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At least 829 records · Page 46Linked to original sources
PubMed2000

Clinical errors in emergency medicine: experience at the emergency department of an Italian teaching hospital.

The level of commitment in the analysis of clinical errors made in the emergency department (ED) is currently focused on organization and processes rather than on individual action. Four major cases of clinical errors made in the ED of a teaching hospital were investigated. Analysis suggested that the process of clinical decision making and the overreliance on the use of patterns during the cognitive process had a major role in causing the errors, rather than factors related to procedures or organization. It appears hard to design system changes and tactics to significantly reduce the probability of making errors associated with the cognitive process involved in clinical decision making. The authors have initiated a systematic analysis of errors made during the diagnostic workup in their ED, and the rate of clinically significant errors is tracked. A file is being created with the purpose to use it for teaching and orientation of all new staff.

Aged↗
PubMed2003

Rhinoplasty for the Mediterranean nose.

Homogenization of world culture through communications media, refinements in surgical techniques, and improved rhinoplasty results have resulted in a more extended dissemination of rhinoplasty among non-Caucasians. This request has led to increasingly anatomic, morphologic, and anthropometrical studies of the non-Caucasian nose upon which surgical techniques have been proposed and addressed to create in these patients nasal features typical of a Caucasian-looking nose. There are few reports in medical literature concerning rhinoplasty that specifically address particular Caucasian ethnic groups (Anglo-Saxon, Germanic, Latin, and Slavic). Generally included within the Latin group are subjects presenting both paradigmatic nasal morphologies (typically, the classic "Greek," "Roman," and "French" noses) and important cultural differences that greatly influence the subjective perception of the defect and, therefore, the type of change requested. These challenging conditions require a highly "customized" approach, both in the phase of the preoperative planning and in the choice of surgical options. The authors, by means of a photographic analysis systematically used with all their rhinoplasty patients, have identified some archetypes of nasal pyramid configurations that are typical of the reference population (44% Northern Italy, 15% Central Italy, 41% Southern Italy) and, on the basis of a medium/long-term evaluation of the relationship between adopted surgical techniques and results, propose some surgical options that are specific for every nasal archetype. This categorization helps the surgeon carry out a structured preoperative aesthetical analysis and provides him/her with both an anticipation of what findings to expect and the ability to deal with already diagnosed problems. Every archetype shows strong similarities in terms of preoperative analysis, surgical solutions, and subjective perception of the success of the surgery. The surgical options used proved to be apt to modify some paradigmatic defects in a satisfactorily predictable way. Combining the different tesserae of this puzzle to reach the goal of a satisfied patient (and not necessarily a beautiful nose) makes rhinoplasty a true challenge that requires a special talent from the surgeon: combining analysis capabilities, surgical logic, and manual skills with artistic sensitivity.

Adolescent↗
PubMed1984

[The alcoholization process in Latin America. Critical analysis of biomedical and sociological production, 1970-1980 (2)].

This work analyses the bibliographical production in the sociological and biomedical fields on alcoholization generated within and for Latin America during the seventies. This production is characterized by a unilaterally "pathologizing" outlook, which contrasts with the outlook dominant in the socio-anthropological fields, and which was analysed in a previous work. Empirical and factorial outlook dominate, in both, theory and methodology. They stress again an approach whose serious limitations have already been shown. The dominant technical elements--the sociological and epidemiological inquest--keep on being utilized, in spite of the many criticisms which they have received. Data obtained not only bears little relevance on the problem, but also stresses facts at a level of depth which is not justified, and do not justify, the theoretical framework of analysis. In spite of the fact that unsystematized empirical data and specific research which has been undertaken in other regional areas have made reference to a continual deficit on the part of the health team for the diagnosis and treatment of the alcoholization process; we hardly have any research which can throw light on the scientific and ideological limitations of medical and paramedical actions. Besides, we do not have a systematic analysis of alternative therapeutic strategics. All bibliographical publications refers, in a very biased way, the process of alcoholization to the lower population strata, without any critical reflection on that association. The biomedical dimension, although it utilizes conceptions and viewpoints which have been taken from anthropological and sociological production, this appropiation has meant a modification, which, in fact, has caused a split between the two dominant productions in Latin America: the biomedical and the anthropological one. This split replicates the conflict between models, that operates within other national and international contexts.

