Structural parameters effect on the electrical and electroluminescence properties of silicon nanocrystals/SiO2 superlattices.

The effect of the oxide barrier thickness (tSiO2) reduction and the Si excess ([Si]exc) increase on the electrical and electroluminescence (EL) properties of Si-rich oxynitride (SRON)/SiO2 superlattices (SLs) is investigated. The active layers of the metal-oxide-semiconductor devices were fabricated by alternated deposition of SRON and SiO2 layers on top of a Si substrate. The precipitation of the Si excess and thus formation of Si nanocrystals (NCs) within the SRON layers was achieved after an annealing treatment at 1150 °C. A structural characterization revealed a high crystalline quality of the SLs for all devices, and the evaluated NC crystalline size is in agreement with a good deposition and annealing control. We found a dramatic conductivity enhancement when the Si content is increased or the SiO2 barrier thickness is decreased, due to a larger interaction of the carrier wavefunctions from adjacent layers. EL recombination dynamics were studied, revealing radiative recombination decay times of the order of tens of microseconds. Lower lifetimes were found at higher [Si]exc, attributed to exciton confinement delocalization, whereas intermediate barrier thicknesses present the slowest decay. The electrical-to-light conversion efficiency increases monotonously at thicker barriers and smaller Si contents. We ascribe these effects mainly to free carriers, which enhance carrier transport through the SLs while strongly quenching light emission. Finally, the combination of the different results led us to conclude that tSiO2 âˆ¼ 2 nm and [Si]exc from 12 to 15 at% are the ideal structure parameters for a balanced electro-optical response of Si NC-based SLs.

Clinical and pathological nodal staging score for urothelial carcinoma of the bladder: an external validation.

PURPOSE: Radical cystectomy (RC) and pelvic lymph node dissection (LND) are standard treatments for muscle-invasive urothelial carcinoma of the bladder. Lymph node staging is a prerequisite for clinical decision-making regarding adjuvant chemotherapy and follow-up regimens. Recently, the clinical and pathological nodal staging scores (cNSS and pNSS) were developed. Prior to RC, cNSS determines the minimum number of lymph nodes required to be dissected; pNSS quantifies the accuracy of negative nodal staging based on pT stage and dissected LNs. cNSS and pNSS have not been externally validated, and their relevance for prediction of cancer-specific mortality (CSM) has not been assessed. METHODS: In this retrospective study of 2,483 RC patients from eight German centers, we externally validated cNSS and pNSS and determined their prediction of CSM. All patients underwent RC and LND. Median follow-up was 44 months. cNSS and pNSS sensitivities were evaluated using the original beta-binominal models. Adjusted proportional hazards models were calculated for pN0 patients to assess the predictive value of cNSS and pNSS for CSM. RESULTS: cNSS and pNSS both pass external validation. Adjusted for other clinical parameters, cNSS can predict outcome after RC. pNSS has no independent impact on prediction of CSM. The retrospective design is the major limitation of the study. CONCLUSIONS: In the present external validation, we confirm the validity of both cNSS and pNSS. cNSS is an independent predictor of CSM, thus rendering it useful as a tool for planning the extent of LND.

Structural Modeling of γ-Secretase Aß n Complex Formation and Substrate Processing.

The intramembrane aspartyl protease γ-secretase (GSEC) cleaves single-span transmembrane helices including the C-terminal fragment of the amyloid precursor protein (APP). This substrate is initially cleaved at the ϵ-site followed by successive processing (trimming) events mostly in steps of three amino acids. GSEC is responsible for the formation of N-terminal APP amyloid-ß (Aß) peptides of different length (e.g., Aß42) that can form aggregates involved in Alzheimer's disease pathogenesis. The molecular mechanism of GSEC-APP substrate recognition is key for understanding how different peptide products are formed and could help in designing APP-selective modulators. Based on the known structure of apo GSEC and the APP-C99 fragment we have generated putative structural models of the initial binding in three different possible modes using extensive molecular dynamics (MD) simulations. The binding mode with the substrate helix located in a cleft between the transmembrane helices 2 and 3 of the presenilin subunit was identified as a most likely binding mode. Based on this arrangement, the processing steps were investigated using restraint MD simulations to pull the scissile bond (for each processing step) into a transition like (cleavable) state. This allowed us to analyze in detail the motions and energetic contributions of participating residues. The structural model agrees qualitatively well with the influence of many mutations in GSEC and C99. It also explains the effects of inhibitors, cross-linking, as well as spectroscopic data on GSEC substrate binding and can serve as working model for the future planning of structural and biochemical studies.

