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[Pain after anterior cruciate ligament reconstruction: detail and treatment].

OBJECTIVE: Several factors can influence the occurrence of pain after anterior cruciate ligament (ACL) ligamentoplasty, namely, factors linked to the selection of graft, the surgical technique and rehabilitation program. The aim of this research was to review the literature for different types of pain experienced after ACL reconstruction to illuminate better prevention and treatment. METHOD: We reviewed reports by searching the PUBMED* research engine using the key words pain, complication, and anterior cruciate ligament. RESULTS: We found an increasing incidence of anterior pain after use of the patellar tendon for ACL reconstruction. Some anterior pain can be mistakenly interpreted as donor site morbidity or patello-femoral problems, but it is in fact linked to graft impingement caused by bad placement of tunnels and/or proliferation of a fibrovascular nodule on the ACL graft ("cyclops syndrome"). Some posterior-external pain, sometimes associated, can occur under the same circumstances. Cartilage, ligament or meniscal lesions or saphenous nerve injuries can explain some occurrences of pain. Pain linked to loco-regional factors such as reflex sympathetic dystrophy appear to be rare with rehabilitation and surgery. CONCLUSION: The treatment of pain after ACL reconstruction lies first in the establishment of an etiologic diagnosis. Prevention, by controlling tendon-muscular and joint stress during rehabilitation, is essential and requires sound knowledge of biomechanical data.

Anterior Cruciate Ligament↗

Direct-aperture optimization applied to selection of beam orientations in intensity-modulated radiation therapy.

Direct-aperture optimization (DAO) was applied to iterative beam-orientation selection in intensity-modulated radiation therapy (IMRT), so as to ensure a realistic segmental treatment plan at each iteration. Nested optimization engines dealt separately with gantry angles, couch angles, collimator angles, segment shapes, segment weights and wedge angles. Each optimization engine performed a random search with successively narrowing step sizes. For optimization of segment shapes, the filtered backprojection (FBP) method was first used to determine desired fluence, the fluence map was segmented, and then constrained direct-aperture optimization was used thereafter. Segment shapes were fully optimized when a beam angle was perturbed, and minimally re-optimized otherwise. The algorithm was compared with a previously reported method using FBP alone at each orientation iteration. An example case consisting of a cylindrical phantom with a hemi-annular planning target volume (PTV) showed that for three-field plans, the method performed better than when using FBP alone, but for five or more fields, neither method provided much benefit over equally spaced beams. For a prostate case, improved bladder sparing was achieved through the use of the new algorithm. A plan for partial scalp treatment showed slightly improved PTV coverage and lower irradiated volume of brain with the new method compared to FBP alone. It is concluded that, although the method is computationally intensive and not suitable for searching large unconstrained regions of beam space, it can be used effectively in conjunction with prior class solutions to provide individually optimized IMRT treatment plans.

Algorithms↗

Investigation of Italy's deadliest building collapse: forensic aspects of a mass disaster.

We describe the investigation of the 1999 collapse of an apartment building in Foggia, Italy. Sixty-one victims were recovered in the rubble of the building, and five people were unaccounted for. All the bodies were well preserved except for two who had been burned. The majority of the victims were identified visually or by comparing body features, clothing, or personal effects with information collected from relatives or friends. Positive identifications of the two victims who were burned were obtained by dental comparison and DNA analysis. Approximately half of the victims (51.6%) sustained fatal injuires, while the remainder died from asphyxia. The injuries were characterized using the Abbreviated Injury Scale (AIS) and the New Injury Severity Score (NISS) systems. Injury severity associated with the location of victims inside the apartment may provide useful information for those involved in building design and/or search and rescue operations. Engineers determined that the collapse was the result of the use of inappropriate foundation material.

Adolescent↗

PISCES: recent improvements to a PDB sequence culling server.

PISCES is a database server for producing lists of sequences from the Protein Data Bank (PDB) using a number of entry- and chain-specific criteria and mutual sequence identity. Our goal in culling the PDB is to provide the longest list possible of the highest resolution structures that fulfill the sequence identity and structural quality cut-offs. The new PISCES server uses a combination of PSI-BLAST and structure-based alignments to determine sequence identities. Structure alignment produces more complete alignments and therefore more accurate sequence identities than PSI-BLAST. PISCES now allows a user to cull the PDB by-entry in addition to the standard culling by individual chains. In this scenario, a list will contain only entries that do not have a chain that has a sequence identity to any chain in any other entry in the list over the sequence identity cut-off. PISCES also provides fully annotated sequences including gene name and species. The server allows a user to cull an input list of entries or chains, so that other criteria, such as function, can be used. Results from a search on the re-engineered RCSB's site for the PDB can be entered into the PISCES server by a single click, combining the powerful searching abilities of the PDB with PISCES's utilities for sequence culling. The server's data are updated weekly. The server is available at http://dunbrack.fccc.edu/pisces.