Alcoholism↗
PubMed2002

Genome-wide analysis of hepatic fibrosis in inbred mice identifies the susceptibility locus Hfib1 on chromosome 15.

BACKGROUND & AIMS: Host genetic factors are likely to contribute to the variable course of hepatic fibrosis in response to chronic liver injury. Similarly, the fibrotic response differs among inbred mouse strains after challenge with CCl(4). Our aim was to identify unknown susceptibility loci for hepatic fibrosis in a cross between fibrosis-susceptible and -resistant inbred mice. METHODS: Seven inbred mouse strains were treated with CCl(4), and hepatic fibrosis was phenotypically characterized by histology, hepatic hydroxyproline levels, and serum surrogate markers. F(1) hybrids of susceptible BALB/cJ and resistant A/J inbred strains were intercrossed to obtain 358 F(2) progeny. Quantitative trait loci (QTL) that determine hepatic fibrosis were identified by genome-wide interval mapping and haplotype analysis. RESULTS: In this model, marked strain differences in fibrosis susceptibility exist, with BALB/c inbred mice being most susceptible. The hydroxyproline levels of F(1) mice resemble the resistant parental strains, indicating that fibrosis susceptibility is a recessive trait. QTL analysis identifies a susceptibility locus on chromosome 15 that significantly affects the stage of fibrosis and hydroxyproline levels. According to standard nomenclature, this locus is called Hfib1 (hepatic fibrogenic gene 1). Hfib1 is defined by genetic markers D15Mit26 and D15Mit122. A suggestive QTL on chromosome 2 colocalizes with the complement factor 5 gene, known to be mutated in the resistant strain A. CONCLUSIONS: The set of inbred strains provides a framework for systematic analysis of fibrogenic genes. QTL mapping is useful to identify genetic susceptibility loci for hepatic fibrosis that might harbor new molecular targets for antifibrotic drug design.

Animals↗
PubMed2004

Does the architecture of hospital facilities influence nosocomial infection rates? A systematic review.

OBJECTIVE: To review the evidence regarding the effects of interventions to improve hospital design and construction on the occurrence of nosocomial infections. METHODS: Systematic review of experimental and non-experimental, architectural intervention studies in intensive care units (ICUs), surgical departments, isolation units, and hospitals in general. The studies dated from 1975, and were in English, French, German, Italian, and Spanish. Regardless of format, the studies were identified through seven medical databases, reference lists, and expert consultation. RESULTS: One hundred seventy-eight scientific articles were identified; however, none of these described a meta-analysis, systematic review, or randomized, controlled trial. Most of the articles were categorized at the lowest level of evidence (expert judgment or consensus statements). Only 17 described completed concurrent or historical cohort studies matching the inclusion criteria (ICUs, 9; surgical departments, 4; isolation units, 2; hospitals in general, 2). The interventions generally included a move to other premises or renovation. However, in many studies, the staff-to-patient ratio was also improved. Some studies showed lower infection rates after intervention, but this finding cannot be generalized because of confounding and frequently small study populations. CONCLUSIONS: The lack of stringent evidence linking hospital design and construction with the prevention of nosocomial infection is partly attributable to the multifactorial nature of these infections, and some improvement will be seen if basic conditions such as the availability of sufficient space, isolation capacity, and facilities for handwashing are met. However, to our knowledge, other factors, especially the improper hand hygiene of medical staff, have greater impact.

Architecture↗
PubMed1998

Autoantibodies against human calpastatin in rheumatoid arthritis: epitope mapping and analysis of patient sera.