Nearly perfect near-infrared luminescence efficiency of Si nanocrystals: A comprehensive quantum yield study employing the Purcell effect.

Thin layers of silicon nanocrystals (SiNC) in oxide matrix with optimized parameters are fabricated by the plasma-enhanced chemical vapor deposition. These materials with SiNC sizes of about 4.5 nm and the SiO2 barrier thickness of 3 nm reveal external quantum yield (QY) close to 50% which is near to the best chemically synthetized colloidal SiNC. Internal QY is determined using the Purcell effect, i.e. modifying radiative decay rate by the proximity of a high index medium in a special wedge-shape sample. For the first time we performed these experiments at variable temperatures. The complete optical characterization and knowledge of both internal and external QY allow to estimate the spectral distribution of the dark and bright NC populations within the SiNC ensemble. We show that SiNCs emitting at around 1.2-1.3 eV are mostly bright with internal QY reaching 80% at room temperature and being reduced by thermally activated non-radiative processes (below 100 K internal QY approaches 100%). The mechanisms of non-radiative decay are discussed based on their temperature dependence.

Interplay of bimolecular and Auger recombination in photoexcited carrier dynamics in silicon nanocrystal/silicon dioxide superlattices.

We report results of investigating carrier recombination in silicon nanocrystal/silicon dioxide superlattices. The superlattices prepared by nitrogen-free plasma enhanced chemical vapour deposition contained layers of silicon nanocrystals. Femtosecond transient transmission optical spectroscopy was used to monitor carrier mechanisms in the samples. The three-particle Auger recombination was observed in accord with previous reports. However, under high pump intensities (high photoexcited carrier densities) the bimolecular process dominated the recombination. Detailed analysis of measured data and fitting procedure made it possible to follow and quantify the interplay between the two recombination processes. The bimolecular recombination was interpreted in terms of the trap-assisted Auger recombination.

Simulation of the structure and dynamics of nonhelical RNA motifs.

Computer simulation methods are increasingly being used to study possible conformations and dynamics of structural motifs in RNA. Recent results of molecular dynamics simulations and continum solvent studies of RNA structures and RNA-ligand complexes show promising agreement with experimental data. Combined with the ongoing progress in the experimental characterization of RNA structure and thermodynamics, these computational approaches can help to better understand the mechanism of RNA structure formation and the binding of ligands.

RNA aptamers as potential pharmaceuticals against infections with African trypanosomes.

Protozoal pathogens cause symptomatic as well as asymptomatic infections. They have a worldwide impact, which in part is reflected in the long-standing search for antiprotozoal chemotherapy. Unfortunately, effective treatments for the different diseases are by and large not available. This is especially true for African trypanosomiasis, also known as sleeping sickness. The disease is an increasing problem in many parts of sub-Saharan Africa, which is due to the lack of new therapeutics and the increasing resistance against traditional drugs such as melarsoprol, berenil and isometamidium. Considerable progress has been made over the past 10 years in the development of nucleic acid-based drug molecules using a variety of different technologies. One approach is a combinatorial technology that involves an iterative Darwinian-type in vitro evolution process, which has been termed SELEX for "systematic evolution of ligands by exponential enrichment". The procedure is a highly efficient method of identifying rare ligands from combinatorial nucleic acid libraries of very high complexity. It allows the selection of nucleic acid molecules with desired functions, and it has been instrumental in the identification of a number of synthetic DNA and RNA molecules, so-called aptamers that recognize ligands of different chemical origin. Aptamers typically bind their target with high affinity and high specificity and have successfully been converted into pharmaceutically active compounds. Here we summarize the recent examples of the SELEX technique within the context of identifying high-affinity RNA ligands against the surface of the protozoan parasite Trypanosoma brucei, which is the causative agent of sleeping sickness.

Modelling ion binding to AA platform motifs in RNA: a continuum solvent study including conformational adaptation.

