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1.
Blood ; 138(23): 2396-2407, 2021 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-34424959

RESUMO

Mastocytosis is a heterogeneous disease characterized by an abnormal accumulation of mast cells (MCs) in 1 or several organs. Although a somatic KIT D816V mutation is detected in ∼85% of patients, attempts to demonstrate its oncogenic effect alone have repeatedly failed, suggesting that additional pathways are involved in MC transformation. From 3 children presenting with both Greig cephalopolysyndactyly syndrome (GCPS, Mendelian Inheritance in Man [175700]) and congenital mastocytosis, we demonstrated the involvement of the hedgehog (Hh) pathway in mastocytosis. GCPS is an extremely rare syndrome resulting from haploinsufficiency of GLI3, the major repressor of Hh family members. From these familial cases of mastocytosis, we demonstrate that the Hh pathway is barely active in normal primary MCs and is overactive in neoplastic MCs. GLI3 and KIT mutations had a synergistic, tumorigenic effect on the onset of mastocytosis in a GCPS mouse model. Finally, Hh inhibitors suppressed neoplastic MC proliferation in vitro and extend the survival time of mice with aggressive systemic mastocytosis (ASM). This work revealed, for the first time, the involvement of Hh signaling in the pathophysiology of mastocytosis and demonstrated the cooperative effects of the KIT and Hh oncogenic pathways in mice with ASM, leading to the identification of new promising therapeutic targets.


Assuntos
Acrocefalossindactilia/complicações , Proteínas Hedgehog/metabolismo , Mastocitose/complicações , Transdução de Sinais , Acrocefalossindactilia/metabolismo , Animais , Células Cultivadas , Criança , Humanos , Mastocitose/metabolismo , Camundongos Endogâmicos C57BL , Camundongos SCID , Células Tumorais Cultivadas
2.
Acta Psychol (Amst) ; 190: 248-257, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30149239

RESUMO

Modelling crowd behavior is essential for the management of mass events and pedestrian traffic. Current microscopic approaches consider the individual's behavior to predict the effect of individual actions in local interactions on the collective scale of the crowd motion. Recent developments in the use of virtual reality as an experimental tool have offered an opportunity to extend the understanding of these interactions in controlled and repeatable settings. Nevertheless, based on kinematics alone, it remains difficult to tease out how these interactions unfold. Therefore, we tested the hypothesis that gaze activity provides additional information about pedestrian interactions. Using an eye tracker, we recorded the participant's gaze behavior whilst navigating through a virtual crowd. Results revealed that gaze was consistently attracted to virtual walkers with the smallest values of distance at closest approach (DCA) and time to closest approach (TtCA), indicating a higher risk of collision. Moreover, virtual walkers gazed upon before an avoidance maneuver was initiated had a high risk of collision and were typically avoided in the subsequent avoidance maneuver. We argue that humans navigate through crowds by selecting only few interactions and that gaze reveals how a walker prioritizes these interactions. Moreover, we pose that combining kinematic and gaze data provides new opportunities for studying how interactions are selected by pedestrians walking through crowded dynamic environments.


Assuntos
Aprendizagem da Esquiva/fisiologia , Aglomeração/psicologia , Fixação Ocular/fisiologia , Estimulação Luminosa/métodos , Realidade Virtual , Adulto , Feminino , Humanos , Masculino , Caminhada/fisiologia , Caminhada/psicologia , Adulto Jovem
3.
Br J Dermatol ; 179(4): 925-932, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29787623

RESUMO

BACKGROUND: Mastocytosis is a heterogeneous group of clinical disorders characterized by the abnormal accumulation of mast cells. The adult and paediatric forms differ in their clinical and genetic features and outcomes. OBJECTIVES: To describe the clinical evolution of a well-characterized cohort of paediatric mastocytosis (PM), and to analyse the relationship between KIT mutation and the clinical course. METHODS: This was a prospective cohort study performed at the National Clinical Reference Center for Mastocytosis. Diagnosis was confirmed by identification of KIT mutation on lesional skin biopsy. Mastocytosis subtype, mast cell mediator-related symptoms (MC MRS) and clinical course were recorded. Fifty-three patients with PM and > 4 years of disease course were enrolled. The mean ± SD age at the final evaluation was 13·2 ± 4·8 years. The main outcome was the type of KIT mutation as a predictor of evolution and clinical characteristics. RESULTS: Patients presented with maculopapular cutaneous mastocytosis (n = 44), diffuse cutaneous mastocytosis (n = 6) or mastocytoma (n = 3). The mean duration of disease was 12·1 years. Substantial or partial cutaneous regression (18 of 53 and 16 of 53), stabilization or aggravation (16 of 53) and complete cutaneous regression (three of 53) were noted. MC MRS mainly regressed (21 of 53). For 22 patients, evolution of MC MRS and evolution of cutaneous lesions were different. No significant association between evolution and KIT mutation or between evolution and type of cutaneous mastocytosis was found. A late onset of the disease (after 2 years) is associated with worse evolution. CONCLUSIONS: PM is not systematically self-regressive. MC MRS manifestations and cutaneous lesions can persist or increase overtime. KIT mutation is not a predictor of evolution.


