Lithium dilution, pulse power analysis, and continuous thermodilution cardiac output measurements compared with bolus thermodilution in anaesthetized ponies.

BACKGROUND: This study compares cardiac output (CO) measurements obtained by lithium dilution (LiDCO), pulse power analysis (PulseCO), and continuous thermodilution (CTD) with bolus thermodilution (BTD) in ponies. METHODS: Eight isoflurane-anaesthetized Shetland ponies received xylazine, ketamine, and midazolam infusions (0.3, 1.2, and 0.018 mg kg(-1) h(-1), respectively). CO was measured with BTD, CTD, LiDCO, and PulseCO. Lithium was injected into the jugular vein and blood was sampled from the facial artery for lithium detection and this artery was also used for PulseCO. Measurements were obtained during four stable haemodynamic conditions in the following order: isoflurane 1% (end-tidal concentration), isoflurane 2%, isoflurane 1%, and isoflurane 1%+dobutamine 5 µg kg(-1) min(-1). RESULTS: The bias (2 sd) was 2.5 (2.1) and 0.5 (2.9) litre min(-1) for LiDCO-BTD and for CTD-BTD comparisons, respectively. The limits of agreement were wider than ±30%; therefore, interchangeability was rejected for both comparisons. A possible error in LiDCO might explain the bias observed because CTD-BTD comparison showed less bias. Changes in PulseCO did not correlate with those of BTD and a weak correlation (r(2)=0.23; P=0.018) and concordance (Pc=0.42) was found between CTD and BTD. CONCLUSIONS: This is the first study to show a large bias for LiDCO-BTD comparison in animals receiving xylazine, ketamine, and midazolam infusions. The trending abilities of neither PulseCO nor CTD were reliable. Further studies are needed to elucidate possible influences of drugs on the accuracy of the LiDCOplus system.

Comparative X-Ray and Neutron Diffraction Study of Bonding Effects in s-Triazine.

X-ray and neutron-diffraction data were combined for study of deviations from spherical symmetry of the atomic charge distributions in the small organic molecule s-triazine. The results indicate that density has migrated from the atomic regions into the bonds and into the nitrogen lone-pair region. Refinement procedures for x-ray data, which do not take these bonding effects into account, give parameters containing small but measurable errors.

Charge distribution in the light-atom mineral kernite.

A charge density analysis of accurate x-ray data for the mineral kernite Na(2)B(4)O(6)(OH)(2). 3H(2)O indicates that the sodium and boron atoms have partial positive charges of 0.4 to 0.5 unit and 0.4 to 0.7 unit, respectively, whereas the oxygen atoms have negative charges of about 0.4 to 0.5 unit. The best agreement with the intensities and with the experimental scale factor is obtained with contracted molecule-optimized atomic orbitals. Difference density maps based on high-order parameters show more density in B-O than in Na-O bonds, thus supporting the covalent nature of the bonds between boron and oxygen atoms.

Electron Population Parameters from Least-Squares Refinement of X-ray Diffraction Data.

A least-squares refinement of x-ray diffraction data has been developed in which the parameters are the populations of atomic orbital products describing the molecular electron density distribution. The procedure is applied to alpha-oxalic acid dihydrate and cyanuric acid. Complementary structural information obtained by neutron diffraction has been used. In the absence of complementary information, the method allows simultaneous determination of structural and charge-density parameters. There is an indication of a migration of charge from the ppi to the psigma orbitals in both molecules.

New Opportunities in Synchrotron X-ray Crystallography.

Several high-intensity synchrotron x-ray sources have been constructed over the past few years in the United States, West Germany, Great Britain, Japan, France, Italy, and the Soviet Union. Crystallographers have begun to use these facilities for experiments that take advantage of the characteristics of synchrotron radiation, namely, a broad distribution of wavelengths, high intensity, low divergence, strong polarization, and a pulsed time structure. In addition to more familiar diffraction experiments on single crystals and powdered samples, new types of crystallographic studies, for example, energy-dispersive and surface diffraction studies, have progressed rapidly with more general accessibility of synchrotron sources. These high-intensity sources allow diffraction experiments to be performed on very small crystals or on large biological molecules, and permit weak magnetic scattering to be detected Anomalous dispersion experiments can exploit he ability to vary the wavelength of the radiation, and the pulsed time structure of the beam makes possible fast time-resolved experiments. Because of the availability of synchrotron x-radiation, these and other kinds of experiments will be in the forefront of crystallographic research for the next several years.

