RESUMEN
BACKGROUND: Targeting the epidermal-growth-factor-receptor (EGFR) in non-small cell lung cancer (NSCLC) is an established treatment option with less toxicity compared to conventional chemotherapy. This study was undertaken to determine whether Erlotinib is non-inferior compared to chemotherapy as a first-line therapy in unselected elderly patients. MATERIALS AND METHODS: Patients ≥ 70 years with untreated, metastatic NSCLC were randomized to Erlotinib (E), 150 mg/day or Carboplatin (AUC5) plus Vinorelbine (25mg/m(2) on days 1 and 8) every three weeks (CV). Primary endpoint was progression-free survival (PFS). After progression, crossover was strongly recommended. Secondary endpoints were duration of response, 1-year survival, overall survival (OS), response rate (RR), quality of life (FACT-L), assessment of comorbidities by simplified comorbidity score (SCS) and Charlsons' comorbidity score, safety and assessment of molecular markers. RESULTS: Between June 2006 and August 2008 284 pts were randomized to E (144) and CV (140). PFS was significantly inferior with E (median PFS 2.4 versus 4.6 months [HR 1.6, 75% CI 1.22-2.09, p: 0.0005]) as well as RR (7.8% v 28.3%, p: 0.0001). No significant difference in OS appeared (median E: 7.3 months versus CV: 8.4 months, HR: 1.24 [75% CI 0.9-1.71]). In never smokers PFS (median PFS: 3.7 v 4.3 m, E v CV, HR 0.72, 75% CI 0.35-1.48) and OS (median: 16.5 versus 17 months, HR 0.99 [75% CI 0.38-2.57]) were comparable. More skin toxicity and diarrhea was seen with E compared to more myelotoxicity, neurotoxicity and constipation with CV. Less severe adverse events were observed with E (81 v 102, E v CV). CONCLUSION: CV had an increased efficacy compared with E in an unselected population of elderly patients with advanced NSCLC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas/uso terapéutico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Clorhidrato de Erlotinib , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Mutación , Estadificación de Neoplasias , Quinazolinas/administración & dosificación , Factores de Riesgo , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , VinorelbinaRESUMEN
Challenged by scattered understanding of protective immunity to Mycobacterium tuberculosis (MTB), we have mapped peptide epitopes to human leukocyte antigen (HLA)-A*0101, A*0201, A*1101, A*2402, B*0702, B*0801 and B*1501 of the secreted mycobacterial antigen Ag85B, a vaccine candidate that may be associated with immune protection. Affinity (ED(50)) and half-life (t(1/2), off-rate) analysis for individual peptide species on HLA-A and HLA-B molecules revealed binding ranges between 10(-3) and 10(-7) M. After selection of the best matches, major histocompatibility complex class I/peptide tetramer complexes were constructed to measure the CD8+ T-cell responses directly ex vivo in peripheral blood mononuclear cells (PBMC) derived from 57 patients with acute pulmonary tuberculosis. Three patterns of (allele-) specific CD8+ recognition were identified: (a). Focus on one dominant epitope with additional recognition of several subdominant T-cell epitopes (HLA-A*0301, A*2402, B*0801 and B*1501); (b). Co-dominant recognition of two distinct groups of peptides presented by HLA-B*0702; and (c). Diverse and broad recognition of peptides presented by HLA-A*0201. Peptides that bound with slow off-rates to class I alleles, that is HLA-A*0201, were associated with low frequency of CD8+ T cells in PBMCs from patients with tuberculosis. HLA-B alleles showed fast off-rates in peptide binding and restricted high numbers (up to 6%) of antigen-specific CD8+ T cells in patients with pulmonary tuberculosis.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Mapeo Epitopo , Genes MHC Clase I , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/genética , Tuberculosis Pulmonar/inmunología , Alelos , Células Cultivadas , Citometría de Flujo , Antígenos HLA-A/genética , Antígenos HLA-A/inmunología , Antígenos HLA-B/genética , Antígenos HLA-B/inmunología , Humanos , Tuberculosis Pulmonar/fisiopatologíaRESUMEN
Novel diagnostic tools are needed to diagnose latent infection and to provide biologically meaningful surrogate markers to define cellular immune responses against Mycobacterium tuberculosis (MTB). Interferon gamma-based assays have recently been developed in addition to the more than 100-year-old tuberculin skin test (TST) for the immune diagnosis of MTB in blood. The advent of soluble MHC/peptide tetramer molecules allows to objectively enumerate antigen-specific T cells. We identified novel MHC class II-restricted MTB epitopes and used HLA-DR4 tetrameric complexes to visualize ex vivo CD4(+) T cells directed against the antigens Ag85B and the 19-kDa lipoprotein, shared between MTB and other Mycobacterium species, and CD4(+) T cells which recognize the MTB-associated ESAT-6 antigen. MTB-reactive CD4(+) T cells reside predominantly in the CD45RA(+) CD28(+) and CD45(-) CD28(+) T-cell subset and recognize naturally processed and presented MTB epitopes. HLA-DR4-restricted, Ag85B or ESAT-6-specific CD4(+) T cells show similar dynamics over time in peripheral blood mononuclear cells (PBMC) when compared with CD8(+) T cells directed against the corresponding HLA-A2-presented MTB epitopes in patients with pulmonary MTB infection and subsequent successful therapy. This was not found to be true for T-cell responses directed against the 19-kDa lipoprotein. The dissection of the cellular immune response in M. tuberculosis infection will enable novel strategies for monitoring MTB vaccine candidates and to gauge CD4(+) T cells directed against MTB.