RESUMO
OBJECTIVE: We evaluated the epidemiology and treatment outcomes of multi-drug-resistant (MDR) and pre-extensively-resistant (pre-XDR) tuberculosis (TB) in migrants at two TB reference centers in Italy. STUDY DESIGN: Patient selection criteria for the present study were as follows: age ≥18 years, international migrants (i.e., person who lives in a country other than his/her country of origin), MDR or pre-XDR-TB based on drug-susceptibility test findings, full availability of microbiological, radiological and clinical data. Non-intersecting populations between the two centers were selected. The primary outcome was the proportion of patients with a successful (i.e., cured and treatment completed) treatment outcome. METHODS: A retrospective cross-sectional study was conducted, from 01/Jan/2000 to 01/Jan/2015, at the Regional TB Reference Centre of Lombardy Region, Villa Marelli Institute/ASST Niguarda Ca' Granda (Milan, Italy) and at the Reference Center for MDR-TB and HIV-TB, Eugenio Morelli Hospital ASST (Sondalo, Italy). All data were made anonymous. Qualitative and quantitative variables were collected in an ad hoc electronic database. The statistical software used for all computations was STATA version 15 (StataCorp, Texas, USA). RESULTS: Overall, 116 MDR-TB and pre-XDR-TB cases were recorded: 82 (70.7%) MDR-TB and 34 (29.3%) pre-XDR-TB patients, respectively. The majority (53.5%) were from the World Health Organization European Region (excluding EU/EEA) and 75 (64.5%) were male. Median (interquartile range) age was 32 (26-39) years. TB/HIV coinfection was found in 12 (10.3%) patients. Pulmonary TB was diagnosed in 107/116 (92.2%) patients. Resistance to fluoroquinolones and second-line injectables was detected in 22/116 (19.0%) and 12/107 (11.2%) patients, respectively. Overall treatment success was reached in 95/116 (81.9%) cases. CONCLUSION: Pre-XDR-TB in migrants coming from high-endemic countries represents a matter of concern; therefore, prevention and control activities targeted to high-risk populations are needed to progress toward TB elimination.
Assuntos
Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Migrantes/estatística & dados numéricos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Estudos Transversais , Feminino , Humanos , Itália/epidemiologia , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A contact investigation following a case of infectious tuberculosis (TB) reported in a call centre in Milan (Italy) led to the identification of three additional cases that had occurred in employees of the same workplace during the previous 5 years, one of whom was the probable source case. Thirty-three latent infections were also identified. At the time of diagnosis, the source case, because of fear of stigma related to TB, claimed to be unemployed and a contact investigation was not performed in the workplace. Cases were linked through genotyping of Mycobacterium tuberculosis. TB stigma has been described frequently, mainly in high-incidence settings, and is known to influence health-seeking behaviours and treatment adherence. The findings in this report highlight that TB-associated stigma may also lead to incomplete contact investigations. Little is known about the causes and impact of TB-related stigma in low-incidence countries and this warrants further exploration. Research is also needed to evaluate the effectiveness of specific interviewing techniques and training interventions for staff in reducing feelings of stigma in TB patients. Finally, the outbreak emphasizes the importance of integrating routine contact investigations with genotyping.
Assuntos
Busca de Comunicante , Estigma Social , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/psicologia , Adulto , Surtos de Doenças , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Tuberculose Pulmonar/transmissãoRESUMO
Drug-resistant paediatric tuberculosis (TB) is an overlooked global problem. In Italy, the epidemiology of TB has recently changed and data regarding drug-resistant forms in the paediatric setting is scanty. The aim of this case series was to report the cases of drug-resistant TB, diagnosed between June 2006 and July 2010 in four Italian tertiary centres for paediatric infectious diseases, in children and adolescents living in Italy. Twenty-two children were enrolled, of these 17 were resistant to one or more drugs and five had multidrug-resistant TB. All but one child were either foreign born or had at least one foreign parent. Twenty-one patients completed their treatment without clinical or radiological signs of activity at the end of treatment, and one patient was lost to follow up. The outcomes were good, with few adverse effects using second-line anti-TB drugs. Although this series is limited, it might already reflect the worrisome increase of drug-resistant TB, even in childhood.
