S. Petruzzelli

High sensitivity of Salmonella TA102 in detecting hexavalent chromium mutagenicity and its reversal by liver and lung preparations.

The recently developed strain TA102, particularly suited to the detection of oxidative mutagens (Levin et al., 1983), was the most sensitive out of 9 strains of S. typhimurium his- in revealing the mutagenicity of Cr(VI) compounds (sodium dichromate, calcium chromate and chromium trioxide). The rank of sensitivity was the following: TA102, TA100, TA97, TA92, TA1978, TA98, TA1538 and TA1537, TA1535 being the only insensitive strain. Cr(III) compounds (chromic acetate, chromic nitrate and chromic potassium sulfate) were totally inactive with all strains. The direct mutagenicity of Cr(VI) was markedly decreased, through NADPH-requiring mechanisms, by rat-liver S9 fractions and, to a lower extent, by human lung S12 fractions, which supports the hypothesis of a metabolically regulated threshold in chromium pulmonary carcinogenicity.

CT evaluation of chronic thromboembolic pulmonary hypertension

Eight patients with chronic thromboembolic pulmonary hypertension (CTPH) that had been demonstrated by perfusion lung scan, pulmonary arteriography, and right heart catheterization had their pulmonary circulation evaluated by CT. Eight subjects without lung pathology were also studied for comparison. High resolution CT from apex to base with 1 cm thick sections after intravenous injection of contrast medium was performed in each individual. Emboli lodged in main pulmonary arteries on arteriography were regularly shown by CT, whereas those in segmental or smaller arteries were not detected. Diameters of the main pulmonary arteries measured on CT correlated with systolic pulmonary artery pressure (p < 0.001). The ratio between diameters of segmental arteries and the corresponding bronchi (A/B ratio) on CT was > 1 in 72 of 144 examined pulmonary segments (18 segments for each patient) in patients with CTPH. The ratio was > 1 in only 10 of 144 examined segments in normal control subjects. Dilatation of bronchial arteries was present in four of eight patients with CTPH. The parenchymal density in patients with CTPH was significantly higher in the axial than in the middle or peripheral lung compartments. In conclusion, CT may help with the diagnosis of CTPH by detecting thrombi of main arteries and by showing characteristic findings; moreover, it is accurate in estimating pulmonary arterial pressure secondary to thromboembolic obstruction.

Presence and persistence of serum anti-benzo[apyrene diolepoxide-DNA adduct antibodies in smokers: Effects of smoking reduction and cessation

Among biomarkers of tobacco smoke (TS)‐induced genotoxic damage, benzo[a]pyrene diolepoxide‐DNA adducts (BPDE‐DNA) are extensively studied. Adducted DNA becomes antigenic and antibodies anti‐BPDE‐DNA (BPDE‐DNA‐Abs) may be found in serum of exposed subjects. Little is known about the persistence of BPDE‐DNA, and no study has been performed to evaluate the persistence of BPDE‐DNA‐Abs after cessation of exposure. Fifty heavy smokers, enrolled in a smoking cessation program with nicotine patch substitution therapy, were evaluated for the presence of BPDE‐DNA‐Abs before (w0) and 1, 3, 6 and 12 weeks (w1–12) after the start of the program. Nicotine or placebo patches were randomly assigned to the subjects. BPDE‐DNA‐Abs were determined in serum by non‐competitive ELISA. After the start of the cessation program, 28 subjects quit smoking (group Q) and the other 22 reduced by about 75% the number of cigarettes smoked per day (group R). At the start of the program (w0) 8% of subjects were positive. At w1 the prevalence of positivity had increased both in subjects who quit smoking (Q: 21%) and in subjects who had reduced the number of cigarettes per day (R: 27%). Positivity remained stable up to w12 (21%) for group Q, whereas it increased to 41% in group R. Serum BPDE‐DNA‐Abs can be detected in smokers, and their persistence for months after smoking cessation suggests their usefulness for relatively long‐term surveys. The low percentage of positivity in actual heavy smokers and the increase in antibody positivity with smoking cessation or reduction must be taken into account when interpretating serum BPDE‐DNA‐Ab measurement in exposed individuals. Int. J. Cancer, 70:145–149, 1997.

