Hickey College

T cells are now known to be vital to the development of experimental hypertension. Hypertension is associated with significant accumulation of T cells into the perivascular fat surrounding the aorta and renal vasculature. While a hypertension-specific neoantigen has been implicated in T cell activation, it is not known whether vascular-infiltrating T cells recognize and are locally activated by an antigen within the vessel wall. We developed live-cell imaging of explanted aortas to identify whether cognate antigens are presented to T cells within the vessel wall of hypertensive mice, evidenced by slower T cell velocities and a greater number of T cells interacting with antigen presenting cells (APCs). Splenic T cells were isolated from normotensive vehicle-treated (nT cells) and hypertensive angiotensin II (Ang II)-infused (0.7mg/kg/day; 14 days; hT cells) C57BL6/J mice. Following anti-CD3/CD28 stimulation (48 hours), cells were fluorescently labelled and co-incubated simultaneously (16 hours) with explanted aorta from normotensive or hypertensive CD11c-YFP mice, where APCs are fluorescently labelled. In CD11c-YFP mouse aorta alone, we detected a ~2-fold increase in CCR5 ligand (CCL3, CCL4 and CCL5) secretion from hypertensive mouse aorta compared to vehicle-treated mouse aorta (*P<0.05; n = 4). Using 2-photon microscopy, we observed a greater number (~2-fold) of hT cells compared to nT cells within Ang II-infused mouse aorta (390 ± 113 Vs 198 ± 49). Importantly, time-lapse recordings of hypertensive mouse aorta revealed hT cells exhibited significantly slower velocity (hT cells 2.0 μm/min Vs nT cells 4.8 μm/min; **P<0.01, n=8-12), and a greater proportion of interactions with APCs (hT cells 4.4 ± 1.1 Vs nT cells 0.8 ± 0.4%). Moreover, activation of local vascular T cells by incubating hypertensive aorta with anti-CD3/CD28 antibodies (16 hours) augmented Ang II-induced endothelial dysfunction (67.5 ± 2.0 Vs Ang II alone 54.5 ± 3.7% maximal relaxation). We have the first evidence that vascular-infiltrating T cells are presented with cognate antigens by APCs within the vessel wall during hypertension; direct activation of these T cell infiltrates further impairs endothelial function, which may promote the development of hypertension.

Theory of Mind (ToM) is a foundational skill related to understanding the thoughts, beliefs, and desires of oneself and others. There are child factors that play an important role in the development of ToM (e.g., language and vocabulary) as well as environmental factors (e.g., conversations among family members and socioeconomic status). In this review, we discuss the role of language in ToM and include the nature of social interactions that scaffold ToM development. We review research on deaf and hard-of-hearing children and children with specific language impairment; 2 groups who experience difficulties with language for different reasons, but both encounter deficits in ToM development. Finally, we conclude with examples of how clinicians can easily assess a child's ToM abilities and offer empirical evidence that aspects of ToM can be scaffolded with explicit instruction.

Introduction: We previously described use of the bispectral index (BIS), a processed EEG modality that integrates EEG power, reactivity, and suppression ratio, to assess severity of hypoxic-ischemic brain injury (HIE) very early after cardiac arrest. We now propose a neurocardiac triage model based on bispectral index and coronary risk, and describe patient outcomes accordingly. Methods: Patients from our prospective cardiac arrest database were retrospectively classified by four cardiac risk groups: STEMI, VT/VF with shock, VT/VF without shock, and PEA/asystole. Neurological injury was described by the “BISi”-the BIS score recorded immediately after the first dose of neuromuscular blockade, and classified as mild (BISi>20), moderate (BISi 10-20), or severe (BISi<10). Results: The BISi was determined at (270±186) minutes after resuscitation (ROSC). Thirty-three patients presented with STEMI; 9 of these had severe HIE - 6 later died of neurological and 1 of cardiac causes. Sixteen patients with STEMI had mild HIE: none died of neurological and 1 of cardiac cause. Fifteen patients presented with VT/VF and shock: 5 had severe HIE - 4 died of neurological and 1 of cardiac etiology. Nine patients with VT/VF and shock had mild HIE: none died of neurological and 4 of cardiac etiology. Of 41 patients with VT/VF and without shock, 16 had severe HIE: 10 died of neurological and 2 of cardiac etiology, 22 had mild brain injury - 2 each died of neurological and cardiac causes. Finally, 80 patients had PEA/asystole; 36 of these had severe HIE - 34 died of neurological and 2 of cardiac causes. Thirty-four patients with PEA/asystole had mild HIE - 8 died of neurological and 9 of cardiac causes. Thirty-eight patients in the total cohort underwent urgent cardiac catheterization (CC) - 8 (21.1%) subsequently died of neurological causes; 5 of those 8 were identified as severe HIE by BISi. Of 56 non-STEMI patients with VT/VF (with or without shock), 24 were identified as having mild HIE yet did not undergo urgent CC - 5 (20.8%) of those patients subsequently died of a cardiac cause. Conclusion: A neurocardiac triage model based on early processed EEG and cardiac risk class suggested possible utility in selecting appropriate patients for urgent coronary angiography and PCI after cardiac arrest.

