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1.
J Biol Regul Homeost Agents ; 34(5): 1729-1737, 2020.
Article in English | MEDLINE | ID: mdl-33143407

ABSTRACT

Molecular characterization of IgE reactivity of specific individual components of allergenic extracts is now possible due to the technology of recombinant allergens derived from studies of molecular biology of allergic pathology. The identification of the immunoreactivity to single allergenic components in allergic subjects allows to specifically define her/his allergic profile and obtain the so-termed Component Resolved Diagnosis (CRD). Molecular allergens can be classified into those that induce the respiratory allergic reactivity and those that identify the food-related allergic pathology. It is also essential to identify those molecular allergens whose immunoreactivity is able to connect the two clinical conditions: respiratory symptoms and food allergy symptoms. The present study was conducted on 50 patients with a clinical history of hypersensitivity to pollen and/or allergy and positivity to Skin Prick Test. The sera were analyzed in our laboratories and the panel of recombinant allergens was applied in the case of positivity of the specific IgE. Of the 50 patients enrolled, 31 were selected as positive to 4 main pan-allergen Bet v1, Par j2, Art v1 and Phl p1; among these, 14 subjects showed one allergen-specific IgE towards natural extracts of tested foods even in absence of clinical history. CRD allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in: a) resolving genuine vs cross-reactive sensitization in poly-sensitized patients, b) assessing, in selected cases, the risk of severe, systemic vs mild, local reactions in food allergy, and c) identifying patients and triggering allergens for specific immunotherapy (ITS). In light of our results, we believe that the transition from a diagnostic based on the use of allergenic extracts to another one based on the use of single allergenic molecules that is able to define the specific allergenic profile of each patient, seems to be able to revolutionize the allergy diagnosis.


Subject(s)
Allergens , Female , Food Hypersensitivity/diagnosis , Humans , Immunoglobulin E , Male , Pollen/immunology , Skin Tests
2.
Eur Ann Allergy Clin Immunol ; 48(4): 116-22, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27425166

ABSTRACT

Near-fatal asthma (NFA) is described as acute asthma associated with a respiratory arrest or arterial carbon dioxide tension greater than 50 mmHg, with or without altered consciousness, requiring mechanical ventilation. Risk factors for near fatal asthma have not been fully elucidated. In 80-85% of all fatal events, a phenotype, characterized by eosinophilic inflammation associated with gradual deterioration occurring in patients with severe and poorly controlled asthma, has been identified. Regarding to the management, acute severe asthma remains a significant clinical problem, which needs to be identified to facilitate early and appropriate therapeutic interventions. The assessment relies on clinical signs, but additional information might be obtained from chest radiography or blood gas analysis. No investigation should delay the initiation of appropriate therapy. The goals of therapy are the maintenance of oxygenation, relief of airflow obstruction, reduction of airways edema and mucus plugging (with Increased use of medications such as beta-agonists via metered dose inhalers and nebulizers, oral and/or intravenous (other than by inhalation) corticosteroids and oral or intravenous theophylline) whereas supporting ventilation as clinically indicated. Of course, the emergency physician needs to consider the wide range of potential complications, as attention to these problems when managing severe acute asthma might significantly improve outcome. An understanding of the available agents and potential pitfalls in the management of NFA is mandatory for the emergency physician.


Subject(s)
Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Acute Disease , Asthma/diagnosis , Asthma/mortality , Combined Modality Therapy , Emergency Medical Services , Humans , Phenotype , Predictive Value of Tests , Respiration, Artificial , Risk Factors , Severity of Illness Index , Treatment Outcome
3.
Eur J Nucl Med Mol Imaging ; 39(6): 956-66, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22237846

