Implementation of active injury management (AIM) in youth with acute concussion: A randomized controlled trial.

BACKGROUND: Nearly 2 million youth seek acute medical care following concussion in the U.S. each year. Current standard of care recommends rest for the first 48 h after a concussion. However, research suggests that prolonged rest may lengthen recovery time especially for patients with certain risk profiles. Research indicates that physical activity and behavioral management interventions (sleep, stress management) may enhance recovery. To date, there is limited empirical evidence to inform acute (<72 h) concussion recommendations for physical activity and behavioral management in adolescents. OBJECTIVE: To determine the effectiveness of physical activity and behavioral management for acute concussion in adolescents and young adults, and to evaluate the role of patient characteristics on treatment response. METHODS: This multicenter prospective randomized controlled trial will determine which combination of physical activity and behavioral management is most effective for patients 11-24 years old who present to the emergency department or concussion clinic within 72 h of injury. Participants are randomized into: 1) rest, 2) physical activity, 3) mobile health application (mHealth) behavioral management, or 4) physical activity and mHealth app conditions. Assessments at enrollment, 3-5 days, 14 days, 1 month, and 2 months include: concussion symptoms, balance, vestibular-ocular and cognitive assessments, quality of life, and recovery time. Somatic symptoms and other risk factors are evaluated at enrollment. Compliance with treatment and symptoms are assessed daily using actigraph and daily self-report. The primary study outcome is symptoms at 14 days. CONCLUSION: Prescribed physical activity and behavioral management may improve outcomes in youth following acute concussion.

Clarifying domains of internalizing psychopathology using neurophysiology.

Current initiatives such as the National Institute of Mental Health's Research Domain Criteria project aim to reorganize classification of mental disorders along neurobiological lines. Here, we describe how consideration of findings from psychiatric research employing two physiological measures with distinct neural substrates--the startle blink reflex and the error-related negativity (ERN)--can help to clarify relations among disorders entailing salient anxiety or depressive symptomatology. Specifically, findings across various studies and reviews reveal distinct patterns of association for both the startle blink reflex and the ERN with three key domains of psychopathology: (1) Fear (or phobic) disorders (distinguished by increased startle to unpleasant stimuli, but normal-range ERN). (2) Non-phobic anxiety disorders and negative affect (associated with increased ERN, increased startle across all types of emotional stimuli and increased baseline startle) and, more tentatively (3) Major depression (for which patterns of response for both startle and ERN appear to vary, as a function of severity and distinct symptomatology). Findings from this review point to distinct neurobiological indicators of key psychopathology domains that have been previously demarcated using personality and diagnostic data. Notably, these indicators exhibit more specificity in their relations with these three domains than has been seen in quantitative-dimensional models. Implications of these findings are discussed.

Obstetric morbidity associated with amniotic sheets.

OBJECTIVE: The objective of this study was to determine whether amniotic sheets are associated with an increase in obstetric and neonatal morbidity. METHODS: Using a cohort study design, we identified all women with amniotic sheets, detected by a second-trimester ultrasound examination at a university hospital over a 6-year period. All women who received an ultrasound examination during that time, without a diagnosis of amniotic sheets, were also identified, and two women from among this group were randomly selected as controls for each case. Maternal and neonatal data were abstracted from the medical records, and maternal and neonatal morbidity were compared between the two groups. RESULTS: One hundred and twenty-two women with pregnancies with a diagnosis of amniotic sheets were identified and compared to 244 women with pregnancies without a diagnosis of amniotic sheets. Composite obstetric morbidity was higher in women with amniotic sheets: 21.3% vs. 8.2% (relative risk (RR) 2.6; 95% CI, 1.5-4.5). Additionally, in women with amniotic sheets, neonates were more likely to be born with a birth weight of < 2500 g (RR 3.3; 95% CI, 1.8-6.4) and were more likely to be admitted to the neonatal intensive care unit (RR 2.3; 95% CI, 1.3-4.3). There were no perinatal deaths observed in either group. CONCLUSION: Amniotic sheets are associated with an increase in adverse obstetric outcomes.

17beta-estradiol regulates the secretion of TGF-beta by cultured human dermal fibroblasts.

