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.

Nutrition in care homes and home care: recommendations - a summary based on the report approved by the Council of Europe.

Undernutrition in home care and care home settings has been acknowledged as a situation with various causes and significant consequences on both an individual and social level. A review article exposing this problem has been recently published. Consequently, scientific experts and other stakeholders were involved in formulating recommendations to tackle undernutrition and sensitize political authorities. The forum held in Brussels and its proceedings were considered as a baseline to interview stakeholders involved in care homes and home care in order to propose solutions on different levels. A full report including guidelines was sent and accepted by the Council of Europe, and can be used as a basis for implementing strategies on a national and international level. A multidisciplinary approach is important to successfully tackle malnutrition on multiple levels: the patients, the health care workers (medical and non-medical), the public, policy makers and society stakeholders. Awareness for patients and caregivers is important; this can be obtained by information and appropriate training. Care home management and kitchen staff activities can be modified in order to promote nutrition. Policy makers should create legal frameworks to confront malnutrition as being a public health concern. Undernutrition in home care and care home settings is a considerable problem and confrontation involves a multidisciplinary approach.

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.

Nutrition in care homes and home care: how to implement adequate strategies (report of the Brussels Forum (22-23 November 2007)).

BACKGROUND & AIMS: Undernutrition in home care and care home settings is an unrecognized problem with significant consequences. The present work was edited after a forum concerning nutrition in these settings was held in Brussels in order to tackle the problem. METHODS: Various aspects of the question were addressed with the participation of scientific experts. The proceedings of the forum were edited and completed by a review of previously published material. RESULTS: Prevalence of undernutrition in home care and care home settings varies between 15% and 65%. Causes of undernutrition are various: medical, social, environmental, organizational and financial. Lack of alertness of individuals, their relatives and health-care professionals play an important role. Undernutrition enhances the risk of infection, hospitalization, mortality and alter the quality of life. Moreover, undernutrition related-disease is an economic burden in most countries. Nutritional assessment should be part of routine global management. Nutritional support combined with physical training and an improved ambiance during meals is mandatory. Awareness, information and collaboration with all the stakeholders should facilitate implementation of nutritional strategies. CONCLUSIONS: Undernutrition in home care and care home settings is a considerable problem and measures should be taken to prevent and treat it.

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.

On the nature of the lowest triplet excited state of the [Rh 2(1,3-diisocyanopropane)(4)]2+ ion.

The nature of the ground state and the lowest triplet excited state of the [Rh(2)(1,3-diisocyanopropane)(4)](2+) ion have been investigated by the density functional theory. Two locally stable geometrical conformations are found on the potential energy surfaces of both the ground and excited states, corresponding to the eclipsed and twisted conformations, the eclipsed conformation being more stable and having the shorter Rh-Rh bond length. While the Rh-Rh distances of the two conformations differ by approximately 0.4 A, they shorten to the same value upon excitation ( approximately 3.1 A). The excited state originates from the d(z)()()2 (metal antibonding) to p(z)() (ligand-metal bonding) electronic transition. The Mayer Rh-Rh bond order increases from approximately 0.2 to more than 0.8 upon excitation, while the Rh-C(N) bond order shows a slight decrease. A topological bond path between the Rh atoms is found in both the ground and excited states, while the electron localization function (ELF) indicates weak Rh-Rh covalent bonding for the excited state only.

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.

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 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.

On the origin of topological differences between experimental and theoretical crystal charge densities

Topological analysis of experimental and theoretical (molecular and crystal) electron densities of p-nitroaniline and p-amino-p'-nitrobiphenyl reveals considerable discrepancies between experiment and theory for the bond critical points properties. Particularly large differences occur for the positive curvature along the bond path (lambda 3). The differences become somewhat smaller when more extended basis sets and correlation effects are introduced in the theoretical calculations. The effect of the crystal matrix on the properties of bond critical points is evaluated for the p-nitroaniline molecule using the 6-21G** and 6-31G** basis sets. The differences between the isolated molecule and the molecule in the crystal are too small to explain the quantitative disagreement between the theoretical and experimental topologies reported in the literature and found in the current study. For most bonds, the observed changes in the properties of the electron density agree well for both basis sets but some discrepancies are found for changes in lambda 3 for N-H and aromatic C-C bonds. When the theoretical densities are projected into the multipole density functions through refinement of the theoretical structure factors, the topological properties change and differences between theory and experiment are reduced. The main origin of the observed discrepancies is attributed to the nature of the radial functions in the experimental multipole model.