ICAM-1-independent adhesion of neutrophils to phorbol ester-stimulated human airway epithelial cells

Intercellular adhesion molecule-1 (ICAM-1) is the only inducible adhesion receptor for neutrophils identified in bronchial epithelial cells. We stimulated human airway epithelial cells with various agonists to evaluate whether ICAM-1-independent adhesion mechanisms could be elicited. Phorbol 12-myristate 13-acetate (PMA) stimulation of cells of the alveolar cell line A549 caused a rapid, significant increase in neutrophil adhesion from 11 +/- 3 to 49 +/- 7% (SE). A significant increase from 17 +/- 4 to 39 +/- 6% was also observed for neutrophil adhesion to PMA-stimulated human bronchial epithelial cells in primary culture. Although ICAM-1 expression was upregulated by PMA at late time points, it was not affected at 10 min when neutrophil adhesion was already clearly enhanced. Antibodies to ICAM-1 had no effect on neutrophil adhesion. In contrast, antibodies to the leukocyte integrin beta-chain CD18 totally inhibited the adhesion of neutrophils to PMA-stimulated epithelial cells. These results demonstrate that PMA stimulation of human airway epithelial cells causes an increase in neutrophil adhesion that is not dependent on ICAM-1 upregulation.Intercellular adhesion molecule-1 (ICAM-1) is the only inducible adhesion receptor for neutrophils identified in bronchial epithelial cells. We stimulated human airway epithelial cells with various agonists to evaluate whether ICAM-1-independent adhesion mechanisms could be elicited. Phorbol 12-myristate 13-acetate (PMA) stimulation of cells of the alveolar cell line A549 caused a rapid, significant increase in neutrophil adhesion from 11 ± 3 to 49 ± 7% (SE). A significant increase from 17 ± 4 to 39 ± 6% was also observed for neutrophil adhesion to PMA-stimulated human bronchial epithelial cells in primary culture. Although ICAM-1 expression was upregulated by PMA at late time points, it was not affected at 10 min when neutrophil adhesion was already clearly enhanced. Antibodies to ICAM-1 had no effect on neutrophil adhesion. In contrast, antibodies to the leukocyte integrin β-chain CD18 totally inhibited the adhesion of neutrophils to PMA-stimulated epithelial cells. These results demonstrate that PMA stimulation of human airway epithelial cells causes an increase in neutrophil adhesion that is not dependent on ICAM-1 upregulation.

Early and Late Follow-Up of Pulmonary Embolism

This study includes 61 patients referred with pulmonary embolism (PE) during 1 year. At admission, blood gas analysis, chest radiography and pulmonary lung scan were obtained in each patient; in a subset of patients pulmonary angiography was also performed to make the definitive diagnosis. Patients were treated with heparin and, later, with oral anticoagulants. Blood gas analysis, chest radiograph and perfusion lung scan were repeated 7, 30, 180 and 365 days after the diagnosis to evaluate the usefulness of these techniques in the follow-up of PE. Arterial hypoxemia and perfusion impairment recovered in parallel, both in the acute phase after embolism (7 days) and later up to 1 year. The great majority of recovery occurred within the first month after embolization. Radiographic signs compatible with PE tended to decrease early and disappeared almost completely after 30 days. Arterial blood gas analysis and perfusion scintigraphy detected 8 recurrences of PE that would be missed by chest radiograph. Arterial hypoxemia and the enlargement of descending pulmonary artery were positively correlated with the number of unperfused lung segments and, thus, may help predicting the severity of perfusion impairment in the acute stage. In conclusion, blood gas analysis and chest radiograph may be employed with or without perfusion lung scan to follow patients with PE up to 1 month after embolization; after that, only blood gas analysis and perfusion lung scan may give useful information about recovery from or recurrence of PE.

