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1.
Indian J Otolaryngol Head Neck Surg ; 76(3): 2361-2366, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38883452

RESUMO

Aims: The oropharyngeal dysphagia (OD) poses substantial health risks and affects quality of life. Patient-reported outcome measures (PROMs) are gaining prominence for their crucial role in early detection and adapting rehabilitation and management decisions. This highlights the need for culturally pertinent versions in different languages, especially when addressing conditions like OD. This study aimed to translate, culturally adapt, and assess the test-retest reliability of the Sydney Swallow Questionnaire (SSQ), a PROM designed to detect the risk of OD, for Dutch-speaking populations. Materials and Methods: The SSQ was translated and adapted based on Beaton's guidelines. Validity and test-retest reliability were assessed in 100 healthy participants, with a subset of 30 participants assessed over a 15-day interval. Intra-class correlation coefficient (ICC) values were calculated to determine test-retest reliability. Results: The SSQ-Dutch was well received and well understood, with a median total score of 65.5/1700. Notably, 95% of participants scored below the established dysphagia risk cut-off, consistent with previous validations. The 15-day interval ICC for the SSQ-Dutch total scores was 0.82 (CI 95%: 0.66-0.91), indicating good reliability. While most questions had moderate-to-good reliability, five showed slightly lower ICC. Conclusion: The SSQ-Dutch emerges as a validated and reliable tool for assessing OD risk in Dutch-speaking individuals. Future studies should evaluate its efficacy in symptomatic populations and consider cultural variations in Dutch-speaking regions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04484-3.

4.
Mult Scler Relat Disord ; 60: 103728, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35290898

RESUMO

BACKGROUND: Multiple sclerosis treatment options are increasing. Evidence-based patient information (EBPI) are therefore crucial to enable patient involvement in decision making. Based on earlier work on decision support, patient information handbooks on 8 MS immunotherapies were developed, piloted and evaluated with support from the German Clinical Competence Network MS and the German MS Society. METHODS: Handbooks were structured according to EBPI concepts. Drafts were commented by patient representatives and neurologists with an MS expertise. Executive boards of the German MS Society and the Competence Network as well as pharmaceutical companies' feedback was included. Handbooks were distributed among MS neurologists by the German MS Society. Evaluation followed applying a mixed methods approach with interviews, focus groups and surveys. One survey addressed persons with MS (pwMS) based on a questionnaire included in each handbook. Neurologists who received printed patient handbooks were invited to give feedback in a second survey. RESULTS: Eight handbooks were developed providing absolute and relative risk information in numbers and figures as well as monitoring needs and drug fact boxes. Despite the high amount of information and the display of low absolute risk reduction rates of treatments, handbooks were overall appreciated by pwMS (n=107) and mostly also by physicians (n=24). For more than 70% of the pwMS the information was new, understandable and supportive for decision making. But patients felt uncomfortable with relative risk information. However, response rates in the evaluation were low, exposing the challenges when implementing EBPI into clinical care. Therefore, conclusions must be considered preliminary. CONCLUSION: EBPI on immunotherapies for MS seem feasible and are appreciated by patients and treating neurologists but more implementation research is needed.


Assuntos
Esclerose Múltipla , Grupos Focais , Humanos , Imunoterapia , Esclerose Múltipla/tratamento farmacológico , Neurologistas , Inquéritos e Questionários
5.
Orphanet J Rare Dis ; 15(1): 83, 2020 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-32248831

