[The causes and consequences of the cellular death (apoptosis and necrosis) in the course of acute poisoning with carbon monoxide]. / Apoptoza i nekroza--przyczyny i skutki w przebiegu ostrego zatrucia tlenkiem wegla.

The flow cytometry is acquiring more and more clinical importance. Despite its wide application in diagnostics, it is not used commonly in the clinical toxicology. The goal of the current investigation was to evaluate the mechanism for cell death (apoptosis or necrosis) and its manifestation in circulating human lymphocytes exposed to toxic concentration of carbon monoxide (CO). Since the large subpopulation of leukocytes have undergone apoptosis the next step of the studies was to assess the mobilization of progenitor cells (CD 34+) occurring in the peripheral blood after CO intoxication. Data were compared with those of 25 healthy controls comparable in terms of age, gender and physical activity. The application of the method in clinical reasoning was also evaluated. Significantly increased apoptosis of the lymphocytes in research group compared to control individuals correlates with the poisoning severity but does not depend on hypoxia. Decreased number of leukocytes caused by the cytotoxic effect of CO, stimulates the release of the CD 34+ to the peripheral blood. Increased cell death seems to be the relevant mechanism in the pathophysiology of acute carbon monoxide poisoning--the delayed apoptosis as the consequence of the reoxygenation can influence the delayed neurological and cardiological sequelae in patients after acute CO poisoning. In order to improve the treatment and help choose best fitting therapy, there should be need to introduce the new diagnostic methods like flow cytometry or innovative imaging techniques to the standard diagnostics in clinical toxicology.

Characteristic genomic imbalances in pediatric pheochromocytoma.

Pheochromocytoma (PCC) in children is rare, genetically not well described, and often related to a poor prognosis. We detected genomic imbalances in all 14 tumors from children analyzed by comparative genomic hybridization. A combinatorial loss of chromatin from 3p and 11p was a common feature in 10 of 14 (72%) patients, which was a result of either a loss of a total chromosome 3 and a total chromosome 11 in 6 of 10 patients, or confined deletions of their p arms in 4 of 10 patients. All patients exhibiting a loss of 3p and 11p carried VHL mutations. The VHL mutations were constitutive in 9 cases and somatic and restricted to tumor DNA in the remaining tumor. On the other hand, VHL mutations were absent in 4 patients, 2 who had other familial syndromes (NF1, SDHD) and 2 with unknown etiology. Our data show that the pattern of imbalances in the tumor DNA of PCC patients strongly correlated with an underlying familial VHL mutation. Furthermore, we show that true sporadic PCC is rare in childhood. Thus, children with PCC should be checked for a related predisposing gene. This would also identify familial syndrome patients requiring long-term monitoring for other syndrome-related malignancies.