Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 172
Filter
Add more filters

Publication year range
1.
Br J Dermatol ; 177(3): 719-734, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28432696

ABSTRACT

Eczema is a common long-term condition, but inadequate support and information can lead to poor adherence and treatment failure. We have reviewed the international literature of interventions designed to promote self-management in adults and children with eczema. MEDLINE, MEDLINE in process, Embase, CINAHL and the Global Resource for EczemA Trials database were searched from their inception to August 2016, for randomized controlled trials. Two authors independently applied eligibility criteria, assessed risk of bias for all included studies and extracted data. Twenty studies (3028 participants) conducted in 11 different countries were included. The majority (n = 18) were based in secondary care and most (n = 16) targeted children with eczema. Reporting of studies, including descriptions of the interventions and the outcomes themselves, was generally poor. Thirteen studies were face-to-face educational interventions, five were delivered online and two were studies of written action plans. Follow-up in most studies (n = 12) was short term (up to 12 weeks). Only six trials specified a single primary outcome. There was limited evidence of effectiveness. Only three studies collected and reported outcomes related to cost and just one study undertook any formal cost-effectiveness analysis. In summary, we have identified a general absence of well-conducted and well-reported randomized controlled trials with a strong theoretical basis. Therefore, there is still uncertainty about how best to support self-management of eczema in a clinically effective and cost-effective way. Recommendations on design and conduct of future trials are presented.


Subject(s)
Eczema/therapy , Self-Management/methods , Adult , Child , Cost-Benefit Analysis , Eczema/economics , Humans , Internet , Patient Education as Topic/economics , Patient Education as Topic/methods , Randomized Controlled Trials as Topic , Self-Management/education , Treatment Outcome
2.
Int J Med Sci ; 13(10): 759-764, 2016.
Article in English | MEDLINE | ID: mdl-27766025

ABSTRACT

Inflammation and dysfunction of endothelial cells are thought to be triggers for the secretion of Von Willebrand factor. The aim of this study was to examine the effects of the inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-α) and the coagulation factors, tissue factor and thrombin on the release and cleavage potential of ultra-large von Willebrand factor (ULVWF) and its cleavage protease by cultured human umbilical vein endothelial cells (HUVEC). HUVEC were treated with IL-6, IL-8, and TNF-α, tissue factor (TF) and thrombin, and combinations thereof for 24 hours under static conditions. The cells were then exposed to shear stress after which the VWF-propeptide levels and the VWF cleavage protease, ADAMTS13 content were measured. All treatments and their combinations, excluding IL-6, significantly stimulated the secretion of VWF from HUVEC. The VWF secretion from the HUVEC was stimulated most by the combination of TF with TNF-α. Slightly lower levels of ADAMTS13 secretion were found with all treatments. This may explain the thrombogenicity of patients with inflammation where extremely high VWF levels and slightly lower ADAMTS13 levels are present.


Subject(s)
ADAMTS13 Protein/metabolism , Cytokines/physiology , Human Umbilical Vein Endothelial Cells/metabolism , Thromboplastin/physiology , von Willebrand Factor/metabolism , Humans , Thrombin/physiology
3.
J Evol Biol ; 25(11): 2161-70, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22998731

ABSTRACT

The evolution of life is characterized by major evolutionary transitions during which independent units cooperated and formed a new level of selection. Relatedness is a common mechanism that reduces conflict in such cooperative associations. One of the latest transitions is the evolution of social insect colonies. As expected, they are composed of kin and mechanisms have evolved that prevent the intrusion of nonrelatives. Yet, there are exceptions an extreme case is the fusion of unrelated colonies. What are the advantages of fusions that have colonies with a high potential for conflict as a consequence? Here, we investigated fitness costs and benefits of colony fusions in a lower termite species, Cryptotermes secundus, in which more than 25% of all colonies in the field are fused. We found two benefits of colony fusion depending on colony size: very small colonies had an increased probability of survival when they fused, yet for most colony sizes mainly a few workers profit from colony fusions as their chance to become reproductives increased. This individual benefit was often costly for other colony members: colony growth was reduced and the current reproductives had an increased chance of dying when fusions were aggressive. Our study suggests that fusion of colonies often is the result of 'selfish' worker interests to become reproductives, and this might have been important for the termites' social evolution. Our results uniquely shows that selfish interests among related colony members can lead to the formation of groups with increased potential for conflict among less related members.


