A review of the EXIT (Ex utero Intrapartum Treatment) procedure.

The EXIT (Ex utero Intrapartum Treatment) procedure is done in cases where difficulty is anticipated in neonatal airway establishment at delivery and is done at the time of caesarean section. The partially delivered fetus is maintained on placental circulation while airway is established and this is carried out by a multidisciplinary team. In this paper, we review the indications, the maternal and fetal considerations of the procedure and the results and outcomes. The review highlights the fact that the benefits far outweigh the risks and that the risk of postpartum haemorrhage is more theoretical than real. As technology improves and more anomalies are diagnosed during the antenatal period, the EXIT procedure can be performed with good results after carefully considering the ethical issues. We have performed a MEDLINE search by using the keywords EXIT, CHAOS, fetal surgery, fetal neck masses and ex utero intrapartum treatment. As there are not many large studies, we have also reviewed smaller case series and case reports.

The utility of infrared spectroscopy for quantitative conformational analysis at a single temperature.

The carbonyl stretching vibration of 2-bromocyclohexanone (1) has been measured in a variety of solvents. It is shown that its component intensities are not only dependent on the populations of the axial and equatorial conformers, but are also dependent on the molar absorptivities (epsilon ) which are specific for each conformer in each solvent. In CCl(4), the axial and equatorial conformers have epsilon values of 417 and 818 l mol(-1) x cm(-1), respectively, while in CH(3)CN solution, the values were 664 and 293 l mol(-1) x cm(-1). These results are supported by results of theoretical calculations of frequencies, which gave an intensity of 223.8 kM mol(-1) x(1782 cm(-1)) for the axial and 174.4 kM mol(-1) x (1802 cm(-1)) for the equatorial conformer, indicating that the axial conformer presents a larger molar absorptivity than the equatorial one in the vapor phase. Moreover, the results presented here clearly demonstrate that although infrared spectroscopy at a single temperature can be an important auxiliary technique for conformational analysis, it must not be used to quantify conformational preferences of a molecule if the absorption molar coefficients for each conformer are not known or not amenable to experimental determination.

Thrombin injection for treatment of brachial artery pseudoaneurysm at the site of a hemodialysis fistula: report of two patients.

We report two patients with arteriovenous hemodialysis fistulas that were complicated by brachial artery pseudoaneurysms. Each pseudoaneurysm was percutaneously thrombosed with an injection of thrombin, using techniques to prevent escape of thrombin into the native brachial artery. In one patient, an angioplasty balloon was inflated across the neck of the aneurysm during thrombin injection. In the second patient, thrombin was injected during ultrasound-guided compression of the neck of the pseudoaneurysm. Complete thrombosis of each pseudoaneurysm was achieved within 30 sec. No ischemic or embolic events occurred. This technique may be useful in treating pseudoaneurysms of smaller peripheral arteries.

Post-cholecystectomy haemobilia: enjoying a renaissance in the laparoscopic era?

Trauma to the right hepatic artery during biliary surgery can lead to false aneurysm formation. Subsequent rupture into the biliary system, which may occur after a considerable delay, will then result in major haemobilia. This report details five cases referred to the Royal Melbourne Hospital over a 12 month period, four of which followed initial laparoscopic procedures, and emphasizes important management procedures to prevent and treat this previously rare complication.

Charge calculations in molecular mechanics. IX. A general parameterisation of the scheme for saturated halogen, oxygen and nitrogen compounds.

The CHARGE2 program for the calculation of partial atomic charges has been amended to include bond parameters for a number of organic functional groups, including halogens, nitrogen and oxygen. These minor amendments to the original scheme produce dipole moments for the fluoro and chloro compounds which are in complete agreement with the observed values. The less complete data sets for the bromo and iodo compounds are also well reproduced, and the dipole moments of a variety of mixed halo compounds are now in better agreement with experiment than previously. The calculated dipole moments of the saturated nitrogen and oxygen compounds are now in much better agreement than in the original scheme, thus the revised parameterisation may be employed with confidence to predict the electrostatic energies of these compounds. Furthermore, the revised scheme now gives a precise proportionality between the charge on the proton in a CH group and the 1H chemical shift of the corresponding proton, allowing the general prediction, in principle, of 1H chemical shifts. In addition, attempts to include variable electronegativity in the alpha effect are described for fluoro compounds.

