Retrograde Instillation of Methylene Blue in the Difficult Diagnosis of BPF.

We report two cases in which we were able to diagnose bronchopleural fistula through retrograde methylene blue instillation during bronchoscopy. In the first case, methylene blue was injected through an abdominal drain, followed by air instillation and detected in the left bronchial tree, demonstrating the presence of a fistula in the lingula's bronchus. In the second case, methylene blue was injected into a pleural drain, through a breach on a surgical suture and detected in the right bronchial tree, demonstrating the presence of a fistula in the right inferior bronchus. The retrograde instillation of methylene blue, through a drain in the abdomen or the thoracic wall, is a safe, cheap, and practical method that allows the bronchoscopist to identify the presence of a fistula and, more importantly, to identify the exact point on the bronchial tree where a fistula is located. This provides the possibility of sealing the fistula with a variety of devices. It is our opinion that this procedure should be considered a primary method of diagnosis when a bronchopleural fistula is suspected and a drain on the thoracic or abdominal wall is positioned such that effusions are able to drain.

Bronchial glomus tumor mimicking a COPD exacerbation.

We report the case of a glomus tumor originating in the left main bronchus diagnosed in a 79 year old Caucasian man. A glomus tumor is an extremely rare neoplasm in the bronchi with nonspecific clinical features. Bronchoscopy allows the diagnosis through biopsy and subsequent histopathological examination of the tissue and in selected cases may represent a valid alternative to surgery permitting a radical tumor excision.

Near-fatal asthma phenotype in the ENFUMOSA Cohort.

BACKGROUND: Near-fatal asthma (NFA) is characterized by severe asthma attacks usually requiring intensive care unit admission. This phenotype of asthma has been studied mainly in acute conditions. METHODS: The aim of our study was to compare the clinical, functional and inflammatory characteristics of NFA patients with mild to severe asthmatics in stable conditions. We recruited 155 asthmatic patients from five centres of the European Network for Understanding Mechanisms of Severe Asthma: 67 patients with mild-to-moderate asthma controlled by low/medium doses of inhaled corticosteroids; 64 with severe asthma that, despite treatment with high doses of inhaled corticosteroids, long-acting beta2-agonists and for 1/3 also with regular oral corticosteroids, had at least one asthma exacerbation in the previous year; 24 with an NFA episode in the previous 5 years in the absence of inclusion criteria for the previous groups. All the patients were examined in stable conditions. RESULTS: NFA patients were taking less corticosteroids and were less compliant to prescribed asthma medications than the other two groups of patients. Lung function, blood gases, atopic status, sputum and blood inflammatory cell count of NFA patients were similar to mild-to-moderate, but not severe, asthmatic patients. CONCLUSIONS: In stable conditions patients with an NFA attack in the previous 5 years cannot be distinguished from patients with mild-to-moderate asthma, while they are different from severe asthmatics both in terms of lung function and of airway inflammation. The risk factor that characterizes this group of patients is reduced usage of prophylactic corticosteroids.

Ectopic thymoma simulating a pericardial cyst.

We present a case of a 53 year old man with a thymoma near the pericardium, a rare ectopic localisation of thymoma. A round radiodensity found at the right cardiophrenic angle was initially suspected at the echocardiography to be a pericardial cyst. The diagnosis of thymoma was made only after histopathological examination of the surgically re-sected lesion.

COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma.

BACKGROUND: Squamous cell carcinoma has a stronger association with tobacco smoking than other non-small cell lung cancers (NSCLC). A study was undertaken to determine whether chronic obstructive pulmonary disease (COPD) is a risk factor for the squamous cell carcinoma histological subtype in smokers with surgically resectable NSCLC. METHODS: Using a case-control design, subjects with a surgically confirmed diagnosis of squamous cell carcinoma were enrolled from smokers undergoing lung resection for NSCLC in the District Hospital of Ferrara, Italy. Control subjects were smokers who underwent lung resection for NSCLC in the same hospital and had a surgically confirmed diagnosis of NSCLC of any histological type other than squamous cell. RESULTS: Eighty six cases and 54 controls (mainly adenocarcinoma, n = 50) were enrolled. The presence of COPD was found to increase the risk for the squamous cell histological subtype by more than four times. Conversely, the presence of chronic bronchitis was found to decrease the risk for this histological subtype by more than four times. Among patients with chronic bronchitis (n = 77), those with COPD had a 3.5 times higher risk of having the squamous cell histological subtype. CONCLUSIONS: These data suggest that, among smokers with surgically resectable NSCLC, COPD is a risk factor for the squamous cell histological subtype and chronic bronchitis, particularly when not associated with COPD, is a risk factor for the adenocarcinoma histological subtype.

An unusual case of congenital short trachea with very long bronchi mimicking bronchial asthma.

Case reports of a short trachea with early branching of the main bronchi are uncommon. The case is presented of a 64 year old woman with upper airway obstruction due to this anatomical abnormality which caused breathlessness and wheezing that was misdiagnosed (and treated) as bronchial asthma for many years.

Pulmonary blastoma: case report in an adult.

