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Biomedical subjects

C Mottet

Publications and source records attributed to C Mottet.

At least 19 recordsLinked to original sources

Appropriate treatment for Crohn's disease: methodology and summary results of a multidisciplinary international expert panel approach--EPACT.

BACKGROUND/AIMS: For many therapeutic decisions in Crohn's disease (CD), high-grade evidence is lacking. To assist clinical decision-making, explicit panel-based appropriateness criteria were developed by an international, multidisciplinary expert panel. METHODS: 10 gastroenterologists, 3 surgeons and 2 general practitioners from 12 European countries assessed the appropriateness of therapy for CD using the RAND Appropriateness Method. Their assessment was based on the study of a recent literature review of the subject, combined with their own expert clinical judgment. Panelists rated clinical indications and treatment options using a 9-point scale (1 = extremely inappropriate; 9 = extremely appropriate). These scenarios were then discussed in detail at the panel meeting and re-rated. Median ratings and disagreement were used to aggregate ratings into three assessment categories: appropriate (A), uncertain (U) and inappropriate (I). RESULTS: 569 specific indications were rated, dealing with 9 clinical presentations: mild/moderate luminal CD (n = 104), severe CD (n = 126), steroid-dependent CD (n = 25), steroid-refractory CD (n = 37), fistulizing CD (n = 49), fibrostenotic CD (n = 35), maintenance of medical remission of CD (n = 84), maintenance of surgical remission (n = 78), drug safety in pregnancy (n = 24) and use of infliximab (n = 7). Overall, 146 indications (26%) were judged appropriate, 129 (23%) uncertain and 294 (52%) inappropriate. Frank disagreement was low (14% overall) with the greatest disagreement (54% of scenarios) being observed for treatment of steroid-refractory disease. CONCLUSIONS: Detailed explicit appropriateness criteria for the appropriate use of therapy for CD were developed for the first time by a European expert panel. Disease location, severity and previous treatments were the main factors taken into account. User-friendly access to EPACT criteria is available via an Internet site, www.epact.ch, allowing prospective evaluation and improvement of appropriateness of current CD therapy.

Crohn Disease↗

Global optimization study of small (10 < or = N < or = 120) Pd clusters supported on MgO(100).

Experimental evidence suggests that Pd clusters on MgO, known to be good reaction catalysts, have face centered cubic (fcc) epitaxial structures. The structure of such clusters is the result of the interplay of Pd-Pd and Pd-substrate bonds, the former inclined to favor icosahedral (Ih) and decahedral (Dh)-like structures, the latter leading to place Pd atoms on top of oxygen sites, according to an epitaxial stacking. This paper shows the results of a basin-hopping global optimization procedure applied to free and MgO-supported Pd clusters in the size range 10 < or = N < or = 120. Pd-MgO interactions are modeled by an analytical function fitted to ab initio results, while Pd-Pd interactions are modeled by a semiempirical potential. Besides the tight-binding Rosato-Guillopé-Legrand (RGL) potential, we have adopted a modified version of RGL that better reproduces the experimental surface energy of palladium, modifying the attractive part of Pd atoms potential energy. We have compared the two potential models, and as a result, the RGL potential favors clusters with epitaxial arrangements, so that cluster structures are epitaxial fcc in almost all the size ranges considered. On the contrary, the alternative potential model preserves some Ih-like characteristics typical of the free Pd clusters, and it suggests that a transition size from Ih-like to epitaxial structures can take place at about 100 atoms.

Journal Article↗

[Inflammatory diseases of the intestines].

5-aminosalicylates preparations are not superior to placebo for the maintenance of medically-induced remission in patients with Crohn's disease. We have to reconsider the potential risks associated with inhibition of lymphocyte trafficking since it can induce serious and potentially lethal infections. Infliximab has shown efficacy in active ulcerative colitis.

Adrenal Cortex Hormones↗

Self-organized growth of nanoparticles on a surface patterned by a buried dislocation network.

The self-organized growth of Co nanoparticles is achieved at room temperature on an inhomogenously strained Ag(001) surface arising from an underlying square misfit dislocation network of 10 nm periodicity buried at the interface between a 5 nm-thick Ag film and a MgO(001) substrate. This is revealed by in situ grazing-incidence small-angle x-ray scattering. Simulations of the data performed in the distorted wave Born approximation framework demonstrate that the Co clusters grow above the dislocation crossing lines. This is confirmed by molecular dynamic simulations indicating preferential Co adsorption on tensile sites.