Energy metabolism during damaging contractile activity in isolated skeletal muscle: a 31P-NMR study.

Creatine kinase (CK) release in response to excessive electrically stimulated contractile activity has been studied in isolated rat soleus muscles. The exacerbation of CK release induced by contractile activity was found to be directly related to the length of time for which the muscle was stimulated and indirectly related to the recovery of force following the end of stimulation. 31P-NMR studies were undertaken using a recirculating superfused muscle preparation and demonstrated that muscles subjected to two different stimulation protocols (stimulation for 0.5 s every 2 s in oxygenated medium or for 1.5 s every 2 s in anoxic medium) had similar falls in ATP content and pH despite a substantially greater release of CK from the muscles stimulated under anoxia. However, stimulated muscles under anoxia showed a more rapid fall and reduced recovery of phosphocreatine and a greater sustained elevation of inorganic phosphate than muscles in oxygenated medium. It is concluded that only part of the increased loss of CK from muscles stimulated in anoxic medium can be explained by release from cells which have lost energy supplies and therefore that other mechanisms must exist which allow release of CK and other cytosolic enzymes from muscle cells.

COSMIC(90): an improved molecular mechanics treatment of hydrocarbons and conjugated systems.

Four modifications to the COSMIC molecular mechanics force field are described, which greatly increase both its versatility and the accuracy of calculated conformational energies. The Hill non-bonded van der Waals potential function has been replaced by a two-parameter Morse curve and a new H-H potential, similar to that in MM3, incorporated. Hydrocarbon energies in particular are much improved. A simple iterative Hückel pi-electron molecular orbital calculation allows modelling of conjugated systems. Calculated bond lengths and rotational barriers for a series of conjugated hydrocarbons and nitrogen heterocycles are shown to be as accurate as those determined by the MM2 SCF method. Explicit hydrogen-bonding potentials for H-bond acceptor-donor atom pairs have been included to give better hydrogen bond energies and lengths. The van der Waals radii of protonic hydrogens are reduced to 0.5 A and the energy well depth is increased to 1.0 kcal mol-1. Two new general atom types, N+sp2 and O-sp3, have been introduced which allow a wide variety of charged conjugated systems to be studied. A minimum of parameterisation is required, as the new types are easily included in the Hückel scheme which automatically adjusts bond and torsional parameters according to the defined bond-order relationships.

Hepatic artery pseudoaneurysms in acute pancreatitis.

The authors present a case of multiple intrahepatic pseudoaneurysms complicating acute gallstone pancreatitis, and they review the relevant literature. The complementary roles of ultrasonography, computed tomography and arteriography are illustrated. Although necrotizing vasculitis with resultant aneurysmal changes in peripancreatic vessels is a recognized complication of chronic pancreatitis, similar pseudoaneurysms have rarely been described in association with acute pancreatitis.

Conformational analysis. Part 16. Conformational free energies in substituted piperidines and piperidinium salts.

The conformational free energies (-delta G degree) of a number of 4-substituted piperdines and piperidinium salts have been determined by the J-value method. For the 4-substituted piperdines (R = Me, Phenyl, CO2Et, Br, OH, F) the relative conformer energies are almost identical to those of the analogous cyclohexanes. The methyl and phenyl compounds showed no change in the couplings on protonation, implying no change in the conformer energies. In contrast, in the remaining compounds with polar 4-substituents an almost constant stabilisation of the axial conformer of ca. 0.7 -0.8 kcal mol-1 was observed on protonation. In three cases (R = F, OH and Br) the conformational preference is reversed on protonation and the axial form is favored. The conformer energies of both the free bases and the piperidinium salts can be quantitatively predicted by molecular mechanics calculations using the COSMIC force-field, in which the electrostatic interactions are calculated by a simple Coulombic model with the partial atomic charges in the molecules given by the CHARGE2 routine, and an effective dielectric constant of five. The precise agreement obtained demonstrates conclusively that the electrostatic interactions between the substituents and the protonated nitrogen are the cause of the conformational changes on protonation, and that these can be modelled successfully using existing force-fields.

