RESUMEN
Tumor pretargeting with biotinylated antibody/avidin complexes improves the therapeutic index of systemically administered biotin-tumor necrosis factor (TNF) conjugates. Since the number of biotins in this conjugate is known to be critical for activity, we have characterized the structure of different biotin-TNF conjugates, prepared by reaction with d-biotinyl-6-aminocaproic acid N-hydroxysuccinimide ester and identified the biotinylation sites by trypsin digestion, reverse-phase chromatography, and electrospray mass spectrometry analyses. The results have shown that N-terminal valine is a preferential biotinylation site at pH 5.8, half of biotins being located on the alpha-amino group of this residue in a conjugate bearing one biotin/trimer (on average). Moreover, evidence has been obtained to suggest that the remaining part of biotins are linked to the epsilon-amino group of lysine 128, 112, and 65, while lysine 11, 90, and 98 were practically unmodified. No evidence of O-biotinylation of serine, threonine and tyrosine was obtained.
Asunto(s)
Biotina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Secuencia de Aminoácidos , Animales , Sitios de Unión , Biotinilación , Células Cultivadas , Cromatografía Líquida de Alta Presión/métodos , Fibroblastos/fisiología , Humanos , Espectrometría de Masas/métodos , Ratones , Datos de Secuencia Molecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/metabolismo , Tripsina/metabolismoRESUMEN
Identification of sulfonylureas in serum is important in the diagnosis of hypoglycemic crisis of unknown origin. Methods based on HPLC with UV or fluorescence detection may give false positive results. Mass spectrometry may successfully avoid this problem. The described method allows the simultaneous identification and quantification of tolbutamide, chlorpropamide, glibenclamide, and glipizide in human serum using one of the tested sulfonylureas as the internal standard. Serum purification is carried out by solid-phase extraction with ENVI-C18 cartridges and samples are analyzed by liquid chromatography-electrospray mass spectrometry. For all drugs, the limit of detection and the limit of quantification are about 2 and 10 ng/ml, respectively.
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Espectrometría de Masas/métodos , Compuestos de Sulfonilurea/sangre , Calibración , Clorpropamida/sangre , Cromatografía Liquida , Glipizida/sangre , Gliburida/sangre , Humanos , Modelos Químicos , Tolbutamida/sangre , Rayos UltravioletaRESUMEN
OBJECTIVES: We attempted to determine whether inflammation is present in induced sputum of patients with seasonal allergic rhinitis (AR) as compared with those with perennial asthma (AS) and examined its relationship with bronchial responsiveness to methacholine. METHODS: Sputum was induced in 30 patients with seasonal rhinitis in response to grass pollens only and in 15 patients with stable, asymptomatic asthma. The AR group was divided according to methacholine PD20 value: the AR- group (n = 15) had a methacholine PD20 greater than 24 micromol; the AR+ group (n = 15) had a methacholine PD20 ranging between 2.2 and 19.6 micromol. In the AS group, methacholine PD20 ranged between 0.42 and 2.6 micromol. The percentage of eosinophils and metachromatic cells (alcian blue-positive) was assessed in sputum by light microscopy. Tryptase-positive cells and EG2+ cells were identified by immunocytochemistry with the mouse anti-human mast cell-tryptase monoclonal antibody and the monoclonal anti-eosinophil cationic protein antibody. RESULTS: We found that the number of eosinophils in the AS group was greater than that in the AR+ group (p < 0.05) and in the AR- group (p < 0.01). Moreover, the eosinophil count was lower in the AR- group compared with the AR+ group (p < 0.05). Similarly, the number of EG2+ cells was greater in the AS group than in the AR group (p < 0.02) and the AR- group (p < 0.05). Moreover, the EG2+ cell count was lower in the AR- group than in the AR+ group (p < 0.05). The number of mast cells and basophils in the AS group was greater than that in the AR group (p < 0.05 and p < 0.01, respectively). Mast cells in sputum were tryptase-positive. Basophils were present in sputum from 23% of patients with AR and 53% of patients with asthma. There was a significant correlation between methacholine PD20 and eosinophils (p < 0.005) and mast cells (p < 0.02) but not with basophils in those patients showing a measurable methacholine PD20 (AR+ and AS groups). CONCLUSIONS: Inflammatory cells are present not only in the airways of patients with asthma but also in airways of patients with seasonal AR, even outside natural exposure. Moreover, we provide evidence for the presence of basophils in sputum of patients with asthma even during clinical remission. The presence of bronchial responsiveness is associated with an increase in the number of eosinophils and metachromatic cells. Our findings are consistent with the hypothesis that eosinophils, as well as mast cells, contribute to bronchial responsiveness not only in AS but also in seasonal AR.