Autoantibodies against calpastatin have recently been described to be highly prevalent in sera of patients with rheumatoid arthritis (RA). When the sera of 45 patients with RA were analysed for autoantibodies against calpastatin by a newly developed enzyme-linked immunosorbent assay (ELISA), only four sera (8.9%) tested positive, which is not significantly different from the frequency observed in healthy controls. Since the ELISA is based on a synthetic peptide containing the C-terminal 27 amino acids of calpastatin bound to the solid phase, this negative result might be the consequence of the small antigen used. Therefore, a systematic analysis of the epitopes for autoantibodies in calpastatin was performed using sera from RA patients and healthy individuals. Recombinant fusion proteins containing fragments of calpastatin or the complete protein were produced and sera analysed by Western blots. In the N-terminal portion (amino acids 1-369), at least two major epitopes exist, against which 65% of normal sera as well as 76% of RA sera show reactivity in Western blot assays. These epitopes are not useful for clinical diagnostics. Only five out of 45 (11.1%) RA sera reacted against the C-terminal portion (amino acids 363-708) of calpastatin, while four out of 52 (7.7%) control sera showed reactivity. Three of the five RA sera and two out of four control sera had autoantibodies against the C-terminal 27 amino acids of calpastatin. These three patient sera had already been tested positive in the ELISA. The fourth patient positive in the ELISA was Western blot negative. The differences between the group of RA patients and controls are not statistically significant. When the clinical characteristics of the four patients with autoantibodies against the carboxyl end of calpastatin were analysed, it became apparent that all four had significantly elevated C-reactive protein (>50 mg/l). This observation might indicate that calpastatin autoantibodies are found in RA patients with more active disease. Thus, while the majority of RA patients do not have an increased prevalence of calpastatin autoantibodies, it cannot be ruled out definitively that a small subgroup may be characterized by autoantibodies to the C-terminus of calpastatin.

Adult↗
PubMedDate not supplied

Molecular biology in arteriosclerosis research.

The topics discussed in this article illustrate how molecular biology will have a dramatic impact on arteriosclerosis research. DNA clones for a small number of relevant proteins have been isolated, and studies are underway in numerous laboratories to extend these initial studies. The techniques of molecular biology will provide major advances in our understanding of numerous proteins directly or indirectly involved in the atherogenic process. Cloning technology will solve the primary structures of many proteins that can not be purified in quantities sufficient for classical methods of analysis. Studies of regulation will benefit from the availability of DNA probes, the ability to generate site-directed antibodies, and the use of reverse genetics to identify nucleic acid sequences involved in the regulation of gene expression. Studies of gene structure and genetic polymorphisms will unravel the genetic basis for defects in lipid and lipoprotein metabolism and should provide valuable reagents for clinical screening and diagnosis. The reverse genetics approach will permit the systematic analysis of structure-function relationships at the protein level in a manner not previously possible. Each of these will contribute to our understanding of the atherogenic process and should provide insight into ways of preventing and treating arteriosclerosis.

Amino Acid Sequence↗
PubMed2003

Interactions within the mammalian DNA methyltransferase family.

BACKGROUND: In mammals, epigenetic information is established and maintained via the postreplicative methylation of cytosine residues by the DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b. Dnmt1 is required for maintenance methylation whereas Dnmt3a and Dnmt3b are responsible for de novo methylation. Contrary to Dnmt3a or Dnmt3b, the isolated C-terminal region of Dnmt1 is catalytically inactive, despite the presence of the sequence motifs typical of active DNA methyltransferases. Deletion analysis has revealed that a large part of the N-terminal domain is required for enzymatic activity. RESULTS: The role played by the N-terminal domain in this regulation has been investigated using the yeast two-hybrid system. We show here the presence of an intra-molecular interaction in Dnmt1 but not in Dnmt3a or Dnmt3b. This interaction was confirmed by immunoprecipitation and was localized by deletion mapping. Furthermore, a systematic analysis of interactions among the Dnmt family members has revealed that DNMT3L interacts with the C-terminal domain of Dnmt3a and Dnmt3b. CONCLUSIONS: The lack of methylating ability of the isolated C-terminal domain of Dnmt1 could be explained in part by a physical interaction between N- and C-terminal domains that apparently is required for activation of the catalytic domain. Our deletion analysis suggests that the tertiary structure of Dnmt1 is important in this process rather than a particular sequence motif. Furthermore, the interaction between DNMT3L and the C-terminal domains of Dnmt3a and Dnmt3b suggests a mechanism whereby the enzymatically inactive DNMT3L brings about the methylation of its substrate by recruiting an active methylase.

Amino Acid Motifs↗
PubMed2002

[Systematic reviews in practice. IX. Determining their place in treatment recommendations in practice guidelines].

