Long-Term outcomes of cecostomy tube insertion for patients with bowel dysfunction: A retrospective review.

BACKGROUND: Constipation is common in the pediatric population and in severe forms it can lead to debilitating fecal incontinence which has a significant impact on quality of life. Cecostomy tube insertion is a procedural option for cases refractory to medical management, however there is limited data investigating the long-term success and complication rate. METHODS: A retrospective review was performed evaluating patients at our centre undergoing cecostomy tube (CT) insertion between 2002 and 2018. The primary outcomes of the study were the rate of fecal continence at 1-year, and the incidence of unplanned exchanges prior to annual scheduled exchange. Secondary outcomes include the frequency of anaesthetic requirements and length of hospital stay. Descriptive statistics, t-test, and chi-square analysis was performed where appropriate using SPSS v25. RESULTS: Of 41 patients, the average age at the time of initial insertion was 9.9 years with the average length of stay in hospital being 3.47 days. The most common etiology of bowel dysfunction was spina bifida, which was present in 48.8% (n = 20) of patients. Fecal continence was achieved in 90% (n = 37) of patients at 1 year and the average rate of cecostomy tube exchange was 1.3/year with an average of 3.6 general anaesthetics being required by patients and the average age of no longer requiring one being 14.9 years. DISCUSSION: Analysis of patients undergoing cecostomy tube insertion at our centre has further supported the use of cecostomy tubes as a safe and effective option for management of fecal incontinence refractory to medical management. However, a number of limitations exist in this study including its retrospective design and failure to investigate changes in quality of life using validated questionnaires. Additionally, while our research provides greater insight to practitioners and patients what degree of care and types of complications or issues they may encounter with an indwelling tube over the long-term, our single-cohort design limits any conclusions that could be made regarding optimal management strategies for overflow fecal incontinence through direct comparison with other management strategies. CONCLUSIONS: CT insertion is a safe and effective method for managing fecal incontinence due to constipation in the pediatric population, however, unplanned exchange of tube due to malfunction, mechanical breakage, or dislodgment occurs frequently and may impact quality of life and independence. LEVEL OF EVIDENCE: IV.

Quadrupole interactions: NMR, NQR, and in between from a single viewpoint.

Nuclear spins with quantum numbers >1/2 can interact with a static magnetic field, or a local electric field gradient, to produce quantized energy levels. If the magnetic field interaction dominates, we are doing nuclear magnetic resonance (NMR). If the interaction of the nuclear electric quadrupole with electric field gradients is much stronger, this is nuclear quadrupole resonance (NQR). The two are extremes of a continuum, as the ratio of one interaction to the other changes. In this work, we look at this continuum from a single, unified viewpoint based on a Liouville-space approach: the direct method. This method does not require explicit operators and their commutators, unlike Hamiltonian methods. We derive both the quadrupole-perturbed NMR solution and also the Zeeman-perturbed NQR results. Furthermore, we examine the polarization of these signals, because this is different between pure NMR and pure NQR spectroscopy. Spin 3/2 is the focus here, but the approach is perfectly general and can be applied to any spin. Copyright © 2016 John Wiley & Sons, Ltd.

Evolution of magnetization due to asymmetric dimerization: theoretical considerations and application to aberrant oligomers formed by apoSOD1(2SH).

A set of coupled differential equations is presented describing the evolution of magnetization due to an exchange reaction whereby a pair of identical monomers form an asymmetric dimer. In their most general form the equations describe a three-site exchange process that reduces to two-site exchange under certain limiting conditions that are discussed. An application to the study of sparsely populated, transiently formed sets of aberrant dimers, symmetric and asymmetric, of superoxide dismutase is presented. Fits of concentration dependent CPMG relaxation dispersion profiles provide measures of the dimer dissociation constants and both on- and off-rates. Dissociation constants on the order of 70 mM are extracted from fits of the data, with dimeric populations of ∼2% and lifetimes of ∼6 and ∼2 ms for the symmetric and asymmetric complexes, respectively. This work emphasizes the important role that NMR relaxation experiments can play in characterizing very weak molecular complexes that remain invisible to most biophysical approaches.