Journal Article↗

Single impurity effect on the melting of nanoclusters.

We show by molecular dynamics simulations that the melting temperature of clusters can be tuned by selective doping. In fact, a single Ni or Cu impurity in Ag icosahedral clusters considerably increases the melting temperature even for sizes of more than a hundred atoms. The upward shift is correlated to the strain relaxation induced by a small central impurity in icosahedral clusters.

Journal Article↗

[Infectious diarrhea].

Traveler's diarrhea is generally a benign condition which resolves spontaneously in 48 h. Information on dietary hygiene, severity of symptoms and dehydration, as well as their management, is essential. Chemoprophylaxis and antibiotic treatment are not recommended, except in very specific situations. The incidence of chronic diarrhea in HIV-positive patients has dramatically decreased since the introduction of HAART. In the absence of any correlation with the initiation of HAART, a stepwise diagnostic workup is indicated (bacteriological cultures and microscopic examination of fecal samples followed by ileocolonoscopy and gastroduodenoscopy). Specific treatment of any pathogens identified, and HAART in the case of microsporidiasis or cryptosporidiosis, constitute the mainstay of therapeutic management of chronic diarrhea in these patients.

Anti-Bacterial Agents↗

[Inflammatory bowel diseases].

COX-2 specific anti-inflammatory agents appear as able to induce a flare of inflammatory bowel disease as classical anti-inflammatory agents. The use of steroids, immunomodulators or infliximab prior to surgery does not appear to increase post-operative complication rates. Cases of hepatitis B reactivation have been described after infliximab therapy, suggesting that hepatitis B serological status should be verified prior to infliximab therapy. Adalimubab, a fully humanized antibody directed against TNF-alpha, is efficacious in patients that have lost response or did not tolerate infliximab. Approval of this agent is still awaited. Leucoapheresis is a promising tool in ulcerative colitis.

Humans↗

Magic polyicosahedral core-shell clusters.

A new family of magic cluster structures is found by genetic global optimization, whose results are confirmed by density functional calculations. These clusters are Ag-Ni and Ag-Cu nanoparticles with an inner Ni or Cu core and an Ag external shell, as experimentally observed for Ag-Ni, and present a polyicosahedral character. The interplay of the core-shell chemical ordering with the polyicosahedral structural arrangement gives high-symmetry clusters of remarkable structural, thermodynamic, and electronic stability, which can have high melting points (they melt higher than pure clusters of the same size), large energy gaps, and (in the case of Ag-Ni) nonzero magnetic moments.

Journal Article↗

Growth of three-shell onionlike bimetallic nanoparticles.

We show by molecular dynamics simulations on three systems (B/A=Pd/Ag, Cu/Ag, and Ni/Ag) that three-shell metallic nanoparticles made by a core of a metal A, an intermediate shell of metal B and an external shell of metal A (A-B-A nanoparticles) can be grown by deposition of B atoms onto an A core. The growth of the intermediate B shell is triggered by the fact that the most favorable positions for isolated B impurities inside A clusters are located just one layer below the cluster surface.

Journal Article↗

Human CD4(+)CD25(+) thymocytes and peripheral T cells have immune suppressive activity in vitro.

CD4(+)CD25(+) T cells in mice and rats are capable of transferring protection against organ-specific autoimmune disease and colitis and suppressing the proliferation of other T cells after polyclonal stimulation in vitro. Here we describe the existence in humans of CD4(+)CD25(+) T cells with the same in vitro characteristics. CD4(+)CD8(-)CD25(+) T cells are present in both the thymus and peripheral blood of humans ( approximately 10 % of CD4(+)CD8(-) T cells), proliferate poorly in response to mitogenic stimulation and suppress the proliferation of CD4(+)CD25(-) cells in co-culture. This suppression requires cell contact and can be overcome by the addition of exogenous IL-2. CD4(+)CD25(+) cells from thymus and blood were poor producers of IL-2 and IFN-gamma, and suppressed the levels of these cytokines produced by CD4(+)CD25(-) cells. However, CD4(+)CD25(+) PBL produced higher levels of IL-4 and similar amounts of IL-10 as CD4(+)CD25(-) cells. Regulatory CD4(+)CD25(+) T cells have an activated phenotype in the thymus with expression of CTLA-4 and CD122 (IL-2Rbeta). The fact that CD4(+)CD25(+) regulatory T cells are present with a similar frequency in the thymus of humans, rats and mice, suggests that the role of these cells in the maintenance of immunological tolerance is an evolutionarily conserved mechanism.