Databases, Protein↗

[Molecular engineering of hemoglobin for transfusion].

The search for a safe alternative to conventional blood transfusion has been directed towards either the use of synthetic perfluorochemicals or the biochemical manipulation of highly purified stroma-free Hb solutions prepared from outdated bank blood. However when using human blood, one does not eliminate the risks of viral infections. A novel source of Hb appeared with recent biotechnology techniques enabling one to synthesize recombinant Hb from microorganisms (E coli or S. cerevisiae) whose genome has been modified to contain globin genes. Normal human Hb A in solution, i.e. outside the red cells, is not suited for direct usage as a blood substitute because i) its high oxygen affinity, due to the absence of 2,3 DPG in the plasma, precludes sufficient O2 unloading to the tissues; ii) at low concentration, relative to that in the red cells, tetrameric Hb dissociates into dimers which escape the circulatory system by renal filtration or rapidly oxidize to the non functional metHb form. Expression of alpha- and beta-globins in Escherichia coli and in Saccharomyces cerevisiae enables one to introduce appropriate mutation(s) in the globin genes resulting in the expression of a synthetic Hb with low oxygen affinity, resembling that of normal whole blood; functional Hb has also been produced in a soluble form either in E. coli or in yeast. The coexpression of beta globin chains and alpha globin subunits linked by a peptide bond results in the direct synthesis of stabilized and fully functional Hb tetramers. Lastly, dilute haemoglobin solutions are prone to autooxidize and the rate of oxidation appears to be inversely proportional with the oxygen affinity of the heme groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Tissue engineering of vascular conduits.

BACKGROUND: Autologous conduits are not available in up to 40 per cent of patients with arteriopathy who require coronary or lower limb revascularization, and access sites for renal dialysis may eventually become exhausted. Synthetic prostheses achieve a poor patency rate in small-calibre anastomoses. This review examines how vascular tissue engineering may be used to address these issues. METHODS: A Medline search was performed, using the keywords "vascular tissue engineering", "small diameter vascular conduit", "vascular cell biology", "biomechanics", "cell seeding" and "graft endothelialization". Key references were hand-searched for relevant papers. RESULTS AND CONCLUSION: In vitro and in vivo approaches are currently being used for guided cell repopulation of both biological and synthetic scaffolds. The major clinical problem has been extended culture time (approximately 6 weeks), which precludes their use in the acute setting. However, recent advances have led not only to improved patency rates for prostheses, but also to a potential reduction in culture time. In addition, increased mobilization of endothelial progenitor cells in the presence of ischaemic tissue may increase the autologous cell yield for scaffold reseeding with further reduction in culture time.

Bioartificial Organs↗

[An computer information system for genetic engineering].

The article describes the vectors data base and the software for its use (the VECTOR-PC system). At present the prototype versions of data base and VECTOR-PC exist and are in test exploitation. The original data base entry format contains 17 main fields for specific genetic engineering information. The VECTOR-PC system includes programs for data base search and support, and also the "genetic engineering designer", which allows the user to design his own hypothetic structures from the objects of data base and to receive detailed information about them. The system is destined for IBM PC or compatible computers.

Genetic Engineering↗

A metabolic network analysis & NMR experiment design tool with user interface-driven model construction for depth-first search analysis.

A Windows program for metabolic engineering analysis and experimental design has been developed. A graphical user interface enables the pictorial, "on-screen" construction of a metabolic network. Once a model is composed, balance equations are automatically generated. Model construction, modification and information exchange between different users is thus considerably simplified. For a given model, the program can then be used to predict all the extreme point flux distributions that optimize an objective function while satisfying balances and constraints by using a depth-first search strategy. One can also find the minimum reaction set that satisfies different conditions. Based on the identified flux distributions or linear combinations, the user can simulate the NMR and GC/MS spectra of selected signal molecules. Alternately, spectra vectorization allows for the automated optimization of labeling experiments that are intended to distinguish between different, yet plausible flux extreme point distributions. The example provided entails predicting the flux distributions associated with deleting pyruvate kinase and designing 13C NMR experiments that can maximally discriminate between the flux distributions.

