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Objective: This study was conducted to determine the efficacy and safety of stent grafts in the treatment of thoracic aortic aneurysms and dissections., Method: Our health technology assessment method combined a critical review of the literature with experts' opinions. Several databases, useful Web sites, and the gray literature were searched from January 1995 to December 2004. Some manually retrieved major articles published in 2005 were also included. The draft report was submitted to and discussed by a working group of 12 members nominated by relevant medical societies. The amended report was submitted to a multidisciplinary group of 12 peer reviewers for comment., Results: Endovascular stent grafting (ESG) repair for lesions of the thoracic aorta, including aneurysms, dissections, and aortic isthmus ruptures, is probably beneficial in terms of operative mortality and severe morbidity, with an incidence of paraplegia of 2.1% (range 0%-7%) for ESG vs 5% (range, 3%-15%) for surgery, provided that there is a rigorous medium-term assessment and that anatomic factors are favorable. A proximal neck length of at least 2 cm is needed to insert the stent graft. Indications for ESG in thoracic aortic aneurysm and dissection are similar to those for surgery. Endovascular stent grafting is particularly appropriate in patients with multiple traumas to the thoracic aorta in whom concomitant lesions are a contraindication to open surgery. Endovascular stent graft repair can only be done in public or private centers with expertise in both endovascular and surgical procedures and with adequate technical facilities. Patients should be informed of the advantages and drawbacks of both methods. A multidisciplinary discussion should address risks of converting to open surgery and possible need for a cardiopulmonary bypass. Patients should be monitored annually by computed tomography scan or magnetic resonance imaging and plain radiographs because long-term results are uncertain (possible stent graft deterioration, onset of aortic disease). They should be told of the need for surveillance and possible further treatment., Conclusions: A prospective registry of all thoracic aorta procedures (endovascular treatment, open surgery, thoracic ESG plus extra-anatomic bypass) needs to be set up. All practitioners and stent graft manufacturers should contribute to this registry. It should include information on patient monitoring in order to (1) select patients who could be treated by ESG repair, (2) assess the feasibility of a randomized controlled study comparing ESG and surgery, (3) assess the medium-term outcome of different devices, and (4) obtain a better understanding of the health economics aspects.

THE IMPACT FACTOR OF MEDICAL JOURNALS: Is a criterion for the assessment of their activity. Three bibliometrical indicators are published every year: the impact factor, the rapidity of citation index, which reflects the upward slope in increased citations and the duration of their actuality, reflecting the downward slope, after the peak. THE JOURNALS USED TO CALCULATE THESE INDICATORS: Are selected according to their periodicity, conformity to international editorial conventions, presence of a reading committee, of their citation frequency and, for a new journal, the earlier publications of the redaction committee and the authors. THERE ARE SEVERAL BIASES IN THE CALCULATION OF THE IMPACT FACTOR: The choice of the citations is subjective and the non-pertinence of the citations is well known. Several variables may intervene, such as the type of journal and its size, domain concerned, language of the publication, self-citations, coding of the articles depending on their nature, and the choice of the manuscripts published ("hot papers"). The impact factor is an indicator of citations and not of their quality, and can certainly not be used to assess an authors' work.

The aim of this study was to establish whether appropriate statistical analysis of 16 volumetric indices corresponding to 16 structures making up the entire telencephalon of Urodela could distinguish between two families, Salamandridae and Plethodontidae. We compared the efficiency of three statistical methods (stepwise discriminant analysis, artificial neural networks, correspondence factor analysis) and the information they provide. All three methods found the same species difficult to classify. However, only correspondence factor analysis could suggest explanations for "misclassifications" as it superimposes the two sets of variables, (sub)species and anatomical variables, thus revealing the correlations between them. The bulbus olfactorius accessorius and the caudal mitral cell layer of the bulbus olfactorius principalis were the most discriminatory structures in separating Salamandridae and Plethodontidae. The correspondence factor analysis mapped species very much in line with accepted taxonomy and highlighted several current controversies [e.g. positioning of certain newts (T. marmoratus, T. vulgaris, T. alpestris), of Salamandrina terdigitata, and of members of the genus Euproctus]. Mapping of Plethodontidae was less clear-cut than that of Salamandridae with more overlap among genera but was quite consistent with knowledge of brain structure complexification. We conclude that relationships derived from analyses of telencephalic structures provide valuable information that might help resolve ambiguities; we have coined the term "neurotaxonomy" for this approach., (Copyright 2002 Elsevier Science Ltd.)