Autoimmunity↗

Control of intestinal inflammation by regulatory T cells.

Transfer of CD4+ T cells to immune-deficient mice in the absence of the CD25+ subset leads to the development of colitis, indicating that regulatory cells capable of controlling a bacteria-driven inflammatory response are present in normal mice. Cells with this function are present in the thymus as well as in the periphery of germ-free mice, suggesting they may be reactive with self-antigen. These cells resemble CD4+CD25+ cells that inhibit organ-specific autoimmunity, suggesting that a similar subset of regulatory T cells may control responses to self and foreign antigens. Development of colitis is dependent on accumulation of activated CD134L+ dendritic cells (DC) in the mesenteric lymph nodes, which is inhibited by CD4+CD25+ cells, indicating that regulatory T cells may control DC activation in vivo. Whilst inhibition of T-cell activation in vitro by CD4+CD25+ cells does not involve interleukin-10 and transforming growth factor-beta, these cytokines are required for the suppression of colitis. It may be that control of responses that activate the innate immune system requires multiple mechanisms of immune suppression. Recently, we identified CD4+CD25+ cells with immune suppressive activity in the thymus and peripheral blood of humans, raising the possibility that dysfunction in this mechanism of immune regulation may be involved in the development of autoimmune and inflammatory diseases.

ADP-ribosyl Cyclase↗

Role of gender upon basal and postprandial systemic and splanchnic haemodynamics in humans.

BACKGROUND: Food intake, accompanied by systemic and splanchnic haemodynamic changes, has only been studied in males. The extent to which splanchnic postprandial hyperaemia shows gender differences is unknown. METHODS: We tested 1) the splanchnic hyperaemic response to food in females and 2) whether postprandial haemodynamic changes show gender differences. Twenty-four healthy women (aged 20-35 years) and 20 healthy men (aged 21-34 years) participated in the study. A liquid test meal (Ensure plus, 1.5 kcal/ml) was perfused intraduodenally for 75 min through an enteral feeding tube at a rate of 3 ml/min after a 45-min basal period. Blood flow parameters were measured using Echo-Doppler technology. RESULTS: Basal diastolic arterial blood pressure was significantly (P < 0.05) lower in females (66+/-2 versus 72+/-2 mmHg), whereas heart rate was the same (58+/-2 b/min, ns). Postprandially, diastolic blood pressure fell, but reached significance only in males (-10+/-3 mmHg; P < 0.05). Mean velocity in the superior mesenteric artery (SMA) was significantly (P < 0.05) higher in females compared to males at baseline (47+/-3 versus 39+/-2 cm/s), whereas maximal postprandial changes were similar (64+/-6 versus 56+/-6 cm/s, ns). Volume flow in the portal vein (PV) at baseline was 656+/-29 and 716+/-35 ml/min females and males, respectively (ns between gender). Maximal postprandial changes amounted to 808+/-86 and 884+/-107 ml/min, respectively (ns). CONCLUSIONS: 1) Perfusion of a liquid test meal induces significant increases in flow parameters in the SMA and PV in both genders. 2) These changes are partly paralleled by alterations in systemic haemodynamics. 3) Postprandial splanchnic flow parameters are qualitatively and quantitatively not different between genders.

Adult↗

Reentrant morphology transition in the growth of free silver nanoclusters

The growth of free silver nanoclusters is studied by molecular dynamics simulations, from a small seed up to sizes N approximately 150. It is shown that the final outcome of the growth process depends crucially on the growth conditions (deposition flux straight phi and temperature T). A reentrant morphology transition is obtained: at intermediate values of T and straight phi a "decahedral window" is found; the window is surrounded by regimes where icosahedra are preferentially grown.

Journal Article↗

Locally inducible CD66a (CEACAM1) as an amplifier of the human intestinal T cell response.

