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91.
Preclinical drug development for visceral pain has largely relied on quantifying pseudoaffective responses to colorectal distension (CRD) in restrained rodents. However, the predictive value of changes in simple reflex responses in rodents for the complex human pain experience is not known. Male rats were implanted with venous cannulas and with telemetry transmitters for abdominal electromyographic (EMG) recordings. [14C]-iodoantipyrine was injected during noxious CRD (60 mmHg) in the awake, nonrestrained animal. Regional cerebral blood flow (rCBF)-related tissue radioactivity was quantified by autoradiography and analyzed in the three-dimensionally reconstructed brain by statistical parametric mapping. 60-mmHg CRD, compared with controls (0 mmHg) evoked significant increases in EMG activity (267 ± 24% vs. 103 ± 8%), as well as in behavioral pain score (77 ± 6% vs. 3 ± 3%). CRD elicited significant increases in rCBF as expected in sensory (insula, somatosensory cortex), and limbic and paralimbic regions (including anterior cingulate cortex and amygdala). Significant decreases in rCBF were seen in the thalamus, parabrachial nucleus, periaqueductal gray, hypothalamus and pons. Correlations of rCBF with EMG and with behavioral pain score were noted in the cingulate, insula, lateral amygdala, dorsal striatum, somatosensory and motor regions. Our findings support the validity of measurements of cerebral perfusion during CRD in the freely moving rat as a model of functional brain changes in human visceral pain. However, not all regions demonstrating significant group differences correlated with EMG or behavioral measures. This suggests that functional brain imaging captures more extensive responses of the central nervous system to noxious visceral distension than those identified by traditional measures. 相似文献
92.
Fanny Lanternier Annick Cohen-Akenine Fabienne Palmerini Fr��d��ric Feger Ying Yang Yael Zermati St��phane Bar��te Beatrix Sans C��dric Baude David Ghez Felipe Suarez Richard Delarue Philippe Casassus Christine Bodemer Adeline Catteau Fr��d��rique Soppelsa Katia Hanssens Michel Arock Hagay Sobol Sylvie Fraitag Dani��le Canioni Alain Moussy Jean Marie Launay Patrice Dubreuil Olivier Hermine Olivier Lortholary for the AFIRMM network 《PLoS Clinical Trials》2008,3(4)
93.
Thierry Poynard Sylvie Naveau Michel Doffoel Karim Boudjema Claire Vanlemmens Georges Mantion Michel Messner Bernard Launois Didier Samuel Daniel Cherqui Georges Pageaux Pierre Henri Bernard Yvon Calmus Jean Pierre Zarski Jean Philippe Miguet Jean Claude Chaput for a multi-centre group 《Journal of hepatology》1999,30(6):1130
Background/Aims: Alcoholic cirrhosis is the most common cause of liver transplantation in US males. The limited number of donor livers calls for“prioritisation”, favouring those patients who will benefit most. The aim was to assess the efficacy of liver transplantation in patients with alcoholic cirrhosis.Methods: We compared the survival of 169 transplantedpatients with two conservatively treated control groups, one of 169 patients matched for prognostic factors (age, cirrhosis severity, bleeding history) and one of 169 simulated patients.Results: The probability of survival to 5 years in the transplanted group was 66% (95% confidence interval 58–74%) vs 52% (44–60; p=0.03) in the matched group and 54% (51–57; p=0.01) in the simulated controls. Transplantation was associated with survival (relative RISK=1.51; p=0.02), independently of risk score (risk=2.07; p<0.001), indication, period of inclusion, centre experience, and alcohol abstinence. Patients with severe disease (Pugh C11–15) benefited most in terms of 5-year survival: 58% (44–72) vs 31% (17–45; p=0.008) in the matched and 35% (30–40; p<0.001) in the simulated control groups. For patients at lower risk there was no significant difference.Conclusions: Liver transplantation increases the 5-year survival of patients with severe alcoholic cirrhosis. In patients at lower risk, efficacy of transplantation should be confirmed by longer follow-up or by randomised trial. 相似文献
94.
