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We have investigated the organization, on the plasma membrane and in detergent-insoluble membrane vesicles, of two neuronal glycosylphosphatidylinositolanchored (GPI) proteins: Thy-1, a negative regulator of transmembrane signalling; and prion protein, whose rapid endocytosis and Cu 2ϩ binding suggest that it functions in metal ion uptake. Prion protein occurred on the neuronal surface at high density in domains, located primarily at the cell body, which were relatively soluble in detergent. Thy-1, although much more abundantly expressed on neurons, occurred at lower density over much of the surface of neurites (and in lower abundance at the cell body) in domains that were highly resistant to detergent solubilization. Detergentinsoluble membrane vesicles contained Thy-1 at a density similar to that on the neuronal surface. Vesicles containing each protein could be separated by immunoaffinity isolation; lectin binding showed that they were enriched in different glycoproteins. Our results demonstrate a structural diversity of the domains occupied by functionally different GPI proteins.

Summary Background Adverse neurodevelopmental outcomes are observed in up to 50% of infants after complex cardiac surgery. We sought to determine the association of perioperative anesthetic exposure with neurodevelopmental outcomes at age 12 months in neonates undergoing complex cardiac surgery and to determine the effect of brain injury determined by magnetic resonance imaging (MRI). Methods Retrospective cohort study of neonates undergoing complex cardiac surgery who had preoperative and 7-day postoperative brain MRI and 12-month neurodevelopmental testing with Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Doses of volatile anesthetics (VAA), benzodiazepines, and opioids were determined during the first 12 months of life. Results From a database of 97 infants, 59 met inclusion criteria. Mean ± sd composite standard scores were as follows: cognitive = 102.1 ± 13.3, language = 87.8 ± 12.5, and motor = 89.6 ± 14.1. After forward stepwise multivariable analysis, new postoperative MRI injury (P = 0.039) and higher VAA exposure (P = 0.028) were associated with lower cognitive scores. ICU length of stay (independent of brain injury) was associated with lower performance on all categories of the Bayley-III (P < 0.02). Conclusions After adjustment for multiple relevant covariates, we demonstrated an association between VAA exposure, brain injury, ICU length of stay, and lower neurodevelopmental outcome scores at 12 months of age. These findings support the need for further studies to identify potential modifiable factors in the perioperative care of neonates with CHD to improve neurodevelopmental outcomes.

Background and Purpose The limits of cerebral blood flow-pressure autoregulation have not been adequately defined for pediatric patients. Mean arterial blood pressure below these limits might contribute to brain injury during cardiac surgery. The purpose of this pilot study was to assess a novel method of determining the lower limits of pressure autoregulation in pediatric patients supported with cardiopulmonary bypass. Methods A prospective, observational pilot study was conducted in children (n=54) undergoing cardiac surgery with cardiopulmonary bypass for correction of congenital heart defects. Cerebral oximetry index (COx) was calculated as a moving, linear correlation coefficient between slow waves of arterial blood pressure and cerebral oximetry measured with near-infrared spectroscopy. An autoregulation curve was constructed for each patient with averaged COx values sorted by arterial blood pressure. Results Hypotension was associated with increased values of COx (P<0.0001). For 77% of patients, an individual estimate of lower limits of pressure autoregulation could be determined using a threshold COx value of 0.4. The mean lower limits of pressure autoregulation for the cohort using this method was 42±7 mm Hg. Conclusions This pilot study of COx monitoring in pediatric patients demonstrates an association between hypotension during cardiopulmonary bypass and impairment of autoregulation. The COx may be useful to identify arterial blood pressure-dependent limits of cerebral autoregulation during cardiopulmonary bypass. Larger trials with neurological outcomes are indicated.

Argyria is a rare cause of cutaneous discolouration caused by silver deposition. We report a case of dramatic and diffuse argyria secondary to ingestion of colloidal silver protein over a 1-year period. Stained electron microscopy with spectral analysis was used to confirm the clinical diagnosis. Silver-protein complexes are deposited in the skin and reduced to inert silver salts by sunlight in a process similar to that harnessed in photography. Our patient had obtained the silver for consumption via mail order. It had been advertised as a cure for a variety of diseases. Colloidal silver protein is commercially available as a 'food supplement', hence circumventing the strict controls placed on medicines.

