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PubMed2004

[Diagnosis and immediate therapeutic management of limb injuries. A systematic review of the literature].

OBJECTIVE: Limb injuries are often underestimated in the diagnostic procedures initiated in the resuscitation room. Missed diagnosis is therefore a frequent consequence in this issue. A systematic analysis of evidence-based procedures was therefore investigated in this paper. METHODS: Clinical trials were systematically collected (Medline, Cochrane and hand searches) and classified into evidence levels (1 to 5 according to the Oxford system). RESULTS: Following admission of a multiple trauma patient vital functions have to be established in first priority. After stabilization a systematic clinical investigation and consecutive specific radiological procedures should rule out extremity injuries. These are the only evidence-based criteria leading to a complete detection of all limb injuries. All other aspects are only based on clinical experience or the opinion of expert committees. CONCLUSION: The quality of shock room management is mostly dependent on the experience of the " trauma team" (and especially of the trauma leader). Guidelines and specific trauma algorithms can provide a helpful instrument in this issue.

Arm Injuries↗
PubMed1997

[Active music therapy for chronic pain: a prospective study].

There are only few publications about the effect of music therapy on pain relief. The intention of this prospective study is to demonstrate the influence of the Nordoff/Robbins method of active music therapy in a group of 12 patients with fibromyalgia, myofascial pain syndromes and polyarthritis on pain reduction, life quality and coping. The clinical parameters of each patient were related to the observations in the audio- and video-documented music therapy settings and to the self-reported changes in pain intensity and pain behaviour. There was a significant reduction of pain intensity and pain-related disability in the music group compared to a control group, but no change in the depression and anxiety score. The influence of music therapy could be even better demonstrated in the systematic analysis of the single cases by individual profiles. Active music therapy affects especially the communicative and emotional dimension of chronic pain. Psychophysiological and psychodynamic models are presented to explain the effectiveness of music therapy on pain reduction. Clinical studies on music therapy as well as on other "art therapies" should relate the analysis of clinical parameters to the descriptive-phenomenological documentation of the therapeutic process to demonstrate systematically the influence of music and art in the individual case.

English Abstract↗
PubMed1997

XDOM, a graphical tool to analyse domain arrangements in any set of protein sequences.

MOTIVATION: To extract the maximum possible information from a set of protein sequences, its modular organization must be known and clearly displayed. This is important both for structural and functional analysis. RESULTS: This paper presents an algorithm and a graphical interface called XDOM which performs a systematic analysis of the modular organization of any set of protein sequences. The algorithm is an automatic method to identify putative domains from sequence comparisons. The graphical tool displays the proteins as a set of linked boxes, corresponding to its domains. The method has been tested on a family of bacterial proteins and on whole genomes. It is currently applied to the complete SWISS-PROT database to build the PRODOM database. AVAILABILITY: XDOM is available free of charge by anonymous ftp:¿¿ftp://ftp.toulouse.inra.fr/pub/xdom¿ ¿. The ProDom database can be consulted at ¿¿http://protein.toulouse.inra.fr/prodom.html¿¿.

Algorithms↗
PubMed1992

Mutational analysis of the human immunodeficiency virus type 1 Eli Nef function.

The studies presented here define an internally consistent experimental system that permits systematic analysis of the effect of nef on the rate of the human immunodeficiency virus type 1 (HIV-1) replication in a CD4+ tumor T-cell line and in primary peripheral blood mononuclear cells. The parental full-length Nef protein, derived from the Eli strain of HIV-1, accelerates virus replication in both cell types. Mutations that destabilize or alter the intracellular location of the protein affect the ability of the Nef protein to accelerate virus replication. A set of mutants was made in amino acids proposed to be required for Nef function, including threonine and serine residues proposed to be targets for phosphorylation, and in sequences thought to resemble the G-1, G-3, and G-4 sites of the family of G proteins. In most cases alterations of the critical amino acids yield stable Nef proteins of parental phenotype. These results challenge the existing theories for the mechanism of Nef function. The results also identify two residues in the carboxyl half of the protein that are important for Nef function.

Amino Acid Sequence↗
PubMed1993

Analysis of the RNA-recognition motif and RS and RGG domains: conservation in metazoan pre-mRNA splicing factors.

