Primary repair of tetralogy of Fallot in infancy

From June 1983 to April 1988, 100 consecutive infants with symptomatic tetralogy of Fallot (without pulmonary atresia) were operated on. Ages ranged from 0.5 to 12 months (mean 7.3 +/- 3.7). Twenty patients were 0.5 to 3 months, 21 were 3 to 6 months, and 59 were 6 to 12 months of age. Mean weight was 6.5 kg +/- 1.7. Seventy patients received a transannular patch. The hospital mortality rate was 3% and there were no late deaths. Cumulative follow-up was 180 patient-years. Causes of death included hypoplastic pulmonary arteries (4 and 5 months old) and right ventricular failure (4 months old). The most important factors influencing right ventricular outflow tract reconstruction were neither weight (p = 0.90) nor age (p = 0.05) but rather were the ratio between weight and pulmonary arterial outflow tract diameter (p = 0.0005) and the ratio between body surface area and pulmonary arterial outflow tract diameter (p less than 0.0001). The last 48 patients were operated on with no deaths. During this period, operative management differed essentially in myocardial protection with blood cardioplegia. The predicted 30-day survivorship after repair was 90% to 99% (95% confidence limits). No ventricular arrhythmias have been detected after repair (mean follow-up 22.2 months). Mean right ventricular/left ventricular end-diastolic dimension ratio was (0.53 +/- 0.10 with M-mode echocardiography. These early results encourage us to proceed with primary repair of infants with symptomatic tetralogy of Fallot thanks to improved surgical management and enhanced myocardial protection.     

Protein ubiquitination in postsynaptic densities after transient cerebral ischemia.

The mechanisms underlying neurologic deficits and delayed neuronal death after ischemia are not fully understood. In the present study, we report that transient cerebral ischemia induces accumulation of ubiquitinated proteins (ubi-proteins) in postsynaptic densities (PSDs). By immunoelectron microscopy, we demonstrated that ubi-proteins were highly accumulated in PSD structures after ischemia. On Western blots, ubi-proteins were markedly increased in purified PSDs at 30 minutes of reperfusion, and the increase persisted until cell death in the CA1 region after ischemia. In the resistant DG area, however, the changes were transient and significantly less pronounced. Deposition of ubi-proteins in PSDs after ischemia correlates well with PSD structural damage in the CA1 region as viewed by electron microscopy. These results suggest that the ubiquitin-proteasome system fails to repair and remove damaged proteins in PSDs. The changes may demolish synaptic neurotransmission, contribute to neurologic deficits, and eventually lead to delayed neuronal death after transient cerebral ischemia.     

Effects of metyrapone on hypothalamic-pituitary-adrenal axis and sleep in women with post-traumatic stress disorder.

BACKGROUND: Metyrapone blocks cortisol synthesis which results in removal of negative feedback, a stimulation of hypothalamic corticotropin releasing factor (CRF) and a reduction in delta sleep. We previously reported a diminished delta sleep and hypothalamic-pituitary-adrenal (HPA) response to metyrapone in men with post-traumatic stress disorder (PTSD). In this study, we aimed to extend these findings to women. METHODS: Three nights of polysomnography were obtained in 17 women with PTSD and 16 controls. On day 3, metyrapone was administered throughout the day up until bedtime. Plasma adrenocorticotropic hormone (ACTH), cortisol, and 11-deoxycortisol were obtained the morning following sleep recordings the day before and after metyrapone administration. RESULTS: There were no significant between-group differences in hormone concentration and delta sleep at baseline. Relative to controls, women with PTSD had decreased ACTH and delta sleep responses to metyrapone. Decline in delta sleep was associated with the magnitude of increase in ACTH across groups. CONCLUSIONS: Similar to our previous findings in men, the ACTH and sleep electroencephalogram response to metyrapone is attenuated in women with PTSD. These results are consistent with a model of downregulation of CRF receptors in an environment of chronically increased CRF activity or with enhanced negative feedback regulation in PTSD.     

Slow versus standard up-titration of paroxetine for the treatment of depression in cancer patients: a pilot study

Objectives  

This study aimed to compare the tolerability and efficacy of two different titrations of paroxetine (slow and standard) in a population of cancer patients with depression.     

A Novel Program Trains Community‐Academic Teams to Build Research and Partnership Capacity

The Community‐Engaged Research Team Support (CERTS) program was developed and tested to build research and partnership capacity for community‐engaged research (CEnR) teams. Led by the Northwestern University Clinical and Translational Sciences Institute (NUCATS), the goals of CERTS were: (1) to help community‐academic teams build capacity for conducting rigorous CEnR and (2) to support teams as they prepare federal grant proposal drafts. The program was guided by an advisory committee of community and clinical partners, and representatives from Chicago''s Clinical and Translational Science Institutes. Monthly workshops guided teams to write elements of NIH‐style research proposals. Draft reviewing fostered a collaborative learning environment and helped teams develop equal partnerships. The program culminated in a mock‐proposal review. All teams clarified their research and acquired new knowledge about the preparation of NIH‐style proposals. Trust, partnership collaboration, and a structured writing strategy were assets of the CERTS approach. CERTS also uncovered gaps in resources and preparedness for teams to be competitive for federally funded grants. Areas of need include experience as principal investigators, publications on study results, mentoring, institutional infrastructure, and dedicated time for research.     

Involvement of PKCα–MAPK/ERK-phospholipase A2 pathway in the Escherichia coli invasion of brain microvascular endothelial cells

Escherichia coli K1 is the most common Gram-negative organism that causes neonatal meningitis following penetration of the blood–brain barrier. In the present study we demonstrated the involvement of cytosolic (cPLA₂) and calcium-independent phospholipase A₂ (iPLA₂) and the contribution of cyclooxygenase-2 products in E. coli invasion of microvascular endothelial cells. The traversal of bacteria did not determine trans-endothelial electrical resistance (TEER) and ZO-1 expression changes and was reduced by PLA₂s siRNA. cPLA₂ and iPLA₂ enzyme activities and cPLA₂ phosphorylation were stimulated after E. coli incubation and were attenuated by PLA₂, PI3-K, ERK 1/2 inhibitors. Our results demonstrate the role of PKCα/ERK/MAPK signaling pathways in governing the E. coli penetration into the brain.