Assuntos
Mastocitoma Cutâneo/genética , Proteínas Proto-Oncogênicas c-kit/genética , Urticaria Pigmentosa/genética , Adolescente , Idade de Início , Biópsia , Criança , Análise Mutacional de DNA , Progressão da Doença , Éxons/genética , Feminino , Humanos , Estudos Longitudinais , Masculino , Mastocitoma Cutâneo/diagnóstico , Mastocitoma Cutâneo/patologia , Mutação , Estudos Prospectivos , Índice de Gravidade de Doença , Pele/patologia , Urticaria Pigmentosa/diagnóstico , Urticaria Pigmentosa/patologia
4.
Addict Behav ; 73: 4-8, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28431292

RESUMO

BACKGROUND: Cannabis consumption is common among cocaine users; however, little is known about its effect on cocaine craving. The objective of this study was to assess whether cannabis co-use is associated with lower cue-induced cocaine craving in non-treatment-seeking cocaine-dependent individuals. METHODS: Data from twenty-eight cocaine-dependent men were analyzed in this pilot study. Cocaine-dependent subjects (n=12) were compared with cocaine-dependent subjects who also abused or were dependent on cannabis (n=16). After at least 72h of cocaine abstinence, verified using the Timeline Followback and a drug screening test, subjects participated in a functional magnetic resonance imaging session during which neutral and drug cue video sequences were presented. Each sequence comprised four video blocks alternating with resting blocks. We report here subjective craving measures that were collected using the Visual Analog Scale, administered before and after each video block as per standard craving measurement paradigms. RESULTS: Cocaine craving was successfully induced, with no significant difference in cue-induced craving between the two groups. However, post-hoc analyses revealed a significant increase in pre-video cocaine craving scores over time among individuals with cannabis use disorders. CONCLUSION: We could not highlight significant differences in cocaine craving induction between groups, but we observed a possible deficit in craving decay in the cocaine and cannabis group. In light of this finding, methodology of craving assessment in non-treatment-seeking users, particularly when different substances are combined, should possibly include outcomes linked to craving decay. Studies examining the association between cocaine craving decay and other outcome measures, such as relapse, are also warranted.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/psicologia , Fissura/efeitos dos fármacos , Sinais (Psicologia) , Abuso de Maconha/psicologia , Adulto , Análise de Variância , Transtornos Relacionados ao Uso de Cocaína/complicações , Humanos , Masculino , Abuso de Maconha/complicações , Pessoa de Meia-Idade , Projetos Piloto , Recidiva , Síndrome de Abstinência a Substâncias/complicações , Síndrome de Abstinência a Substâncias/psicologia
5.
J Viral Hepat ; 24(1): 43-52, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27808453

RESUMO

Cross-continental phylogenetic analysis is important to understand subtle molecular differences of currently circulating hepatitis C virus (HCV) subtypes. Existence of such differences can be crucial in pursuing a universal hepatitis C vaccine. We characterized molecular epidemiology of early HCV infections identified across nine cohorts [North America (n=4), Australia (n=4) and Europe (n=1)] in the International Collaborative of Incident HIV and Hepatitis C in Injecting Cohorts (InC3 ). One hundred and ninety-two full-length HCV genomes were amplified from plasma of incident infections and subjected to next generation sequencing to establish the largest cross-continental, full-length acute HCV genomic data set available to date. Genomes from the most common subtypes (1a: n=94, 2b: n=15 and 3a: n=68) were used in phylogenetic analysis. Using full genome trees, 78 sequences (44%) were found to lie within 29 phylogenetic clusters/pairs defined on the basis of molecular similarity of consensus sequences. Of these, 26 each had exclusively Australian or North American sequences indicating a strong geographical bias for molecular similarity. On further analysis of behavioural and demographic associations, binary logistic regression analysis showed that older age and non-Caucasian ethnicity were significantly associated with clustering. HCV probably evolves in micro-epidemics within geographically isolated communities.