In a systematic review (SR), the available evidence for a clinical problem is systematically and comprehensively collected from different studies, the likelihood of bias is assessed and the results are summarised in a reproducible manner. The results of an SR can be used in either individual patient care or the formulation of a practice guideline. Throughout the world, (national) organisations for guideline development use systems for classifying the validity of evidence according to the study design ('levels of evidence'), and this is also the case in the Netherlands. In formulating a treatment recommendation, consideration must be given to the various factors which determine the strength of the evidence: study design, consistency of the results (if more studies are available), quality of the individual studies, magnitude and precision of the reported effect and the clinical relevance of the outcome measures. If insufficient studies with the same outcome measure are available, problems can arise in an SR. In practice, problems can also arise with respect to estimating the cogency of an SR compared to another review or primary studies. For the same subject, there might be discordant reviews, differences between reviews and megatrials might exist or just one randomised clinical trial might be available. These problems can often be solved with the aid of a systematic analysis. This requires both methodological and clinical expertise.

Bias↗
PubMed1980

Effects of endogenous sex hormones on mouse liver ethylmorphine N-demethylase.

For most commonly used mouse strains there is either no sex difference in drug metabolism, or females have a higher rate of metabolism than males of the same strain. In the CRL:CD-1 strain, for example, the males have a lower Vmax and a higher Km than females for ethylmorphine N-demethylation. By contrast, kinetic analysis for this pathway of drug metabolism in the BALB/cJ mouse strain demonstrated that males have a higher Vmax and a lower Km than females. Although gonadal hormones appear to play a similar role in both the strains with respect to body weight, liver weight, microsomal protein content, and the weights of sex hormone responsive organs, a strict dependence of the sex differences in ethylmorphine (EM) metabolism on gonadal hormones could not be demonstrated. A systematic analysis of the spectral interactions of EM with cytochrome P-450 (P-450), the activities of NADPH P-450 reductase and NADPH oxidase in these mouse strains did not reveal a common regulatory site for gonadal hormones. Moreover, sex differences in EM N-demethylase activity are not a direct function of the total P-450 present in hepatic microsomes since, for both strains, males have higher P-450 content than females. We conclude, therefore, that sex differences in hepatic EM N-demethylase activity in the BALB/cJ and CRL:DC-1 mouse strains may depend on the relative quantities of the individual forms of microsomal P-450 which appear to be under genetic and/or hormonal control.

Animals↗
PubMed2004

Mutation analysis in Spanish patients with hereditary hemorrhagic telangiectasia: deficient endoglin up-regulation in activated monocytes.

BACKGROUND: Mutations in the endoglin (ENG) or ALK1 genes are responsible for hereditary hemorrhagic telangiectasia types 1 and 2 (HHT1 and HHT2), respectively, a dominant vascular dysplasia caused by haploinsufficiency. No formal mutation studies of patients with HHT have been conducted in Spain. METHODS: ENG and ALK1 mutation analyses were carried out in 13 Spanish HHT patients diagnosed according to the Curacao criteria. Because endoglin is up-regulated at the cell surface during the monocyte-macrophage transition, endoglin concentrations in activated monocytes were determined by immunofluorescence flow cytometry in a systematic analysis. As controls, 40 non-HHT volunteers were studied for up-regulation of endoglin in activated monocytes. RESULTS: The mutation responsible for HHT was identified in eight patients belonging to two unrelated families. One of the families has a nonsense mutation in exon 4 (c.511C>T; R171X) of the ENG gene, and accordingly the disorder was identified as HHT1. The other family has a missense mutation affecting exon 8 (c.1120C>T; R374W) of the ALK1 gene, and hence is a HHT2 family. Interestingly, endoglin up-regulation was deficient in activated monocytes of both HHT1 and HHT2 patients compared with controls. By contrast, endoglin up-regulation was age-independent in control donors across a broad range of ages. The extent of endoglin up-regulation in activated monocytes was most diminished in those patients with the most severe symptoms. CONCLUSIONS: Endoglin up-regulation in activated monocytes is impaired in HHT1 and HHT2 patients and is age-dependent in both HHT types. Endoglin expression may predict the clinical severity of HHT.

Antigens, CD↗
PubMedDate not supplied

[Ethical analysis of the decision-making process in occupational health practice].

