Surgical treatment of cervical spine fractures in ankylosing spondylitis patients: posterior stabilization using intraoperative CT scanner-based navigation.

INTRODUCTION: The authors analyzed a series of ankylosing spondylitis patients with cervical spine fracture undergoing posterior stabilization using spinal navigation based on intraoperative CT imaging. The purpose of this study was to evaluate the accuracy and safety of navigated posterior stabilization and to analyze the adequacy of this method for treatment of fractures in ankylosed cervical spine. METHODS: Prospectively collected clinical data, together with radiological documentation of a series of 8 consecutive patients with 9 cervical spine fracture were included in the analysis. The evaluation of screw insertion accuracy based on postoperative CT imaging, description of instrumentation-related complications and evaluation of morphological and clinical results were the subjects of interest. RESULTS: Of the 66 implants inserted in all cervical levels and in upper thoracic spine, only 3 screws (4.5%) did not meet the criteria of anatomically correct insertion. Neither screw malposition nor any other intraoperative events were complicated by any neural, vascular or visceral injury. Thus we did not find a reason to change implant position intraoperatively or during the postoperative period. The quality of intraoperative CT imaging in our group of patients was sufficient for reliable trajectory planning and implant insertion in all segments, irrespective of the habitus, positioning method and comorbidities. In addition to stabilization of the fracture, the posterior approach also allows reducing preoperative kyphotic position of the cervical spine. In all patients, we achieved a stable situation with complete bone fusion of the anterior part of the spinal column and lateral masses at one year follow-up. CONCLUSION: Spinal navigation based on intraoperative CT imaging has proven to be a reliable and safe method of stabilizing cervical spine with ankylosing spondylitis. The strategy of posterior stabilization seems to be a suitable method providing high primary stability and the conditions for a subsequent high fusion rate.

T2-relaxation time increases in lumbar intervertebral discs after 21d head-down tilt bed-rest.

OBJECTIVES: Spaceflight back pain and intervertebral disc (IVD) herniations cause problems in astronauts. Purpose of this study was to assess changes in T2-relaxation-time through MRI measurements before and after head-down tilt bed-rest, a spaceflight analog. METHODS: 8 men participated in the bed-rest study. Subjects remained in 6° head down tilt bed-rest in two campaigns of 21 days, and received a nutritional intervention (potassium bicarbonate 90 mmol/d) in a cross-over design. MRI measurements were performed 2 days before bed-rest, as well as one and five days after getting up. Image segmentation and data analysis were conducted for the IVDs Th12/L1 to L5/S1. RESULTS: 7 subjects, average age of 27.6 (SD 3.3) years, completed the study. Results showed a significant increase in T2-time in all IVDs (p⟨0.001), more pronounced in the nucleus pulposus than in the annulus fibrosus (p⟨0.001). Oral potassium bicarbonate did not show an effect (p=0.443). Pfirrmann-grade correlated with the T2-time (p⟨0.001). CONCLUSIONS: 6° head-down tilt bed-rest leads to a T2-time increase in lumbar IVDs. Oral potassium bicarbonate supplementation does not have an effect on IVD T2-time.

Terpenols as substituents for the diastereoselective formation of enantiomerically pure triple lithium-bridged helicate type-coordination compounds.

The terpenols l(-)-borneol, (1S2S3S5R)-3-pinanol, (-)-menthol, and (-)-myrtenol are easily available chiral alcohols for the preparation of enantiomerically pure catechol esters -H2. Those ligands are used for the hierarchical assembly of triple lithium-bridged dinuclear titanium(iv) triscatecholate helicates Li[Li3()6Ti2]. In solution, the dimeric species are in a solvent dependent equilibrium with the monomer Li2[()3Ti]. The equilibrium is studied by (1)H NMR. CD spectroscopy indicates that the configuration at the complex units of the enantiomerically pure dimeric α-chiral derivatives Li[Li3()6Ti2] is opposite to the configuration of the monomers Li2[()3Ti]. For the γ-chiral complex Li2[()3Ti] only a de of 25% is observed and in this case no interpretation of the mechanism of stereocontrol is possible.

[Intraoperative CT-based spinal navigation: the initial 295 implants experience]. / Navigace v páterní chirurgii zalozená na intraoperacním CT zobrazení: zkusenost s iniciálními 295 implantáty.