Subject(s)
Genetic Fitness , Isoptera/physiology , Social Behavior , Aggression , Animals , Biological Evolution , Conflict, Psychological , Population Density , Reproduction , Species Specificity
4.
J Trace Elem Med Biol ; 69: 126891, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34749033

ABSTRACT

OBJECTIVE: To examine associations between local and systemic symptoms and the wear of the tin weld of Essure implants. DESIGN: study of a series of cases. SETTINGS: Two French hospitals. PARTICIPANTS: Eighteen patients explanted by hysterectomy and salpingectomy for removal of their Essure implants between September 2019 and July 2020, have had a common anatomopathological process. MAIN OUTCOME MEASURES: anatomopathological examination by optical microscopy and mineralogical analysis of the fallopian tube or uterine horn with scanning electron microscopy coupled with energy dispersive X-ray (SEM-EDX). Evaluation of local and systemic symptoms with a questionnaire. Examination of blood metal assays (nickel, chromium, and tin). RESULTS: anatomopathological examination highlights foreign body granulomas, fibrosis, adenomyosis, nonspecific inflammation, cysts and myomas in the Fallopian tubes, uterine horns, or both and mentions the presence of foreign bodies in seven cases. SEM-EDX analyses showed, systematically, the presence of tin particles integrated in the wall near the weld, generally in clusters, and with a size ranging from about one micron to several dozen microns. The questionnaire shows that the most frequent local symptoms were pelvic pain, urinary disorders, bleeding, and pains during intercourse. The most common systemic symptoms were: asthenia, visual disturbances, amnesia, giddiness, dorsal pains, headaches, and joint pains. The majority of local and systemic symptoms decreased after explantation, but sometimes incompletely. Before explantation, high levels of nickel, tin and chromium were observed in 11/17, 1/7 and 2/17 patients. After explantation, tin levels were high in 3/11 patients. CONCLUSIONS: our new anatomopathological process systematically demonstrates the presence of tin particles in tissue near the weld. These particles could be responsible for granulomatous inflammations as well as local symptoms. Many of the systemic symptoms are consistent with chronic organotin poisoning but further studies are needed to find out whether tin from the solder can be converted to organotin in the patients' bodies.


Subject(s)
Fallopian Tubes , Sterilization, Tubal , Chromium , Female , Humans , Nickel , Tin
5.
Gynecol Obstet Fertil Senol ; 50(3): 211-219, 2022 03.
Article in French | MEDLINE | ID: mdl-35063688

ABSTRACT

OBJECTIVES: To provide clinical practice guidelines about fertility preservation (FP) for women with benign gynecologic disease (BGD) developed by a modified Delphi consensus process for oocyte vitrification in women with benign gynecologic disease. METHODS: A steering committee composed of 14 healthcare professionals and a patient representative with lived experience of endometriosis identified 42 potential practices related to FP for BGD. Then 114 key stakeholders including various healthcare professionals (n=108) and patient representatives (n=6) were asked to participate in a modified Delphi process via two online survey rounds from February to September 2020 and a final meeting. Due to the COVID-19 pandemic, this final meeting to reach consensus was held as a videoconference in November 2020. RESULTS: Survey response of stakeholders was 75 % (86/114) for round 1 and 87 % (75/86) for round 2. Consensus was reached for the recommendations for 28 items, that have been distributed into five general categories: (i) Information to provide to women of reproductive age with a BGD, (ii) Technical aspects of FP for BGD, (iii) Indications for FP in endometriosis, (iv) Indications for FP for non-endometriosis BGD, (v) Indications for FP after a fortuitous diagnosis of an idiopathic diminished ovarian reserve. CONCLUSION: These guidelines provide some practice advice to help health professionals better inform women about the possibilities of cryopreserving their oocytes prior to the management of a BGD that may affect their ovarian reserve and fertility. STUDY FUNDING/COMPETING INTEREST(S): The CNGOF (Collège National des Gynécologues Obstétriciens Français) funded the implementation of the Delphi process.