RESUMO

BACKGROUND: Late-onset Pompe disease (LOPD) is a rare, hereditary, progressive disorder that is usually characterized by limb-girdle muscle weakness and/or respiratory insufficiency. LOPD is caused by mutations in the acid alpha-glucosidase (GAA) gene and treated with enzyme replacement therapy (ERT). METHODS: We studied the clinical, brain imaging, and genetic features of the Belgian cohort of late-onset Pompe disease patients (N = 52), and explored the sensitivity of different outcome measures, during a longitudinal period of 7 years (2010-2017), including the activity limitations ActivLim score, 6 min walking distance (6MWD), 10 m walk test (10MWT), MRC sum score, and forced vital capacity (FVC) sitting/supine. RESULTS: In Belgium, we calculated an LOPD prevalence of 3.9 per million. Mean age at onset of 52 LOPD patients was 28.9 years (SD: 15.8 y), ranging from 7 months to 68 years. Seventy-five percent (N = 39) of the patients initially presented with limb-girdle weakness, whereas in 13% (N = 7) respiratory symptoms were the only initial symptom. Non-invasive ventilation (NIV) was started in 37% (N = 19), at a mean age of 49.5 years (SD: 11.9 y), with a mean duration of 15 years (SD: 10.2 y) after symptom onset. Brain imaging revealed abnormalities in 25% (N = 8) of the patients, with the presence of small cerebral aneurysm(s) in two patients and a vertebrobasilar dolichoectasia in another two. Mean diagnostic delay was 12.9 years. All patients were compound heterozygotes with the most prevalent mutation being c.-32-13 T > G in 96%. We identified two novel mutations in GAA: c.1610_1611delA and c.186dup11. For the 6MWD, MRC sum score, FVC sitting and FVC supine, we measured a significant decrease over time (p = 0.0002, p = 0.0001, p = 0.0077, p = 0.0151), which was not revealed with the ActivLim score and 10MWT (p > 0.05). CONCLUSIONS: Awareness on LOPD should even be further increased because of the long diagnostic delay. The 6MWD, but not the ActivLim score, is a sensitive outcome measure to follow up LOPD patients.


Assuntos
Doença de Depósito de Glicogênio Tipo II , Bélgica/epidemiologia , Diagnóstico Tardio , Terapia de Reposição de Enzimas , Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , Doença de Depósito de Glicogênio Tipo II/epidemiologia , Doença de Depósito de Glicogênio Tipo II/genética , Humanos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , alfa-Glucosidases/uso terapêutico
6.
Rev Sci Instrum ; 89(8): 083503, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30184720

RESUMO

A variable configuration V-band heterodyne Doppler back-scattering diagnostic has been recently made operational in the tokamak à configuration variable. This article describes the hardware setup options, flexible quasi-optical launcher antenna, data-analysis techniques, and first data. The diagnostic uses a fast arbitrary waveform generator as the main oscillator and commercial vector network analyzer extension modules as the main mm-wave hardware. It allows sweepable single or multi-frequency operation. A flexible quasi-optical launcher antenna allows 3D poloidal (10°-58°) and toroidal (-180° to 180°) steering of the beam with 0.2° accuracy. A pair of fast HE11 miter-bend polarizers allow flexible coupling to either O or X mode and programmable polarization changes during the shot. These have been used to measure the magnetic-field pitch angle in the edge of the plasma by monitoring the backscattered signal power. Ray-tracing simulations reveal an available k⊥ range between 3 and 16 cm-1 with a resolution of 2-4 cm-1. Perpendicular rotation velocity estimates compare well against ExB plasma poloidal rotation estimates from charge exchange recombination spectroscopy.

7.
J Mycol Med ; 28(2): 403-406, 2018 Jun.
Artigo em Francês | MEDLINE | ID: mdl-29477782

RESUMO

Endophthalmitis is a rare infection of the vitreous and/or aqueous. It can be bacterial or fungal. Exogenous endophthalmitis is the most common form and results from direct inoculation of a pathogen after eye surgery or penetrating trauma. Endophthalmitis can also be endogenous, secondary to disseminated infection. Fungal endophthalmitis is associated with poor prognosis and treatment is difficult given the low penetration of most of the antifungal agents available and the emergence of resistant filamentous fungi like Fusarium. To our knowledge, we describe the first endogenous fungal endophthalmitis due to Fusarium dimerum, a ubiquitous pathogen found in soil and plants. A 71-year-old woman, diagnosed with acute myeloid leukemia, was hospitalized for surveillance after induction chemotherapy. Prophylaxis by antibiotics and posaconazole was ongoing when she complained of pain and decreased vision in the left eye. A voluminous chorioretinal abscess developed and after multiple sterile aqueous humour samples, only vitrectomy allowed diagnosis with fungal hyphae seen on May-Grünwald Giemsa stained smear and positive cultures. The fungus was identified as Fusarium dimerum. The treatment, that included intravitreal injections of voriconazole and amphotericin B associated with systemic administration of voriconazole, allowed complete control of the infection. The source of this infection could not be confirmed despite the discovery of several possible infection sites including a periungual whitlow on the left hand and a lesion on a nail, from which samples were negative in microbiology laboratories. Unfortunately, damages of the retina were too important and the patient did not recover sight of her left eye.