We present a case of biphasic pulmonary blastoma, a rare primary malignant lung neoplasm, in a 48 year old man. Despite its resection followed by postoperative chemotherapy, the neoplasm recurred and the patient survived only 41 months after the diagnosis.

Antioxidant activity of carbocysteine lysine salt monohydrate.

BACKGROUND: Reactive oxygen radicals are involved in many respiratory diseases, including chronic obstructive pulmonary disease (COPD). Carbocysteine lysine salt monohydrate (CLS) is a mucoactive drug effective in the treatment of bronchopulmonary diseases characterized by mucus alterations, including COPD. In the present study, the antioxidant activity of CLS was studied in vitro in three different oxygen radical producing systems, i.e. bronchoalveolar lavages (BAL) from patients affected by COPD, ultrasound treated human serum and cultured human lung endothelial cells challenged with elastase. METHODS: BAL, exposed or not to different concentrations of CLS (1.5-30 mM), was assayed for free radical content by fluorometric analysis of DNA unwinding (FADU) or by cytochrome c reduction kinetics. Human serum was treated with ultrasound in the presence or absence of CLS (1.5, 2.5 mM) or N-acetyl cysteine (NAC; 4, 5 mM) and assayed for free radical content by FADU. Human endothelial cells cultured in vitro from pulmonary artery were incubated with elastase (0.3 IU/mL), in the presence or absence of glutathione (GSH; 0.65 mM) or CLS (0.16 mM). The supernatant was tested for cytochrome c reduction kinetics whereas cell homogenates were assessed for xanthine oxidase (XO) content by SDS-PAGE. RESULTS: Results showed that CLS is more effective as an in vitro scavenger in comparison to GSH and NAC. CLS reduced the damage of DNA from healthy donors exposed to COPD-BAL and was able to quench clastogenic activity induced in human serum by exposure to ultrasound at concentrations as low as 2.5 mM. NAC protect DNA from radical damage, starting from 5 mM. In human lung endothelial cells cultured in presence of elastase, CLS (0.16 mM) decreased xanthine oxidase activity. CONCLUSIONS: These results suggest that CLS could act by interfering with the conversion of xanthine dehydrogenase into superoxide-producing xanthine oxidase. The antioxidant activity of CLS could contribute to its therapeutic activity by reducing radical damage to different lung structures.

Congenital diaphragmatic hernia in an adult simulating a pleural liposarcoma.

We report the case of a 32-year-old man with the onset of exercise-related dyspnea, chest pain and chest radiography simulating a pleural effusion. The computed tomography of the chest showed signs suggesting pleural liposarcoma. Because of these findings, a videothoracoscopy was performed which surprisingly showed the presence in the left pleural space of intrapleural omentum and spleen. This report underlines that the clinical manifestations of Bochdalek hernia in adults are variegate and in most cases preoperative diagnosis is not possible.

[Hemoptysis in a patient with post-obstructive pneumonia due to a broncholith]. / Emottisi in un paziente con polmonite post-ostruttiva da broncolita.

A case of a 51-year-old man admitted to the hospital for hemoptysis after a three-week history of fever and cough is presented. The chest x-ray film revealed consolidation in the left upper lobe. Because microbiologic studies of the bronchial lavage showed the grew of Pseudomonas aeruginosa, the patient was treated with piperacilline and pefloxacin. Haemoptysis and abnormal temperature was persistent for several days. Revaluation of the chest x-ray permitted to discover a little calcified nodule of 1 mm diameter. CT scan of the thorax confirmed the consolidation of the left upper lobe and the little calcification. A second fiberoptic bronchoscopy was performed in 10th day, using a bronchoscope with a smaller diameter; it was possible to observe the occlusion of the subsegment bronchus LB 1&2 due to a mobile protruding mass. The mass was gentle removed by the use of alligator bioptic forceps; it presented as a grey, hard, 2 mm diameter body with irregular surface like a "floating mine". On microscopical examination of the mass, aspergillus hyphae appeared as broad septate filaments. Culture of the samples were negative. Haemoptysis and fever stopped after FOB. Chest x-ray in 19th day was negative: consolidation and calcification were absent.

Detection of xanthine oxidase activity products by EPR and HPLC in bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease.

Xanthine oxidase (xanthine: oxygen oxidoreductase, EC 1.1.3.22), a molybdenum-containing hydroxylase that produces superoxide and uric acid from purine substrates and molecular oxygen, is involved in the oxidative stress underlying several human pathologies including lung diseases. An enzymatic activity similar to xanthine oxidase was previously reported in bronchoalveolar lavage fluid of patients with chronic obstructive pulmonary disease (COPD-BAL), by fluorometric analysis of DNA unwinding and cytochrome c reduction kinetics. Here we report the detection of xanthine oxidase activity products by electron paramagnetic resonance (EPR) in presence of the spin-trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and reversed-phase high-performance liquid chromatography (RP-HPLC) in COPD-BAL (n = 14, average age of patients 65 years, range 38-81) and BAL from healthy nonsmoker controls (n = 6, average age 64 years, range 44-73). Superoxide DMPO adducts were detected in COPD-BAL and in an in vitro system containing xanthine and xanthine oxidase (XA/XO), but not in BAL controls and when superoxide dismutase (SOD, 1000 I.U./ml) was added to COPD-BAL. The HPLC analyses after addition of xanthine showed production of uric acid in COPD-BAL and in the XA/XO system but not in BAL controls. These results support the involvement of xanthine oxidase in the mechanisms of superoxide production by BAL supernatant, which increases oxidative stress in chronic obstructive pulmonary disease.

