

Conclusions:

Specialist care of heart failure following emergency admission results in more appropriate pharmacotherapy of heart failure. However, increased polypharmacy and drug–interactions are an inevitable consequence independent of age, sex and renal function. We advocate a practice of systematic evaluation of polypharmacy in all heart failure patients to identify potential problems and modify therapy where appropriate.
Improved systolic and diastolic myocardial function with intracoronary pyruvate in patients with congestive heart failure
Authors: Hermann Hans‐Peter , Arp Jordis , Pieske Burkert , Kögler Harald , Baron Steffen , Janssen Paul M.L. , Hasenfuss Gerd
Published: February 2004

Background:

Pyruvate increases myocardial performance in isolated myocardium and improves hemodynamics in patients with congestive heart failure.

Aims:

To investigate the influence of pyruvate on detailed parameters of systolic and diastolic left ventricular (LV) function.

Methods and Results:

In patients with heart failure due to dilated cardiomyopathy (LVEF 30±4%, n=9) pyruvate was infused intracoronarily. LV function was analysed before, during and after application of different pyruvate concentrations using a LV‐micromanometer catheter. LV volumes were determined using cine ventriculography. Pyruvate increased maximum rate of LV isovolumic pressure rise (Peak +dP/dt) from 802±106 to 1125±103 mmHg/s (P<0.05). Left ventricular end‐diastolic pressure declined in parallel from 17±2 to 12±2 mmHg (P<0.05) and heart rate decreased from 79±4 to 72±5 min−1 (P<0.05). Stroke volume index increased from 34±4 to 43±6 ml/m2 (P<0.05), end‐diastolic LV volume remained unchanged, thus left ventricular ejection fraction increased with pyruvate from 30±4 to 39±4% (P<0.05). Maximum rate of LV isovolumic pressure decline (Peak −dP/dt) was significantly increased with pyruvate (from 794±94 to 980±108 mmHg/s; P<0.05) and mean arterial pressure increased from 80±5 to 88±4 mmHg (P<0.05). Discontinuation of pyruvate resulted in immediate reversibility of its effects.

Conclusion:

Intracoronary pyruvate improves systolic and diastolic myocardial function and increases ejection fraction without increasing heart rate. Pyruvate thus exhibits the profile of a favourable inotropic agent, however, further investigation for the treatment of patients with acute heart failure is mandatory.
Long‐term effects of non‐excitatory cardiac contractility modulation electric signals on the progression of heart failure in dogs
Authors: Morita Hideaki , Suzuki George , Haddad Walid , Mika Yuval , Tanhehco Elaine J. , Goldstein Sidney , Ben‐Haim Shlomo , Sabbah Hani N.
Published: February 2004

Objective:

We previously showed that acute delivery of non‐excitatory cardiac contractility modulation (CCM) electric signal during the absolute refractory period improved LV function in dogs with chronic heart failure (HF). In the present study we examined the long‐term effects of CCM signal delivery on the progression of LV dysfunction and remodeling in dogs with chronic HF.

Methods:

Chronic HF was produced in 12 dogs by multiple sequential intracoronary microembolizations. The CCM signal was delivered using a lead implanted in the distal anterior coronary vein. A right ventricular and a right atrial lead were implanted and used for timing of CCM signal delivery. In six dogs, CCM signals were delivered continuously for 6 h daily with an average amplitude of 3.3 V for 3 months. Six HF dogs did not have leads implanted and served as controls.

Results:

In control dogs, LV end‐diastolic volume (EDV) and LV end‐systolic volume (ESV) increased (64±5 ml vs. 75±6 ml, P=0.003; 46±4 ml vs. 57±4 ml, P=0.003; respectively), and ejection fraction (EF) decreased (28±1% vs. 23±1%, P=0.001) over the course of 3 months of follow‐up. In contrast, CCM‐treated dogs showed a smaller increase in EDV (66±4 vs. 73±5 ml, P=0.01), no change in ESV, and an increase in EF from 31±1 to 34±2% (P=0.04) after 3 months of therapy.