Assuntos
Endoftalmite/tratamento farmacológico , Endoftalmite/microbiologia , Fusarium/isolamento & purificação , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Anfotericina B/uso terapêutico , Antibacterianos/administração & dosagem , Antifúngicos/uso terapêutico , Endoftalmite/diagnóstico , Olho/microbiologia , Olho/patologia , Feminino , Humanos , Hifas/efeitos dos fármacos , Hifas/isolamento & purificação , Hospedeiro Imunocomprometido , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/microbiologia , Resultado do Tratamento , Triazóis/administração & dosagem , Vitrectomia , Voriconazol/uso terapêutico
8.
J Clin Microbiol ; 55(9): 2661-2670, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28637907

RESUMO

Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry has emerged as a reliable technique to identify molds involved in human diseases, including dermatophytes, provided that exhaustive reference databases are available. This study assessed an online identification application based on original algorithms and an extensive in-house reference database comprising 11,851 spectra (938 fungal species and 246 fungal genera). Validation criteria were established using an initial panel of 422 molds, including dermatophytes, previously identified via DNA sequencing (126 species). The application was further assessed using a separate panel of 501 cultured clinical isolates (88 mold taxa including dermatophytes) derived from five hospital laboratories. A total of 438 (87.35%) isolates were correctly identified at the species level, while 26 (5.22%) were assigned to the correct genus but the wrong species and 37 (7.43%) were not identified, since the defined threshold of 20 was not reached. The use of the Bruker Daltonics database included in the MALDI Biotyper software resulted in a much higher rate of unidentified isolates (39.76 and 74.30% using the score thresholds 1.7 and 2.0, respectively). Moreover, the identification delay of the online application remained compatible with real-time online queries (0.15 s per spectrum), and the application was faster than identifications using the MALDI Biotyper software. This is the first study to assess an online identification system based on MALDI-TOF spectrum analysis. We have successfully applied this approach to identify molds, including dermatophytes, for which diversity is insufficiently represented in commercial databases. This free-access application is available to medical mycologists to improve fungal identification.


Assuntos
Arthrodermataceae/classificação , Bases de Dados Factuais , Dermatomicoses/diagnóstico , Técnicas de Tipagem Micológica/métodos , Sistemas On-Line , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Algoritmos , Dermatomicoses/microbiologia , Humanos , Técnicas de Tipagem Micológica/instrumentação , Software
9.
J Mycol Med ; 26(3): 261-4, 2016 Sep.
Artigo em Francês | MEDLINE | ID: mdl-27289448

RESUMO

Disseminated fungal infections due to Magnusiomyces capitatus are rare, occurring exclusively in immunocompromised patients. We report the first case in a liver transplant patient with chronic rejection and portal thrombosis who had a M. capitatus fungemia with a refractory septic shock. Despite an antibacterial and antifungal treatment with caspofungin empirical treatment, the patient died from multiple organ failure. Subsequently, mycological examinations of blood cultures, bronchoalveolar lavage fluid and urine were positive to M. capitatus identified by mass spectrometry and confirmed by sequencing respectively. The stain was resistant to caspofungin and fluconazole. The best treatment appears to be the combination of amphotericin B and voriconazole or amphotericin B and 5 fluorocytosine.