Subject(s)
COVID-19 , Endometriosis , Consensus , Delphi Technique , Endometriosis/complications , Endometriosis/therapy , Female , Humans , Oocytes/physiology , Pandemics , SARS-CoV-2 , Vitrification
6.
Ann Trop Med Parasitol ; 105(2): 107-22, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21396247

ABSTRACT

Anopheles darlingi, one of the main malaria vectors in the Neotropics, is widely distributed in French Guiana, where malaria remains a major public-health problem. Elucidation of the relationships between the population dynamics of An. darlingi and local environmental factors would appear to be an essential factor in the epidemiology of human malaria in French Guiana and the design of effective vector-control strategies. In a recent investigation, longitudinal entomological surveys were carried out for 2-4 years in one village in each of three distinct endemic areas of French Guiana. Anopheles darlingi was always the anopheline mosquito that was most frequently caught on human bait, although its relative abundance (as a proportion of all the anophelines collected) and human biting rate (in bites/person-year) differed with the study site. Seasonality in the abundance of human-landing An. darlingi (with peaks at the end of the rainy season) was observed in only two of the three study sites. Just three An. darlingi were found positive for Plasmodium (either P. falciparum or P. vivax) circumsporozoite protein, giving entomological inoculation rates of 0·0-8·7 infectious bites/person-year. Curiously, no infected An. darlingi were collected in the village with the highest incidence of human malaria. Relationships between malaria incidence, An. darlingi densities, rainfall and water levels in the nearest rivers were found to be variable and apparently dependent on land-cover specificities that reflected the diversity and availability of habitats suitable for the development and reproduction of An. darlingi.


Subject(s)
Anopheles/parasitology , Insect Vectors/parasitology , Malaria/epidemiology , Animals , Anopheles/classification , Ecosystem , Female , French Guiana/epidemiology , Humans , Incidence , Malaria/transmission , Plasmodium/isolation & purification , Rain , Rivers , Seasons
8.
Ann Cardiol Angeiol (Paris) ; 70(5): 286-293, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34130804

ABSTRACT

BACKGROUND: The E/e' index measured in spectral tissue Doppler is included in the recommendations for the diagnosis by transthoracic Doppler echocardiography of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction. While E/e' is influenced by age in healthy individuals, no studies have evaluated this index in elderly patients. This study addressed the clinical relevance of E/e' in assessment of left ventricular diastolic function in elderly patients with preserved ejection fraction and its relevance from both a diagnostic and prognostic perspective based on the existing literature. METHODS: A total of 76 patients≥70years of age were prospectively included. The analysis of left ventricular diastolic function was adapted from the 2016 ASE/EACVI recommendations without consideration of E/e'. RESULTS: The mean age was 85years. In all, 42 patients had moderate-to-severe diastolic dysfunction (elevated left atrial pressure). Mean E/e' was significantly correlated with diastolic function (r=0.58, P<0.001). Mean E/e'>13.3 had a sensitivity of 86% and a specificity of 91% in the diagnosis of moderate-to-severe diastolic dysfunction (AUC: 0.92). E/(e'xs') (AUC: 0.89) and NT pro-BNP (AUC: 0.80) did not perform better than E/e'. The existing literature offers large body of evidence that E/e' provides essential diagnostic and prognostic information in older patients with cardiovascular disease. CONCLUSION: E/e' is accurate in the diagnosis of significant diastolic dysfunction, in the diagnosis of heart failure with preserved ejection fraction and in risk stratification in older patients with cardiovascular disease.


Subject(s)
Ventricular Dysfunction, Left , Ventricular Function, Left , Aged , Aged, 80 and over , Diastole , Echocardiography, Doppler , Humans , Stroke Volume , Ventricular Dysfunction, Left/diagnostic imaging
9.
Ann Cardiol Angeiol (Paris) ; 70(5): 281-285, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34130805