Estrogen plays an important role in skin homeostasis, as demonstrated by the changes seen in the skin of post-menopausal women, changes reversed by HRT. Estrogen also has a role in wound healing, since estrogen deficiency as occurs post-menopausally and in ovariectomised animals, is associated with a reduced rate of wound healing. Estrogen appears to modulate all phases of wound healing with effects on inflammatory cells, epithelialization, angiogenesis, extracellular matrix deposition and tissue remodelling. This study was designed to investigate the effects of 17beta-estradiol on cultured human dermal fibroblasts using an in vitro wound-healing assay. The end points investigated were cell migration, proliferation, total collagen secretion and active TGF-beta1 secretion. 17beta-estradiol significantly increased the migration and proliferation of cultured dermal fibroblasts following mechanical wounding, although the secretion of total soluble collagen was not altered. An increase in TGF-beta1 was demonstrated by unwounded confluent dermal fibroblast monolayers in response to 17beta-estradiol, but paradoxically, a decrease in the secretion of TGF-beta1 was demonstrated in the mechanically wounded dermal fibroblasts. These results identify human dermal fibroblasts as estrogen target cells and provide further evidence for a role by which estrogen regulates this particular cell type as part of the wound-healing process. However, the paradoxical nature of the effect of estrogen on TGF-beta1 secretion following mechanical wounding suggests that the cellular mechanism of action is complex. A greater understanding of the cell-specific action of estrogen may help to develop therapies that will improve cutaneous wound healing in the future.

Neurological changes and emotional functioning in adults with Down Syndrome.

This study was designed to examine emotional changes in adults with Down Syndrome (DS) over time and whether changes in these psychological variables were associated with brain atrophy on MRI scan and the presence of pathological reflexes on the neurological examination. Participants were 26 adults with DS and their caregivers. Caregivers completed a measure of emotional functioning about individuals with DS at two different time points (1 year apart). Levels of cognitive functioning were measured and neurological and MRI examinations were performed on all subjects at initial testing. Significant group effect separated those with and without pathological findings on MRI and neurological exam across three different scales: depression, indifference, and pragmatic language functioning. Problems of poor pragmatic language functioning appeared later in the course of suspected Alzheimer's disease (AD), as demonstrated by a significant group effect at time 2, but not at initial testing. In these subjects, the primary emotional change was a decline in social discourse (e.g. conversational style, literal understanding, verbal expression in social contexts). These emotional levels were stable over time, regardless of degree of cognitive decline. Specific emotional changes occur during the course of AD which were associated with abnormal findings from MRI and from neurological examination. These results, along with abnormalities in brain imaging and the presence of pathological reflexes, suggested that frontal lobe dysfunction is likely to be an early manifestation of Alzheimer's Disease in Down Syndrome.

Percutaneous dilational tracheostomy: a comparison of single- versus multiple-dilator techniques.

OBJECTIVE: To compare the safety and efficacy of single- vs. multiple-dilator techniques in the performance of percutaneous dilational tracheostomy. DESIGN: Prospective randomized trial. SETTING: Intensive care units at a level 1 trauma center. PATIENTS: Fifty consecutive patients requiring tracheostomy for airway control or prolonged mechanical ventilatory support. INTERVENTIONS: Patients were randomized to receive a percutaneous dilational tracheostomy by either the single- or multiple-dilator technique described by Ciaglia. MEASUREMENTS AND MAIN RESULTS: Percutaneous dilational tracheostomy was performed using the single-dilator technique in 6:01 +/- 3:03 mins and by the multiple-dilator technique in 10:01 +/- 4:26 mins (p <.0006). There were no statistically significant differences in complication rates between the two techniques. No major complications occurred with either technique. CONCLUSION: The single-dilator percutaneous tracheostomy technique is a safe, cost-effective, and more rapidly performed method for bedside tracheostomy in the intensive care unit.

Mathematical coupling does not explain the relationship between right ventricular end-diastolic volume and cardiac output.