Assuntos
Emigração e Imigração/estatística & dados numéricos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adolescente , Antituberculosos/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Itália/epidemiologia , Masculino , Estudos Retrospectivos , Centros de Atenção Terciária , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Tuberculose/transmissão , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/transmissão , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/transmissãoRESUMO
INTRODUCTION: Health care workers (HCWs) are at high risk of latent tubercular infection (LTBI). In this study predictors of anti-tubercular treatment interruption in HCWs with LTBI are evaluated. METHODS: 1056 HCWs with LTBI were followed up to register adverse events and predictors of treatment interruption. RESULTS: 289 workers did not complete the treatment. Predictors of treatment interruption were adverse events (OR 1.47; 95CI% 1.07-2.03) and to be born in South-America (OR 1.55; 95CI% 1.06-2.26). CONCLUSION: The higher risk in South-Americans supports the need of targeted formative interventions on these workers.
Assuntos
Antituberculosos/uso terapêutico , Pessoal de Saúde , Tuberculose Latente/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Migrantes , Feminino , Humanos , Itália , MasculinoRESUMO
BACKGROUND: Treatment outcomes in multidrug-resistant TB (MDR-TB) patients are suboptimal in several low-incidence countries.METHODS: The primary outcome measure was the proportion of successfully treated patients in Italy during an 18-year period. Secondary outcomes were treatment outcomes in certain drug-containing regimens and the possibility for the WHO shorter MDR-TB regimen.RESULTS: In the 191 patients included (median age at admission: 33 years; 67.5% male, following drug-resistance patterns were found: MDR-TB in 68.6%, pre-extensively drug-resistant TB (pre-XDR-TB) in 30.4% and XDR-TB in 1.1% patients. The most frequently prescribed drugs were fluoroquinolones in 84.6% cases, amikacin in 48.7%, linezolid in 34.6% and meropenem/clavulanic acid in 29.5%. The median duration of treatment was 18 months. Treatment success was achieved in 71.2% patients, of whom, 44% were cured and 27.2% completed treatment. Treatment success rates did not statistically differ between the MDR- (68.8%) and pre-XDR-TB (77.6%) groups (P = 0.26). Treatment success rates had large variability between North and South of Italy (81.3% vs. 53.3%). Only 22.5% of the cases would have been eligible for shorter MDR-TB regimensCONCLUSION: Our study highlights variability in treatment outcomes in MDR- and pre-XDR-TB patients. Study findings confirmed the potential utility of linezolid and, for patients with limited oral options, meropenem/clavulanic acid and amikacin.
Assuntos
Tuberculose Extensivamente Resistente a Medicamentos , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologiaRESUMO
The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.
Assuntos
Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Nitroimidazóis/uso terapêutico , Oxazóis/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
BACKGROUND: Recent immigrants from developing countries (<2 years since immigration) are at very high risk of active TB disease due to reactivation of latent infections acquired in the country of origin. In industrialized low-incidence TB countries targeted testing programs for high risk groups could allow the detection of latently infected persons who would likely benefit from a course of preventive treatment. In this study we evaluated the tuberculin skin test (TST) and interferon-gamma enzyme-linked immunosorbent assay (QuantiFERON TB-gold in tube, QFT-IT) strategies for TB infection screening programs in recent immigrants from highly endemic countries. PATIENTS AND METHODS: This is a prospective cross-sectional study. Paired tests performed in 1,130 immigrants attending an outpatient ward, between 2005 and 2007 for any health problem were evaluated by intention-to-treat (ITT) and per-protocol (PP) analysis for efficiency and efficacy of screening program. RESULTS: Positive TST and QFT-IT were observed in 36.04 versus 29.82% (ITT) and in 45.27 versus 30.22% (PP) respectively. A higher drop-out rate was observed for TST (20.35 vs. 1.33%) (p < 0.0001). Second level assessment was accepted by half of the TST positive patients. Overall agreement rate between 887 paired tests was fair (k = 0.38). Higher k values were observed for higher TB prevalence rate in the country of origin (k = 0.43), for TST induration diameters >20 mM (k = 0.47), in subjects aged 40-50 years (k = 0.41) and in unvaccinated persons (k = 0.40). In a multiple logistic regression model continent of origin, class of TB prevalence in the country of origin and contacts with TB patients were found to be significantly associated with the probability of TST and QFT-IT positive result. Low education levels were associated only to an increased risk of TST positive results. CONCLUSIONS: The drawback of the TST screening strategy in recent immigrants from highly endemic countries is due to low sensitivity/specificity of the test and to high drop-out rate with an overall significant lowering in strategy efficacy/efficiency. The higher QFT-IT specificity prevents unnecessary overload of the health care system and, although more expensive, might represent a cost-effective alternative to TST in targeted screening programs directed to high risk populations.