ABSTRACT

BACKGROUND: The diagnosis of heart failure with preserved ejection fraction is characterized by its complexity, especially for physicians without great experience in comprehensive transthoracic Doppler echocardiography. Peak mitral E-wave (E) velocity has been successfully correlated to invasive left ventricular diastolic pressures in patients with structural heart disease. The aim of the study was to address the accuracy of E in the diagnosis of heart failure with preserved ejection fraction in elderly patients with acute dyspnea. METHODS: This prospective study included 29 consecutive patients ≥70 years of age with heart failure with preserved ejection fraction and acute dyspnea and 29 controls ≥70 years of age. The final diagnosis was supported by the 2016 ASE/EACVI recommendations. RESULTS: Mean age of the overall population was 85±7 years. E was strongly correlated with left atrial volume index (r=0.72, P<0.001) and with peak velocity of tricuspid regurgitation (r=0.77, P<0.001). E >85cm/s was 90% sensitive and 93% specific in the diagnosis of heart failure with preserved ejection fraction (AUC, 0.95). E/e' (0.95) and E/(e'xs') (0.92) did not perform better. CONCLUSION: E/e' and E/(e'xs') provide essential diagnostic and prognostic information in heart failure with preserved ejection fraction and deserve to be included in every report of comprehensive transthoracic Doppler echocardiography. E velocity is a very simple and user-friendly parameter that can be used for the sole diagnostic purpose in elderly patients with acute dyspnea by operators without great deal of experience, such as cardiologists without formal training, emergency physicians, intensive care anesthetists, internists and geriatricians.


Subject(s)
Heart Failure , Ventricular Function, Left , Aged , Aged, 80 and over , Dyspnea/etiology , Heart Failure/diagnosis , Humans , Prospective Studies , Stroke Volume
10.
Food Chem ; 376: 131917, 2021 Dec 23.
Article in English | MEDLINE | ID: mdl-34968913

ABSTRACT

Understanding the mechanisms leading to the multitude of newly-formed compounds generated during the thermal processing of food is important for the reasoned construction of quality. Thanks to a solid food model with a structure and technological history comparable to that of a real sponge cake and containing only known amounts of precursors (glucose with or without leucine), an adapted reaction scheme unravelling Maillard and caramelization reactions was built and then compared to experimental kinetic data measured on numerous reaction markers (precursors, α-dicarbonyl intermediates and furanic compounds). For caramelization, this study showed that glucose mainly formed 1,2-enediol and then fructose rather than glucosone and glyoxal. 5-hydroxymethylfurfural started to form when there were sufficient quantities of fructose, and 3,4-dideoxyoglucosone was not generated until after this step. Furfural was mainly formed via 3-deoxyglucosone. The involvement of leucine tended to accelerate the breakdown of sugars as more degradation pathways (via enaminols) were added.

11.
Arch Pediatr ; 28(8): 689-695, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34756657

ABSTRACT

BACKGROUND AND AIMS: Healthcare for the increasing number of migrants in Europe, and particularly of unaccompanied minors (UMs) seeking asylum, has become a major challenge. We aimed to describe the health issues of UMs managed in a dedicated pediatric consultation service in a care center in Paris. METHODS: All UMs attending a dedicated migrant medical consultation service in Robert Debré Hospital, Paris, France, were included in a single-center retrospective observational study from September 1, 2017, to September 30, 2018. RESULTS: Out of the 107 UMs who were included, 87% had a health problem (n=93) and 52% had an infectious disease (n=56). The main infectious diagnoses were schistosomiasis (22%), latent tuberculosis (22%), intestinal parasitosis (16%), and chronic hepatitis B (8%). Posttraumatic stress disorder (PTSD) and overweight were common (35% and 20%, respectively). The median age was 15 years old (IQR, 14-16), the male/female ratio was 95/12. Most of the children were from sub-Saharan Africa (n=67), 46% had crossed Libya (n=49) and, when compared to the other migration routes, faced an increasing risk of violence (69%, p=0.04), imprisonment (53%, p=0.03), and forced labor (48%, p=0.02). The median duration of the trip before reaching France was 6 months (IQR, 2-13), the median time to consultation was 2 months (0-5) and was not associated with an increased risk of health problems. A total of 43 UMs were lost to follow-up. CONCLUSION: Health problems, particularly infectious diseases and PTSD, are common among UMs and should prompt an early medical consultation with psychiatric evaluation. Follow-up is problematic and could be improved by an on-line health book.