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/microbiología , Epítopos de Linfocito T/sangre , Antígenos de Histocompatibilidad Clase II/sangre , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/inmunología , Secuencia de Aminoácidos , Presentación de Antígeno , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Antígenos de Histocompatibilidad Clase II/química , Humanos , Datos de Secuencia Molecular , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/patologíaRESUMEN
BACKGROUND: A phase III trial in patients with malignant pleural mesothelioma demonstrated a survival advantage for pemetrexed plus cisplatin compared with single-agent cisplatin. Because post-study chemotherapy (PSC) may have influenced the outcome of the trial, we examined its use and association with survival. PATIENTS AND METHODS: Eighty-four patients from the pemetrexed plus cisplatin arm and 105 patients from the single-agent cisplatin arm received PSC. Kaplan-Meier survival estimates were compared by treatment groups, and by PSC and non-PSC subgroups. RESULTS: The percentage of patients receiving PSC was imbalanced between the treatment arms. Fewer pemetrexed plus cisplatin treated patients received PSC (37.2% versus 47.3%). A multiple regression analysis performed in this trial showed that PSC had a statistically significant correlation with prolonged survival (P <0.01), adjusting for baseline prognostic factors and treatment intervention. The adjusted hazard ratio for PSC over non-PSC subgroups was 0.56 (confidence interval 0.44-0.72). CONCLUSIONS: PSC in malignant pleural mesothelioma was significantly associated with prolonged survival. It is not known whether the reduced risk of death was associated with PSC or whether patients who had prolonged survival tended to receive more PSC. The pemetrexed plus cisplatin treatment group had a statistically significant survival advantage even though fewer patients from that arm of the trial received PSC. The potentially beneficial role of PSC should be assessed in prospective trials.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/uso terapéutico , Glutamatos/administración & dosificación , Guanina/análogos & derivados , Mesotelioma/tratamiento farmacológico , Neoplasias Pleurales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Cisplatino/administración & dosificación , Femenino , Guanina/administración & dosificación , Humanos , Masculino , Mesotelioma/mortalidad , Persona de Mediana Edad , Pemetrexed , Neoplasias Pleurales/mortalidad , Estudios RetrospectivosRESUMEN
PURPOSE: To evaluate whether cisplatin-based chemotherapy (gemcitabine, vinorelbine, and cisplatin [GVP]) prolongs overall survival in comparison to cisplatin-free chemotherapy (gemcitabine and vinorelbine [GV]) as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between September 1999 and June 2001, 300 patients with NSCLC stage IIIB with malignant pleural effusion or stage IV disease were randomly assigned to receive GV (gemcitabine 1000 mg/m(2) + vinorelbine 25 mg/m(2) on days 1 and 8 every 3 weeks) or GVP (gemcitabine 1000 mg/m(2) + vinorelbine 25 mg/m(2) on days 1 and 8 + cisplatin 75 mg/m(2) on day 2 every 3 weeks). Primary end point of the study was overall survival. RESULTS: Two hundred eighty-seven patients (GV, 143 patients; GVP, 144 patients) were eligible for analysis. At the time of analysis, April 15, 2002, 209 patients (GV, 103 patients; GVP, 106 patients) of 287 patients had died (73%). No statistically significant difference was observed for overall survival (P =.73; median survival, 35.9 versus 32.4 weeks; 1-year survival rate, 33.6% versus 27.5%) as well as for event-free survival (P =.35; median time-to-event, 19.3 versus 22.3 weeks) between GV and GVP. Two hundred fourteen patients were assessable for best response. The overall response rates were 13.0% for GV versus 28.3% for GVP (P =.004; complete responders, 0% versus 3.8%; partial responders, 13.0% versus 24.5%). Hematologic and nonhematologic toxicity was significantly lower in the GV treatment arm compared with GVP. No statistically significant difference in quality of life was observed. CONCLUSION: In this phase III study, the cisplatin-based GVP regimen showed no survival benefit as first-line chemotherapy in advanced NSCLC when compared with the cisplatin-free GV regimen, which was substantially better tolerated.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/administración & dosificación , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Vinblastina/análogos & derivados , Vinblastina/administración & dosificación , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/efectos adversos , Desoxicitidina/efectos adversos , Esquema de Medicación , Enfermedades Hematológicas/inducido químicamente , Humanos , Persona de Mediana Edad , Calidad de Vida , Tasa de Supervivencia , Vinblastina/efectos adversos , Vinorelbina , GemcitabinaRESUMEN