Conclusions:

In dogs with HF, long‐term CCM therapy prevents progressive LV dysfunction and attenuates global LV remodeling. These findings provide compelling rationale for exploring the use of CCM for the treatment of patients with chronic HF.
The epidemiological enigma of heart failure with preserved systolic function
Authors: Thomas Martin D. , Fox Kevin F. , Coats Andrew J.S. , Sutton George C.
Published: February 2004

Background:

Current epidemiological evidence suggests that the prevalence of preserved systolic function in patients with heart failure varies widely from 13 to 74%. This inconsistency suggests a lack of consensus as to what this condition really is and how it has been characterised for epidemiological studies.

Aims:

In this review, we summarise and discuss the current understanding of the epidemiology of heart failure with preserved systolic function and the challenges that this raises.

Methods:

Studies were identified from Medline and Embase Literature Database searches using the subject headings heart failure, diastolic heart failure, epidemiology, incidence, prevalence, diagnosis, prognosis and mortality.

Results:

Sixty‐one studies of congestive heart failure with preserved systolic function were reviewed. There is great diversity in the criteria used to determine whether heart failure is present, the patient population, the setting of the study and methods of evaluating left ventricular function. This makes epidemiological studies of prevalence, morbidity and mortality impossible to compare.

Conclusions:

The diagnosis of this syndrome might be better defined in terms of symptoms, elevated neuro hormones and impaired cardiac workload. This would allow accurate identification of cases so that further research could be conducted to measure outcome and assess therapeutic benefit.
NT‐brain natriuretic peptide levels in pleural fluid distinguish between pleural transudates and exudates
Authors: Tomcsányi János , Nagy Erzsébet , Somlói Miklós , Moldvay Judit , Bezzegh Attila , Bózsik Béla , Strausz János
Published: February 2004

Background:

Pleural effusion is not pathognomic and distinguishing between transudates and exudates often presents a diagnostic dilemma. The purpose of our study was to examine whether the inclusion of pleural fluid brain natriuretic peptide (BNP) measurement into the analysis improves the diagnostic accuracy of pleural effusion.

Methods:

The pleural effusion of 14 patients with CHF (group A) and 14 subjects with different pleural pathology (group B) were analyzed. Samples of pleural fluid and serum were obtained from all patients on admission and biochemical analysis, bacterial and fungal culture, acid‐fast bacilli smear and culture and cytology were performed on the pleural fluid. In vitro quantitative determination of N‐terminal pro‐Brain natriuretic peptide (NT‐proBNP) in serum and pleural fluid were performed by electrochemiluminescence immunoassay proBNP method on an Elecsys 2010 (Roche) analyzer.

Results:

The median NT‐proBNP levels in groups A and B were 6295 pg/ml and 276 pg/ml, respectively: (P=0.0001). There was no overlap between the two groups. While the Light's criteria had a sensitivity of 93% and specificity of 43% for transudates, the pleural fluid NT‐proBNP level accurately differentiated between the two groups.

Conclusions:

The pleural NT‐proBNP levels were elevated in all patients who had transudate. Therefore if the NT‐proBNP levels of pleural effusion are within the normal range, transudate resulting from congestive heart failure can be ruled out. Our results suggest that the inclusion of pleural fluid NT‐proBNP measurement in the routine diagnostic panel would enhance discrimination among the different causes of pleural effusions.
Application of NT‐proBNP and BNP measurements in cardiac care: a more discerning marker for the detection and evaluation of heart failure
Authors: Seino Yoshihiko , Ogawa Akio , Yamashita Teruyo , Fukushima Masato , Ogata Ken‐ichi , Fukumoto Hiroko , Takano Teruo
Published: February 2004

Background:

Measurement of brain natriuretic peptide (BNP) has become a potent diagnostic aid as a means of identifying patients with systolic or diastolic dysfunction. Due to better stability in circulating blood, we reasoned that measurement of N‐terminal proBNP (NT‐proBNP) may be a more discerning marker for the detection and evaluation of chronic heart failure.

Methods:

The relationships between plasma concentrations of NT‐proBNP and BNP, and aetiology, New York Heart Association (NYHA) classification, and left ventricular ejection fraction (LVEF) were analyzed in 105 patients with chronic heart failure. Sixty‐seven healthy volunteers were studied as the controls.