OBJECTIVE: To evaluate the clinical significance of mathematical coupling on the correlation between cardiac output and right ventricular end-diastolic volume (RVEDV) through measurement of cardiac output by two independent techniques. DESIGN: Prospective, observational study. SETTING: Surgical intensive care unit in a level 1 trauma center. PATIENTS: Twenty-eight critically ill surgical patients who received mechanical ventilation and hemodynamic monitoring with a pulmonary artery catheter. INTERVENTIONS: A pulmonary artery catheter designed to measure right ventricular ejection fraction (RVEF) and cardiac output by the intermittent bolus thermodilution (TDCO) method and continuous cardiac output by the pulsed thermal energy technique was placed. A computerized data logger was used to collect data simultaneously from the RVEF/TDCO system and the continuous cardiac output system. MEASUREMENTS AND MAIN RESULTS: Two hundred forty-nine data sets from 28 patients were compared. There is statistical correlation between TDCO and continuous cardiac output measurements (r = 0.95, p < 0.0001) with an acceptable bias (-0.11 L/min) and precision (+/-0.74 L/min). The correlation was maintained over a wide range of cardiac outputs (2.3-17.8 L/min). There is a high degree of correlation between RVEDV and both TDCO (r = 0.72, p < 0.0001) and independently measured continuous cardiac output (r = 0.68, p < 0.0001). These correlation coefficients are not statistically different (p = 0.15). CONCLUSIONS: The continuous cardiac output technique accurately approximates cardiac output measured by the TDCO method. RVEDV calculated from TDCO correlates well with both TDCO and independently measured continuous cardiac output. Because random measurement errors of the two techniques differ, mathematical coupling alone does not explain the correlation between RVEDV estimates of preload and cardiac output.

Handling and culture of bovine embryos: survey of media used by 26 embryo transfer companies in the USA.

Embryo transfer has evolved from a few highly centralized clinics to a widespread number of clinics offering both clinic and on-the-farm services. Practitioners in the field have made very few changes in the handling and culture of embryos. A short review of general handling techniques, plus a survey of media used by 26 companies in the USA, is presented here. Currently, phosphate-bufferend saline (PBS) plus two other commercially available media (EMCARE and ViGro) are used by these companies. Fourteen different combinations of these products were reported and only 11 of the 26 consistently used the same medium for flushing, culture and freezing.

Clinical and research implications of revising psychological tests.

This article integrates those of other contributors to this special section, "Methods and Implications of Revising Assessment Instruments," to underscore important conceptual factors to consider when undertaking test revisions. These considerations include determination of when test measures have become sufficiently understood to be incorporated in a test revision, cohort effects, revision of administration formats and test instructions, and comparisons of performance levels across test versions. The discussion of these factors also takes into consideration clinical practice and educational implications of making a transition to revised test versions.

Adoptive transfer from interferon-alpha-fed mice is associated with inhibition of active experimental autoimmune encephalomyelitis by decreasing recipient tumor necrosis factor-alpha secretion.

Ingested type I interferon (IFN) suppresses clinical relapse in murine chronic experimental autoimmune encephalomyelitis (EAE), inhibits clinical attacks more effectively than subcutaneous doses, and decreases the adoptive transfer of EAE. To determine whether splenocytes from IFN-fed donors were "suppressor-like" populations, donor SJL/J mice were immunized and fed with mock IFN-alpha or with IFN-alpha every other day for at least 4 weeks after initial clinical attack. Recipients of adoptively transferred CD8+ T cells from mock IFN-alpha-fed donors showed no clinical improvement of clinical disease compared with actively immunized controls. In contrast, recipients of adoptively transferred CD8+ T cells from IFN-alpha-fed donors showed decreased clinical disease compared with recipients of mock IFN-alpha-fed CD8+ T cells. To evaluate the mechanism of protection by donor CD8+ T cells and to determine if ingested IFN-alpha activates natural immunomodulatory cell populations, the authors used the acute EAE model and naïve-fed donor animals as sources of T cells and CD8+ T cells. Con A-activated spleen T cells from naïve nonimmunized mock IFN-alpha-fed donors inhibited actively induced disease and showed decreased recipient TNF-alpha secretion compared with recipients of T cells from mock IFN-fed mice. Donor activated spleen CD8+ T cells from naïve nonimmunized IFN-alpha-fed animals suppressed actively induced EAE in recipients and showed decreased IFN-gamma and TNF-alpha proinflammatory secretion. Decreased recipient TNF-alpha secretion correlates best with the disease protection from IFN-fed T and CD8+ T cells.

The yeast STM1 gene encodes a purine motif triple helical DNA-binding protein.