Objective Knowledge remains limited regarding cerebral blood flow autoregulation after cardiac arrest and during post-resuscitation hypothermia. We determined the relationship of cerebral blood flow to cerebral perfusion pressure in a swine model of pediatric hypoxic-asphyxic cardiac arrest during normothermia and hypothermia and tested novel measures of autoregulation derived from near-infrared spectroscopy. Design Prospective, balanced animal study. Setting Basic physiology laboratory at an academic institution. Subjects Eighty-four neonatal swine. Interventions Piglets underwent hypoxic-asphyhxic cardiac arrest or sham surgery and recovered for 2 hours with normothermia followed by 4 hours of either moderate hypothermia or normothermia. In half of the groups, blood pressure was slowly decreased through inflation of a balloon catheter in the inferior vena cava to identify the lower limit of cerebral autoregulation at 6 hours post-resuscitation. In the remaining groups, blood pressure was gradually increased by inflation of a balloon catheter in the aorta to determine the autoregulatory response to hypertension. Measures of autoregulation obtained from standard laser-Doppler flowmetry and indices derived from near-infrared spectroscopy were compared. Measurements and Main Results Laser-Doppler flux was lower in post-arrest animals compared to sham-operated controls during the 2-hour normothermic period after resuscitation. During the subsequent 4-hour recovery, hypothermia decreased laser-Doppler flux in both the sham surgery and post-arrest groups. Autoregulation was intact during hypertension in all groups. With arterial hypotension, post-arrest, hypothermic piglets had a significant decrease in the perfusion pressure lower limit of autoregulation compared to post-arrest, normothermic piglets. The near-infrared spectroscopy-derived measures of autoregulation accurately detected loss of autoregulation during hypotension. Conclusions In a pediatric model of cardiac arrest and resuscitation, delayed induction of hypothermia decreased cerebral perfusion and decreased the lower limit of autoregulation. Metrics derived from non-invasive near-infrared spectroscopy accurately identified the lower limit of autoregulation during normothermia and hypothermia in piglets resuscitated from arrest.

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; and the Cerebral Autoregulation Study Group IMPORTANCE Delirium occurs in up to 52% of patients after cardiac surgery and may result from changes in cerebral perfusion. Using intraoperative cerebral autoregulation monitoring to individualize and optimize cerebral perfusion may be a useful strategy to reduce the incidence of delirium after cardiac surgery. OBJECTIVE To determine whether targeting mean arterial pressure during cardiopulmonary bypass (CPB) using cerebral autoregulation monitoring reduces the incidence of delirium compared with usual care. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial nested within a larger trial enrolled patients older than 55 years who underwent nonemergency cardiac surgery at a single US academic medical center between October 11, 2012, and May 10, 2016, and had a high risk for neurologic complications. Patients, physicians, and outcome assessors were masked to the assigned intervention. A total of 2764 patients were screened, and 199 were eligible for analysis in this study. INTERVENTION In the intervention group, the patient's lower limit of cerebral autoregulation was identified during surgery before CPB. On CPB, the patient's mean arterial pressure was targeted to be greater than that patient's lower limit of autoregulation. In the control group, mean arterial pressure targets were determined according to institutional practice. MAIN OUTCOMES AND MEASURES The main outcome was any incidence of delirium on postoperative days 1 through 4, as adjudicated by a consensus expert panel. RESULTS Among the 199 participants in this study, mean (SD) age was 70.3 (7.5) years and 150 (75.4%) were male. One hundred sixty-two (81.4%) were white, 26 (13.1%) were black, and 11 (5.5%) were of other race. Of 103 patients randomized to usual care, 94 were analyzed, and of 102 patients randomized to the intervention 105 were analyzed. Excluding 5 patients with coma, delirium occurred in 48 of the 91 patients (53%) in the usual care group compared with 39 of the 103 patients (38%) in the intervention group (P = .04). The odds of delirium were reduced by 45% in patients randomized to the autoregulation group (odds ratio, 0.55; 95% CI, 0.31-0.97; P = .04). CONCLUSIONS AND RELEVANCE The results of this study suggest that optimizing mean arterial pressure to be greater than the individual patient's lower limit of cerebral autoregulation during CPB may reduce the incidence of delirium after cardiac surgery, but further study is needed. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00981474