BACKGROUND: Changes in workplaces and work organizations represent a challenge for governments, social partners and occupational health professionals whose aim is to appropriately satisfy emerging requirements and needs. An increasing number of occupational health problems requires a high-quality standard practice supported by ethically consistent decisions. The ethical aspect of the practice is strictly linked to that of appropriateness, involving requirements of effectiveness, efficiency and respect of ethical principles of the individual, community and society. OBJECTIVES AND METHODS: The paper aims at focusing the ethical components of the quality of an occupational health program by taking a systematic approach to the ethical problems. The approach consists of a 2-step process. The first step consists of appraising the basic ethical principles of the dilemma ("to do good": to prevent or to remove evil and to do or to promote good; "not to do evil", implying not to inflict evil; to do no harm; autonomy implying respect of other's freedom and self-determination; justice implying equity, solidarity and non discrimination). The second step consists of detecting the stakeholders involved or interested in the decision. The alternatives are discussed according to the assessment of ethical costs (violating the consistentprinciple) and ethical benefits (fulfilment of the consistent principle) for the stakeholders. RESULTS: Systematic analysis of the ethical components of the dilemma according to ethical principles and their discussion within a framework involving different stakeholders makes it possible to recognise ethical costs and ethical benefits of the alternative decisions. The decisions may have different costs and benefits, which should be considered and weighed to take a proper decision. Although there is no certainty about the suitability of the decision, the assessment of the ethical components may be a valuable tool in decision-making based on the awareness that any ethical aspect has been considered. CONCLUSION: Occupational health professionals are requested to act with respect for general ethical principles and preferences of the individual, groups and setting. A high-quality practice will take into account the ethical content and the ethical conduct and any intervention will include analysis of ethical principles to compare alternative decisions and their consequences for the different stakeholders. This approach guarantees a practice based on, in addition to scientific evidence, the assessment of ethical costs and ethical benefits to favour decisions preventing conflicts.

Cost-Benefit Analysis↗
PubMed1975

[Interaction between construction and fixation of knee endoprostheses (author's transl)].

The two completely different total knee-endoprostheses (hinge type and sled or runner type) have been compared concerning construction and ability for take up or transmission of forces and moments. The difference to the real knee joint are described. The reactions on fixing of endoprostheses in the bone caused by the construction are emphasized. By a systematic analysis of the so called sled-prostheses is to be shown to differantiate between real sled-prostheses with rotation and sliding mobility and pseudo-sled-prostheses (better rotation-segment-prostheses). They have only one possibility of rotation to realize the knee bending. The kind and number of existing "degrees of freedom" are used as a significant characteristic to differentiate the various endoprostheses principles and their variants. This study should mainly inspirate for a systematic comparison of efficiency of the different types of knee-endoprostheses. This should give the operating surgeon for a length of time an objective aid to decision.

Biomechanical Phenomena↗
PubMed1996

Nif- phenotype of Azotobacter vinelandii UW97. Characterization and mutational analysis.

We have identified the molecular basis for the nitrogenase negative phenotype exhibited by Azotobacter vinelandii UW97. This strain was initially isolated following nitrosoguanidine mutagenesis. Recently, it was shown that this strain lacks the Fe protein activity, which results in the synthesis of a FeMo cofactor-deficient apodinitrogenase. Activation of this apodinitrogenase requires the addition of both MgATP and wild-type Fe protein to the crude extracts made by A. vinelandii UW97 (Allen, R.M., Homer, M.J., Chatterjee R., Ludden, P.W., Roberts, G.P., and Shah, V.K. (1993) J. Biol. Chem. 268 23670-23674). Earlier, we proposed the sequence of events in the MoFe protein assembly based on the biochemical and spectroscopic analysis of the purified apodinitrogenase from A. vinelandii DJ54 (Gavini, N., Ma, L., Watt, G., and Burgess, B.K. (1994) Biochemistry 33, 11842-11849). Taken together, these results imply that the assembly process of apodinitrogenase is arrested at the same step in both of these strains. Since A. vinelandii DJ54 is a delta nifH strain, this strain is not useful in identifying the features of the Fe protein involved in the MoFe protein assembly. Here, we report a systematic analysis of an A. vinelandii UW97 mutant and show that, unlike A. vinelandii DJ54, the nifH gene of A. vinelandii UW97 has no deletion in either coding sequence or the surrounding sequences. The specific mutation responsible for the Nif- phenotype of A. vinelandii UW97 is the substitution of a non-conserved serine at position 44 of the Fe protein by a phenylalanine as shown by DNA sequencing. Furthermore, oligonucleotide site-directed mutagenesis was employed to confirm that the Nif- phenotype in A. vinelandii UW97 is exclusively due to the substitution of the Fe protein residue serine 44 by phenylalanine. By contrast, replacing Ser-44 with alanine did not affect the Nif phenotype of A. vinelandii. Therefore, it seems that the Nif- phenotype of A. vinelandii UW97 is caused by a general structural disturbance of the Fe protein due to the presence of the bulky phenylalanine at position 44.