Singularities in the lineshape of a second-order perturbed quadrupolar nucleus. The magic-angle spinning case.

For a nucleus with a half-integral spin and a strong quadrupole coupling, the central transition (from magnetic quantum number -1/2 to +1/2) in the spectrum shows a characteristic lineshape. By strong coupling, we mean an interaction strong enough so that second-order perturbation theory is needed, yet still sufficient. The spectrum of a static sample is well-known and the magic-angle-spinning (MAS spectrum) is different, but still can be calculated. The important features of both these spectra are singularities and steps in the lineshape, since these are the main tools in fitting the calculated spectrum to experimental data. A useful tool in this investigation is a plot of the frequency as a function of orientation over the surface of the unit sphere. These plots have maxima, minima and saddle points, and these correspond to the features of the spectrum. We used these plots to define both the positions and derive new formulae for the heights of the features and we now extend this to the magic-angle spinning case. For the first time, we identify the orientations corresponding to the features of the MAS spectra and derive formulae for the heights. We then compare the static and MAS cases and show the relationships between the features in the two spectra.

Singularities in the lineshape of a second-order perturbed quadrupolar nucleus and their use in data fitting.

Even for large quadrupolar interactions, the powder spectrum of the central transition for a half-integral spin is relatively narrow, because it is unperturbed to first order. However, the second-order perturbation is still orientation dependent, so it generates a characteristic lineshape. This lineshape has both finite step discontinuities and singularities where the spectrum is infinite, in theory. The relative positions of these features are well-known and they play an important role in fitting experimental data. However, there has been relatively little discussion of how high the steps are, so we present explicit formulae for these heights. This gives a full characterization of the features in this lineshape which can lead to an analysis of the spectrum without the usual laborious powder average. The transition frequency, as a function of the orientation angles, shows critical points: maxima, minima and saddle points. The maxima and minima correspond to the step discontinuities and the saddle points generate the singularities. Near a maximum, the contours are ellipses, whose dimensions are determined by the second derivatives of the frequency with respect to the polar and azimuthal angles. The density of points is smooth as the contour levels move up and down, but then drops to zero when a maximum is passed, giving a step. The height of the step is determined by the Hessian matrix-the matrix of all partial second derivatives. The points near the poles and the saddle points require a more detailed analysis, but this can still be done analytically. The resulting formulae are then compared to numerical simulations of the lineshape. We expand this calculation to include a relatively simple case where there is chemical shielding anisotropy and use this to fit experimental (139)La spectra of La2O3.

Complete description of the interactions of a quadrupolar nucleus with a radiofrequency field. Implications for data fitting.

We present a theory, with experimental tests, that treats exactly the effect of radiofrequency (RF) fields on quadrupolar nuclei, yet retains the symbolic expressions as much as possible. This provides a mathematical model of these interactions that can be easily connected to state-of-the-art optimization methods, so that chemically-important parameters can be extracted from fits to experimental data. Nuclei with spins >1/2 typically experience a Zeeman interaction with the (possibly anisotropic) local static field, a quadrupole interaction and are manipulated with RF fields. Since RF fields are limited by hardware, they seldom dominate the other interactions of these nuclei and so the spectra show unusual dependence on the pulse width used. The theory is tested with (23)Na NMR nutation spectra of a single crystal of sodium nitrate, in which the RF is comparable with the quadrupole coupling and is not necessarily on resonance with any of the transitions. Both the intensity and phase of all three transitions are followed as a function of flip angle. This provides a more rigorous trial than a powder sample where many of the details are averaged out. The formalism is based on a symbolic approach which encompasses all the published results, yet is easily implemented numerically, since no explicit spin operators or their commutators are needed. The classic perturbation results are also easily derived. There are no restrictions or assumptions on the spin of the nucleus or the relative sizes of the interactions, so the results are completely general, going beyond the standard first-order treatments in the literature.

The garuganin and garugamblin diarylether heptanoids: total synthesis and determination of chiral properties using dynamic NMR.