INTRODUCTION: The authors describe the system of spinal navigation based on intraoperative CT imaging and the results of an initial series of patients. MATERIAL AND METHODS: Spinal screws inserted during 50 surgical procedures in the period between November 2012 and October 2013 were evaluated for insertion accuracy, intraoperative complications and the accessibility of the method for the selected spinal level. RESULTS: Out of the total of 295 screws inserted throughout all the spinal levels from C0 to S1, only 4 (1.3%) pedicle screws were found to be incorrectly inserted: a single L5 screw breached the lower cortex of the pedicle, two thoracic pedicular screws penetrated the anterior margin of the vertebral body not exceeding 3 mm of the shaft length, and a single C3 pedicle screw penetrated the upper vertebral body end-plate. None of these complications caused morbidity or required re-operation. Intraoperative CT imaging together with the navigation procedure increased the time of surgery by 30 minutes on average and patient radiation exposure during the initial and accuracy control CT scan was increased. CONCLUSION: Our initial experience has shown that the CT-based computer-assisted spinal navigation system is a precise surgical modality. It enables higher accuracy in spinal screw positioning, resulting in lower surgical morbidity and increased safety for the patient. This benefit should outweigh the longer operation time as well as a higher radiation exposure of the patients.

[Acalculous cholecystitis in hantavirus infections]. / Akalkulöse Cholezystitis bei Hantavirusinfektionen.

HISTORY AND ADMISSION FINDINGS: Three men, aged 32, 56 and 41 years, respectively, were hospitalized within two weeks because of flu-like symptoms, limb pain and abdominal pain. Being in a febrile, impaired general condition, pressure pains in the upper abdomen and flank pains were particularly noteworthy. INVESTIGATIONS: The results of the examinations, indicating acute renal insufficiency, thrombocytopenia and elevated lactate dehydrogenase were typical of a hantavirus infection, and positive serology for the puumala virus confirmed this suspicion. Ultrasonography indicated nephritic changes in all cases. Striking and unusual, however, was the finding of an acalculous cholecystitis. TREATMENT AND COURSE: In one of the three cases, antibiotic therapy with ceftriaxone was performed, in the other two cases symptomatic therapy. The cholecystitis was closely monitored sonographically and healed without complications in all cases. CONCLUSIONS: Hantavirus infections are common in an endemic area such as the Swabian Alb in Southern Germany, but an acalculous cholecystitis was rarely described in such a context. This accumulation is very remarkable, and the knowledge about it can both help to detect complications at an early stage and prevent unnecessary cases of cholecystectomy.

Microwave guiding of electrons on a chip.

We demonstrate the transverse confinement and guiding of a low energy electron beam of several electron volts in a miniaturized linear quadrupole guide. The guiding potential is generated by applying a microwave voltage to electrodes fabricated on a planar substrate, which allows the potential landscape to be precisely shaped on a microscopic scale. We realize transverse trapping frequencies of 100 MHz and guide electrons along a circular section of 37 mm length. A detailed characterization of the guiding properties in terms of potential depth and dynamic stability is given. This new technique of electron guiding promises various applications in guided matter-wave experiments such as electron interferometry.

[Surgical treatment of fracture of the ring of axis - "hangman's fracture"]. / Chirurgické resení fraktury oblouku epistrofeu - "katovské zlomeniny".

PURPOSE OF THE STUDY: To evaluate surgical management of the fracture of the ring of axis (FRA), known as "hangman's fracture", and to discuss adequacy of this treatment. MATERIAL AND METHODS: Between 1994 and 2004, 41 patients with FRA were surgically treated in our hospital. We present a retrospective study of 30 cases treated by anterior cervical fixation and fusion and 11 cases treated by a posterior, CT-guided approach (published recently). Our diagnostic algorithm for evaluation of FRA included plain radiographs for basic diagnosis, detailed CT scan, MRI and finally passive lateral flexion-extension fluoroscopy (performed by physician) to assess stability. We also consider discography in selected cases, allowing further evaluation of discoligamentous injury. Fractures were classified according to Levine. Posterior compressive osteosynthesis according to Judet was performed in 11 patients with Levine type I fractures with fracture fragment distraction > 3 mm. Anterior graft and plate fixation was chosen in 30 patients with type II (25 patients) and type I (5 patients) fractures where C2/3 disc injury was confirmed by MRI or discography. There was no case of facet dislocation in our series (type III). Pain, motion restriction and overall satisfaction with neck status were assessed on a scale 1-5 (1 = best) in patients treated with anterior approach. Self-evaluation questionnaires were administered during follow-up (average, 7.3 years; 24 months to 11 years). RESULTS: Anatomically reduced fracture fusion was achieved in all cases (100%) at one year follow-up. Both autologous tricortical (22) and fibular allografts (8) were used for anterior approach. No perioperative complications occurred and no case was aborted. Average hospital stay in patients with standalone FRA was 6.8 days (3-15). Patients wore Philadelphia collar for 4-6 weeks. One patient died during follow up due to unrelated causes. None of the 29 patients treated with the anterior approach reported severe or very severe pain (grades 4 or 5). The average pain score was 1.28. Three patients with isolated FRAs reported slight subjective restriction of movement (grade 2). The "satisfaction with overall neck status" scale showed an average score of 1.62, never worse than grade 2. DISCUSSION: Despite increasing popularity of anterior surgical approach in the treatment of type II FRA, most authors still recommend conservative treatment. Surgical treatment is consensually recommended in type III fractures only. Type I is treated exclusively conservatively. There is currently no evidence-based data supporting any method of treatment of so called "hangman's fracture". The majority of treating surgeons do not consider the status of the intervertebral disc. Dynamic films, simulating the peak point of injury, are usually not performed. Hence, potentially unstable fractures are overlooked. This also explains the lack of long term follow-up data regarding the radiological status of C2/3 intervertebral disc as well as patients' subjective complaints. CONCLUSIONS: Surgery provides plausible results. Compared to conservative treatment, it can offer significant benefits: 1) immediate, better and stable reposition; 2) high fusion rate; 3) shortening of the treatment period with better quality of life. Contrary to conservative treatment modalities, surgery possesses a potential for further development.