Assuntos
Hepacivirus/classificação , Hepacivirus/genética , Hepatite C/virologia , Filogenia , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Austrália/epidemiologia , Usuários de Drogas , Europa (Continente)/epidemiologia , Feminino , Genoma Viral , Genótipo , Hepacivirus/isolamento & purificação , Hepatite C/epidemiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Epidemiologia Molecular , América do Norte/epidemiologia , Plasma/virologia , Análise de Sequência de DNA , Adulto Jovem
6.
J Viral Hepat ; 24(1): 37-42, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27666440

RESUMO

Several direct-acting antivirals (DAAs) have been approved for the treatment of chronic hepatitis C virus (HCV) infections, opening the door to highly effective interferon-free treatment regimens. Resistance-associated substitutions (RASs) have been reported both in treatment-naïve patients and following treatment with protease (NS3), phosphoprotein (NS5A) and polymerase (NS5B) inhibitors. The prevalence of naturally occurring RASs in untreated HCV-infected individuals has mostly been analysed in those infected with genotype 1 (GT1), in the late phase of infection, and only within limited regions of the genome. Furthermore, the geographic distribution of RASs remains poorly characterized. In this study, we used next-generation sequencing to analyse full-length HCV genomes for the prevalence of RASs in acute HCV infections identified in nine international prospective cohorts. RASs were analysed in 179 participants infected with all six major HCV genotypes (GT1-GT6), and the geographic distribution of RASs was assessed in 107 GT1a and GT3a samples. While RASs were detected at varied frequencies across the three genomic regions, and between genotypes, RASs relevant to multiple DAAs in the leading IFN-free regimens were rarely detected in combination. Low-frequency RASs (<10% of the viral population) were also shown to have a GT-specific distribution. The main RASs with geographic associations were NS3 Q80K in GT1a samples and NS5B N142T in GT3a. These data provide the backdrop for prospective surveillance of RASs during DAA treatment scale-up.


Assuntos
Substituição de Aminoácidos , Farmacorresistência Viral , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Adulto , Feminino , Frequência do Gene , Hepacivirus/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Proteínas Mutantes/genética , Filogeografia , Estudos Prospectivos , Análise de Sequência de DNA , Proteínas não Estruturais Virais/genética , Adulto Jovem
7.
Clin Exp Immunol ; 186(3): 336-346, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27506421

RESUMO

Carriage of certain inhibitory natural killer (NK) cell receptor (iNKR)/HLA ligand pairs is associated with protection from infection and slow time to AIDS implicating NK cells in HIV control. NK cells acquire functional potential through education, which requires the engagement of iNKRs by their human leucocyte antigen (HLA) ligands. HIV infection down-regulates cell surface HLA-A/B, but not HLA-C/E. We investigated how NK cell populations expressing combinations of the iNKRs NKG2A, KIR2DL3 (2DL3) and KIR3DL1 (3DL1) responded to autologous HIV infected CD4 (iCD4) cells. Purified NK cells from HIV-uninfected individuals were stimulated with autologous HIV iCD4 or uninfected CD4 T cells. Using flow cytometry we gated on each of the 8 NKG2A+/- 2DL3+/- 3DL1+/- populations and analysed all possible combinations of interferon (IFN)-γ, CCL4 and CD107a functional subsets responding to iCD4 cells. Infected CD4 cells induced differential frequencies of NKG2A+/- 2DL3+/- 3DL1+/- populations with total IFN-γ+ , CCL4+ and CD107a+ functional profiles. 2DL3+ NKG2A+ NK cells had a higher frequency of responses to iCD4 than other populations studied. A higher frequency of 2DL3+ NK cells responded to iCD4 from individuals that were not HLA-C1 homozygotes. These results show that 2DL3+ NK cells are mediators of HIV-specific responses. Furthermore, responses of NK cell populations to iCD4 are influenced not only by NK cell education through specific KIR/HLA pairs, but also by differential HIV-mediated changes in HLA expression.


Assuntos
Quimiocina CCL4/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Receptores KIR2DL3/metabolismo , Receptores KIR3DL1/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Células Cultivadas , Genótipo , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , HIV-1/imunologia , Antígenos HLA/genética , Antígenos HLA/imunologia , Antígenos HLA-C/genética , Antígenos HLA-C/imunologia , Homozigoto , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária , Receptores KIR2DL3/genética , Receptores KIR3DL1/genética
8.
J Clin Immunol ; 36(5): 423-8, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27072857

