Dermatologie esthétique et correctrice: applications cliniques et rôle social [Esthetic and corrective dermatology: clinical applications and social role].

Skin diseases may have severe aesthetic and psychological repercussions leading sometimes to discriminations and social isolation. Dermatologists have contributed to the development of many cosmetic procedures: peelings, botulinum toxin or hyaluronic acid injections, lasers, blepharoplasty, facelift, etc. Many of these treatments have interesting clinical applications and may help numerous patients with skin diseases to return to a normal social life.

Comparison of the efficacy and longevity of nonpenetrating glaucoma surgery with and without a new, nonabsorbable hydrophilic implant.

BACKGROUND AND OBJECTIVE: To compare the efficacy and longevity of nonpenetrating glaucoma surgery with and without the use of a nonabsorbable hydrophilic implant at the Oxford Eye Centre, Johannesburg, South Africa, and the Glaucoma Unit, Jules Gonin Ophthalmic Hospital, Lausanne, Switzerland. PATIENTS AND METHODS: In a nonrandomized, prospective study between March 1997 and December 2001, 48 eyes of 32 patients aged 18 to 86 years with primary open-angle glaucoma underwent nonpenetrating glaucoma surgery; 25 eyes with the implant and 23 eyes without it. Intraocular pressure (IOP) was recorded preoperatively and postoperatively at 1, 7, and 14 days, at 1, 3, and 6 months, and thereafter every 6 months. RESULTS: The mean preoperative IOP was 27.5 +/- 11.8 mm Hg (range, 20 to 64 mm Hg) in the implant group and 24.8 +/- 7.1 mm Hg (range, 16 to 38 mm Hg) in the control group. During the first 18 months of follow-up, both groups showed identical IOP progression and the mean IOP remained less than 14 mm Hg. After 2 years of follow-up, the IOP started to rise in the control group but remained stable in the implant group. After 30 months, the mean IOP was 12.4 +/- 2 mm Hg and the IOP decrease in percentage was 62% +/- 6% in the implant group (n = 13) versus 16.1 +/- 3 mm Hg and 34% +/- 13% in the control group (n = 15) (mean IOP, P = .0022; mean IOP decrease in percentage, P = .01). CONCLUSIONS: During the first 18 months, there was no difference in the outcomes between the two groups. After 2 years of follow-up, the mean IOP was lower and the IOP decrease in percentage was greater in the implant group compared with the control group.

Liver kidney microsomes type 1 antibodies are associated with 80% reduction of the CYP2D6 activity in patients with chronic hepatitis C

Introduction Liver kidney microsomal type 1 (LKM-1) antibodies have been shown to decrease CYP2D6 activity in vitro. We investigated whether LKM-1 antibodies might reduce CYP2D6 activity also in vivo.Materials and Methods All patients with chronic hepatitis C and LKM-1 antibodies enrolled in the Swiss Hepatitis C Cohort Study (SCCS) were assessed: ten were eligible and fi tted to patients without LKM-1 antibodies. Patients were genotyped for CYP2D6 variants to exclude individuals with a poor metabolizer genotype. CYP2D6 activity was measured by a specifi c substrate using the dextromethorphan/dextrorphan (DEM/DOR) metabolic ratio to classify patients into four activity phenotypes (i.e. ultrarapid, extensive, intermediate and poor metabolizers). The concordance between phenotype based on DEM/DOR ratio and phenotype expected from genotype was examined in LKM-1 positive and negative patients. Groups were compared with respect to the DEM/DOR metabolic ratio.Results All patients had a CYP2D6 extensive metabolizer genotype. The observed phenotype was concordant with CYP2D6 genotype in most LKM-negative patients, whereas only three (30%) LKM-1 positive patients had a concordant phenotype (six presented an intermediate and one a poor metabolizer phenotype). The median DEM/DOR ratio was six-fold higher in LKM-1 positive than in LKM-1 negative patients (0.096 vs. 0.016, p = 0.004), indicating that CYP2D6 metabolic function was significantly reduced in the presence of LKM-1 antibodies.Conclusion In chronic hepatitis C patients with LKM-1 antibodies, the CYP2D6 metabolic activity was on average reduced by 80%. The impact of LKM-1 antibodies on CYP2D6-mediated drug metabolism pathways warrants further translational studies in the setting of new protease inhibitor therapies

Histopathology of peripapillary choroidal neovascularization.

