RESUMEN
We report 2 cases of multifocal cystic (type 1) pleuropulmonary blastoma, diagnosed during the first 6 months of life. This rare entity must be recognized before evolution into the prognostically unfavorable type 2 or type 3 pleuropulmonary blastoma.
Asunto(s)
Neoplasias Pulmonares/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Pleurales/patología , Blastoma Pulmonar/patología , Femenino , Humanos , Recién Nacido , MasculinoRESUMEN
A five-month-old infant presented with a sudden choking cough and mild dyspnea. Bilateral cystic pulmonary images were found on a chest X-ray, leading to exploratory surgery. A pleuropulmonary blastoma, a rare malignant embryonic tumor of childhood, was diagnosed on histologic examination. This case illustrates the necessity of performing surgical resection and histologic evaluation of any pulmonary cystic malformations, particularly when bilateral.
Asunto(s)
Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Blastoma Pulmonar/diagnóstico por imagen , Blastoma Pulmonar/patología , Quistes/diagnóstico por imagen , Quistes/patología , Diagnóstico Diferencial , Humanos , Lactante , Radiografía TorácicaRESUMEN
Diseases associated with pathological fibroproliferation represent a major cause of morbidity and mortality. Despite the importance of this class of disorders, current therapy is of limited value, and no therapy is available to reduce the fibroblast population size within existing fibrotic lesions. In this regard, constitutive expression of growth-promoting genes can sensitize cells to undergo apoptosis. Studies in our laboratory have demonstrated that lovastatin potently induces apoptosis in fibroblasts constitutively expressing Myc, and that lung fibroblasts isolated from fibrotic lesions constitutively express growth-promoting genes. In this study, we sought to determine if nontransformed lung fibroblasts would manifest susceptibility to lovastatin-induced apoptosis similar to that observed in fibroblasts ectopically expressing Myc. Here we show that clinically achievable concentrations of lovastatin induce apoptosis in normal and fibrotic lung fibroblasts in vitro, as evidenced by acridine orange staining, terminal transferase nick end translation (TUNEL), and DNA laddering. Apoptosis of human lung fibroblasts was dose- and time-dependent, and blocked by exogenous mevalonic acid. Furthermore, apoptosis was associated with decreased levels of mature Ras, a molecule directly implicated in fibroblast rescue from apoptosis. The ability of lovastatin to induce fibroblast apoptosis in vivo was examined using a guinea pig wound chamber model. Lovastatin (5 microM, 8 d) reduced granulation tissue formation in the wound chambers by 64.7%, with associated ultrastructural evidence of fibroblast apoptosis. These findings support further study of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors as potential therapy for patients with fibroproliferative disorders.
Asunto(s)
Apoptosis , Fibroblastos/fisiología , Lovastatina/farmacología , Pulmón/efectos de los fármacos , Pulmón/fisiología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Fibrosis , Tejido de Granulación/efectos de los fármacos , Cobayas , Humanos , Lovastatina/antagonistas & inhibidores , Pulmón/citología , Ácido Mevalónico/farmacología , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Fibrosis Pulmonar/terapia , Valores de Referencia , Cicatrización de Heridas/efectos de los fármacos , Proteínas ras/antagonistas & inhibidores , Proteínas ras/metabolismoRESUMEN
The mechanisms leading to the severe lung damage seen in some sheep naturally infected with the visna-maedi virus, and to pulmonary lesions in other lentiviral diseases, appear to involve the recruitment of large numbers of uninfected inflammatory cells. Only a few alveolar macrophages from experimentally infected lambs express virus, but high levels of interleukin (IL)-8 mRNA are present in the macrophage population. In vitro infection with visna-maedi virus at low multiplicity of alveolar macrophages from uninfected sheep also strongly induced the expression of IL-8 mRNA and the accumulation of IL-8 in the extracellular medium. An initial peak of IL-8 mRNA expression at 3 or 6 h after infection was followed by a fall, then a more persistent expression lasting at least 48 h after infection. The early peak was accompanied by expression of mRNA for IL-1beta, and a possible rise in tumor necrosis factor alpha (TNFalpha) mRNA, although this was frequently elevated in uninfected ovine alveolar macrophages. Interestingly, these events occurred identically in cells treated with non-infectious heat-treated virus, suggesting that interaction between viral components and cellular membrane receptors could suffice for both early and late IL-8 induction. The level of IL-8 mRNA induced by treatment with live or inactivated virus could be severely reduced by pretreatment of the macrophages with genistein but not with staurosporine, suggesting the involvement of a tyrosine-kinase signaling pathway. The early induction of IL-1beta and possibly of TNFalpha may explain the occurrence of a later persistent expression of IL-8 mRNA through an autocrine mechanism.