Assuntos
Fungemia/diagnóstico , Fungemia/microbiologia , Transplante de Fígado , Saccharomycetales/isolamento & purificação , Evolução Fatal , Fungemia/complicações , Rejeição de Enxerto/microbiologia , Humanos , Hospedeiro Imunocomprometido , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Sepse/complicações , Sepse/microbiologia
10.
J Clin Microbiol ; 54(6): 1487-1495, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27008872

RESUMO

Pneumocystis jirovecii pneumonia (PCP) is an acute and life-threatening lung disease caused by the fungus Pneumocystis jirovecii The presentation of PCP in HIV-positive patients is well-known and consists of a triad of dyspnea, fever, and cough, whereas the presentation of PCP in HIV-negative patients is atypical and consists of a sudden outbreak, O2 desaturation, and a rapid lethal outcome without therapy. Despite the availability of direct and indirect identification methods, the diagnosis of PCP remains difficult. The cycle threshold (CT) values obtained by quantitative PCR (qPCR) allow estimation of the fungal burden. The more elevated that the fungal burden is, the higher the probability that the diagnosis is pneumonia. The purposes of the present study were to evaluate the CT values to differentiate colonization and pneumonia in a population of immunocompromised patients overall and patients stratified on the basis of their HIV infection status. Testing of bronchoalveolar lavage (BAL) fluid samples from the whole population of qPCR-positive patients showed a mean CT value for patients with PCP of 28 (95% confidence interval [CI], 26 to 30) and a mean CT value for colonized patients of 35 (95% CI, 34 to 36) (P < 10(-3)). For the subgroup of HIV-positive patients, we demonstrated that a CT value below 27 excluded colonization and a CT value above 30 excluded PCP with a specificity of 100% and a sensitivity of 80%, respectively. In the subgroup of HIV-negative patients, we demonstrated that a CT value below 31 excluded colonization and a CT value above 35 excluded PCP with a specificity of 80% and a sensitivity of 80%, respectively. Thus, qPCR of BAL fluid samples is an important tool for the differentiation of colonization and pneumonia in P. jirovecii-infected immunocompromised patients and patients stratified on the basis of HIV infection status with different CT values.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Infecções por HIV/complicações , Técnicas de Diagnóstico Molecular/métodos , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/genética , Estudos Prospectivos , Sensibilidade e Especificidade
11.
Top Curr Chem ; 370: 113-34, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26589507

RESUMO

Photodynamic therapy (PDT) is a well-established technique employed to treat aged macular degeneration and certain types of cancer, or to kill microbes by using a photoactivatable molecule (a photosensitizer, PS) combined with light of an appropriate wavelength and oxygen. Many PSs are used against cancer but none of them are highly specific. Moreover, most are hydrophobic, so are poorly soluble in aqueous media. To improve both the transportation of the compounds and the selectivity of the treatment, nanoparticles (NPs) have been designed. Thanks to their small size, these can accumulate in a tumor because of the well-known enhanced permeability effect. By changing the composition of the nanoparticles it is also possible to achieve other goals, such as (1) targeting receptors that are over-expressed on tumoral cells or neovessels, (2) making them able to absorb two photons (upconversion or biphoton), and (3) improving singlet oxygen generation by the surface plasmon resonance effect (gold nanoparticles). In this chapter we describe recent developments with inorganic NPs in the PDT domain. Pertinent examples selected from the literature are used to illustrate advances in the field. We do not consider either polymeric nanoparticles or quantum dots, as these are developed in other chapters.


Assuntos
Compostos Inorgânicos/administração & dosagem , Nanopartículas , Fotoquimioterapia , Humanos , Espécies Reativas de Oxigênio/metabolismo
12.
Br J Pharmacol ; 172(7): 1769-82, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25521311