Computer Simulation↗

Potential of genetic algorithms in protein folding and protein engineering simulations.

Genetic algorithms are very efficient search mechanisms which mutate, recombine and select amongst tentative solutions to a problem until a near optimal one is achieved. We introduce them as a new tool to study proteins. The identification and motivation for different fitness functions is discussed. The evolution of the zinc finger sequence motif from a random start is modelled. User specified changes of the lambda repressor structure were simulated and critical sites and exchanges for mutagenesis identified. Vast conformational spaces are efficiently searched as illustrated by the ab initio folding of a model protein of a four beta strand bundle. The genetic algorithm simulation which mimicked important folding constraints as overall hydrophobic packaging and a propensity of the betaphilic residues for trans positions achieved a unique fold. Cooperativity in the beta strand regions and a length of 3-5 for the interconnecting loops was critical. Specific interaction sites were considerably less effective in driving the fold.

Algorithms↗

Comparison of bacterial and phage display peptide libraries in search of target-binding motif.

Genetic engineering allows modification of bacterial and bacteriophage genes, which code for surface proteins, enabling display of random peptides on the surface of these microbial vectors. Biologic peptide libraries thus formed are used for high-throughput screening of clones bearing peptides with high affinity for target proteins. There are reports of many successful affinity selections performed with phage display libraries and substantially fewer cases describing the use of bacterial display systems. In theory, bacterial display has some advantages over phage display, but the two systems have never been experimentally compared. We tested both techniques in selecting streptavidin-binding peptides from two commercially available libraries. Under similar conditions, selection of phage-displayed peptides to model protein streptavidin proved convincingly better.

Amino Acid Sequence↗

Physical stability enhancement of theophylline via cocrystallization.

The crystal form adopted by the respiratory drug theophylline was modified using a crystal engineering strategy in order to search for a solid material with improved physical stability. Cocrystals, also referred to as crystalline molecular complexes, were prepared with theophylline and one of several dicarboxylic acids. Four cocrystals of theophylline are reported, one each with oxalic, malonic, maleic and glutaric acids. Crystal structures were obtained for each cocrystal material, allowing an examination of the hydrogen bonding and crystal packing features. The cocrystal design scheme was partly based upon a series of recently reported cocrystals of the molecular analogue, caffeine, and comparisons in packing features are drawn between the two cocrystal series. The theophylline cocrystals were subjected to relative humidity challenges in order to assess their stability in relation to crystalline theophylline anhydrate and the equivalent caffeine cocrystals. None of the cocrystals in this study converted into a hydrated cocrystal upon storage at high relative humidity. Furthermore, the theophylline:oxalic acid cocrystal demonstrated superior humidity stability to theophylline anhydrate under the conditions examined, while the other cocrystals appeared to offer comparable stability to that of theophylline anhydrate. The results demonstrate the feasibility of pharmaceutical cocrystal design based upon the crystallization preferences of a molecular analogue, and furthermore show that avoidance of hydrate formation and improvement in physical stability is possible via pharmaceutical cocrystallization.

Bronchodilator Agents↗

The Veterans Affairs root cause analysis system in action.

BACKGROUND: The patient safety program in the Department of Veterans Affairs (VA) began in 1998, when the National Center for Patient Safety (NCPS) was established to lead the effort on a day-to-day basis. NCPS provides the structure, training, and tools, and VA facilities provide front-line expertise, feedback about the process, and root cause analysis (RCA) of adverse events and close calls. MONITORING THE PROCESS: Facility patient safety managers determine the disposition of adverse events and close calls occurring at their facilities. They use a safety assessment code (SAC) to prioritize the actual and potential severity and frequency of an event. BEFORE-AND-AFTER STUDY: Before the new RCA system was implemented in 2000, the VA used another adverse event reporting system, focused review (FR). A comparison of the two processes indicates that the RCA process has shifted analyses of adverse events toward a human factors engineering approach-entailing a search for system vulnerabilities rather than human errors and other less actionable root causes. CASE EXAMPLES: Two case examples--on hazards in the magnetic resonance imaging (MRI) room and on a cardiac pacemaker malfunction--illustrate how the RCA system works in actual operation. The cases illustrate that broadly applicable, high-impact actions can result from a thorough RCA process. DISCUSSION: NCPS monitors the quality and completeness of RCAs through the immediate review and feedback process. Still to be investigated is the effectiveness of RCA actions addressing the hypothesized root causes and contributing factors of the close calls and adverse events.