Binding of monovalent and divalent cations to two adenine-adenine platform structures from the Tetrahymena group I intron ribozyme has been studied using continuum solvent models based on the generalised Born and the finite-difference Poisson-Boltzmann approaches. The adenine-adenine platform RNA motif forms an experimentally characterised monovalent ion binding site important for ribozyme folding and function. Qualitative agreement between calculated and experimental ion placements and binding selectivity was obtained. The inclusion of solvation effects turned out to be important to obtain low energy structures and ion binding placements in agreement with the experiment. The calculations indicate that differences in solvation of the isolated ions contribute to the calculated ion binding preference. However, Coulomb attraction and van der Waals interactions due to ion size differences and RNA conformational adaptation also influence the calculated ion binding affinity. The calculated alkali ion binding selectivity for both platforms followed the order K(+) > Na(+) > Rb(+) > Cs(+) > Li(+) (Eisenman series VI) in the case of allowing RNA conformational relaxation during docking. With rigid RNA an Eisenman series V was obtained (K(+) > Rb(+) > Na(+) > Cs(+) > Li(+)). Systematic energy minimisation docking simulations starting from several hundred initial placements of potassium ions on the surface of platform containing RNA fragments identified a coordination geometry in agreement with the experiment as the lowest energy binding site. The approach could be helpful to identify putative ion binding sites in nucleic acid structures determined at low resolution or with experimental methods that do not allow identification of ion binding sites.

Diagnostics and therapy of lymphoceles after kidney transplantation.

Lymphocele incidence after kidney transplantation is as high as 18%. We retrospectively studied the therapy of 42 lymphoceles that occurred in our clinic between 1990 and 2005, focusing on possible predisposing factors for their formation and the results of several therapy variants: conservative, operative, percutaneous puncture, and laparoscopic or open marsupialization. There was no connection between lymphocele formation and the following parameters: the extent to which the iliac vessels had been prepared, the materials used for the preparation, or whether clips or ligatures were applied. Lymphoceles may originate either from the lymphatic system of the recipient or the transplanted kidney. The most sensible measures to prevent their occurrence therefore seems to be to restrict the transplant bed to the smallest permissible level with careful ligature of the lymphatic vessels in the area of the kidney hilus. Treatment for lymphoceles should start with minimally invasive measures. We use the following algorithm in our clinic: puncture to differentiate between urinoma/lymphocele and to test for bacterial infection, sclerotization (200 mg doxycyclin), and finally marsupialization if persistent. The choice of operative technique depends on the location. This algorithm resulted in a relapse rate of 9.5% during the postoperative observation period of up to 15 years.

Conformational analysis of single-base bulges in A-form DNA and RNA using a hierarchical approach and energetic evaluation with a continuum solvent model.

The analysis and prediction of non-canonical structural motifs in RNA is of great importance for an understanding of the function and design of RNA structures. A hierarchical method has been employed to generate a large variety of sterically possible conformations for a single-base adenine bulge structure in A -form DNA and RNA. A systematic conformational search was performed on the isolated bulge motif and neighboring nucleotides under the constraint to fit into a continuous helical structure. These substructures were recombined with double-stranded DNA or RNA. Energy minimization resulted in more than 300 distinct bulge conformations. Energetic evaluation using a solvation model based on the finite-difference Poisson-Boltzmann method identified three basic classes of low-energy structures. The three classes correspond to conformations with the bulge base stacked between flanking nucleotides (I), location of the bulge base in the minor groove (II) and conformations with a continuous stacking of the flanking helices and a looped out bulge base (III). For the looped out class, two subtypes (IIIa and IIIb) with different backbone geometries at the bulge site could be distinguished. The conformation of lowest calculated energy was a class I structure with backbone torsion angles close to those in standard A -form RNA. Conformations very close to the extra-helical looped out bulge structure determined by X-ray crystallography were also among the low-energy structures. In addition, topologies observed in other experimentally determined bulge structures have been found among low-energy conformers. The implicit solvent model was further tested by comparing an uridine and adenine bulge flanked by guanine:cytosine base-pairs, respectively. In agreement with the experimental observation, a looped out form was found as the energetically most favorable form for the uridine bulge and a stacked conformation in case of the adenine bulge. The inclusion of solvation effects especially electrostatic reaction field contributions turned out to be critically important in order to select realistic low-energy bulge structures from a large number of sterically possible conformations. The results indicate that the approach might be useful to model the three-dimensional structure of non-canonical motifs embedded in double-stranded RNA, in particular, to restrict the number of possible conformations to a manageable number of conformers with energies below a certain threshold.

Bulge-induced bends in RNA: quantification by transient electric birefringence.

