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INTRODUCTION: Cystic fibrosis (CF) is the most frequent recessive autosomal disorder in the Caucasian population. It is caused by mutations that result in a deficient or dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein activity. Among CFTR modulators, potentiator compounds increase channel opening, whereas corrector compounds increase CFTR quantity in the cell surface. OBJECTIVE: To report real-life effects of a generic formulation of lumacaftor-ivacaftor use in patients with CF homozygous for the Phe508del CFTR mutation. PATIENTS AND METHODS: Clinical variables (body mass index [BMI], pulmonary exacerbations, sweat test, and pulmonary function) were analyzed in 30 CF patients homozygous for the Phe508del CFTR mutation, treated with lumacaftor-ivacaftor for 12 months, at the Respiratory Center of Hospital de Niños Ricardo Gutiérrez. These clinical variables were compared with those before the use of modulators. RESULTS: A total of 30 patients with CF homozygous for the Phe508del CFTR mutation receiving lumacaftor-ivacaftor therapy were included in this study. The median (interquartile range [IQR]) age at the start of treatment was 10.79 (7.08-14.05) years. Nineteen patients were male. Before treatment, median (IQR) sweat chloride concentration was 80 (72-92) mEq/L, and it had decreased to 74 (68-78) mEq/L (p = .05) 12 months after treatment. Median (IQR) BMI z-score improved from -0.33 (-0.86 to 0.21) to -0.13 (-0.66 to 0.54) (p = .003). A spirometry was performed in 28 of 30 patients. Median (IQR) ppFEV1 was 83.5 (71-91) before treatment and 86.5 (67-103) after treatment (p = .38), 73.3% of patients referred decreased sputum production and 40% reported improvement in their dyspnea at 12 months. Severe pulmonary exacerbations significantly decreased from 60% in the year before treatment, to 30% at 12 months after treatment (p = .037); 13 patients showed an improvement in their exacerbation rates, 2 showed an increased rate, and 15 showed no change. CONCLUSIONS: The use of a generic formulation of lumacaftor-ivacaftor in patients homozygous for the Phe508del CFTR mutation was associated with improvement in nutritional status and respiratory symptoms, and a significant reduction in severe pulmonary exacerbations.
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Fibrose Cística , Humanos , Masculino , Criança , Adolescente , Feminino , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/uso terapêutico , Combinação de Medicamentos , Aminofenóis , Aminopiridinas , Benzodioxóis/efeitos adversos , MutaçãoRESUMO
We relay the case of a teenage female with severe facial acne vulgaris and a past psychiatric history of major depressive disorder who presented to the emergency department with a primary complaint of ongoing suicidal ideation. Defining features of this case stem from the patient endorsing that her suicidal ideation was a result of her severe acne and the coinciding social perturbation it caused. Additionally, the patient reported that just four months prior to the current presentation, her dermatologist started her on isotretinoin therapy for the management of acne vulgaris. To the best of the authors' knowledge, there have been no reported cases which describe a teenage female presenting with active suicidal ideation secondary to severe acne vulgaris while concurrently undergoing treatment with isotretinoin. Given the controversial but reported association between isotretinoin and increased suicidality, we considered the appropriateness of continuing this medication for our patient. We then conducted a literature search evaluating the evidence concerning this association. In what follows, we present a unique case report and provide a thorough review of the evidence-or lack thereof-surrounding the relationship between isotretinoin and suicidality. Additionally, the authors aim to provide recommendations for the management of future patients who may present under similar circumstances.
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The initial mechanism by which antimicrobial peptides target microbes occurs via electrostatic interactions; however, the mechanism is not well understood. We investigate the interaction of the antimicrobial peptide bactenecin with a 50:50 w:w% 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DMPG) phospholipid mixture at the air-water interface with different NaCl concentrations (0.01, 0.05, 0.1, 0.5 M) in the subphase. A larger shift of DPPC:DMPG isotherms was obtained for 0.1 M salt concentration at lower and higher pressures, demonstrating the influence of the negative charge of DMPG molecules and the screening of the electrostatic interaction by the salt concentration. Raman spectroscopy of monolayers demonstrated the presence of cysteine-cysteine bridges in bactenecin loops. The peptide adsorption in DPPC:DMPG monolayers observed by AFM images suggests a self-assembled aggregation process, starting with filament-like networks. Domains similar to carpets were formed and pore structures were obtained after a critical peptide concentration, according to the carpet model.
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Membranas Artificiais , Peptídeos Cíclicos/química , Fosfolipídeos/química , Ar , Cátions/química , Propriedades de Superfície , Água/químicaRESUMO
We describe a case of pure red cell aplasia developing within two months after kidney transplant in a patient who was actively receiving immunosuppression. His hemoglobin was 9.5 g/dL and his reticulocyte count was 0%. WBC and platelet counts were normal and a bone marrow showed hypercellularity with normal myelocytic and megakaryocytic elements. The erythrocytic series was completely absent except for an increased number of giant proerythronormoblasts with cytoplasmic vacuolization. The titers for IgG and IgM for Parvovirus were negative. However, DNA PCR for Parvovirus B19 was positive. After receiving IV human immunoglobulin, the patient's hemoglobin increased in 4-6 weeks to 13.1 g/dL and his reticulocyte count became normal. The cause of his anemia was attributed to Parvovirus B19. Parvovirus B19 should be considered as a cause of unexplained progressive anemia in this setting and in any immunosuppressed patient. The reticulocyte count, bone marrow picture and PCR for DNA for Parvovirus B19 are essential for diagnosis.