Accidental Falls↗

PROANAL version 2: multifunctional program for analysis of multiple protein sequence alignments and for studying the structure--activity relationships in protein families.

A new version of the program PROANAL is described. A multiple linear regression analysis of the protein structure--activity relationship allows one to investigate the combinations of protein sites and factors influencing the activity. The program also provides the possibility to seek out protein sites, conservative or variable in variations of physicochemical characteristics, and regions with high or low values of these characteristics. PROANAL2 may be useful in the simulation of protein-engineering experiments and in the search of a number of protein regions such as functional sites, secondary structures, solvent-exposed regions, T- and B-cell antigenic determinants, etc.

Algorithms↗

Proteomic identification of oxidatively modified retinal proteins in a chronic pressure-induced rat model of glaucoma.

PURPOSE: Based on the evidence of an amplified production of reactive oxygen species (ROS) during glaucomatous neurodegeneration, proteomic analysis was performed to determine oxidative modification of retinal proteins after experimental elevation of intraocular pressure (IOP). METHODS: IOP elevation was induced in rats by hypertonic saline injections into episcleral veins. Protein expression was determined by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) of retinal protein lysates obtained from eyes matched for the cumulative IOP exposure and axon loss. To determine protein oxidation levels, protein carbonyls were detected through 2D-oxyblot analysis of 2,4-dinitrophenylhydrazine (DNPH)-treated samples using an anti-DNP antibody. For identification of oxidized proteins, peptide masses were analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS) and liquid chromatography-tandem mass spectrometry (LC/MS/MS). In addition to use of different engines in a bioinformatic database search and performance of peptide sequencing and 2D-Western blot analysis for confirmation of the identified proteins, immunohistochemistry was used for further validation of the proteomic findings. RESULTS: Comparison of 2D-oxyblots with Coomassie Blue-stained 2D-gels revealed that approximately 60 protein spots obtained with retinal protein lysates from ocular hypertensive eyes (of >400 spots) exhibited protein carbonyl immunoreactivity, which reflects oxidatively modified proteins. There was a significant increase in anti-carbonyl reactivity in individual protein spots obtained with retinal protein lysates from ocular hypertensive eyes compared with the control (P < 0.01). The identified proteins through peptide mass fingerprinting and peptide sequencing included glyceraldehyde-3-phosphate dehydrogenase, a glycolytic enzyme; HSP72, a stress protein; and glutamine synthetase, an excitotoxicity-related protein. Immunolabeling of retina sections with specific antibodies demonstrated cellular localization of these proteins as well as retinal distribution of the increased protein carbonyl immunoreactivity in ocular hypertensive eyes. CONCLUSIONS: The findings of this in vivo study provide novel evidence for oxidative modification of many retinal proteins in ocular hypertensive eyes and identify three specific targets of retinal protein oxidation in these eyes, thereby supporting the association of oxidative damage with neurodegeneration in glaucoma. By using a proteomic approach, this study also exemplifies that proteomics provide a very promising way to elucidate pathogenic mechanisms in glaucoma at the protein level.

Animals↗

VKCDB: voltage-gated potassium channel database.

BACKGROUND: The family of voltage-gated potassium channels comprises a functionally diverse group of membrane proteins. They help maintain and regulate the potassium ion-based component of the membrane potential and are thus central to many critical physiological processes. VKCDB (Voltage-gated potassium [K] Channel DataBase) is a database of structural and functional data on these channels. It is designed as a resource for research on the molecular basis of voltage-gated potassium channel function. DESCRIPTION: Voltage-gated potassium channel sequences were identified by using BLASTP to search GENBANK and SWISSPROT. Annotations for all voltage-gated potassium channels were selectively parsed and integrated into VKCDB. Electrophysiological and pharmacological data for the channels were collected from published journal articles. Transmembrane domain predictions by TMHMM and PHD are included for each VKCDB entry. Multiple sequence alignments of conserved domains of channels of the four Kv families and the KCNQ family are also included. Currently VKCDB contains 346 channel entries. It can be browsed and searched using a set of functionally relevant categories. Protein sequences can also be searched using a local BLAST engine. CONCLUSIONS: VKCDB is a resource for comparative studies of voltage-gated potassium channels. The methods used to construct VKCDB are general; they can be used to create specialized databases for other protein families. VKCDB is accessible at http://vkcdb.biology.ualberta.ca.