The incommensurate modulation of the 2212 bi-sr-ca-cu-o superconductor.

The incommensurate modulation evident in the diffraction pattern of the superconductor Bi(2)Sr3-xCa(x)Cu(2)O8+y consists of almost sinusoidally varying displacements of up to 0.4A of the Bi and Sr atoms in the a-and c-directions of the unit cell, and of up to 0.3 A of the Cu atoms in the c direction only. Thus, a newly discovered feature of the Bi(2)Sr3-xCaxCu(2)O8+y structure is sizable Cu displacement, which is related to static wave formation in the Cu-O sheets. Reported thermal parameters give evidence that similar distortions occur on cooling of the thallium-containing superconductors.

Anomalous scattering study of the bi distribution in the 2212 superconductor: implications for cu valency.

The distribution of the bismuth atoms over the cation sites in the 2212 Bi-Sr-Ca-Cu-O superconductor has been determined by anomalous scattering synchrotron crystallography. The analysis of reflection pairs measured at wavelengths of 0.9243 and 0.9600 angstrom shows a delocalization of the bismuth atoms over the calcium and strontium sites. The "mixed" plane between the CuO(2) layers contains 6.0(1.4) percent bismuth (where the number in brackets represents the statistical standard deviation derived from the least-squares refinement of the data), and a much smaller amount of strontium than often assumed. The strontium deficiency is charge-compensated by the creation of electron holes in the CuO(2) layer. The result supports the view that neither extra oxygen nor overlap of the bismuth 6p and copper 3d bands is needed to account for the holes, which are an essential feature of the superconductivity mechanism.

Cardiac arrhythmias related to continuous thermodilution cardiac output measurement in an anaesthetized sheep.

A case of cardiac arrhythmias related to continuous thermodilution cardiac output (CCO) is reported. A sheep anaesthetized for experimental purpose was instrumented with a special Swan-Ganz catheter-type to be used for CCO measurements. One hour after starting the CCO monitoring, isolated ventricular extrasystoles were noticed on the electrocardiogram with an increasing frequency. Subsequently bursts of extrasystoles occurred. Atrioventricular dissociation was also observed. The peaks of temperature of the thermal filament were within the normal range and their presence was noticed when arrhythmias appeared. Mean blood pressure and cardiac output did not change during this episode. When the CCO was switched off, no more arrhythmias were observed. The CCO Swan-Ganz by itself did not generate any arrhythmia. The sheep recovered uneventfully. When arrhythmias occur during anaesthesia where CCO is used, a thermal filament induced origin of the arrhythmia must be considered.

Use of botanicals in food supplements. Regulatory scope, scientific risk assessment and claim substantiation. 2005.

BACKGROUND/AIMS: In the European Union, an elaborate legal framework regulates botanical products both under food and medicinal law. The decision as to which legal framework applies to an individual product may differ between the Member States. In the case of botanical food supplements, all food law provisions apply to their manufacturing, composition and marketing, including the new claims legislation. METHODS: Elements from EU and national law, scientific and other publications are brought together to investigate how to clarify the differentiation between the use of botanicals for medicinal and health-promoting purposes on a scientific basis. RESULTS: Guidance on the safety assessment and quality evaluation of botanicals is proposed in light of the different approaches described in the scientific literature with particular attention to the concept of long-term use as an integral part of safety evaluation. Guidance on claims substantiation is also included, taking into consideration the proposed legislation, the concept of long-term experience and grading of evidence. CONCLUSIONS: A model for safety and efficacy assessment of botanical food supplements in the EU is proposed, and should be taken into consideration in the development of legislation and scientific research on botanicals.