RESUMO

BACKGROUND AND PURPOSE: Selective agonists of the sigma-1 receptor (σ1 protein) are generally reported to protect against neuronal damage and modulate oligodendrocyte differentiation. Human and rodent lymphocytes possess saturable, high-affinity binding sites for compounds binding to the σ1 protein and potential immunomodulatory properties have been described for σ1 protein ligands. Experimental autoimmune encephalomyelitis (EAE) is recognized as a valuable model of the inflammatory aspects of multiple sclerosis (MS). Here, we have assessed the role of a σ1 protein agonist, containing the tetrahydroisoquinoline-hydantoin structure, in EAE. EXPERIMENTAL APPROACH: EAE was induced in SJL/J female mice by active immunization with myelin proteolipid protein (PLP)139-151 peptide. The σ1 protein agonist was injected i.p. at the time of immunization (day 0). Disease severity was assessed clinically and by histopathological evaluation of the CNS. Phenotyping of B-cell subsets and regulatory T-cells were performed by flow cytometry in spleen and cervical lymph nodes. KEY RESULTS: Prophylactic treatment of EAE mice with the σ1 protein agonist prevented mononuclear cell accumulation and demyelination in brain and spinal cord and increased T2 B-cells and regulatory T-cells, resulting in an overall reduction in the clinical progression of EAE. CONCLUSIONS AND IMPLICATIONS: This σ1 protein agonist, containing the tetrahydroisoquinoline-hydantoin structure, decreased the magnitude of inflammation in EAE. This effect was associated with increased proportions of B-cell subsets and regulatory T-cells with potential immunoregulatory functions. Targeting of the σ1 protein might thus provide new therapeutic opportunities in MS.


Assuntos
Encefalomielite Autoimune Experimental/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Receptores sigma/agonistas , Animais , Linfócitos B/imunologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Citocinas/sangue , Encefalomielite Autoimune Experimental/sangue , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Imunoglobulina G/sangue , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Camundongos , Esclerose Múltipla/sangue , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Proteína Proteolipídica de Mielina/imunologia , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/imunologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Baço/efeitos dos fármacos , Baço/imunologia , Linfócitos T Reguladores/imunologia , Receptor Sigma-1
13.
J Mycol Med ; 23(4): 270-3, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24210582

RESUMO

OBJECTIVE: Treatment of chronic lymphocytic leukaemia (CLL) is rapidly evolving, with emerging new drugs. Alemtuzumab is a monoclonal antibody recognizing CD52 antigen approved in the treatment of relapsing-refractory CLL. A frequent side effect is the immunosuppression and patients treated with alemtuzumab risk to develop fungal infections such as aspergillosis. PATIENT AND METHODS: This case report is about a patient who developed an uncommon localization of aspergillosis: prostatic and renal, after a treatment by alemtuzumab monotherapy. During the week 8 of alemtuzumab, the patient presented fever, urinary frequency and urologic symptoms. Persistance of fever with common antibiotherapy led to realize a tomography that showed prostatic and renal abscess (70mm and 29mm). It was decided to realize a prostatic biopsy. RESULTS: Histological findings showed suppurative abscess with ischemic necrosis and fungal proliferation, with branched fungal hyphae. Direct examination was negative. Culture on Sabouraud's agar revealed a mould identified as Aspergillus fumigatus. The organism was susceptible to voriconazole (MIC: voriconazole 0,25ug/mL). CONCLUSION: Because of the main side effect of alemtuzumab is immunosuppression, we have to research fungal infections such as Aspergillosis, particularly in patients with fever resistant to common antibiotherapy.


Assuntos
Abscesso/microbiologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Aspergilose/microbiologia , Aspergillus fumigatus/isolamento & purificação , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Nefrite/microbiologia , Prostatite/microbiologia , Abscesso/etiologia , Aciclovir/análogos & derivados , Aciclovir/uso terapêutico , Alemtuzumab , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antifúngicos/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aspergilose/etiologia , Farmacorresistência Fúngica , Humanos , Hospedeiro Imunocomprometido , Leucemia Linfocítica Crônica de Células B/complicações , Masculino , Pessoa de Meia-Idade , Nefrite/etiologia , Prostatite/etiologia , Terapia de Salvação , Valaciclovir , Valina/análogos & derivados , Valina/uso terapêutico , Voriconazol/uso terapêutico
14.
Infection ; 41(3): 621-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23463185