ABSTRACT

PURPOSE: Radioimmunotherapy with (90)Y-ibritumomab tiuxetan has been used successfully used in the treatment of CD20-positive non-Hodgkin's lymphoma (NHL). Pretherapy imaging with (111)In-ibritumomab tiuxetan has been used in provisional dosimetry studies. Posttherapy imaging of (90)Y-ibritumomab tiuxetan for clinical use is appealing as it would simplify the data acquisition process and allow measurements of actual doses absorbed during treatment. METHODS: The study included 29 patients with non-Hodgkin's lymphoma, of whom 16 (group I) received a pretherapy (111)In-ibritumomab tiuxetan diagnostic study and (90)Y-ibritumomab tiuxetan treatment 1 week later, and 13 (group II) received only (90)Y-ibritumomab tiuxetan treatment. Planar imaging and blood sampling were performed in all patients. The doses absorbed by organs at risk were calculated using a whole-body average attenuation correction factor (relative dosimetry approach) and, in the case of the (111)In-ibritumomab tiuxetan image sets, also using organ-specific attenuation correction factors (absolute dosimetry method). Red marrow absorbed doses were based on gamma counting of blood samples. RESULTS: The estimated red marrow absorbed doses from (111)In and (90)Y data were equivalent. In all cases, the doses absorbed by organs at risk were found to be within prescribed limits. The relative dosimetry approach applied to both the (90)Y and (111)In data significantly underestimated the doses relative to those obtained with the (111)In absolute dosimetry method which is generally accepted as the reference method (MIRD 16). In the case of (111)In, the relative dosimetry approach values were highly correlated (R(2) = 0.61) with the reference method values. Relative dosimetry estimates may be adjusted multiplying by a correction factor of 2.8. The (90)Y-ibritumomab tiuxetan relative dosimetry data correlated poorly with the reference method values (R (2) = 0.02). CONCLUSION: Based on patient-specific dosimetry, the administered activity may be increased by an average factor of 2.4, indicating that most patients could be undertreated. The relative dosimetry approach based on planar imaging largely underestimates doses relative to reference values. Dosimetry based on planar bremsstrahlung imaging is not a dependable alternative to (111)In dosimetry.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Adult , Antibodies, Monoclonal/pharmacokinetics , Feasibility Studies , Female , Humans , Indium Radioisotopes/therapeutic use , Lymphoma, Non-Hodgkin/metabolism , Lymphoma, Non-Hodgkin/radiotherapy , Male , Radioimmunotherapy , Radiometry , Radiotherapy Dosage
4.
Biomarkers ; 11(3): 233-40, 2006.
Article in English | MEDLINE | ID: mdl-16760132

ABSTRACT

The study was designed to investigate whether exhaled breath condensate, obtained by cooling exhaled air in spontaneous breathing, could be a suitable matrix for toluene quantitative analyses. Nine healthy subjects were exposed for a short period (20 min) to a known concentration of toluene. Exhaled breath condensate samples were collected before and at the end of the exposure, while the environmental concentration of toluene was continuously monitored. Toluene was analysed by head-space gas-chromatography mass spectrometry, and assay repeatability was also estimated in vitro. Baseline and post-exposure measurement of hippuric acid, the urinary toluene metabolite, was performed to assess current toluene exposure. Before the exposure toluene concentrations in the exhaled breath condensate were lower than the detectable limit in all subjects, while after the exposure toluene was detectable with a median value 0.35 microg l-1 (range 0.15-0.55 microg l-1) in all the exhaled breath condensate samples. As compared with the standard calibration in distilled water, the curves obtained by exhaled breath condensate were linear and comparable with the range examined in vivo for toluene. A significant correlation was found between the environmental toluene levels and toluene in the exhaled breath condensate at the end of exposure. Furthermore, a significant relationship between increased exhaled breath condensate toluene levels and urinary hippuric acid after the exposure was found. In conclusion, exhaled breath condensate is a promising matrix for toluene assessment, although its application in humans requires further investigations.