Subject(s)
Referral and Consultation/statistics & numerical data , Refugees/statistics & numerical data , Adolescent , Child , Female , Hospitals/statistics & numerical data , Humans , Male , Minors/psychology , Paris , Pediatrics/methods , Pediatrics/statistics & numerical data , Referral and Consultation/classification , Retrospective Studies
12.
J Exp Med ; 178(6): 2231-5, 1993 Dec 01.
Article in English | MEDLINE | ID: mdl-7504062

ABSTRACT

The Fas gene encodes a cell surface molecule that is a member of the the nerve growth factor/tumor necrosis factor receptor family of proteins and can mediate programmed cell death (apoptosis) in certain transformed cell lines. To characterize further the biological function of Fas, particularly with regard to its function in normal cells, a panel of monoclonal antibodies (mAbs) was generated against the extracellular portion of human Fas. Some of these mAbs induced apoptosis in transformed cell lines expressing Fas, but only when immobilized on the culture vessel. One of the new Fas mAbs (M38) was used for studies on normal lymphoid cells and found to stimulate the proliferation of purified human T cells and thymocytes when immobilized on culture wells along with CD3 antibody. T cell proliferation induced by Fas mAb was largely interleukin 2 independent and was demonstrated to be due to a direct effect on the precursor T cell. Thus, the data demonstrate that in addition to a role in the induction of apoptosis in certain transformed cell lines, the Fas protein may also play an important role in the activation and proliferation of normal T cells.


Subject(s)
Antigens, Surface/physiology , T-Lymphocytes/immunology , Antibodies, Monoclonal/immunology , Humans , Lymphocyte Activation , Receptors, Cell Surface/physiology , Signal Transduction , fas Receptor
13.
J Exp Med ; 184(5): 1953-62, 1996 Nov 01.
Article in English | MEDLINE | ID: mdl-8920882

ABSTRACT

Dendritic cells (DC) are the most efficient APC for T cells. The clinical use of DC as vectors for anti-tumor and infectious disease immunotherapy has been limited by their trace levels and accessibility in normal tissue and terminal state of differentiation. In the present study, daily injection of human Flt3 ligand (Flt3L) into mice results in a dramatic numerical increase in cells co-expressing the characteristic DC markers-class II MHC, CD11c, DEC205, and CD86. In contrast, in mice treated with either GM-CSF, GM-CSF plus IL-4, c-kit ligand (c-kitL), or G-CSF, class II+ CD11c+ cells were not significantly increased. Five distinct DC subpopulations were identified in the spleen of Flt3L-treated mice using CD8 alpha and CD11b expression. These cells exhibited veiled and dendritic processes and were as efficient as rare, mature DC isolated from the spleens of untreated mice at presenting allo-Ag or soluble Ag to T cells, or in priming an Ag-specific T cell response in vivo. Dramatic numerical increases in DC were detected in the bone marrow, gastro-intestinal lymphoid tissue (GALT), liver, lymph nodes, lung, peripheral blood, peritoneal cavity, spleen, and thymus. These results suggest that Flt3L could be used to expand the numbers of functionally mature DC in vivo for use in clinical immunotherapy.


Subject(s)
Antigens, CD , Dendritic Cells/drug effects , Lectins, C-Type , Membrane Proteins/pharmacology , Animals , Antigen Presentation , CD8 Antigens/analysis , Female , Granulocyte Colony-Stimulating Factor/pharmacology , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , Histocompatibility Antigens Class II , Integrin alphaXbeta2/analysis , Interleukin-4/pharmacology , Lymphocyte Activation , Major Histocompatibility Complex , Membrane Glycoproteins/analysis , Mice , Mice, Inbred C57BL , Minor Histocompatibility Antigens , Receptors, Cell Surface/analysis , Spleen/cytology , Spleen/immunology , Stem Cell Factor/pharmacology , T-Lymphocytes/immunology , Tissue Distribution
14.
Ann Cardiol Angeiol (Paris) ; 69(5): 294-298, 2020 Nov.
Article in French | MEDLINE | ID: mdl-32800317