The different therapeutic responses observed among choroidal neovascularization (CNV) of different etiologies, ages, and locations might be related to the presence of varied mediators. Two surgically removed peripapillary CNVs from two different patients were analyzed. One of the patients had received one intravitreous injection of bevacizumab 3 months earlier. CNV was analyzed using conventional histology and immunohistochemistry. Histological analysis showed intense neovascularization and epithelial and glial components. Vascular endothelial growth factor (VEGF) receptors were found in the endothelial cells and the epithelial cells of the CNV. VEGF was expressed in the patient who had not been previously treated with anti-VEGF. The CNV was deeply infiltrated by glial cells and invaded by microglial cells in one case. VEGF and VEGF receptors may be expressed, suggesting that therapies aiming at VEGF may be efficient only for a subtype of CNV and at a certain time point of their evolution.

Biophysical characterization of the interaction of endotoxins with hemoglobins.

Bacterial endotoxin (lipopolysaccharide, LPS) is the major component of the outer leaflet of the outer membrane in gram-negative bacteria. During severe infections, bacteria may reach the blood circuit of humans, and endotoxins may be released from the bacteria due to cell division or cell death. In particular enterobacterial forms of LPS represent extremely strong activator molecules of the human immune system causing a rapid induction of cytokine production in monocytes and macrophages. Various mammalian blood proteins have been documented to display LPS binding activities mediating normally decreasing effects in the biological activity of LPS. In more recent studies, the essential systemic oxygen transportation protein hemoglobin (Hb) has been shown to amplify LPS-induced cytokine production on immune cells. The mechanism responsible for this effect is poorly understood. Here, we characterize the interaction of hemoglobin with LPS by using biophysical methods. The data presented, revealing the changes of the type and size of supramolecular aggregates of LPS in the presence of Hb, allow a better understanding of the hemoglobin-induced increase in bioactivity of LPS.

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Pulmonary involvement in Fabry disease has received less attention than the effects of the disease on the kidneys, nervous system or heart. However, data from FOS -the Fabry Outcome Survey - are now helping to elucidate the pulmonary manifestations of Fabry disease. Twenty-three patients out of a cohort of 67 analysed in FOS have been identified with airway obstruction, as defined by a ratio of forced expiratory volume in 1 second to forced vital capacity of less than 0.7. This prevalence is much greater than would be expected in the general population, with the main risk factors appearing to be increasing age and male gender. Spirometric analysis has revealed that the airway obstruction is clinically much more similar to chronic obstructive pulmonary disease than to asthma. Although little is known about the anatomical changes responsible for airway obstruction in patients with Fabry disease, airway wall hyperplasia and/or fibrosis are potential causes. Treatment of patients with moderate or severe airway obstruction should include inhaled bronchodilators, and individuals who smoke should be encouraged to stop. Further studies and future analyses of FOS data should determine whether enzyme replacement therapy is able to help or prevent the pulmonary manifestations of Fabry disease.

Estimating attributable mortality due to nosocomial infections acquired in intensive care units.

BACKGROUND: The strength of the association between intensive care unit (ICU)-acquired nosocomial infections (NIs) and mortality might differ according to the methodological approach taken. OBJECTIVE: To assess the association between ICU-acquired NIs and mortality using the concept of population-attributable fraction (PAF) for patient deaths caused by ICU-acquired NIs in a large cohort of critically ill patients. SETTING: Eleven ICUs of a French university hospital. DESIGN: We analyzed surveillance data on ICU-acquired NIs collected prospectively during the period from 1995 through 2003. The primary outcome was mortality from ICU-acquired NI stratified by site of infection. A matched-pair, case-control study was performed. Each patient who died before ICU discharge was defined as a case patient, and each patient who survived to ICU discharge was defined as a control patient. The PAF was calculated after adjustment for confounders by use of conditional logistic regression analysis. RESULTS: Among 8,068 ICU patients, a total of 1,725 deceased patients were successfully matched with 1,725 control patients. The adjusted PAF due to ICU-acquired NI for patients who died before ICU discharge was 14.6% (95% confidence interval [CI], 14.4%-14.8%). Stratified by the type of infection, the PAF was 6.1% (95% CI, 5.7%-6.5%) for pulmonary infection, 3.2% (95% CI, 2.8%-3.5%) for central venous catheter infection, 1.7% (95% CI, 0.9%-2.5%) for bloodstream infection, and 0.0% (95% CI, -0.4% to 0.4%) for urinary tract infection. CONCLUSIONS: ICU-acquired NI had an important effect on mortality. However, the statistical association between ICU-acquired NI and mortality tended to be less pronounced in findings based on the PAF than in study findings based on estimates of relative risk. Therefore, the choice of methods does matter when the burden of NI needs to be assessed.