Aim: We investigated the use of non-linear, multidimensional factor analysis for the study of observational data on death from breast cancer. These data were obtained in the context of a clinical practice and not in a clinical trial. We looked into the correlations between patient characteristics and time of death and/or disease-free interval., Patients and Methods: We first analyzed the characteristics of a population of patients that had died from breast cancer (n = 295), then of a population including patients still alive 7 years after surgery (n = 344). We used correspondence analysis (CA) which is based on chi(2)-metrics, does not assume linear relationships, and provides graphic overviews., Results: The CA mapped variables (clinical stage, histoprognostic grade, node status, receptor positivity) in a way that fits in well with available knowledge on their importance as prognostic factors. We observed, however, that death occurred during three main periods (1-3, 4-7, < OR = 8 years after surgery) defined by different mixes of variables as if the disease progressed by stage rather than continuously. The CA distinguished long-term survivors (>7 years) from patients who died 8-10 years after surgery. Long-term survivors tended to be node-negative; those who died at 8-10 years tended to be the youngest patients (under 40)., Conclusions: Because correspondence analysis combines the advantages of multidimensional and non-linear methods, it is a valuable exploratory tool for describing multiple correlations within a population before attempting to establish statistical significance of selected variables by more classic methods.

Treatments on offer to an individual with suspected disease are based on concepts which, like products, go through life-cycles (introduction, growth, maturity, decline). We argue that randomized controlled trials, meta-analyses, and guidelines have reached maturity and/or are already on the decline and note renewed interest in case reports and qualitative medicine. The latter emphasize individual rather than 'average' patients. Moreover, we point out that scientific evidence relates not only to variables that can be measured but also to categorical variables that are often neglected. An appropriate treatment strategy is probably one which is indicated by several methods based on different concepts rather than by a single standard method. The doctor's role is to use his critical judgement and experience to appraise evidence from formal trials and from analyses of observational data and to share his views with the patient.

Flavonoids are metabolized in vivo to monocyclic phenolic acids. We investigated whether 18 phenolic acids of the benzoic, phenylacetic, phenylpropanoic or cinnamic series-known or potential metabolites of flavonoids-inhibit reactive oxygen species (ROS) released by human polymorphonuclear neutrophils (PMNs). Chemiluminescence was measured after PMN stimulation with three agents (N-fMetLeuPhe, phorbol myristate acetate (PMA), or opsonised zymosan) using two probes (lucigenin or luminol) with or without horseradish peroxidase (HRP) in order to derive specificity profiles for each test compound. The profiles of the phenolic acids and flavonoids were compared by a multivariate (correspondence) factor analysis. Overall, the phenolic acids were less specific than the flavonoids and, with a few exceptions, less potent. Phenolic acids had virtually no effect on the chemiluminescence related to O2- formation that is measured by lucigenin but inhibited luminol luminescence. Inhibition for all but two phenolic acids was sensitive to HRP and might be explained by a scavenger mechanism. Few structure-activity relationships emerged suggesting that simple properties such as radical scavenging and/or redox activity rather than overall structure might be the key determinants of chemiluminescence inhibition. Whatever the mechanism, however, we conclude that part of the in vivo pharmacological activity of flavonoids may readily be accounted for by phenolic acids.