Results:

Both NT‐proBNP and BNP showed progressive increases (P<0.001) in proportion to the NYHA classification; the increment of NT‐proBNP was larger than that of BNP. Elevated NT‐proBNP significantly correlated with BNP (r=0.737, P<0.001). Receiver operating characteristics analysis to detect LVEF<40% showed similar values (area under the curve, AUC: NT‐proBNP 0.754 vs. BNP 0.770), however, AUC to detect LVEF<50% tended to be greater for NT‐proBNP than that for BNP (NT‐proBNP 0.820 vs. BNP 0.794).

Conclusion:

NT‐proBNP may be a more discerning marker for the detection and evaluation of heart failure than BNP.
Value of N‐terminal pro brain natriuretic peptide in the elderly: data from the prospective Copenhagen Hospital Heart Failure study (CHHF)
Authors: Nielsen Olav Wendelboe , Kirk Vibeke , Bay Morten , Boesgaard Søren , Nielsen Henrik
Published: February 2004

We describe the value of Nt‐proBNP in relation to cardiac normality and risk of major adverse cardiac events (MACE) in consecutive hospitalised patients below and above 75 years of age. Method: During a 10 month period 2224 consecutive patients, admitted to all departments in a general city hospital, had a full cardiac examination and were prospectively followed for 1 year. We identified a normal group (without obvious heart disease) and a group with MACE (significant heart disease at admission or a cardiac event within the following 90 days). NT‐proBNP measurements were done using an ELISA—a two‐step sandwich assay with streptavidin coated microtitre plates. Results: The age dependent 90th percentiles of Nt‐proBNP in the normal group were approximately 3 times higher than values reported in previous community studies. Elderly patients had 3‐fold higher absolute cut off values than did patients under the age of 75 years. One‐hundred‐and‐sixteen patients had a MACE, and areas under the receiver operating curve (ROC) to predict a MACE were 0.83 (from 40 to 59 years), 0.82 (60 to 74) and 0.79 (from 75 years). In younger patients, the upper limit of Nt‐proBNP in normal patients was similar to the value, which defined the top quintile of risk. In patients aged greater than 75 years the predictive cut point included more than 40% of the population.

Conclusion:

Nt‐proBNP was useful at all ages but specificity was slightly lower in the elderly. Cut off values in hospitalised cardiac normal patients are approximately three times higher than community derived values.
Use of NT‐proBNP in routine testing and comparison to BNP
Authors: Pfister R. , Scholz M. , Wielckens K. , Erdmann E. , Schneider C.A.
Published: February 2004

Objectives:

B‐type natriuretic peptide (BNP) is a strong diagnostic predictor of left‐ventricular (LV)‐dysfunction. Recently, the aminoterminal portion of pro‐BNP (NT‐proBNP) has been introduced, which could be even more sensitive because of its longer half‐life. The aim of this study was to evaluate the new marker NT‐proBNP within a large, heterogeneous population of patients with suspected cardiovascular disease at risk of cardiovascular dysfunction and to compare it with the established diagnostic parameter BNP.

Subjects and methods:

NT‐proBNP and BNP were measured in 339 hospitalised patients undergoing diagnostic angiography (median age 66 years, 244 male vs. 95 female).

Results:

Median values of NT‐proBNP increased with worsening LV‐dysfunction and higher NYHA class. The area under the receiver operator characteristics curve (AUC) of NT‐proBNP for detecting severe systolic dysfunction or for detecting any systolic LV‐dysfunction was 0.83 and 0.77, respectively. The latter improved (AUC=0.81) when patients with clinically relevant heart disease like valvular dysfunction were included, independent of the haemodynamic values. Compared to BNP, NT‐proBNP tended to be more accurate in identifying lesser degrees of LV‐dysfunction.