Assuntos
Emigrantes e Imigrantes/estatística & dados numéricos , Ensaio de Imunoadsorção Enzimática/métodos , Interferon gama/metabolismo , Tuberculose Latente/diagnóstico , Teste Tuberculínico/métodos , Adulto , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Humanos , Tuberculose Latente/metabolismo , Modelos Logísticos , Masculino , Programas de Rastreamento/métodos , Estudos Prospectivos , Fatores de RiscoRESUMO
SETTING: Screening for latent tuberculous infection (LTBI) of groups at high risk of active tuberculosis (TB) is a key component of the End TB Strategy. OBJECTIVE: To conduct a retrospective descriptive analysis of LTBI rates among foreign-born individuals applying to shelters in the metropolitan area of Milan, Italy. DESIGN: All foreign-born individuals registering for accommodation centres in the city of Milan from November 2009 to April 2017 were screened for active TB and LTBI. Individuals aged <36 years with a tuberculin skin test (TST) induration of >10 mm were offered confirmatory testing with QuantiFERON®-TB Gold In-Tube (QFT-GIT). RESULTS: Of the 2666 TST-positive migrants aged <36 years who underwent LTBI confirmation testing, 1322 (49.6%) tested negative, 1339 (50.2%) were positive and five (0.2%) had indeterminate results. In the multivariate analysis, TB incidence in the country of origin and age were significantly associated with QFT-GIT positivity. Although estimated TB incidence in Eritrea, Morocco and Romania was îº100/100 000 person-years (py), the probability of being QFT-GIT-positive in individuals from these countries were not statistically significantly different from individuals from countries with TB incidence > 250/100 000 person-years. CONCLUSION: Our data showed a high proportion of LTBI among individuals coming from intermediate TB burden countries.
Assuntos
Emigrantes e Imigrantes/estatística & dados numéricos , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Adolescente , Adulto , Emigração e Imigração , Feminino , Humanos , Itália/epidemiologia , Modelos Logísticos , Masculino , Programas de Rastreamento , Análise Multivariada , Mycobacterium tuberculosis/isolamento & purificação , Estudos Retrospectivos , Teste Tuberculínico/métodos , Adulto JovemRESUMO
Essentials Missense mutations often impair protein folding, and thus intracellular trafficking and secretion. Cellular models of severe type I hemophilia B were challenged with chaperone-like compounds. Sodium phenylbutyrate improved intracellular trafficking and secretion of the frequent p.R294Q. The increased coagulant activity levels (â¼3%) of p.R294Q would ameliorate the bleeding phenotype. SUMMARY: Background Missense mutations often impair protein folding and intracellular processing, which can be improved by small compounds with chaperone-like activity. However, little has been done in coagulopathies, where even modest increases of functional levels could have therapeutic implications. Objectives To rescue the expression of factor IX (FIX) variants affected by missense mutations associated with type I hemophilia B (HB) through chaperone-like compounds. Methods Expression studies of recombinant (r)FIX variants and evaluation of secreted levels (ELISA), intracellular trafficking (immunofluorescence) and activity (coagulant assays) before and after treatment of cells with chaperone-like compounds. Results As a model we chose the most frequent HB mutation (p.R294Q, ~100 patients), compared with other recurrent mutations associated with severe/moderate type I HB. Immunofluorescence studies revealed retention of rFIX variants in the endoplasmic reticulum and negligible localization in