We describe the synthesis of a novel series of bis-basic substituted benzamides and their relative potency in inhibiting rat brain protein kinase alpha (PKC alpha) activity. None of the compounds inhibited enzyme activity via the catalytic domain but several did via the regulatory domain at 1-5 microM concentrations. Inhibition was comparable to that of several di- and triphenylacrylonitriles and triphenylethylenes. According to a multivariate factor (correspondence) analysis of QSAR descriptors, hydrophobicity (log p) and hydration energy were the most discriminant descriptors, much more so than molecular mass, molar refractivity, polarizability, molecular volume and solvent-accessible surface. Inhibitory activity was correlated with high hydrophobicity and low hydration energy. The higher potency of GL9 (N,N'-oxalyl-bis[(o-amino)[2-(diethylamino)ethyl]-benzamide]) that differed from its congener (GL25) by the presence of an oxamide rather than succinamide moiety was tentatively explained by the greater negative charges associated with the carbonyl groups of its oxamide residue. The higher potency of GL22 (N,N'-tere-phthalyl-bis[(o-amino)[2-(diethylamino)ethyl]-benzamide ] in which an aromatic ring is inserted between two benzamide moieties in para, para' rather than ortho, ortho' positions as in GL23 might be due to a planar conformation facilitating membrane insertion. In conclusion, correspondence analysis is a neat way of highlighting similarities and differences in molecular properties (QSAR descriptors and potency). Therapeutic doses of many classes of drug might interfere with the regulatory domain of PKC alpha if, like our test-compounds, they have basic side-chain(s), high hydrophobicity, low hydration energy, a planar conformation and/or a highly charged reactive (oxamide) moiety.

The aim of the study was to examine the potential of multidimensional analysis, and in particular of correspondence analysis (CA), in bringing to light the influence of sex and age on trace element (TE) concentrations in hair from an unselected French population. Sixteen elements (S, Hg, Se, Zn, Pb, Cd, Ni, Co, Mn, Fe, Cr, Mg, Al, Ca, Cu, Ag) were assayed by inductively coupled argon plasma (ICAP) emission spectroscopy in the scalp hair of 135 men and 346 women. In spite of the high background noise, CA was able to reveal the differing patterns in males and females. For instance, in this population, higher relative levels of the essential elements, Ca, Mg, Zn, and Cu, but also of Ag, characterized women's hair, whereas higher relative levels of the heavy metals, Fe and Pb, were associated with men's hair. Al and Ag were unexplainedly high in the hair of the youngest members of the population. The Cu and Co of youth seemed to give way to a predominance of Zn in maturity. The hair of individuals in their forties tended to be richest in Ca and Mg, but these elements decreased with advancing age. Heavy metals (Hg, Pb, Fe) accumulated with age, whereas Se, Mn, and Cr seemed independent of age. CA is manifestly a very useful tool for revealing underlying dimensions in complex dynamic systems and unsuspected relationships among variables. Clearly, the significance of the high Al and Ag contents in the hair of certain members of the population, especially of the very young, needs to be investigated from both physiological and toxicological aspects.

The global amino-acid composition of a protein, although a cruder variable than sequence, is nevertheless informative and has been correlated with protein structural class. In the present study, we have applied complementary multivariate methods based on chi 2-metrics (correspondence factor analysis (CFA), minimum spanning tree (MST), ascending hierarchical classification (AHC)) to the analysis of the amino-acid frequency patterns of the C-terminal domain of 39 members of the nuclear receptor superfamily. The correlations we observed among receptors by this simple approach were, with few exceptions, in line with published phylogenetic dendrograms derived by sequence alignment. Further multivariate analyses were performed on the receptor population combined with 26 serine protease inhibitors (SERPINS) in view of the analogies detected between these superfamilies by hydrophobic cluster analysis (HCA), which were at the origin of the choice of alpha 1-antitrypsin as a 3-dimensional (3D) model for the receptor hormone-binding domain. Both the MST and AHC identified two distinct protein populations which in the principal phi 1 phi 2 CFA plot showed virtually no overlap, thus suggesting that receptors and SERPINS have different overall folding patterns, although the lower-order phi 3 phi 4 plot did reveal some similarities, essentially in the use of hydrophobic amino acids, that might account for analogies in HCA patterns. Receptors had a preference for those amino acids that are more frequent in alpha-helices and SERPINS for those in beta-strands and also tended to use different amino acids in turns. We therefore propose that multivariate analysis of amino-acid composition may prove helpful in identifying proteins for subsequent HCA.