RESUMO

PURPOSE: To describe the antifungal stewardship programme in our hospital and to assess its impact on total antifungal prescriptions and their cost, and on the process of care measures regarding the diagnostic and therapeutic management of invasive aspergillosis and candidaemia. METHODS: We conducted a prospective observational study describing the multifaceted antifungal stewardship programme in place at our French teaching tertiary-care hospital since 2005. Several actions were implemented successively, including the systematic evaluation of all costly antifungal prescriptions (echinocandins, lipid formulations of amphotericin B, posaconazole and voriconazole). RESULTS: A total of 636 antifungal prescriptions were discussed by the antifungal management team from 2005 to 2010 inclusive, mainly from the haematology department (72 %). In 344/636 cases (54 %), a piece of advice was fed back to the physician in charge of the patient, with an 88 % compliance rate. Optimal standard of care was achieved for galactomannan antigen testing, performance of chest computed tomography (CT) scan and voriconazole therapeutic drug monitoring for invasive aspergillosis, with no combination therapies used since 2008. Regarding candidaemia, optimal standard of care was achieved for the timing of antifungal therapy, recommended first-line therapy, duration of therapy and the removal of central venous catheters. Total antifungal prescriptions (in defined daily doses, DDD) and their cost were contained between 2003 and 2010. CONCLUSIONS: The implementation of an antifungal stewardship programme was feasible, sustainable and well accepted. We observed an improved quality of care for some process of care measures, and antifungal use and cost were contained in our hospital.


Assuntos
Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Prescrições de Medicamentos/normas , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Adolescente , Adulto , Antifúngicos/economia , Criança , Pré-Escolar , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , França , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitais de Ensino , Humanos , Estudos Prospectivos
15.
Mucosal Immunol ; 6(3): 485-97, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22968421

RESUMO

Hypoxia-inducible factor (HIF) has important roles in promoting pro-inflammatory and bactericidal functions in myeloid cells. Conditional genetic ablation of its major subunit Hif1α in the myeloid lineage consequently results in decreased inflammatory responses in classical models of acute inflammation in mice. By contrast, we report here that mice conditionally deficient for Hif1α in myeloid cells display enhanced sensitivity to the development of airway allergy to experimental allergens and house-dust mite antigens. We support that upon allergen exposure, MyD88-dependent upregulation of Hif1α boosts the expression of the immunosuppressive cytokine interleukin (IL)-10 by lung interstitial macrophages (IMs). Hif1α-dependent IL-10 secretion is required for IMs to block allergen-induced dendritic cell activation and consequently for preventing the development of allergen-specific T-helper cell responses upon allergen exposure. Thus, this study supports that, in addition to its known pro-inflammatory activities, myeloid Hif1α possesses immunoregulatory functions implicated in the prevention of airway allergy.


Assuntos
Antígenos de Dermatophagoides/imunologia , Macrófagos Alveolares/imunologia , Oxigenases de Função Mista/metabolismo , Células Mieloides/imunologia , Hipersensibilidade Respiratória/imunologia , Animais , Apresentação de Antígeno/genética , Células Dendríticas/imunologia , Modelos Animais de Doenças , Feminino , Terapia de Imunossupressão , Interleucina-10/imunologia , Interleucina-10/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/imunologia , Fator 88 de Diferenciação Mieloide/metabolismo , Especificidade de Órgãos/genética , Pyroglyphidae/imunologia , Transdução de Sinais/genética , Linfócitos T Auxiliares-Indutores/imunologia
16.
Int J Cardiol ; 168(1): 76-9, 2013 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-23041008