the Golgi, thus indicating impaired intracellular trafficking. Consistently, and in agreement with coagulation phenotypes in patients, all missense mutations resulted in impaired secretion (< 1% wild-type rFIX). Sodium phenylbutyrate (NaPBA) quantitatively improved trafficking to the Golgi and dose dependently promoted secretion (from 0.3 ± 0.1% to 1.5 ± 0.3%) only of the rFIX-294Q variant. Noticeably, this variant displayed a specific coagulant activity that was higher (~2.0 fold) than that of wild-type rFIX in all treatment conditions. Importantly, coagulant activity was concurrently increased to levels (3.0 ± 0.9%) that, if achieved in patients, would ameliorate the bleeding phenotype. Conclusions Altogether, our data detail molecular mechanisms underlying type I HB and candidate NaPBA as affordable 'personalized' therapeutics for patients affected by the highly frequent p.R294Q mutation, and with reduced access to substitutive therapy.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Fator IX/genética , Fator IX/metabolismo , Hemofilia B/tratamento farmacológico , Mutação de Sentido Incorreto , Fenilbutiratos/farmacologia , Relação Dose-Resposta a Droga , Células HEK293 , Hemofilia B/sangue , Hemofilia B/genética , Humanos , Transporte Proteico , Via SecretóriaRESUMO
Essentials Potentially null homozygous Factor(F)7 nonsense mutations are associated to variable bleeding symptoms. Readthrough of p.Ser112X (life-threatening) and p.Cys132X (moderate) stop codons was investigated. Readthrough-mediated insertion of wild-type or tolerated residues produce functional proteins. Functional readthrough over homozygous F7 nonsense mutations contributes to the bleeding phenotype. SUMMARY: Background Whereas the rare homozygous nonsense mutations causing factor (F)VII deficiency may predict null conditions that are almost completely incompatible with life, they are associated with appreciable differences in hemorrhagic symptoms. The misrecognition of premature stop codons (readthrough) may account for variable levels of functional full-length proteins. Objectives To experimentally evaluate the basal and drug-induced levels of FVII resulting from the homozygous p.Cys132X and p.Ser112X nonsense mutations that are associated with moderate (132X) or life-threatening (112X) symptoms, and that are predicted to undergo readthrough with (132X) or without (112X) production of wild-type FVII. Methods We transiently expressed recombinant FVII (rFVII) nonsense and missense variants in human embryonic kidney 293 cells, and evaluated secreted FVII protein and functional levels by ELISA, activated FX generation, and coagulation assays. Results The levels of functional FVII produced by p.Cys132X and p.Ser112X mutants (rFVII-132X, 1.1% ± 0.2% of wild-type rFVII; rFVII-112X, 0.5% ± 0.1% of wild-type rFVII) were compatible with the occurrence of spontaneous readthrough, which was magnified by the addition of G418 - up to 12% of the wild-type value for the rFVII-132X nonsense variant. The predicted missense variants arising from readthrough abolished (rFVII-132Trp/Arg) or reduced (rFVII-112Trp/Cys/Arg, 22-45% of wild-type levels) secretion and function. These data suggest that the appreciable rescue of p.Cys132X function was driven by reinsertion of the wild-type residue, whereas the minimal p.Ser112X function was explained by missense changes permitting FVII secretion and function. Conclusions The extent of functional readthrough might explain differences in the bleeding phenotype of patients homozygous for F7 nonsense mutations, and prevent null conditions even for the most readthrough-unfavorable mutations.