Conclusions:

Even after optimisation of target criteria, there was still a substantial overlap of NT‐proBNP values between patients with and without relevant heart disease. Therefore, NT‐proBNP is not suitable as a screening test for LV‐dysfunction in the community. Nevertheless, because of its good negative predictive value, NT‐proBNP could be an easy and effective tool to rule out severe systolic LV‐dysfunction in high risk patients. No clinically significant advantage of BNP testing could be found.
N‐terminal proBNP and mortality in hospitalised patients with heart failure and preserved vs. reduced systolic function: data from the prospective Copenhagen Hospital Heart Failure Study (CHHF)
Authors: Kirk V. , Bay M. , Parner J. , Krogsgaard K. , Herzog T.M. , Boesgaard S. , Hassager C. , Nielsen O.W. , Aldershvile J. , Nielsen H.
Published: February 2004

Preserved systolic function among heart failure patients is a common finding, a fact that has only recently been fully appreciated. The aim of the present study was to examine the value of NT‐proBNP to predict mortality in relation to established risk factors among consecutively hospitalised heart failure patients and secondly to characterise patients in relation to preserved and reduced systolic function.

Material:

At the time of admission 2230 consecutively hospitalised patients had their cardiac status evaluated through determinations of NT‐proBNP, echocardiography, clinical examination and medical history. Follow‐up was performed 1 year later in all patients.

Results:

161 patients fulfilled strict diagnostic criteria for heart failure (HF). In this subgroup of patients 1‐year mortality was approximately 30% and significantly higher as compared to the remaining non‐heart failure population (approx. 16%). Using univariate analysis left ventricular ejection fraction (LVEF), New York Heart Association classification (NYHA) and plasma levels of NT‐proBNP all predicted mortality independently. However, regardless of systolic function, age and NYHA class, risk‐stratification was provided by measurements of NT‐proBNP. Having measured plasma levels of NT‐proBNP, LVEF did not provide any additional prognostic information on mortality among heart failure patients (multivariate analysis).

Conclusion:

The results show that independent of LVEF, measurements of NT‐proBNP add additional prognostic information. It is concluded that NT‐proBNP is a strong predictor of 1‐year mortality in consecutively hospitalised patients with heart failure with preserved as well as reduced systolic function.
NT‐proBNP in heart failure: therapy decisions and monitoring
Authors: Richards Mark , Troughton Richard W.
Published: February 2004

With increasing cardiac dysfunction, a complex neurohormonal response results in increasing circulating levels of an array of plasma hormones. Increments in plasma levels of atrial natriuretic peptide (ANP) and B‐type natriuretic peptide (BNP) and their amino‐terminal congeners are more closely related to cardiac structure and function and to cardiovascular prognosis than changes in other plasma neurohormones. Reports suggest that changes in plasma BNP levels in the course of treatment of acutely decompensated heart failure provide a more powerful prognostic indicator of the likelihood of survival or recurrent decompensation than symptomatic assessment. This observation requires a randomised controlled trial in which changes in peptide levels determine aggression and duration of in‐patient therapy in order to establish whether this indicator can improve results from management of acute in‐patient heart failure. Plasma BNP or NT‐proBNP is a powerful independent predictor of mortality and morbidity in long‐term follow‐up of heart failure cohorts. In addition, it appears likely to be a good predictor of beneficial response to the addition of beta blockade to anti‐heart failure pharmacotherapy. Finally, adjustment of therapy for heart failure according to serial measurements of NT‐proBNP promises to improve outcomes in comparison with adjusting therapy according to unassisted clinical acumen.
NT‐proBNP in unstable coronary artery disease—experiences from the FAST, GUSTO IV and FRISC II trials
Authors: Jernberg Tomas , James Stefan , Lindahl Bertil , Stridsberg Mats , Venge Per , Wallentin Lars
Published: February 2004

Background:

Risk stratification is important in patients with unstable coronary artery disease (CAD), i.e. unstable angina or non‐ST‐elevation myocardial infarction. This article focuses on the emerging role of N‐terminal pro brain natriuretic peptide (NT‐proBNP) and the results from the FAST, GUSTO IV and FRISC II trials.

Methods:

In the FAST study, NT‐proBNP was measured on admission in 755 patients admitted because of symptoms suggestive of unstable CAD. Follow up was performed after 40 months. The GUSTO IV and the FRISC II‐trials included patients with unstable CAD and NT‐proBNP was analyzed in 6806 and 2019 patients, with follow up after 1 and 2 years, respectively.