The synthesis of the garuganin and garugamblin diarylether heptanoids using an intramolecular Ullmann coupling is reported. Alkene stereoisomers, vinylogous ester regioisomers, and ß-diketone congeners are also synthesized. The chiral properties and free energies of activation for racemization of the garuganin and garugamblin diarylether heptanoids and congeners are determined using dynamic NMR methods. A combination of techniques including coalescence measurements, line shape analysis, and selective inversion experiments are used to measure racemization barriers. None of the garuganin or garugamblin diarylether heptanoids are chiral, despite their reported specific rotation values.

Dynamical theory of spin relaxation.

The dynamics of a spin system is usually calculated using the density matrix. However, the usual formulation in terms of the density matrix predicts that the signal will decay to zero, and does not address the issue of individual spin dynamics. Using stochastic calculus, we develop a dynamical theory of spin relaxation, the origins of which lie in the component spin fluctuations. This entails consideration of random pure states for individual protons, and how these pure states are correctly combined when the density matrix is formulated. Both the lattice and the spins are treated quantum mechanically. Such treatment incorporates both the processes of spin-spin and (finite temperature) spin-lattice relaxation. Our results reveal the intimate connections between spin noise and conventional spin relaxation.

Spin-lattice relaxation in aluminum-doped semiconducting 4H and 6H polytypes of silicon carbide.

NMR spin-lattice relaxation efficiency is similar at all carbon and silicon sites in aluminum-doped 4H- and 6H-polytype silicon carbide samples, indicating that the valence band edge (the top of the valence band), where the holes are located in p-doped materials, has similar charge densities at all atomic sites. This is in marked contrast to nitrogen-doped samples of the same polytypes where huge site-specific differences in relaxation efficiency indicate that the conduction band edge (the bottom of the conduction band), where the mobile electrons are located in n-doped materials, has very different charge densities at the different sites. An attempt was made to observe (27)Al NMR signals directly, but they are too broad, due to paramagnetic line broadening, to provide useful information about aluminum doping.

Designing optimal universal pulses using second-order, large-scale, non-linear optimization.

Recently, RF pulse design using first-order and quasi-second-order pulses has been actively investigated. We present a full second-order design method capable of incorporating relaxation, inhomogeneity in B(0) and B(1). Our model is formulated as a generic optimization problem making it easy to incorporate diverse pulse sequence features. To tame the computational cost, we present a method of calculating second derivatives in at most a constant multiple of the first derivative calculation time, this is further accelerated by using symbolic solutions of the Bloch equations. We illustrate the relative merits and performance of quasi-Newton and full second-order optimization with a series of examples, showing that even a pulse already optimized using other methods can be visibly improved. To be useful in CPMG experiments, a universal refocusing pulse should be independent of the delay time and insensitive of the relaxation time and RF inhomogeneity. We design such a pulse and show that, using it, we can obtain reliable R(2) measurements for offsets within ±Î³B(1). Finally, we compare our optimal refocusing pulse with other published refocusing pulses by doing CPMG experiments.

Interconversion study in 1,4-substituted six-membered cyclohexane-type rings. Structure and dynamics of trans-1,4-dibromo-1,4-dicyanocyclohexane.

Cyclohexane is an extremely flexible molecule that oscillates, at room temperature, between two clearly distinct and extreme conformations that cannot be distinguished at room temperature; so much so that the NMR spectrum is a single line that includes all 12 protons be they axial or equatorial. This raises the interesting question as to what happens when there are equal substituents at the 1 and 4 carbon atoms of the ring. Therefore substitution in the 1,4-positions in the cyclohexane ring has been the subject of considerable interest because some form of interconversion between extreme conformations could lead to the existence of a rather unusual behavior. To study this problem, the interconversion in (di- or tetra-1,4)-substituted six-membered cyclohexane-type rings, trans-1,4-dibromo-1,4-dicyanocyclohexane, was found to be a particularly suitable candidate. Although X-ray diffraction studies on the crystalline solid found the molecule to be centrosymmetric, it still shows a significant dipole moment µ in solution, as determined with a procedure that leads to the vapor phase values of µ. Furthermore, the low magnetic field proton NMR spectrum at ambient temperature appears as a single line, a situation that changes with increasing field intensity and different solvents. Both these effects are attributed to dynamics, because small distortions can easily disrupt the exact cancellation of the individual dipoles (which are quite strong) associated with each end of the molecule. The molecule can exist in two forms, with both the bromines in an axial geometry or both in an equatorial position. Interconversion between these forms is observed, as in the parent cyclohexane. The single NMR line observed at low magnetic fields is due to fast exchange and requires that the two forms have roughly equal populations. Spectra obtained at low temperature confirm this, and variable-temperature studies allow measurement of the rates, leading to an enthalpy of activation of 62 kJ mol(-1). More details of the interconversion are provided by some new calculation methods. Even for a relatively small molecule like this, calculation of a full potential energy surface is prohibitive. However, methods are now available to follow the molecule along the reaction coordinate in quite an efficient way. The results of these calculations lead to an extremely detailed picture of chair-chair interconversion in a di- and tetrasubstituted six-membered ring of the cyclohexane family.