Biochemical and kinetic analysis of the RNase active sites of the integrase/tyrosine family site-specific DNA recombinases.

In this study, we have used multiple strategies to characterize the mechanisms of the type I and type II RNA cleavage activities harbored by the Flp (pronounced here as "flip") site-specific DNA recombinase (Flp-RNase I and II, respectively). Reactions using half-sites pre-bound by step-arrest mutants of Flp agree with a "shared active site" being responsible for the type I reaction (as is the case with normal DNA recombination). In a "pre-cleaved" type I substrate containing a 3'-phosphotyrosyl bond, the Flp-RNase I activity can be elicited by either wild type Flp or by Flp(Y343F). Kinetic analyses of the type I reaction are consistent with the above observations and support the notion that the DNA recombinase and type I RNase active sites are identical. The type II RNase activity is expressed by Flp(Y343F) in a half-site substrate and is unaffected by the catalytic constitution of a Flp monomer present on a partner half-site. Reaction conditions that proscribe the assembly of a DNA bound Flp dimer have no effect on Flp-RNase II. These biochemical results, together with kinetic data, are consistent with the reaction being performed from a "non-shared active site" contained within a single Flp monomer. The Flp-related recombinase Cre, which utilizes a non-shared recombination active site, exhibits the type I RNA cleavage reaction. So far, we have failed to detect the type II RNase activity in Cre. Despite their differences in active site assembly, Cre functionally mimics Flp in being able to provide two functional active sites from a trimer of Cre bound to a three-armed (Y-shaped) substrate.

Dinuclear titanium(IV) complexes from amino acid bridged dicatechol ligands: formation, structure, and conformational analysis.

Amino acid bridged dicatechol ligands 3a-e-H4 form dinuclear double-stranded coordination compounds [(3a-e)2Ti2(OCH3)2]2- with titanium(IV) ions. Due to the directionality of the ligands, the chirality of the strand, and the chiral complex units, up to seven isomers, I-VII, can be obtained for the double-stranded complexes of ligands 3a-e-H4. The composition of the mixture of isomeric compounds in solution is strongly dependent on the conditions of complex formation. Under thermodynamic control, only a few isomers are obtained, one of which is the major component of the mixture. X-ray structure analyses were performed for K2[(3b)2Ti2(OH)2] and K2[(3d)2Ti2(OH)2] (type I), and for the meso complex Na2[(3e)(3e')Ti2(OCH3)2]. A conformational analysis that uses Ramachandrans method revealed that the conformation of the amino acids in the ligand strands can be compared with those found for amino acids in helical peptide structures. The most favored isomer of [(3)2Ti2(OCH3)2]2- appears to be of type I, with the catecholamide unit located at the N terminus of the ligand strand that binds to a lambda-configurated titanium(IV) complex unit and the dihydroxybenzyl group at the C terminus that coordinates to a delta-configurated titanium(IV) complex unit. The lambda configuration at the N terminus induces the conformation of a right-handed helix in the amino acid residue, while the delta configuration induces the less favored left-handed helix.

Base-induced heterochiral dimerization of an oxiranyl carbaldimine: stereoselective synthesis of a highly functionalized aziridine.

