Fluoroscopic imaging: New advances.

Today's orthopedic surgery could not be imagined without intraoperative x-ray-based imaging. This enables surgeons to assess operative interim steps as well as the result before wound closure and finishing the procedure. Although there have been mobile C-arms used for decades, there are recent advances that do not only affect the quality of the imaging itself but also the way, the information is processed and presented. These very exciting developments will change the integration of imaging into the surgical workflows, giving options of augmented reality, reduction of radiation dose, automatized acquisition and analysis of images and low-level guidance in procedures. This paper gives a review of current innovations and possible future trends in fluoroscopic 2D and 3D imaging.

[Evolution and principles of intramedullary locked nailing]. / Entwicklung und Prinzipien der Verriegelungsmarknagelung.

Key factors for successful osteosynthetic fracture stabilization are anatomical fracture reduction, restoration of axis and torsion alignment as well as tissue-preserving operative techniques. In long bone fractures, the use of intramedullary long bridging nailing offers ideal conditions for bone healing, as axial and rotational stability is provided by canal-filling nails and locking screws. In addition, the tissue in the fracture region is protected as the intramedullary nail insertion is distant from the fracture. The indication spectrum for modern intramedullary locked nailing includes diaphyseal fractures of long bones, metaphyseal fractures and reconstructions, as well as treatment of nonunion, osteotomy and arthrodesis of the lower extremities. Continuous improvements in nail design and instrumentation as well as the introduction of anatomical reconstruction nails will optimize the spectrum and effectiveness of intramedullary osteosynthesis even further.

Triphos derivatives and diphosphines as ligands in the ruthenium-catalysed alcohol amination with NH3.

The ruthenium-triphos and diphosphine-catalysed amination of alcohols with ammonia is reported. Various types of triphos derivatives with electron-donating functional group were synthesized and used as ligands in the Ru-catalysed alcohol amination with NH3. The triphos derivatives are effective for the formation of primary amines. On the other hand, if hemilabile diphosphines as tridentate ligands are used, mixtures of secondary-along with primary amines are obtained. It was found that even simple diphosphines can be used as ligands for the selective formation of the secondary amines. The diphosphine system allows a new entry to the Ru-catalysed formation of secondary amines.

5,5'-Diamino-BIPHEP ligands bearing small selector units for non-covalent binding of chiral analytes in solution.

A dynamic axially chiral BIPHEP-ligand with 3,5-dichlorobenzoyl amide selector units for non-covalent binding of phenylalanine derivatives has been developed. Interaction studies in solution were performed with rhodium(i) complexes under exclusion of the metal being involved in binding. (Rax, S(Phe)) and (Sax, S(Phe)) adducts were observed as significantly separated species in NMR spectroscopy.

[Intramedullary nailing vs. locking plate osteosynthesis in proximal humeral fractures: Long-term outcome]. / Marknagel- vs. winkelstabile Plattenosteosynthese bei proximalen Humerusfrakturen: Langzeitergebnisse.

BACKGROUND: For the treatment of proximal humeral fractures two major therapeutic principles can be employed: intramedullary nailing (PHN) or locking plate osteosynthesis. The aim of this study was to evaluate and compare clinical and radiological long-term outcome of proximal humeral fracture stabilization using PHN or angular stable plating. MATERIALS AND METHODS: In a retrospective study between March 2009 and March 2010, we analyzed 72 out of 118 patients with unified proximal humeral fracture who had been treated at least 3 years previously using PHN (44 patients) or angular stable plating (28 patients) in a level 1 trauma center. Functional and radiological outcomes were assessed at least 3 years after trauma using the Constant and Murley score and SF-36 score. RESULTS: According to the Neer classification, there were 31 3-part fractures (PHN: 23; plate: 8) and 41 4-part fractures (PHN: 21; plate: 20), respectively. No clinical symptoms after 3 years were observed in 42 patients, whereas in 30 patients clinical symptoms were evaluated related to pain and/or loss of function. Functional outcome using the Constant and Murley score demonstrated a total score of 73 points (ipsilateral side) vs. 88 points (contralateral side) in all evaluated patients, on average. CONCLUSION: Both PHN and angular stable plating are adequate treatment options for proximal humeral fractures. Both systems require precise preoperative planning and advanced surgical experience. No significant differences in long-term clinical and radiological outcome between implants regarding fracture classification, age of patient, and choice of implant were found.