Asunto(s)
Asma/patología , Basófilos/patología , Hiperreactividad Bronquial/patología , Eosinófilos/patología , Mastocitos/patología , Cloruro de Metacolina , Rinitis Alérgica Estacional/patología , Esputo/citología , Adulto , Asma/metabolismo , Asma/fisiopatología , Hiperreactividad Bronquial/fisiopatología , Pruebas de Provocación Bronquial , Recuento de Células , Femenino , Humanos , Inmunohistoquímica , Masculino , Rinitis Alérgica Estacional/metabolismo , Rinitis Alérgica Estacional/fisiopatología , Esputo/efectos de los fármacosRESUMEN
BACKGROUND: Inhaled furosemide has been shown recently to produce a protective effect against bronchoconstriction induced by several indirect stimuli, including ultrasonically nebulized distilled water (UNDW). Since there is a close parallel between its experimental effects and those reported for cromolyn,/it has been suggested that they may share some common mechanisms of action. Their protective effect, however, has never been compared directly. In this study, therefore, we have investigated the ability of equal doses (30 mg) of inhaled furosemide and cromolyn to modulate bronchoconstriction induced by UNDW in a group of ten asthmatic patients. METHODS: Subjects with documented bronchial response to UNDW were enrolled in a randomized, double-blind, placebo-controlled study. Treatments were administered five minutes prior to increasing outputs of UNDW and the response was expressed as the provocative output causing a 20% fall in FEV1 (PO20, in mL/min) and as the output-response slope. RESULTS: Geometric mean PO20 increased from 1.53 to 4.05 mL/min (P < .0004) after furosemide. After inhaling the highest output of UNDW (5.2 mL/min), PO20 was not measurable in six of ten patients when pretreated with furosemide and in all patients when pretreated with cromolyn. This difference was statistically significant (P < .05). Geometric mean values of output-response slope significantly decreased from 13.6 to 2.97 after furosemide (P < .0001) and from 13.6 to 1.43 (P < .0002) after cromolyn. CONCLUSIONS: These results suggest that cromolyn has a slightly greater anti-reactive activity in UNDW-induced bronchoconstriction compared to furosemide.
Asunto(s)
Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Broncoconstricción/efectos de los fármacos , Cromolin Sódico/uso terapéutico , Diuréticos/uso terapéutico , Furosemida/uso terapéutico , Administración por Inhalación , Adolescente , Adulto , Antiasmáticos/administración & dosificación , Pruebas de Provocación Bronquial , Cromolin Sódico/administración & dosificación , Diuréticos/administración & dosificación , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado , Furosemida/administración & dosificación , Humanos , Masculino , Compuestos de Metacolina/farmacología , Persona de Mediana Edad , Nebulizadores y Vaporizadores , Agua/farmacologíaRESUMEN
BACKGROUND: Nonallergic rhinitis with eosinophilia syndrome (NARES) is characterized by persistent nasal symptoms without allergy and by a marked eosinophil recruitment in the nasal cavities. OBJECTIVE: We studied whether patients with NARES had bronchial responsiveness to methacholine and airway inflammation and examined the relationship between these factors. METHODS: We selected a group of 39 patients referred to our allergy clinic for symptoms of perennial rhinitis. Atopic status was excluded by skin prick tests and RASTs. None of the patients had a history of respiratory symptoms. We preliminarily performed nasal lavage in all patients, and the diagnosis of NARES was made on the basis of the presence of at least 10% eosinophils in nasal lavage fluid. A methacholine challenge and sputum induction were also done on two different days. RESULTS: Eosinophils in nasal lavage fluid ranged between 10% and 86%. Serum IgE levels were within normal range. Total circulating eosinophils ranged between 40 and 890/mm3. Methacholine PD20 values were measurable in only 18 patients (range, 0.32 to 22.56 micromol; group 1). In the remaining 21 patients, methacholine PD20 values were greater than 24 micromol (group 2). We found that differential cell counts in nasal lavage fluid in group 1 were not different from those in group 2. Methacholine PD20 values were not significantly related to any cell count in the nasal lavage fluid. Induced sputum was accomplished only in 22 patients. Eosinophils in induced sputum ranged between 0% and 56.5%. Numbers of total cells, macrophages, lymphocytes, neutrophils, and epithelial cells in the two subgroups were not different. The number of metachromatic cells tended to be higher in group 1 compared with group 2 (0.31% vs 0.05%), but the difference was not significant. The eosinophil count in the induced sputum was significantly higher in group 1 compared with group 2 (16.8% vs 3.1%; p < 0.05). In the entire population, methacholine PD20 values were significantly correlated with the number of eosinophils in sputum (r = -0.63; p < 0.001). CONCLUSION: We showed that 46% of patients with NARES but without histories of respiratory symptoms had a measurable bronchial responsiveness. The presence of bronchial responsiveness was associated with an increased number of eosinophils in induced sputum but not with the inflammatory process in the nose.