Subject(s)
Air Pollutants, Occupational/analysis , Exhalation , Toluene/analysis , Adult , Calibration , Cold Temperature , Environmental Monitoring/methods , Environmental Monitoring/standards , Gas Chromatography-Mass Spectrometry , Hippurates/analysis , Humans , Male , Methods , Middle Aged , Occupational Exposure/analysis
5.
Pulm Pharmacol Ther ; 14(4): 321-7, 2001.
Article in English | MEDLINE | ID: mdl-11440561

ABSTRACT

Circulating and urinary levels of endothelin (ET), an endothelium-derived vasoconstrictive and mitogenic peptide have been reported to increase in patients with chronic obstructive pulmonary disease (COPD), but the mechanisms of these abnormalities are not fully understood. Our study objectives were to evaluate pulmonary and renal ET clearance in COPD patients during an acute exacerbation. Our participants included nine consecutive patients with moderate to severe COPD without signs of right heart failure admitted for acute exacerbation and ten healthy volunteers (HV) as controls. ET was detected by radioimmunoassay in venous and arterial blood as well as in a timed urine specimen. For each subject, arterial/venous immunoreactive ET ratio (ir-ETart/ir-ETven) was evaluated as an index of its pulmonary clearance. Creatinine clearance was employed in each case to obtain a corrected renal ir-ET clearance. Glomerular filtration rate (GFR) was also assessed by dynamic(99m)Tc-diethylenetriamine pentaacetic acid renal scintigraphy in six COPD patients during acute exacerbation and at recovery. The ratio ir-ETart/ir-ETven was comparable in COPD patients (0.75+/-0.12) and in HV (0.82+/-0.09). A significant difference was found with respect to 24 h ir-ET urinary excretion between COPD patients during exacerbation as well as at recovery (respectively 142.1+/-12.8 ng/24 h and 89.0+/-15.1 ng/24 h) and HV (65.1+/-10.1 ng/24 h). ET renal clearance was higher in COPD patients than in HV (29.2+/-5.2 ml min(-1)in COPD during exacerbation; 17.5+/-3.9 ml min(-1)at recovery and 13.6+/-2.4 ml min(-1)in HV, P<0.001). GFR was 69.4+/-10.0 ml min(-1)in COPD patients during exacerbation and it significantly increased at the recovery (95.5+/-20.9 ml min(-1)P<0.001). Corrected renal clearance of the peptide was significantly correlated to GFR values during the exacerbation (r=-0.81, P<0.05). Furthermore change in renal ET production resulted associated with changes in paCO(2)(r=0.83, P<0.001) and in paO(2)(r=-0.73, P<0.05). Acute exacerbation in COPD patients causes an increase in renal ET production which is partially reversible at the recovery, in the absence of significant changes in ET-1 circulating levels. ET might contribute to the renal response to hypoxaemia and hypercapnia in COPD.


Subject(s)
Endothelin-1/biosynthesis , Endothelin-1/pharmacokinetics , Kidney/physiology , Lung Diseases, Obstructive/complications , Acute Disease , Aged , Glomerular Filtration Rate , Humans , Hypercapnia/complications , Hypercapnia/etiology , Hypoxia/complications , Hypoxia/etiology , Male , Middle Aged
6.
Int J Tuberc Lung Dis ; 5(6): 551-8, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11409583

ABSTRACT

Rapidly progressive multidrug-resistant tuberculosis (MDR-TB) is well documented in human immunodeficiency virus (HIV) positive subjects, but it is not fully recognised in HIV-negative subjects in the familial environment. We report three cases of MDR-TB in three young HIV-negative subjects from the same family. All the patients showed signs of meningitis during the course of their disease, and in two cases a resistant strain of Mycobacterium tuberculosis was isolated in cerebrospinal fluid. Two of the three subjects died from neurological complications; the other was successful treated utilising both systemic and intrathecal therapy for tuberculous meningitis. By a retrospective analysis of DNA obtained from Lowenstein-Jensen cultures, the strains were confirmed as M. tuberculosis resistant to rifampicin and isoniazid, and were closely related in the two cases where specimens were available for analysis. The resistance was acquired in two patients initially infected with a susceptible strain; in the other patient, the resistance was present on the first sensitivity test for which results were available. This report demonstrates the high risk of fatality from MDR-TB for HIV-negative subjects in the absence of reliable early diagnostic and preventive tools. It also reinforces the concept that genetic susceptibility to M. tuberculosis may be an important factor in the clinical presentation and outcome of MDR-TB.