Bulges represent one of the most common non-helical elements in RNA, often displaying a strong degree of phylogenetic conservation, both in location and sequence, within larger RNA molecules. Thus, knowledge of the conformation and flexibility of RNA bulges is an important prerequisite for understanding the rules governing the formation of tertiary structure within the larger molecules. In the current investigation, the magnitudes of the bends induced in a 148 base-pair duplex RNA molecule by single, centrally located bulges of varying size (n = 1 to 6) and base composition (An and Un series) have been determined through the use of transient electric birefringence (TEB). The TEB approach is highly sensitive to the changes in the global shape of RNA (or DNA) helices that accompany the introduction of points of bending or flexibility near the center of the helix. In the current instance, bulge angles deduced from TEB measurements ranged from approximately 7 degrees to approximately 93 degrees, with the angle increasing with increasing n for both An and Un series. For both An and Un series in the absence of Mg2+, the angle increment per added nucleotide varied from approximately 20 degrees to approximately 8 degrees as n increased from 1 to 6. These angle increments remained unchanged for the An series in the presence of Mg2+; however, the angle increments for the Un series were reduced by a factor of 2 for all values of n. Thus the current observations have identified structural transitions in one of the simplest non-helical elements in RNA, transitions that are dependent on both sequence and counterion valence. Finally, the measured bend angles are strongly correlated with the degree of reduction in electrophoretic mobility of bulge-containing RNA helices. The observed correlation was used to obtain a semi-empirical relationship between bend angle and mobility in order that additional angles might be assigned, by interpolation, through the use of gel data alone.

The influence of symmetric internal loops on the flexibility of RNA.

Internal loops are structural elements, often highly conserved, that are found in many RNA molecules of biological importance. They consist of short stretches of sequence in which the bases in one strand are not able to form canonical pairs with bases in the other strand, and are bounded on either side by helical RNA. In an effort to examine the influence of internal loops on the relative angular orientations of the flanking helices, we have quantified the apparent bend angles for symmetric internal loops of the form A(n)-A(n) and U(n)-U(n) (n=2, 4, and 6), located at the center of 150 to 154 bp RNA molecules, using the method of transient electric birefringence. This hydrodynamic method exploits the extreme sensitivity of the rate of rotational reorientation of the RNA molecules to the presence and magnitude of internal bends and/or points of increased flexibility. The birefringence decay behavior of the loop-containing RNA molecules was found to be much less strongly influenced by the presence of symmetric internal loops than by bulges of the same sequence and size. This general observation is mirrored by the electrophoretic behavior of the loop-containing molecules, which are much less strongly retarded on polyacrylamide gels than are corresponding, bulge-containing RNA molecules. The apparent bend angles for the symmetric loops range from approximately 20 degrees to 40 degrees as n is increased 2 to 6 with a marginal shift to smaller angles in the presence of Mg2+. The apparent angles were similar when represented either as fixed bends of the specified angles (static representation), or as points of increased flexibility of specified root-mean-square angle (dynamic representation). For the. For the latter representation, the corresponding angular dispersion would correspond to a loop persistence length of approximately 60 to 150 A, compared to 700 A for duplex RNA and depending slightly on sequence and buffer conditions.

Combined conformational search and finite-difference Poisson-Boltzmann approach for flexible docking. Application to an operator mutation in the lambda repressor-operator complex.

The N-terminal domain of the phage lambda repressor binds as a dimer to its palindromic DNA operator sequence. In addition to a helix-turn-helix DNA recognition motif, the first six amino acids of the phage lambda repressor form a flexible peptide segment which wraps around DNA. Site-directed mutagenesis studies have shown that amino acid replacements or partial removal of the arm structure, or changes in the DNA sequence contacting the N-terminal arm, can lower the repressor-operator binding affinity by several orders of magnitude. The finite-difference Poisson-Boltzmann approach in combination with a conformational search procedure was used to study energetic contributions of the lambda arm to repressor-operator recognition based on the high resolution X-ray structure. It allows for the local relaxation of the structure upon changing the DNA sequence in the lambda arm binding region. A simplified potential energy function including torsional, truncated Lennard-Jones and approximate electrostatic terms is used in the initial step to screen out energetically unfavorable structures. The electrostatic energy of selected conformations is subsequently calculated more accurately using the finite-difference Poisson-Boltzmann approach. The method was applied to study the effect of a C-->T mutation at position 6 of the consensus half-site of the operator. This base-pair contacts Lys4 which is part of the arm segment. Keeping only the Lys4 side-chain mobile and with the wild-type DNA operator sequence, several conformations close to the X-ray structure were identified as those with lowest energy. In the case of the DNA mutation, lowest energy conformations differed significantly from those selected for the wild-type sequence. These initial calculations indicate that the approach might be a useful tool to estimate conformational and energetic effects upon mutagenesis of protein-DNA complexes.