Asunto(s)
Bronquios/patología , Hiperreactividad Bronquial/patología , Eosinofilia/patología , Rinitis/patología , Adolescente , Adulto , Anciano , Recuento de Células Sanguíneas , Bronquios/fisiopatología , Hiperreactividad Bronquial/sangre , Hiperreactividad Bronquial/fisiopatología , Recuento de Células , Eosinofilia/sangre , Eosinofilia/fisiopatología , Femenino , Humanos , Inflamación/sangre , Inflamación/patología , Inflamación/fisiopatología , Masculino , Persona de Mediana Edad , Líquido del Lavado Nasal/citología , Rinitis/sangre , Rinitis/fisiopatología , Esputo/citología , SíndromeRESUMEN
One hundred and fifty years after the original description of spirometry by Hutchinson and 50 years after the definition of his famous ratio by Tiffeneau, a certain number of physiological advances have enabled a better understanding of the determinants of the forced expired manoeuvre and to mitigate some of its inconveniences. This review focuses on three of these advances. The first is the influence of an inspiratory manoeuvre which precedes a forced expiration, on the expiratory flow. This influence is probably a consequence of viscoelastic phenomena and impose some strains on standardisation in current practice. The second is the possibility of detecting in a reproducible and simple fashion, without the need for co-operation on the part of the subject, a limitation in expiratory flow by the application of a negative expiratory pressure at the opening of the airways (NEP for negative expiratory pressure). The third is the possibility to verify in a simple fashion the quality of the expiratory performance achieved by the patient and thus to detect an insufficient effort in the force of a falling expiratory flow.
Asunto(s)
Volumen Espiratorio Forzado/fisiología , Disnea/fisiopatología , Elasticidad , Flujo Espiratorio Forzado/fisiología , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Inhalación/fisiología , Rendimiento Pulmonar/fisiología , Enfermedades Pulmonares Obstructivas/fisiopatología , Flujo Espiratorio Máximo/fisiología , Curvas de Flujo-Volumen Espiratorio Máximo/fisiología , Ventilación Voluntaria Máxima/fisiología , Reproducibilidad de los Resultados , Espirometría/historia , Capacidad Pulmonar Total/fisiología , ViscosidadRESUMEN
It has been shown that in normal subjects and chronic obstructive pulmonary disease (COPD) patients the maximal expiratory flows and FEV1 are significantly higher if the FVC maneuver is preceded by a rapid inspiration without an end-inspiratory pause (maneuver 1) compared with a slow inspiration with an end-inspiratory pause of approximately 5 s (maneuver 2). This time dependency of FVC was attributed primarily to loss of lung recoil (stress relaxation) during breath-holding at TLC, in association with time constant inequality within the lungs, and changes in bronchomotor tone. To examine the role of bronchomotor tone on time dependency of FVC, 11 COPD and 10 asthmatic patients performed FVC maneuvers 1 and 2 before and after administration of a bronchodilator drug (salbutamol). In addition, using the same approach, the effects of changing airway resistance per se were assessed in another group of 10 COPD patients and 10 normal subjects, while breathing air and after equilibration with 80% helium in oxygen. Main findings were: peak expiratory flow (PEF), FEV1, and maximal midexpiratory flow rate (MMF) were significantly larger with maneuver 1 than 2; after salbutamol administration and during helium-oxygen breathing, all indices increased significantly with both maneuvers but the relative differences between maneuvers 1 and 2 were unchanged. We conclude that time dependency of maximal expiratory flow-volume (MEFV) curves, as indexed by PEF, FEV1, and MMF, is largely independent of bronchomotor tone and gas density, and probably reflects mainly stress relaxation of the respiratory tissues. The relevance of time dependency of FVC maneuver in the assessment of bronchodilator response and density dependence is discussed.
