RESUMEN
STUDY OBJECTIVES: Define the incidence of obstructive atelectasis in patients presenting with small cell lung cancer and their response to treatment. DESIGN: Retrospective review of clinical records and radiographic studies. SETTING: Single federal government institution-the National Cancer Institute-Naval Medical Oncology Branch. PATIENTS: One hundred seventy-two consecutive patients treated between 1983 and 1993. INTERVENTIONS: Patients presenting with obstructive atelectasis were identified. The incidence of dyspnea, cough, and sputum production before starting treatment and 1, 3, and 6 months later was determined. Fiberoptic bronchoscopy and chest radiographs performed before starting treatment were compared with those obtained later in the patients' clinical course. MEASUREMENTS AND RESULTS: Thirty-seven of 172 (22%) patients had obstructive atelectasis. Initial symptoms included cough in 25 (68%), dyspnea in 24 (65%), and productive cough in 10 (27%). The patients' symptoms of cough, dyspnea, and sputum production decreased to one third of the initial prevalence 1 month after the start of treatment. Fiberoptic bronchoscopy and chest radiographs performed 3 months after starting treatment demonstrated bronchial patency in 90%. CONCLUSIONS: Obstructive atelectasis occurs in approximately one fifth of patients presenting with small cell lung cancer. Chemotherapy and chemotherapy plus chest radiotherapy lead to symptomatic, bronchoscopic, and radiographic resolution in similar proportions of patients with obstructive atelectasis.
Asunto(s)
Carcinoma de Células Pequeñas/complicaciones , Neoplasias Pulmonares/complicaciones , Atelectasia Pulmonar/etiología , Anciano , Antineoplásicos/uso terapéutico , Broncoscopía , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/mortalidad , Femenino , Humanos , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Masculino , Atelectasia Pulmonar/diagnóstico por imagen , Radiografía , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by the expansion of activated oligoclonal CD4+ T cells and macrophages at sites of disease. To investigate the immunopathogenesis of sarcoidosis, we analyzed patterns of cytokine expression in bronchoalveolar lavage cells and fluid from patients with pulmonary sarcoidosis and idiopathic pulmonary fibrosis and from normal volunteers. We found dominant type 1 cytokine expression, with elevated mRNA and protein levels of IFN-gamma, but not IL-4, in sarcoid lung cells and fluid compared with those in normal samples. To define immunoregulatory mechanisms important to this type 1 response, we analyzed the expression of IL-12 and IL-10 in lung cells and fluid. Using semiquantitative PCR, we found significantly higher mRNA expression of the regulated IL-12 p40 subunit, but not IL-10, in sarcoid compared with normal lung cells. Consistent with these observations, strikingly elevated levels of p40 protein were found in sarcoid compared with normal bronchoalveolar lavage fluid. Unstimulated and Staphylococcus aureus-stimulated sarcoid alveolar macrophages produced greater amounts of IL-12 than normal alveolar macrophages when cultured in vitro. We hypothesize that sarcoidosis is a Th1-mediated disease driven by chronic, dysregulated production of IL-12 at sites of disease.
