Functional age-dependent changes in bronchoalveolar lavage rat cells.

Alveolar macrophages (AM) are located at the first line of non-specific defense against inhaled antigens in the lower respiratory tract and therefore represent the major effector cell in antimicrobial defense. Since children under 2 years are known to manifest increased susceptibility to lung infections we used a rat model to study functional capacities of the AM during different stages of development We analyzed several steps of the phagocytic process (adherence, chemotaxis and ingestion) as well as two different mechanisms of cytotoxicity [antibody dependent cellular cytotoxicity (ADCC) and cytotoxicity triggered by immune complex (ICC)] and tumor necrosis factor (TNF-alpha) secretion. We used young (4-6 weeks old), intermediate (16-25 weeks old) and adult (36-45 weeks old) rats. Adherence and phagocytic capacities of AM were lower in young rats compared to intermediate and adult animals. Chemotaxis towards the C5a complement component was low in the first two months of life, then it increased in the intermediate group and fell again in adults. Bronchoalveolar lavage (BAL) cells from young rats did not produce detectable TNF-alpha levels even when stimulated with phorbol 12-myristate 13-acetate (PMA). When we studied two different cytotoxic mechanisms we found that ICC markedly declines from youth to adulthood while ADCC showed a steady increase from youth to adulthood. In conclusion, our data show differences that may help to explain in part the enhanced susceptibility to pulmonary infections found in young children.

Association between liver transplantation for Langerhans cell histiocytosis, rejection, and development of posttransplant lymphoproliferative disease in children.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is an unusual indication for orthotopic liver transplantation in children. Data from limited case reports suggest that orthotopic liver transplantation for LCH is associated with excellent survival rates and a low incidence of disease recurrence. However, in our experience, children who have transplantation for LCH appeared to experience a high incidence of refractory rejection and posttransplant lymphoproliferative disease (PTLD). STUDY DESIGN: Data from 398 liver transplants performed in 298 children younger than 16 years of age were reviewed to determine the presence of risk factors for PTLD in patients with LCH and other causes of liver failure. RESULTS: The incidence of PTLD was significantly higher in children who received transplants for LCH compared with all indications (p < 0.001) and specific indications that were associated with the development of PTLD (p < 0.002). Among patients in whom PTLD developed, there was no significant difference in the incidence of primary Epstein-Barr virus infections in patients who receive transplantation for LCH (4/4, 100%) versus all other indications (12/14, 86%). Children who had transplantation for LCH were older than those who had transplantation for other indications (LCH median age 3.1 years, other indications 1 year). The incidence of rejection, especially refractory rejection, was greater in patients who had transplantation for LCH (100% and 50%, respectively) compared with those who had transplantation for other indications (70% and 10%, p < 0.02 for refractory rejection). CONCLUSIONS: Patients who had transplantation for liver disease related to LCH experienced a 67% long-term survival (median follow up 5.8 years, range 2.1 to 7.5 years). Recurrent LCH occurred in only 33% of patients and was easily managed. However, PTLD developed in two thirds of these patients, perhaps in part because of the high incidence of refractory rejection. This series therefore demonstrates an association between a primary disease process and the development of PTLD. Although the data indicate that children with LCH-induced liver failure benefit from transplantation, special care must be exercised in screening for and preemptive treatment of PTLD.

Evaluating a fluorosis hazard after a volcanic eruption.

The August, 1991 eruption of Mt. Hudson (Chile) deposited ash across southern Argentina and contributed to the deaths of thousands of grazing sheep. Early ash analysis revealed high levels of fluoride, a potential ash constituent toxic to humans and animals. In order to evaluate fluorosis as the cause of sheep deaths and to examine the possibility that similar ash and airborne toxins could also have an effect on the human population, we conducted an investigation that included health provider interviews, hospital record review, physical examination of sheep, determination of sheep urine fluoride levels, and complete constituent analysis of ash samples collected at proscribed distances from the volcano. Ash deposited farthest from the volcano had highest fluoride levels; all fluoride measurements were normal after rainfall. There were no signs or symptoms of fluorosis observed in sheep or humans. Sheep deaths resulted from physical, rather than chemical properties of the ash.