In chyloptysis, SP-A affects the clearance of serum lipoproteins entering the airways.

Serum lipoproteins may enter the airways and appear in sputum (chyloptysis) when the lymphatic circulation is impaired by inflammation, neoplasia, or an abnormal proliferation of smooth muscle cells. While analyzing the bronchoalveolar lavage fluid of a patient with chyloptysis, we noticed that surfactant could not be separated from contaminating serum lipoproteins and speculated that lipoproteins might interact with surfactant components. To clarify this point we immobilized surfactant protein (SP) A on microtiter wells and incubated it with 125I-labeled very low density lipoproteins (VLDLs), low-density lipoproteins, and high-density lipoproteins. We found that SP-A binds lipoproteins. Studying in greater detail the interaction of SP-A with VLDLs, we found that the binding is time and concentration dependent; is inhibited by unlabeled lipoproteins, phospholipids, and antibodies to SP-A; is increased by Ca2+; and is unaffected by methyl alpha-D-mannopyranoside. Whole surfactant is a potent inhibitor of binding. Furthermore, we found that SP-A increases the degradation of VLDLs by alveolar macrophages and favors the association of VLDLs with alveolar surfactant. We conclude that SP-A influences the disposal of serum lipoproteins entering the airways and speculate that binding to alveolar surfactant might represent an important step in the interaction between exogenous substances and the lung.

Xanthine oxidase activity in bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a serious respiratory pathology characterized by irreversible limitation of expiratory flow and includes chronic obstructive bronchitis, chronic airflow limitation, and emphysema. To determine whether xanthine oxidase activity increased in the airspaces of COPD patients, we examined bronchoalveolar lavage fluid (BAL) from COPD patients recruited during a 2-year clinical study. Filtered BAL supernatant from COPD patients and healthy nonsmoking controls was examined by fluorometric analysis of DNA unwinding (FADU) and spectrophotometric assays (cytochrome c reduction kinetics and uric acid kinetics). Compared to controls, filtered BAL supernatant of subjects with COPD exhibited a detectable clastogenic activity probably related to superoxide production. The method of BAL preparation as an acellular system strongly suggests that superoxide production may be due to xanthine oxidase activity.

[Pyrrolidone and piperidone derivatives with antihistaminic and antianaphylactic activities. Synthesis and pharmacological study]. / Derivati pirrolidonici e piperidonici ad attivita' antiistaminica ed antianafilattica. Sintesi e studio farmacologico.

The preparation of several derivatives to oxatomide (A), with the benzimidazolinone moiety replaced by another heterocyclic residue is described. In some cases changes to the basic chain of (A) were also considered. All the new compounds were evaluated as antihistaminics (H1) and antianaphylactics. The derivatives where the heterocyclic moiety was an unsubstituted or phenylsubstituted 2-pyrrolidone or 2-piperidone residue showed antihistaminic and antianaphylactic activities similar to those of oxatomide while modification of the basic side chain with elimination of the benzhydryl group, gave a complete loss of activity. The pharmacological screening was completed by the evaluation of the barbiturate induced sleep prolongation and of acute toxicity.

[Methionine derivatives with liver protecting activity]. / Derivati della metionina ad attività epatoprotettrice.

Some methionine derivatives with the amine group acylated with an aliphatic group bearing a free, esterified or etherified thiol group in the omega position were prepared and tested for protection against CCl4, paracetamol, ethyl alcohol and ethionine intoxication. Acid (XIV) (MG 28013) (Table I) and some of its alkyl derivatives (XVIII) (MG 28228) and (XIX) (MG 28226) proved to have significant activity in these tests. A more in-depth study on MG 28226 however indicated a slight intolerance when subacute toxicity was examined (90 gg).

[New derivatives of clofibrate and probucol. Preliminary study of their hypolipemic activity]. / Nuovi derivati del clofibrato e del probucol. Studio preliminare dell'attività ipolipemizzante.

The preparation is reported of compounds with a free or esterified hydroxyisobutyric acid grouping characteristic of clofibrate, on various supporting molecules related to clofibrate itself or to probucol. Some compounds showed clear hypolipemic activity and for one compound (MG 6893) the effect was not accompanied by hepatomegalia.

Pantetheine and pantethine esters with hypolipidemic nicotinic acid derivatives.

We prepared several esters of pantetheine and pantethine, respectively, with 3-pyridineacetic acid and with 3-(3-pyridinemethoxycarbonyl)propionic acid, and we tested these products for their capacity to lower serum non-esterified fatty acids and triglycerides in normal animals. Among the products thus tested, the tetraester of pantethine with 3-(3-pyridinemethoxycarbonyl)propionic acid (MG 28362) displayed marked hypolipidemic activity, the action being of uncommonly long duration.