Asunto(s)
Interleucina-8/metabolismo , Macrófagos Alveolares/metabolismo , Proteínas Tirosina Quinasas/fisiología , Ovinos/virología , Virus Visna-Maedi/fisiología , Animales , Citocinas/análisis , Citocinas/genética , Inhibidores Enzimáticos/farmacología , Genisteína/farmacología , Mediadores de Inflamación/metabolismo , Interleucina-1/genética , Interleucina-1/metabolismo , Interleucina-8/genética , Cinética , Macrófagos Alveolares/química , Macrófagos Alveolares/virología , Inhibidores de Proteínas Quinasas , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/genética , ARN Mensajero/fisiología , Transducción de Señal , Factores de Tiempo , Visna/fisiopatologíaRESUMEN
Ad CFTR, a replication-deficient adenovirus expressing the human cystic fibrosis transmembrane conductance regulator (CFTR), was administered by aerosolization in a single escalating dose to three pairs (cohorts) of cystic fibrosis (CF) patients. Buffer only was administered to the nose and lungs 9-14 days before nasal instillation of virus followed the day after by aerosolization of Ad CFTR to the lung. Nasal doses (defined in terms of viral plaque forming units, pfu) were 10(5), 10(7), and 4 x 10(8), whereas aerosolized doses were 10(7), 10(8), 5.4 x 10(8) for each cohort, respectively. No acute toxic effects were observed in the first 4 weeks after virus treatment. Shedding of infectious Ad CFTR was never detected, whereas detection of vector DNA sequences and CFTR expression demonstrated DNA transfer to the nose and airways of patients. No significant deviations in immunological and inflammatory parameters were observed in serum and in bronchoalveolar lavage (BAL). Importantly, for all patients, the serum anti-adenovirus antibody levels did not change significantly from baseline and no antibodies against adenovirus were found in BAL.
Asunto(s)
Adenoviridae/metabolismo , Aerosoles/uso terapéutico , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Terapia Genética , Adolescente , Adulto , Southern Blotting , Lavado Broncoalveolar , Regulador de Conductancia de Transmembrana de Fibrosis Quística/análisis , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , ADN/análisis , Femenino , Expresión Génica/genética , Vectores Genéticos/genética , Humanos , Inmunohistoquímica , Masculino , Mucosa Nasal/citología , Mucosa Nasal/metabolismo , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisisRESUMEN
Body composition using standard anthropometric methods and dual-energy X-ray absorptiometry (DEXA) was determined in a cross-sectional study among 26 pediatric renal transplant recipients. At the same time, spiroergometry exam, pulmonary function tests, dynamometry and tremometry exams were performed in all patients. Fat body mass obtained by DEXA correlated inversely with maximal physical load during spiroergometry exam (r2 = 0.51, p = 0.0001). The study demonstrates good tolerance of increased physical load in children after renal transplantation. An inverse relationship was found between fat body mass and physical performance. Exercise training programs for children after renal transplantation are therefore suggested.
Asunto(s)
Composición Corporal/fisiología , Ejercicio Físico/fisiología , Trasplante de Riñón/fisiología , Absorciometría de Fotón , Adolescente , Índice de Masa Corporal , Niño , Ergometría , Femenino , Hemodinámica , Humanos , Fallo Renal Crónico/cirugía , Masculino , Periodo Posoperatorio , EspirometríaRESUMEN
Enterocytozoon bieneusi is a major cause of chronic diarrhea and malabsorption in patients with AIDS. We report what we believe is the first case of intestinal infection due to E. bieneusi in a heart-lung transplant recipient who was seronegative for human immunodeficiency virus (HIV). The clinical presentation and the evolution of the disease were identical to those usually observed in patients with AIDS and included diarrhea, massive weight loss, and persistent infection despite treatment with albendazole. E. bieneusi was identified in the patient's duodenal mucosa by electron microscopy. No other etiologic agent was detected. We conclude that E. bieneusi may be responsible for serious intestinal infections in patients whose immunosuppression is not related to HIV.
Asunto(s)
Diarrea/etiología , Trasplante de Corazón-Pulmón/efectos adversos , Microsporida/patogenicidad , Microsporidiosis/etiología , Animales , Enfermedad Crónica , Diarrea/parasitología , Duodeno/parasitología , Seronegatividad para VIH , Humanos , Terapia de Inmunosupresión/efectos adversos , Masculino , Microscopía Electrónica , Microsporida/aislamiento & purificación , Microsporida/ultraestructura , Microsporidiosis/diagnóstico , Microsporidiosis/parasitología , Persona de Mediana EdadRESUMEN
At present it is conceivable to think that gene therapy represents a way to treat or even prevent the respiratory manifestations of cystic fibrosis. Consistent to such a concept, there is sufficient evidence that Ad-CFTR, a recombinant replication-deficient adenovirus expressing the human cystic fibrosis transmembrane conductance regulator cDNA, can vectorize the expression of a functional CFTR (cystic fibrosis transmembrane conductance regulator) to the nasal and airway epithelia. The clinical protocol was designed to assess the safety of single escalating doses of a replication defective adenovirus expressing the cystic fibrosis transmembrane conductance regulator gene (Ad-CFTR) when administered to the tracheobronchial portion of the airways and whether biological efficacy of CFTR delivery could be demonstrated. Six cystic fibrosis patients received nasal instillation and subsequent aerosol (Optineb, Air Liquide, Paris, France) administration of Ad-CFTR the following day. Doses (pfu) applied to the nose were 10(5) (patients SG and PB), 10(7) (patients FP and EP) and 4 x 10(8) (patients DS and FG), while aerosolised doses were 10(7) (patients SG and PB), 10(8) (patients FP and EP) and 5.4 x 10(8) (patients DS and FG), respectively. No acute toxic effects, no increase in the titer of anti-adenovirus antibodies and no spreading or shedding of Ad-CFTR were detected. In one patient Ad-CFTR DNA was found in the urine and blood two days after aerosolisation. Ad-CFTR DNA was detected in nasal and bronchial brush samples, in BAL, in saliva and tonsils 21, 8, 14 and 4 days post virus administration, respectively. Ad-CFTR mRNA (RT-PCR on bronchial cells) and CFTR protein (immunochemistry on nasal and bronchial cells) were detected up to 14 days following Ad-CFTR administration. These results show that the nebulisation of Ad-CFTR is a possible approach for treating the respiratory manifestation of cystic fibrosis.