Definitive solid-state 185/187Re NMR spectral evidence for and analysis of the origin of high-order quadrupole-induced effects for I=5/2.

Rhenium-185/187 solid-state nuclear magnetic resonance (SSNMR) experiments using NaReO(4) and NH(4)ReO(4) powders provide unambiguous evidence for the existence of high-order quadrupole-induced effects (HOQIE) in SSNMR spectra. Fine structure, not predicted by second-order perturbation theory, has been observed in the (185/187)Re SSNMR spectrum of NaReO(4) at 11.75 T, where the ratio of the Larmor frequency (ν(0)) to the quadrupole frequency (ν(Q)) is ∼2.6. This is the first experimental observation that under static conditions, HOQIE can directly manifest in SSNMR powder patterns as additional fine structure. Using NMR simulation software which includes the quadrupole interaction (QI) exactly, extremely large (185/187)Re nuclear quadrupole coupling constants (C(Q)) are accurately determined. QI parameters are confirmed independently using solid-state (185/187)Re nuclear quadrupole resonance (NQR). We explain the spectral origin of the HOQIE and provide general guidelines that may be used to assess when HOQIE may impact the interpretation of the SSNMR powder pattern of any spin-5/2 nucleus in a large, axially symmetric electric field gradient (EFG). We also quantify the errors incurred when modeling SSNMR spectra for any spin-5/2 nucleus within an axial EFG using second-order perturbation theory. Lastly, we measure rhenium chemical shifts in the solid state for the first time.

Solvent effects on chemical exchange in a push-pull ethylene as studied by NMR and electronic structure calculations.

NMR measurements of chemical exchange in a push-pull ethylene, dissolved in a number of different solvents, are presented. These are complemented by high-level electronic structure calculations, using both gas-phase conditions and those which simulate solvents. The results show that it is essential to include entropy effects in order to understand the observed trends. For instance, the equilibrium state in this case represents the state with lowest Gibbs free energy, as it must, but not the lowest enthalpy. The particular molecule is methyl 3-dimethylamino-2-cyanocrotonate (MDACC). The geometry at the carbon-carbon double bond can be either E or Z with roughly equal populations at ambient temperature. We have measured the equilibrium constant and the rates for the exchange between these states in a number of solvents: methanol, chloroform, acetonitrile, toluene, dichloromethane, acetone, and tetrahydrofuran. Furthermore, the N,N-dimethylamino group attached to the double bond also shows restricted rotation, and this has been measured in both the E and Z conformations. The equilibrium constant and the three rotational barriers provide excellent probes of the solvent effects. Electronic structure calculations with a number of basis sets up to the 6-311++G(2df,2p) level, using both Hartree-Fock and density functional (B3LYP) methods were used to predict the E and Z ground states, and the three transition states. The calculations were done for an isolated molecule and also for solvent models representing toluene, acetone, and ethanol. The E conformation is more stable in solution, is the structure in the crystal, and is also the prediction for the gas phase from the calculations. However, the dependence of the equilibrium constant on temperature shows that the Z conformation actually has lower enthalpy. The stability of the E conformation in solution must be due to entropic effects. Similarly, the solvent effect on the E-Z barrier is primarily due to entropy. The measured enthalpy of activation is similar in all the solvents, but the entropy of activation increases with the solvent polarity. The barrier to rotation of the N,N-dimethylamino group shows a combination of entropy and enthalpy effects. This combination of experiments and theory gives an extraordinarily detailed picture of solvent-solute interactions.