We present a systematic analysis of sequence motifs found in metazoan protein factors involved in constitutive pre-mRNA splicing and in alternative splicing regulation. Using profile analysis we constructed a database enriched in protein sequences containing one or more presumptive copies of the RNA-recognition motif (RRM). We provide an accurate alignment of RRMs and structure-based criteria for identifying new RRMs, including many that lack the prototype RNP-1 submotif. We present a comprehensive table of 125 sequences containing 252 RRMs, including 22 previously unreported RRMs in 17 proteins. The presence of a putative RRM in these proteins, which are implicated in a variety of cellular processes, strongly suggests that their function involves binding to RNA. Unreported homologies in the RRM-enriched database to the metazoan SR family of splicing factors are described for an Arg-rich human nuclear protein and two yeast proteins (S. pombe mei2 and S. cerevisiae Npl3). We have rigorously tested the phylogenetic relationships of a large sample of RRMs. This analysis indicates that the RRM is an ancient conserved region (ACR) that has diversified by duplication of genes and intragenic domains. Statistical analyses and classification of repeated Arg-Ser (RS) and RGG domains in various protein splicing factors are presented.

Amino Acid Sequence↗
PubMed1996

Immunodominance analysis of CTL responses to influenza PR8 virus reveals two new dominant and subdominant Kb-restricted epitopes.

In the present study, a systematic analysis of the influenza (Flu) PR8 determinants recognized by H-2b mice was undertaken. A single Db-restricted immunodominant epitope (NP(366)) was previously known in this system. Twenty-three different Flu PR8-derived peptides that bound either Kb or Db molecules in vitro were identified. Sixteen were immunogenic following peptide immunization of C57BL/6 mice, yet CTL induced by peptide immunization recognized PR8-infected target cells only in the case of the NP(366) and NS2(114) epitopes. Similarly, CTL responses following whole-PR8 virus immunization were detected only for the same two determinants. CTL recognizing these dominant epitopes had high avidity for peptide-pulsed target cells, with 5 to 200 pM of peptide required for 30% specific lysis. In contrast, most (80%) of the remaining epitopes were recognized with lower avidity (30% effective concentration in the range of 0.4-50 nM). Repeated in vitro stimulation of primary CTL cultures revealed one additional Kb-restricted epitope (M1(128)). This peptide bound Kb with high affinity (4.6 nM) and induced CTL that effectively recognized PR8-infected cells. These results suggest that 1) this epitope is produced by natural processing in relatively high amounts and 2) low precursor frequency might be related to the subdominant status of the M1(128) epitope. Taken together, these results illustrate the crucial contributions of MHC-binding capacity, and T cell repertoire availability, to the shaping of the repertoire of CTL specificities for Flu Ag virus.

Animals↗
PubMed2004

Transcript profiling during preimplantation mouse development.

Studies using low-resolution methods to assess gene expression during preimplantation mouse development indicate that changes in gene expression either precede or occur concomitantly with the major morphological transitions, that is, conversion of the oocyte to totipotent 2-cell blastomeres, compaction, and blastocyst formation. Using microarrays, we characterized global changes in gene expression and used Expression Analysis Systematic Explorer (EASE) to identify biological and molecular processes that accompany and likely underlie these transitions. The analysis confirmed previously described processes or events, but more important, EASE revealed new insights. Response to DNA damage and DNA repair genes are overrepresented in the oocyte compared to 1-cell through blastocyst stages and may reflect the oocyte's response to selective pressures to insure genomic integrity; fertilization results in changes in the transcript profile in the 1-cell embryo that are far greater than previously recognized; and genome activation during 2-cell stage may not be as global and promiscuous as previously proposed, but rather far more selective, with genes involved in transcription and RNA processing being preferentially expressed. These results validate this hypothesis-generating approach by identifying genes involved in critical biological processes that can be the subject of a more traditional hypothesis-driven approach.

Animals↗
PubMed2006

Comparative structure-activity analysis of insect kinin core analogs on recombinant kinin receptors from Southern cattle tick Boophilus microplus (Acari: Ixodidae) and mosquito Aedes aegypti (Diptera: Culicidae).