Asunto(s)
Asma/fisiopatología , Enfermedades Pulmonares Obstructivas/fisiopatología , Respiración/efectos de los fármacos , Pruebas de Función Respiratoria/métodos , Adulto , Anciano , Albuterol/uso terapéutico , Asma/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Femenino , Helio/farmacología , Humanos , Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The antitussive activity of inhaled furosemide has been attributed to its blocking effect on the Na(+)-2Cl(-)-K+ cotransporter. It is likely that the antitussive activity of inhaled diuretics is more complex because amiloride, a diuretic that has no effect on the Na(+)-2Cl(-)-K+ cotransporter, also shows a significant effect against cough induced by low-chloride-ion solutions. Apart from pharmacokinetics of inhaled diuretics, this activity could also depend on the inhibition of carbonic anhydrase. OBJECTIVES: We therefore studied the effect of inhaled acetazolamide, a selective inhibitor of carbonic anhydrase activity, on cough induced by the inhalation of different chloride ion solutions in a group of normal subjects. This was compared with the antitussive effect of furosemide. In addition, we attempted to determine whether the effect of acetazolamide is dose-dependent. METHODS: Cough challenge consisted of consecutive inhalations of four solutions having decreasing concentrations of chloride ions (150, 75, 37.5 and 0 mmol/L). Nine normal subjects underwent the cough challenge 5 minutes after the inhalation of saline placebo, acetazolamide (500 mg), and furosemide (30 mg) according to a randomized, double-blind study design. A group of six subjects were challenged according to the same procedure and study design, after the inhalation of saline placebo and of two doses of acetazolamide (250 mg and 500 mg). RESULTS: Inhaled acetazolamide significantly reduced cough response to 37.5 and 0 mmol/L chloride solutions compared with placebo (p less than 0.015 and p less than 0.015, respectively). Furosemide showed a similar protective effect (p less than 0.015 and p less than 0.025, respectively). Acetazolamide provided a significantly better protective effect than furosemide (p less than 0.025 and p less than 0.015, respectively). The antitussive activity of the two doses of acetazolamide was not statistically different. CONCLUSION: These results demonstrate that inhaled acetazolamide, a selective inhibitor of carbonic anhydrase, attenuates cough induced by low-chloride-ion solutions in normal subjects. At the applied doses, its antitussive activity is slightly greater than furosemide. This finding suggests that the inhibition of carbonic anhydrase activity is likely involved in modulating changes caused by absence of a chloride ion in the airway microenvironment of human beings.
Asunto(s)
Acetazolamida/farmacología , Antitusígenos/farmacología , Tos/inducido químicamente , Tos/prevención & control , Furosemida/farmacología , Cloruro de Sodio/efectos adversos , Acetazolamida/uso terapéutico , Adulto , Antitusígenos/uso terapéutico , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Concentración Osmolar , Distribución Aleatoria , SolucionesRESUMEN
Although the inhalation of low Cl- ion solutions has often been used to induce cough, the prevalence and repeatability of the challenge has never been studied in detail. We, therefore, examined cough response in a group of 59 volunteers (aged 15-57 yrs; 34 females and 25 males; 20 smokers) to ascertain prevalence and repeatability. Each subject performed, 2 weeks apart, two identical cough challenges by inhaling four isosmolar solutions with decreasing Cl- ion concentrations (150, 75, 37.5 and 0 mM). Each solution was delivered by a DeVilbiss 65 ultrasonic nebulizer (mean output: 1.9 mL.min-1) for 1 min, and the number of coughs was counted during the inhalation. Cough response was expressed as number of coughs.min-1. Significance of response to the cough challenge was assessed on the basis of mean number of coughs.min-1 and 95% upper confidence limit (CL) of response to the Cl- free solution in the whole population. Cough threshold for a significant response was greater than 8 coughs.min-1. Out of 59 subjects, only 20 exceeded the cough threshold (34%) after inhaling the Cl- free solution. A concentration-response effect was evident only when inhaling 37.5 and 0 mM Cl- ion solutions. A significant cough response was more likely among females (p = 0.03). Smoking did not significantly affect the prevalence of response. Coefficients of repeatability of cough response to 37.5 and 0 mM Cl- solutions in 20 responders were equal to 10.1 and 12.6, respectively. We conclude that a significant cough response to low Cl- ion solutions develops in approximately 1 out of 3 of challenged volunteers and that repeatability is not satisfactory. We suggest that cough threshold and repeatability should be preliminarily assessed, especially when the challenge is used to study the antitussive activity of drugs.