Sensitive assay for laboratory evolution of hydroxylases toward aromatic and heterocyclic compounds.

Powerful directed evolution methods have been developed for tailoring proteins to our needs in industrial applications. Here, the authors report a medium-throughput assay system designed for screening mutant libraries of oxygenases capable of inserting a hydroxyl group into a C-H bond of aromatic or O-heterocyclic compounds and for exploring the substrate profile of oxygenases. The assay system is based on 4-aminoantipyrine (4-AAP), a colorimetric phenol detection reagent. By using 2 detection wavelengths (509 nm and 600 nm), the authors achieved a linear response from 50 to 800 microM phenol and standard deviations below 11% in 96-well plate assays. The monooxygenase P450 BM-3 and its F87A mutant were used as a model system for medium-throughput assay development, identification of novel substrates (e.g., phenoxytoluene, phenylallyether, and coumarone), and discovery of P450 BM-3 F87A mutants with 8-fold improvement in 3-phenoxytoluene hydroxylation activity. This activity increase was achieved by screening a saturation mutagenesis library of amino acid position Y51 using the 4-AAP protocol in the 96-well format.

Interventions for protecting renal function in the perioperative period.

BACKGROUND: A number of methods have been used to try to protect kidney function in patients undergoing surgery. These include the administration of dopamine, diuretics, calcium channel blockers, angiotensin converting enzyme inhibitors and hydration fluids. OBJECTIVES: For this review, we selected randomized controlled trials, which employed different methods to protect renal function during the perioperative period. In examining these trials, we looked at outcomes such as renal failure and mortality, as well as changes in the renal function tests, including urine output, creatinine clearance, free water clearance, fractional excretion of sodium and renal plasma flow. SEARCH STRATEGY: We searched the Cochrane Central register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2004), MEDLINE (1966 to 2004) and EMBASE (1988 to 2004) and hand searched six journals (British Journal of Anaesthesia; Anesthesia and Analgesia; Anesthesiology; Annals of Surgery; Journal of Thoracic and Cardiovascular Surgery and Journal of Vascular Surgery). SELECTION CRITERIA: We selected all randomized controlled trials in adult population undergoing surgery where a treatment measure was used for the purpose of renal protection in the perioperative period. DATA COLLECTION AND ANALYSIS: We selected 37 studies for inclusion in this review. As well as analysis of the data from all the studies, we also performed subgroup analysis for type of interventions, types of surgical procedures and those with pre-existing renal dysfunction. We undertook sensitivity analysis on studies with high methodological quality. MAIN RESULTS: The review included data from 37 studies, comprising a total of 1227 patients. Of these, 658 received some form of treatment and 569 acted as controls. The interventions were mostly employing different pharmaceutical agents such as dopamine, diuretics, calcium channel blockers. ACE inhibitors or selected hydration fluids. The results indicated that certain interventions showed some benefits, but all the results suffered from significant heterogeneity. Hence we can draw no conclusions about the effectiveness of these interventions in protecting the kidneys during surgery. AUTHORS' CONCLUSIONS: There is no reliable evidence from available literature to suggest that interventions during surgery can protect the kidneys from damage. However, there is a need for more studies of high methodological quality. One particular area for further studies may be on patients with pre-existing renal dysfunction undergoing surgery.

The importance of individual nucleotides for the structure and function of rRNA molecules in E. coli. A mutagenesis study.

Methods of in vitro mutagenesis were employed to determine the importance of individual nucleotides within the ribosomal RNAs for the structure and function of E. coli ribosomes. A series of defined nucleotides in the genes for the 5 S and 16 S RNA were altered by transition and transversion mutations using either oligonucleotide-directed or bisulfite-catalyzed mutation procedures. Plasmids harbouring the mutated rRNA genes were expressed and the ribosomes containing such altered RNAs were investigated for impairments in RNA-protein interaction assembly and mRNA-coded tRNA binding.

Analysis of sequence elements important for the synthesis and control of ribosomal RNA in E coli.