RESUMO

BACKGROUND: Homozygous mutations in ANO5, a gene encoding anoctamin 5, a putative calcium-activated chloride channel, have recently been reported in patients with adult-onset myopathies or isolated high-CK levels. Cardiomyopathy has not previously been reported in these populations despite a proven expression of anoctamin 5 in the cardiac muscle. METHODS: Patients presenting for the management of high-CK levels or overt myopathy with proven ANO5 mutations were prospectively investigated between June 2010 and March 2012 in Pitié Salpêtrière Hospital, according to a standardised protocol. Neurological and cardiological clinical examinations, CK assessment, electrocardiogram (ECG), and echocardiography were performed, as well as cardiac MRI and coronary CT angiography in patients with left ventricular (LV) dysfunction. RESULTS: Our study included 19 consecutive patients (male=15, age=46.2 ± 12.7 years) from 16 families. Five had asymptomatic high-CK levels and 14 had overt myopathy. One patient had a personal history of stable coronary artery disease with normal ventricular function. ECG showed ventricular premature beats in one patient. Echocardiography displayed LV dilatation in two patients, LV dysfunction in one, and both abnormalities in two who fulfilled criteria for dilated cardiomyopathy which was confirmed by cardiac MRI and normal CT angiography. CONCLUSIONS: Dilated cardiomyopathy is a potential complication in patients with myopathies due to mutations in the ANO5 gene whose screening requires specific procedures.


Assuntos
Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/genética , Canais de Cloreto/genética , Mutação/genética , Adulto , Idoso , Anoctaminas , Cardiomiopatia Dilatada/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Ann Cardiol Angeiol (Paris) ; 61(5): 317-22, 2012 Nov.
Artigo em Francês | MEDLINE | ID: mdl-23021591

RESUMO

BACKGROUND: The association of acute chest pain, elevation of the cardiac enzymes and biological markers of inflammation suggests the diagnosis of myocarditis. The aim of the present study is to evaluate the diagnostic value of the multidetectors cardiac tomodensitometry (MDCT) for the confirmation of this diagnosis. PATIENTS AND METHODS: From October 2005 to April 2011, 39 patients aged 15.4 to 75.7years (mean 43.3±15.1) underwent a MDCT for suspected acute myocarditis (chest pain, elevation of troponin I, systemic inflammation). The electrocardiogram highlighted repolarization disorders in 27 (69%) patients (negative T waves, elevation of ST segment). The MDCT consisted in a first acquisition phase (imaging of coronary arteries) followed 7minutes later by a late acquisition, with thicker slices (imaging of the myocardium). When the MDCT was performed after a coronary angiography, only the late acquisition was performed. Sixteen patients then underwent a cardiac MRI. RESULTS: No significant coronary stenoses were found in all patients. The MDCT showed homogeneous myocardial enhancement on the early acquisition. A subepicardial late enhancement was found in 30 (76.9%) patients. The subepicardial enhancement was mainly found in the lateral myocardium. In patients who underwent cardiac MRI and MDCT (n=16), there was a good correlation between the enhanced segments. MDCT found differential diagnosis in 11 patients (myocardial infarction, Tako-Tsubo). CONCLUSION: The ECG-gated MDCT is a non-invasive and reliable diagnostic tool in patient with suspected myocarditis. It allows at the same time to rule out a significant coronary disease, when no coronary angiography was performed, and to show subepicardial enhancement confirming the diagnosis of myocarditis. While cardiac MRI remains the gold standard, MDCT could prove useful when there is no access to or contraindication for an MRI, studying both the coronary arteries and the myocardium.


Assuntos
Imageamento por Ressonância Magnética , Tomografia Computadorizada Multidetectores , Miocardite/diagnóstico por imagem , Doença Aguda , Adolescente , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Pacientes Internados , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Miocardite/diagnóstico , Valor Preditivo dos Testes , Sensibilidade e Especificidade
18.
J Clin Microbiol ; 50(7): 2305-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22553230