Recombinant human erythropoietin in patients with myelodysplastic syndromes.

As anemia is frequently the main problem in myelodysplastic syndromes (MDS), we studied the efficacy of human erythropoietin (rhEpo) in stimulating the erythroid lineage in 14 patients, starting with 40 U/kg three times a week and doubling the dose every 6 weeks until a response was observed. The highest doses administered were 80 (n = 1), 160 (n = 4), 320 (n = 8) and 640 U/kg (n = 1). One patient (refractory anemia with an excess of blasts, RAEB) showed an increase of hemoglobin, white blood cells and platelets with 80 U/kg rhEpo. However, this patient developed acute leukemia while on therapy. Two other patients (RAEB and RAEB in transformation) also transformed to acute leukemia. In the other 11 patients no response was observed. There was no correlation between in vitro culture data and in vivo responsiveness. The treatment was well tolerated and no nonhematological side effects were observed. From this study we conclude that rhEpo, even when given at high doses, has a low response rate in patients with MDS. Further investigation is needed in order to clarify whether rhEpo increases the potential risk of transformation to acute leukemia.

Relativistic analytical wave functions and scattering factors for neutral atoms beyond Kr and for all chemically important ions up to I-.

Relativistic wave functions for elements with Z = 37-54 [Su & Coppens (1998). Acta Cryst. A54, 646-652] have been fitted with a linear combination of Slater-type functions as defined by Bunge, Barrientos & Bunge [At. Data Nucl. Data Tables (1993), 53, 113-162], for use in charge-density analysis and other applications. In addition, numerical relativistic wave functions have been calculated for all chemically relevant ions up to Z = 54, and corresponding analytical expressions have been derived. X-ray scattering factors calculated from the numerical wave functions are parameterized [in the sin(straight theta)/lambda ranges 0.0-2.0, 2.0-4.0 and 4.0-6.0 A(-1)] with six Gaussian functions, using the same method applied previously by Su & Coppens [Acta Cryst. (1997), A53, 749-762].

Critical examination of the radial functions in the Hansen-Coppens multipole model through topological analysis of primary and refined theoretical densities.

A double-zeta (DZ) multipolar model has been applied to theoretical structure factors of four organic molecular crystals as a test of the ability of the multipole model to faithfully retrieve a theoretical charge density. The DZ model leads to significant improvement in the agreement with the theoretical charge density along the covalent bonds and its topological parameters, and eliminates some of the bias introduced by the limited flexibility of the radial functions when a theoretical density is projected into the conventional multipole formalism. The DZ model may be too detailed for analysis of experimental data sets of the accuracy and resolution typically achieved at present, but provides guidance for the type of algorithms to be adapted in future studies.

About the Coulomb potential in crystals.

The Coulomb potential in a crystal is discussed. It is shown that its Fourier series expansion has a singularity for the V(0, 0, 0) component, which is important when comparing different compounds, or when using the Coulomb potential as a probe for reactivity. Methods to calculate this term are discussed. Sum rules for multipolar moments of crystals in terms of structure factors are derived, which are of interest for the comparison of microscopic and macroscopic dielectric properties.

On the mapping of electrostatic properties from the multipole description of the charge density.

A method is presented to calculate the electrostatic potential, the electric field and the electric-field gradient in a crystal from the atomic multipole expansion of the experimental charge density, as described by the Hansen-Coppens formalism [Hansen & Coppens (1978), Acta Cryst. A34, 909-921]. The electrostatic properties are expressed in terms of the positions and the charge-density parameters of the individual atoms. Contributions due to the procrystal charge density and the deformation charge density are compared. The method is illustrated by the calculation of the electrostatic potential maps of fully deuterated benzene and of iron(II) tetraphenylporphyrin.

Density-optimized radial exponents for X-ray charge-density refinement from ab initio crystal calculations.