Biphasic pulmonary blastoma (BPB) is a rare primary neoplasm of the lung and its histogenesis is still uncertain. It has been proposed that BPB is derived from mesoderm or endoderm. Others suggested an origin from a single pluripotential cell. We present a case of a BPB with emphasis on expression of the stem cell factor receptor KIT (CD117). We describe a 61-year-old male patient with a BPB of the upper right lobe. Immunohistochemical analysis was performed using a panel of several antibodies including anti-CD117. Strong cytoplasmic expression of CD117 was found in the epithelium (cytokeratin-positive) as well as in the spindle cells (cytokeratin-negative). Expression of CD117 in both mesenchymal and epithelial cells suggests a single origin and supports the idea that BPB arises from a pluripotential cell that can differentiate into both stromal and epithelial morphologies. The role of CD117 in the pathogenesis of BPB and its possible therapeutic relevance require further investigation.
Asunto(s)
Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogénicas c-kit/metabolismo , Humanos , Inmunohistoquímica , Pulmón/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: The primary objective of this phase II study was to determine the tumor remission rates in previously untreated patients with advanced or metastatic non-small cell lung cancer (stage IIIB and IV), after treatment with gemcitabine plus carboplatin. Secondary objectives of this study were to determine toxicity, median survival and progression free survival in the same patient population treated with gemcitabine plus carboplatin. PATIENTS AND METHODS: Chemonaive patients with histological or cytological diagnosis of stage IIIB or IV NSCLC and Karnofsky performance status >/=60 received gemcitabine 1000 mg/m(2) over 30 min on days 1 and 8 and carboplatin AUC 5.0 over 30 min on day 1 after the gemcitabine infusion. Treatment cycles were repeated every 21 days for a maximum of six cycles, or until disease progression or unacceptable toxicity occurred. RESULTS: Of the 60 patients qualified for efficacy analysis, five achieved complete remissions, 15 partial remissions and 33 had stable disease, for an overall objective response rate (CR+PR) of 33.3% (95% CI, 21.7-46.7%). Four patients had progressive disease. The predominant toxicity was hematologic, with grade 3/4 leucopoenia being most common (35% patients). The median duration of response was 5 months, median time to progression was 6 months and median survival was 9 months with 80% of patients censored. CONCLUSION: Gemcitabine plus carboplatin is an effective and well tolerated treatment for advanced NSCLC.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/secundario , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Tasa de Supervivencia , Factores de Tiempo , GemcitabinaRESUMEN
Acute histoplasmosis is usually a benign, self-limited infection in endemic areas. Since protection against Histoplasma capsulatum infection requires specific, cell-mediated immunity, histoplasmosis is well documented in patients with acquired T cell deficiencies e.g. due to HIV infection. We report here for the first time a case of pleural effusion due to H. capsulatum infection in a patient with idiopathic CD4 lymphocytopenia (ICL). A 25-year-old woman presented with chest pain, dyspnea on exertion and a moderate weight loss. Chest X-ray showed a large left pleural effusion, and thoracentesis yielded an exudate. Histologic examination of pleural biopsies identified H. capsulatum. Laboratory tests revealed lymphocytopenia with low CD4+ T cell counts (<100/microl) and a decreased CD4/CD8 ratio. Serology, including HIV, was repeatedly negative. The diagnosis of pleural effusion due to H. capsulatum infection in a patient with idiophatic ICL was established. There was no evidence of any other opportunistic infection. Treatment with itraconazole was initiated and pleural effusion resolved within 2 weeks of treatment. Moreover, the patient was found to have idiopathic thrombocytopenic purpura, as confirmed by the detection of autoantibodies against thrombocytes. In a 1-year follow-up, the patient remained asymptomatic without relapse or any new infection. Treatment with itraconazole was given for 12 months. Because of persistent CD4+ T cell counts below 100/microl, prophylactic antibiotic treatment is continued.
