Polymorphisms in the fetal progesterone receptor and a calcium-activated potassium channel isoform are associated with preterm birth in an Argentinian population.

OBJECTIVE: To investigate genetic etiologies of preterm birth (PTB) in Argentina through evaluation of single-nucleotide polymorphisms (SNPs) in candidate genes and population genetic admixture. STUDY DESIGN: Genotyping was performed in 389 families. Maternal, paternal and fetal effects were studied separately. Mitochondrial DNA (mtDNA) was sequenced in 50 males and 50 females. Y-chromosome anthropological markers were evaluated in 50 males. RESULT: Fetal association with PTB was found in the progesterone receptor (PGR, rs1942836; P=0.004). Maternal association with PTB was found in small conductance calcium activated potassium channel isoform 3 (KCNN3, rs883319; P=0.01). Gestational age associated with PTB in PGR rs1942836 at 32-36 weeks (P=0.0004). MtDNA sequencing determined 88 individuals had Amerindian consistent haplogroups. Two individuals had Amerindian Y-chromosome consistent haplotypes. CONCLUSION: This study replicates single locus fetal associations with PTB in PGR, maternal association in KCNN3, and demonstrates possible effects for divergent racial admixture on PTB.

Sequential pulmonary function measurements during treatment of infantile chronic interstitial pneumonitis.

Three infants with histologically confirmed chronic interstitial pneumonitis were treated with monthly intravenously administered high doses of methylprednisolone with or without daily hydroxychloroquine therapy. We applied the multiple occlusion technique to measure the static respiratory system compliance, and the end-inspiratory occlusion technique to measure passive respiratory system compliance, resistance, and time constant. When assessed by clinical criteria and pulmonary function measurements, all three patients showed improvement with this treatment. Clinical improvement was associated with an increase in respiratory system compliance as measured by both techniques (60% to 100% increase in all patients). The passive respiratory resistance and the time constant did not closely reflect the clinical course. We conclude (1) that high doses (pulses) of methylprednisolone and daily oral doses of hydroxychloroquine are effective in the treatment of infantile chronic interstitial pneumonitis and (2) that the respiratory system compliance, measured by both pulmonary function techniques, correlates well with the response to treatment and change in clinical status.

Total resistance of the respiratory system in preterm infants with and without an endotracheal tube.

The passive compliance and resistance of the respiratory system were measured in 12 spontaneously breathing newborn infants before and after endotracheal extubation. End-inspiratory airway occlusions were used to relax the respiratory muscles, allowing occlusion pressure to be measured and respiratory system compliance and resistance to be calculated from the flow volume relationship of the subsequent passive expiration. Airway pressure was measured from an endotracheal tube or a face mask, expiratory flow from a pneumotachograph, and expiratory volume from the integrated flow signal. In six of the infants, diaphragmatic electromyography was also performed before and after extubation. Resistance and EMG findings were both decreased by extubation (mean decrease 43.9%, P less than 0.001 and 27.3%, P less than 0.05, respectively), but compliance was unchanged. Thus, by substantially increasing resistance, an endotracheal tube causes the diaphragm to increase its activity to maintain ventilation.