Structure factors based on periodic density-functional (DFT) calculations on 25 molecular crystals have been used to evaluate trends in refined values of the kappa and kappa' expansion-contraction parameters of the Hansen-Coppens multipole formalism. As found previously and expected physically, the spherical-valence-shell kappa parameters are closely related to the net atomic charges, negative atoms being expanded and vice versa. kappa' parameters, which scale the radial dependence of the non-spherical deformation functions, are remarkably consistent for particular bonding environments. Systematic trends are observed for both carbon and oxygen, but the values obtained for nitrogen show a larger variation. Average values for oxygen and carbon in different bonding environments are tabulated and can be used whenever refinement of experimental data is affected by lack of uniqueness of the charge-density parameter set. Values for nitrogen must be more finely tuned to the specific bonding environment. The relation between atomic charge and kappa offers the possibility of introducing a constraint in the charge-density refinement of very large molecules, for which reduction of the size of the parameter set may be essential.

The Gram-Charlier and multipole expansions in accurate X-ray diffraction studies: can they be distinguished?

The Gram-Charlier temperature factor formalism has been applied to a set of accurate low-temperature data on bis(pyridine)(meso-tetraphenylporphinato)iron(II), and to a theoretical set of static structure factors on the hexaaquairon(II) ion. The refinements are compared with the multipole treatment for atomic asphericity due to chemical bonding. In a treatment of the experimental data in which only the iron atom asphericity is considered, the 'thermal motion' formalism is as efficient as the multipole formalism in accounting for the observations. It is slightly less efficient when applied to the static theoretical data, though model maps based on the two treatments are remarkably similar. A high-order Gram-Charlier refinement of the porphyrin data, followed by a multipole refinement of all data with the Gram-Charlier parameters initially fixed, and later varied, shows that simultaneous refinement of anharmonic and aspherical effects is possible, though the resulting separation may not be accurate. A combined Gram-Charlier multipole refinement on the static data, however, leads to non-significant thermal parameters. It is concluded that the statistical Gram-Charlier formalism is remarkably successful in representing bonding effects in the valence charge density if these are not specifically accounted for in the scattering formalism. Statistical anharmonic thermal motion formalisms should only be used for X-ray data analysis in combination with a formalism accounting for the effect of bonding on the atomic charge density.

The experimental charge-density approach in the evaluation of intermolecular interactions. Application of a new module of the XD programming package to several solids including a pentapeptide.

A new module interfaced to the XD programming package has been used in the evaluation of intermolecular interactions and lattice energies of the crystals of p-nitroaniline, L-asparagine monohydrate and the pentapeptide Boc-Gln-D-Iva-Hyp-Ala-Phol (Boc = butoxycarbonyl, Iva = isovaline = ethylalanine, Phol = phenylalaninol). The electrostatic interactions are evaluated with the atom-centered distributed multipoles from KRMM (kappa'-restricted multipole model) refinements, using the Buckingham expression for non-overlapping charge densities. Results for p-nitroaniline are compared with Hartree-Fock (HF), density functional (DFT) and Moller-Plesset (MP2) supermolecular calculations and with HF and DFT periodic calculations. The HF and DFT methods fail to predict the stability of the p-nitroaniline crystal but the results of the experimental charge-density approach (ECDA) are in good agreement with both MP2 interaction energies and the experimental lattice energy. ECDA results for L-asparagine monohydrate compare well with those from DFT supermolecular and periodic HF calculations. The disorder of the terminal group in the pentapeptide, which persists at the experimental temperature of 20 K, corresponds to an energy difference of only 0.35 kJ mol(-1), which is too small to be reproduced with current methods.

Intraperitoneal administration of recombinant human erythropoietin.