This study, using 62 rabbits, examines the rate and pattern of vascular outgrowth from a subcutaneously implanted vascular pedicle, how the newly formed vessels connect to preexisting skin vessels, and whether local application of basic fibroblast growth factor can accelerate the angiogenic process. When the femoral artery and vein of rabbits are implanted beneath the skin, angiogenesis from both the pedicle and small blood vessels within the adjacent skin begins within 3 days. Perfusion with India ink reveals connections between the pedicle and dermal vessels as early as 5 days after implantation of the pedicle. Provided the pedicle does not thrombose, skin flaps based on it may survive completely when elevated as early as 2 weeks after implantation. Flap survival depends on the development of a small number of vascular connections between vessels arising from the pedicle and preexisting dermal vessels. If elevation is delayed until 4 weeks after implantation a flap may survive even if its pedicle has thrombosed. Prolonged release of basic fibroblast growth factor adjacent to the pedicle significantly increases the survival of flaps elevated 1 week after implantation but does not alter the survival of flaps elevated at 2 and 4 weeks.

A regional anesthetic technique formerly used in adults for tonsillectomy was adapted to provide posttonsillectomy pain relief in children. Injection of 3-10 mL of 0.25%-0.5% bupivacaine into each lateral pharyngeal space appeared to provide good postsurgical analgesia. A retrospective chart review failed to link the technique to airway-related complications. A prospective, randomized, double-blind, placebo-controlled trial comparing the analgesic effectiveness and postsurgical complications in patients undergoing tonsillectomy and receiving either bupivacaine or placebo was begun after institutional approval and informed consent. The study was terminated after eight children had been enrolled because two of four children receiving bupivacaine developed severe upper airway obstruction (UAO) after extubation of the trachea. We conclude that the volume and concentration of bupivacaine were sufficient to block the vagus nerves proximal to the take off of the recurrent laryngeal nerves and/or the hypoglossal nerves, resulting in severe UAO. The short distance between the hyoid and jugular foramen would predispose children and adults with a short neck to the development of this complication. In conclusion, bilateral local anesthetic injection into the lateral pharyngeal space may result in severe UAO and loss of protective reflexes.

There are quantitative deficiencies in the coagulation system for at least the first 6 mo of life. Clinical experience, however, does not indicate an increased risk of excessive bleeding during surgical procedures. Thrombelastography, a test providing a functional evaluation of coagulation, was used to assess the hemostatic system of pediatric patients under 2 yr of age. Thrombelastographic data were obtained from 237 healthy pediatric patients less than 2 yr of age undergoing elective noncardiac surgery. Five groups were distinguished: under 30 days, 1-3 mo, 3-6 mo, 6-12 mo, and 12-24 mo. Thrombelastography revealed no defects in coagulation when these groups were compared to each other or to adults, indicating a functionally intact hemostatic process even in neonates. Indeed, children less than 12 mo of age were found to initiate and develop clot faster than adults, with the coagulation process slowing to adult rates after 1 yr of age. In addition to defining functional integrity, our data represents a set of pediatric control thrombelastographic values that have not been previously reported and that may become important in understanding coagulation changes that accompany disease states and surgery in pediatric patients.

