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1.
Clin Rheumatol ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31916109

RESUMO

Although several genetic associations with scleroderma (SSc) are defined, very little is known on genetic susceptibility to SSc-associated interstitial lung disease (SSc-ILD). A number of common polymorphisms have been associated with SSc-ILD, but most have not been replicated in separate populations. Four SNPs in IRF5, and one in each of STAT4, CD226 and IRAK1, selected as having been previously the most consistently associated with SSc-ILD, were genotyped in 612 SSc patients, of European descent, of whom 394 had ILD. The control population (n = 503) comprised individuals of European descent from the 1000 Genomes Project. After Bonferroni correction, two of the IRF5 SNPs, rs2004640 (OR (95% CI)1.30 (1.10-1.54), pcorr = 0.015) and rs10488631 (OR 1.48 (1.14-1.92), pcorr = 0.022), and the STAT4 SNP rs7574865 (OR 1.43 (1.18-1.73), pcorr = 0.0015) were significantly associated with SSc compared with controls. However, none of the SNPs were significantly different between patients with SSc-ILD and controls. Two SNPs in IRF5, rs10488631 (OR 1.72 (1.24-2.39), pcorr = 0.0098), and rs2004640 (OR 1.39 (1.11-1.75), pcorr = 0.03), showed a significant difference in allele frequency between controls and patients without ILD, as did STAT4 rs7574865 (OR 1.86 (1.45-2.38), pcorr = 6.6 × 10-6). A significant difference between SSc with and without ILD was only observed for STAT4 rs7574865, being less frequent in patients with ILD (OR 0.66 (0.51-0.85), pcorr = 0.0084). In conclusion, IRF5 rs2004640 and rs10488631, and STAT4 rs7574865 were significantly associated with SSc as a whole. Only STAT4 rs7574865 showed a significant difference in allele frequency in SSc-ILD, with the T allele being protective against ILD.Key points• We confirm the associations of the IRF5 SNPs rs2004640 and rs10488631, and the STAT4 SNP rs7574865, with SSc as a whole.• None of the tested SNPs were risk factors for SSc-ILD specifically.• The STAT4 rs7574865 T allele was protective against the development of lung fibrosis in SSc patients.• Further work is required to understand the genetic basis of lung fibrosis in association with scleroderma.

4.
Lancet Respir Med ; 6(10): 759-770, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30170904

RESUMO

BACKGROUND: In fibrotic interstitial lung diseases, exertional breathlessness is strongly linked to health-related quality of life (HRQOL). Breathlessness is often associated with oxygen desaturation, but few data about the use of ambulatory oxygen in patients with fibrotic interstitial lung disease are available. We aimed to assess the effects of ambulatory oxygen on HRQOL in patients with interstitial lung disease with isolated exertional hypoxia. METHODS: AmbOx was a prospective, open-label, mixed-method, crossover randomised controlled clinical trial done at three centres for interstitial lung disease in the UK. Eligible patients were aged 18 years or older, had fibrotic interstitial lung disease, were not hypoxic at rest but had a fall in transcutaneous arterial oxygen saturation to 88% or less on a screening visit 6-min walk test (6MWT), and had self-reported stable respiratory symptoms in the previous 2 weeks. Participants were randomly assigned (1:1) to either oxygen treatment or no oxygen treatment for 2 weeks, followed by crossover for another 2 weeks. Randomisation was by a computer-generated sequence of treatments randomly permuted in blocks of constant size (fixed size of ten). The primary outcome, which was assessed by intention to treat, was the change in total score on the King's Brief Interstitial Lung Disease questionnaire (K-BILD) after 2 weeks on oxygen compared with 2 weeks of no treatment. General linear models with treatment sequence as a fixed effect were used for analysis. Patient views were explored through semi-structured topic-guided interviews in a subgroup of participants. This study was registered with ClinicalTrials.gov, number NCT02286063, and is closed to new participants with all follow-up completed. FINDINGS: Between Sept 10, 2014, and Oct 5, 2016, 84 patients were randomly assigned, 41 randomised to ambulatory oxygen first and 43 to no oxygen. 76 participants completed the trial. Compared with no oxygen, ambulatory oxygen was associated with significant improvements in total K-BILD scores (mean 55·5 [SD 13·8] on oxygen vs 51·8 [13·6] on no oxygen, mean difference adjusted for order of treatment 3·7 [95% CI 1·8 to 5·6]; p<0·0001), and scores in breathlessness and activity (mean difference 8·6 [95% CI 4·7 to 12·5]; p<0·0001) and chest symptoms (7·6 [1·9 to 13·2]; p=0·009) subdomains. However, the effect on the psychological subdomain was not significant (2·4 [-0·6 to 5·5]; p=0·12). The most common adverse events were upper respiratory tract infections (three in the oxygen group and one in the no-treatment group). Five serious adverse events, including two deaths (one in each group) occurred, but none were considered to be related to treatment. INTERPRETATION: Ambulatory oxygen seemed to be associated with improved HRQOL in patients with interstitial lung disease with isolated exertional hypoxia and could be an effective intervention in this patient group, who have few therapeutic options. However, further studies are needed to confirm this finding. FUNDING: UK National Institute for Health Research.