Asunto(s)
Citocinas/metabolismo , Interleucina-12/metabolismo , Sarcoidosis Pulmonar/inmunología , Células TH1/inmunología , Adulto , Anciano , Líquido del Lavado Bronquioalveolar/química , Femenino , Humanos , Interleucina-10/metabolismo , Pulmón/inmunología , Macrófagos Alveolares/inmunología , Masculino , Persona de Mediana Edad , Células Th2/inmunologíaRESUMEN
Sarcoidosis is a systemic granulomatous disease of unknown etiology in which CD4+ T cells seem to be critically involved. In the lungs of patients with pulmonary disease, CD4+ T cells accumulate in large numbers, and a subset of these cells is activated. By using both quantitative PCR and anti-V beta mAbs, we analyzed the TCR repertoire of total and activated bronchoalveolar lavage T cells, the latter subset being defined by the ability to proliferate in short-term culture supplemented with IL-2. Overall, there was little difference when TCR V beta expression of freshly isolated lung and peripheral blood cells was compared in individual patients. Some individuals did demonstrate a modest increase in a few V beta-expressing subsets. However, after 1 to 2 wk of in vitro growth in IL-2-supplemented media, bronchoalveolar lavage cells from most patients, but not from any healthy individuals, demonstrated a selective expansion of particular V beta-expressing subsets. Interestingly, different V beta-bearing subsets were expanded in different patients. Junctional region sequencing indicated that the proliferating T cells in culture were strikingly oligoclonal and were derived from T cell clones already selectively expanded in vivo. These results provide evidence for a disease process that involves recognition of local Ag(s) by specific subsets of CD4+ T cells. Analysis of the Ag specificity of these IL-2-expanded populations is likely to provide insight into the pathogenesis of this disease.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Sarcoidosis Pulmonar/inmunología , Adulto , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Células Clonales , Femenino , Citometría de Flujo , Expresión Génica/genética , Humanos , Interleucina-2/farmacología , Masculino , Receptores de Antígenos de Linfocitos T alfa-beta/biosíntesisRESUMEN
Sarcoidosis is a multisystem disease of unknown etiology characterized by the presence of noncaseating granulomas in involved tissues. To investigate a potential role for gamma/delta T cells in the pathogenesis of pulmonary sarcoidosis, we studied lung and blood T cells from patients for preferential expression of particular gamma/delta T cell receptors. An abnormally high percentage of gamma/delta cells was found in the blood of some patients. However, the increased percentage did not reflect an increase in absolute number, and appeared to be secondary to a decrease in T cells expressing alpha/beta receptors. Furthermore, as in normals, the circulating gamma/delta cells in patients predominantly expressed V gamma 9/V delta 2 receptors, a subset that was not enriched at the site of disease. In contrast, in the lung, an increased percentage of gamma/delta cells expressing V delta 1 was found in a subset of patients. Importantly, these cells demonstrated evidence of prior activation by selectively expanding in vitro in the presence of interleukin 2. Furthermore, an analysis of junctional region sequences revealed their clonal nature. These clonal expansions of V delta 1+ cells in pulmonary sarcoidosis provide evidence for a disease process that involves specific recognition of a local antigen by T cells, and contributes new information regarding the nature of the as yet undefined antigenic stimulus.
Asunto(s)
Enfermedades Pulmonares/inmunología , Pulmón/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Sarcoidosis/inmunología , Linfocitos T/inmunología , Adulto , Anticuerpos Monoclonales , Secuencia de Bases , Líquido del Lavado Bronquioalveolar/inmunología , Complejo CD3/análisis , Células Cultivadas , ADN/genética , Femenino , Humanos , Interleucina-2/farmacología , Enfermedades Pulmonares/sangre , Enfermedades Pulmonares/patología , Masculino , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos , Reacción en Cadena de la Polimerasa/métodos , Receptores de Antígenos de Linfocitos T gamma-delta/análisis , Proteínas Recombinantes/farmacología , Valores de Referencia , Sarcoidosis/sangre , Sarcoidosis/patología , Homología de Secuencia de Ácido Nucleico , Subgrupos de Linfocitos T/inmunología , Linfocitos T/efectos de los fármacosRESUMEN
Multiple sclerosis is an autoimmune disease in which T lymphocytes reactive to myelin basic protein (BP) could play a central role. T cells specific for BP were cloned from the blood of multiple sclerosis patients and normal individuals, and expression of T-cell receptor variable region genes was analyzed. A remarkable bias for use of beta-chain variable region (V beta) 5.2 and, to a lesser extent, V beta 6.1 was seen among BP-specific clones from patients but not from controls. The preferential use of V beta 5.2 for BP recognition did not reflect altered expression of this V beta in the peripheral repertoire. Interestingly, shared V beta 5.2 usage was apparent for clones specific for different BP determinants, even when derived from the same individual. The concurrent demonstration by others (J. R. Oksenberg, M. A. Panzara, A. B. Begovich, H. Erlich, R. Murray, M. Sherritt, S. Stuart, C. C. Bernard, and L. Steinman, personal communication) that T cells within demyelinating areas of multiple sclerosis brains preferentially express V beta 5.2 and V beta 6.1 suggests that the BP-specific clones derived from blood may be relevant to disease pathogenesis. These findings may have important implications for the treatment of multiple sclerosis.