Fast and precise access to enantiomerization rate constants in dynamic chromatography.

An analytical solution of the unified equation to evaluate elution profiles of interconverting enantiomers in dynamic chromatography is presented. Rate constants k1 and k(-1) and Gibbs activation energies are directly obtained from the chromatographic parameters (retention times tR A and tR A of the interconverting enantiomers, the peak widths at half height wA and wB, and the relative plateau height hp), and the initial amounts A0 and B0 of the enantiomers without any iterative and time consuming computational step. Therefore, this equation is no longer limited to racemic analytes. The analytical solution presented here was validated by comparison with a dataset of 125,000 simulated elution profiles of enantiomerizations. Furthermore, it was found that the recovery rate from a defined dataset is on average 40% higher using the unified equation compared to evaluation methods based on iterative computer simulation. The new equation was applied to determine the enantiomerization rate constant of 1-n-butyl-2-tert-butyldiaziridine by enantioselective gas chromatography. The activation parameters (DeltaH(double dagger) = 112.6 +/- 2.5 kJ/mol and DeltaS(double dagger) = -27 +/- 2 J/(K mol) were obtained from temperature-dependent measurements between 100 degrees C and 140 degrees C in 10K steps.

Unified equation for access to rate constants of first-order reactions in dynamic and on-column reaction chromatography.

A unified equation to evaluate elution profiles of reversible as well as irreversible (pseudo-) first-order reactions in dynamic chromatography and on-column reaction chromatography has been derived. Rate constants k1 and k(-1) and Gibbs activation energies are directly obtained from the chromatographic parameters (retention times tR(A) and tR(B) of the interconverting or reacting species A and B, the peak widths at half-height wA and wB, and the relative plateau height h(p)), the initial amounts A0 and B0 of the reacting species, and the equilibrium constant K(A/B). The calculation of rate constants requires only a few iterative steps without the need of performing a computationally extensive simulation of elution profiles. The unified equation was validated by comparison with a data set of 125,000 simulated elution profiles to confirm the quality of this equation by statistical means and to predict the minimal experimental requirements. Surprisingly, the recovery rate from a defined data set is on average 35% higher using the unified equation compared to the evaluation by iterative computer simulation.

Evaluation and prediction of stereoisomerizations in comprehensive two-dimensional chromatography.

Conformational and configurational changes such as isomerizations, epimerizations, diastereomerizations and, enantiomerizations are important for the investigation of a large variety of processes ranging from protein folding to the stereostability of drugs. Under optimized conditions, these processes lead to an elution profile characterized by a plateau formation between the two interconverting species in chromatographic separations in a certain temperature range. By temperature-dependent measurements and subsequent computer simulation of the experimental chromatograms, the forward and backward rate constants k1 and k(-1), the Gibb's energy DeltaG++, activation enthalpy DeltaH++, and entropy DeltaS++ can be obtained. Due to its high efficiency two-dimensional chromatography is able to resolve the time-dependent distribution of the two species in the second dimension, thereby yielding the precise ratio of stereoisomers. An algorithm for the simulation and evaluation of two-dimensional chromatographic experiments has been developed, based on the theoretical plate model, which allows the determination of rate constants and barriers of isomerization, epimerization, and enantiomerization processes from two-dimensional chromatographic experiments. In the present article a detailed description of the extended theoretical plate model required for the simulation, the methods available, and examples for the evaluation of complex experimental data and the prediction of the separation conditions to observe isomerization, epimerizations, and enantiomerizations in two-dimensional chromatography are given.

The control of the nitrogen inversion in alkyl-substituted diaziridines.

For the first time the nitrogen inversion barriers in 3,3-unsubstituted trans-diaziridines, such as 1,2-di-tert-butyldiaziridine (1) and 1,2-di-n-butyldiaziridine (2) were determined. Enantioselective stopped-flow multidimensional gas chromatography was used to investigate the enantiomerization barrier of 1 between 126.2 and 171.0 degrees C (DeltaG ++ gas (150.7 degrees C) = 135.8+/-0.2 kJ mol(-1), DeltaH++ gas = 116.1+/-2.5 kJ mol(-1), DeltaS ++ gas == -46+/-2 J K(-1) mol(-1)). The separation of the enantiomers has been achieved in presence of the chiral stationary phase (CSP) Chirasil-beta-Dex with a high separation factor (alpha = 1.44 at 80 degrees C). In a complementary approach, the enantiomerization barriers of 1,2-di-tert-butyldiaziridine (1), 1,2-di-n-butyldiaziridine (2), 1-n-butyl-3,3-dimethyldiaziridine (3), and 1,2,3,3-tetramethyldiaziridine (4) were determined for comparison by enantioselective dynamic chromatography (DGC) and computer simulation of the dynamic elution profiles. The enantiomerization barrier of 2 was shown to be the highest among the nonsterically hindered diaziridines studied so far, whereas 1 exhibited the highest value found for strained nitrogen-containing rings, that is, aziridines, diaziridines and oxaziridines.