Assuntos
Doenças Pulmonares Intersticiais/terapia , Oxigenoterapia/métodos , Oxigênio/administração & dosagem , Fibrose Pulmonar/terapia , Qualidade de Vida , Idoso , Estudos Cross-Over , Feminino , Humanos , Análise de Intenção de Tratamento , Modelos Lineares , Doenças Pulmonares Intersticiais/psicologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fibrose Pulmonar/psicologia , Resultado do Tratamento
5.
Respir Med ; 138: 95-101, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29724400

RESUMO

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) has been described in hypersensitivity pneumonitis (HP) yet its functional implications are unclear. Combined pulmonary fibrosis and emphysema (CPFE) has occasionally been described in never-smokers with HP, but epidemiological data regarding its prevalence is sparse. CTs in a large HP cohort were therefore examined to identify the prevalence and effects of PPFE and emphysema. METHODS: 233 HP patients had CT extents of interstitial lung disease (ILD) and emphysema quantified to the nearest 5%. Lobar percentage pleural involvement of PPFE was quantified on a 4-point categorical scale: 0 = absent, 1 = affecting <10%, 2 = affecting 10-33%, 3 = affecting >33%. Marked PPFE reflected a total lung score of ≥3/18. Results were evaluated against FVC, DLco and mortality. RESULTS: Marked PPFE prevalence was 23% whilst 23% of never-smokers had emphysema. Following adjustment for patient age, gender, smoking status, and ILD and emphysema extents, marked PPFE independently linked to reduced baseline FVC (p = 0.0002) and DLco (p = 0.002) and when examined alongside the same covariates, independently linked to worsened survival (p = 0.01). CPFE in HP demonstrated a characteristic functional profile of artificial lung volume preservation and disproportionate DLco reduction. CPFE did not demonstrate a worsened outcome when compared to HP patients without emphysema beyond that explained by CT extents of ILD and emphysema. CONCLUSIONS: PPFE is not uncommon in HP, and is independently associated with impaired lung function and increased mortality. Emphysema was identified in 23% of HP never-smokers. CPFE appears not to link to a malignant microvascular phenotype as outcome is explained by ILD and emphysema extents.


