Dynamic interaction network involving the conserved intrinsically disordered regions in human eIF5.

Translation initiation in eukaryotes requires multiple eukaryotic translation initiation factors (eIFs) and involves continuous remodeling of the ribosomal preinitiation complex (PIC). The GTPase eIF2 brings the initiator Met-tRNAi to the PIC. Upon start codon selection and GTP hydrolysis, promoted by eIF5, eIF2-GDP is released in complex with eIF5. Here, we report that two intrinsically disordered regions (IDRs) in eIF5, the DWEAR motif and the C-terminal tail (CTT) dynamically contact the folded C-terminal domain (CTD) and compete with each other. The eIF5-CTD•CTT interaction favors eIF2ß binding to eIF5-CTD, whereas the eIF5-CTD•DWEAR interaction favors eIF1A binding, which suggests how intramolecular contact rearrangement could play a role in PIC remodeling. We show that eIF5 phosphorylation by CK2, which is known to stimulate translation and cell proliferation, significantly increases the eIF5 affinity for eIF2. Our results also indicate that the eIF2ß subunit has at least two, and likely three eIF5-binding sites.

Firearms in the home: parental perceptions.

BACKGROUND: Each year, thousands of children are injured or killed from unintentional gunshot wounds. Discovering a gun while playing in the home places children at risk of being injured by the firearm. OBJECTIVES: To determine parental firearm storage practices and parental perceptions of the behavior of their children around guns. METHODS: Cross-sectional survey of parents of children from 4 to 12 years of age. A sample of 424 parents, bringing their children to one of five pediatric ambulatory care centers, were asked to complete a 20-point self-administered questionnaire at the time of their visit. RESULTS: A total of 400 parents (94%) completed the questionnaire; 113 parents (28%) reported keeping a firearm (most often a handgun) in the home. Firearm owners were predominantly male, 30 years of age or older, white, and married. Of the gun owners, 52% stored their firearms loaded or unlocked, and 13% kept one or more guns loaded and unlocked. Three fourths of gun-owning parents believed that their 4- to 12-year-old child could tell the difference between a toy gun and a real gun, and 23% believed that their child could be trusted with a loaded gun. Although the majority of gun-owning parents (53%) endorsed safe storage as the best firearm injury prevention strategy, 61% of parents who do not own firearms endorse not owning guns as the best way to prevent pediatric firearm injuries. CONCLUSION: A majority of gun-owning parents store their firearms loaded or unlocked, substantially underestimating the risk of injury to their children. Many firearm-owning parents trust their child with a loaded gun and believe that their young child can tell the difference between a toy gun and a real gun.

Laceration repair using a tissue adhesive in a children's emergency department.

OBJECTIVE: To determine the effectiveness of a tissue adhesive, Histoacryl Blue (HAB), for laceration repair in children. DESIGN: Prospective, randomized clinical trial. SETTING: A tertiary care pediatric emergency center at Egleston Children's Hospital. PARTICIPANTS: Children who presented for laceration repair between October 1994 and February 1995 were prospectively evaluated. Patients less than 1 or greater than 18 years of age, those with lacerations greater than 5 cm, and those with lacerations located on the eyelids, ears, nose, lips, hands, feet, joints, or perineum were excluded. INTERVENTIONS: Following consent and routine wound management, including subcutaneous closure when deemed necessary, patients were randomized to receive skin sutures or HAB for cutaneous closure. METHODS: Length of time required for laceration repair was recorded. Parental perception of the pain experienced by their child was assessed using a visual analogue scale. Photographic documentation of scar appearance at the 2-month follow-up visit was evaluated by plastic surgeons using a visual analogue scale. RESULTS: Sixty-one children were enrolled: HAB group (N = 30), suture group (N = 31). No differences occurred between groups in laceration length, depth, location, or patient demographics. Length of time required for repair was decreased (median, HAB 7 minutes vs suture 17.0 minutes) and parental assessment of their child's pain was significantly less in the HAB group. Parents were more likely to recommend HAB over suturing to other parents or guardians. Cosmetic outcome in the HAB group was assessed to be as good as, or better than, the cosmetic outcome in the suture group as evaluated by two plastic surgeons. CONCLUSION: The use of HAB for laceration repair is an acceptable alternative to conventional suturing with a comparable cosmetic outcome. Advantages include less pain to the child, no need for suture removal, and more efficient use of physician time. Parents were also more likely to recommend HAB over suturing for laceration repair.

Caregiver knowledge and delivery of a commonly prescribed medication (albuterol) for children.