The systematic analysis of structure-activity relationships of insect kinins on two heterologous receptor-expressing systems is described. Previously, kinin receptors from the southern cattle tick, Boophilus microplus (Canestrini), and the dengue vector, the mosquito Aedes aegypti (L.), were functionally and stably expressed in CHO-K1 cells. In order to determine which kinin residues are critical for the peptide-receptor interaction, kinin core analogs were synthesized as an Ala-replacement series of the peptide FFSWGa and tested by a calcium bioluminescence plate assay. The amino acids Phe(1) and Trp(4) were essential for activity of the insect kinins in both receptors. It was confirmed that the pentapeptide kinin core is the minimum sequence required for activity and that the C-terminal amide is also essential. In contrast to the tick receptor, a large increase in efficacy is observed in the mosquito receptor when the C-terminal pentapeptide is N-terminally extended to a hexapeptide. The aminoisobutyric acid (Aib)-containing analog, FF[Aib]WGa, was as active as superagonist FFFSWGa on the mosquito receptor in contrast to the tick receptor where it was statistically more active than FFFSWGa by an order of magnitude. This restricted conformation Aib analog provides information on the conformation associated with the interaction of the insect kinins with these two receptors. Furthermore, the analog FF[Aib]WGa has been previously shown to resist degradation by the peptidases ACE and nephrilysin and represents an important lead in the development of biostable insect kinin analogs that ticks and mosquitoes cannot readily deactivate.

Aedes↗
PubMed2001

Dipeptide frequency/bias analysis identifies conserved sites of nonrandomness shared by cysteine-rich motifs.

This report describes the application of a simple computational tool, AAPAIR.TAB, for the systematic analysis of the cysteine-rich EGF, Sushi, and Laminin motif/sequence families at the two-amino acid level. Automated dipeptide frequency/bias analysis detects preferences in the distribution of amino acids in established protein families, by determining which "ordered dipeptides" occur most frequently in comprehensive motif-specific sequence data sets. Graphic display of the dipeptide frequency/bias data revealed family-specific preferences for certain dipeptides, but more importantly detected a shared preference for employment of the ordered dipeptides Gly-Tyr (GY) and Gly-Phe (GF) in all three protein families. The dipeptide Asn-Gly (NG) also exhibited high-frequency and bias in the EGF and Sushi motif families, whereas Asn-Thr (NT) was distinguished in the Laminin family. Evaluation of the distribution of dipeptides identified by frequency/bias analysis subsequently revealed the highly restricted localization of the G(F/Y) and N(G/T) sequence elements at two separate sites of extreme conservation in the consensus sequence of all three sequence families. The similar employment of the high-frequency/bias dipeptides in three distinct protein sequence families was further correlated with the concurrence of these shared molecular determinants at similar positions within the distinctive scaffolds of three structurally divergent, but similarly employed, motif modules.

Amino Acid Motifs↗
PubMed1989

The quantitative analysis of agrammatic production: procedure and data.

Despite the long-standing interest in structural aspects of aphasic production, no method has emerged for the systematic analysis of aphasic speech. This paper attempts to address that need by outlining a procedure for the quantitative assessment of narrative speech which yields measures for both morphological and structural characteristics of aphasic production. In addition to complete instructions for carrying out this analysis, data for three groups of subjects are presented: agrammatic aphasics, aphasics who are similarly nonfluent but not clinically judged as agrammatic, and normal controls. While the agrammatics were distinguishable from the nonagrammatic patients on most measures, both nonfluent groups showed comparable reductions in the structural complexity of their propositional utterances. Other findings include indications from individual patient data that aspects of grammatical morphology may dissociate in agrammatism.

Adult↗
PubMed1998

Effects of critical coronary stenosis on global systolic left ventricular function quantified by pressure-volume relations during dobutamine stress in the canine heart.

OBJECTIVES: In this study we quantified the effects of a critical coronary stenosis on global systolic function using pressure-volume relations at baseline and during incremental dobutamine stress. BACKGROUND: The effects of coronary stenosis have previously been analyzed mainly in terms of regional (dys)function. Global hemodynamics are generally considered normal until coronary flow is substantially reduced. However, pressure-volume analysis might reveal mechanisms not fully exposed by potentially load-dependent single-beat parameters. Moreover, no systematic analysis by pressure-volume relations of the effects of dobutamine over a wide dose range has previously been presented. METHODS: In 14 dogs left ventricular volume and pressure were measured by conductance and micromanometer catheters, and left circumflex coronary flow by Doppler probes. Measurements in control and with left circumflex stenosis were performed at baseline and at five levels of dobutamine (2.5 to 20 microg/kg/min). The end-systolic pressure-volume relation (ESPVR) dP/dtMAX vs. end-diastolic volume (dP/dtMAX - V(ED)) and the relation between stroke work and end-diastolic volume (preload recruitable stroke work [PRSW]) were derived from data obtained during gradual caval occlusion. RESULTS: In control, dobutamine gradually increased heart rate up to 20 microg/kg/min, the inotropic effect blunted at 15 microg/kg/min. With stenosis, the chronotropic effect was similar, however, contractile state was optimal at approximately 10 microg/kg/min and tended to go down at higher levels. At baseline, the positions of ESPVR and PRSW, but not of dP/dtMAX - V(ED), showed a significant decrease in function with stenosis. No differences between control and stenosis were present at 2.5 microg/kg/min; the differences were largest at 15 microg/kg/min. CONCLUSIONS: Pressure-volume relations and incremental dobutamine may be used to quantify the effects of critical coronary stenosis. The positions of these relations are more consistent and more useful indices than the slopes. The positions of the ESPVR and PRSW show a reduced systolic function at baseline, normalization at 2.5 microg/kg/min and a consistent significant difference between control and stenosis at dobutamine levels of 5 microg/kg/min and higher.