The formation of triple helical DNA has been evoked in several cellular processes including transcription, replication, and recombination. Using conventional and affinity chromatography, we purified from Saccharomyces cerevisiae whole-cell extract a 35-kDa protein that avidly and specifically bound a purine motif triplex (with a K(d) of 61 pM) but not a pyrimidine motif triplex or duplex DNA. Peptide microsequencing identified this protein as the product of the STM1 gene. Confirmation that Stm1p is a purine motif triplex-binding protein was obtained by electrophoretic mobility shift assays using either bacterially expressed, recombinant Stm1p or whole-cell extracts from stm1Delta yeast. Stm1p has previously been identified as G4p2, a G-quartet nucleic acid-binding protein. This suggests that some proteins actually recognize features shared by G4 DNA and purine motif triplexes, e.g. Hoogsteen hydrogen-bonded guanines. Genetically, the STM1 gene has been identified as a multicopy suppressor of mutations in several genes involved in mitosis (e.g. TOM1, MPT5, and POP2). A possible role for multiplex DNA and its binding proteins in mitosis is discussed.

Ingested endotracheal tube in an adult following intubation attempt for head injury.

General surgeons are often consulted for assistance in the management of ingested foreign bodies. Deglutition of an endotracheal tube is an unusual complication of airway management. In these cases, the artificial airway is "lost" when it becomes lodged deep into the esophagus. Endoscopic extraction has been described as therapeutic. We report a case in which prehospital endotracheal intubation attempt for the management of closed head injury resulted in a swallowed endotracheal tube. The tube remained undetected until radiographs were performed for a second unrelated traumatic event 2 years later. Endoscopic extraction was unsuccessful, due to rigidity of the tube. Surgical extraction via gastrotomy was uneventful. Surgeons involved in trauma and other emergency settings should be aware of this complication and options in management.

Right heart volumetric monitoring: measuring preload in the critically injured patient.

Accurate assessment of preload status is a major concern in the resuscitation of the critically injured patient. Of the three physiologic determinants of stroke volume, preload is the variable that is most frequently influenced by an insult or intervention or both in the trauma patient. In the critically injured patient, clinicians focus on the preload status to restore and maintain intravascular volume in attempts to optimize cardiac output and oxygen delivery. Until recently, efforts to measure and optimize ventricular preload have focused on intracardiac filling pressures (central venous pressure and pulmonary artery occlusion pressure). The purpose of this review is to discuss the application of volumetric measurements that provide a more accurate means of determining recruitable ventricular preload in the critically injured patient.

Renal arteriolar Na+/Ca2+ exchange in salt-sensitive hypertension.

The present studies were performed to assess Na+/Ca2+ exchange activity in afferent and efferent arterioles from Dahl/Rapp salt-resistant (R) and salt-sensitive (S) rats. Renal arterioles were obtained by microdissection from S and R rats on either a low-salt (0.3% NaCl) or high-salt (8.0% NaCl) diet. On the high-salt diet, S rats become markedly hypertensive. Cytosolic calcium concentration ([Ca2+]i) was measured in fura 2-loaded arterioles bathed in a Ringer solution in which extracellular Na (Nae) was varied from 150 to 2 mM (Na was replaced with N-methyl-D-glucamine). Baseline [Ca2+]i was similar in afferent arterioles of R and S rats fed low- and high-salt diet. The change in [Ca2+]i (Delta[Ca2+]i) during reduction in Nae from 150 to 2 mM was 80 +/- 10 and 61 +/- 3 nM (not significant) in afferent arterioles from R rats fed the low- and high-salt diet, respectively. In afferent arterioles from S rats on a high-salt diet, Delta[Ca2+]i during reductions in Nae from 150 to 2 mM was attenuated (39 +/- 4 nM) relative to the Delta[Ca2+]i of 79 +/- 13 nM (P < 0.05) obtained in afferent arterioles from S rats on a low-salt diet. In efferent arterioles, baseline [Ca2+]i was similar in R and S rats fed low- and high-salt diets, and Delta[Ca2+]i in response to reduction in Nae was also not different in efferent arterioles from R and S rats fed low- or high-salt diets. Differences in regulation of the exchanger in afferent arterioles of S and R rats were assessed by determining the effects of protein kinase C (PKC) activation by phorbol 12-myristate 13-acetate (PMA, 100 nM) on Delta[Ca2+]i in response to reductions in Nae from 150 to 2 mM. PMA increased Delta[Ca2+]i in afferent arterioles from R rats but not from S rats. These results suggest that Na+/Ca2+ exchange activity is suppressed in afferent arterioles of S rats that are on a high-salt diet. In addition, there appears to be a defect in the PKC-Na+/Ca2+ exchange pathway that might contribute to altered [Ca2+]i regulation in this important renal vascular segment in salt-sensitive hypertension.