Changes in the transcriptional profile of transporters in the intestine along the anterior-posterior and crypt-villus axes.

BACKGROUND: The purpose of this work was to characterize the expression of drug and nutrient carriers along the anterior-posterior and crypt-villus axes of the intestinal epithelium and to study the validity of utilizing whole gut tissue rather than purified epithelial cells to examine regional variations in gene expression. RESULTS: We have characterized the mRNA expression profiles of 76 % of all currently known transporters along the anterior-posterior axis of the gut. This is the first study to describe the expression profiles of the majority of all known transporters in the intestine. The expression profiles of transporters, as defined according to the Gene Ontology consortium, were measured in whole tissue of the murine duodenum, jejunum, ileum and colon using high-density microarrays. For nine transporters (Abca1, Abcc1, Abcc3, Abcg8, Slc10a2, Slc28a2, Slc2a1, Slc34a2 and Slc5a8), the mRNA profiles were further measured by RT-PCR in laser micro-dissected crypt and villus epithelial cells corresponding to the aforementioned intestinal regions. With respect to differentially regulated transporters, the colon had a distinct expression profile from small intestinal segments. The majority (59 % for p cutoff < or = 0.05) of transporter mRNA levels were constant across the intestinal sections studied. For the transporter subclass "carrier activity", which contains the majority of known carriers for biologically active compounds, a significant change (p < or = 0.05) along the anterior-posterior axis was observed. CONCLUSION: All nine transporters examined in laser-dissected material demonstrated good replication of the region-specific profiles revealed by microarray. Furthermore, we suggest that the distribution characteristics of Slc5a8 along the intestinal tract render it a suitable candidate carrier for monocarboxylate drugs in the posterior portion of the intestine. Our findings also predict that there is a significant difference in the absorption of carrier-mediated compounds in the different intestinal segments. The most pronounced differences can be expected between the adjoining segments ileum and colon, but the differences between the other adjoining segments are not negligible. Finally, for the examined genes, profiles measured in whole intestinal tissue extracts are representative of epithelial cell-only gene expression.

Conditional compositional biplots: theory and application

The biplot has proved to be a powerful descriptive and analytical tool in many areasof applications of statistics. For compositional data the necessary theoreticaladaptation has been provided, with illustrative applications, by Aitchison (1990) andAitchison and Greenacre (2002). These papers were restricted to the interpretation ofsimple compositional data sets. In many situations the problem has to be described insome form of conditional modelling. For example, in a clinical trial where interest isin how patients’ steroid metabolite compositions may change as a result of differenttreatment regimes, interest is in relating the compositions after treatment to thecompositions before treatment and the nature of the treatments applied. To study thisthrough a biplot technique requires the development of some form of conditionalcompositional biplot. This is the purpose of this paper. We choose as a motivatingapplication an analysis of the 1992 US President ial Election, where interest may be inhow the three-part composition, the percentage division among the three candidates -Bush, Clinton and Perot - of the presidential vote in each state, depends on the ethniccomposition and on the urban-rural composition of the state. The methodology ofconditional compositional biplots is first developed and a detailed interpretation of the1992 US Presidential Election provided. We use a second application involving theconditional variability of tektite mineral compositions with respect to major oxidecompositions to demonstrate some hazards of simplistic interpretation of biplots.Finally we conjecture on further possible applications of conditional compositionalbiplots

Laser-ultraviolet-A induced ultra weak photon emission in human skin cells: A biophotonic comparison between keratinocytes and fibroblasts.