Subject(s)
Antitubercular Agents/therapeutic use , Isoniazid/therapeutic use , Mycobacterium tuberculosis/drug effects , Rifampin/therapeutic use , Tuberculosis, Meningeal/drug therapy , Tuberculosis, Meningeal/genetics , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/genetics , Adolescent , Adult , Culture Media , Fatal Outcome , Female , Humans , Male , Microbial Sensitivity Tests , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Recurrence , Survival Rate , Tuberculosis, Meningeal/mortality , Tuberculosis, Meningeal/transmission , Tuberculosis, Multidrug-Resistant/mortality , Tuberculosis, Multidrug-Resistant/transmission
7.
Water Res ; 35(17): 4237-42, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11791855

ABSTRACT

Regeneration of ion exchange resins with NaCl produces brine containing high concentrations of nitrate that can be difficult to remove using standard biological, physical, or chemical technologies. In this study. Halomonas campisalis (ATCC #700597) (Mormile et al., 1999) was shown to completely reduce nitrate at 125 g/L NaCl and pH 9. This organism was also used in experiments to determine nitrate-reduction rates and biomass yields. Kinetic parameters were measured separately with glycerol, lactate. acetate, ethanol, and methanol. The specific nitrate-reduction rate coefficient was highest in cultures amended with acetate, while lactate and glycerol (a natural osmoticum in hypersaline environments) had lower reduction rates. No evidence of nitrate reduction was observed when ethanol or methanol was provided as an electron donor. Kinetic modeling provided values for nitrate and nitrite-reduction rate coefficients and for biomass yields. Measured rates and yields were similar to reported parameters obtained from non-halophilic nitrate-reducing cultures under low salt concentrations. Therefore, for highly saline solutions, the use of halophiles to selectively remove nitrate from these brines may represent a viable treatment option.


Subject(s)
Halomonas/physiology , Nitrates/metabolism , Hydrogen-Ion Concentration , Ion Exchange Resins , Kinetics , Osmosis , Sodium Chloride/chemistry , Waste Disposal, Fluid
8.
Syst Appl Microbiol ; 22(4): 551-8, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10794143

ABSTRACT

The isolation and characterization of a denitrifying bacterium that is both moderately halophilic and alkaliphilic is described. The organism was isolated for use in the development of a bioprocess that could potentially reduce the costs of ion exchange resin regenerant disposal. The process of ion exchange, after resin regeneration, produces a briny, alkaline waste that is difficult and expensive to dispose. The biological removal of nitrate and subsequent reuse of these brines can potentially provide a cost-saving alternative to disposing of this waste product. To achieve our objective, a moderately halophilic, alkaliphilic bacterium was isolated from sediment samples taken from the salt plain of Alkali Lake in Washington State (USA). The haloalkaliphilic bacterium, designated strain 4A, is motile with rod-shaped cells that are 3 to 5 microm long and 1 microm wide. Electron acceptors used include oxygen, nitrate, and nitrite. In addition, it has similar specific nitrate reduction rates and biomass yields as non-halophilic denitrifying bacteria. It is capable of using a variety of electron donors. This organism can grow at NaCl concentrations ranging from 0.2 to 4.5 M with optimum growth occurring at 1.5 M and pH values ranging from 6 to 12 with 9.5 being the optimum pH. The temperature range for growth of strain 4A is 4-50 degrees C with optimal growth occurring at 30 degrees C. The G + C content is 66 mol%. Phylogenetic analyses based upon 16S rDNA gene sequence placed isolate 4A in the genus Halomonas. In addition, DNA-DNA hybridization experiments clearly indicate that it is a unique species. Phenotypic and phylogenetic studies indicate that isolate 4A represents a new species. We propose the name Halomonas campisalis for this species and strain 4A (ATCC 700597) as the type strain. Due to its denitrification ability, broad carbon utilization range and its high salinity and pH tolerance this organism, and similar ones, hold promise for the treatment of saline, alkaline waste.