Asunto(s)
Histoplasma/aislamiento & purificación , Histoplasmosis/complicaciones , Derrame Pleural/etiología , Linfocitopenia-T Idiopática CD4-Positiva/complicaciones , Adulto , Femenino , HumanosRESUMEN
In response to antigenic stimulation, naive MHC-class I restricted and antigen-specific CD8+ CD45RA+ CD28+ T cells undergo clonal expansion, differentiate into CD8+ CD45RO+ memory T cells and convert to CD8+ CD45RA+ CD28- T cells displaying potent immune effector functions upon re-encounter with the nominal antigen. We show that the effector CD8+ CD45RA+ CD28- T cell subset is expanded in peripheral blood lymphocytes (PBL) from patients with human papilloma virus (HPV)+ cervical lesions as well as in PBL from patients with pulmonary tuberculosis. Flow-cytometric cell sorted CD8+ CD45RA+ CD28- and CD8+ CD45RA+ CD28- T cells were tested for recognition of HLA-A2 restricted peptides derived either from the human papillomavirus (HPV)16-E7 gene product, or from M. tuberculosis antigens. Mostly CD8+ CD45+ CD28- T cells define antigen/peptide-specific and MHC-restricted responses. These data were confirmed in PBL from patients with tuberculosis using HLA-A2 tetramer-complexes loaded with a peptide from the M. tuberculosis Ag85b antigen by flow cytometry. The sorting of this T cell subset enables to determine the fine specificity of CD8+ effector T cells without the need for in vitro manipulation.
Asunto(s)
Proteínas Bacterianas/inmunología , Antígeno HLA-A2 , Antígenos Comunes de Leucocito , Linfocitos T Reguladores/inmunología , Proteínas Virales/inmunología , Reacciones Antígeno-Anticuerpo , Antígenos Bacterianos/inmunología , Antígenos CD28 , Diferenciación Celular , División Celular , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Mycobacterium tuberculosis/inmunología , Infecciones por Papillomavirus/inmunología , Tuberculosis Pulmonar/inmunología , Neoplasias del Cuello Uterino/inmunologíaRESUMEN
CD8+ T cells can be grouped into two different types of secretory T lymphocytes, based on the cytokine-secretion pattern upon antigen exposure: those with a T-cell cytotoxic type 1 response (Tc1), which secrete interferon-gamma (IFN-gamma), or those with a T-cell cytotoxic type 2 response, which secrete interleukin (IL)-4 and IL-10. We examined the CD8+ T-cell response directed against an immunodominant human leucocyte antigen (HLA)-A2-presented peptide derived from a 19-kDa Mycobacterium tuberculosis-associated antigen. T cells were examined by functional analysis and by T-cell receptor (TCR) complementarity-determining region 3 (CDR3)-spectratyping, which defines the complexity of a T-cell response. T-cell stimulation with the immunodominant VLTDGNPPEV epitope yielded a Tc2 (IL-4) cytokine-secretion pattern and resulted in oligoclonal expansion of TCR-variable beta chain (VB) families, which differed from patient to patient. Generation of T-cell clones corroborated the notion that the CD8+ T-cell response directed against the HLA-A2-presented VLTDGNPPEV epitope leads to a Tc2 cytokine-secretion pattern in CD8+ T cells, as defined by IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) release. Characterization of the cytokine-secretion profile in HLA-A2/VLTDGNPPEV-tetramer sorted T cells from patients with active tuberculosis supported this observation: peptide-specific T cells from three of three patients secreted IL-4 and only one of three patients produced IFN-gamma in response to the nominal target epitope. Permutation of this T-cell epitope may aid to elicit a qualitatively different CD8+ T-cell response in patients with M. tuberculosis infection.