RESUMO

Patients with Down syndrome are more susceptible to autoimmune pathologies, in particular endocrine or digestive diseases such as celiac disease. Autoimmune enteropathy is another form of digestive autoimmune disease, non-gluten-dependant, more often diagnosed in male neonates with immunodysregulation and polyendocrinopathy such as the Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome. It also exists in the adult, but this pathology is less known and therefore frequently under-diagnosed. Clinical manifestations are similar to celiac disease, but not improved after a gluten-free diet. Autoimmune enteropathy is frequently associated with other autoimmune diseases, such as thyroiditis, myasthenia gravis, lupus or immune deficiencies, as Common Variable Immunodeficiency. Pathological analysis of intestinal biopsies can frequently distinguish autoimmune enteropathy and celiac disease. Autoimmune enteropathy usually has an important lymphoplasmacytic infiltration of the mucosa and a lack of intraepithelial lymphocytes in the gastrointestinal mucosal surface, while celiac disease usually has a polymorph infiltration of the mucosa and an important intraepithelial lymphocytes infiltration. Nevertheless, the two pathological patterns may overlap. Here we report the first case of a patient with Down syndrome associated to autoimmune enteropathy (initially diagnosed as celiac disease), chronic pancreatitis and cutaneous lupus erythematosus. Even if autoimmune pathologies are much more common in patients with Down syndrome, we would like to report on this rare and original association found in our patient.


Assuntos
Doença Celíaca/diagnóstico , Síndrome de Down/diagnóstico , Intestinos/patologia , Linfócitos/imunologia , Poliendocrinopatias Autoimunes/diagnóstico , Adulto , Autoimunidade , Biópsia , Pré-Escolar , Diagnóstico Diferencial , Diarreia , Síndrome de Down/complicações , Feminino , Humanos , Intestinos/imunologia , Poliendocrinopatias Autoimunes/complicações , Adulto Jovem
9.
J Viral Hepat ; 22(12): 1020-32, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26098993

RESUMO

Pegylated interferon therapy is highly effective in recently acquired HCV. The optimal timing of treatment, regimen and influence of host factors remains unclear. We aimed to measure sustained virological response (SVR) during recent HCV infection and identify predictors of response. Data were from five prospective cohorts of high-risk individuals in Australia, Canada, Germany and the United States. Individuals with acute or early chronic HCV who commenced pegylated interferon therapy were included. The main outcome was SVR, and predictors were assessed using logistic regression. Among 516 with documented recent HCV infection, 237 were treated (pegylated interferon n = 161; pegylated interferon/ribavirin n = 76) (30% female, median age 35 years, 56% ever injected drugs, median duration of infection 6.2 months). Sixteen per cent (n = 38) were HIV/HCV co-infected. SVR among those with HCV mono-infection was 64% by intention to treat; SVR was 68% among HCV/HIV co-infection. Independent predictors of SVR in HCV mono-infection were duration of HCV infection (the odds of SVR declined by 8% per month of infection, aOR 0.92, 95% CI 0.85-0.99, P = 0.033), IFNL4 genotype (adjusted OR 2.27, 95% CI 1.13-4.56, P = 0.021), baseline HCV RNA <400 000 IU/mL (aOR 2.06, 95% CI 1.03-4.12, P = 0.041) and age ≥40 years (vs <30: aOR 2.92, 95% CI 1.31-6.49, P = 0.009), with no difference by drug regimen, HCV genotype, symptomatic infection or gender. The effect of infection duration on odds of SVR was greater among genotype-1 infection. Interferon-based HCV treatment is highly effective in recent HCV infection. Duration of infection, IFNL4 genotype and baseline HCV RNA levels can predict virological response and may inform clinical decision-making.


Assuntos
Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Interleucinas/genética , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Antivirais/uso terapêutico , Austrália , Canadá , Coinfecção/tratamento farmacológico , Quimioterapia Combinada , Feminino , Alemanha , Infecções por HIV/complicações , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Humanos , Interferon alfa-2 , Masculino , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Estados Unidos , Carga Viral/efeitos dos fármacos
10.
J Epidemiol Community Health ; 69(8): 745-52, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25814695