Assuntos
Alveolite Alérgica Extrínseca/epidemiologia , Pleura/patologia , Enfisema Pulmonar/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alveolite Alérgica Extrínseca/diagnóstico por imagem , Alveolite Alérgica Extrínseca/fisiopatologia , Tecido Elástico/patologia , Feminino , Fibrose/diagnóstico por imagem , Fibrose/epidemiologia , Fibrose/fisiopatologia , Volume Expiratório Forçado/fisiologia , Humanos , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Pleura/diagnóstico por imagem , Prevalência , Prognóstico , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/fisiopatologia , Testes de Função Respiratória , Fumar/epidemiologia , Tomografia Computadorizada por Raios X , Capacidade Vital/fisiologia
6.
Am J Respir Crit Care Med ; 198(6): 767-776, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29684284

RESUMO

RATIONALE: Quantitative computed tomographic (CT) measures of baseline disease severity might identify patients with idiopathic pulmonary fibrosis (IPF) with an increased mortality risk. We evaluated whether quantitative CT variables could act as a cohort enrichment tool in future IPF drug trials. OBJECTIVES: To determine whether computer-derived CT measures, specifically measures of pulmonary vessel-related structures (VRSs), can better predict functional decline and survival in IPF and reduce requisite sample sizes in drug trial populations. METHODS: Patients with IPF undergoing volumetric noncontrast CT imaging at the Royal Brompton Hospital, London, and St. Antonius Hospital, Utrecht, were examined to identify pulmonary function measures (including FVC) and visual and computer-derived (CALIPER [Computer-Aided Lung Informatics for Pathology Evaluation and Rating] software) CT features predictive of mortality and FVC decline. The discovery cohort comprised 247 consecutive patients, with validation of results conducted in a separate cohort of 284 patients, all fulfilling drug trial entry criteria. MEASUREMENTS AND MAIN RESULTS: In the discovery and validation cohorts, CALIPER-derived features, particularly VRS scores, were among the strongest predictors of survival and FVC decline. CALIPER results were accentuated in patients with less extensive disease, outperforming pulmonary function measures. When used as a cohort enrichment tool, a CALIPER VRS score greater than 4.4% of the lung was able to reduce the requisite sample size of an IPF drug trial by 26%. CONCLUSIONS: Our study has validated a new quantitative CT measure in patients with IPF fulfilling drug trial entry criteria-the VRS score-that outperformed current gold standard measures of outcome. When used for cohort enrichment in an IPF drug trial setting, VRS threshold scores can reduce a required IPF drug trial population size by 25%, thereby limiting prohibitive trial costs. Importantly, VRS scores identify patients in whom antifibrotic medication prolongs life and reduces FVC decline.


Assuntos
Fibrose Pulmonar Idiopática/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Testes de Função Respiratória , Capacidade Vital
7.
J Neurol Sci ; 365: 132-6, 2016 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-27206890

RESUMO

Guillain-Barré syndrome (GBS) is considered a monophasic disorder yet recurrences occur in up to 6% of patients. We retrospectively studied an Italian-Japanese population of 236 GBS and 73 Miller Fisher syndrome (MFS) patients and searched for factors which may be associated with recurrence. A recurrent patient was defined as having at least two episodes that fulfilled the diagnostic criteria for GBS and MFS with an identifiable recovery after each episode and a minimum of 2months between episodes. Preceding Campylobacter jejuni (C. jejuni) infection and antiganglioside antibodies were also assessed. Seven (3%) recurrent GBS and one (1.4%) recurrent MFS patients were identified. In the individual patient the clinical features during episodes were usually similar varying in severity whereas the preceding infection differed. None of the patients had GBS in one episode and MFS in the recurrence or vice versa. Recurrent GBS patients, compared with monophasic GBS, did not have preceding diarrhea at the first episode and considering the electrophysiological subtypes, acute inflammatory demyelinating polyneuropathies recurred more frequently than axonal GBS (6.5% vs 0.9%, p=0.04). In conclusion in a GBS population with a balanced number of demyelinating and axonal subtypes less frequent diarrhea and demyelination at electrophysiology were associated with recurrence.


