Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
Mais filtros










Base de dados
Tipo de estudo
Intervalo de ano de publicação
1.
Proc Natl Acad Sci U S A ; 116(33): 16463-16472, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31346092

RESUMO

Heterozygous in-frame mutations in coding regions of human STAT3 underlie the only known autosomal dominant form of hyper IgE syndrome (AD HIES). About 5% of familial cases remain unexplained. The mutant proteins are loss-of-function and dominant-negative when tested following overproduction in recipient cells. However, the production of mutant proteins has not been detected and quantified in the cells of heterozygous patients. We report a deep intronic heterozygous STAT3 mutation, c.1282-89C>T, in 7 relatives with AD HIES. This mutation creates a new exon in the STAT3 complementary DNA, which, when overexpressed, generates a mutant STAT3 protein (D427ins17) that is loss-of-function and dominant-negative in terms of tyrosine phosphorylation, DNA binding, and transcriptional activity. In immortalized B cells from these patients, the D427ins17 protein was 2 kDa larger and 4-fold less abundant than wild-type STAT3, on mass spectrometry. The patients' primary B and T lymphocytes responded poorly to STAT3-dependent cytokines. These findings are reminiscent of the impaired responses of leukocytes from other patients with AD HIES due to typical STAT3 coding mutations, providing further evidence for the dominance of the mutant intronic allele. These findings highlight the importance of sequencing STAT3 introns in patients with HIES without candidate variants in coding regions and essential splice sites. They also show that AD HIES-causing STAT3 mutant alleles can be dominant-negative even if the encoded protein is produced in significantly smaller amounts than wild-type STAT3.

2.
Pediatr Pulmonol ; 54(7): 977-983, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30854801

RESUMO

OBJECTIVE: To describe the prevalence of cystic fibrosis-related diabetes (CFRD) before and after lung transplantation (LT); to analyse the survival and renal function after LT according to the CFRD status before LT. METHODS: Sixty cystic fibrosis (CF) patients transplanted at the Lyon University Hospital between 2004 and 2014 were included. Genotype, pancreatic status, age at LT, survival were recorded. Glucose tolerance status, daily insulin dose requirement, glomerular filtration rate (GFR), and daily glucocorticoid (GC) dose were recorded before LT and until December 2016. RESULTS: The median follow-up was 5.6 (3.8-8.2) years, and nine patients died. Survival was poorest for patients with CFRD before LT compared with those without CFRD (P = 0.03) but was not correlated with the GFR before LT, with sex, age at LT, or CF genotype. The prevalence of CFRD was 68% at 2 years and 54% at 5 years. For persistent insulin-treated CFRD, the insulin requirement decreased (-2.1 IU/d/y; P < 0.01) and was correlated with the daily GC dose (+0.4 IU/d for one additional milligram, P = 0.012). Seven (11%) patients who had insulin-treated CFRD before LT became nondiabetic after LT, with a median time of 2 (1-4) years. After LT, the GFR decreased (-5.3 ml/min/1.73 m 2 /y; P < 0.001) and was not correlated with the CFRD status before LT. CONCLUSIONS: CFRD before LT is associated with poor survival after LT, which should lead to better management of diabetes. Some patients with pre-LT CFRD became nondiabetic after LT. CFRD is not associated with renal insufficiency after LT.

3.
ERJ Open Res ; 4(4)2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30510957

RESUMO

Patient age at diagnosis of pulmonary hypertension is steadily increasing. The present study sought to analyse clinical characteristics, time to diagnosis and prognosis of pulmonary hypertension in elderly and very elderly patients. A study was conducted in a French regional referral centre for pulmonary hypertension. All consecutive patients diagnosed with pre-capillary pulmonary hypertension were included and categorised according to age: <65 years ("young"), 65-74 years ("elderly") and ≥75 years ("very elderly"). Over a 4-year period, 248 patients were included: 101 (40.7%) were young, 82 (33.1%) were elderly and 65 (26.2%) were very elderly. The median age at diagnosis among the total population was 68 years. Compared with young patients, elderly and very elderly patients had a longer time to diagnosis (7±48, 9±21 and 16±32 months, respectively; p<0.001). Patients ≥75 years also more often had group 4 pulmonary hypertension. The median overall survival was 46±1.4 months, but was only 37±4.9 months in elderly patients and 28±4.7 months in very elderly patients. Survival from the first symptoms and survival adjusted to comorbidity was similar across age groups. Patient age should be taken into account when diagnosing pulmonary hypertension as it is associated with a specific clinical profile and a worse prognosis. The difference in prognosis is likely to be related to a delay in diagnosis and a greater number of comorbidities.