RESUMO

BACKGROUND: Hepatitis C virus (HCV) testing and counselling have the potential to impact individual behaviour and transmission dynamics at the population level. Evidence of the impact of an HCV-positive status notification on injection risk reduction is limited. The objective of our study was to (1) assess drug and alcohol use and injection risk behaviours following notification; (2) to compare behaviour change in people who inject drugs (PWID) who received a positive test result and those who remained negative; and (3) to assess the effect of age on risk behaviour. METHODS: Data from the International Collaboration of Incident HIV and HCV Infection in Injecting Cohorts (InC3 Study) were analysed. Participants who were initially HCV seronegative were followed prospectively with periodic HCV blood testing and post-test disclosure and interview-administered questionnaires assessing drug use and injection behaviours. Multivariable generalised estimating equations were used to assess behavioural changes over time. RESULTS: Notification of an HCV-positive test was independently associated with a small increase in alcohol use relative to notification of a negative test. No significant differences in postnotification injection drug use, receptive sharing of ancillary injecting equipment and syringe borrowing postnotification were observed between diagnosis groups. Younger PWID receiving a positive HCV test notification demonstrated a significant increase in subsequent alcohol use compared with younger HCV negative. CONCLUSIONS: The proportion of PWID reporting alcohol use increased among those receiving an HCV-positive notification, increased the frequency of alcohol use postnotification, while no reduction in injection drug use behaviours was observed between notification groups. These findings underscore the need to develop novel communication strategies during post-test notification to improve their impact on subsequent alcohol use and risk behaviours.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Hepatite C/diagnóstico , Testes Sorológicos/psicologia , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Distribuição por Idade , Feminino , Hepacivirus/isolamento & purificação , Hepatite C/psicologia , Hepatite C/transmissão , Humanos , Estudos Longitudinais , Masculino , Estudos Multicêntricos como Assunto , Uso Comum de Agulhas e Seringas/psicologia , Uso Comum de Agulhas e Seringas/estatística & dados numéricos , New South Wales , Educação de Pacientes como Assunto , Quebeque , Assunção de Riscos , São Francisco , Testes Sorológicos/estatística & dados numéricos , Abuso de Substâncias por Via Intravenosa/psicologia , Vitória , Adulto Jovem
11.
Clin Exp Immunol ; 181(2): 275-85, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25644502

RESUMO

Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) has been linked to protection from HIV infection and slower progression towards AIDS. However, antibody-dependent activation of NK cells results in phenotypical alterations similar to those observed on NK cells from individuals with progressive HIV infection. Activation of NK cells induces matrix metalloproteinase (MMP)-mediated cleavage of cell surface CD16. In the present study we assessed the phenotype and functional profile of NK cells exhibiting post-activation MMP-mediated CD16 cleavage. We found that NK cells achieving the highest levels of activation during stimulation exhibit the most profound decreases in CD16 expression. Further, we observed that educated KIR3DL1(+) NK cells from human leucocyte antigen (HLA)-Bw4-carrying donors exhibit larger decreases in CD16 expression post-activation than the KIR3DL1(-) NK cell subset containing cells educated via other inhibitory receptor/ligand combinations and non-educated NK cells. Lastly, we assessed the ex-vivo expression of CD16 on educated KIR3DL1(+) NK cells and the KIR3DL1(-) NK cell subset from HLA-Bw4-carrying HIV-uninfected and HIV-infected donors. Suggestive of in-vivo activation of KIR3DL1(+) NK cells during HIV infection, CD16 expression was higher on KIR3DL1(+) than KIR3DL1(-) NK cells in uninfected donors but similar on both subsets in HIV-infected donors. These results are discussed in the context of how they may assist with understanding HIV disease progression and the design of immunotherapies that utilize antibody-dependent NK cell responses.


Assuntos
Infecções por HIV/imunologia , Células Matadoras Naturais/imunologia , Metaloproteinases da Matriz/imunologia , RNA Viral/sangue , Receptores de IgG/imunologia , Anticorpos/farmacologia , Citotoxicidade Celular Dependente de Anticorpos , Progressão da Doença , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/imunologia , Expressão Gênica , Infecções por HIV/genética , Infecções por HIV/patologia , Infecções por HIV/virologia , HIV-1/imunologia , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Teste de Histocompatibilidade , Humanos , Imunofenotipagem , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/patologia , Células Matadoras Naturais/virologia , Ativação Linfocitária , Metaloproteinases da Matriz/genética , Fenótipo , Cultura Primária de Células , Proteólise , Receptores de IgG/genética , Receptores KIR3DL1/genética , Receptores KIR3DL1/imunologia , Transdução de Sinais , Carga Viral
12.
Br J Dermatol ; 172(3): 642-51, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25662299

RESUMO

Paediatric mastocytosis was previously considered to be a benign and spontaneously regressing disease. However, this evolution is impossible to predict. To clarify the characteristics and course of paediatric mastocytosis, we performed a literature review of 1747 cases published between 1950 and April 2014. Lesions occurred before the age of 2 years in 90% of cases, and presented as urticaria pigmentosa (75% of cases), mastocytoma (20%) or diffuse cutaneous mastocytosis (5%). The male-to-female ratio was 1·4. KIT D816V mutation was detected in 34% of 215 tested patients. Clinical regression (complete or partial) occurred in 67% of cases and stabilization in 27%. However, the outcome was fatal in 2·9% of patients.