Charge calculations in molecular mechanics. Part 8. Partial atomic charges from classical calculations.

The CHARGE2 programme, which involves the classical calculation of both the inductive and resonance contributions to the partial atomic charges in molecules is described, and the charges and electrostatic potentials obtained presented for some illustrative examples. In substituted methanes (CH3X, CF3X, CCl3X) the effects of varying the electronegativity of the substituents and the alpha- and beta-substituent contributions are clearly illustrated for a variety of substituent groups X. The problems involved in the inclusion of silicon into this scheme are detailed, together with the methods of overcoming them. The partial atomic charges (sigma and pi contributions) and electrostatic potentials for some silicon oxygen compounds are presented and discussed. The partial atomic charges from CHARGE2 for all the natural amino acids as their N-acetyl, N'-methylamides are given and compared with those obtained from the AMBER and ECEPP/2 force fields. Considerable differences in these figures are observed, with the AMBER charges consistently much larger than those from the other two methods. The CHARGE2 partial atomic charges and electrostatic potentials for the four common nucleic acids, adenine, cytosine, guanine and thymine, are given and compared with those derived from other calculations. Again there is general similarity but also there are considerable differences, with those from the AMBER force field somewhat larger than the other methods.

Molecular modelling of poly(aryl ether ketones). I. Aryl..aryl interactions in crystal structures.

Non-bonded potentials for the aryl..aryl interaction have been derived using crystal structure data of a number of small aromatic molecules. The potentials, based on atom-centered interactions, give an accurate reproduction of the benzene crystal geometry and sublimation energy when used in conjunction with coulombic energies evaluated using point atomic charges. An examination of the charge distribution on benzene suggested values of 0.13e (H) and -0.13e (C) to be suitable. The transferability of the potentials has been shown by prediction of crystal geometries and sublimation energies of other hydrocarbon molecules and, with additional interactions for the oxygen atom included, preliminary polymer crystal structure calculations have been carried out. These demonstrate the validity of the derived parameters by successfully predicting crystallographic unit cell dimensions and ring conformations in the poly(phenylene oxide) and poly(aryl ether ketone) crystals.

Energy dependence of cytosolic enzyme efflux from rat skeletal muscle.

(1) A recirculating isolated superfused skeletal muscle preparation has been developed for the study of rat soleus muscles at physiological temperature using 31P Nuclear Magnetic Resonance (NMR). (2) This system has been used to study intracellular muscle high energy phosphate content and pH during experimental damage to the muscle induced by 2,4-dinitrophenol, deoxycholate and the calcium ionophore, A23187. (3) Results indicate that release of intracellular cytosolic enzymes from damaged skeletal muscle may be induced by phosphocreatine (PCr) and adenosine trisphosphate (ATP) depletion, but under certain circumstances intracellular enzymes can be released from skeletal muscle without any fall in muscle PCr or ATP content.

Charge calculations in molecular mechanics 7: application to polar pi systems incorporating nitro, cyano, amino, C=S and thio substituents.

A previously described method for calculating partial atomic charges in molecules has been applied to a variety of different functional groups with pi electrons. The pi charges have been determined by varying the relevant Hükel coulombic and resonance integrals so as to reproduce the experimental dipole moments of known compounds. These include nitro, cyano, mercapto and thiocarbonyl compounds, anilines and a series of heterocyclic ring compounds involving nitrogen, oxygen and sulphur atoms. The calculated dipole moments are in good agreement with experimental values and are a considerable improvement on other calculated values, while requiring only a fraction of the computational time necessary for more rigorous methods. The resulting pi densities compare favourably with other theoretical (CNDO, MNDO and STO-3G) methods.

A theoretical study of the Si-O bond in disiloxane and related molecules.

