Although the screened group had a higher proportion of patients with pancreatic insufficiency, their growth indices were significantly better than those of the control group during the 13-year follow-up evaluation and, therefore, this randomized clinical trial of early CF diagnosis must be interpreted as unequivocally positive. Our conclusions did not change when the height and weight data before 4 years of age for the controls detected by unblinding were included in the analysis. Also, comparison of growth outcomes after 4 years of age in all subjects showed persistence of the significant differences. Therefore, selection bias has been eliminated as a potential explanation. In addition, the results show that severe malnutrition persists after delayed diagnosis of CF and that catch-up may not be possible. We conclude that early diagnosis of CF through neonatal screening combined with aggressive nutritional therapy can result

As part of the ongoing Wisconsin Cystic Fibrosis (CF) Neonatal Screening Project, we had the unique opportunity to study the longitudinal relationship between Pseudomonas aeruginosa (Pa) acquisition and infection and developing lung disease in children with CF. The primary objective was to determine whether acquisition of Pa was associated with a measurable change in the progression of lung disease. Two outcome measures were used to study 56 patients who were diagnosed through newborn screening: 1) Wisconsin additive chest radiograph score (WCXR), based on the average of scores from a pulmonologist and a radiologist, and 2) the highest forced expired volume in 1 sec (FEV(1))/forced vital capacity (FVC) ratio. We used two measures of Pa acquisition: 1) time of first positive protocol-determined oropharyngeal (with cough) culture, and 2) the magnitude of antibody titer detected by ELISA assays, using as antigen a crude cell lysate, purified exotoxin A, or an elastase toxoid prepared from three Pa strains. Other predictor variables included age, pancreatic status, height-for age, and weight-for-age-percentiles. The best regression model for predicting changes in the WCXR included time to first positive culture and antibody titer for Pa elastase. Prior to Pa acquisition, WCXR worsened by 0.45 points/year (P > 0.25); after Pa acquisition, the rate of worsening increased significantly (P < 0.001) to 1.40 points/year. Each antibody titer level (log base 2) increased the score by 0.48 points (P < 0.001). The best regression model for predicting change in the FEV(1)/FVC included only time to first positive culture. Prior to Pa acquisition, the FEV(1)/FVC ratio declined by 1.29%/year; after Pa infection, the rate of decrease significantly accelerated to 1.81%/year (P = 0.001). Our data show that Pa acquisition is associated with declining pulmonary status in children with CF, and that this effect is probably gradual rather than precipitous. Because these patients were diagnosed and treated aggressively, our estimates of the effects of Pa acquisition may be conservative. We also conclude that the WCXR appears to be more sensitive than FEV(1)/FVC in detecting early changes in lung disease associated with CF.

In CF patients diagnosed through neonatal screening, P aeruginosa pulmonary infections occurred 6 to 12 months before the organism was isolated from respiratory secretions. The longitudinal monitoring of P aeruginosa antibody titers, in concert with WCXR score, should facilitate diagnosis and treatment of P aeruginosa pulmonary infections in young children with CF.

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Inhaled helium-oxygen improves the overall respiratory status of children with acute RSV lower respiratory tract infection. In patients with mild-to-moderate bronchiolitis (Clinical Asthma Scores of <6), the beneficial effects of helium-oxygen were most pronounced in children with the greatest degree of respiratory compromise.

Naringin (NRG), a bioflavonoid found in citrus fruit extracts, has been pharmacologically evaluated as a potential anticancer agent. This study confirmed a novel mechanism of the anticancer effects of NRG in the human cervical cancer HeLa cell line (HeLa cells). Exposure of HeLa cells to NRG resulted in growth inhibition, as evidenced by a decrease in cell viability. In addition, NRG treatment induced apoptosis, as indicated by the increased apoptotic percentage and the cleaved caspase-3 expression. Importantly, exposure of the cells to NRG attenuated the expression levels of phosphorylated (p) nuclear factor κB (NF-κB) p65 subunit, cyclooxygenase-2 (COX-2) and cysteinyl aspartate proteinase-1 (caspase-1). Treatment with PDTC (an inhibitor of NF-κB) or NS-398 (an inhibitor of COX-2) or SC-3069 (an inhibitor of caspase-1) markedly induced growth inhibition and apoptosis. Treatment with PDTC or NS-398 also reduced caspase-1 expression. Interestingly, PDTC treatment blocked the expression of COX-2 and NS-398 reduced the p-NF-κB p65 expression. Taken together, this study provides novel evidence that NRG induces growth inhibition and apoptosis by inhibiting the NF-κB/COX-2-caspase-1 pathway and that a positive interaction between NF-κB and COX-2 pathway contributes to the growth and antiapoptotic effect in HeLa cells.

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