Assuntos
Mastocitose Cutânea/patologia , Idade de Início , Biópsia/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mastocitose Cutânea/genética , Mutação/genética , Gravidez , Prognóstico , Proteínas Proto-Oncogênicas c-kit/genética , Urticaria Pigmentosa/etiologia
13.
J Viral Hepat ; 22(10): 792-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25586516

RESUMO

The role of primary care physicians (PCP) in hepatitis C virus (HCV) prevention is increasingly emphasized. Yet, little is known about the patterns of contacts with PCP among persons who inject drugs (PWID). We sought to assess the 6-month prevalence of PCP visiting among PWID at risk of HCV infection and to explore the associated factors. Baseline data were collected from HCV-seronegative PWID recruited in HEPCO, an observational Hepatitis Cohort study (2004-2011) in Montreal, Canada. An interviewer-administered questionnaire elicited information on socio-demographic factors, drug use patterns and healthcare services utilization. Blood samples were tested for HCV antibodies. Using the Gelberg-Andersen Behavioral Model, hierarchical logistic regression analyses were conducted to identify predisposing, need and enabling factors associated with PCP visiting. Of the 349 participants (mean age = 34; 80.8% male), 32.1% reported visiting a PCP. In the multivariate model, among predisposing factors, male gender [adjusted odds ratio (AOR) = 0.45 (0.25-0.83)], chronic homelessness [AOR = 0.08 (0.01-0.67)], cocaine injection [AOR = 0.46 (0.28-0.76)] and reporting greater illegal or semi-legal income [AOR = 0.48 (0.27-0.85)] were negatively associated with PCP visits. Markers of need were not associated with the outcome. Among enabling factors, contact with street nurses [AOR = 3.86 (1.49-9.90)] and food banks [AOR = 2.01 (1.20-3.37)] was positively associated with PCP visiting. Only one third of participating PWID reported a recent visit to a PCP. While a host of predisposing factors seems to hamper timely contacts with PCP among high-risk PWID, community-based support services may play an important role in initiating dialogue with primary healthcare services in this population.


Assuntos
Hepatite C/diagnóstico , Aceitação pelo Paciente de Cuidados de Saúde , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Canadá , Estudos de Coortes , Feminino , Anticorpos Anti-Hepatite C/sangue , Humanos , Entrevistas como Assunto , Masculino , Visita a Consultório Médico , Atenção Primária à Saúde/estatística & dados numéricos
14.
J Viral Hepat ; 22(9): 708-17, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25580520

RESUMO

Improved understanding of natural history of hepatitis C virus (HCV) RNA levels in chronic infection provides enhanced insights into immunopathogenesis of HCV and has implications for the clinical management of chronic HCV infection. This study assessed factors associated with HCV RNA levels during early chronic infection in a population with well-defined early chronic HCV infection. Data were from an international collaboration of nine prospective cohorts studying acute HCV infection (InC(3) study). Individuals with persistent HCV and detectable HCV RNA during early chronic infection (one year [±4 months] postinfection) were included. Distribution of HCV RNA levels during early chronic infection was compared by selected host and virological factors. A total of 308 individuals were included. Median HCV RNA levels were significantly higher among males (vs females; 5.15 vs 4.74 log IU/mL; P < 0.01) and among individuals with HIV co-infection (vs no HIV; 5.89 vs 4.86; P = 0.02). In adjusted logistic regression, male sex (vs female, adjusted odds ratio [AOR]: 1.93; 95%CI: 1.01, 3.69), interferon lambda 4 (IFNL4) rs12979860 CC genotype (vs TT/CT; AOR: 2.48; 95%CI: 1.42, 4.35), HIV co-infection (vs no HIV; AOR: 3.27; 95%CI: 1.35, 7.93) and HCV genotype G2 (vs G3; AOR: 5.40; 95%CI: 1.63, 17.84) were independently associated with high HCV RNA levels (>5.6 log IU/mL = 400 000 IU/mL). In conclusion, this study demonstrated that IFNL4 rs12979860 CC genotype, male sex, HIV co-infection and HCV genotype G2 are associated with high HCV RNA levels in early chronic infection. These factors exert their role as early as one year following infection.