RESUMO

This study aimed to assess the interlaboratory reproducibility at four university hospital laboratories in the southeast region of France of the Etest technique for the determination of caspofungin (CAS) and amphotericin B (AMB) MICs and to compare it to the CLSI broth microdilution reference method. Consecutive clinical yeast isolates (n = 198) were included in the study. AMB and CAS MICs were read at 24 and 48 h. Interlaboratory reproducibility was estimated by using (i) an intraclass correlation coefficient (ICC), (ii) essential agreement (EA), and (iii) categorical agreement (CA). For Etest interlaboratory reproducibility for CAS, ICCs were 0.80 (95% confidence interval [CI], 0.76 to 0.84) and 0.81 (95% CI, 0.77 to 0.85) at 24 and 48 h, respectively. For AMB, the ICCs were 0.51 (95% CI, 0.43 to 0.58) and 0.69 (95% CI, 0.63 to 0.74) at 24 and 48 h, respectively. At 48 h, the between-center EAs ranged from 94.4 to 99.0% for both antifungals. For the comparison of the CLSI method and the Etest, the between-technique ICCs were 0.69 (95% CI, 0.63 to 0.74) and 0.62 (95% CI, 0.55 to 0.68) for CAS and AMB, respectively. The EAs ranged from 76.5 to 98.5% for CAS and from 90.3 to 97.4% for AMB according to the centers. CAs ranged from 87.9% to 91.4%, with four very major errors for 2 strains (1 Candida albicans strain and 1 Candida krusei strain), for CAS and from 97.5 to 99.5%, with four major errors, for AMB. In conclusion, the Etest showed a good interlaboratory reproducibility and a good correlation with the CLSI technique. It is well suited for the routine clinical laboratory and can thus be used to monitor clinical yeast isolates' in vitro susceptibilities in this setting.


Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Equinocandinas/farmacologia , Candida/isolamento & purificação , Caspofungina , França , Hospitais Universitários , Humanos , Lipopeptídeos , Testes de Sensibilidade Microbiana/normas , Reprodutibilidade dos Testes
19.
Rev Mal Respir ; 29(2): 178-90, 2012 Feb.
Artigo em Francês | MEDLINE | ID: mdl-22405112

RESUMO

INTRODUCTION: Intrapulmonary Percussive Ventilation (IPV) is used to treat peripheral airway obstruction as well as disorders of ventilation. STATE OF THE ART: The medical literature shows that IPV can be deployed for both symptomatic and prophylactic purposes. When conventional techniques of chest physiotherapy have been ineffective, IPV may be delivered in a variety of severe respiratory diseases via both invasive and non-invasive interfaces. Diseases such as advanced neuromuscular disorders with severe bronchial congestion, stable or decompensated cystic fibrosis and chronic obstructive pulmonary disease whether in the stable condition, during exacerbations or after extubation as well as atelectasis or other severe respiratory complications may all benefit from therapeutic effects of IPV. Very few contra-indications are reported in the literature. PERSPECTIVES: The precise physiological effects of IPV are not yet well demonstrated. Despite significant progresses, the level of evidence for the clinical effectiveness of IPV remains insufficient. CONCLUSIONS: IPV can be considered as a technique that may offer valuable assistance in the treatment of severe respiratory diseases that are refractory to conventional techniques of respiratory therapy.


Assuntos
Ventilação de Alta Frequência/métodos , Doenças Respiratórias/terapia , Obstrução das Vias Respiratórias/terapia , Contraindicações , Humanos
20.
Rev Mal Respir ; 29(2): 347-54, 2012 Feb.
Artigo em Francês | MEDLINE | ID: mdl-22405124

RESUMO

Intrapulmonary Percussion Ventilation (IPV) was designed to promote airway clearance, to recruit areas of lung and to improve pulmonary gas exchange. Its principle is to administer bursts of small tidal volume at high frequency. This article describes IPV devices, especially the Phasitron(®), which provides a dynamic interface between the pneumatic source of gas and the patient. Although not fully understood, the principles of action are also discussed. Finally, available settings of IPV are proposed following two strategies. In patients with obstructive respiratory disease and ventilatory autonomy, the vibrations and percussions are applied with a frequency more than 300 cycles/min and pressure in the proximal airways ranging from 10-20cm. H(2)O. In patients with restrictive pulmonary disease but without ventilatory autonomy, IPV is expected to improve gas exchange. The frequency of percussion will be slower (80-200 cycles/min) but the proximal airway pressure may reach 40cm H(2)O. During the sessions, the frequency may be modified to alternate from a percussive pattern (high frequencies promoting the mobilization of secretions) to a ventilatory pattern (slow frequencies encouraging alveolar ventilation and clearance of secretions).


Assuntos
Ventilação de Alta Frequência/métodos , Ventiladores Mecânicos , Humanos
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