Assuntos
Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/fisiopatologia , Síndrome de Miller Fisher/epidemiologia , Condução Nervosa/fisiologia , Adolescente , Adulto , Idoso , Anticorpos/metabolismo , Infecções por Campylobacter/epidemiologia , Infecções por Campylobacter/imunologia , Criança , Estimulação Elétrica , Feminino , Gangliosídeos/imunologia , Humanos , Itália/epidemiologia , Japão/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher/fisiopatologia , Recidiva , Estudos Retrospectivos , Estatísticas não Paramétricas , Adulto Jovem
9.
J Neuroimmunol ; 276(1-2): 207-12, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25283719

RESUMO

We tested autoantibodies to neurofascin-186 (NF186) and gliomedin in sera from patients with multifocal motor neuropathy (MMN, n=53) and chronic inflammatory demyelinating polyneuropathy (CIDP, n=95) by ELISA. IgG antibodies to NF186 or gliomedin were found in 62% of MMN and 1% of CIDP sera, and IgM antibodies to the same antigens in 12% of MMN and 1% of CIDP sera. These autoantibodies activated complement. Ten percent of the MMN sera without IgM anti-GM1 reactivity had anti-NF186 antibodies. Because NF186 and gliomedin play a crucial role for salutatory conduction, the autoantibodies may contribute to produce motor nerve conduction block and muscle weakness in MMN.


Assuntos
Autoanticorpos/sangue , Moléculas de Adesão Celular/imunologia , Proteínas de Membrana/imunologia , Doença dos Neurônios Motores/sangue , Fatores de Crescimento Neural/imunologia , Proteínas do Tecido Nervoso/imunologia , Polineuropatias/sangue , Animais , Moléculas de Adesão Celular/genética , Biologia Computacional , Ensaio de Imunoadsorção Enzimática , Feminino , Gangliosídeo G(M1)/genética , Gangliosídeo G(M1)/imunologia , Humanos , Masculino , Proteínas de Membrana/genética , Doença dos Neurônios Motores/complicações , Fatores de Crescimento Neural/genética , Proteínas do Tecido Nervoso/genética , Polineuropatias/complicações , Isoformas de Proteínas/imunologia , Ratos , Transfecção
10.
Mol Diagn Ther ; 18(5): 505-22, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24935523

RESUMO

Interstitial lung diseases (ILD) are protean conditions with substantial overlap in terms of diagnosis, prognostic evaluation, and management. However, the management of idiopathic pulmonary fibrosis is different from that of more immunologically driven ILD patterns, such as ILD associated with connective tissue diseases. It is important to provide accurate diagnosis and patient selection for prognostication and timely treatment, preferably at baseline. Validated non-invasive biomarkers fulfilling these unmet clinical needs are warranted. Although no ILD biomarker has been adopted in clinical practice so far, advancements in this field have been achieved, especially with the implementation of high-throughput techniques and clinical-laboratory multi-parametric panels. This review focuses on selected validated and/or potentially interesting biomarkers investigated in the peripheral blood and lung tissue of patients with ILD. Current issues and future directions in various aspects of ILD biomarkers research and its clinical application are explored.


Assuntos
Biomarcadores/sangue , Biomarcadores/metabolismo , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Pulmão/metabolismo , Pulmão/patologia , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/metabolismo
11.
Respirology ; 19(3): 353-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24286447