OBJECTIVE: To determine the efficacy and safety of intraperitoneal administration of recombinant human erythropoietin (rHuEPO) in continuous ambulatory peritoneal dialysis (CAPD) patients compared to subcutaneous rHuEPO. DESIGN: Prospective analysis of an open, nonrandomized investigation. SETTING: Outpatient CAPD clinics in two university hospitals. PATIENTS: Nine adult CAPD patients receiving rHuEPO intraperitoneally and 8 patients receiving rHuEPO subcutaneously. INTERVENTION: One hundred units of rHuEPO per kilogram of body weight were administered three times a week for 8 weeks or until the target hematocrit of 35% was reached. Thereafter, dosages of rHuEPO were adjusted for response. Intraperitoneal rHuEPO was administered in 1 L of dialysis solution during the night. MEASUREMENTS: Efficacy was assessed by measuring the increase in hemoglobin. Tolerance was assessed by monitoring side effects. RESULTS: In the first 8 weeks of treatment hemoglobin concentration increased from 64.5 +/- 12.9 g/L to 98.3 +/- 16.1 g/L (p < 0.0005) in the intraperitoneally treated group. In the subcutaneously treated group hemoglobin increased significantly faster (p < 0.05) from 72.5 +/- 4.8 g/L to 119.2 +/- 11.3 g/L (p < 0.0005) in the same period. Antihypertensive medication had to be increased or instituted in most of the patients in both groups. The incidence of peritonitis in the intraperitoneally treated group was not increased when compared to the pretreatment incidence. CONCLUSIONS: Subcutaneously administered rHuEPO is superior to intraperitoneally administered rHuEPO with regard to the required dosages. However, the results of this study show that intraperitoneal administration of rHuEPO might be a convenient and safe alternative when subcutaneous administration is undesirable.

Interaction between the aortic valve leaflets and a Millar dual-micromanometer catheter during recording of the aortic component of the second heart sound in dogs.

The influence of the closure of the aortic valve leaflets on a dual-micromanometer Millar catheter is investigated with respect to the power spectrum of the aortic component (A2) of the second heart sound in dogs. The catheter inserted through the aortic valve is used to simultaneously record A2 in the left ventricle and in the aorta and to study the transmission of A2 up to the body surface. Results indicate that the interaction of the valve leaflets with the Millar dual-micromanometer catheter during the closure and vibration of the aortic valve does not produce a clapping artefact. The main effect is a change in the natural modes of vibration (resonant frequencies) of the aortic valve resulting from a modification of the vibrating structure (combined structure composed of the catheter, the aortic valve and the surrounding blood and tissues) because of the tight mechanical coupling between the aortic valve leaflets and the catheter. In addition, this modification of the natural modes of resonance does not invalidate the estimation of the frequency response of the transfer function between the aortic root and the thoracic recording site, even if the mean gain of the transfer function is affected and the phase slightly increased with frequency. On the contrary, the interaction of the aortic valve leaflets with the catheter seems to slightly increase the spectral contribution (coherence) of the intra-aortic A2 to the thoracic A2.

Acoustic transmission of the aortic component of the second heart sound within the ascending aorta of dogs.

The spectral characteristics of the acoustic transmission of the aortic component of the second heart sound within the ascending aorta was studied using a Millar dual-micromanometer catheter. The tip micromanometer was located close to the aortic valve leaflets while the second micromanometer was located 3 cm above the aortic valve. The frequency response of the transmission properties (amplitude and phase) of the blood and the aortic wall was modelled by an equivalent acoustic transmission system. The signal recorded by the tip micromanometer located near the aortic valve was considered to be the input signal of the equivalent system and the signal recorded by the second micromanometer was used as the output signal. Results of the spectral analysis of the input and output signals show that the acoustic transmissibility of blood in the ascending aorta is high at 20 Hz (the attenuation is negligible). Between 20 and 60 Hz, the transmissibility decreases at a rate of -3 dB per octave while between 60 and 120 Hz it decreases at a rate of -14 dB per octave. Above 120 Hz the transmissibility is low and the resulting attenuation is greater than 20 dB. The phase of the transfer function is shifted by -60 degrees at 20 Hz and decreases at a mean rate of -2.0 degrees Hz-1 between 20 and 100 Hz and -0.75 degrees Hz-1 up to 400 Hz. The phase velocity of the sound transmission is relatively constant (5.5 ms-1) between 40 and 100 Hz and increases up to 9 ms-1 at 300 Hz.