Subject(s)
Halomonas/classification , Halomonas/isolation & purification , Nitrates/metabolism , Sodium Chloride/metabolism , Water Microbiology , Biodegradation, Environmental , DNA, Ribosomal/analysis , DNA, Ribosomal/genetics , Halomonas/genetics , Halomonas/physiology , Hydrogen-Ion Concentration , Industrial Waste , Ion Exchange , Molecular Sequence Data , Nitrites/metabolism , Phylogeny , RNA, Ribosomal, 16S/genetics
9.
Respir Med ; 91(6): 335-40, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9282235

ABSTRACT

The role of nitric oxide (NO) as a bronchodilator has been studied in humans with controversial results. The aim of the present study was to investigate the role of endogenous NO on bronchial tone by studying whether nitric oxide synthase (NOS) inhibition with NGnitro-L-arginine-methyl-ester (L-NAME) influences basal bronchial tone, or potentiates methacholine-induced bronchoconstriction. In a preliminary experiment in five subjects, a significant reduction in exhaled NO was found after delivering L-NAME (15 mg in saline) (from 3.9 +/- 1.2 to 2.4 +/- 1.1 nmol min-1, P < 0.05). In nine healthy non-smokers, specific airway conductance (SGAW), as a measure of airway calibre, was recorded after delivering, in a double-blind, controlled vs. placebo fashion, both nebulized L-NAME and saline, at baseline and after methacholine-induced bronchoconstriction. There was no significant difference between the baseline SGAW values before and after delivering L-NAME (0.264 +/- 0.04 and 0.267 +/- 0.05 cm H2O-1 s-1, respectively). After pre-treatment with L-NAME, SGAW values during methacholine-induced bronchoconstriction were not different in comparison to values obtained after saline inhalation. It is concluded that decreased endogenous NO does not influence bronchial tone in healthy people, nor does it modify methacholine-induced bronchoconstriction.


Subject(s)
Airway Resistance/drug effects , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide/physiology , Adult , Breath Tests , Bronchoconstrictor Agents , Double-Blind Method , Female , Humans , Male , Methacholine Chloride
10.
Appl Environ Microbiol ; 62(5): 1583-8, 1996 May.
Article in English | MEDLINE | ID: mdl-16535310

ABSTRACT

Forty-two samples taken from two landfills were monitored for CH(inf4) production and apparent steady-state H(inf2) concentration. The rates of methanogenesis in these samples ranged from below the detection limit to 1,900 (mu)mol kg (dry weight)(sup-1) day(sup-1), and the median steady-state hydrogen concentration was 1.4 (mu)M in one landfill and 5.2 (mu)M in the other. To further investigate the relationship between hydrogen concentration and methanogenesis, a subset of seven landfill samples was selected on basis of their rates of CH(inf4) production, H(inf2) concentrations, sample pHs, and moisture contents. Samples with H(inf2) concentrations of <20 nM had relatively small amounts of volatile fatty acids (VFAs) (undetectable to 18.6 mmol of VFA kg [dry weight](sup-1)), while samples with H(inf2) concentrations of >100 nM had relatively high VFA levels (133 to 389 mmol of VFA kg [dry weight](sup-1)). Samples with high H(inf2) and VFA contents had relatively low pH values (<=6.3). However, methanogenic and syntrophic bacteria were present in all samples, so the lack of methanogenesis in some samples was not due to a lack of suitable inocula. The low rates of methanogenesis in these samples were probably due to inhibitory effects of low pH and VFA accumulation, resulting from a thermodynamic uncoupling of fatty acid oxidation. As in other anaerobic ecosystems, H(inf2) is a critical intermediate that may be used to monitor the status of landfill fermentations.

11.
Respiration ; 63(5): 292-7, 1996.
Article in English | MEDLINE | ID: mdl-8885002

ABSTRACT

Searching for IgG and IgM against the mycobacterial antigen A60 has been recognized as a potential diagnostic tool for pulmonary tuberculosis. The role of detection of anti-A60 IgA in improving diagnostic accuracy of serology is not well known. In this study we measured with ELISA serum levels of both anti-A60 IgG and IgA in 216 subjects. 88 healthy volunteers (44 PPD- and 44 PPD+), 44 patients suffering from nontuberculous lung disease and 15 subjects with healed pulmonary tuberculosis constituted the control population; 69 patients with active pulmonary tuberculosis (35 cavitary forms, 26 productive forms and 8 miliary forms) were examined. The sensitivity of IgG test was 73.9% in pulmonary tuberculosis (77.1% in cavitary forms, 65.4% in productive forms, 87.5% in miliary forms); the specificity of the test was 95.9%. For the IgA test we observed a sensitivity of 72.5% (74.3 in cavitary forms, 69.2% in productive forms, 75.0 in miliary forms) and a specificity of 93.9%. Combination of the two tests increased the sensitivity to 84.0% (+10.1% compared to IgG test, +11.5% compared to IgA test); the specificity decreased to 92.5% (-3.4% vs. IgG test; -1.4 vs. IgA test). In conclusion, the combined use of evaluation of anti-A60 IgG and IgA increases the accuracy of serological diagnosis of pulmonary tuberculosis.


Subject(s)
Antigens, Bacterial/immunology , Immunoglobulin A/immunology , Tuberculin/immunology , Tuberculosis, Pulmonary/immunology , Adult , Female , Humans , Immunoglobulin A/analysis , Immunoglobulin G/analysis , Male , Middle Aged , Sensitivity and Specificity , Serologic Tests
12.
Ann Ital Med Int ; 10(4): 242-5, 1995.
Article in Italian | MEDLINE | ID: mdl-8718659

ABSTRACT

The relationship between growth hormone deficiency (GHd) and ventilatory function is not well understood. We studied 7 patients with GHd since childhood who had been adequately treated with replacement therapy until cartilage fusion. Together with 7 well-matched (age and body-type) healthy control subjects, they underwent spirometry including determination of residual volume, and lung diffusing capacity. Also recorded were maximal respiratory muscle pressure during inspiration (PImax) and expiration (PEmax). Patients with GHd showed a significant reduction in total lung capacity and vital capacity while residual volume and lung diffusing capacity remained unchanged. All patients had a significant reduction of both PImax and PEmax. Previously treated adult subjects with GHd present a persistent decrease in lung mobilizing volumes associated with reduced respiratory muscle strength. These alterations may have implications in the management of GHd in adult patients.


Subject(s)
Growth Hormone/deficiency , Respiration , Respiratory Muscles/physiopathology , Adult , Female , Humans , Male , Muscle Contraction , Respiration/physiology , Respiratory Function Tests
13.
Sarcoidosis ; 12(2): 118-23, 1995 Sep.
Article in English | MEDLINE | ID: mdl-8532958

ABSTRACT

Endothelin-1 (ET-1) is a vasoactive, mitogenic peptide that is variably increased in Bronchoalveolar Lavage Fluid (BALF) and immunohistochemically found in lung tissue of patients with Interstitial Lung Disease (ILD). To assess if endogenous ET-1 production is increased in ILD we evaluated 24 hour (24h) urine excretion of ET-1 in 20 patients with ILD and 10 healthy age-matched controls (HC). Eight patients with active pulmonary sarcoidosis (S), 6 with idiopathic pulmonary fibrosis (IPF) and 6 with focal lung fibrosis due to inactive pulmonary tuberculosis (hTB) were studied. Plasma ET-1 levels (ET-1pl, pg/ml) and 24h ET-1 levels in urine (ET-1ur, ng/24h) were measured by a specific radio-immunoassay. Determinations of ET-1p1 and ET-1ur were repeated in S and IPF patients after 30 days of prednisone (0.75 mg/kg/day) treatment. ET-1p1 concentrations were not different between HC (5.34 +/- 0.48), S (5.95 +/- 0.96), IPF (4.75 +/- 1.37) and hTB (5.97 +/- 1.05) groups. ET-1ur was significantly higher in S (189.50 +/- 60.57) than in HC (69.00 +/- 10.76), IPF (62.17 +/- 19.07) and hTB (82.00 +/- 24.97). After prednisone, ET-1ur in the S group decreased significantly (189.50 +/- 60.57 to 94.00 +/- 13.60), and the decrease paralleled the improved clinical status. In S patients, ET-1ur was not significantly correlated to the degree of respiratory impairment, but it was significantly correlated to the intensity of lymphocytic alveolitis (r = 0.80).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Endothelins/urine , Lung Diseases, Interstitial/urine , Sarcoidosis, Pulmonary/urine , Adult , Biomarkers/urine , Female , Humans , Lung Diseases, Interstitial/drug therapy , Male , Middle Aged , Prednisone/therapeutic use
14.
Monaldi Arch Chest Dis ; 50(2): 109-13, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7613540

ABSTRACT

Controlled short-term studies (< 6 months) have yielded conflicting results as to the steroid-sparing effect of methotrexate (MTX) and its effectiveness in treating patients with chronic corticosteroid-dependent asthma (CDA). In an open study, we treated 13 patients with MXT (7.5-20 mg.week-1) for > or = 12 months (range 54-72 weeks). After 12 weeks of treatment, the intake of steroids had fallen by 36 +/- 22% (mean +/- SD); the clinical score was not significantly different from baseline (1.7 +/- 0.44 vs 1.4 +/- 0.52). At 52 weeks, steroid intake was reduced by 87 +/- 23% and 9 of the 13 patients no longer required corticosteroids. Moreover, both the clinical and functional scores were significantly better with respect to run-in values forced expiratory volume in one second (FEV1) 75 +/- 6 vs 60 +/- 10% predicted; forced vital capacity (FVC) 84 +/- 10 vs 77 +/- 13% pred; arterial oxygen tension (PaO2) 11.3 +/- 1.0 vs 10.7 +/- 1.3 kPa (84.5 +/- 7.8 vs 80.6 +/- 9.6 mmHg). No serious side-effects were recorded during the study; transaminase levels were increased in 62% of cases. In patients affected by chronic corticosteroid dependent asthma, the steroid-sparing effects of methotrexate and clinical improvement were apparent after 6 months treatment.


Subject(s)
Asthma/drug therapy , Methotrexate/therapeutic use , Prednisolone/therapeutic use , Adult , Female , Forced Expiratory Volume/drug effects , Humans , Longitudinal Studies , Male , Methotrexate/administration & dosage , Middle Aged , Oxygen/blood , Prednisolone/administration & dosage , Prednisolone/adverse effects , Pulmonary Diffusing Capacity/drug effects , Spirometry , Transaminases/blood , Vital Capacity/drug effects
15.
Respiration ; 61(5): 263-8, 1994.
Article in English | MEDLINE | ID: mdl-7800957

ABSTRACT

Abnormalities in endothelin-1 (ET-1) pulmonary metabolism have been reported in patients with pulmonary hypertension, asthma and chronic obstructive pulmonary disease (COPD). In this study we have evaluated the 24-hour urinary excretion of ET-1 in COPD patients both during acute exacerbation and stable phase of the disease. ET-1 plasma and urinary levels were measured in 13 COPD patients on admission to the hospital for an acute exacerbation and at the recovery period. Ten healthy volunteers were also studied. Determination of plasma and 24-Hour urinary ET-1 levels were carried out with a radioimmunoassay test. Plasma ET-1 levels in COPD patients were similar during exacerbation and recovery and were not significantly different from those in the healthy subjects. 24-hour urinary excretion of ET-1 was increased in COPD patients during acute exacerbation; it decreased during recovery, but remained elevated when compared to normal subjects. A negative correlation was found between arterial oxygen pressure and ET-1 excretion; no correlation was found between plasma and urinary ET-1 values. In conclusion, COPD patients excrete higher amounts of ET-1 compared to healthy subjects. Urinary ET-1 values are further increased during acute exacerbation of the disease.


Subject(s)
Endothelins/urine , Lung Diseases, Obstructive/urine , Adult , Aged , Endothelins/blood , Female , Humans , Lung Diseases, Obstructive/blood , Male , Middle Aged , Radioimmunoassay
17.
Respiration ; 60(2): 89-95, 1993.
Article in English | MEDLINE | ID: mdl-8341860

ABSTRACT

Endothelin (ET) is an endothelial regulatory peptide present also in pulmonary tissue where it exerts several biological actions both on bronchial and vascular smooth muscle cells. It has been shown to increase in bronchoalveolar lavage fluid (BALF) from asthmatic patients; but changes in other chronic respiratory disease have not been well studied. We measured by a radioimmunoassay (RIA) ET-immunoreactive (IR) levels on BALF (BALF-ETIR, pg/ml) from 5 normal subjects (NS), 5 patients with chronic extrapulmonary disease (ED) without signs of lung involvement, 5 patients with allergic bronchial asthma (BA), 10 patients with idiopathic lung fibrosis (ILF) and 9 patients with miscellaneous interstitial lung disease (MILD). In 5/5 NS and 4/5 ED BALF-ETIR was lower than sensibility of RIA test used (0.8 pg/ml). BALF-ETIR was dosable in all patients with bronchopulmonary disease; means were 2.45 pg/ml in BA, 12.37 pg/ml in ILF, 2.90 pg/ml in MILD--Wilcoxon's rank test (two tailed) versus NS, p < 0.05. There was an inverse correlation between BALF-ETIR values and the degree of ventilatory impairment (forced vital capacity % of predicted value, r = -0.61 p < 0.01; forced expiratory volume in 1 s % of predicted value, r = -0.71 p < 0.01) and the level of arterial pressure of O2 (PaO2; r = -0.75 p < 0.01); a positive correlation was found with number of neutrophils/ml of BALF (r = 0.52 p < 0.01)--Spearman's rank correlation. Though rarely detected on BALF from normal lungs, ET increases on BALF in patients with bronchopulmonary disease, raising the question of its involvement in pathogenic mechanisms or evolution of bronchial asthma and interstitial lung disease.


Subject(s)
Asthma/metabolism , Bronchoalveolar Lavage Fluid/chemistry , Endothelins/analysis , Pulmonary Fibrosis/metabolism , Adult , Asthma/diagnosis , Female , Humans , Male , Middle Aged , Pulmonary Fibrosis/diagnosis , Radioimmunoassay , Respiratory Function Tests
18.
Drugs ; 46 Suppl 1: 111-4, 1993.
Article in English | MEDLINE | ID: mdl-7506147

ABSTRACT

Hypersecretion of mucus is the main feature of chronic bronchitis and is associated with an increased susceptibility to bronchial infections. Although airway inflammation is present in patients with chronic bronchitis and is recognised as a contributing factor in the development of bronchial hyper-reactivity and obstruction, the role of anti-inflammatory drugs in the treatment of chronic bronchitis has not been established. Nimesulide is a nonsteroidal anti-inflammatory drug that can modulate the function of neutrophils and block the effects of several inflammatory mediators. We found that a 3-week treatment course of nimesulide in patients with chronic mucus hypersecretion decreased sputum viscosity, thus significantly improving symptoms. The effect of nimesulide on the rheological properties of mucus was slower and weaker than that of classic mucolytics and was more likely to be related to a reduction in bronchovascular permeability. The clinical usefulness of nimesulide in chronic bronchitis deserves further investigation.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Bronchitis/drug therapy , Sulfonamides/therapeutic use , Chronic Disease , Humans
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