[reaction: see text] Treatment of the oxiranyl carbaldimine with base (LDA or LDA/KOtBu) leads in an one-step procedure to the polyfunctionalized aziridine. This highly diastereoselective reaction is explained by a new type of an Aza-Darzens reaction, in which one enantiomer of the starting material is deprotonated to form an oxiranyl anion, which attacks the imine carbon atom of the other enantiomer (mutual kinetic resolution by double diastereofacial selection).

Noncovalent interactions between tetrazole and an N,N'-diethyl-substituted benzamidine.

Amidines have long been known to form strong noncovalent complexes with carboxylates and phosphates. However, their interaction with tetrazoles, which are acidic heterocycles and important bioisosteric replacements for carboxylic acids in medicinal chemistry, has remained unexplored so far. The binding of a tetrazole to an N,N'-diethyl-substituted benzamidine has been studied for the first time by X-ray crystallography, solution NMR methods, and electrospray mass spectrometry. The amidinium group of model complex 3 was found to prefer an E,Z configuration in the crystal. Benzamidinium and tetrazolate groups alternate along an infinite chain of hydrogen bonds and salt bridges between the amidine-NH groups and the two tetrazole-N atoms next to the ring carbon. In solution, a 1:1 complex was evident from Job's method of continuous variation, and an association constant of 4.0 x 10(3) +/- 1.6 x 10(3) M(-)(1) (in CDCl(3)/CD(3)CN, 6:1) could be determined by (1)H NMR dilution experiments. Tetrazolate was not only found to be a weaker ligand than carboxylates but, surprisingly, the binding mode also changed with concentration in neat CDCl(3). At low concentrations, the amidine group in complex 3 adapted an E,E configuration as it does in a related carboxylic acid complex 4. With increasing concentration, the E,Z isomer starts to predominate. A free activation enthalpy DeltaG(298)() of 64 +/- 1 kJ mol(-)(1) for the E,E to E,Z isomerization was determined by line shape analysis at different magnetic fields. Binding strength was further probed in a competition experiment between a bisamidine, a carboxylate, and a tetrazolate by electrospray mass spectrometry.

Synthesis of enantiomerically enriched allenes by (-)-sparteine-mediated lithiation of alkynyl carbamates.

[reaction: see text]. The alpha-deprotonation of alkynyl carbamates 3 with the chiral base (-)-sparteine (4)/n-butyllithium, transmetalation with ClTi(O(i)()Pr)3, and subsequent substitution with an aldehyde results in the formation of enantioenriched 4-hydroxyallenyl carbamates 11. Stereoselection is determined by dynamic resolution of the lithium/(-)-sparteine complexes by selective crystallization.

"Dimers" and "trimers" of tetrahydroindenes and hexahydroazulenes, respectively generated from [2-(1-cycloalkenyl)ethynyl]carbene complexes (M = W, Cr) by cascade cyclization/cycloaddition reactions.

A cascade of cyclization/cycloaddition reactions was triggered by addition of protic oxygen nucleophiles ROH 2 (RO = CH3CO2, PhCO2, PhO) to [2-(1-cyclohexenyl)ethynyl]carbene complexes 1b and 1c (M=W, Cr, respectively), affording highly strained "dimers" 11/11' and "trimers" 12 of the carbene ligand. The first reaction step involved the formation of 1-metalla1,3,5-hexatrienes 7, which readily gave tetrahydroindenes 8 by pi cyclization and extrusion of the metal unit. "Dimers" 11/11' were generated from tetrahydroindenes 8 by a highly exo selective [4+2] cycloaddition of compounds 1b and 1c to afford 1-metalla-1,3,5-hexatriene intermediates 9, and a spontaneous pi cyclization of the latter compounds involving the disengagement of the metal unit. Propenylidene cyclohexenes 13/13' were formed in "ene"-type side reactions to the pi cyclization of 1-metalla-1,3,5-hexatrienes 7, by loss of the metal unit. "Dimers" 11 were transformed into "trimers" 12 by a [4+2] cycloaddition and subsequent pi-cyclization of the resulting 1-metalla-1,3,5-hexatriene system. The course of the reaction was elucidated by means of model reactions with (2-phenylethynyl)carbene complex 14, in which 1-metalla-1,3,5-hexatriene intermediates 16 and 17 were isolated and characterized. Alkynyl benzene derivatives 19 were obtained by an unprecedented ring-expansion of a cyclopentadiene unit of "dimers" 11a and 11c, involving the insertion of a carbene carbon atom of compound 14 into a C=C bond. A reaction cascade leading to "dimers" 24/24' could also be triggered by treatment of compounds 2 with [2-(1-cycloheptenyl)ethynyl]carbene tungsten complex 1d.