Asunto(s)
Antígenos Bacterianos/inmunología , Linfocitos T CD8-positivos/inmunología , Antígeno HLA-A2/inmunología , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/inmunología , Línea Celular , Células Clonales/inmunología , Regiones Determinantes de Complementariedad/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/biosíntesis , Humanos , Epítopos Inmunodominantes/inmunología , Interferón gamma/biosíntesis , Interleucina-4/biosíntesis , Activación de Linfocitos/inmunología , Fragmentos de Péptidos/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/inmunologíaRESUMEN
Detection of latent tuberculosis infection is an important step in the control of tuberculosis. The tuberculin skin test is the only proven method for identifying tuberculosis infection in patients who do not have tuberculosis disease. The prevalence of tuberculosis infection among hospitalized patients in a pneumological department of an inner-city hospital was evaluated, using the intradermal tuberculin skin test (Mantoux technique). Interpretation of the Mantoux test was based on the size of induration in millimeters and the individual risk profile of the patients, according to the guidelines of the American Thoracic Society and the Centers for Disease Control, revised in 1989. Of 697 tested patients, 252 showed test results consistent with tuberculosis infection (36.2%). 55 of these 697 patients had active tuberculosis disease or a prior history of tuberculosis (7.9%). A positive tuberculin skin test was found in 197 of 642 patients (30.7%) with a diagnosis different from tuberculosis (COPD, pneumonia, cancer and others). In our study, the sensitivity of the tuberculin skin test for active tuberculosis infection was 95%. The present study revealed a high prevalence of tuberculosis infection among hospitalized patients in a pneumological department. Further studies are needed to assess the usefulness of routine tuberculin skin testing in hospitalized populations.
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Pacientes Internos , Tuberculosis Pulmonar/epidemiología , Tuberculosis/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Centers for Disease Control and Prevention, U.S. , Femenino , Guías como Asunto , Departamentos de Hospitales , Humanos , Enfermedades Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Sociedades Médicas , Prueba de Tuberculina , Estados UnidosRESUMEN
Aspiration of large amounts of barium sulfate is a rare incident during radiographic contrast procedures. Here we describe two patients, who developed acute dyspnea after aspiration of significant amounts of barium into the lung during an upper gastrointestinal radiographic contrast study. The regions of the lung involved depended on the position of the patients during and after aspiration. Arterial blood gas analysis revealed hypoxemia due to alveolar shunt with V/Q distribution disturbances. Bronchoscopy was performed to extract the contrast medium from the tracheobronchial tree. The patients could be discharged a few days later with normal lung function. Long-term prognosis is generally excellent due to the inert character of barium sulfate, even though impressive radiographic findings remain.
Asunto(s)
Sulfato de Bario , Medios de Contraste , Neumonía por Aspiración/etiología , Anciano , Alcoholismo/complicaciones , Femenino , Cuerpos Extraños , Humanos , Pulmón , Masculino , Persona de Mediana Edad , Neumonía por Aspiración/diagnóstico , Neumonía por Aspiración/terapia , PronósticoRESUMEN
OBJECTIVE: To describe the role of sputum and brush cytology in the diagnosis of lung carcinoma and to elucidate the influence of tumor location, histologic tumor type and stage on the sensitivity of both methods. STUDY DESIGN: Retrospective and performed on 415 lung cancer patients. Two hundred of them were investigated only by sputum collection, 119 only by brushing and 96 by both methods. RESULTS: The overall sensitivity of the sputum technique was 0.403 and that of the brush method 0.500, while a combination of both showed a sensitivity of 0.640. The diagnostic yield depended on tumor location, histologic tumor type and stage. Sputum specimens were most valuable in the detection of early and peripheral carcinomas, whereas brushing was superior in finding more advanced and centrally located malignancies. Regarding tumor type, squamous cell carcinomas were diagnosed to the greatest extent by both methods. CONCLUSION: A complementary role of both cytologic techniques can be postulated by our data as well as by a literature review.