Jaccard A Gachard N Marin B Rogez S Audrain M Suarez F Tilly H Morschhauser F Thieblemont C Ysebaert L Devidas A Petit B de Leval L Gaulard P Feuillard J Bordessoule D Hermine O;GELA GOELAMS Intergroup 《Blood》2011,117(6):1834-1839
Extranodal NK/T-cell lymphoma, nasal type, is a rare and highly aggressive disease with a grim prognosis. No therapeutic strategy is currently identified in relapsing patients. We report the results of a French prospective phase II trial of an L-asparaginase-containing regimen in 19 patients with relapsed or refractory disease treated in 13 centers. Eleven patients were in relapse and 8 patients were refractory to their first line of treatment. L-Asparaginase-based treatment yielded objective responses in 14 of the 18 evaluable patients after 3 cycles. Eleven patients entered complete remission (61%), and only 4 of them relapsed. The median overall survival time was 1 year, with a median response duration of 12 months. The main adverse events were hepatitis, cytopenia, and allergy. The absence of antiasparaginase antibodies and the disappearance of Epstein-Barr virus serum DNA were significantly associated with a better outcome. These data confirm the excellent activity of L-asparaginase-containing regimens in extranodal NK/T-cell lymphoma. L-Asparaginase-based treatment should thus be considered for salvage therapy, especially in patients with disseminated disease. First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma warrants evaluation in prospective trials. This trial is registered at www.clinicaltrials.gov as #NCT00283985. 相似文献
95.
IkappaBalpha/IkappaBepsilon deficiency reveals that a critical NF-kappaB dosage is required for lymphocyte survival 下载免费PDF全文
96.
Damien Gruson Michel F. Rousseau Sylvie Ahn François Van Linden Frédéric Thys Jean‐Marie Ketelslegers 《Scandinavian journal of clinical and laboratory investigation》2013,73(5):410-414
Objective. B‐type natriuretic peptide (BNP) and N‐terminal‐pro‐BNP (Nt‐proBNP) are commonly used for the triage of patients in the emergency department (ED) with dyspnoea and/or chest pain. The aim of our study was to determine the accuracy of N‐terminal‐pro‐ANP (Nt‐proANP) in such patients. Material and methods. Nt‐proANP was measured by home‐made radioimmunoassay in 137 ED patients admitted with cardiovascular and/or pulmonary disorders. BNP and Nt‐pro‐BNP were determined with automated assays. Final diagnosis was confirmed at discharge or after follow‐up. Results. Nt‐proANP levels were significantly influenced by the diagnostic subgroups (ANOVA: p<0.001) and were [geometric mean (range)]: 19727?ng/L (5260–45200) in congestive heart failure (CHF, n = 31), 6575?ng/L (1350–36000) in coronary artery disease (CAD, n = 19), 5324?ng/L (1710–13150) in pulmonary embolism (PE, n = 20), 5035?ng/L (1510–16600) in pulmonary diseases (PD, n = 24) and 3001?ng/L (750–11860) in patients without cardiopulmonary diseases (n = 43). Pairwise comparisons demonstrated that CHF patients had Nt‐pro‐ANP values higher than all other groups (p<0.05) and that patients without cardiopulmonary diseases had the lowest values (p<0.05). For diagnosis of CHF, the area under the ROC curve of Nt‐proANP was 0.94 (95?% CI: 0.89–0.98) and was equivalent to Nt‐proBNP (0.91; p = 0.284) and BNP (0.93; p = 0.572). Conclusions. The diagnostic accuracy of Nt‐proANP was equivalent to BNP and Nt‐proBNP in the present cohort of patients admitted to ED with dyspnoea and/or chest pain. 相似文献
97.
Management and treatment of hepatitis C virus in patients with HIV and hepatitis C virus coinfection: A practical guide for health care professionals 下载免费PDF全文
Pierre Ct Jean-Guy Baril Marie-Nicole Hbert Marina Klein Richard Lalonde Marc Poliquin Danielle Rouleau Rachel Therrien Sylvie Vzina Bernard Willems Harold Dion Patrice Junod Normand Lapointe Dominic Lvesque Lyse Pinault Ccile Tremblay Benoît Trottier Sylvie Trottier Chris Tsoukas Alain Pich 《Journal canadien des maladies infectieuses》2007,18(5):293-303
Concomitant HIV and hepatitis C virus (HCV) is a common yet complex coinfection. The present document is a practical guide for treating HCV infection in people coinfected with HIV. Effective antiretroviral therapies have prolonged survival rates for HIV-infected people over the past decade, which have made latent complications of HCV major causes of morbidity and mortality in these patients. Advances in the treatment of HCV (eg, combined pegylated interferon and ribavirin) offer the possibility of eradicating HCV infection in coinfected persons. The treatment of HCV must be considered in all cases. Intensive management of the adverse effects of HCV treatment is one of the factors for the success of these therapies. HCV eradication is predicted to decrease the mortality associated with coinfection and reduce the toxicity of HIV treatment. 相似文献
98.