OBJECTIVE: To evaluate caregiver knowledge and delivery of a prescription medication (albuterol) for children. DESIGN: Prospective convenience sample. PARTICIPANTS: Caregivers listing albuterol as one of their child's medications. SETTING: Two urban, university-affiliated pediatric emergency departments. INTERVENTIONS: Caregivers were asked about their knowledge of the medication, the child's dose, frequency, duration of use, and where it was prescribed. In a mock scenario, they measured and demonstrated medication delivery to their child. Common measuring devices and formulations were offered. RESULTS: Forty-one caregivers were enrolled. Thirty-six (88%) were high school educated and 39 (95%) had a primary care provider. Twenty-six (63%) were out of medication, 7 (17%) stated an incorrect dose, 18 (44%) reported an incorrect frequency, and 10 (24%) stated an inadequate duration of use. Formulations chosen were liquid (n = 15, 37%), nebulizers (n= 15, 37%), and inhalers (n = 11, 27%). Metered dosing (metered-dosing inhaler or premixed solution) were chosen by 22 caregivers (54%), calibrated measuring tools (droppers, syringes) by 15 (37%), and noncalibrated delivery devices (teaspoon) by 4 (10%). An improper dose was measured by 9 (22%), and the dose intended was inaccurately measured by 7 (17%). All caregivers using a teaspoon inaccurately measured their intended dose of the liquid formulation. CONCLUSIONS: Metered dosing and calibrated measuring devices aided in the accurate delivery of this prescription medication. However, considerable concern exists with the use of noncalibrated measuring devices (teaspoons), improper frequency, and duration of use. Refilling of medication was also a concern since 63% were out of albuterol. Caregiver education on use, delivery, and refilling of medications must be stressed and assessed at all emergency department and primary care visits. In addition, metered dosing and the use of calibrated measuring devices should be encouraged.

Over-the-counter medications. Do parents give what they intend to give?

OBJECTIVE: To evaluate caregiver (parent or guardian) use of over-the-counter medications (OTCs) as related to the accuracy and correctness of dosing for children seen at a pediatric emergency department with nonemergent concerns. DESIGN: Prospective patient series. SETTING: A tertiary care pediatric emergency center. PARTICIPANTS: A representative sample of children with nonemergent chief complaints. INTERVENTIONS: A questionnaire about general demographic characteristics, recent OTC use, and medical history of the patients was given to each caregiver. A mock scenario was then presented that required the caregivers to determine and measure a correct dose of acetaminophen for their child. A dose of 9 to 16.5 mg/kg was considered correct. Accuracy of measuring was considered within +/-20% of the caregivers' stated intended dose for their child. RESULTS: One hundred caregivers were enrolled in the study. Mean caregivers' age was 29 years, with 82% having at least a high school education. Seventy-seven percent of their children used OTCs within the previous 2 months, and Tylenol (acetaminophen) was the most commonly used. While 66% of the caregivers reported Tylenol use, only 8% reported the use of acetaminophen. During the dosing scenario, only 40% of the caregivers stated an appropriate dose for their child and only 67% accurately measured the amount of acetaminophen they intended. Forty-three percent measured out a correct amount of acetaminophen for their child. However, almost one third of these occurred strictly by accident because they inaccurately measured an improper intended dose. Combining these results, only 30% of the caregivers were able to demonstrate both an accurately measured and correct dose for their child. CONCLUSIONS: Although a large number of caregivers administer OTCs, knowledge of these medications, and accuracy and correctness of dosing remain a marked concern. Improved caregiver education on the accuracy and correctness of dosing OTCs is necessary.

Intravenous ketorolac in the emergency department management of sickle cell pain and predictors of its effectiveness.

OBJECTIVES: To evaluate the effectiveness of intravenous (IV) ketorolac tromethamine in the treatment of children with sickle cell disease with moderate to severe acute vaso-occlusive pain (VOP) and to develop a predictive model that would determine who would need additional IV analgesics. DESIGN: A prospective case series. SETTING: The emergency department of an urban children's hospital in the southeastern United States. PATIENTS: A convenience sample of 51 children aged 6 to 18 years, representing 70 distinct episodes of VOP requiring IV analgesics. INTERVENTION: All patients were given 0.5 to 1 mg/kg IV ketorolac and IV fluids. MAIN OUTCOME MEASURES: Patients, parents, nurses, and physicians assessed pain before and after ketorolac using a standard 100-mm visual analog scale (VAS). RESULTS: Of the 70 episodes of VOP, 37 (53%) adequately resolved with IV ketorolac and IV fluids and required no IV opioids (group A). Thirty-one episodes (47%) required the addition of an IV opioid (group B). Group B had a significantly greater proportion of episodes reporting 4 or more painful sites than group A, 43% (12/28) vs 9% (3/33), respectively (P<.01). Group B also had significantly higher mean initial VAS scores than group A as assessed by the patient (81 vs 60; P<.01), parent (71 vs 54; P<.01), nurse (78 vs 51, P<.01), and physician (69 vs 53; P =.01). Of the patient assessments with an initial VAS score greater than 70, 69% (18/26) required the addition of an opioid. CONCLUSIONS: First-line therapy with IV ketorolac and IV fluids resulted in adequate resolution of pain in 53% of episodes with acute VOP. A reported 4 or more painful sites and an initial VAS score greater than 70 were predictors of the likelihood to need additional IV analgesics.