Photons participate in many atomic and molecular interactions and processes. Recent biophysical research has discovered an ultraweak radiation in biological tissues. It is now recognized that plants, animal and human cells emit this very weak biophotonic emission which can be readily measured with a sensitive photomultiplier system. UVA laser induced biophotonic emission of cultured cells was used in this report with the intention to detect biophysical changes between young and adult fibroblasts as well as between fibroblasts and keratinocytes. With suspension densities ranging from 1-8 x 106 cells/ml, it was evident that an increase of the UVA-laser-light induced photon emission intensity could be observed in young as well as adult fibroblastic cells. By the use of this method to determine ultraweak light emission, photons in cell suspensions in low volumes (100 microl) could be detected, in contrast to previous procedures using quantities up to 10 ml. Moreover, the analysis has been further refined by turning off the photomultiplier system electronically during irradiation leading to the first measurements of induced light emission in the cells after less than 10 micros instead of more than 100 milliseconds. These significant changes lead to an improvement factor up to 106 in comparison to classical detection procedures. In addition, different skin cells as fibroblasts and keratinocytes stemming from the same donor were measured using this new highly sensitive method in order to find new biophysical insight of light pathways. This is important in view to develop new strategies in biophotonics especially for use in alternative therapies.

Clinical evaluation of a method for detecting superficial surgical transitional cell carcinoma of the bladder by light-induced fluorescence of protoporphyrin IX following the topical application of 5-aminolevulinic acid: preliminary results.

BACKGROUND AND OBJECTIVE: In bladder cancer, conventional white light endoscopic examination of the bladder does not provide adequate information about the presence of "flat" urothelial lesions such as carcinoma in situ. In the present investigation, we examine a new technique for the photodetection of such lesions by the imaging of protoporphyrin IX (PpIX) fluorescence following topical application of 5-aminolevulinic acid (ALA). STUDY DESIGN/MATERIALS AND METHODS: Several hours after bladder instillation of an aqueous solution of ALA in 34 patients, a Krypton ion laser or a filtered Xenon arc-lamp was used to excite PpIX fluorescence. Tissue samples for histological analysis were taken while observing the bladder wall either by means of a video camera, or by direct endoscopic observation. RESULTS: A good correlation was found between the PpIX fluorescence and the histopathological diagnosis. On a total of 215 biopsies, 143 in fluorescent and 72 in nonfluorescent areas, all visible tumors on white light cytoscopy appeared in a bright red fluorescence with the photodetection technique. In addition, this method permitted to discover 47 unsuspected carcinomatous lesions on white light observation, among which 40% were carcinoma in situ. CONCLUSION: PpIX fluorescence induced by instillation into the bladder of 5-ALA is an efficient method of mapping the mucosa in bladder carcinoma.

Novel markers of the human follicle-associated epithelium identified by genomic profiling and microdissection.

BACKGROUND & AIMS: Regulation of gene expression in the follicle-associated epithelium (FAE) over Peyer's patches is largely unknown. CCL20, a chemokine that recruits immature dendritic cells, is one of the few FAE-specific markers described so far. Lymphotoxin beta (LTalpha1beta2) expressed on the membrane of immune cells triggers CCL20 expression in enterocytes. In this study, we measured expression profiles of LTalpha1beta2-treated intestinal epithelial cells and selected CCL20 -coregulated genes to identify new FAE markers. METHODS: Genomic profiles of T84 and Caco-2 cell lines treated with either LTalpha1beta2, flagellin, or tumor necrosis factor alpha were measured using the Affymetrix GeneChip U133A. Clustering analysis was used to select CCL20 -coregulated genes, and laser dissection microscopy and real-time polymerase chain reaction on human biopsy specimens was used to assess the expression of the selected markers. RESULTS: Applying a 2-way analysis of variance, we identified regulated genes upon the different treatments. A subset of genes involved in inflammation and related to the nuclear factor kappaB pathway was coregulated with CCL20 . Among these genes, the antiapoptotic factor TNFAIP3 was highly expressed in the FAE. CCL23 , which was not coregulated in vitro with CCL20 , was also specifically expressed in the FAE. CONCLUSIONS: We have identified 2 novel human FAE specifically expressed genes. Most of the CCL20 -coregulated genes did not show FAE-specific expression, suggesting that other signaling pathways are critical to modulate FAE-specific gene expression.