Asunto(s)
Adenocarcinoma/diagnóstico , Carcinoma de Células Grandes/diagnóstico , Carcinoma de Células Pequeñas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Esputo/citología , Adenocarcinoma/patología , Carcinoma de Células Grandes/patología , Carcinoma de Células Pequeñas/patología , Carcinoma de Células Escamosas/patología , Técnicas Citológicas , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Sensibilidad y EspecificidadRESUMEN
We investigated the reaction of the cellular immune system of liver and blood in the C57BL/6 mouse to a metastasizing Lewis lung carcinoma. The cellular immune system of the liver consists of mature and immature macrophages, B-cells, T-cells including their subpopulations, and natural killer cells, and their percentage frequencies differ significantly from those in the corresponding mononuclear blood cell (MBC) compartment. This suggests that the hepatic immune cells represent a system with autonomous function showing a typical homing of its members. Imminent metastasis to the liver is signalled by impressive alterations in the percentage frequencies of nonparenchymal liver cells (NPLC). There are a dramatic loss of mature macrophages, an increase in immature macrophages, a reduction of T-helper cells leading to a low CD4/CD8 ratio, and an increase in natural killer cells. In the blood, the corresponding precursor cells show comparable changes with a delay of at least 2 days. Early metastasis is accompanied by a significant increase in mononuclear NPLC producing tumour necrosis factor alpha. The alterations in percentage frequencies of the NPLC during tumour metastasis differ markedly from the changes in these cells in the liver during endotoxinaemia.
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Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/secundario , Hígado/inmunología , Neoplasias Pulmonares/inmunología , Animales , Linfocitos B/inmunología , Relación CD4-CD8 , Recuento de Células , Femenino , Inmunohistoquímica , Hígado/ultraestructura , Recuento de Linfocitos , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica , Linfocitos T/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Factor de Necrosis Tumoral alfa/análisisRESUMEN
20 specimens of normal pleural mesothelium were investigated with six lectins using isolated cells and tissue specimens as well as two different fixation techniques (glutaraldehyde and formaldehyde) and 10 monoclonal antibodies (MAb) on cytologic preparations only. Lectin binding sites for ConA, WGA, and PNA were present in all cases, whereas binding sites for the lectins HPA, SBA, and UEA-I could never be found. There was no staining difference with the two preparation and fixation techniques proving that they may be used to compare directly histologic and cytologic studies. Ten of fourteen histologic specimens were positive for the blood group antigen Lewis(y), three of them were positive for the antigen Lewis(b), all fourteen specimens were negative for Lewis(a) and Lewis(x). In all cases, mesothelial cells expressed ICAM1 and pancytokeratin. The antibodies against EMA, CEA, CD24, CD15, CD20, CD5, and HEA125 showed no reaction in mesothelial cells. Because HPA, UEA-I, SBA as well as CEA and HEA125 react in a high percentage with adenocarcinomas, non reactive cells of pleural effusions negative with these markers may be confidentially considered to be mesothelial in origin.
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Carbohidratos/análisis , Lectinas/metabolismo , Pleura/química , Sistema del Grupo Sanguíneo ABO , Anticuerpos Monoclonales , Sitios de Unión , Metabolismo de los Hidratos de Carbono , Recuento de Células , Células Epiteliales , Epitelio/química , Epitelio/metabolismo , Formaldehído , Humanos , Inmunohistoquímica , Antígenos del Grupo Sanguíneo de Lewis/análisis , Pleura/citología , Pleura/metabolismo , Fijación del TejidoRESUMEN
Increasing evidence suggests a role for activated T cells and cytokines in the regulation of eosinophilic inflammation in asthma. In this study, we investigated the distribution of leukocytes, lymphocytes, their activation state, and the cytokine profile in BAL from 10 atopic asthmatics with positive skin prick tests and elevated specific IgE levels to birch or grass pollen. Using segmental allergen challenge, 250 PNU of the appropriate allergen or saline were instilled into different segments, which were lavaged 10 min (10 min) and 18 h (18 h) after allergen challenge or 18 h after saline challenge (C). In peripheral blood the number of neutrophils and activated IL-2R+/CD4+ T cells increased significantly 18 h after allergen provocation; there was no change in eosinophils, other leukocytes, or lymphocyte subsets. In contrast, numbers of eosinophils, neutrophils, and IL-2R+/CD4+ T cells increased significantly in BAL samples at 18 h. The numbers of neutrophils and eosinophils were not significantly different in the lavage performed at 10 min and at C. Analysis of cytokines in concentrated BAL fluid revealed significantly increased levels of IL-5, IL-2, IL-1, TNF-alpha, IL-6, IL-8, and GM-CSF, but not of IL-4 and IFN-gamma at 18 h compared with those at C and at 10 min. The correlation between IL-5 levels, eosinophil numbers, and activated T cells supports a role for T-cell-derived IL-5 in causing tissue eosinophilia in allergic asthma.