ABSTRACT

BACKGROUND: Hypoalbuminemia has now emerged as a powerful prognosticator in heart failure regardless of age, clinical presentation, left ventricular ejection fraction and usual prognostic markers. Growing evidence is that this prognostic value persists after adjusting for causative factors for hypoalbuminemia such as malnutrition, inflammation and liver dysfunction. OBJECTIVE: To address the prognostic relevance of hypoalbuminemia in frail elderly patients with well-characterized cardiogenic pulmonary edema at high risk for adverse outcome, beyond causative factors for low serum albumin levels. Serum albumin was measured after clinical stabilization to avoid hypervolemia. RESULTS: In all, 67 patients with a mean age of 86 years were included. Hospital mortality was 30%. Patients who died and who survived were similar in age, ejection fraction, BNP concentration, serum creatinine, serum hemoglobin, total bilirubin and prealbumin. Patients who died had lower serum albumin levels (P<0.001), higher blood urea nitrogen (P=0.03) and higher C-reactive protein (P=0.02). In multivariate analysis, serum albumin was the sole independent predictor of hospital death (P<0.01), after adjusting for malnutrition (prealbumin P=ns), inflammation (C-reactive protein P=ns) and liver dysfunction (total bilirubin P=ns). CONCLUSION: Serum albumin is a powerful prognosticator in frail elderly patients with acute cardiogenic pulmonary edema even after adjusting for main causative factors. These results suggest that hypoalbuminemia may contribute to the worsening of heart failure given the physiological properties of serum albumin that includes antioxidant activity and plasma colloid osmotic pressure action. Further studies are critically needed to address the relevance of prevention and correction of hypoalbuminemia in heart failure.


Subject(s)
Frailty/complications , Heart Failure/etiology , Hypoalbuminemia/complications , Symptom Flare Up , Aged , Aged, 80 and over , Female , Humans , Male , Prognosis , Pulmonary Edema/complications
15.
J Cell Biol ; 107(2): 721-30, 1988 Aug.
Article in English | MEDLINE | ID: mdl-3047147

ABSTRACT

A pepsin-resistant triple helical domain (chain 50,000 Mr) of type VIII collagen was isolated from bovine corneal Descemet's membrane and used as an immunogen for the production of mAbs. An antibody was selected for biochemical and tissue immunofluorescence studies which reacted both with Descemet's membrane and with type VIII collagen 50,000-Mr polypeptides by competition ELISA and immunoblotting. This antibody exhibited no crossreactivity with collagen types I-VI by competition ELISA. The mAb specifically precipitated a high molecular mass component of type VIII collagen (EC2, of chain 125,000 Mr) from the culture medium of subconfluent bovine corneal endothelial cells metabolically labeled for 24 h. In contrast, confluent cells in the presence of FCS and isotope for 7 d secreted a collagenous component of chain 60,000 Mr that did not react with the anti-type VIII collagen IgG. Type VIII collagen therefore appears to be synthesized as a discontinuous triple helical molecule with a predominant chain 125,000 Mr by subconfluent, proliferating cells in culture. Immunofluorescence studies with the mAb showed that type VIII collagen was deposited as fibrils in the extracellular matrix of corneal endothelial cells. In the fetal calf, type VIII collagen was absent from basement membranes and was found in a limited number of tissues. In addition to the linear staining pattern observed in the Descemet's membrane, type VIII collagen was found in highly fibrillar arrays in the ocular sclera, in the meninges surrounding brain, spinal cord, and optic nerve, and in periosteum and perichondrium. Fine fibrils were evident in the white matter of spinal cord, whereas a more generalized staining was apparent in the matrices of cartilage and bone. Despite attempts to unmask the epitope, type VIII collagen was not found in aorta, kidney, lung, liver, skin, and ligament. We conclude that this unusual collagen is a component of certain specialized extracellular matrices, several of which are derived from the neural crest.


Subject(s)
Collagen/analysis , Cornea/analysis , Extracellular Matrix/analysis , Animals , Antibodies, Monoclonal/immunology , Cattle , Cells, Cultured , Collagen/immunology , Cornea/immunology , Cornea/ultrastructure , Cross Reactions , Culture Media , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique , Hybridomas , Immunoassay , Precipitin Tests
16.
Br J Cancer ; 99(1): 143-50, 2008 Jul 08.
Article in English | MEDLINE | ID: mdl-18577996