Asunto(s)
Cloruros/administración & dosificación , Tos/etiología , Administración por Inhalación , Adolescente , Adulto , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Concentración Osmolar , Reproducibilidad de los Resultados , Cloruro de SodioRESUMEN
BACKGROUND: We compared the effect of nasal azelastine (0.56 mg/day), nasal beclomethasone dipropionate (BDP, 200 micrograms/day) and matched placebo on seasonal symptoms, nasal cytology, and the increase in bronchial responsiveness occurring during pollen season in a group of subjects with history of allergic rhinitis to grass pollens only. METHODS: The study was completed by nine subjects in the azelastine group, 13 subjects in the BDP group, and 13 subjects in the placebo group. Treatments were randomly administered for 6 weeks. Each subject recorded daily nasal, eye and chest symptoms and additional treatment requirement for the entire pollen season. Each subject performed nasal lavage 4 weeks into the pollen season. Bronchial responsiveness to methacholine was measured before and 4 weeks into the pollen season. Response was expressed as provocative dose causing a 20% fall in forced expiratory volume in 1 second in micromoles. RESULTS: Azelastine-treated subjects had significantly fewer nasal symptoms during week 4 (p < 0.05), and BDP-treated subjects had fewer nasal symptoms during week 4 (p < 0.05) and week 5 (p < 0.05) compared with subjects given placebo. Both treatments significantly reduced the need for additional medications. BDP, but not azelastine, treatment significantly reduced the percent of eosinophils recovered in nasal lavage (p < 0.05). Neither azelastine nor BDP protected against the increase in bronchial responsiveness to methacholine occurring during the pollen season. CONCLUSION: We demonstrated that both azelastine and BDP are effective treatments for nasal symptoms of seasonal allergic rhinitis after 4 weeks of therapy. However, we were not able to demonstrate an antiinflammatory activity of nasally administered azelastine. Nasal therapy with azelastine and BDP did not block the increase in bronchial responsiveness to methacholine caused by seasonal allergen exposure.
Asunto(s)
Beclometasona/administración & dosificación , Bronquios/efectos de los fármacos , Broncodilatadores/administración & dosificación , Cloruro de Metacolina , Líquido del Lavado Nasal/citología , Ftalazinas/administración & dosificación , Polen/inmunología , Rinitis Alérgica Estacional/tratamiento farmacológico , Administración Intranasal , Adolescente , Adulto , Bronquios/fisiopatología , Pruebas de Provocación Bronquial , Método Doble Ciego , Femenino , Humanos , Masculino , Poaceae , Rinitis Alérgica Estacional/patología , Rinitis Alérgica Estacional/fisiopatologíaRESUMEN
Thirteen patients with chronic obstructive pulmonary disease (COPD) performed forced vital capacity (FVC) maneuvers either immediately after a rapid inspiration (maneuver 1) or after a slow inspiration with a 4- to 6-s end-inspiratory pause (maneuver 2). Seated in a body plethysmograph, they breathed through a pneumotachograph. Inspirations were initiated from resting end-expiratory lung volume. Abdominal muscle activity was recorded by means of surface electrodes. With maneuver 1: (1) expiratory flows were 20 to 40% larger in the volume range 10 to 95% FVC; (2) peak expiratory flow was on average 30% higher; and (3) FEV1, expressed as percent of FVC, increased by about 8%. No substantial differences in the pattern of abdominal muscle activity occurred between maneuvers. The dependence of maximal flow-volume curves on the time course of the preceding inspiration is probably related in part to the viscoelastic elements present within the respiratory system, which, stretched during rapid inspirations, increase the effective elastic recoil during the FVC maneuver 1. This cannot occur with maneuver 2, because of stress relaxation of the viscoelastic elements during the 4- to 6-s breathhold preceding the FVC maneuver. Other factors (e.g., time constant inequality) might also be involved. In any case, the results imply that the inspiratory maneuver prior to FVC must be standardized.