Assuntos
Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , RNA Viral/sangue , Carga Viral , Adulto , Feminino , Genótipo , Infecções por HIV/complicações , Hepacivirus/classificação , Hepacivirus/genética , Humanos , Interleucinas/genética , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Sexuais , Adulto Jovem
15.
J Eur Acad Dermatol Venereol ; 28(7): 967-71, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23763569

RESUMO

BACKGROUND: Mastocytosis is a heterogeneous disease whose different subtypes also vary in aggressivity. Children typically present with cutaneous mastocytosis. We identified, in our previous work, a peripheral CD34-c-Kit+mast cell precursor by flow cytometry in systemic forms but not in cutaneous forms of adult mastocytosis. OBJECTIVES: We wanted to know if such a mast cell precursor exists among children with mastocytosis. METHODS: We analysed 10 children with mastocytosis for c-Kit+CD34- mast cell precursors by flow cytometry. RESULTS: In contrast to adults with mastocytosis, we did not detect any circulating mast cell precursors by flow cytometry in the peripheral blood of children with mastocytosis. CONCLUSION: The clinical symptoms observed among children with cutaneous mastocytosis could be induced by cutaneous mast cell mediators and not by circulating mast cells. These results may help to better understand the differences between adult and childhood mastocytosis.


Assuntos
Mastócitos/patologia , Mastocitose Cutânea/patologia , Mastocitose Cutânea/fisiopatologia , Células-Tronco/patologia , Adulto , Fatores Etários , Contagem de Células , Proliferação de Células , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Humanos , Lactente , Masculino
16.
Med Sante Trop ; 23(2): 225, 2013 May 01.
Artigo em Francês | MEDLINE | ID: mdl-24001639

RESUMO

Seeking to understand how humans, by the settlements they create (among other means), influence the operation of the pathogen system of sleeping sickness, the authors performed a diachronic analysis of the landscape and settlement dynamics by comparing topographic maps from 1957, a satellite image from 2004, and georeferenced censuses from 2009 and 2001. It appears that the extreme mobility of the population between the continent and the islands is the principal cause for the continuation of this disease at the mouth of the Rio Pongo.


Assuntos
Rios , Tripanossomíase Africana/epidemiologia , Emigração e Imigração , Geografia , Guiné/epidemiologia , Humanos , Fatores de Risco
17.
J Epidemiol Community Health ; 62(9): 804-10, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18701731

RESUMO

BACKGROUND: Studies indicate that needle-exchange programmes (NEPs) can reduce the incidence of HIV infection; however, a positive impact of syringe-supply programmes has not been consistently demonstrated. The associations between high-risk injection behaviour and distance to and patterns of utilisation of syringe-supply programmes in injection drug users (IDUs) were investigated. METHODS: Participants in a cohort of IDUs (n = 456) residing in Montreal were interviewed between 2004 and 2006. Behavioural questionnaires were administered by trained interviewers, and venous blood samples were drawn and tested for HIV antibodies. The distance from regular IDU dwelling places to nearest NEP or pharmacy was calculated using a Geographic Information System. Logistic regression was used to assess relations with high-risk injection behaviour. RESULTS: Associations between high-risk injection behaviour and distance to syringe-supply source were not linear. The odds of high-risk behaviour grew modestly as distance from the NEP site increased to 1600 m, followed by a flat trend to 3000 m, and thereafter decreased with distance beyond this point. The odds of high-risk behaviour dropped sharply for the relatively few IDUs residing 1 km or more from the nearest pharmacy but this measure was not strongly associated with the outcome. IDUs who exclusively acquired syringes at NEPs or pharmacies had less than half the odds of reporting high-risk injection behaviour than IDUs with inconsistent syringe-access patterns. CONCLUSIONS: The study confirms that Montreal NEPs were implemented where they are most needed. These results also suggest that sterile syringe acquisition patterns might influence high-risk injection behaviour.


Assuntos
Infecções por HIV/prevenção & controle , Acessibilidade aos Serviços de Saúde , Programas de Troca de Agulhas/estatística & dados numéricos , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Estudos de Coortes , Serviços Comunitários de Farmácia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Pesquisa sobre Serviços de Saúde/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Quebeque/epidemiologia , Assunção de Riscos , Abuso de Substâncias por Via Intravenosa/epidemiologia
18.
Int J Tuberc Lung Dis ; 8(8): 988-93, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15305482

RESUMO

BACKGROUND: Regardless of their HIV status, injection drug users (IDUs) are at increased risk of developing active tuberculosis (TB) if they have latent TB infection (LTBI). We quantified the prevalence and predictors of LTBI and level of adherence to medical evaluation in a population of IDUs in Montreal. METHODS: Participants were recruited from an ongoing dynamic cohort of IDUs followed for HIV seroconversion risk behaviour. Subjects with a tuberculin skin test (TST) of > or =5 mm were referred to designated TB clinics for medical evaluation. A financial incentive was provided for TST readings. RESULTS: Of the 262 subjects tested, 246 (94%) returned for TST reading. The overall prevalence of positive TSTs was 22% (5% in HIV-positive, 28% in HIV-negative participants). Older age at first injection drug use (OR per 10 year increase in age 1.4, 95%CI 1.2-1.8), duration of injection drug use (OR per 10 year increase 1.6, 9.5%CI 1.5-2.2) and negative HIV status (OR 11.2, 95%CI 3.2-4.0) were independent predictors of a positive TST. Nine per cent of all TST-positive participants completed LTBI treatment. CONCLUSION: TB screening activities with incentives can be successful in detecting TST-positive individuals, but better strategies are needed for medical follow-up in this high-risk group.