A Way to Select on Clinical Grounds Patients with High Risk for Pulmonary Embolism: A Retrospective Analysis in a Nested Case-Control Study

We studied 196 patients with suspicion of pulmonary embolism (PE), subsequently confirmed in 98 by positive pulmonary angiography and excluded in 98 by normal or near-normal perfusion lung scan. Patients had a clinical questionnaire for history, and, soon after. a radiograph, blood gas analysis, and an ECG. Clinical and instrumental signs were matched in patients with confirmed and unconfirmed PE to find those more frequent in embolic patients and, thus, more characteristic of PE. The following were: previous PE, immobilization and thrombophlebitis (p < 0.05); dyspnea and cough (p < 0.05); enlarged descending pulmonary artery (DPA), enlarged right heart, pulmonary infarction, Westermark sign (p < 0.001), and elevated diaphragm (p < 0.05); hypoxemia. No ECG sign was more frequent in PE. Thereafter, all variables were processed separately with a logistic multiple regression analysis and those significantly associated to PE were tested in a final logistic model that was able to predict the actual result of angiography or scintigraphy; accordingly, previous PE, immobilization, thrombophlebitis, enlarged DPA, pulmonary infarction, Westermark sign, hypoxemia were significantly associated with a high risk of PE (from 2.8 to 15 times greater than in patients without these signs). Therefore, we may conclude that clinical assessment and noninvasive tests may help to detect patients at higher risk for PE where heparin coverage should be started while waiting for conclusive diagnostic procedures.

Metabolic activation and deactivation of mutagens by preparations of human lung parenchyma and bronchial tree.

69 S12 preparations of human lung (43 of peripheral lung parenchyma and 26 bronchial preparations) were assayed for their ability to activate procarcinogens to mutagenic metabolites in the Ames test or to lower the mutagenic response of direct-acting compounds. No sample activated polycyclic aromatic hydrocarbons, such as 3-methylcholanthrene, benzo[a]pyrene or its metabolites 3-hydroxy-B(a)P and B(a)P-trans-7,8-diol, and only borderline effects were observed with cigarette-smoke condensates. Conversely, some activating ability was detected in the case of 2-aminofluorene and of cyclophosphamide. The same samples produced a slight decrease of mutagenicity of epichlorohydrin and ICR-191 and a more pronounced loss of activity of sodium dichromate and 4-nitroquinoline N-oxide.

Presence of epoxide hydrolase and glutathione S-transferase in human pulmonary alveolar macrophages

SummaryPulmonary alveolar macrophages (PAMs) were obtained from 11 patients by bronchoalveolar lavage. Epoxide hydrolase and glutathione S-transferase in sonicated PAMs were measured using benzo(a)pyrene-4,5-oxide as the substrate.The activity of epoxide hydrolase was 0.24±0.10 nmol/min/mg protein (mean±SD), and of glutathione S-transferase 0.22±0.12 nmol/min/mg protein.There was a significant difference in enzyme activities in the PAMs from smokers and non-smokers. Epoxides may be metabolized in PAMs.

Improvement of screening for pulmonary embolism with a standardized questionnaire

The anamnesis is believed to be poor in identifying patients with pulmonary embolism (PE), but the method of data collection may be critical for inference on this issue. We compared the prevalences of history findings recorded after a free verbal interview (VI) by the referring physicians with those recorded after completion of a standardized questionnaire (SQ) by the admitting physicians in a group of 177 consecutive patients referred to our Emergency Unit with the suspicion of PE (subsequently confirmed in 97). VI data were incomplete in 18 patients. In the remaining 159 patients, prevalences of symptoms and predisposing factors were higher after SQ than after VI. Accordingly, 8 items (obesity, prolonged immobilization, surgery, varicose leg veins, deep venous thrombosis, pleuritic chest pain, and sudden-onset dyspnea) were significantly more prevalent in patients with confirmed PE after SQ, compared to only 2 items (prolonged immobilization and pleuritic chest pain) after VI. When we tested for the agreement between the two methods of data collection, kappa values ranged from high values (for surgery and hemoptysis) to very low values (for prolonged immobilization and recurrent phlebitis). These results show that the use of an SQ could improve the accuracy of collecting clinical data in patients with suspected PE, as they are also consistent in separating patients with PE from those with unconfirmed suspicion of PE. Moreover, it allows the clinician to be alert towards findings which could be missed when not carefully searched for and which may be useful to raise or strengthen the suspicion of this disease.

Fatal peripheral airway cystic disease in a young woman

Diffuse cystic transformation of both lungs was rapidly fatal in a 33-year-old woman. This disorder, a rare congenital condition in infants, has apparently not been described in adulthood.