Asunto(s)
Enfermedades Pulmonares Obstructivas/fisiopatología , Mecánica Respiratoria/fisiología , Músculos Abdominales/fisiopatología , Anciano , Electromiografía/estadística & datos numéricos , Volumen Espiratorio Forzado , Humanos , Masculino , Curvas de Flujo-Volumen Espiratorio Máximo , Persona de Mediana Edad , Pletismografía Total/estadística & datos numéricos , Factores de Tiempo , Capacidad VitalRESUMEN
OBJECTIVE: We measured lung function, in terms of lung volumes, forced expiratory flow-volume curves and diffusing capacity of carbon monoxide (DLCO), in a group of 61 patients with juvenile chronic arthritis (42 female; age range 5 to 33 years) to ascertain whether disease activity and treatment with low dose methotrexate (MTX) influenced these parameters. The whole population was divided into subgroups based on onset type (systemic, n = 27; pauciarticular, n = 12; polyarticular, n = 22), disease activity (active, n = 42; inactive, n = 19), and MTX treatment (treated, n = 27; not treated, n = 34). RESULTS: We found that maximal-mid expiratory flow (MMEF) was significantly reduced in patients with active disease (p < 0.025). The mean DLCO value, expressed as a percentage of the predicted value, and DLCO corrected for the hemoglobin value were lower than expected (67% and 80%, respectively). Multiple regression analysis showed that the forced vital capacity (FVC), forced expiratory flow in one second (FEV1) and DLCO were all correlated to the clinical subtype of the disease (p < 0.05, p < 0.02, p < 0.02, respectively), and MMEF was related to disease activity (p < 0.025). There was no evidence of any effect of MTX treatment on the pulmonary parameters. CONCLUSION: This study confirms that JCA is characterized by an impairment of lung function, mainly involving the small airways, and by interstitial damage. These changes are related to the clinical subtypes of the disease and to disease activity.
Asunto(s)
Artritis Juvenil/fisiopatología , Capacidad de Difusión Pulmonar , Adolescente , Adulto , Artritis Juvenil/tratamiento farmacológico , Monóxido de Carbono , Niño , Preescolar , Femenino , Humanos , Masculino , Metotrexato/uso terapéutico , Pruebas de Función RespiratoriaRESUMEN
Lambert-Eaton myasthenic syndrome (LEMS) is one of the neurologic paraneoplastic syndromes often found in patients with lung cancer. It is characterized by a generalized deficit of neurotransmitter release. Patients with small cell lung cancer (SCLC) in particular may develop LEMS, and SCLC is very often detected in patients affected by LEMS. LEMS is an autoimmune disease, and autoantibodies that interfere with neurotransmitter release by binding to presynaptic voltage-operated calcium channels (VOCCs) have been found in sera of patients with LEMS. Both human neuronal and SCLC cell lines express omega-conotoxin-sensitive VOCCs, and autoantibodies from patients affected by LEMS can precipitate these channels. We have now screened a large population of patients and control subjects in order to define the specificity and sensitivity of the anti-VOCC antibody assay. We have tested sera from 52 patients with LEMS with and without SCLC; 32 sera from patients with SCLC without LEMS, 31 from patients with non-SCLC, 34 from patients with inflammatory lung diseases, 17 from patients with other neurologic disorders, and 48 from healthy control subjects. We have found that a positive result with this radioimmunoassay is highly specific for LEMS, with or without SCLC, when the antibody titer is higher than 14.21 pM. Anti-VOCC antibodies have also been found in about 40% of patients with SCLC without LEMS, but they were absent in all the other populations tested. We can conclude that this serologic assay is a very useful aid in the diagnosis of LEMS, and it might be useful also for the early diagnosis of SCLC.
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Autoanticuerpos/análisis , Canales de Calcio/inmunología , Carcinoma de Células Pequeñas/inmunología , Síndrome Miasténico de Lambert-Eaton/inmunología , Neoplasias Pulmonares/inmunología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Células Pequeñas/complicaciones , Humanos , Síndrome Miasténico de Lambert-Eaton/complicaciones , Neoplasias Pulmonares/complicaciones , Neumonía/inmunología , Curva ROC , Sensibilidad y EspecificidadRESUMEN