Assuntos
Abuso de Substâncias por Via Intravenosa , Teste Tuberculínico , Tuberculose/diagnóstico , Adulto , Idoso , Antituberculosos/uso terapêutico , Distribuição de Qui-Quadrado , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Cooperação do Paciente , Prevalência , Quebeque/epidemiologia , Fatores de Risco , Abuso de Substâncias por Via Intravenosa/epidemiologia , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia
19.
AIDS Care ; 15(2): 187-95, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12856340

RESUMO

In Canada, very little is known about the factors and processes that cause drug-related harm among female intravenous drug users (IDUs). Women who inject drugs and participate in the survival sex trade are considered to be at increased risk for sexual and drug-related harms, including HIV infection. Between September 1999 and September 2000, women participating in the VIDUS cohort in Vancouver and the St. Luc Cohort in Montreal completed interviewer-administered questionnaires. Analyses were conducted to compare the demographic characteristics, sexual risk behaviours, risky injection practices and drug use patterns among women who self-identified as participating in the sex trade with those who did not identify as participating in the sex trade. Logistic regression was used to identify factors independently associated with exchanging sex for money or drugs. HIV prevalence at the study visit (September 1999-2000) was 29% for sex trade workers and 29.2% for non-sex trade workers. While patterns of sexual risk were similar, the risky injection practice and drug use patterns between sex trade workers and non-sex trade workers were markedly different. Logistic regression analysis of cross-sectional data revealed that independent behaviours associated with the sex trade included: greater than once per day use of heroin (adjusted OR 2.7), smokeable crack cocaine (adjusted OR = 3.3) and borrowing used syringes (adjusted OR = 2.0). Creative, client-driven interventions are urgently needed for women who trade sex for money or for drugs.


Assuntos
Infecções por HIV/transmissão , Trabalho Sexual , Abuso de Substâncias por Via Intravenosa/complicações , Adolescente , Adulto , Idoso , Canadá/epidemiologia , Estudos de Coortes , Feminino , Infecções por HIV/epidemiologia , Humanos , Pessoa de Meia-Idade , Prevalência , Assunção de Riscos , Comportamento Sexual , Abuso de Substâncias por Via Intravenosa/epidemiologia
20.
Int. j. morphol ; 21(4): 309-313, 2003. tab
Artigo em Espanhol | LILACS | ID: lil-388116

RESUMO

La obesidad en el mundo se ha convertido en un problema de salud pública, no escapando a esta situación los adolescentes de Chile. Los estudios de la composición corporal, estado nutricional e índice de masa corporal (IMC) son los parámetros recomendados por la OMS, para determinar el estado nutricional del Hombre. Realizamos este estudio para conocer la real situación de los adolescentes de Temuco, . Evaluamos 208 sujetos de ambos sexos, entre 10 y 13 años de edad, de un colegio privado de la ciudad de Temuco, Novena Región Chile. Los sujetos fueron evaluados en el Centro de Alto Rendimiento del Instituto Nacional del Deporte. Para obtener el somatotipo utilizamos el método antropométrico de Heath & Carter, efectuándose la clasificación del IMC de acuerdo a las normas de la OMS. Los hombres resultaron ser más mesomórficos que las mujeres, siendo esta diferencia estadísticamente significativa. Los componentes endomórfico y ectomorfico no presentaron diferencias estadísticamente significativas de acuerdo al sexo. El IMC mostró valores de 47 por ciento sobre lo normal en los hombres y de 33 por ciento sobre lo normal en las mujeres. La muestra presentó un predominio del componente mesoendomórfico. Estos resultados demostraron la existencia de una gran cantidad de tejido adiposo en los adolescentes, con el consecuente aumento de peso y obesidad. Esto último, producto de la falta de actividad física, cambios de los hábitos alimenticios y por la propia naturaleza de nuestra región, la cual presenta un extenso periodo invernal.


Assuntos
Adolescente , Índice de Massa Corporal , Pesos e Medidas Corporais , Somatotipos/fisiologia , Antropometria , Chile
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