ABSTRACT

Dysregulation of growth factors and their receptors is central to human hepatocellular carcinoma (HCC). We previously demonstrated that the Frizzled-7 membrane receptor mediating the Wnt signalling can activate the beta-catenin pathway and promotes malignancy in human hepatitis B virus-related HCCs. Expression patterns of all the 10 Frizzled receptors, and their extracellular soluble autoparacrine regulators (19 Wnt activators and 4 sFRP inhibitors) were assessed by real-time RT-PCR in 62 human HCC of different etiologies and their matched peritumorous areas. Immunostaining was performed to localise Frizzled on cell types in liver tissues. Regulation of three known Frizzled-dependent pathways (beta-catenin, protein kinase C, and C-Jun NH(2)-terminal kinase) was measured in tissues by western blot. We found that eight Frizzled-potentially activating events were pleiotropically dysregulated in 95% HCC and 68% peritumours as compared to normal livers (upregulations of Frizzled-3/6/7 and Wnt3/4/5a, or downregulation of sFRP1/5), accumulating gradually with severity of fibrosis in peritumours and loss of differentiation status in tumours. The hepatocytes supported the Wnt/Frizzled signalling since specifically overexpressing Frizzled receptors in liver tissues. Dysregulation of the eight Frizzled-potentially activating events was associated with differential activation of the three known Frizzled-dependent pathways. This study provides an extensive analysis of the Wnt/Frizzled receptor elements and reveals that the dysregulation may be one of the most common and earliest events described thus far during hepatocarcinogenesis.


Subject(s)
Carcinoma, Hepatocellular/genetics , Frizzled Receptors/genetics , Liver Neoplasms/genetics , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Frizzled Receptors/biosynthesis , Gene Expression Regulation , Humans , Liver Neoplasms/pathology
17.
J Clin Microbiol ; 46(8): 2723-30, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18508941

ABSTRACT

Hepatocellular carcinoma (HCC) and cirrhosis are important causes of mortality worldwide. Persistent hepatitis B virus (HBV) infection is a major cause of these diseases. Double mutations in the basal core promoter (BCP) (A1762T and G1764A) and precore (pre-C) (G1896A) regions of the virus are associated with progression to HCC. The current study is aimed at developing a simple method for screening and detecting BCP and pre-C mutations in HBV carriers. We have developed and validated an oligonucleotide ligation assay (OLA) to detect point mutations in the HBV core gene. We have applied OLA methods to samples from HBV-infected carriers recruited from the Gambia Liver Cancer Study (GLCS) comprising asymptomatic HBsAg carriers, patients with cirrhosis, and patients with HCC. We observed an 89.3% and 95.8% concordance between the OLA and DNA sequencing for BCP and pre-C mutations, respectively. OLA detected the mutations in single-strain infections and in infections with mixtures of wild-type and mutant viruses under conditions where sequencing detected only the single dominant strains. BCP mutations were detected in 75.7% of patients with advanced liver disease (cirrhosis/HCC) compared to 47.6% of asymptomatic carriers, while pre-C mutations were detected in 34.5% of advanced liver disease patients and in 47.6% of asymptomatic HBsAg carriers. There was a significant association between the presence of BCP mutations and advanced liver disease. In conclusion, OLA is a simple, economical, and reliable assay for detection of pre-C and BCP mutations. Its application can lead to improvement in diagnosis and clinical care in regions where HBV is endemic.


Subject(s)
Carcinoma, Hepatocellular/virology , Hepatitis B Core Antigens/genetics , Hepatitis B virus/genetics , Ligation/methods , Oligonucleotide Probes/genetics , Point Mutation , Promoter Regions, Genetic , Carcinoma, Hepatocellular/diagnosis , Gambia , Humans , Liver/pathology , Liver/virology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/virology , Severity of Illness Index , Statistics as Topic
18.
Arch Mal Coeur Vaiss ; 100(2): 113-20, 2007 Feb.
Article in French | MEDLINE | ID: mdl-17474496

ABSTRACT

BACKGROUND: B-type natriuretic peptide (BNP) has been largely validated in the etiologic diagnosis of acute dyspnea. Nevertheless, its reliability in the setting of a preserved left ventricular systolic function (ejection fraction >50%) has not been adequately established. OBJECTIVE: the study addressed the usefulness of BNP in the diagnosis of new-onset heart failure with a preserved systolic function in hypertensive patients hospitalized for acute dyspnea. METHODS: 59 consecutive hypertensive patients without history of heart failure and coronary disease were included. BNP was measured at presentation with the Triage system. Noninvasive estimation of left ventricular filling pressures by bedside tissue Doppler echocardiography at presentation was incorporated in the diagnostic criteria. RESULTS: the 30 patients with heart failure were not significantly different from the 29 patients with noncardiac cause of acute dyspnea regarding age, gender, body mass index and ejection fraction. Median levels of BNP were significantly higher in heart failure (447 [245-644] versus 87 [43-139] pg/mL). By multivariate logistic regression analysis, BNP (odds ratio of 44, [3.6-531], p=0.003) provided independent and incremental diagnostic information over the clinical score of Boston criteria (2.25, [1.3-3.9], p=0.0037). A BNP value of >142 pg/mL (area under the ROC curve of 0.89, p<0.0001) was 93 sensitive and 79% specific for the diagnosis of heart failure in this setting. CONCLUSION: BNP is a reliable biomarker of new-onset heart failure with a preserved systolic function in hypertensive patients, in particular older, hospitalized for acute dyspnea and can be safely integrated in the diagnostic strategy.