We studied the reproducibility of early (EAR) and late (LAR) asthmatic response to allergen challenge in 13 asthmatic children (four girls, age range: 10 to 17 years) sensitized only to Dermatophagoides pteronyssinus (Dp). Further, changes in bronchial responsiveness to inhaled methacholine following LAR were examined by measuring PC20FEV1 methacholine after 24, 48, and 72 hours. We carried out two carefully controlled allergen challenges with the same allergen dose within 4 to 6 weeks, at least 3 weeks apart, in each subject. On each study day, a bronchial challenge with methacholine was performed before and at different intervals after LAR. We found that EAR (maximal % fall in FEV1 within the 1st hour) measured on two different days was highly reproducible (37.8% +/- 8.9 and 38.7% +/- 12.1; CR: 12.1; Ri: 0.92; CoV: 15.1). Late asthmatic response (maximal % fall in FEV1 between 2nd and 12th hour) was also highly reproducible (47.5% +/- 12.4 and 46.1% +/- 13.4; CR: 10.1; Ri: 0.96; CoV: 10.1). All patients showed increases in nonspecific bronchial responsiveness to methacholine after LAR. Geometric mean PC20 M measured before the two allergen challenges was 0.609 mg/mL and 0.620 mg/mL, respectively. These values significantly decreased 24, 48, and 72 hours after LAR (after 1st allergen challenge: 0.086, 0.116, and 0.295 mg/mL; after 2nd allergen challenge: 0.075, 0.141, and 0.263 mg/mL). Ratio changes in PC20 methacholine (pre-allergen PC20 methacholine/lowest postallergen PC20) were highly reproducible (Ri: 0.95). We concluded that bronchial response to allergen challenge and the associated increase in responsiveness to methacholine are highly reproducible in well selected asthmatic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Alérgenos/efectos adversos , Asma/inmunología , Pruebas de Provocación Bronquial , Adolescente , Alérgenos/inmunología , Antígenos Dermatofagoides , Niño , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Pruebas Cutáneas , Factores de TiempoRESUMEN
Inhaled furosemide has been shown to reduce the bronchoconstriction induced by several indirect stimuli, including ultrasonically nebulized distilled water (UNDW). Because the protective effect could be due to the inhibition of the Na(+)-2Cl(-)-K+ cotransport system of bronchial epithelium, we have compared the protective effect of inhaled furosemide with that of inhaled torasemide, a new and more potent loop diuretic, on UNDW-induced bronchoconstriction in a group of 12 asthmatic subjects. UNDW challenge was performed by constructing a stimulus-response curve with five increasing volume outputs of distilled water (from 0.5 to 5.2 ml/min) and the bronchial response expressed as the provocative output causing a 20% fall in FEV1 (PO20UNDW). On different days, each subject inhaled an equal dose (28 mg) of furosemide and torasemide in a randomized, double-blind, placebo-controlled study 5 min prior to an UNDW challenge. Furosemide and torasemide had no significant effect on resting lung function. The geometric mean value of PO20UNDW measured after placebo was 1.73 ml/min. This was significantly lower than that recorded after furosemide (4.25 ml/min; p < 0.025), but not after torasemide (3.05 ml/min; p = 0.07). Inhaled furosemide totally blocked bronchial response to UNDW in five subjects. In two of five subjects the response was also blocked by inhaled torasemide. A remarkable increase in diuresis was noted only after torasemide in most subjects. We conclude that inhaled furosemide has a better protective effect than does inhaled torasemide against UNDW-induced bronchoconstriction. However, the protective effect of furosemide is variable, with some asthmatic patients showing no change in bronchial response to UNDW.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Asma/tratamiento farmacológico , Broncoconstricción/efectos de los fármacos , Diuréticos/uso terapéutico , Furosemida/uso terapéutico , Sulfonamidas/uso terapéutico , Administración por Inhalación , Adolescente , Adulto , Asma/inducido químicamente , Asma/fisiopatología , Pruebas de Provocación Bronquial , Diuréticos/administración & dosificación , Diuréticos/farmacología , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Furosemida/administración & dosificación , Furosemida/farmacología , Humanos , Masculino , Persona de Mediana Edad , Nebulizadores y Vaporizadores , Sulfonamidas/administración & dosificación , Sulfonamidas/farmacología , Torasemida , Agua/efectos adversosRESUMEN
Arterial computed PO2 (PO2 com) was computed from SaO2 ear and finger capillary pH using equations of Severinghaus and Ellis, and compared with measured arterial PaO2 in 100 patients with chronic obstructive pulmonary disease (76 men, aged 42 to 82 yr). SaO2 ear ranged from 73 to 98%. There was no significant difference between SaO2 ear and SaO2 com (calculated from PaO2 and arterial pH), nor between arterial pH and pHc (capillary blood). Mean directly measured finger capillary oxygen tension, PcO2, was lower than PaO2 by 10.1 mm Hg +/- 5.4 SD. Mean bias of (PaO2-PO2 com) was -0.22 mm Hg +/- 2.6 SD. When subdivided by range, bias, and SD of mean bias of (PaO2-PO2 com) were -0.47 mm Hg +/- 2.5 with SaO2 ear less than 95% and 0.1 mm Hg +/- 2.9 with SaO2 ear greater than 95%. We conclude that PaO2 may be reliably computed from SaO2 ear and capillary pH when SaO2 ear is less than 98%.