Asunto(s)
Genes , Esclerosis Múltiple/inmunología , Proteína Básica de Mielina/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Linfocitos T/inmunología , Secuencia de Bases , Antígenos CD4/análisis , Células Clonales , Variación Genética , Humanos , Datos de Secuencia Molecular , Esclerosis Múltiple/sangre , Esclerosis Múltiple/genética , Oligodesoxirribonucleótidos , Reacción en Cadena de la PolimerasaRESUMEN
In this report, we review the hospital course of four patients who presented with an acute pulmonary syndrome after inhaling freebase cocaine and compare them with previously described case reports. Two patients had prolonged inflammatory pulmonary injury associated with fever, hypoxemia, hemoptysis, respiratory failure, and diffuse alveolar infiltrates. Lung tissue specimens from both patients revealed diffuse alveolar damage, alveolar hemorrhage, and interstitial and intraalveolar inflammatory cell infiltration notable for the prominence of eosinophils. Immunofluorescent staining performed on one of the biopsy specimens showed a striking deposition of IgE in both lymphocytes and alveolar macrophages. Both patients were treated with systemic corticosteroids and rapidly improved. In contrast, two patients presented acutely with diffuse pulmonary alveolar infiltrates associated with dyspnea and hypoxemia, but without fever, and within 36 h of discontinuing cocaine their pulmonary infiltrates and symptoms had spontaneously resolved. Our report further supports the finding that an acute pulmonary syndrome can occur after inhalation of freebase cocaine. Furthermore, the lung injury may respond to systemic corticosteroid therapy when it is associated with a prominent inflammatory cell infiltration.
Asunto(s)
Cocaína/efectos adversos , Enfermedades Pulmonares/inducido químicamente , Trastornos Relacionados con Sustancias/complicaciones , Enfermedad Aguda , Adulto , Femenino , Hemoptisis/inducido químicamente , Humanos , Pulmón/patología , Enfermedades Pulmonares/diagnóstico por imagen , Masculino , Radiografía , SíndromeRESUMEN
We studied a 66-year-old woman with spontaneous periodic hypothermia (Shapiro's syndrome) to determine the mechanisms that result in increased plasma norepinephrine (NE) levels. In comparison with age-matched control subjects, compartmental analysis of NE kinetics revealed an increased NE release rate into the extravascular compartment and decreases in NE clearance and volume of distribution of NE in the intravascular compartment. Clonidine therapy was associated with an initial dramatic decrease in the frequency of diaphoretic episodes as well as with a fall in NE release rate and increases in NE clearance and volume of distribution. We conclude that increased NE release and decreased plasma NE clearance result in elevated plasma NE levels in Shapiro's syndrome. Clonidine, which was associated with changes in NE kinetics, may provide effective treatment for this disorder.
Asunto(s)
Agenesia del Cuerpo Calloso , Hipotermia/metabolismo , Norepinefrina/metabolismo , Anciano , Clonidina/uso terapéutico , Femenino , Humanos , Hipotermia/tratamiento farmacológico , Hipotermia/etiología , Persona de Mediana Edad , Recurrencia , SíndromeRESUMEN
Sneezing in response to bright light has been found in 25% of a sample of the British population, and pedigrees are compatible with an autosomal dominant mode of inheritance. The mechanism of the response is discussed.
Asunto(s)
Genes Dominantes , Luz , Reflejo , Estornudo , Femenino , Humanos , Masculino , Reino UnidoAsunto(s)
Fenómenos Biomecánicos , Marcha , Miembros Artificiales , Ingeniería Biomédica , Humanos , Pierna , EscociaRESUMEN
Rats were subjects to right hemicolectomy (including removal of the caecum), left hemicolectomy or subtotal colectomy. Body weight resumed and maintained a rate of increase very similar to that in control rats. After hemicolectomy, food intake showed no change. Faecal weight increased by about one-third after right hemicolectomy, but did not increase after left hemicolectomy. After right hemicolectomy, the remaining--that is, downstream--portion of the colon showed increase in weight, and so did the (upstream) small intestine, in which the increase involved all three-thirds of its length and was predominantly mucosal. No such changes in the remaining colon or in small intestine were found after left hemicolectomy. After subtotal hemicolectomy, rats ate 30-40% more food than control rats, and faecal weight increased 60% at three months after operation. Study of energy intake and output indicated diminished absorption. All three-thirds of the small intestine showed increase in weight, predominantly mucosal in the upper two-thirds and predominantly seromuscular in the lowest third; villi were taller at all levels. Evidence suggests that the increase in food intake is not due to cessation of coprophagy, and that the small intestine changes are not due solely to increased food intake and occur when the colon is bypassed but not removed.