Caroline Boda Bertrand Courtioux Pierre Roques Lynda Pervieux Gdon Vatunga Thophile Josenando Constant Roger Ayenengoye Bernard Bouteille Marie-Odile Jauberteau Sylvie Bisser 《PLoS Clinical Trials》2009,4(7)
Human African trypanosomiasis (HAT) is a deadly vector-born disease caused by an extracellular parasite, the trypanosome. Little is known about the cellular immune responses elicited by this parasite in humans. We used multiparameter flow cytometry to characterize leukocyte immunophenotypes in the blood and cerebrospinal fluid (CSF) of 33 HAT patients and 27 healthy controls identified during a screening campaign in Angola and Gabon. We evaluated the subsets and activation markers of B and T lymphocytes. Patients had a higher percentage of CD19+ B lymphocytes and activated B lymphocytes in the blood than did controls, but lacked activated CD4+ T lymphocytes (CD25+). Patients displayed no increase in the percentage of activated CD8+ T cells (HLA-DR+, CD69+ or CD25+), but memory CD8 T-cell levels (CD8+CD45RA−) were significantly lower in patients than in controls, as were effector CD8 T-cell levels (CD8+CD45RA+CD62L−). No relationship was found between these blood immunophenotypes and disease severity (stage 1 vs 2). However, CD19+ B-cell levels in the CSF increased with disease severity. The patterns of T and B cell activation in HAT patients suggest that immunomodulatory mechanisms may operate during infection. Determinations of CD19+ B-cell levels in the CSF could improve disease staging. 相似文献
99.
Rosaria Orlandi Sylvie Mnard Maria I. Colnaghi Cinda M. Boyer Franco Felici 《European journal of immunology》1994,24(11):2868-2873
To recover peptides that antigenically and immunogenically mimic the p185HER2 oncoprotein, we selected the phage-peptide libraries pVIII-9aa and pVIII-9aa. Cys using murine monoclonal antibodies (mAb) MGr2 and MGr6, directed against two distinct epitopes of the p185HER2 extracellular domain. Phagedisplayed peptides containing consensus amino acid motifs were recovered and shown to compete specifically for mAb binding on tumor cells that overexpress p185HER2. The deduced amino acid sequence of the peptides suggests that both epitopes defined by the mAb on p185HER2 are discontinuous and that hydrophobic interactions are involved in binding with the mAb. A phage clone displaying the GPLDSLFAQ peptide elicited a specific immune response against the p185HER2 in BALB/c mice, demonstrating that this phage-displayed peptide represents an immunological equivalent of the MGr2 epitope on p185HER2 and might be used as a substitute for this oncoprotein in in vitro and in vivo immunological studies. 相似文献
100.
Riedel F Adam S Feick P Haas S Götte K Hörmann K;Mannheim Alcohol Study Group 《International journal of molecular medicine》2004,13(2):267-272
Interleukin-18 (IL-18), a recently described cytokine secreted mainly by macrophages, stimulates interferon-gamma (IFN-gamma) production by natural killer cells and T cells. The purpose of this study was to determine tissue expression and serum levels of IL-18 in head and neck squamous cell carcinoma (HNSCC) and to evaluate ethanol and endotoxin-driven cytokine secretion. In 24 patients with primary HNSCC and 28 healthy controls, PBMC were isolated and incubated with 50 mM ethanol, LPS (doses 25 ng/ml, 250 ng/ml, 2500 ng/ml) and both agents for 24 h. Levels of IL-18 in serum, and cell supernatants were analysed by capture ELISA, IL-18 tissue level by immunoblotting. Serum levels of IL-8, IL-10 and IL-12, IFN-gamma, and endotoxin plasma levels were also determined. Statistical analysis involved Welch t-test and Page's test for trend. The majority of patients with HNSCC had high concentrations of serum IL-18. The level of IL-18 in the sera of these patients had a mean level of 271.7 pg/ml, while the mean IL-18 serum level in healthy controls was 174,0 pg/ml (p<0.001). Levels of IL-10 and IL-12, IFN-gamma were not increased in patients. Endotoxin was not detectable in either group. LPS stimulated dose-dependently IL-18 secretion from PBMC of patients and controls in vitro (p<0.05). Incubation with ethanol alone did not affect basal IL-18 secretion, but ethanol reduced LPS-stimulated IL-18 secretion compared to LPS stimulation alone. The mRNA expression of IL-18 in unstimulated PBMC and the response of PBMC to ethanol and LPS was similar in patients and controls. Our data on elevated serum levels of IL-18 in the majority of HNSCC cancer patients, irrespective of its biological activity, suggest that serum IL-18 might be a candidate for a new marker for HNSCC. The pathways for IL-18 production and its mechanisms of action in patients with HNSCC remain to be determined. Understanding of the immunological pathways might offer new therapeutic options in head and neck cancer in the future. 相似文献