4.
BMC Infect Dis ; 18(1): 659, 2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30547753

RESUMO

BACKGROUND: Nontuberculous mycobacteria (NTM) lung diseases are increasingly recognized as chronic opportunistic infections, occurring in individuals with a wide variety of underlying conditions. In the absence of systemic immunodeficiency, decision of NTM lung disease treatment must relies on a careful risk/benefit assessment, given the requirement of long-term administration of multidrug therapies supported by limited evidence. The primary objective was to identify the factors associated with anti-NTM treatment initiation. Clinical and radiological outcome upon treatment were studied. METHODS: This retrospective, single center study (2013-2016, 45 months) addressed the criteria supporting treatment decision among adults with NTM lung disease without systemic immunodeficiency at our institution, with the assigned goal to harmonize the practice. All patients matched the current international definitions of NTM lung disease according to the American Thoracic Society criteria. Factors associated with anti-NTM treatment were investigated by conditional logistic regression. Clinical and radiological outcomes of treated and untreated NTM-disease cases were examined. Mortality rate was assessed. An expert radiologist conducted a blinded computed tomography (CT)-scan review of the treated and untreated patients. RESULTS: Among 51 cases of NTM lung diseases, 25 (49%) received anti-NTM treatment. In univariate analysis, a body mass index (BMI) < 18 kg/m2 (odds ratio (OR), 4.2 [95% confidence interval (CI) 1.2-15.2]; p = 0.042), hemoptysis (OR, 11.8 [95% CI 1.35-12.9]; p = 0.026), excavation(s) (OR, 4.8 [95% CI 1.4-16.4], p = 0.012), prior anti-NTM treatment (OR, 5.65 [95% CI 1.06-29.9]; p = 0.042), Aspergillus spp. co-infection (OR, 6.3 [95% CI 1.8-22.2]; p = 0.004) were associated with treatment initiation. In multivariate analysis, Aspergillus spp. co-infection was the only independent determinant of treatment initiation (OR, 5.3 [95% CI 1.1-25.4]; p = 0.036). Twenty-one (81%) patients received ≥3 anti-NTM drugs. Median treatment duration and follow-up were 36.3 (interquartile range [IQR], 13.1-64.4) weeks and 17.1 (IQR, 8.7-27.1) months, respectively. Regarding radiological outcome, 85 CT-scans were reviewed, showing similar rates of regression or stabilization in treated and untreated patients. Overall mortality rate was not different in treated and untreated patients. CONCLUSION: The most relevant variable associated with anti-NTM treatment initiation was Aspergillus spp. co-infection. Radiological regression or stabilization of pulmonary lesions was not different between the treated and untreated patients.


Assuntos
Infecções por Micobactéria não Tuberculosa , Adulto , Tomada de Decisão Clínica , Humanos , Modelos Logísticos , Infecções por Micobactéria não Tuberculosa/diagnóstico por imagem , Infecções por Micobactéria não Tuberculosa/epidemiologia , Infecções por Micobactéria não Tuberculosa/terapia , Estudos Retrospectivos
5.
Pulm Circ ; 8(4): 2045894018799272, 2018 Oct-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30124132

RESUMO

Right heart catheterization (RHC) is the reference test in diagnosing pulmonary hypertension (PH). The increasing age of patients at the time of diagnosis raises the issue of the morbidity of this invasive test in elderly individuals. We hypothesized that the morbidity associated with RHC would be increased in elderly patients and highlight differences in hemodynamic characteristics compared to younger patients. A retrospective study was conducted in a regional referral center for PH. Data for all consecutive RHCs performed during the study period were analyzed. Over a five-year period, 1060 RHCs were performed. Of the patients, 228 (21.5%) were aged ≥75 years and 832 (78.5%) were aged <75 years. Duration of the procedure and site of puncture did not differ according to age group (all P > 0.05). Nine procedures (0.9%) led to complications: three (1.3%) in patients aged >75 years and six (0.7%) in younger patients aged ( P = 0.5). Eight were local vascular injuries, directly related to a femoral vein puncture ( P < 0.001). Pulmonary arterial pressure and cardiac output were lower in patients aged >75 years than in younger patients ( P = 0.001). RHC may be performed regardless of patient age. The rate of RHC complications is not increased in individuals aged >75 years. As most complications were related to femoral vein puncture, this route should be avoided whenever possible.