Animals↗

Nursing record systems: effects on nursing practice and health care outcomes.

BACKGROUND: A nursing record system is the record of care planned and/or given to individual patients/clients by qualified nurses or other caregivers under the direction of a qualified nurse. Nursing record systems may be an effective way of influencing nurse practice. OBJECTIVES: To assess the effects of nursing record systems on nursing practice and patient outcomes. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, Cinahl, Sigle, and databases of the Royal College of Nursing, King's Fund, the NHS Centre for Reviews and Dissemination, and the Institute of Electrical Engineers up to August 1999; and OCLC First Search, Department of Health database, NHS Register of Computer Applications and the Health Visitors' Association database up to the end of 1995. We hand searched the Journal of Nursing Administration (1971-1999), Computers in Nursing (1984-1999), Information Technology in Nursing (1989-1999) and reference lists of articles. We also hand searched the major health informatics conference proceedings. We contacted experts in the field of nursing informatics, suppliers of nursing computer systems, and relevant Internet groups. SELECTION CRITERIA: Randomised trials, controlled before and after studies and interrupted time series comparing one kind of nursing record system with another, in hospital, community or primary care settings. The participants were qualified nurses, students or health care assistants working under the direction of a qualified nurse and patients receiving care recorded and/or planned using nursing record systems. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Six trials involving 1407 people were included. In three studies of client held records, there were no overall positive or negative effects, although some administrative benefits through fewer missing notes were suggested. A paediatric pain management sheet study showed a positive effect on the children's pain intensity. A computerised nursing care planning study showed a negative effect on documented nursing care planning. A controlled before-and-after study of two paper nursing record systems showed improvement in meeting documentation standards. REVIEWER'S CONCLUSIONS: No evidence was found of effects on practice attributable to changes in record systems. Although there is a paucity of studies of sufficient methodological rigour to yield reliable results in this area, it is clear from the literature that it is possible to set up randomised trials or other quasi-experimental designs needed to produce evidence for practice. The research undertaken so far may have suffered both from methodological problems and faulty hypotheses.

Humans↗

Protein engineering of the tissue inhibitor of metalloproteinase 1 (TIMP-1) inhibitory domain. In search of selective matrix metalloproteinase inhibitors.

Studies of the structural basis of the interactions of tissue inhibitors of metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) may provide clues for designing MMP-specific inhibitors. In this paper we report combinations of mutations in the major MMP-binding region that enhance the specificity of N-TIMP-1. Mutants with substitutions for residues 4 and 68 were characterized and combined with previously studied Thr(2) mutations to generate mutants with improved selectivity or binding affinity to specific MMPs. Some combinations of mutations had non-additive effects on DeltaG of binding to MMPs, suggesting interactions between subsites in the reactive site. The T2L/V4S mutation generates an inhibitor that binds to MMP-2 20-fold more tightly than to MMP-3(DeltaC) and over 400-fold more tightly than to MMP-1. The T2S/V4A/S68Y mutant is the strongest inhibitor for stromelysin-1 among all mutants characterized to date, with an apparent K(i) for MMP-3(DeltaC) in the picomolar range. A third mutant, T2R/V4I, has no detectable inhibitory activity for MMP-1 but is an effective inhibitor of MMP-2 and -3. These selective TIMP variants may provide useful tools for investigation of biological roles of specific MMPs and for possible therapy of MMP-related diseases.

Animals↗

In search of an inherent ordering of vowel phonemes, or do pilots hear like engineers do?

To test the hypothesis that formant frequencies might provide an inherent ordering scheme for vowel sounds, two groups of subjects were asked to place six Italian vowel phonemes (A, O, U, AE, E, and I) into the most musically pleasing order. A subsequent chi 2 analysis of selections of the first group (21 music students and engineers) indicated a reliable consistency in vowel order supporting the hypothesis. Analysis of the second group (12 pilots) did not indicate any consistent ordering. The results are discussed in terms of hearing damage associated with exposure to high frequency aircraft noise.

Aerospace Medicine↗