RESUMO

BACKGROUND AND OBJECTIVE: In patients with severe interstitial lung disease (ILD) progressing despite conventional immunosuppression, rituximab, a B-lymphocyte depleting monoclonal antibody, may offer an effective rescue therapy. METHODS: Retrospective assessment of 50 patients with severe, progressive ILD (of varying aetiologies, excluding idiopathic pulmonary fibrosis (IPF)) treated with rituximab between 2010 and 2012. Change in pulmonary function tests compared with pre-rituximab levels was assessed at 6-12 months post-treatment. RESULTS: ILD was associated with connective tissue disease in 33 patients, hypersensitivity pneumonitis in 6 patients and miscellaneous conditions in 11 patients. At the time of rituximab administration, patients had severe physiologic impairment with a median forced vital capacity (FVC) of 44.0% (24.0-99.0%) and diffusing capacity of carbon monoxide (DLCO ) of 24.5% (11.4-67.0%). In contrast with a median decline in FVC of 14.3% and DLCO of 18.8% in the 6-12 months prior to rituximab, analysis of paired pulmonary function data revealed a median improvement in FVC of 6.7% (P < 0.01) and stability of DLCO (0% change; P < 0.01) in the 6-12 months following rituximab treatment. Two patients developed serious infections (pneumonia) requiring hospitalization following rituximab, and 10 patients died from progression of underlying ILD, a median of 5.1 (1.2-24.5) months after treatment. CONCLUSIONS: In patients with severe, progressive non-IPF ILD unresponsive to conventional immunosuppression, rituximab may offer an effective therapeutic intervention. Future prospective, controlled trials are warranted to validate these findings, and to assess safety outcomes.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Idoso , Progressão da Doença , Feminino , Humanos , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Estudos Retrospectivos , Rituximab , Resultado do Tratamento
12.
J Rheumatol ; 40(4): 435-46, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23378460

RESUMO

OBJECTIVE: Biomarkers of progression of interstitial lung disease (ILD) are needed to allow early therapeutic intervention in patients with scleroderma-associated disease (SSc-ILD). METHODS: A panel of 8 serum cytokines [interleukin 6 (IL-6), IL-8, IL-10, CCL2, CXCL10, vascular endothelial growth factor, fibroblast growth factor 2, and CX3CL1] was assessed by Luminex bead technology in exploratory cohorts of 74 patients with SSc and 58 patients with idiopathic pulmonary fibrosis (IPF). Mortality and significant lung function decline [forced vital capacity (FVC) ≥ 10%; DLCO ≥ 15%] from date of serum collection were evaluated by proportional hazards analysis. Based on these findings, the prognostic value of serum IL-6, evaluated by ELISA, was assessed in a larger test cohort of 212 patients with SSc-ILD. RESULTS: In the exploratory cohort, only serum IL-6 was an independent predictor of DLCO decline in both IPF and SSc-ILD. The IL-6 threshold level most predictive of DLCO decline within a year was 7.67 pg/ml. In the larger test cohort, serum IL-6 > 7.67 pg/ml was predictive of decline in FVC (HR 2.58 ± 0.98, p = 0.01) and in DLCO (HR 3.2 ± 1.7, p = 0.02) within the first year, and predictive of death within the first 30 months (HR 2.69 ± 0.96, p = 0.005). When stratified according to severity (FVC < 70%), serum IL-6 > 7.67 pg/ml was predictive of functional decline or death within the first year in patients with milder disease (OR 3.1, 95% CI 1.4-7.2, p = 0.007), but not in those with severe ILD. CONCLUSION: In SSc-ILD, serum IL-6 levels appear to be predictive of early disease progression in patients with mild ILD, and could be used to target treatment in this group, if confirmed by prospective studies.


Assuntos
Interleucina-6/sangue , Doenças Pulmonares Intersticiais/sangue , Escleroderma Sistêmico/sangue , Adulto , Idoso , Citocinas/sangue , Progressão da Doença , Feminino , Humanos , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Testes de Função Respiratória , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/mortalidade , Capacidade Vital
13.
Chron Respir Dis ; 8(1): 53-82, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21339375

