Pharmacokinetics and clinical efficacy of indomethacin in premature infants with patent ductus arteriosus

Despite a considerable amount of investigation, controversy continues concerning the use of indomethacin in inducing the closure of patent ductus arteriosus. This controversy may be attributable to differences in dosage, route of administration, postnatal age at treatment and the variable pharmacokinetics of the drug in premature infants. The pharmacokinetics and clinical efficacy of i.v. administered indomethacin in five premature infants with PDA were evaluated. There was considerable intersubject variability in the half life of elimination (63.1 +/- 38 h). This variability was mainly due to clearance (0.0086 +/- 0.0069 l/h/kg) rather than to distribution volume variability (0.54 +/- 0.27 l/kg). A reduction of half life was observed after the second dose, probably due to a maturation process. A permanent closure of the ductus was obtained in two patients after the first dose and in two patients after the second dose. The side-effects observed in our infants were transient and no long-term complication was attributable to this drug.     

Modification of some markers of inflammation during treatment for acute respiratory exacerbation in cystic fibrosis

An objective approach for monitoring the treatment of acute pulmonary exacerbation in cystic fibrosis was evaluated. Eleven biochemical markers of inflammation (erythrocyte sedimentation rate, neutrophil count, C-reactive protein, alpha-1 antitrypsin, haptoglobin, ceruloplasmin, fibronectin, alpha-1 glycoprotein, alpha-2 macroglobulin, C3, granulocyte elastase and anti-Pseudomonas IgG) were measured in blood serum and plasma from 46 cystic fibrosis patients with chronic Pseudomonas aeruginosa colonization before and after treatment. The overall outcome in each patient was evaluated by means of a pondered sum of clinical, chest X-ray and lung function scores. Biochemical markers were related to the overall clinical improvement: haptoglobin, ceruloplasmin, fibronectin and alpha-1 glycoprotein showed a good sensitivity (64-70%), specificity (60-70%) and positive predictive value (86-89%). Granulocyte elastase showed a similar sensitivity (67%) and positive predictive value (85%) but a lower specificity (33%). The negative predictive value was generally poor (32-39%). Our data suggest that the combined measurement of some markers of inflammation and of conventional clinical parameters, may help in evaluating the efficacy of anti-infective treatment in cystic fibrosis.     

Breast masses: mammographic evaluation

The systematic mammographic evaluation of a breast mass involves independent assessments of its size, location, density, shape, clarity of margins, and interval change from prior examination. Additional fine-detail mammograms should be obtained to facilitate this analysis, especially when an equivocal interpretation is planned. Definitively benign masses (those localized to the skin, of fat density, or of mixed density) will not require more attention. Among the remaining water-density lesions, those that have an even slightly stellate appearance should be considered suspicious for malignancy; virtually all of them will undergo biopsy. Well-circumscribed masses should next be evaluated by aspiration or US examination to establish or exclude the diagnosis of simple benign cyst. Only solid and indeterminate lesions will require further evaluation, with the ultimate decision for biopsy versus mammographic follow-up depending on the probability of malignancy determined by the combination of mammographic and physical findings as well as pertinent data from the medical history.