Overexpression of hnRNPA2/B1 in bronchoscopic specimens: a potential early detection marker in lung cancer.

BACKGROUND: Overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 has recently been suggested to be a promising marker for early detection of lung cancer. The aim of this study was to determine the utility of its detection in bronchoscopic specimens. PATIENTS AND METHODS: Brushing and biopsy specimens were obtained from 61 patients suspected of having lung cancer, as well as from 30 healthy subjects (controls), who underwent bronchoscopy. hnRNPA2/B1 expression levels were evaluated by immunoblotting. RESULTS: Specificity of hnRNP A2/B1 overexpression was 75.9% in brushing and 78.3% in biopsy. Sensitivity in non-small cell lung cancer was 84.8% in brushing and 80.8% in biopsies, while in small cell lung cancer it was 66.7 % and 75%, respectively. Overexpression of hnRNPA2/B1 was also detected in bronchoscopic specimens of nine patients initially undiagnosed. The follow-up of these patients 2 years later showed that seven of them had developed lung cancer. CONCLUSION: Overexpression of hnRNPA2/B1 was significantly higher in patients suffering from lung cancer and may be useful in the early detection of lung cancer.

Immunohistochemical detection of p53 protein in neoplastic, preneoplastic and normal bronchial mucosa specimens obtained during diagnostic bronchoscopy.

The expression of p53 protein was evaluated immunochemically in cancer tissue, preneoplastic lesions and normal bronchial mucosa obtained during diagnostic bronchoscopy from 53 patients with lung cancer and 12 patients with benign lung diseases. In lung cancer patients, positive p53 staining was detected in 26/53 (49%) of the tumour specimens. In preneoplastic lesions p53 positive staining was found in 8 of 24 (33.3%) squamous metaplasia, 1 of 4 hyperplasia and 1 of 3 dysplasia lesions. In the same group of patients, 12 cases were found with positive p53 cells in normal bronchial mucosa. In patients with benign diseases, positive p53 staining was found in 1 of 4 cases with squamous metaplasia and in one normal mucosa. Our results provide evidence that somatic genetic alterations may occur in early stages of lung tumorigenesis, raising the possibility that molecular analyses is useful in the early diagnosis of precancerous lesions of the bronchial mucosa, and results indicate that p53 expression can be studied in small tissue specimens obtained during bronchoscopy.

Bioavailability of a new sustained-release anhydrous theophylline product.

The bioavailability of a new sustained-release anhydrous theophylline product (Theophylline Lavipharm) was evaluated and compared with the bioavailability of a well-established product, Theodur. Two groups of 12 healthy non-smokers were given single doses of 200 or 300 mg of each product and two groups of 12 patients with asthma or chronic obstructive lung disease were given doses of 200 or 300 mg of each product every 12 h for 5-day periods. The values of the area under the plasma theophylline concentration against time curve (AUC), the maximum plasma theophylline concentration (Cmax) and the time taken to reach Cmax (Tmax) for the two products did not differ significantly in the healthy groups or in the patients. The minimum and the average plasma theophylline concentrations and the fluctuation index were also calculated for the patients and there were no significant differences between the values for the two products. The new anhydrous theophylline product, Theophylline Lavipharm, appears to show very similar bioavailability to Theodur. No adverse reactions to the new product were reported.

Alveolar partial pressures of carbon dioxide and oxygen measured by a helium washout technique.

A non-invasive technique was developed for measuring alveolar carbon dioxide and oxygen tension during tidal breathing. This was achieved by solving the Bohr equations for mean alveolar carbon dioxide and oxygen tensions (PACO2, PAO2) from known values of the dead-space:tidal volume ratio measured by helium washout, and from the mixed expired partial pressure of carbon dioxide and oxygen. The derived values of wPACO2 and wPAO2 were compared with PaCO2 obtained from arterial gas analysis and PAO2 calculated from the ideal air equation. Four normal subjects and 58 patients were studied. Calculated and measured PCO2 values agreed closely with a difference in mean values (wPACO2 - PaCO2) of 0.01 kPa; the SD of the differences was 0.7 kPa. The difference in mean values between wPAO2 and PAO2 was 0.02 kPa; the SD of the differences was 0.93 kPa. The method is simple and not time consuming, and requires no special cooperation from the patients. It can be applied in the laboratory or at the bedside to any subject breathing tidally. Physiological deadspace:tidal volume ratio, PAO2 and PACO2, static lung volumes, respiratory exchange ratio, carbon dioxide production, oxygen uptake, tidal volume, and total ventilation can be measured with acceptable accuracy and reproducibility in one test. An arterial blood sample is needed initially to provide an independent measure of PaCO2 and for measurement of the alveolar-arterial PO2 difference. Subsequently, PaCO2 can be estimated from wPACO2 sufficiently well for clinical purposes and PaO2 or SaO2 can be monitored by non-invasive methods.

Distributions of an ultra-fine 99Tcm aerosol and 81Krm gas in human lungs compared using a gamma camera.

A 99Tcm aerosol of particle size 0.12 micron and the gas 81Krm were administered to four normal subjects and to eleven patients with airway disease. Posterior-anterior gamma camera images of erect lungs were compared qualitatively and quantitatively, and 99Tcm clearance rates were measured. Qualitatively the two images were similar in normal subjects but differed in most patients owing to small regions of high count density in the 99Tcm images. In a few patients, regional variations in ventilation were defined more finely by the aerosol. In both groups a significant vertical gradient in 99Tcm count density relative to 81Krm count density was found. Penetration of 99Tcm to the lung periphery relative to the hilar region was similar to that of 81Krm in the normal subjects and less than that of 81Krm in the patients. Possible causes of the differing distributions are discussed. The images obtained with the aerosol in the two groups studied were similar to those reported for larger particle aerosols.