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Asma/inmunología , Pruebas de Provocación Bronquial , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/fisiología , Subgrupos de Linfocitos T/fisiología , Adulto , Asma/fisiopatología , Linfocitos T CD4-Positivos/fisiología , Citocinas/biosíntesis , Eosinófilos , Femenino , Humanos , Interleucinas/biosíntesis , Interleucinas/fisiología , Recuento de Leucocitos , Masculino , NeutrófilosRESUMEN
We have tried to find a reliable panel of markers that would allow distinction between mesotheliomas and carcinomas metastatic to the pleura. In a prospective study, we evaluated 54 pleural effusions: In 27 of the patients, a diagnosis of histologically proven metastatic carcinoma was subsequently established, 7 patients had biopsy-proven malignant mesotheliomas and 20 had benign, reactive effusions whose benign etiologies were established by more than 2 years clinical follow-up. The MAb (monoclonal antibody) IOB3 proved to be diagnostic for carcinomas in all 27 cases (100%), whereas CEA (carcinoembryonic antigen) expression was found in only 22 out of 27 (81%). None of the malignant mesotheliomas, nor benign reactive mesothelial cells reacted with these two markers. All carcinomas, as well as one malignant mesothelioma, reacted with the MAb HEA125. Antibodies against 12 single cytokeratins, vimentin, and EMA (epithelial membrane antigen) were not helpful in the differentiation between malignant mesotheliomas and malignant carcinomatous pleural effusions. We conclude that adding the antibody IOB3 to the CEA assay should allow a reliable differentiation between these two entities.
Asunto(s)
Antígenos CD/análisis , Biomarcadores de Tumor/análisis , Carcinoma/secundario , Glicoproteínas de Membrana , Mesotelioma/patología , Derrame Pleural Maligno/patología , Neoplasias Pleurales/patología , Neoplasias Pleurales/secundario , Adulto , Anciano , Anticuerpos Monoclonales , Antígeno CD24 , Antígeno Carcinoembrionario/análisis , Carcinoma/patología , Diagnóstico Diferencial , Femenino , Humanos , Técnicas para Inmunoenzimas , Queratinas/análisis , Masculino , Persona de Mediana Edad , Pleura/patología , Valor Predictivo de las Pruebas , Vimentina/análisisRESUMEN
This paper documents dose-dependent effects of ornithine aspartate (OA) on postprandial hyperammonemia and plasma amino acids. Ten patients with cirrhosis were randomized to undergo 1 out of 4 infusion series. Each series consisted of four 8-h infusions (09:00 h-17:00 h), with placebo (NaCl), 5 g, 20 g or 40 g of OA being administered on separate days in varying sequences. This 4-fold crossover design was double-blind. On infusion days, patients received 2 oral protein loads (0.25 g/kg at 09:00 h and 0.5 g/kg at 13:00 h). Venous blood samples were drawn every 2 h and the 24-h urine was collected. In addition to measuring plasma ammonia and amino acids, the urea production rate, serum glucose and serum insulin were analyzed. A significant postprandial rise in the ammonia concentration was noted during the infusions of placebo and 5 g of OA but did not occur with the dosages of 20 g (after the second protein load) and 40 g (after both protein loads). Furthermore, the latter dose, compared with placebo, significantly reduced plasma ammonia after the minor protein load. Urea production rate increased when 20 g or 40 g of OA was administered. Of the amino acids involved in the metabolic pathways of ornithine and/or aspartate, glutamate showed a rise in its plasma level following infusion of 40 g of OA, whereas glutamine did not. Concentrations of methionine, phenylalanine, tyrosine, threonine, serine and glycine declined progressively with increasing doses of OA (5-40 g). The highest dose of the drug caused hyperglycemia and hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)