Use of continuous optimization methods to find carbon links in 2D INADEQUATE spectra.

The 2-D INADEQUATE experiment is a useful experiment for determining carbon structures of organic molecules, which is known for having low signal-to-noise ratios. A non-linear optimization method for solving low-signal spectra resulting from this experiment is introduced to compensate. The method relies on the peak locations defined by the INADEQUATE experiment to create boxes around these areas and measure the signal in each. By measuring pairs of these boxes and applying penalty functions that represent a priori information, we are able to quickly and reliably solve spectra with an acquisition time approximately a quarter of that required by traditional methods. Examples are shown using the spectrum of sucrose.

Exact solution of the CPMG pulse sequence with phase variation down the echo train: application to R2 measurements.

An implicit exact algebraic solution of CPMG experiments is presented and applied to fit experiments. Approximate solutions are also employed to explore oscillations and effective decay rates of CPMG experiments. The simplest algebraic approximate solution has illustrated that measured intensities will oscillate in the conventional CPMG experiments and that using even echoes can suppress errors of measurements of R2 due to the imperfection of high-power pulses. To deal with low-power pulses with finite width, we adapt the effective field to calculate oscillations. An optimization model with the effective field approximation and dimensionless variables is proposed to quantify oscillations of measured intensities of CPMG experiments of different phases of the π pulses. We show, as was known using other methods, that repeating one group of four pulses with different phases in CPMG experiments, which we call phase variation, but others call phase alternation or phase cycling, can significantly smooth the dependence of measured intensities on frequency offset in the range of ±½Î³B1. In this paper, a second-order expression with respect to the ratio of frequency offset to π-pulse amplitude is developed to describe the effective R2 of CPMG experiments when using a group phase variation scheme. Experiments demonstrate that (1) the exact calculation of CPMG experiments can remarkably eliminate systematic errors in measured R2s due to the effects of frequency offset, even in the absence of phase variation; (2) CPMG experiments with group phase variation can substantially remove oscillations and effects of the field inhomogeneity; (3) the second-order expression of the effective decay rate with phase variation is able to provide reliable estimates of R2 when offsets are roughly within ±½Î³B1; and, most significantly, (4) the more sophisticated optimization model using an exact solution of the discretized CPMG experiment extends, to ±Î³B1, the range of offsets for which reliable estimates of R2 can be obtained when using the preferred phase variation scheme.

Exact solution to the Bloch equations and application to the Hahn echo.

The exact symbolic solution of the Bloch equations is given in the Lagrange form and illustrated with R2 experiments using a Hahn echo. Two different methods are also applied to approximately solve the Bloch equations, we find that splittings with effective-field interpretations are very substantially better than other approximations by comparing the errors. Estimates of transverse relaxation, R2, from Hahn echos are effected by frequency offset and field inhomogeneity. We use exact solutions of the Bloch equations and simulations to quantify both effects, and find that even in the presence of expected B0 inhomogeneity, off-resonance effects can be removed from R2 measurements, when∥ω∥⩽0.5γB1, by fitting the exact solutions of the Bloch equations. Further, the experiments and simulations show that the fitting models with the exact solutions of the Bloch equations do not depend on the sampling density and delay times.

NMR spectroscopic evidence for the intermediacy of XeF(3)(-) in XeF(2)/F(-) exchange, attempted syntheses and thermochemistry of XeF(3)(-) salts, and theoretical studies of the XeF(3)(-) anion.