Results:

In the FAST study, patients in the 2nd, 3rd, and 4th NT‐proBNP quartile had a relative risk of subsequent death of 4.2 (1.6–11.1), 10.7 (4.2–26.8) and 26.6 (10.8–65.5), respectively. In the GUSTO IV trial, increasing quartiles of NT‐proBNP were related to short and long term mortality which at 1 year was; 1.8%, 3.9%, 7.7% and 19.2% (P<0.001), respectively. In multivariable analyses including well‐known predictors of outcome, NT‐proBNP level was independently associated to mortality in all three studies. In the FRISC II trial, the NT‐proBNP level, especially if combined with a marker of inflammation, identified those with the greatest benefit from an early invasive strategy.

Conclusion:

NT‐proBNP is strongly associated with mortality in patients with suspected or confirmed unstable CAD and, combined with a marker of inflammation, seems helpful in identifying those with greatest benefit from an early invasive strategy.
NT‐proBNP and BNP: biomarkers for heart failure management
Authors: Bettencourt Paulo
Published: February 2004

Guidelines for the pharmacological treatment of heart failure (HF) are based on results from large clinical trials demonstrating benefit. State of the art pharmacological management of HF assumes that target doses should be the same as those used in trials. Thus equal doses are recommended for all in practical guidelines, but this strategy might not fit individual needs. NT‐proBNP and BNP emerged as potential biomarkers of clinical interest in HF management. NT‐proBNP and BNP are related to HF severity and to clinical status. NT‐proBNP and BNP are strongly associated with prognosis across the whole spectrum of HF patients. A pilot study has shown that NT‐proBNP‐guided therapy is associated with improved outcome in HF. Although at present there are still few data to make firm recommendations on the use of NT‐proBNP or BNP levels as biomarkers for HF management, future studies will provide further insight on this issue.
NT‐proBNP in severe chronic heart failure: rationale, design and preliminary results of the COPERNICUS NT‐proBNP substudy
Authors: Hartmann Franz , Packer Milton , Coats Andrew J.S. , Fowler Michael B. , Krum Henry , Mohacsi Paul , Rouleau Jean L. , Tendera Michal , Castaigne Alain , Trawinski Jürgen , Amann‐Zalan Ildiko , Hoersch Silke , Katus Hugo A.
Published: February 2004

Background:

Neither profiles nor prognostic value of cardiac N‐terminal proBNP (NT‐proBNP) have been prospectively evaluated in a sufficient number of patients with severe chronic heart failure (CHF) treated with carvedilol or placebo.

Methods:

Baseline and follow‐up plasma concentrations of NT‐proBNP were measured in the European part of the COPERNICUS Trial. This study enrolled patients with an ejection fraction <25% and symptoms of CHF at rest or on minimal exertion, equally randomized to placebo or carvedilol.

Results:

NT‐proBNP concentrations were increased at baseline (mean±S.D.=579±822 pmol/l, median=322.5 pmol/l) with a marked decrease during follow‐up in the carvedilol, but not in the placebo group. One‐year mortality rates were 3.9, 12 and 27.9% in the lower, middle and upper tertiles of NT‐proBNP, respectively. When mortality was calculated separately in the placebo and carvedilol group, rates were 0.8, 6.3 and 19.1% in the carvedilol treated but 6.7, 17.9 and 36.9% in the placebo treated patients.

Conclusions:

NT‐proBNP was a powerful predictor of subsequent all‐cause mortality in patients with severe CHF. This marker should therefore be further evaluated for risk stratification and monitoring of therapy in CHF.
NT‐proBNP and the diagnosis of heart failure: a pooled analysis of three European epidemiological studies
Authors: McDonagh T.A. , Holmer S. , Raymond I. , Luchner A. , Hildebrant P. , Dargie H.J.
Published: February 2004