Amino Acid Sequence↗
PubMed2004

Effects of embryo culture on global pattern of gene expression in preimplantation mouse embryos.

Culture of preimplantation embryos affects gene expression. The magnitude of the effect on the global pattern of gene expression, however, is not known. We compared global patterns of gene expression in blastocysts cultured from the one-cell stage in either Whitten's medium or KSOM + amino acids (KSOM/AA) with that of blastocysts that developed in vivo, using the Affymetrix MOE430A chip. The analysis revealed that expression of 114 genes was affected after culture in Whitten's medium, whereas only 29 genes were mis-expressed after culture in KSOM/AA. Expression Analysis Systematic Explorer was used to identify biological and molecular processes that are perturbed after culture and indicated that genes involved in protein synthesis, cell proliferation and transporter function were down-regulated after culture in Whitten's medium. A common set of genes involved in transporter function was also down-regulated after culture in KSOM/AA. These results provide insights as to why embryos develop better in KSOM/AA than in Whitten's medium, and highlight the power of microarray analysis to assess global patterns of gene expression.

Amino Acids↗
PubMed2005

Determination and analysis of the pre-mRNA cleavage sites in Arabidopsis.

Alignment of the Arabidopsis cDNA to genome DNA sequences revealed that approximately half of the mRNAs were found to contain 3' non-templated nucleotide addition prior to the poly(A) sequence. These findings suggest that we can more precisely determine the cleavage sites. Based on the nucleotide downstream of cleavage sites, we are able to derive a hierarchy of cleavage preferences A>>U>C>>G. Interestingly, the completely different hierarchy of preferences was derived to be U>>A>>G>C, based on the nucleotide upstream of cleavage sites. Dinucleotide AU is the most preferred composition for cleavage. The determination of the cleavage sites and systematical analysis can help in the enhancement of 3'-processing site prediction and mechanistic understanding of 3'-end processing in plant.

Arabidopsis↗
PubMed2005

All systems go: launching cell simulation fueled by integrated experimental biology data.

Biological simulation serves to unify the basic elements of systems biology, namely, model selection, experimentation and model refinement. To select biochemical models for simulation, metabolome analysis can be performed using capillary electrophoresis or liquid chromatography coupled with mass spectrometry. In this manner, selected models can be elaborated with temporal/spatial gene and protein expression data obtained from model organisms such as Escherichia coli. The E. coli single gene deletion mutant library (KO collection) and His-tag/GFP-fusion single open reading frame clone expression library (ASKA) are powerful resources for this task. The integration of parallel experimental datasets into dynamic simulation tools forms the remaining challenge for the systematic analysis and elucidation of biological networks and holds promise for biotechnological applications.

Cell Physiological Phenomena↗
PubMed2005

Effect of alcohols on protein hydration: crystallographic analysis of hen egg-white lysozyme in the presence of alcohols.

Organic solvents are known to bring about dehydration of proteins, the molecular basis of which has remained uncharacterized. The dehydration effect in many cases leads to eventual unfolding of proteins through the macroscopic solvent effect. In some cases, the organic solvent molecules also bind to protein surfaces, thereby forcing local unfolding. The X-ray structure of hen egg-white lysozyme co-crystallized in the presence of alcohols with varying hydrophobicities has been studied. It was noticed that although the alcohols have very little effect on the conformation of the overall protein structure, they profoundly affect protein hydration and disorder of the bound waters. Systematic analysis of the water structure around the lysozyme molecule suggests that an increasing order of hydrophobicity of alcohols is directly proportional to the higher number of weakly bound waters in the protein. As anticipated, the water molecules in the native structure with high temperature factors (>/=40 A(2)) attain higher disorder in the presence of alcohols. It is believed that the disorder induced in the water molecules is a direct consequence of alcohol binding.

1-Butanol↗