Asunto(s)
Recolección de Muestras de Sangre/métodos , Oxígeno/sangre , Adulto , Anciano , Anciano de 80 o más Años , Arterias , Estudios de Evaluación como Asunto , Femenino , Humanos , Enfermedades Pulmonares Obstructivas/sangre , Enfermedades Pulmonares Obstructivas/fisiopatología , Masculino , Persona de Mediana Edad , PresiónRESUMEN
Recent evidence has suggested that human neoplastic patients show decreased blood histamine levels and cutaneous responses to intradermal histamine. In this study we evaluate the skin response to intradermal injections of histamine and IgE levels in 34 male patients with lung cancer (of which 21 had metastasis) and in 16 control subjects. Analysis of our data does not reveal any difference in the areas of wheal and flare between control subjects and lung cancer patients with or without metastasis. Moreover the evaluation of the different histologic cell type of lung cancer provides the same results. In addition, the sensitivity (Histamine Threshold Concentration) and reactivity (slopes) to histamine is not statistically different. No difference is found for IgE levels between controls and cancer patients. In the light of our finding we believe that in lung cancer patients skin response to intradermal histamine is not decreased, and therefore that the hypothesis concerning the existence of H1-histamine receptor antagonist released by tumour is not confirmed.
Asunto(s)
Histamina/inmunología , Inmunoglobulina E/sangre , Neoplasias Pulmonares/inmunología , Anciano , Humanos , Masculino , Persona de Mediana Edad , Pruebas CutáneasRESUMEN
Recent experimental and clinical reports have demonstrated that beta-adrenergic blockade impairs and beta-adrenergic stimulation enhances in vivo extrarenal potassium uptake in man. In some allergic patients extrarenal potassium disposal in vivo was reduced compared with normal subjects. In the present study we report that in vitro salbutamol induced potassium uptake by red blood cells may be reduced in some atopic patients. By using a ligand binding assay on cultured human A431 cells, we tried to determine whether in the sera of these atopic subjects there could be anti beta-adrenergic receptor autoantibodies. The results suggest that the observed reduced response to salbutamol of atopics' red blood cells does not depend on autoantibody activity.
Asunto(s)
Albuterol/farmacología , Autoanticuerpos/análisis , Eritrocitos/metabolismo , Hipersensibilidad/sangre , Potasio/sangre , Receptores Adrenérgicos beta/inmunología , Agonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/metabolismo , Adulto , Anticuerpos Monoclonales , Asma/sangre , Medios de Cultivo , Regulación hacia Abajo , Humanos , Concentración Osmolar , Potasio/metabolismo , Propanolaminas/metabolismo , Valores de Referencia , Células Tumorales Cultivadas/metabolismoRESUMEN
Any meaningful relationship of histamine concentrations, serum IgE concentrations, and the prevalence of cancer is unproven. Several reports indicate that tumor growth is associated with an increased synthesis of histamine. Others demonstrate decreased blood histamine levels and reduced cutaneous response to intradermal histamine in patients with solid malignant tumors. We have evaluated skin sensitivity to intradermal histamine injection, and IgE levels in cancer patients either with or without metastasis. Our data reveal no differences for histamine-induced wheal and flare areas between normal subjects and patients with neoplastic disease (with or without metastasis). In addition serum IgE concentrations were not statistically different. Skin sensitivity to intradermal histamine is not decreased in patients with cancer.
Asunto(s)
Histamina/farmacología , Neoplasias/fisiopatología , Piel/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Femenino , Histamina/sangre , Humanos , Inmunoglobulina E/análisis , Inyecciones Intradérmicas , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Concentración Osmolar , Análisis de Regresión , Pruebas CutáneasRESUMEN
The aim of this study is to determine whether some tests proposed as diagnostic of small airways obstruction (SAO) are useful in identifying the subjects at risk of developing chronic airflow limitation. Eighty five healthy male workers (46 nonsmokers and 39 smokers, aged 21-41 yrs), living in the same area and not exposed to occupational pollutants were re-examined after an interval of 6 yrs. At the first survey 39 had functional evidence of SAO as determined by the presence of one of: maximal mid-expiratory flow (MMEF) less than 65% of predicted value (pred); maximal expiratory flow when 25% forced vital capacity remains to be expired (Vmax25) less than 60% pred; closing capacity (CC) greater than 130% pred; 46 had all functional values in the normal range. We considered four subgroups: smokers and nonsmokers with and without SAO. The rate of decline in FEV1, the decline in %delta FEV1 and delta FEV1.height-3, have been evaluated and compared in the subgroups. Initial values of specific tests (MMEF, Vmax25, CC and slope of phase III) have been examined for a possible relationship with decline of FEV1. Statistical analysis of our data showed that only CC was related to FEV1 decline. However, there were no significant differences in FEV1 decline among the subgroups. We conclude that in young adult subjects functional characteristics of SAO have no predictive value for development of chronic airways obstruction.