Many studies have shown that the B‐type natriuretic peptides (BNP and NT‐proBNP) are proven diagnostic markers for heart failure due to left ventricular systolic dysfunction. The manner in which they are to be used is still being unravelled; most single centre studies have chosen the best concentration of the peptide on ROC analysis as their cut‐point resulting in numerous different values for both BNP and NT‐proBNP appearing in the literature. We report a different approach of defining an age and sex corrected abnormal concentration for NT‐proBNP, derived from normal individuals within a large sample of 3051 subjects pooled from three European epidemiology studies and applying that to the entire population to detect HF and LVD. Three thousand and fifty one subjects were studied. Of these 10% (305) had significant LVD and 3.1% (94) had HF. The median concentrations of NT‐proBNP (IQR) in normals, those with LVD and in heart failure subjects were 20 pg/ml (10.30), 117.3 pg/ml (28.145) and 269.6 pg/ml (54.323), P<0.001, respectively. The area under the ROC curve for NT‐proBNP for the detection of ‘heart failure’ was 0.85 and 0.69 for LVD. NT‐proBNP was an independent predictor of the presence of HF on multivariate analysis. An abnormal NT‐proBNP was defined as being >95th centile for normals, age and sex corrected, and diagnosed HF with a sensitivity of 75% and a negative predictive value of 99%. In an additional analysis in a breathless subgroup of our population, in 30% a raised NT‐proBNP concentration could be explained by HF due to LVD, in another 64% the high BNP level was associated with some other structural of functional cardiac abnormality or renal impairment. We were unable to assign a possible cause to the high NT‐proBNP values in 5.9% of this breathless subgroup of the population. An abnormal NT‐proBNP concentration is an accurate diagnostic test both for the exclusion of HF in the population and in ruling out LVD in breathless subjects. An elevated NT‐proBNP merely indicates the presence of ‘cardio‐renal distress’ and should prompt referral for further investigation.
Analytical performance of the N terminal pro B type natriuretic peptide (NT‐proBNP) assay on the Elecsys™ 1010 and 2010 analysers
Authors: Collinson P.O. , Barnes S.C. , Gaze D.C. , Galasko G. , Lahiri A. , Senior R.
Published: February 2004

The Elecsys NT‐proBNP assay is based on two polyclonal antibodies directed at residues 1–21 and 39–50 of the NT‐proBNP molecule. Analytical performance was assessed using NCCLS protocol EP‐5A using three serum pools in a preliminary study then as part of a multicentre evaluation (16 instruments in 8 hospitals). Using pools of 350 pg/l, 8700 pg/l and 13000 pg/l single site within run %CV was 0.7–1.6 (1010) and 1.2–1.5 (2010) and between run CV 5.3–6.7 (1010) and 4.4–5.0 (2010). In the multicentre evaluation within run CV was 1.0–2.5% with total imprecision 1.5–2.5% and between labs imprecision 3.8–4.0%. Functional sensitivity of <50 pg/l and measuring range to 35000 pg/l. There was excellent agreement between instrument platforms, y=0.97x+2.6; r=1.00 (n=215) for Elecsys 2010 (x) vs. Elecsys 1010 (y) and y=1.02x−0.3; r=1.00 (n=99) for Elecsys 2010 (x) vs. E 170 (y). Serum and heparin plasma samples showed good agreement but lower values were seen in EDTA plasma. Samples were stable for 7 days at room temperature; 21 days at 4 °C and for 5 freeze thaw cycles. Samples were obtained from a population of 1205 (671 male, 534 female) apparently healthy individuals screened by echocardiography and symptom questionnaire. There was poor correlation with NT‐proANP (ELISA) (rs 0.33) and modest correlation with BNP (rs 0.89) with NT‐proBNP values approximately 5 times greater than BNP (Biosite Triage). In a subset of 320 with normal ejection fraction (>50%) and no risk factors, NT‐proBNP values increased with age and were higher in women than men.
Generation of Arabidopsis thaliana plants with complex N‐glycans lacking β1,2‐linked xylose and core α1,3‐linked fucose
Authors: Strasser R. , Altmann F. , Mach L. , Glössl J. , Steinkellner H.
Published: February 2004

The plant glycosyltransferases, β1,2‐xylosyltransferase (XylT) and core α1,3‐fucosyltransferase (FucT), are responsible for the transfer of β1,2‐linked xylose and core α1,3‐linked fucose residues to glycoprotein N‐glycans. These glycan epitopes are not present in humans and thus may cause immunological responses, which represent a limitation for the therapeutic use of recombinant mammalian glycoproteins produced in transgenic plants. Here we report the genetic modification of the N‐glycosylation pathway in Arabidopsis thaliana plants. Knockout plants were generated with complete deficiency of XylT and FucT. These plants lack antigenic protein‐bound N‐glycans and instead synthesise predominantly structures with two terminal βN‐acetylglucosamine residues (GlcNAc2Man3GlcNAc2).
Pressure pain thresholds of tender point sites in patients with fibromyalgia and in healthy controls
Authors: Maquet Didier , Croisier Jean‐Louis , Demoulin Christophe , Crielaard Jean‐Michel
Published: February 2004