RESUMO

The lung is frequently involved in connective tissue diseases (CTDs), although the frequency of lung manifestations varies according to the type of CTD. Interstitial lung diseases (ILD) are frequently seen in CTDs, particularly systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM) and rheumatoid arthritis (RA), accounting for a significant proportion of deaths. A large percentage of patients with CTD-associated ILD has limited and stable disease, not requiring treatment. However, a significant minority has severe and/or progressive disease, necessitating prompt initiation of treatment. CTD-ILD histological patterns include non-specific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and lymphocytic interstitial pneumonia (LIP). NSIP is the most common pattern in all CTDs, except for RA, characterized by a higher frequency of UIP. ILD can present acutely or chronically, with acute presentations being more common in systemic lupus erythematosus and PM/DM. Idiopathic pulmonary fibrosis (IPF) is a progressively worsening ILD characterized by inflammation and fibrosis. The characteristic histological pattern of IPF is UIP. Interestingly, a UIP pattern is associated with a significantly better survival in CTD-related disease compared to the idiopathic variety. Prognosis in IPF is dismal, with a median survival since diagnosis of 2-3 years. No treatment regimen has been shown to improve survival in IPF. By contrast, although there have been only two randomized placebo-controlled trials investigating the effect of immunosuppressive treatment in SSc-associated ILD, clinical experience suggests that immunosuppressive drugs in CTD-related ILDs are capable of benefiting a significant proportion of patients, particularly those with certain histological patterns of disease. This review will essentially focus on CTD-associated ILD and will compare aspects of clinical presentation and management to those of IPF.


Assuntos
Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/patologia , Fibrose Pulmonar Idiopática/patologia , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/patologia , Corticosteroides/uso terapêutico , Doenças do Tecido Conjuntivo/tratamento farmacológico , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/mortalidade , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/mortalidade , Prognóstico
14.
Muscle Nerve ; 40(1): 50-4, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19533665

RESUMO

We evaluated serum glial fibrillary acidic protein (GFAP) levels by enzyme-linked immunosorbent assay (ELISA) in controls (n = 30) and in patients with chronic sensory-motor axonal neuropathy (CSMAN) (n = 30), chronic inflammatory demyelinating polyneuropathy (CIDP) (n = 30), multifocal motor neuropathy (MMN) (n = 30), and primary muscular spinal atrophy (PMSA) (n = 15). GFAP levels, expressed as optical density, were increased in CSMAN (median = 1.05) compared to controls (median = 0.41; P < 0.05) and CIDP (median = 0.53, P < 0.05). They were also increased in PMSA (median = 0.99) compared to controls (P < 0.05) and MMN (median = 0.66; P < 0.05). To differentiate CSMAN from CIDP and PMSA from MMN, we applied a cutoff of GFAP levels at 0.66, and we obtained good sensitivity and specificity. In neuropathies, serum GFAP correlated with summated sensory nerve action potential amplitudes (r = -0.57; P = 0.0006) and disease severity (r = 0.37; P = 0.0011). Thus, we propose serum GFAP as a marker of axonal damage and severity in chronic neuropathies.


Assuntos
Axônios/patologia , Proteína Glial Fibrilar Ácida/sangue , Polirradiculoneuropatia/sangue , Polirradiculoneuropatia/patologia , Adolescente , Adulto , Doença Crônica , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Neuropatia Hereditária Motora e Sensorial/sangue , Neuropatia Hereditária Motora e Sensorial/patologia , Neuropatia Hereditária Motora e Sensorial/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Polirradiculoneuropatia/classificação , Polirradiculoneuropatia/fisiopatologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/sangue , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/fisiopatologia , Curva ROC , Nervo Sural/patologia , Nervo Sural/fisiopatologia , Adulto Jovem
15.
Tumori ; 95(1): 13-22, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19366050