The laryngeal mask airway (LMA) has become a popular tool for airway management in selected adult and pediatric patients undergoing routine surgical procedures. The relationship between end-tidal and arterial carbon dioxide during controlled ventilation via the LMA in infants under 10 kg has not been reported. After induction of general anesthesia, the LMA was placed in 12 healthy infants and mechanical ventilation initiated. After maintaining steady-state level of end-tidal carbon dioxide (minimum 5 min), an arterial blood sample was obtained and end-tidal carbon dioxide level noted. The laryngeal mask was then removed, the trachea intubated, and mechanical ventilation resumed with initial ventilatory variables. After reaching a steady-state level of end-tidal carbon dioxide, a second arterial sample was obtained and end-tidal carbon dioxide level noted. The mean end-tidal carbon dioxide and arterial partial pressure of carbon dioxide obtained during ventilation were 42.2 +/- 7.9 and 47.1 +/- 11.0 (LMA) and 37.4 +/- 4.6 and 42.6 +/- 6.7 (endotracheal tube), respectively. Analysis of differences between partial pressure of carbon dioxide and end-tidal carbon dioxide using the Bland and Altman method revealed bias+/-precision of 4.9 +/- 3.9 and 5.3 +/- 3.2 with ventilation via the laryngeal mask and endotracheal tube. Our data indicate that, while ventilating infants under 10 kg with LMA, end-tidal carbon dioxide is an accurate indicator of arterial partial pressure of carbon dioxide.

We performed a prospective, randomized, placebo-controlled, double-blind trial to assess the efficacy of aprotinin in 61 children (median age 3.7 yr) undergoing reoperative open heart surgery (OHS). Three demographically similar groups were studied: large-dose aprotinin (ALD), small-dose aprotinin (ASD), and placebo (P). Over the first 24 postoperative hours fewer patients in the aprotinin groups received packed red cells (ALD, 53%; ASD, 89%; and P, 95%; P = 0.001), platelets (ALD, 32%; ASD, 50%; and P, 65%; P = 0.04), and fresh frozen plasma (ALD, 16%; ASD, 17%; and P, 60%; P = 0.003) than placebo patients. Most importantly, aprotinin patients had fewer exposures to banked blood components (ALD, median 1 U; and ASD, median 2 U) than P (median 6 U; P = 0.001), with no difference in overall complication rate. Use of aprotinin was associated with a savings in the patient charges for blood components, operating room time, and duration of hospitalization. In conclusion, aprotinin decreased the number of units of banked blood components used during the first 24 postoperative hours in reoperative pediatric OHS. Aprotinin thus decreases the risks associated with exposure to banked blood components and reduces hospital charges.

To evaluate muscle relaxant onset times and tracheal intubating conditions, 60 children (ASA physical status I or II) aged 18 to 72 mo were randomly assigned to receive a bolus of either rocuronium 0.6 mg/kg, vecuronium 0.1 mg/kg, or atracurium 0.5 mg/kg. After induction of anesthesia with etomidate 0.2-0.4 mg/kg and fentanyl 1-3 mg/kg, lungs were ventilated with 50% nitrous oxide in oxygen via a face mask. The evoked electromyogram of the adductor pollicis to a train-of-four stimulation every 20 s was monitored. After administration of the muscle relaxant, endotracheal intubation was attempted every 30 s, beginning 30 s after drug administration, until intubation could be achieved with good or excellent conditions. Rocuronium produced acceptable intubating conditions significantly faster (all tracheas intubated within 60 s) compared with vecuronium (120 s) and atracurium (180 s). The quality of intubating conditions at the time of completed intubation was rated significantly better with rocuronium than with vecuronium or atracurium. However, onset to 95% block at the adductor pollicis muscle was not significantly different after rocuronium (92 +/- 46.9 s), vecuronium (112 +/- 33.3 s), or atracurium (134 +/- 57.1 s), and mean neuromuscular block achieved at the point of successful intubation was not complete in all groups. We conclude that clinically acceptable intubating conditions are produced more rapidly with rocuronium than with atracurium or vecuronium.