Evaluation of net atomic charges and atomic and molecular electrostatic moments through topological analysis of the experimental charge density

The atoms in molecules (AIM) theory may be used to derive atomic charges, atomic volumes and molecular dipole moments from the charge density. The theory is applied to theoretical periodic Hartree-Fock (PHF), density-functional (DFT) and experimental X-ray densities of p-nitroaniline using the program TOPOND and a newly developed program, TOPXD, for topological analysis of densities described by the Coppens-Hansen multipole formalism. Results show that, like dipole moments derived directly from the multipole refinement, AIM-derived atomic and molecular moments are dependent on the multipole model used. As expected, large differences are found between charges derived from the monopole parameters and those from AIM analysis of the experimental model density. Differences between the k'-restricted multipole model (KRMM) and the unrestricted multipole model (UMM) results are preserved in the AIM analysis. The enhancement of the molecular dipole moment of p-nitroaniline in the solid state is confirmed by both experiment and theory but the experimental dipole moment is in much better agreement with theoretical periodic Hartree-Fock and, especially, periodic DFT (PDFT) data when KRMM is used in the refinement. The AIM analysis allows a rigorous definition of the charges of the atoms in molecules and provides a realistic basis for comparison between molecules and between experiment and theory.

On the photochemical behavior of the [Ru(NH3)4(NO)nicotinamide]3+ cation and the relative stability of light-induced metastable isonitrosyl isomers of Ru complexes.

Low-temperature IR experiments on crystalline samples of trans-[Ru(NH3)4(NO) nicotinamide]3+ salts show a light-induced absorption band typical for MS1 NO linkage isomers upon exposure to 300-500 nm light from a Xe source. The formation of a metastable species is confirmed by DSC measurement on a sample irradiated at low temperature with 457 nm light from an Ar+ laser. The light-induced species decays between 250 and 260 K according to both IR and DSC results. This decay temperature (Td) is somewhat below that observed for other high-Td linkage isomers, even though the NO-stretching frequency of the of [Ru(NH3)4(NO) nicotinamide]3+ ion is above that of the other isomers, demonstrating a lack of precise correlation between the two physical properties. The 90 K crystal structure of trans-[Ru(NH3)4(NO)nicotinamide](SiF6)(NO3).H2O is reported. The geometry from theoretical DFT calculations of the ground-state structure agrees well with the experimental results, except for the orientation of the CONH2 substituent in the pyridine ring, which is rotated by 180 degrees in the crystal due to packing effects. The MS1 and MS2 linkage isomers are found to correspond to local minima on the ground-state potential energy surface, and their geometries and energies are reported.

Instrumentation for photocrystallographic experiments of transient species.

Instrumentation for stroboscopic time-resolved diffraction studies at low temperatures is described. Exciting laser light is delivered to the crystal through an optical fiber. During the diffraction experiment, fluorescence from the sample is focused onto a fiber optic bundle surrounding the laser-light fiber, and monitored by a photodiode. A rotating slotted disk produces a pulsed X-ray beam with pulse frequencies suitable for the study of molecular excited states with lifetimes of 10 micros or longer. Synchronization of the laser-pump/X-ray-probe pulses is achieved through a trigger signal from a photosensor mounted on the rotating disk, or from an X-ray sensitive photodiode inserted in the beamstop. For the study of shorter-lived species the time structure of the synchrotron beam is to be used. Equations are derived for the maximum and average fractional excited-state populations as a function of lifetime, pulse frequency and the fraction of molecules being excited by the laser pulse.

On the errors in molecular dipole moments derived from accurate diffraction data.

The error in the molecular dipole moment as derived from accurate X-ray diffraction data is shown to be origin dependent in the general case. It is independent of the choice of origin if an electroneutrality constraint is introduced, even when additional constraints are applied to the monopole populations. If a constraint is not applied to individual moieties, as is appropriate for multicomponent crystals or crystals containing molecular ions, the geometric center of the entity considered is a suitable choice of origin for the error treatment.

Experimental bilateral lobar lung transplantation and its application in humans.

BACKGROUND: The critical lack of donor organs from people of small size or children has created great difficulties in transplantation for recipients who are of smaller size. Surgical techniques of organ reduction and partial transplantation may to some extent solve the problem of disparity in organ size, be it liver or lung, and lessen the problem of scarcity of paediatric organs. METHODS: In a series of experiments on dogs the surgical technique of pulmonary partition of a large organ from a grown dog followed by transplantation of lobes, either unilaterally or bilaterally, into a young dog was studied. Two series of experiments were performed in two groups of animals; in group 1 transplantation of a single right lobe (n = 6) or single left lobe (n = 6) from a split adult lung was carried out and in group 2 (n = 10) animals received bilateral lobar transplants from a single split adult lung. The animals were sacrificed at fixed intervals (days 8-120 in group 1, days 7-10 in group 2) and the results of the surgical technique were assessed. RESULTS: Healing of lobar bronchial anastomoses was found to be excellent with no histological evidence of dehiscence or ulceration. There was one bronchial anastomotic stenosis and one arterial thrombosis. Morphological and functional adaptation of the lobes in the thorax was found to be excellent in both groups of animals. The technique has been applied in a clinical setting and the first patient with bilateral lobar lung transplantation followed for 30 months is reported. CONCLUSION: Lung partition and subsequent lobar transplantation, either unilaterally or bilaterally, is associated with satisfactory early results in an animal experimental model. Initial clinical experience in one patient has been successful.