Assuntos
Códon sem Sentido , Deficiência do Fator VII/genética , Fator VII/genética , Mutação , Coagulação Sanguínea , Códon de Terminação , Fator VII/metabolismo , Vetores Genéticos , Genótipo , Células HEK293 , Hemorragia , Homozigoto , Humanos , Mutagênese , Mutação de Sentido Incorreto , Fenótipo , Proteínas Recombinantes/metabolismoRESUMO
BACKGROUND: Correct identification of individuals with latent tuberculosis infection (LTBI) is a crucial element of the elimination strategy, allowing their adequate treatment. In addition to tuberculin skin test (TST), the Quantiferon test (QFT, based on whole blood gamma-interferon release) had been recently proposed. Aim of the study is to compare this test to TST for identification of LTBI in a non-selected population, in order to verify their value in identifying truly infected individuals (entitled to receive preventive chemotherapy), and to exclude from treatment those having a positive TST for other reasons (e.g. after BCG vaccination). METHODS: 136 consecutive persons (78 males, mean age 34 +/- 9 years) referred to the clinic for TST were recruited (78 born in low--or middle--income countries). Based on their history, the cases were divided into 4 groups: 1) recently traced contacts of whom 18 TST negative and 28 TST positive; 2) 22 screening subjects, all TST negative; 3) BCG vaccinated subjects (14); and 4) 54 subjects already undergoing treatment of LTBI for exposure to TB. RESULTS: The overall agreement between TST and QFT was 72% (64% in TST positive and 88.4% in TST negative subjects). The proportion of TST positive/QFT negative BCG vaccinated individuals was 23.1%. The K coefficient was 0.474 in recently traced contacts, 0.366 in BCG vaccinated individuals and 0.451 overall. CONCLUSIONS: The study results suggest that agreement between TST and QFT is lower in TST positive than in negative subjects, being lower in individuals treated for LTBI. Quantiferon does not seem to have brought significant improvement in the diagnosis of LTBI.
Assuntos
Anticorpos Antibacterianos/análise , Interferon gama/imunologia , Mycobacterium tuberculosis/imunologia , Teste Tuberculínico/métodos , Tuberculose/diagnóstico , Adulto , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Interferon gama/sangue , Masculino , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tuberculose/sangueRESUMO
This investigation explored the factor structure, reliability, and validity of the Devereux Elementary School Behavior Rating Scale, employing a large (n = 648) sample of children. Factor analysis suggested that the Devereux scale can be described by four factors, which were named Disruptive-Oppositional, Poor Comprehension-Disattention, Cooperative-Initiating, and Performance Anxiety. All four factors showed high internal consistency, and three of the four were stable over a 17-mo. period. Correlations of the four factors with academic achievement, IQ, socioeconomic status, and peer ratings of social competence are presented. All four factors showed significant relations with these variables, with Poor Comprehension-Disattention the strongest of all. Multiple regression analysis indicated that the Poor Comprehension-Disattention factor accounted for significant variance in academic achievement even after IQ was taken into account. Large differences between classroom means on the factor scores suggested that Devereux ratings for individual students may need to be interpreted cautiously.
Assuntos
Transtornos do Comportamento Infantil/diagnóstico , Determinação da Personalidade , Ensino , Logro , Criança , Análise Fatorial , Feminino , Humanos , Masculino , Testes de Personalidade , Psicometria , Estudantes/psicologiaRESUMO
SETTING: Villa Marelli Institute (VMI), Niguarda Ca'Granda Hospital, Milan, Italy. BACKGROUND: A recent report on the fatal side effects of isoniazid preventive therapy (IPT) from the United States has re-ignited discussion on the safety of this intervention. OBJECTIVE: To evaluate IPT feasibility, treatment completion and adverse events (AE) and their determinants under field conditions. METHODS: Data from consecutive subjects undergoing IPT at the VMI were recorded in an electronic database from 1992 to 2009. Logistic regression analysis was performed to detect completion and AE determinants. RESULTS: A total of 11,963 patients were included in the study. AE (odds ratio [OR] 2.70, 95%CI 2.22-3.28) and human immunodeficiency virus positive status (OR 5.20, 95%CI 2.10-12.93) were the main determinants of treatment interruption among Italians, while social weakness (no housing/job; OR 2.88, 95%CI 2.43-3.42), AEs (OR 1.33, 95%CI 1.15-1.53, 2.22-3.28) and screening in undocumented subjects (OR 1.20, 95%CI 1.01-1.44) prevailed among foreigners. Age was the main determinant of transaminase increase (OR 1.03, 95%CI 1.03-1.04), as were AEs of the gastrointestinal (OR 1.02, 95%CI 1.02-1.03), central nervous (OR 1.02, 95%CI 1.02-1.05) and peripheral nervous systems (OR 1.04, 95%CI 1.02-1.05). CONCLUSION: This analysis demonstrates the feasibility and safety of IPT, with determinants of interruption and AEs being predictable and addressable.