[Surgical therapy of advanced gallbladder carcinoma]. / Die chirurgische Therapie des fortgeschrittenen Gallenblasen--Karzinoms.

The use of surgery for the treatment of advanced gall bladder cancer is controversially discussed. This retrospective study included 204 patients who were subjected to surgery due to advanced gall bladder cancer at the Klinikum Grosshadern. Mean survival time of all patients was 4.5 months. Advancement of the tumor stage resulted in a decreased percentage of possible R0 resections (T3 n = 48, R0 31%, T4 n = 87, R0 13%). Nonetheless, R0 resections of T3 tumors significantly increased the survival rate compared to R1 and R2 resections (mean survival 20.2 vs. 4.5 months). R0 resections of T4 tumors also significantly attenuated the survival rate (18.1 vs. 2.4 months compared to R1 and R2 resections). Thus, diagnostic procedures have to focus on identifying patients with possible R0 resections and perform extensive resections on those patients.

Determination of the enantiomerization barrier of thalidomide by dynamic capillary electrokinetic chromatography.

Enantioselective chromatographic methods, representing the most commonly used techniques for the determination of enantiomeric ratios, can also be used for the evaluation of stereochemical integrity. In the present study, dynamic capillary electrokinetic chromatography (DEKC) was employed to determine the enantiomerization barrier of thalidomide. In the presence of the chiral mobile phase additive carboxymethyl-beta-cyclodextrin, the interconverting enantiomers of thalidomide produced characteristic elution profiles exhibiting plateaus and/or peak broadening between 25 and 55 degrees C at pH 8. To obtain the enantiomerization barrier of thalidomide from experimental data, the fast and efficient simulation program ChromWin was used to simulate the experimental interconversion profiles and to obtain the apparent rate constants k1app(T). Additionally, these values were compared with the novel approximation function for the direct calculation of enantiomerization barriers from chromatographic parameters of elution profiles. From the rate constants k1app(T) of temperature-dependent measurements the kinetic activation parameters deltaG(T)#,deltaH#, and deltaS# of the enantiomerization of thalidomide were obtained. At 25 degrees C, the enantiomerization barrier deltaG# was determined to be 102 +/- 1 kJ/mol at pH 8 in the dynamic electrokinetic chromatographic experiment.

Determination of the cis-trans isomerization barrier of several L-peptidyl-L-proline dipeptides by dynamic capillary electrophoresis and computer simulation.

Dynamic capillary electrophoresis (DCE) and computer simulation of the elution profiles with the theoretical plate and the stochastic model has been applied to determine the isomerization barriers of the three dipeptides L-alanyl-L-proline, L-leucyl-L-proline, and L-phenylalanyl-L-proline. The separation of the rotational cis-trans isomers has been performed in an aqueous 70 mM borate buffer at pH 9.5. Interconversion profiles featuring plateau formation and peak broadening were observed. To determine the rate constants k1 and k(-1) of the cis-trans isomerization in dynamic capillary electrophoresis, equations have been derived for the theoretical plate model and stochastic model. The electropherograms were simulated with the ChromWin software which uses the experimental data plateau height h(plateau), peak width at half height Wh, the total migration times of the cis-trans isomers tR and the electroosmotic break-through time t0 as well as the peak ratio [cis]/[trans]. From temperature-dependent measurements, the rate constants k1 and k(-1) and the kinetic activation parameters deltaG#, deltaH# and deltaS# of the cis-trans isomerization of the three dipeptides were obtained.

Time-resolved cryogenic modulation reveals isomer interconversion profiles in dynamic chromatography.