Enaminone substitutents attached to cyclopentadienes: 3E/3Z stereochemistry of 1-metalla-1,3,5-hexatriene intermediates (M = Cr, W) as a functional criterion for the formation of cyclopentadienes and six-membered heterocycles, respectively.

Reactions of NH-enaminones 2 with [2-(1-cycloalkenyl)ethynyl]carbene complexes 7 (M=W, Cr) gave tetrahydropentalenes, tetrahydroindenes, and hexahydroazulenes 8a-i, in which the NH-enaminone moiety is attached to the cyclopentadiene unit. The reaction involved formation of (3E)-1-metalla-1,3,5-hexatriene intermediates, which underwent pi cyclization faster than 3E/3Z isomerization. Tungsten complexes 12 and 13 were characterized as reaction intermediates. Compounds 8 are potentially bidentate ligands with respect to coordination both of the cyclopentadienyl and the enaminone moieties.

The configurational stability of an enantioenriched alpha-thiobenzyllithium derivative and the stereochemical course of its electrophilic substitution reactions; synthesis of enantiomerically pure, tertiary benzylic thiols.

The lithium compound (S)-7, formed by deprotonation of the (S)-S-1-phenylethyl thiocarbamate (S)-10, is configurationally stable at -70 degrees C. Even at elevated temperatures it racemizes only very slowly. It represents the first essentially enantiopure alpha-thiocarbanion derivative and can be utilized in asymmetric synthesis. Most electrophiles (except proton acids) add to (S)-7 with complete stereoinversion. Cleavage of the substitution products leads to practically enantiopure, tertiary 1-phenylalkanethiols.

Inhibition of Flp recombinase by the topoisomerase I-targeting drugs, camptothecin and NSC-314622.

Recombinases of the lambda-Int family and type IB topoisomerases act by introducing transient single strand breaks in DNA using chemically identical reaction schemes. Recent structural data have supported the relationship between the two enzyme groups by revealing considerable similarities in the architecture of their catalytic pockets. In this study we show that the Int-type recombinase Flp is inhibited by the two structurally unrelated topoisomerase I-directed anti-cancer drugs, camptothecin (CPT) and NSC-314622. The interaction of these drugs with topoisomerase I is very specific with several single amino acid substitutions conferring drug resistance to the enzyme. Thus, the observed interaction of CPT and NSC-314622 with Flp, which is comparable to their interaction with the cleavage complex formed by topoisomerase I, strongly supports a close mechanistic and evolutionary relationship between the two enzymes. The results suggest that Flp and other Int family recombinases may provide model systems for dissecting the molecular mechanisms of topoisomerase I-directed anti-cancer therapeutic agents.

Highly selective formation of [4+2] and [4+3] cycloadducts of tetrahydroindenes generated in situ from a (1-alkynyl)carbene tungsten complex by the metalla-1,3,5-hexatriene route.

1-Amino-3-ethoxytetrahydro-3aH-indenes 8 can be readily generated together with pentacarbonyl(pyridine)tungsten in a template induced three-component reaction of [(1-cyclohexenyl)ethynyl]carbene tungsten complex 1 with secondary amines 2a-d and pyridine. Even though the compounds 8 are thermally quite unstable and undergo a fast rearrangement to tetrahydro-7aH-indenes 7. they can be trapped by formation of (rather strained) [4+2] cycloadducts 12 with maleimide 11. If 1-amino-3-ethoxytetrahydro-3aH-indenes 8 are generated in the presence of electron-poor alkynes 2a and 2b, they undergo a 1,5-shift to give tetrahydro-7aH-indenes 7, which in turn afford [4+2] cycloadducts 4a-d. Condensation of 1-tungsta-1,3,5-hexatrienes (3E)-5a-d with 1-metalla-1,3-butadienes 14 (M = Cr, W) give [4+3] cycloadducts 15a-e of tetrahydro-7aH-indenes 7 in good yields with high regio- and stereoselectivity.

alpha-Onocerin chloroform hemisolvate.

The triterpenoid natural product alpha-onocerin [8, 14-secogammacera-8(26),14(27)-diene-3,21-diol], determined here as the chloroform hemisolvate, C(30)H(50)O(2).0.5CHCl(3), consists of two independent symmetric trans-decalin C(15) building blocks. Hydrogen bonds between the hydroxyl groups form an infinite two-dimensional network perpendicular to the c axis.