Assuntos
Antituberculosos/uso terapêutico , Isoniazida/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Tuberculose/prevenção & controle , Adolescente , Adulto , Fatores Etários , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Bases de Dados Factuais , Estudos de Viabilidade , Feminino , Seguimentos , Infecções por HIV/epidemiologia , Humanos , Isoniazida/administração & dosagem , Isoniazida/efeitos adversos , Itália , Modelos Logísticos , Masculino , Estudos Prospectivos , Adulto JovemAssuntos
Alcoolismo/complicações , Tuberculose Pulmonar/complicações , Anemia/etiologia , Fígado Gorduroso/etiologia , Cardiopatias/etiologia , Humanos , Hipoglicemia/etiologia , Náusea/etiologia , Pancreatite/etiologia , Psicoses Alcoólicas , Tuberculose Pulmonar/tratamento farmacológico , Vômito/etiologiaRESUMO
Ferulic acid, in the form of feruloyl CoA, occupies a central position as an intermediate in the phenylpropanoid pathway. Due to the allelopathic function, its effects were tested on root growth, H(2)O(2) and lignin contents, and activities of cinnamyl alcohol dehydrogenase (CAD, EC 1.1.1.195) and peroxidase (POD, EC 1.11.1.7) from soybean (Glycine max (L.) Merr.) root seedlings. Three-day-old seedlings were cultivated in half-strength Hoagland's solution (pH 6.0), with or without 1.0 mM ferulic acid in a growth chamber (25 degrees C, 12/12 hr light/dark photoperiod, irradiance of 280 micromol m(-2) s(-1)) for 24 or 48 hr. Exogenously supplied ferulic acid induced premature cessation of root growth, with disintegration of the root cap, compression of cells in the quiescent center, increase of the vascular cylinder diameter, and earlier lignification of the metaxylem. Moreover, the allelochemical decreased CAD activity and H(2)O(2) level and increased the anionic isoform PODa5 activity and lignin content. The lignin monomer composition of ferulic acid-exposed roots revealed a significant increase of guaiacyl (G) units. When applied jointly with piperonylic acid (an inhibitor of the cinnamate 4-hydroxylase, C4H), ferulic acid increased lignin content. By contrast, the application of 3,4-(methylenedioxy) cinnamic acid (an inhibitor of the 4-coumarate:CoA ligase, 4CL) with ferulic acid did not. Taken together, these results suggest that ferulic acid may be channeled into the phenylpropanoid pathway (by the 4CL reaction) and, further, may increase the lignin monomer amount solidifying the cell wall and restricting the root growth.