6.
Lung India ; 34(1): 85-87, 2017 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28144069

RESUMO

A 40-year-old cystic fibrosis woman with a history of double-lung transplantation 2 years previously was admitted for a progressive respiratory distress. Physical examination revealed fever (39°C) and diffuse bilateral lung crackles. Laboratory findings included severe hypoxemia and inflammatory syndrome. Bronchoalveolar lavage and serological test were positive for mycoplasma pneumonia. As the patient did not improve after 3 days of antibiotics and donor-specific HLA antibodies had been detected, an acute antibody-mediated graft rejection was treated with high-dose corticosteroids, plasma exchange, intravenous immunoglobulin, and rituximab. The patient rapidly improved. Unfortunately, 6 months after this episode, she developed a bronchiolitis obliterans syndrome with a dependence to noninvasive ventilator leading to the indication of retransplantation. This case illustrates the possible relationship between infection and humoral rejection. These two diagnoses should be promptly investigated and systematically treated in lung transplant recipients.

8.
Infect Drug Resist ; 7: 183-97, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25045274

RESUMO

Actinomycosis is a rare chronic disease caused by Actinomyces spp., anaerobic Gram-positive bacteria that normally colonize the human mouth and digestive and genital tracts. Physicians must be aware of typical clinical presentations (such as cervicofacial actinomycosis following dental focus of infection, pelvic actinomycosis in women with an intrauterine device, and pulmonary actinomycosis in smokers with poor dental hygiene), but also that actinomycosis may mimic the malignancy process in various anatomical sites. Bacterial cultures and pathology are the cornerstone of diagnosis, but particular conditions are required in order to get the correct diagnosis. Prolonged bacterial cultures in anaerobic conditions are necessary to identify the bacterium and typical microscopic findings include necrosis with yellowish sulfur granules and filamentous Gram-positive fungal-like pathogens. Patients with actinomycosis require prolonged (6- to 12-month) high doses (to facilitate the drug penetration in abscess and in infected tissues) of penicillin G or amoxicillin, but the duration of antimicrobial therapy could probably be shortened to 3 months in patients in whom optimal surgical resection of infected tissues has been performed. Preventive measures, such as reduction of alcohol abuse and improvement of dental hygiene, may limit occurrence of pulmonary, cervicofacial, and central nervous system actinomycosis. In women, intrauterine devices must be changed every 5 years in order to limit the occurrence of pelvic actinomycosis.

11.
J Travel Med ; 19(1): 64-5, 2012 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22221815

RESUMO

Pulmonary histoplasmosis is a rare disease in France, where all cases are imported. Diagnosis is difficult in nonendemic areas, often based on travel history and observation of epidemic in a group. We report three cases of pulmonary histoplasmosis that occurred in a group of 12 French cavers traveling to Cuba.


Assuntos
Histoplasmose/diagnóstico , Pneumopatias Fúngicas/diagnóstico , Viagem , Adolescente , Adulto , Cuba , França , Humanos , Masculino , Pessoa de Meia-Idade
12.
Hemoglobin ; 34(5): 505-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20854126

RESUMO

We report the clinical and biochemical studies of a patient initially diagnosed with ß-thalassemia intermedia (ß-TI), which, with age, has progressed to a severe transfusion-dependent form. The patient is a compound heterozygote for the -30 (T>A) ß(+)-thalassemia (ß(+)-thal) mutation and the rare δ(0)ß(+)-Senegalese deletion. Many complications are reported as well as the specific treatments initiated.


Assuntos
Globinas beta/genética , Talassemia beta/genética , Globinas delta/genética , Adulto , Transfusão de Sangue , Humanos , Masculino , Mutação , Deleção de Sequência , Talassemia beta/diagnóstico , Talassemia beta/terapia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA