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Biomedical subjects

L Carratù

Publications and source records attributed to L Carratù.

At least 19 recordsLinked to original sources
PubMed2002

Nitric oxide attenuates platelet-activating factor induced nasal airway plasma extravasation in healthy subjects.

BACKGROUND: Paranasal sinuses and the nose are important sources of nitric oxide (NO) in humans but the relevance of NO production to the control of nasal airway plasma exudation and its response to inflammatory mediators such as platelet-activating factor (PAF) in healthy subjects is not well known. DESIGN: In this study we aimed to evaluate the effect of the nitric oxide synthase (NOS) inhibitor NG L-arginine methyl ester (L-NAME) on nasal airway plasma extravasation at baseline and after an acute challenge with PAF that induces most symptoms of rhinitis. Eleven healthy subjects were enrolled in the study. Plasma extravasation in the nasal airway was assessed by measuring the albumin content of nasal lavage. RESULTS: PAF challenge caused a significant increase in concentrations of albumin in the nasal lavage fluid (from 0.59 +/- 0.13 mg dL(-1) to 2.46 +/- 0.45 mg dL(-1)) after placebo. Pretreatment with L-NAME significantly prevented the increase of albumin in the nasal lavage fluid induced by PAF as compared to placebo (from 0.53 +/- 0.11 mg dL(-1) to 1.70 +/- 0.28 mg dL(-1); P < 0.005). CONCLUSION: Topical administration of a NO inhibitor is able to attenuate the nasal airway plasma extravasation induced by PAF, suggesting that NO release in vivo is involved in the nasal response to PAF.

Administration, Intranasal↗
PubMed2001

Abnormalities of renal endothelin during acute exacerbation in chronic obstructive pulmonary disease.

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.

Acute Disease↗
PubMed2001

Effect of nitric oxide inhibition on nasal airway resistance after nasal allergen challenge in allergic rhinitis.

BACKGROUND: Nitric oxide has been detected by chemiluminescence in the lumen of nasal airway, which is increased in nasal breathing in patients with seasonal rhinitis during a chronic exposure. The purpose of this study was to determinate the effect of a NO-synthase inhibitor NGL-arginine methyl ester (L-NAME) on nasal airway resistance (NAR) in patients with seasonal allergic rhinitis after an acute challenge to the allergen. METHODS: Nitric oxide levels in the nose were measured by the chemiluminescence method in nine non-atopic volunteers and in seven patients with seasonal rhinitis at rest and after an acute challenge with the allergen. NAR were measured by active anterior rhinomanometry. RESULTS: Basal nasal NO concentration in allergic rhinitis was 496.5 +/- 151.4 parts per billion (ppb). (n = 7) and it was not significantly different from levels found in the control group: 458.4 +/- 105.9 ppb (n = 9). The topical administration of L-NAME in allergic rhinitis reduced the NO concentration (338.6 +/- 99.3 ppb, P < 0.001; n = 7). In the rhinitic patients the challenge with the allergen did not modify the nasal NO levels (504.5 +/- 138.5 ppb). The application of the allergen after the pretreatment with placebo caused a significant increase in NAR (from 0.32 +/- 0.11 Pa s cm-3 to 1.01 +/- 0.12 Pa s cm-3, P < 0.001; n = 7). Pre-treatment with L-NAME did not prevent the increase in NAR induced by allergen challenge (from 0.36 +/- 0.15 Pa s cm-3 to 1.06 +/- 0.26 Pa s cm-3). CONCLUSIONS: The results indicate that nasal administration of a NOS inhibitor L-NAME, at doses capable of decreasing nasal NO levels, has no effect on NAR and it does not prevent the NAR increase induced by an acute challenge with allergen in subjects with seasonal rhinitis.

Administration, Intranasal↗
PubMed2001

Exhaled nitric oxide after inhalation of isotonic and hypotonic solutions in healthy subjects.

Airway nitric oxide (NO) homoeostasis is influenced by chemical and mechanical stimuli in humans; airway epithelium, which is an important site of NO production, is sensitive to osmotic challenge. The effect of inhaled hypotonic solutions on exhaled NO (eNO) is not known. In this study we evaluated the effect of ultrasonically nebulized distilled water (UNDW), a hypotonic indirect stimulus, on eNO levels. A total of 10 non-smoking healthy subjects were enrolled in the study. eNO was detected by chemiluminescence, and specific airway conductance (sGaw) was measured by plethysmography. Bronchial challenges with UNDW and with an isotonic solution were performed according to a double-blind experimental design. Baseline levels of eNO were 28.1+/-14.7 p.p.b. UNDW did not cause any significant change in sGaw (from 0.190+/-0.029 to 0.181+/-0.036 cm H(2)O x s(-1)). With respect to baseline values, the eNO concentration decreased significantly after inhalation of 8 or 16 ml of UNDW (from 26.0+/-13.1 to 17.2+/-8.5 and 16.6+/-7.7 p.p.b. respectively; P<0.001, n=10). After bronchial challenge with UNDW, eNO was significantly reduced in comparison with after inhalation of the isotonic solution. In five subjects, pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor NO synthesis, decreased NO levels from 21.7+/-8.5 to 10.0+/-3.3 p.p.b. Subsequent inhalation of 16 ml of UNDW did not cause any further decrease in NO levels (10.1+/-3.7 p.p.b.; not significant compared with L-NAME). We conclude that inhalation of aqueous solutions decreases eNO levels in healthy subjects, and that this effect is not associated with any significant change in airway calibre. The UNDW-induced decrease in eNO is not enhanced by pretreatment with the NO synthase inhibitor L-NAME, suggesting that inhaled solutions may interfere with the airway NO pathway in humans.

Adult↗
PubMed2000

The effect of platelet-activating factor (PAF) on nasal airway resistance in healthy subjects is not mediated by nitric oxide.

BACKGROUND: The nose is an important source of nitric oxide (NO) in man, but the relevance of NO production to the response to inflammatory mediators is not clear. METHODS: In this study, we evaluated the effect of NO inhibition on nasal airway resistance (NAR) at baseline, after an acute challenge with platelet-activating factor (PAF), a potent proinflammatory factor, and after an acute challenge with bradykinin (BK), both of which are mediators of allergic rhinitis in man. Eight healthy subjects were enrolled in the study. Nasal NO production was measured by the chemiluminescence method, and NAR was measured by active anterior rhinomanometry. RESULTS: Basal nasal NO concentration was 500.6+/-115.6 ppb; it significantly decreased after topical administration of the NO-synthase inhibitor L-NAME, and the NO-synthase substrate L-arginine caused a recovery in NO production. The administration of L-NAME did not cause any change in basal NAR. In a double-blind fashion, we performed nasal challenge with PAF and BK after topical pretreatment with either placebo or L-NAME. After placebo pretreatment, both PAF and BK caused a significant increase in NAR (respectively, from 0.29+/-0.11 Pa s cm(-3) to 0.75+/-0.21 Pa s cm(-3), and from 0.36+/-0.18 Pa s cm(-3) to 0.71+/-0.25 Pa s cm(-3); P<0.001, n=8). Pretreatment with L-NAME did not prevent the PAF-induced increase in NAR (from 0.31+/-0.10 Pa s cm(-3) to 0.71+/-0.27 Pa s cm(-3)), whereas it prevented the BK-induced increase in NAR (from 0.33+/-0.15 Pa s cm(-3) to 0.43+/-0.16 Pa s cm(-3)). CONCLUSIONS: Topical administration of the NO-synthase inhibitor L-NAME at doses sufficient to decrease NO nasal production does not prevent the PAF-induced increase in NAR, indicating that NO generation in vivo is not involved in the nasal response to PAF.

Adult↗
PubMed1997

Characterization of platelet-activating factor acetylhydrolase in human bronchoalveolar lavage.

Platelet-activating factor (PAF) is a mediator produced in human airways during acute and chronic inflammatory lung diseases. The levels of PAF are regulated by acetylhydrolase (AH), the enzyme that converts PAF to lyso-PAF. To determine whether AH was present in human bronchoalveolar lavage (BAL) fluid, BAL was obtained from normal donors (n = 18) and from adult patients with mild bronchial asthma (n = 15) or with lung fibrosis (n = 15). AH activity was consistently found in the cell-free BAL fluid. BAL-AH is an enzyme different from secretory phospholipase A2 and from plasma AH and erythrocyte AH. Furthermore, BAL-AH is inhibited as much as 95% by exposure to an oxygen radical-generating system (xanthine/xanthine oxidase). BAL-AH is significantly correlated with the number of BAL macrophages (rs = 0.63; p < 0.02). In addition, BAL macrophages release AH both spontaneously and after stimulation with tumor necrosis factor-alpha (TNF-alpha) (100 ng/ml). BAL-AH activity in patients with bronchial asthma (1.32 +/- 0.18 pmol of PAF converted to lyso-PAF/min) is significantly lower than that in normal donors (2.25 +/- 0.26 pmol/min; p < 0.001). In contrast, BAL-AH activity in patients with lung fibrosis (6.13 +/- 0.81 pmol/min) is higher than that found in normal donors (p < 0.01). The variations in BAL-AH activity in patients with bronchial asthma or lung fibrosis are due to a reduction and to an increase, respectively, in the number of active molecules rather than to changes in enzyme affinity. These data demonstrate that human BAL fluid contains an extracellular AH activity that inactivates PAF released in the airways. BAL-AH is secreted by alveolar macrophages and is highly sensitive to oxygen radical-induced damage. The secretion and inactivation of BAL-AH may influence the levels of this enzyme in BAL fluid during acute and chronic inflammatory lung diseases and, ultimately, regulate the proinflammatory activities of PAF in these disorders.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1996

Membrane lipid perturbation modifies the set point of the temperature of heat shock response in yeast.

Addition of a saturated fatty acid (SFA) induced a strong increase in heat shock (HS) mRNA transcription when cells were heat-shocked at 37 degrees C, whereas treatment with an unsaturated fatty acid (UFA) reduced or eliminated the level of HS gene transcription at 37 degrees C. Transcription of the delta 9-desaturase gene (Ole1) of Histoplasma capsulatum, whose gene product is responsible for the synthesis of UFA, is up-regulated in a temperature-sensitive strain. We show that when the L8-14C mutant of Saccharomyces cerevisiae, which has a disrupted Ole1 gene, is complemented with its own Ole1 coding region under control of its own promoter or Ole1 promoters of H. capsulatum, the level of HS gene transcription depends on the activity of the promoters. Fluorescence anisotropy of mitochondrial membranes of completed strains corresponded to the different activity of the Ole1 promoter used. We propose that the SFA/UFA ratio and perturbation of membrane lipoprotein complexes are involved in the perception of rapid temperature changes and under HS conditions disturbance of the preexisting membrane physical state causes transduction of a signal that induces transcription of HS genes.

Blotting, Northern↗
PubMed1996

IgA immune response against the mycobacterial antigen A60 in patients with active pulmonary tuberculosis.

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.

Adult↗
PubMed1995

Efficacy and tolerability of azithromycin versus amoxicillin/clavulanic acid in acute purulent exacerbation of chronic bronchitis.

An open randomized trial was conducted in 142 hospitalized and out-patients with acute purulent exacerbation of chronic bronchitis to compare the clinical efficacy and tolerability of azithromycin (n = 69) and amoxicillin/clavulanic acid (n = 73). Azithromycin (500 mg) was administered as a single dose for three days and amoxicillin/clavulanic acid (amoxicillin 875 mg-clavulanic acid 125 mg) was given b.i.d. for 8 days (8.16 +/- 1.18). Before therapy and 24-48 hours after the end of treatment, sputum culture (by positioning five orthodontal swabs at the opening of salivary gland ducts after a washing of the oral cavity with sterile saline solution to avoid oral contamination), chest X-rays, arterial blood gas analysis, trials of respiratory functions and routine blood tests were performed. In the azithromycin group (69 patients) the efficacy rate was 67.6% (46 patients: 34 cured and 12 improved); in 22 patients (32.4%) the treatment failed; 1 patient was not evaluated because of no follow-up. The overall efficacy rate in the amoxicillin/clavulanic acid group (73 patients) was 97.3% (71 patients: 60 cured and 11 improved); in 1 patient (1.4%) the treatment failed and 1 patient was a drop-out for side effects. All pathogens isolated before treatment were susceptible to the antibiotics administered. At the end of treatment microbiological efficacy was 67.1% in the azithromycin group and 98.6% in the amoxicillin/clavulanic acid group. The tolerability was judged good in both treatment groups. Side effects were observed in 1 patient treated with amoxicillin/clavulanic acid (diarrhea), which imposed interruption of treatment, and in 2 patients from the azithromycin group (gastralgia and biochemical laboratory tests: renal function).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Long-term treatment with methotrexate in patients with corticosteroid-dependent bronchial asthma.

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.

Adult↗
PubMed1995

Endothelin-1 excretion in urine in active pulmonary sarcoidosis and in other interstitial lung diseases.

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)

Adult↗
PubMed1994

Morphological transition in the human fungal pathogen Histoplasma capsulatum.

Considerable information has accumulated recently about specific genes of Histoplasma capsulatum that are expressed during the process of adaptation when the organism undergoes morphological transition at the onset of infection. The study of these genes is crucial to identify targets for the development of novel antifungal agents.

Histoplasma↗
PubMed1994

Increased 24-hour endothelin-1 urinary excretion in patients with chronic obstructive pulmonary disease.

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.

Adult↗
PubMed1993

Increased endothelin-like immunoreactive material on bronchoalveolar lavage fluid from patients with bronchial asthma and patients with interstitial lung disease.

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.

Adult↗
PubMed1993

Nimesulide in the treatment of chronic bronchitis.

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.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

The biology of the heat shock response in parasites.

The heat shock response is a general homeostatic mechanism that protects cells and the entire organism from the deleterious effects of environmental stress. It has been shown that heat shock proteins play major roles in many cellular processes and have a unique role in several areas of cell biology, from chronic degenerative diseases to immunology and from cancer research to interactions between host and parasite. In this review, Bruno Maresca and Luisella Carratu deal with some of the unique characteristics of the heat shock response in parasitic organisms.

Journal Article↗
PubMed1991

Endobronchial administration of iodine-131 B72.3 monoclonal antibody in patients with lung cancer.

We tested the feasibility of endobronchial administration of radiolabelled monoclonal antibodies (MoAbs) and the biodistribution of the radiotracer. Ten patients with histological confirmed adenocarcinoma or squamous cell carcinoma were studied. Nine received 470 muCi (103 micrograms) of Iodine-131-B72.3, a monoclonal antibody reacting against TAG 72 antigen, while one patient received 502 muCi (291 micrograms) of 131I-4C4, an indifferent antibody used for comparison in a negative control study. The radiolabelled antibody was administered through a flexible fiberoptic bronchoscope and placed on the tumour mass under visual monitoring. Scans with a large field-of-view gamma-camera showed retention of 131I-B72.3 at the tumour site up to 6-9 days in six of eight patients. No other organs were visualized with the exception of faint activity in the gastrointestinal tract, bladder and thyroid. On the contrary, the indifferent antibody 131I-4C4 was not retained at the tumour site 6 days after MoAb administration, and more prominent activity was found in the gastrointestinal tract. In one patient the study was not technically adequate because of failure of the delivery system. The vascular compartment contained less than 3% of the administered dose. We conclude that endobronchial administration is a feasible technique and allows stable and specific targetting of bronchial tumours. Furthermore, the low activity found in the plasma and other organs suggests that this approach may be used to deliver therapeutic doses of MoAbs to lung cancers.

Adenocarcinoma↗