We hypothesized that lipids and bile acids in meconium may induce pulmonary insufficiency in newborns. Because albumin may bind these components we studied the effect of albumin on meconium-induced lung injury in piglets. We measured concentration of FFA in the meconium (110 mg dry weight/mL) and added albumin to provide a molar FFA to albumin ratio of 1:1. Newborn piglets, 0-2 d of age, artificially ventilated and exposed to hypoxemia by ventilation with 8% O2, were randomized to group A receiving meconium (n = 12) or group B receiving meconium + albumin (n = 12), 3 mL/kg intratracheally. The animals were reoxygenated for 8 h. Reoxygenation was started when mean blood pressure was <20 mm Hg or base excess was <-20 mM. Pulmonary function was assessed in parallel with pulmonary hemodynamics. From the start of reoxygenation and the next 8 h we found a significant difference (by ANOVA) between the two groups in oxygenation index (p = 0.005), with an increase from 1.6 +/- 0.2 to 6.1 +/- 6.8 (p = 0.04) in the meconium group and from 1.8 +/- 0.3 to 3.1 +/- 3.1 (NS) in meconium + albumin group. There were also significant differences (by ANOVA) between the groups in favor of the treatment group concerning need of inspired fraction of O2, mean airway pressure, dynamic compliance of the respiratory system, time constant, ventilation index, and pulmonary vascular resistance. In conclusion, albumin given concurrently with meconium significantly reduced detrimental effects of meconium aspiration in the lungs of newborn piglets.

The effects of blocking endothelin (ET) receptors in pulmonary circulation during hypoxemia and reoxygenation were studied in five groups of piglets. Ten minutes before hypoxemia, the Hyp group (n = 10) was given saline and the 1-mg (n = 9) and 5-mg group (n = 9), respectively, were given 1 and 5 mg/kg i.v. SB 217242 (an ET receptor antagonist). Two groups served as normoxic controls. The piglets were ventilated with 8% O2 until base excess was <-20 mmol/L or mean arterial blood pressure was <20 mm Hg. Reoxygenation was performed with air. The increase of mean pulmonary artery pressure was significantly attenuated during hypoxemia and reoxygenation in the 1-mg group (p = 0.006). The pulmonary vascular resistance index increased significantly at the end of hypoxemia in the Hyp and 5-mg groups but was comparable to baseline in the 1-mg group. During the study period, the changes in pulmonary vascular resistance index were significantly attenuated in the 1-mg group compared with the 5-mg group. Stroke volume index was significantly attenuated compared with baseline in the 5-mg group during both hypoxemia and reoxygenation, whereas, in the Hyp and 1-mg group, stroke volume index was attenuated only at the end of hypoxemia. During hypoxemia, plasma ET-1 decreased from 1.9+/-0.2 to 1.3+/-0.3 ng/L (p = 0.008) in the Hyp group, remained unchanged in the 1-mg group, and increased from 1.6+/-0.2 to 6.6+/-1.6 ng/L (p = 0.008) in the 5-mg group. We conclude that blocking ET receptors attenuates pulmonary vasoconstriction during hypoxemia and reoxygenation in piglets.

ABCA3 mutations were the basis for lung disease in all three patients. Children with lung disease due to ABCA3 deficiency may not have symptoms at birth. The finding of five novel mutations indicates allelic heterogeneity for ABCA3 mutations within the Norwegian population.

No abstract

Meconium aspiration induces pulmonary inflammation and reduces surfactant function. We hypothesized that albumin mixed with meconium attenuates pulmonary inflammation and improves surfactant function after meconium aspiration. We measured the concentration of free fatty acids (FFA) in the meconium (110 mg dry weight/mL) and added albumin to provide a molar FFA:albumin ratio of 1:1. Newborn piglets, 0-2 day of age, artificially ventilated and exposed to hypoxemia by ventilation with 8% O2, were randomized to group A receiving meconium (n = 12), or group B receiving meconium + albumin (n = 12), 3 ml/kg intratracheally. The animals were reoxygenated for 8 h. Reoxygenation was started when mean arterial blood pressure was < 20 mm Hg or base excess was < -20 mmol/L. During 8 h of reoxygenation the interleukin-8 concentrations in tracheobronchial aspirates increased 5-fold more in the meconium vs. the meconium + albumin groups (93 +/- 56 vs. 18 +/- 4 pg/mL, p < 0.005). There were no differences between the groups for tumor necrosis factor alpha in tracheobronchial aspirates, recruitment of inflammatory cells in the airspaces or surfactant function in bronchoalveolar lavage fluid. In conclusion, albumin significantly decreased interleukin-8 concentrations in tracheobronchial aspirates after meconium aspiration.

Commercial cow's milk protein added to human milk was as good as human milk protein supplementation in supporting growth and erythropoiesis. Fifty IU/kg r-HuEpo thrice weekly during AOP stimulated erythropoiesis significantly, but less so than 100 IU/kg. Even when using high oral doses of iron to preterms receiving r-HuEpo, our data suggested a certain degree of iron deficient erythropoiesis.

To understand the pathogenesis of meconium aspiration syndrome, we compared the pulmonary and inflammatory effects of the water and lipid extracts of human meconium instilled into the lungs of newborn piglets. The piglets were artificially ventilated, made hypoxemic, and randomized into three groups. At start of reoxygenation, 3 ml/kg of one of the following mixtures was instilled intratracheally: (1) meconium (n = 12); (2) water extract of meconium (n = 12), and (3) lipid extract of meconium (n = 12). During 8 h of reoxygenation, hemodynamics, pulmonary gas exchange, lung mechanics, and interleukin-8 concentrations in tracheobronchial aspirates were monitored. Oxygenation index (p = 0.04) and mean airway pressure (p = 0.04) increased more in the lipid extract group than in the water extract group. Dynamic compliance and mean arterial blood pressure decreased (p < 0.05) in the meconium and lipid extract groups, but not in the water extract group. At 8 h of reoxygenation, the interleukin-8 concentration in the tracheobronchial aspirates was three times higher in the lipid extract group as compared with the water extract group (110 ± 102 vs. 37 ± 27 pg/ml; p = 0.02). In conclusion, pulmonary dysfunction in meconium aspiration syndrome is caused by both the water- and lipid-soluble fractions of meconium, with stronger inflammatory and more detrimental effects promoted by the lipid extract than the water extract.

Discussion | "Rash" is a commonly reported adverse effect of immune checkpoint inhibitors; eruption patterns include eczematous maculopapular and lichenoid lesions, both types diffusely distributed on trunk and extremities. [1][2][3][4] Eczematous eruption has no specific histopathologic findings and has been described as spongiotic dermatitis with lymphocytes and eosinophils. 5 Lichenoid eruption consists of an interface dermatitis with CD4-positive T cells in the dermis and scattered CD8-positive intraepidermal lymphocytes, frequently with spongiotic features. 4 The 2 patients described herein were treated with immune checkpoint inhibitors for metastatic melanoma and developed a spongiotic eruption with eosinophils only in the areas of their locoregional melanoma metastases. These cases may exemplify a variant of locus minoris resistentiae, in which an area of the body is more vulnerable than others. 6 In the cases described, eruption due to immunotherapy may be a result of activated melanoma-associated antigen-specific T cells homing to an area of enhanced melanoma cell presence due to locoregional metastases, resulting in a localized inflammatory eruption. These cases typify the diverse skin manifestations in patients treated with immune checkpoint inhibitors of which dermatologists should remain aware. They also provide another interesting example of locus minoris resistentiae within dermatology. 6