The regulation of the synthesis of ribosomal RNA is a key problem for the understanding of bacterial growth. Many different regulatory mechanisms involving cis and trans acting components participate in a concerted way to achieve the very efficient, flexible and coordinated production of this class of molecules. We have studied three different sequence regions within a ribosomal RNA transcription unit which are believed to control different stages of ribosomal RNA expression. In the first part of the study the function of AT-rich sequences upstream of the -35 hexamer of rRNA promoter P1 in the activation of rRNA transcription was analyzed. We confirm that a sequence dependent bend upstream of P1 is responsible for the high promoter activity. Experiments employing linker scanning mutations demonstrated that the distance as well as the angular orientation of the bent DNA is crucial for the degree of activation. In addition, the effect of the trans activating protein Fis on the transcription initiation of promoter P1 was investigated. We can show, using the abortive initiation assay, that the predominant effect of Fis is due to an increase in the affinity of RNA polymerase for the promoter (binding constant KB) while the isomerisation rate (kf) from a closed to an open RNA polymerase promoter complex is not altered significantly. We also describe the characterization of sequence determinants important for stringent regulation and growth rate control. Evidence is provided that the discriminator motif GCGC is a necessary but not sufficient element for both types of control. Furthermore we show that not simply a particular DNA primary structure but the higher order conformation of the complete promoter region is recognized and triggers the two regulatory mechanisms, both of which are apparently mediated by the effector molecule guanosine tetraphosphate (ppGpp). Finally, we have carried out a systematic mutational analysis of the rrnB leader region preceding the structural gene for 16S RNA. We could demonstrate that highly conserved sequence elements within the rrnB leader, which were believed to be involved in transcription antitermination have post-transcriptional functions. We present evidence that these sequence elements direct the biogenesis of active ribosomal particles.

Efficient search on energy minima for structure prediction of nucleic acid motifs.

Structure prediction of non-canonical motifs such as mismatches, extra unmatched nucleotides or internal and hairpin loop structures in nucleic acids is of great importance for understanding the function and design of nucleic acid structures. Systematic conformational analysis of such motifs typically involves the generation of many possible combinations of backbone dihedral torsion angles for a given motif and subsequent energy minimization (EM) and evaluation. Such approach is limited due to the number of dihedral angle combinations that grows very rapidly with the size of the motif. Two conformational search approaches have been developed that allow both an effective crossing of barriers during conformational searches and the computational demand grows much less with system size then search methods that explore all combinations of backbone dihedral torsion angles. In the first search protocol single torsion angles are flipped into favorable states using constraint EM and subsequent relaxation without constraints. The approach is repeated in an iterative manner along the backbone of the structural motif until no further energy improvement is obtained. In case of two test systems, a DNA-trinucleotide loop (sequence: GCA) and a RNA tetraloop (sequence: UUCG), the approach successfully identified low energy states close to experiment for two out of five start structures. In the second method randomly selected combinations of up to six backbone torsion angles are simultaneously flipped into preset ranges by a short constraint EM followed by unconstraint EM and acceptance according to a Metropolis acceptance criterion. This combined stochastic/EM search was even more effective than the single torsion flip approach and selected low energy states for the two test cases in between two and four cases out of five start structures.

Comparative efficacy and pharmacokinetics of racemic bupivacaine and S-bupivacaine in third molar surgery.

PURPOSE: To compare the efficacy and pharmacokinetics of racemic bupivacaine (rac-bupivacaine) with S-bupivacaine as primary local anesthetic agent in bilateral impacted third molar extractions. METHOD: A randomised, double blind, two period cross-over design was employed. Six subjects (2 males, 4 females; age 19-25 years; weight 69.2+/-9.4 kg) received bupivacaine hydrochloride injection (6.6 ml) as rac-bupivacaine (0.5% as salt) or S-bupivacaine (0.5% as base) prior to extraction of impacted third molars on one side and three weeks later on the other side. Anesthesia, blood loss associated with surgery and post-operative pain experience were evaluated. Plasma samples were analysed for bupivacaine enantiomers by chiral HPLC. RESULTS: In 7/12 operations, anesthesia adequate for surgery was delayed (>10 min) or unsatisfactory requiring lidocaine rescue medication. Despite this, there were no significant differences in onset and duration of anesthesia, blood loss or post-operative pain experience between the two arms of the study. Pharmacokinetic parameters were not significantly different and there was no evidence of chiral inversion after dosing with S-bupivacaine. CONCLUSIONS: Both study drugs were inadequate as single anesthetic agent for third molar surgery. Any decision to use S-bupivacaine for oral surgery must rest on evidence that it is less toxic than the racemic drug.

Bolus dose with continuous infusion of midazolam as sedation for outpatient surgery.

This double-blind, randomised, cross-over trial in 41 patients for 3rd molar surgery compared the safety, amnesic properties and psychomotor recovery between a bolus injection of midazolam and a bolus injection followed by continuous infusion of midazolam. The latter showed good safety and better amnesia to events during the procedure, but prolonged the recovery time.