Preload assessment in patients with an open abdomen.

BACKGROUND: Intra-abdominal hypertension and abdominal compartment syndrome cause significant morbidity and mortality in surgical and trauma patients. Maintenance of intravascular preload and use of open abdomen techniques are essential. The accuracy of pulmonary artery occlusion pressure (PAOP) and central venous pressure (CVP) in patients with intra-abdominal hypertension has been questioned. METHODS: Twenty surgical and trauma patients with intra-abdominal hypertension requiring open abdominal decompression were monitored using volumetric thermodilution pulmonary artery catheters. Hemodynamic, oxygenation, inspiratory, and intravesicular pressure measurements were collected prospectively. PAOP, CVP, and right ventricular end-diastolic volume index (RVEDVI) were compared as estimates of preload status. RESULTS: Multiple regression analysis demonstrated that cardiac index correlated significantly better with RVEDVI (r = 0.69) than with PAOP (r = -0.27) or CVP (r = -0.28) during resuscitation after open abdominal decompression (p < 0.0001). CONCLUSION: RVEDVI is superior to PAOP and CVP as an estimate of preload status in patients with an open abdomen.

Right ventricular end-diastolic volume index as a predictor of preload status in patients on positive end-expiratory pressure.

OBJECTIVE: To evaluate the clinical utility of right ventricular end-diastolic volume index (RVEDVI) and pulmonary artery occlusion pressure (PAOP) as measures of preload status in patients with acute respiratory failure receiving treatment with positive end-expiratory pressure. DESIGN: Prospective, cohort study. SETTING: Surgical intensive care unit in a Level I trauma center/university hospital. PATIENTS: Sixty-four critically ill surgical patients with acute respiratory failure. INTERVENTIONS: All patients were treated for acute respiratory failure with titrated levels of positive end-expiratory pressure (PEEP) with the goal of increasing arterial oxygen saturation to > or =0.92, reducing FIO2 to <0.5, and reducing intrapulmonary shunt to < or =0.2. Serial determinations of RVEDVI, PAOP, and cardiac index (CI) were recorded. MEASUREMENTS AND MAIN RESULTS: Two hundred-fifty sets of hemodynamic variables were measured in 64 patients. The level of PEEP ranged from 5 to 50 cm H2O (mean 12+/-9 [SD] cm H2O). At all levels of PEEP, CI correlated significantly better with RVEDVI than with PAOP. At levels of PEEP > or =15 cm H2O, CI was inversely correlated with PAOP, but remained positively correlated with RVEDVI. CONCLUSIONS: CI correlates significantly better with RVEDVI than PAOP at all levels of PEEP up to 50 cm H2O. RVEDVI is a more reliable predictor of volume depletion and preload recruitable increases in CI, especially in patients receiving higher levels of PEEP where PAOP is difficult to interpret.

Evaluation of acute mental status change in the nonhead injured trauma patient.

Acute mental status change in the first 24 hours after trauma is uncommon in nonhead injured patients who initially present with a normal sensorium. Although arterial hypoxemia is the classic etiology for such a mental status change, three less common etiologies should always be considered: cerebral fat embolism, blunt carotid artery injury, and vertebrobasilar artery thrombosis. Prompt diagnosis and appropriate treatment can significantly improve patient morbidity and mortality. Three nonhead injured trauma patients are described illustrating cerebral fat embolism, blunt carotid artery injury, and vertebrobasilar artery thrombosis as causes of acute mental status change. Each patient initially presented with a clear sensorium, but subsequently developed neurological deficits within 24 hours after admission. All had a normal admission CT scan of the head. MRI or conventional arteriography was diagnostic in each case. Any patient who is initially lucid and subsequently develops a neurological deficit, or a patient whose neurological status does not correlate with brain CT findings should undergo immediate evaluation for possible cerebral fat embolism or cervical vessel injury. An algorithm for management of nonhead injured trauma patients with acute mental status deterioration is presented.