Gene expression profiling for molecular distinction and characterization of laser captured primary lung cancers.

METHODS: We examined gene expression profiles of tumor cells from 29 untreated patients with lung cancer (10 adenocarcinomas (AC), 10 squamous cell carcinomas (SCC), and 9 small cell lung cancer (SCLC)) in comparison to 5 samples of normal lung tissue (NT). The European and American methodological quality guidelines for microarray experiments were followed, including the stipulated use of laser capture microdissection for separation and purification of the lung cancer tumor cells from surrounding tissue. RESULTS: Based on differentially expressed genes, different lung cancer samples could be distinguished from each other and from normal lung tissue using hierarchical clustering. Comparing AC, SCC and SCLC with NT, we found 205, 335 and 404 genes, respectively, that were at least 2-fold differentially expressed (estimated false discovery rate: < 2.6%). Different lung cancer subtypes had distinct molecular phenotypes, which also reflected their biological characteristics. Differentially expressed genes in human lung tumors which may be of relevance in the respective lung cancer subtypes were corroborated by quantitative real-time PCR. Genetic programming (GP) was performed to construct a classifier for distinguishing between AC, SCC, SCLC, and NT. Forty genes, that could be used to correctly classify the tumor or NT samples, have been identified. In addition, all samples from an independent test set of 13 further tumors (AC or SCC) were also correctly classified. CONCLUSION: The data from this research identified potential candidate genes which could be used as the basis for the development of diagnostic tools and lung tumor type-specific targeted therapies.

[Sleep apnea syndrome--hypertension--cardiac failure]. / Schlafapnoe--Hypertonie--Herzinsuffizienz.

Especially middle-aged persons frequently suffer from sleep-related breathing disorders. In particular, in sleep apnea syndrome various interactions are known concerning the development or deterioration of hypertension. Cardiac failure may as well be a consequence of a sleep apnea syndrome. It may negatively influence sleep apnea. The causes of cardiovascular secondary and concomitant diseases are blood gas alterations, intrathoracic fluctuations in pressure and consecutive arousal reactions, which again cause various secondary and concomitant disorders. The various and partly incompletely discovered relationships between sleep apnea syndrome on the one hand and hypertension and cardiac failure on the other hand offer the possibility of causal treatment for these disorders.

Altered blood rheology in obstructive sleep apnea as a mediator of cardiovascular risk.

BACKGROUND: Cardiovascular complications are common in patients with obstructive sleep apnea (OSA). Blood rheology is a major determent of coagulation and an established risk factor for cardiovascular events. Since nocturnal hypoxemia could influence parameters of blood rheology, we hypothesized that OSA alters blood rheology independent of other cardiovascular risk factors. METHODS: One hundred and ten consecutive patients admitted to the sleep laboratory were included. The association of plasma fibrinogen and viscosity (as parameters of blood rheology) with OSA was evaluated. RESULTS: One hundred and ten patients aged 61.4+/-10.1 years (body mass index 28.4+/-4.1 kg/m2) were included. OSA was confirmed in 63 patients (57.2%) with an apnea-hypopnea index (AHI) of 28.7+/-14.9 events/hour. Patients with OSA showed higher levels of plasma viscosity (1.36+/-0.09 vs. 1.31+/-0.08 mPas, p=0.005). Nevertheless, hypertensive apneics have even higher levels of plasma viscosity than nonapneics (1.38+/-0.091 vs. 1.32+/-0.028 mPas, p=0.018). Similar results were found in patients with coronary artery disease, where OSA was associated with elevated plasma viscosity (1.36+/-0.076 vs. 1.31+/-0.081 mPas, p=0.007). Plasma fibrinogen was correlated with nocturnal minimal oxygen saturation (r=-0275, p=0.0036) and AHI (r=0.297, p=0.001). OSA was associated with higher plasma fibrinogen (353+/-83 vs. 317+/-62 mg/dl, p=0.015). These differences persist with control for cardiovascular risk factors. CONCLUSIONS: Patients with OSA have elevated morning fibrinogen levels and a higher plasma viscosity, which correlate positively with indices of sleep apnea severity. These changes in blood rheology are independent of cardiovascular risk factors, and therefore, might be specific mechanisms of OSA. This supports the pathophysiological concept that sleep apnea is a cardiovascular risk factor.

Combined broncho-oesophagoscopy for diagnosis of HIV-associated disorders.

The aim of the study was to characterize the value of combined endoscopy of tracheobronchial tree and oesophagus within 1 session for diagnosis of HIV-associated disorders. Hospitalized HIV-positive patients who underwent combined flexible broncho-oesophagoscopies between 1999 and 2002 in 2 units for infectious diseases were studied retrospectively. 54 HIV patients were analysed; 89% were at stage CDC C, 79% were male, mean age was 40 y. Bronchoscopy led to a diagnosis in 57.4% (95% CI 43.2-70.8). In 40.7%, these were AIDS-defining events (ADE) and 16.7% were general disorders (GD). Oesophagoscopy was diagnostic in 46.3% (95% CI 32.6-60.4). In 35.2% these were ADE, and 11.1% were GD. Patients with pathological oesophagoscopy had a significantly lower CD4 cell count and a higher viral load. There was no association of pathological bronchoscopy with pathological oesophagoscopy regarding ADE. No severe complication was recorded. It is concluded that combined flexible broncho-oesophagoscopy is a valuable and safe method for the diagnosis of HIV-associated disorders. The diagnostic output is highest in patients with advanced disease. A pathological finding in oesophagoscopy cannot be predicted by the presence of bronchoscopic abnormalities. Prospective studies are necessary to confirm these results.