The dynamic chromatographic study of interconversion of E and Z forms of oximes has been investigated by using a novel cryogenic modulation method in a two-dimensional gas chromatographic array. The primary column is a conventional capillary GC column on which the molecular interconversion proceeds. In this case, the molecular dynamical process leads to a peak profile describing the kinetics and thermodynamics of the interconverting molecules during its chromatographic elution. Thus an interconversion region intercedes the elution of the individual stereoisomers of the reaction. Since the molecules are isomers, classical molecular identification methods such as gas chromatography-mass spectrometry are unable to study the individual instantaneous amounts of each of the compounds. Hence the infinitesimal profiles of interconversion along the entire column have never been experimentally observed; rather the total profile is normally subjected to mathematical modelling studies in order to match experiment with theory, and to gain the kinetic parameters of the process. In the present study, an instantaneous ratio of the individual isomers can be found during the chromatographic elution by direct measurement. This is achieved by using a cryogenic zone focussing process, with rapid longitudinal modulation of a cold trap and continual pulsing of collected zones into a fast-analysis high-resolution capillary column on which isomer interconversion is minimized. The data can be displayed as a two-dimensional contour plot to demonstrate the individual isomer profiles. The two-dimensional analysis also allows easy measurement of the peak ratios of the two isomers which is an indicator of the extent of interconversion that has taken place. Two model systems, acetaldoxime and butyraldoxime, were chosen to illustrate the use of the cryogenic modulation procedure. It is anticipated that the procedure could be applied to other molecules which exhibit gas-phase isomerizations or reactions.

Determination of enantiomerization barriers by dynamic and stopped-flow chromatographic methods.

In recent years, dynamic chromatography and stopped-flow chromatographic techniques have become versatile tools for the determination of enantiomerization and isomerization barriers. Increasing demands for the stereochemical safety of chiral drugs contributed to the rapid development of new techniques. New computer-aided evaluation systems allow the on-line determination of interconversion barriers from the experimental chromatograms. Both dynamic chromatography and stopped-flow chromatography have been applied to the entire range of chromatographic methods (GC, SFC, HPLC, CE).

Determination of interconversion barriers by dynamic gas chromatography: epimerization of chalcogran.

The four stereoisomers of chalcogran 1 ((2RS,SRS)-2-ethyl-1,6-di-oxaspiro[4.4]nonane), the principal component of the aggregation pheromone of the bark beetle pityogenes chalcographus, are prone to interconversion at the spiro center (C5). During diastereo- and enantioselective dynamic gas chromatography (DGC), epimerization of 1 gives rise to two independent interconversion peak profiles, each featuring a plateau between the peaks of the interconverting epimers. To determine the rate constants of epimerization by dynamic gas chromatography (DGC), equations to simulate the complex elution profiles were derived, using the theoretical plate model and the stochastic model of the chromatographic process. The Eyring activation parameters of the experimental interconversion profiles, between 70 and 120 C in the presence of the chiral stationary phase (CSP) Chirasil-beta-Dex, were then determined by computer-aided simulation with the aid of the new program Chrom-Win: (2R,5R)-1: deltaG(++) (298.15 K) = 108.0 +/-0.5 kJ mol(-1), deltaH(++) = 47.1+/-0.2 kJ mol(-1), deltaS(++) = -204+/-6 JK(-1) mol(-1): (2R,5S)-1: deltaG(++) (298.15 K) = 108.5+/-0.5 kJ mol(-1), deltaH(++) = 45.8+/-0.2 kJ mol(-1), deltaS(++) = -210 +/-6 J K mol(-1); (2S,5S)-1: deltaG(++) (298.15 K)= 108.1+/-0.5 kJ mol(-1), deltaH(++) = 49.3+/-0.3 kJ mol(-1), deltaS(++) = -197+/-8 J K(-1) mol(-1); (2S,5R)-1: deltaG(++) (298.15 K)=108.6+/-0.5 kJ mol(-1), deltaH(++) = 48.0+/-0.3 kJ mol(-1), deltaS(++) = -203+/-8 J K(-1) mol(-1). The thermodynamic Gibbs free energy of the E/Z equilibrium of the epimers was determined by the stopped-flow multidimensional gas chromatographic technique: deltaG(E/Z) (298.15 K)= -0.5 kJ mol(-1), deltaH(E/Z) = 1.4 kJ mol(-1) and deltaS(E/Z) = 6.3 J K(-1) mol(-1). An interconversion pathway proceeding through ring-opening and formation of a zwitterion and an enol ether/alcohol intermediate of 1 is proposed.

