Regional impairments of cortical folding in premature infants.

OBJECTIVE: This study was undertaken to evaluate the influence of preterm birth and other factors on cerebral cortical maturation. METHODS: We have evaluated the effects of preterm birth on cortical folding by applying cortical cartography methods to a cohort of 52 preterm infants (<31 weeks gestation, mild or no injury on conventional magnetic resonance imaging) and 12 term-born control infants. All infants were evaluated at term-equivalent postmenstrual age. RESULTS: Preterm infants had lower values for the global measures of gyrification index (GI; 2.06 ± 0.07 vs 1.80 ± 0.12, p < 0.001; control vs preterm) and cortical surface area (CSA; 316 ± 24 cm(2) vs 257 ± 40 cm(2) , p < 0.001). Regional analysis of sulcal depth and cortical shape showed the greatest impact of preterm birth on the insula, superior temporal sulcus, and ventral portions of the pre- and postcentral sulci in both hemispheres. Although CSA and GI are related, CSA was more sensitive to antenatal and postnatal factors than GI. Both measures were lower in preterm infants of lower birth weight standard deviation scores and smaller occipitofrontal circumference at time of scan, whereas CSA alone was lower in association with smaller occipitofrontal circumference at birth. CSA was also lower in infants with higher critical illness in the first 24 hours of life, exposure to postnatal steroids, and prolonged endotracheal intubation. INTERPRETATION: Preterm birth disrupts cortical development in a regionally specific fashion with abnormalities evident by term-equivalent postmenstrual age. This disruption is influenced by both antenatal growth and postnatal course.

Tumor location is not an independent prognostic factor in early stage non-small cell lung cancer.

BACKGROUND: Conventional thoracic surgical teaching suggests a worse outcome for lower lobe lung cancers. It is unclear whether this is due to stage migration or whether lobar location is an independent negative prognostic factor. METHODS: We performed a retrospective review of our institutional database of patients undergoing resection for pathologic stage I or stage II lung cancer between Jan 2000 and December 2006. Survival analysis was used to compare outcomes in various groups using the log-rank test. Logistic regression analysis was used to compare the primary dependent variables; age, size, and location of tumor (both laterality and lobe), histology (adenocarcinoma, squamous, large cell, or neuroendocrine and others) and type of resection (wedge, lobectomy or segmentectomy, and pneumonectomy). RESULTS: A total of 841 patients met the inclusion criteria. The mean age of patients was 64.9 years, mean tumor size 3.3 cm, and, 144 patients had N1 disease. The three-year and five-year survivals for stage I tumors were 346 of 478 (72.4%) and 277 of 497 (55.7%), respectively. There was no difference in survival based upon lobar location. The three-year and five-year survivals for stage II tumors were 81 of 175 (46.3%) and 39 of 150 (26%), respectively, and lobar location did not influence survival. Logistic regression analysis showed that for stage I tumors increasing age and having undergone a pneumonectomy were associated with worse survival, and for stage II tumors increasing age and adenocarcinoma histology were associated with worse survival. CONCLUSIONS: Tumor location within the lung does not predict survival in pathologic stage I/II non-small cell lung carcinoma. Increasing age, adenocarcinoma histology, and pneumonectomy as the resection may lead to worse long-term survival.

Design, synthesis and in vitro evaluation of potent, novel, small molecule inhibitors of plasminogen activator inhibitor-1.

We have synthesized and evaluated a series of tetramic acid-based and hydroxyquinolinone-based inhibitors of plasminogen activator inhibitor-1 (PAI-1). These studies resulted in the identification of several compounds which showed excellent potency against PAI-1. The design, synthesis and SAR of these compounds are described.