A comparison of semi-empirical (MNDO) and ab initio (GAUSSIAN) calculations for disiloxane and related molecules is given. The STO-3G* basis set well produced the observed geometries of disiloxane (less than SiOSi observed 144 degrees, calculated 140 degrees), dimethoxy-dimethylsilane (less than OSiO obsd tetrahedral, calc 102 degrees), methyl silyl ether (less than COSi obsd 121 degrees, calc 118 degrees) and correctly predicted the planar geometry found for cyclotrisiloxane. In contrast, more complex basis sets (3-21G(*), DZP, TZVP) gave much poorer agreement with the observed geometries. Comparison of the STO-3G* and the STO-3G basis sets demonstrates the necessity of including d-orbitals on the silicon. However, the semi-empirical MNDO program gave, despite the absence of d-orbitals, a better approximation to the molecular geometry than the complex ab initio basis sets. Force field parameters have been calculated for kSiOSi, kOSiO, 0.089 and 0.73 mdyneA/rad2, and the SiOSiO torsion which has a V1 potential of -0.68 kcal/mol. In addition, the HSiOH torsion is shown to have a three-fold potential of 0.78 kcal/mol. These are profoundly different from the analogous carbon-oxygen force constants, demonstrating that C-O parameters cannot be transferred to the corresponding Si-O systems.

The gating of nucleotide-sensitive K+ channels in insulin-secreting cells can be modulated by changes in the ratio ATP4-/ADP3- and by nonhydrolyzable derivatives of both ATP and ADP.

The 31P-NMR technique has been used to assess the intracellular ratios and concentrations of mobile ATP and ADP and the intracellular pH in an insulin-secreting cell line, RINm5F. The single-channel current-recording technique has been used to investigate the effects of changes in the concentrations of ATP and ADP on the gating of nucleotide-dependent K+ channels. Adding ATP to the membrane inside closes these channels. However, in the continued presence of ATP adding ADP invariably leads to the reactivation of ATP-inhibited K+ channels, even at ATP4-/ADP3- concentration ratios greater than 7:1. Interactions between ATP4- and ADP3- seem competitive. An increase in the concentration ratio ATP4-/ADP3- consistently evoked a decrease in the open-state probability of K+ channels; conversely, a decrease in ATP4-/ADP3- increased the frequency of K+ channel opening events. Channel gating was also influenced by changes in the absolute concentrations of ATP4- and ADP3-, at constant free concentration ratios. ADP-evoked stimulation of ATP-inhibited channels did not result from phosphorylation of the channel, as ADP-beta-S, a nonhydrolyzable analog of ADP, not only stimulated but enhanced ADP-induced activation of K+ channels, in the presence of ATP. Similarly, ADP was able to activate K+ channels in the presence of two nonhydrolyzable derivatives of ATP, AMP-PNP and beta gamma methylene ATP.

A modification to the COSMIC parameterisation using ab initio constrained potential functions.

The H..H non-bonded potential employed in the current COSMIC force field has been contrasted with H..H potentials used in a number of other force fields. Initial conversion of the variety of functions to a Morse format, achieved using a simple graphical fitting procedure, allowed a direct comparison to be made, showing the COSMIC potential to differ considerably from the other potentials. This difference was reflected in the failure of COSMIC to reproduce ab initio and experimental energies for molecules with significant H..H interactions, with particular reference to the energy curves of benzophenone and diphenyl ether. Considerable improvement in these energies is produced by the use of a Morse function originally based on the H..H potential used in MM3.

Charge calculations in molecular mechanics 6: the calculation of partial atomic charges in nucleic acid bases and the electrostatic contribution to DNA base pairing.

A previously described scheme for the direct calculation of the partial atomic charges in molecules (CHARGE2) is applied to the nucleic acid bases. It is shown that inclusion of the omega-technique for the calculation of HMO derived pi charges is of particular importance for these highly polar systems. The molecular dipole moments obtained for the resulting charges are in very good agreement with the observed values for a variety of substituted purine and pyrimidine bases. The partial atomic charges for cytosine, thymine, guanine and adenine (as the 1-methyl and 9-methyl forms) are given and compared with values calculated by a variety of molecular orbital and empirical schemes. All the schemes reproduce the same general trends, with the possible exception of those calculated by the Del Re method, though the charges given by Kollman are in general somewhat larger than the others. The electrostatic contribution to the Watson-Crick base pair interaction energies are calculated using these partial atomic charges. The electrostatic contributions obtained from the M.O. derived atomic charges are less than half the observed values, as are those obtained by the Gasteiger method. The electrostatic contributions calculated from the CHARGE2 atomic charges and those of Kollman are in reasonable agreement with the observed values. The influence of a distant-dependent dielectric constant is examined, but no clear pattern emerges.