CD66a is an adhesion molecule member of the carcinoembryonic antigen immunoglobulin-like family present on the surface of epithelial cells, granulocytes and IL-2 activated T cells. We studied whether CD66a is expressed in vivo by T lymphocytes and whether it affects TCR-mediated activation. CD66a was detected by histochemistry, flow cytometry analysis, reverse transcription PCR and Western blot on fresh colon biopsies and T cell clones. A fraction of T cells in the lamina propria express CD66a, which is induced by IL-7 and IL-15 cytokines. T cells express four different CD66a splice variants and at least two forms of the protein are glycosylated in a cell type-specific manner. Triggering of CD66a on T cells with physiological ligands or with specific mAb increases TCR-mediated lymphokine release, in an antigen dose-independent manner. This effect requires the presence of the CD66a intracytoplasmic domain, which contains two immunoglobulin receptor family tyrosine-based inhibitory motif-like domains, as shown by stimulation of Jurkat cells transfected with different CD66a isoforms and is associated with increased induction of AP1 and NFkappaB transcription factors. These data indicate that CD66a amplifies T cell activation and thus could facilitate crosstalk between epithelial cells and T lymphocytes in intestinal immune response.

Antigens, CD↗

Dose-dependent gastrointestinal effects of the somatostatin analog lanreotide in healthy volunteers.

OBJECTIVE: To investigate the gastrointestinal effects of intravenous lanreotide. METHODS: Twenty healthy male subjects participated in 2 subsequent placebo-controlled, double-blind crossover studies. The effects of 3 doses of lanreotide (50, 100, and 200 microg/h) were investigated on 24-hour intragastric acidity (study I), food-stimulated gallbladder contraction, and plasma cholecystokinin release (study II). RESULTS: Lanreotide showed linear pharmacokinetics. It raised median intragastric pH significantly and in a dose-dependent manner: from 1.4+/-0.2 (placebo) to 2.5+/-0.8 (P < .002) during administration of 50 microg/h lanreotide, to 3.2+/-0.7 (P < .001) during 100 microg/h lanreotide, and to 4.3+/-0.7 (P < .001) during 200 microg/h lanreotide. However, no significant inhibition of gastrin secretion could be established. All doses completely inhibited postprandial gallbladder contraction. CONCLUSION: Intravenous administration of lanreotide at rates applied in this study was able to significantly inhibit intragastric acid secretion and postprandial gallbladder contraction; under these conditions few untoward effects were noted.

Adult↗

Hemodynamic effects of the somatostatin analog lanreotide in humans: placebo-controlled, cross-over dose-ranging Echo-Doppler study.

Because of their vasoactive effects, somatostatin and its analogs are increasingly used in the management of complications of chronic liver diseases such as variceal bleeding. Postprandial hyperemia augments splanchnic blood flow, subsequently increasing portal pressure. The aim of this study was to explore effects of the somatostatin analog, lanreotide, on food-stimulated hemodynamic parameters in healthy human subjects. A dose-response curve was constructed in eight healthy male subjects in a placebo-controlled cross-over study. On 4 different days, either 0 (placebo), 50, 100, or 200 microg/h of lanreotide was infused intravenously in random order, starting at 45 minutes for 7 hours. On each day, a liquid test meal (Ensure plus, 1.5 kcal/mL) was perfused intraduodenally at a rate of 3 mL/min over 7 hours after a 45-minute basal period. Diastolic arterial pressure (dBP), heart rate (HR), superior mesenteric arterial (SMA) average flow velocity (SMA-V), SMA pulsatility index (SMA-PI), portal venous volume flow (PV-F), and renal artery (RA) resistance index (RA-RI) were measured on regular intervals (flows using Echo-Doppler technology). Lanreotide at all doses abolished food-stimulated splanchnic hyperemia both in the SMA and PV over 7 hours. The fall in dBP and increase in HR after food perfusion were blunted under lanreotide. Food as well as lanreotide did not modify RA-RI. In summary: 1) lanreotide inhibits food-induced splanchnic hyperemia in normal subjects; 2) in parallel, systemic hemodynamic alterations to food stimulation are abolished with lanreotide; and 3) renal vascular resistance is unchanged. Because of its persistent splanchnic vasoconstrictive effect, lanreotide should be tested in patients with portal hypertension.

Adult↗