Approximation function for the direct calculation of rate constants and Gibbs activation energies of enantiomerization of racemic mixtures from chromatographic parameters in dynamic chromatography.

An approximation function for enantioselective dynamic chromatography of racemic mixtures of interconverting enantiomers has been derived that allows the direct calculation of enantiomerization rate constants (k1 and k(-1)) and Gibbs activation energies of enantiomerization, deltaG++ , from chromatographic parameters, i.e., retention times of the enantiomers A and B ((t(A)R and t(B)R), peak widths at half height (WA and wB) and the relative plateau height (hplateau), without computer simulation. The reaction rate constants of enantiomerization, k(-1), obtained with this approximation function, have been validated by comparison with a simulated dataset of 15,625 chromatograms. The mean, standard deviation and confidence interval show a high correlation between the approximated and simulated rate constants. The average deviation from the Gibbs activation enthalpy of enantiomerization, deltaG++, has been estimated to be as small as about +/- 0.11 RT.

ChromWin--a computer program for the determination of enantiomerization barriers in dynamic chromatography.

The software program ChromWin simulates interconversion profiles in dynamic chromatography (rearrangements, isomerizations, epimerizations, diastereomerizations and, notably, enanatiomerizations) on a personal computer in a user-friendly environment. ChromWin is especially suited for systems involving large plate numbers, e.g. gas chromatography (GC) and capillary electrophoresis (CE, CEC, MEKC), and first or pseudo-first order reactions. ChromWin (1) simulates the elution profiles of interconverting enantiomers by different models and yields the rate constant, (2) allows automation of the 'find enantiomerization barrier' function, (3) helps to optimise separation parameters by visualization of the separation process and (4) provides other useful tools for chromatography. In addition to the theoretical plate and the stochastic model a modified and improved stochastic model has been developed and implemented in the program.

Determination of the enantiomerization barrier of oxazepam by dynamic micellar electrokinetic chromatography--comparison of experiment and simulation with ChromWin 99.

The pH-dependent and temperature-controlled enantiomerization of oxazepam has been studied by dynamic micellar electrokinetic chromatography in an aqueous buffer system with sodium cholate as the chiral surfactant. Experimental interconversion profiles featuring plateau formation were simulated by the new program ChromWin 99. Peak form analysis yielded rate constants and kinetic activation parameters of the enantiomerization of oxazepam between 5 degrees C and 25 degrees C.

Enantioselective stopped-flow multidimensional gas chromatography. Determination of the inversion barrier of 1-chloro-2,2-dimethylaziridine.

Enantioselective stopped-flow multidimensional gas chromatography (stopped-flow MDGC) is a fast and simple technique to determine enantiomerization (inversion) barriers in the gas phase in a range of delta G#gas(T)=70-200 kJ mol(-1). After complete gas-chromatographic separation of the enantiomers in the first column, gas phase enantiomerization of the heart-cut fraction of one single enantiomer is performed in the second (reactor) column at increased temperature and afterwards this fraction is separated into the enantiomers in the third column. From the observed de novo enantiomeric peak areas a(j), the enantiomerization time t and the enantiomerization temperature T, the enantiomerization (inversion) barrier delta G#gas(T) is determined and from temperature-dependent experiments, the activation enthalpy delta H#gas and the activation entropy delta S#gas are obtained. Enantiomerization studies on chiral 1-chloro-2,2-dimethylaziridine by stopped-flow MDGC yielded activation parameters of nitrogen inversion in the gas phase, i.e., delta G#gas(353 K)=110.5+/-0.5 kJ mol(-1), delta H#gas=71.0+/-3.8 kJ mol(-1) and delta S#gas=-109+/-11 J mol(-1) K(-1). By the complementary method of dynamic gas chromatography (GC), the apparent enantiomerization (inversion) barrier of 1-chloro-2,2-dimethylaziridine in the gas-liquid biphase system was found delta G#app(353 K)=108 kJ mol(-1). The values obtained by stopped-flow MDGC in the gas phase were used to calculate the activation parameters of nitrogen inversion of 1-chloro-2,2-dimethylaziridine in the liquid phase in the presence of the chiral selector Chirasil-nickel(II), i.e.. deltaG#liq(353 K)=106.0+/-0.4 kJ mol(-1), delta H#liq=68.3+/-1.4 kJ mol(-1) and deltaS#liq=-106+/-3.0 J mol(-1) K(-1).