Effect of interleukin 8 in meconium on in-vitro neutrophil chemotaxis.

BACKGROUND: Pneumonitis, characterised by large numbers of neutrophils in the lung, is an important feature of the meconium aspiration syndrome. The mechanism underlying the neutrophil influx is not known. We have investigated whether meconium has chemotactic activity and whether such activity is related to the presence of interleukin 8. METHODS: The chemotactic activity of meconium on neutrophils from newborn infants was assessed in a Boyden-chamber assay. Interleukin 8 and formyl-methionyl-leucyl-phenylalanine (f-MLP) served as positive controls. Inhibition of chemotaxis was assessed with monoclonal antibody to interleukin 8. The interleukin-8 concentration was measured by ELISA. FINDINGS: Sterile meconium suspension from seven unrelated newborn babies increased migration of neutrophils from neonates in comparison with random migration (79, 72, 70, 50, 58, 88 microm vs 46 microm; p<0.001). This effect was greatest at a meconium concentration of 5 g/L, although differences between samples from individual babies were observed. Interleukin 8 was present in all meconium suspensions (480-3980 ng/L). Anti-interleukin-8 inhibited neutrophil migration. INTERPRETATION: Interleukin 8 is present in meconium and it induces chemotaxis of neutrophils in vitro. This mechanism may have a role in the pathogenesis of pneumonitis in meconium aspiration syndrome.

The role of radioactive iodine in the treatment of advanced differentiated thyroid carcinoma.

OBJECTIVE: 131I therapy may be beneficial for patients with advanced differentiated thyroid cancer (DTC) but there have been relatively few studies of the prognostic factors which influence the outcome. We have evaluated differences in outcome in relation to histology, localization of tumour, differentiation grade, age and sex after 131I as the only secondary treatment for advanced stages of DTC. DESIGN: Retrospective study of a selected patient group treated according to a fixed protocol. PATIENTS: We studied the outcome in 86 patients with stage pN3, pT4 or pM1 out of total of 432 patients treated for DTC from 1970 until 1991. RESULTS: The overall cure rate of 131I therapy after a mean follow-up of 12.1 years was 50% (papillary 65% vs follicular 23%). The overall 5-year progression free survival (PFSR) was 66%. Three out of 11 patients with bone metastases from follicular cancer were cured after a mean dose of 13.2 GBq, significantly less than the average dose of 28.4 GBq given to all patients with bone metastases. In the univariate analysis of 5-year PFSR histology (papillary 79% vs follicular 43%), differentiation grade (well differentiated 81% and moderately differentiated 31%), tumour stage (pN3100%, pT4 77% and M1 48%), and age (< or = 60 years 85% vs > 60 years 46%) were significant prognostic factors. A multivariate analysis showed differentiation grade, histology and age to be significant prognostic variables for outcome (moderately vs well differentiated: RR = 3.16, follicular vs. papillary: RR = 2.56 and age > 60 vs age < or = 60: RR = 2.43). CONCLUSIONS: 131I can be an effective treatment in patients with advanced differentiated thyroid cancer at all sites and can cure, on average, 50% of all patients with advanced differentiated thyroid cancer.