Assuntos
Ácidos Cumáricos/farmacologia , Glycine max/crescimento & desenvolvimento , Lignina/análise , Oxirredutases do Álcool/metabolismo , Peróxido de Hidrogênio/análise , Microscopia Eletrônica de Varredura , Peroxidase/metabolismo , Raízes de Plantas/enzimologia , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/ultraestrutura , Glycine max/enzimologia , Glycine max/metabolismo , Glycine max/ultraestruturaRESUMO
The diagnosis of pleural tuberculosis (plTB) by the analysis of pleural effusions (PEs) with standard diagnostic tools is difficult. In routine clinical practice, the present authors evaluated the performance of a commercially available Mycobacterium tuberculosis (MTB)-specific enzyme-linked immunospot assay on peripheral blood mononuclear cells (PBMCs) and pleural effusion mononuclear cells (PEMCs) in patients with suspect plTB. The T-SPOT.TB test (Oxford Immunotec Ltd, Abingdon, UK) was performed on PBMCs and PEMCs in 20 patients with a clinical and radiological suspect of plTB and in 21 control subjects with a diagnosis of PE of nontuberculous origin at four centres participating in the European Tuberculosis Network. In total, 18 (90%) out of 20 patients with plTB tested T-SPOT.TB-positive on PBMCs and 19 (95%) out of 20 on PEMCs. Among controls, T-SPOT.TB was positive in seven out of 21 (33%) patients when performed on PBMCs (these patients were assumed to be latently infected with MTB) and five (23%) out of 21 when performed on PEMCs. Sensitivity and specificity of T-SPOT.TB for the diagnosis of active plTB when performed on PEMCs were 95 and 76%, respectively. Enumerating Mycobacterium tuberculosis-specific T-cells in pleural effusion mononuclear cells by ELISPOT is feasible in routine clinical practice and may be useful for a rapid and accurate diagnosis of pleural tuberculosis.
Assuntos
Testes Diagnósticos de Rotina/métodos , Interferon gama/metabolismo , Linfócitos T/metabolismo , Tuberculose Pleural/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias , Proteínas de Bactérias , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T/microbiologiaRESUMO
The aim of this study was to compare the performance of the T-SPOT.TB test, a T-cell-based test, with the tuberculin skin test (TST) in the diagnosis of latent tuberculosis (TB) infection. The study was carried out in 138 immunosuppressed haematology patients who had been nosocomially exposed to a case of smear-positive TB. Overall, 44.2% of the contacts were positive by T-SPOT.TB test, and 17.4% by TST (concordance 67.8%). The apparent prevalence of infection fell from 25.9 to 14.5% with the TST with increasing immunosuppression, although this difference was not significant. In contrast, the apparent prevalence of infection with the T-SPOT.TB test was unaffected at 44.6 and 44.3%, respectively. The T-SPOT.TB test had an overall indeterminate rate of 4.3%, and this was also unaffected by the level of immunosuppression. This study suggests that the T-SPOT.TB test maintains its sensitivity and performance in immunocompromised patients, identifying a large number of truly infected patients anergic to the tuberculin skin test.
Assuntos
Testes Hematológicos/métodos , Terapia de Imunossupressão , Linfócitos T/microbiologia , Teste Tuberculínico/métodos , Tuberculose/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/farmacologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Reprodutibilidade dos Testes , Linfócitos T/citologiaRESUMO
The correlates of social and academic competence were investigated in 9-14 yr old children. Factor analysis of multiple measures of cognitive functioning, excluding IQ identified three dimensions: (1) Social Comprehension; (2) Cognitive Efficiency and (3) Divergent Thinking. The social comprehension dimension was derived from measures of humor and social cognition. Although strongly related to IQ, Social Comprehension still had a substantial unique relation to social competence in a school setting, as assessed by teachers and peers. While this dimension was the best predictor of social competence, IQ was by far the most powerful predictor of academic competence.
Assuntos
Desenvolvimento Infantil , Cognição , Inteligência , Ajustamento Social , Adolescente , Criança , Feminino , Humanos , Relações Interpessoais , Masculino , Resolução de Problemas , Testes Psicológicos , Pensamento , Senso de Humor e Humor como AssuntoRESUMO
Serologic HLA typing was carried out on 71 seropositive and 40 seronegative patients with rheumatoid arthritis and compared with values in 134 normal controls. A significant increase of HLA DR4 antigen, compared with control values, was found only in seropositive rheumatoid arthritis; HLA A1 and B35 antigens were significantly increased in seronegative rheumatoid arthritis patients (p less than 0.05), when compared with control values, but only HLA A1 antigen remained significantly higher when the p-correct test was performed.