Subject(s)
Cardiac Output, Low/diagnosis , Hypertension , Natriuretic Peptide, Brain/blood , Acute Disease , Aged , Aged, 80 and over , Biomarkers/blood , Body Mass Index , Cardiac Output, Low/complications , Dyspnea/etiology , Echocardiography, Doppler , Female , Humans , Male , Predictive Value of Tests , Reproducibility of Results , Sensitivity and Specificity , Systole , Ventricular Function, Left
19.
Ann Cardiol Angeiol (Paris) ; 66(5): 303-308, 2017 Nov.
Article in French | MEDLINE | ID: mdl-29025686

ABSTRACT

Atrial fibrillation is the most common cardiac rhythm disorder encountered in daily clinical practice. It carries high morbidity and mortality rates, mainly related to sudden death, heart failure and stroke. Validation of noninvasive markers in the diagnosis of heart failure with preserved ejection fraction and risk stratification is therefore attractive in this clinical setting. The spectral tissue Doppler-derived E/e' ratio is a simple and user-friendly index which has been validated in the assessment of left ventricular diastolic pressures, regardless of rhythm. A septal E/e' >11 is associated with invasive left ventricular diastolic pressures >15mmHg in patients with atrial fibrillation. Several studies have reported the clinical relevance of abnormal values of E/e' at rest and during exercise in the diagnosis and risk stratification of heart failure with preserved ejection fraction in patients with atrial fibrillation. There is now convincing evidence that increased E/e' is associated with adverse outcome in patients with atrial fibrillation and predicts the recurrence of arrhythmia after cardioversion or catheter ablation. In conclusion, we recommend the measurement of E/e' in each patient with atrial fibrillation referred for clinically indicated transthoracic Doppler echocardiography.


Subject(s)
Atrial Fibrillation/diagnostic imaging , Echocardiography, Doppler , Humans , Prognosis
20.
BMJ Open ; 7(1): e012338, 2017 01 27.
Article in English | MEDLINE | ID: mdl-28131998

ABSTRACT

OBJECTIVE: To explore the methodologies employed in studies assessing transition of care interventions, with the aim of defining goals for the improvement of future studies. DESIGN: Systematic review of comparative studies assessing transition to adult care interventions for young people with chronic conditions. DATA SOURCES: MEDLINE, EMBASE, ClinicalTrial.gov. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: 2 reviewers screened comparative studies with experimental and quasi-experimental designs, published or registered before July 2015. Eligible studies evaluate transition interventions at least in part after transfer to adult care of young people with chronic conditions with at least one outcome assessed quantitatively. RESULTS: 39 studies were reviewed, 26/39 (67%) published their final results and 13/39 (33%) were in progress. In 9 studies (9/39, 23%) comparisons were made between preintervention and postintervention in a single group. Randomised control groups were used in 9/39 (23%) studies. 2 (2/39, 5%) reported blinding strategies. Use of validated questionnaires was reported in 28% (11/39) of studies. In terms of reporting in published studies 15/26 (58%) did not report age at transfer, and 6/26 (23%) did not report the time of collection of each outcome. CONCLUSIONS: Few evaluative studies exist and their level of methodological quality is variable. The complexity of interventions, multiplicity of outcomes, difficulty of blinding and the small groups of patients have consequences on concluding on the effectiveness of interventions. The evaluation of the transition interventions requires an appropriate and common methodology which will provide access to a better level of evidence. We identified areas for improvement in terms of randomisation, recruitment and external validity, blinding, measurement validity, standardised assessment and reporting. Improvements will increase our capacity to determine effective interventions for transition care.


Subject(s)
Research Design , Transition to Adult Care , Humans
SELECTION OF CITATIONS
SEARCH DETAIL