The existence of the trifluoroxenate(II) anion, XeF(3)(-), had been postulated in a prior NMR study of the exchange between fluoride ion and XeF(2) in CH(3)CN solution. The enthalpy of activation for this exchange, ΔH(⧧), has now been determined by use of single selective inversion (19)F NMR spectroscopy to be 74.1 ± 5.0 kJ mol(-1) (0.18 M) and 56.9 ± 6.7 kJ mol(-1) (0.36 M) for equimolar amounts of [N(CH(3))(4)][F] and XeF(2) in CH(3)CN solvent. Although the XeF(3)(-) anion has been observed in the gas phase, attempts to prepare the Cs(+) and N(CH(3))(4)(+) salts of XeF(3)(-) have been unsuccessful, and are attributed to the low fluoride ion affinity of XeF(2) and fluoride ion solvation in CH(3)CN solution. The XeF(3)(-) anion would represent the first example of an AX(3)E(3) valence shell electron pair repulsion (VSEPR) arrangement of electron lone pair and bond pair domains. Fluorine-19 exchange between XeF(2) and the F(-) anion has also been probed computationally using coupled-cluster singles and doubles (CCSD) and density functional theory (DFT; PBE1PBE) methods. The energy-minimized geometry of the ground state shows that the F(-) anion is only weakly coordinated to XeF(2) (F(2)Xe---F(-); a distorted Y-shape possessing C(s) symmetry), while the XeF(3)(-) anion exists as a first-order transition state in the fluoride ion exchange mechanism, and is planar and Y-shaped (C(2v) symmetry). The molecular geometry and bonding of the XeF(3)(-) anion has been described and rationalized in terms of electron localization function (ELF) calculations, as well as the VSEPR model of molecular geometry. Quantum-chemical calculations, using the CCSD method and a continuum solvent model for CH(3)CN, accurately reproduced the transition-state enthalpy observed by (19)F NMR spectroscopy, and showed a negative but negligible enthalpy for the formation of the F(2)Xe---F(-) adduct in this medium.

Problems, artifacts and solutions in the INADEQUATE NMR experiment.

The INADEQUATE experiment can provide unequalled, detailed information about the carbon skeleton of an organic molecule. However, it also has the reputation of requiring unreasonable amounts of sample. Modern spectrometers and probes have mitigated this problem, and it is now possible to get good structural data on a few milligrams of a typical organic small molecule. In this paper, we analyze the experiment step by step in some detail, to show how each part of the sequence can both contribute to maximum overall sensitivity and can lead to artifacts. We illustrate these methods on three molecules: 1-octanol, the steroid 17alpha-ethynylestradiol and the isoquinoline alkaloid beta-hydrastine. In particular, we show that not only is the standard experiment powerful, but also a version tuned to small couplings can contribute vital structural information on long-range connectivities. If the delay in the spin echo is long, pairs of carbons with small couplings can create significant double-quantum coherence and show correlations in the spectrum. These are two- and three-bond correlations in a carbon chain or through a heteroatom in the molecule. All these mean that INADEQUATE can play a viable and important role in routine organic structure determination.

Magnetic resonance tensors in uracil: calculation of 13C, 15N, 17O NMR chemical shifts, 17O and 14N electric field gradients and measurement of 13C and 15N chemical shifts.

The experimental (13)C NMR chemical shift components of uracil in the solid state are reported for the first time (to our knowledge), as well as newer data for the (15)N nuclei. These experimental values are supported by extensive calculated data of the (13)C, (15)N and (17)O chemical shielding and (17)O and (14)N electric field gradient (EFG) tensors. In the crystal, uracil forms a number of strong and weak hydrogen bonds, and the effect of these on the (13)C and (15)N chemical shift tensors is studied. This powerful combination of the structural methods and theoretical calculations gives a very detailed view of the strong and weak hydrogen bond formation by this molecule. Good calculated results for the optimized cluster in most cases (except for the EFG values of the (14)N3 and (17)O4 nuclei) certify the accuracy of our optimized coordinates for the hydrogen nuclei. Our reported RMSD values for the calculated chemical shielding and EFG tensors are smaller than those reported previously. In the optimized cluster the 6-311+G** basis set is the optimal one in the chemical shielding and EFG calculations, except for the EFG calculations of the oxygen nuclei, in which the 6-31+G** basis set is the optimal one. The optimal method for the chemical shielding and EFG calculations of the oxygen and nitrogen nuclei is the PW91PW91 method, while for the chemical shielding calculations of the (13)C nuclei the B3LYP method gives the best results.