Pressure pain threshold (PPT) is defined as the minimum force applied which induces pain. This measure has proven to be commonly useful in evaluating tenderness symptom. Our aim was to study the intra‐examiner reproducibility of PPT measurement, define cutoffs in normal groups, and compare these results with patients with fibromyalgia (FM). Fifty healthy females, 50 healthy males, and 20 patients with FM participated in the study. PPTs were assessed for 18 specific tender point sites by a dolorimeter. The intra‐individual coefficient of variation determined by a test—retestPPT measurement procedure with 3‐days interval reached, respectively, 17% and 13% in healthy females and males, versus 24% in patients with FM. PPTs were significantly lower in healthy females than in healthy males (p<0.01). Statistical analysis failed to show any differences between the dominant and nondominant side for both normal groups. PPTs were lower over all examined areas in patients with FM than those obtained in healthy females (p<0.000). Lower cutoff levels were calculated from normal values for all specific tender point sites. On average, 14 tender point sites in patients with FM were under the established lower cutoffs. In conclusion, pressure pain sensitivity was influenced by the anatomical localization of tender point and gender differences. Lowest PPTs were localized in trapezius, occiput, anterior cervical, and second rib. The reduction of total tender point score in patients with FM averaged 60% comparatively with normal values. PPT reproducibility and discrimination between the two groups were optimal for the gluteal and knee sites.
Psychosomatic pain in children: A psychomuscular tension reaction?
Authors: Alfvén R.G.J.
Published: February 2004

Although recurrent psychosomatic pain is a common paediatric condition, our understanding of it is still limited. In this article, the clinical picture is presented and the concept of psychosomatic pain is discussed. Some recent scientific data are presented including a controlled blind study of pain pressure thresholds showing significantly reduced mean values over common pain areas in a group of children with psychosomatic pain. According to another study, these children also have significantly reduced concentrations of the hypothalamic hormone oxytocin and cortisol. With these data as a point of departure, a model for psychosomatic pain reaction is outlined in which stress is assumed to induce muscular tension, in turn triggering the nociceptive process. In this psychosomatic reaction, the hypothalamus is believed to have a central regulatory function.
No analgesic effect of ibuprofen or paracetamol vs placebo for hysterectomies
Authors: Dahl V. , Ernø P.E. , Ræder J.C.
Published: February 2004

The aim of the present study was to evaluate the postoperative opioid‐sparing effect of a pre‐operative nonsteroidal anti‐inflammatory drug (NSAID) (ibuprofen) vs paracetamol in a prospective, double‐blind, placebo‐controlled study. It was also investigated whether the use of ibuprofen or paracetamol would influence the amount of surgical bleeding.

Sixty‐six women scheduled for elective open hysterectomy were randomized into one of three groups. All patients received premeditation (diazepam 10 mg) and test drugs orally 1 h before the start of anaesthesia: Group 1 (n = 23) received 800 mg ibuprofen; Group 2 (n = 22) received 1000 mg paracetamol; and Group 3 (n = 21) received placebo. General anaesthesia was given with thiopentone‐fentanyl‐atracurium induction, and maintained with nitrous oxide‐isoflurane. Postoperatively, the patients were evaluated hourly during the recovery period, and 1 and 4 days after the procedure.

Postoperative pain was measured by visual analogue scale (VAS), verbal pain score and the need of standardized opioid rescue medication. Intra‐operative bleeding was measured, as well as reduction in blood haemoglobin content 24 h and 4 days after the procedure.

No differences were found between the groups in postoperative pain measured by any variable or opioid consumption at any time. The amount of surgical bleeding was equal in the three groups.

Ibuprofen or paracetamol given pre‐operatively to hysterectomy patients do not have a postoperative analgesic or opioid‐sparing effect. Perioperative surgical bleeding is not influenced by these drugs.