Animals↗
PubMed2004

Assessing progress in analysis interminable.

A case study is provided of a schizoid patient in her mid-sixties who in a lengthy analysis had made significant clinical improvement. The treating analyst's impression of clinical improvement was independently verified through systematic analysis of transcripts of audiotapes of thirty-six sessions over a four-year period of treatment. The patient showed significant improvement on measures of character pathology, object relations, mentalization, and superego anxiety. The results suggest that some patients with entrenched character pathology who seem to be in analysis interminable may still make clinically significant improvement. It is suggested that the scientific status of psychoanalysis would be greatly enhanced if the anecdotal evidence generated in private practice were supported by independent verification. The current study illustrates one methodology, "case study plus," for providing independent verification while retaining the richness of the traditional case study.

Female↗
PubMedDate not supplied

Chemotherapy response rates in recurrent/progressive pediatric glioma; results of a systematic review.

The optimum treatment strategy for recurrent childhood glioma is unknown. This report presents a systematic analysis of the currently available clinical data on chemotherapeutic management of this disease. A study protocol was prospectively developed outlining the objectives and methods of analysis including literature search strategy, eligibility criteria for published trials to be included, key data elements to be extracted and a plan for statistical analysis. Summary statistics were analyzed for the primary outcome variables. Data on recognized prognostic factors were recorded in order to adjust the outcome measures for these factors. A total of 27 non-randomized clinical trails were included in the analysis. Studies were stratified into 6 chemotherapy classes based on the frequency of drug used across studies. Average median response (complete + partial) across all drug categories was approximately 14% (range 10.4-23.5%). Adding patients with stable disease to complete and partial responders at least doubled average median response rates. Time to tumor progression ranged from 29.4 weeks to 49.7 weeks. The most frequently used drugs were the platinum analogs which demonstrated a mean TTP of 42.0 = /-23.4 weeks. Small sample sizes and the overall poor quality of the available data precluded definitive conclusions regarding the clinical impact of the various drug classes on the natural history of this disease.

Adolescent↗
PubMed2005

An evaluation, comparison, and accurate benchmarking of several publicly available MS/MS search algorithms: sensitivity and specificity analysis.

MS/MS and associated database search algorithms are essential proteomic tools for identifying peptides. Due to their widespread use, it is now time to perform a systematic analysis of the various algorithms currently in use. Using blood specimens used in the HUPO Plasma Proteome Project, we have evaluated five search algorithms with respect to their sensitivity and specificity, and have also accurately benchmarked them based on specified false-positive (FP) rates. Spectrum Mill and SEQUEST performed well in terms of sensitivity, but were inferior to MASCOT, X!Tandem, and Sonar in terms of specificity. Overall, MASCOT, a probabilistic search algorithm, correctly identified most peptides based on a specified FP rate. The rescoring algorithm, PeptideProphet, enhanced the overall performance of the SEQUEST algorithm, as well as provided predictable FP error rates. Ideally, score thresholds should be calculated for each peptide spectrum or minimally, derived from a reversed-sequence search as demonstrated in this study based on a validated data set. The availability of open-source search algorithms, such as X!Tandem, makes it feasible to further improve the validation process (manual or automatic) on the basis of "consensus scoring", i.e., the use of multiple (at least two) search algorithms to reduce the number of FPs. complement.

Algorithms↗
PubMed1996

Motifs and conformational analysis of amino acid residues adjoining beta-turns in proteins.