RESUMO

BACKGROUND: A meta-analysis of published studies was performed in order to clarify the risk of gastric cancer associated with cigarette smoking status. METHODS: Eligible studies were all the case-control studies investigating an association between smoking status and gastric cancer published from January 1, 1997, until June 30, 2006. In order to evaluate the quality of the published data, a qualitative scoring of papers was applied. The principal outcome measure was the odds ratio for the risk of gastric cancer associated with the smoking status using a random effects model. Cigarette smoking status was assessed in two ways: ever (current and ex) versus never smokers; current versus never smokers. RESULTS: We found a statistically significant result for the association between ever smoking status and gastric cancer risk (OR = 1.48; 95% CI, 1.28-1.71), considering 14,442 cases and 73,918 controls. Moreover, we found an odds ratio of 1.69 for current smoker status in comparison to never smokers (95% CI, 1.35-2.11). Considering only high quality studies, the odds ratio increased by 43% for gastric cancer risk in ever smokers (OR = 1.43; 95% CI, 1.24-1.66; Q = 378.60, P < 0.00001; 12 = 90%) and by 57% in current smokers (OR = 1.57; 95% CI, 1.24-2.01). We also considered separately Caucasians and Asian studies, finding for ever smokers an odds ratio of 1.46 (95% CI, 1.25-1.70; Q = 125.68, P < 0.00001; 12 = 82.5%) and of 1.47 (95% CI, 1.13-1.91; Q = 366.77, P < 0.00001; I2 = 94%), respectively. CONCLUSIONS: From the results of this quantitative meta-analysis, it appears that cigarette smoking has to be considered an important risk factor. The use of qualitative scoring decreases the magnitude of the relationship both for ever and current smoker exposure by 5-12%. Future studies on this topic need to clarify the biological interaction between environmental factors (such as cigarette smoking) and different polymorphisms on gastric cancer.


Assuntos
Fumar/efeitos adversos , Neoplasias Gástricas/etiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Razão de Chances , Fatores de Risco , Neoplasias Gástricas/epidemiologia
16.
Muscle Nerve ; 38(1): 899-903, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18508349

RESUMO

Glial fibrillary acid protein (GFAP) is increased in serum and cerebrospinal fluid of patients with dementia, traumatic brain injury, stroke, and multiple sclerosis. To determine whether GFAP is increased in Guillain-Barré syndrome (GBS) we evaluated serum GFAP in 30 controls, 20 patients with acute inflammatory demyelinating neuropathy (AIDP), and 17 with primary axonal GBS. Serum GFAP levels were increased in axonal GBS (median, 0.74) compared with controls (median, 0.41; P < 0.0001) and AIDP (median, 0.58; P = 0.0015). GFAP levels correlated with Hughes grades (serum r = 0.74; P < 0.0001) 6 months after neuropathy onset. Applying the cutoff value in serum of 0.63 to the diagnosis of axonal GBS, we obtained a sensitivity of 76.5% and a specificity of 86%. Thus, serum GFAP levels may be used in GBS as a diagnostic marker of the axonal variant and to predict outcome.


Assuntos
Proteína Glial Fibrilar Ácida/metabolismo , Síndrome de Guillain-Barré/metabolismo , Síndrome de Guillain-Barré/terapia , Potenciais de Ação/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Criança , Interpretação Estatística de Dados , Eletromiografia , Ensaio de Imunoadsorção Enzimática , Feminino , Proteína Glial Fibrilar Ácida/sangue , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Síndrome de Guillain-Barré/sangue , Síndrome de Guillain-Barré/líquido cefalorraquidiano , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios Motores/fisiologia , Razão de Chances , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Resultado do Tratamento
17.
J Cancer Res Clin Oncol ; 134(1): 93-100, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17611777