Using a data set of 250 non-homologous high-resolution globular proteins, a systematic analysis of the conformations that precede and succeed (positions i and i + 3) the various classical beta-turn types has been carried out. The collective conformation of a specific beta-turn type, including the flanking positions, termed motif, has been studied. In all the four turn types, the majority of examples are preceded and succeeded by extended conformation. Some of the other observations are: (1) In a type I beta-turn, Gly at position i + 3 has a higher favorability to occur with positive phi and does not prefer the major motif beta-alpha R-alpha R-beta. (2) The left-handed alpha-helical conformation (alpha L) is not preferred at both the flanking positions for type I' and II' beta-turns. (3) The beta--beta motif is favourable for all the turn types and the motif beta--alpha L very highly favourable for type I.

Amino Acids↗
PubMed2005

Probing the interactions between the folding elements early in the folding of Escherichia coli dihydrofolate reductase by systematic sequence perturbation analysis.

One of the necessary conditions for a protein to be foldable is the presence of a complete set of folding elements (FEs) that are short contiguous peptide segments distributed over an amino acid sequence. Previous studies indicated the FE assembly model of protein folding, in which the FEs interact with each other and coalesce to form an intermediate(s) early in the folding reaction. This suggests that a clue to the understanding of the determinants of protein foldability can be found by investigating how the FEs interact with each other early in the folding and thereby elucidating roles of the FEs in protein folding. To reveal the formation process of FE-FE interactions, we studied the early folding events of Escherichia coli dihydrofolate reductase (DHFR) utilizing systematic sequence perturbation analysis. Here, systematic single amino acid substitutions were introduced inside of the FEs (W30X in FE2, V40X in FE3, N59X in FE4, and I155X in FE10; X refers to various amino acid residues), and their kinetic refolding reactions were measured by stopped-flow circular dichroism and fluorescence. We show that the interactions around Trp30 and Ile155 are formed in the burst phase intermediate, while those around Val40 and Asn59 are formed in the transition state of the subsequent folding phase (tau5-phase) and in much later processes, respectively. These and previous results suggest that FE2 and FE10, and also FE1 and FE7, involved in the loop subdomain of DHFR, interact with each other within a millisecond time range, while the stable FE3-FE4 interactions are formed in the later processes. This may highlight the important roles of the FEs mainly inside of the loop subdomain in formation of the burst phase intermediate having a hydrophobic cluster and native-like overall topology and in acquisition of the foldability of DHFR.

Amino Acid Sequence↗
PubMed2006

[Mortality analysis as a tool for quality improvement in a general surgery service].

OBJECTIVES: The present study aims to propose a method to improve healthcare quality based on systematic analysis of mortality and mortality-related adverse effects. PATIENTS AND METHODS: We analyzed all deaths in the surgery service between January, 1997 and December, 2003. There were 10,905 hospital admissions and 194 deaths. The mean number of deaths per year was 28 (range 24-36). The mean number of deaths/discharges per year was 1.77 (SD 0.2; range 1.5-2.13). The overall mean age was 80.5 years (SD 9.5; range 47-100). By sex there were 104 women (53.6%) and 90 men (46.6%). During the study period 9,437 patients underwent surgery. We defined the concept of death secondary to a hospital problem (DSHP): this easily objectified concept includes any hospital problem occurring from admission to death associated directly or indirectly with death, or simply precipitating a foreseeable death. RESULTS: We detected 33 DSHP. Of all deaths, 17% were DSHP. In these DSHP, 37 problems were detected (some deaths involved more than one problem). The most frequent types of problem were three nosocomial infections, 19 problems secondary to therapeutic or diagnostic techniques, seven insufficient evaluations or treatment omissions or delays, and eight harmful incidents. No deaths occurred because of organizational or structural problems. The number of DSHP in relation to discharges was 0.3%. CONCLUSIONS: We present a system of continuous self-evaluation, in which problems are recognized and a constructive attitude is adopted. The model can be extrapolated to other hospitals but the results must be evaluated in the specific context of each hospital. Nevertheless, the results can be used for monitoring within a single center over a period of years.

Aged↗
PubMed1979

Analysis of hospital capital decision alternatives: a priority assignment model.

In the not-for-profit sector in general and in the hospital industry in particular, the systematic analysis of capital decision alternatives is often not attempted because those decision making criteria which do not have objective measures, but for which judgments must be rendered, are not explicitly integrated into the analysis of decision alternatives. Rather, judgments on these criteria enter the decision making process in some vague manner after an attempt has been made to develop a quantitative profile for each of the decision alternatives. The purpose of this paper is to examine a priority assignment model which (1) uses judgmental transitivity as a measure of the quality of the judgments rendered, and (2) provides for the mathematical integration of the quality adjusted judgmental information into the development of priority weights. Various operational aspects of the model are examined and illustrated and an example of its application provided.

Capital Expenditures↗