RESUMO

PURPOSE: As risk-modifiers of alcohol and tobacco effects, metabolic genes polymorphisms were investigated as susceptibility candidates for squamous cell carcinoma of the head and neck (SCCHN). METHODS: A total of 210 cases and 245 hospital controls, age and gender matched, were genotyped for CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms. A measurement of the biological interaction among two risk factors was estimated by the attributable proportion (AP) due to interaction and its 95% confidence interval (CI). RESULTS: SCCHN risk was associated with high-levels of alcohol intake [OR = 3.50 (95%CI: 1.93-6.35) and OR = 6.47 (95%CI: 2.92-14.35) for 19-30 g/day and >30 g/day, respectively], cigarette smoking [OR = 3.47 (95%CI: 1.88-6.41) and OR = 7.65 (95%CI: 4.20-13.90) for 1-25 and >25 pack-years of smoking, respectively] and low-fruit and vegetables consumption (OR = 2.45; 95%CI: 1.53-3.92). No differences were observed for the genotypes or haplotypes distributions among cases and controls, and no biological interaction emerged from gene-gene and gene-environment interaction analyses. An attributable proportion (AP) due to biological interaction of 0.65 (95%CI: 0.40-0.90) was detected for heavy drinkers with a low intake of fruit and vegetables, and an AP of 0.40 (95%CI: 0.10-0.72) resulted forever smokers with low fruit and vegetables consumption. CONCLUSIONS: Even in presence of high alcohol consumption or cigarette smoking, a high intake of fruit and vegetables might prevent the development of around one quarter of SCCHN cases. The lack of interaction between the studied polymorphisms and the environmental exposures suggests that chronic consumption of tobacco and alcohol overwhelm enzyme defences, irrespective of genotype.


Assuntos
Consumo de Bebidas Alcoólicas , Dieta , Enzimas/genética , Neoplasias de Cabeça e Pescoço/genética , Polimorfismo Genético/genética , Fumar , Arilamina N-Acetiltransferase/genética , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/prevenção & controle , Estudos de Casos e Controles , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP2E1/genética , Epóxido Hidrolases/genética , Éxons/genética , Feminino , Seguimentos , Frutas , Predisposição Genética para Doença , Genótipo , Glutationa Transferase/genética , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/prevenção & controle , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Gestão de Riscos , Inquéritos e Questionários , Verduras
18.
Carcinogenesis ; 28(1): 101-6, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16837478

RESUMO

Studies investigating the association between cytochrome P450 2E1 (CYP2E1) 5'-flanking region (PstI/RsaI) polymorphism and gastric cancer risk report conflicting results. The rationale for this meta-analysis was to determine whether CYP2E1*2 (c2) variant allele of CYP2E1 increases gastric cancer risk, especially by interacting with smoking, alcohol and other metabolic gene polymorphisms. Two investigators independently searched the Medline and Embase databases. A qualitative scoring of papers was applied to their evaluation. Authors of the identified papers were contacted to obtain data on the mentioned co-exposures. A measurement of the biological interaction among two putative risk factors was estimated by the attributable proportion (AP) due to interaction. We identified 13 case-control studies, which included 2066 gastric cancer cases and 2754 controls. Using the random effects model, we found no association between PstI/RsaI genotype and gastric cancer risk [odds ratio (OR) = 0.97 (95% confidence interval (CI): 0.79-1.18) for c2 allele carriers and OR = 1.36 (95% CI: 0.82-2.25) for c2 homozygotes compared with homozygotes wild-type]. When only high-quality scored studies were considered, a statistically significant increased risk appeared among Asians [OR = 1.50 (95% CI: 1.16-1.94) for c2 carriers and OR = 2.62 (95% CI: 1.23-5.57) for c2 homozygotes]. No interaction was detected between CYP2E1-smoking/alcohol (AP = 0), while an AP of 60% appeared for individuals both c2 homozygotes and glutathione S-transferase M1 (GSTM1) null compared with both homozygotes wild-type. This meta-analysis suggests that the CYP2E1 PstI/RsaI polymorphism may be a risk factor for gastric cancer in Asians, and that a synergic relation among GSTM1 and CYP2E1 may account for a proportion of gastric cancer cases.


Assuntos
Citocromo P-450 CYP2E1/genética , Etanol , Predisposição Genética para Doença , Glutationa Transferase/genética , Polimorfismo Genético/genética , Neoplasias Gástricas/genética , Tabaco , Estudos de Casos e Controles , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Genótipo , Humanos , Fatores de Risco , Fumar
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