Serum ethanol clearance in intoxicated children and adolescents presenting to the ED.

OBJECTIVE: To determine the rate of serum ethanol clearance in 39 children and adolescents who presented intoxicated to one ED. METHODS: All pediatric patients presenting to a university hospital ED, for whom serial ethanol levels had been determined between January 1989 and May 1993, were evaluated. Age, gender, presenting complaint, initial serum glucose concentration, timed serum ethanol concentrations, and rate of serum clearance were determined retrospectively for all the patients. RESULTS: 39 pediatric patients had had serial serum ethanol concentrations determined. The patients ranged in age from 6 weeks to 17 years (mean 14.6 years). Initial serum ethanol levels ranged from 13.7 to 84.2 mmol/L (63-388 mg/dL) and the mean serum ethanol clearance rate was 4.0 mmol/L/hr (18.6 mg/dL/hr), consistent with clearance rates previously reported for adults. CONCLUSION: These data suggest that the rate of serum ethanol clearance in children and adolescents presenting to the ED approaches that previously reported for adults. Clinical diminution of intoxication should not be more rapid for children and adolescents than it is for adults.

Lacerations against Langer's lines: to glue or suture?

This study evaluated the effects of initial wound orientation on the cosmetic outcome of facial lacerations repaired with histoacryl blue (HAB), a tissue adhesive, vs. conventional suturing. This was a retrospective analysis of patients from a prospective randomized clinical trial on the use of HAB. Children in the initial cohort who had facial lacerations and were also evaluated for cosmetic appearance at a 2-month follow-up appointment were eligible. Orientation along Langer's Lines, which define the functional anatomy of the underlying structures to the skin, was determined by two investigators blinded to the initial method of repair. Photographs of the wounds were reviewed and the wounds were categorized as being: Langer (+) (<20 degrees deviated from Langer's Lines) or Langer (-) (> or =20 degrees deviated from Langer's Lines). Photographic appearance at follow-up was evaluated using a 100-mm visual analog scale (0=best, 100=worst) by two plastic surgeons blinded to the method of repair. Sixty-one patients were enrolled in the initial cohort, with 55 (90%) evaluated at the 2-month follow-up. Forty-eight of the 55 (87%) had facial lacerations, therefore meeting present study criteria: [HAB (n=26), Suturing (n=22), Langer (+) (n=27), Langer (-) (n=21)]. Langer (+) patients were comparable to Langer (-) for demographics, wound characteristics, and method of repair. There was no difference in overall cosmetic appearance of facial wounds closed with HAB vs. conventional suturing. Follow-up appearance was significantly worse for sutured Langer (-) vs. Langer (+) wounds. In contrast, cosmetic appearance of lacerations closed by HAB were comparable between Langer (-) and Langer (+) wounds. In conclusion, initial wound orientation had a greater impact on the cosmetic appearance for lacerations closed by suturing compared to HAB. HAB may be the preferred method of cutaneous closure for facial lacerations oriented against Langer's Lines.

Pediatric Emergency Medicine Fellowship survey: 1991-1992.

This study was designed to determine the general characteristics, training expectations, and career goals of those individuals entering Pediatric Emergency Medicine Fellowships in 1992 through the NRMP Pediatric Emergency Medicine Match. A 20-item questionnaire was developed and sent to those individuals who successfully obtained fellowship positions through the 1991-1992 Match. All of the respondents will have completed a formal pediatric residency program, and 90% will have completed their residency since 1990. Eighty-eight percent of the respondents have not completed formal postgraduate training other than a pediatric residency, and none of the respondents were from training programs in emergency medicine. Ninety percent of the respondents are planning on two years of training, while 10% are either entering a three-year program or planning an optional third year. Ninety-four percent of the individuals who responded had not applied for Pediatric Emergency Medicine Fellowships in the past, but, while many of the individuals were concerned about obtaining a position, only 6% applied for a fellowship in an alternative field. If the respondents had not obtained positions this year, 79% felt that they would have reapplied next year. When asked why they are pursuing a Pediatric Emergency Medicine Fellowship, 85% listed opportunities in clinical medicine as their primary reason, while 10% claimed that research opportunity was the most important factor. When their fellowships are completed, 77% hope to practice at a university-based children's hospital, and 10% hope to practice at a private children's hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Confidence in performance of pediatric emergency medicine procedures by community emergency practitioners.

OBJECTIVE: To survey a cohort of physicians who work in general community emergency departments (ED) in order to assess their comfort levels in performing urgent and emergent medical procedures on children. METHODS: One hundred seventeen emergency physicians were surveyed at 23 institutions within the referral base of Hasbro Children's Hospital, a tertiary care pediatric ED. Physicians rated their comfort levels (4-point scale: 1 = comfortable, 2 = moderately comfortable, 3 = uncomfortable but would perform in an emergency, 4 = uncomfortable and would never perform) for all procedures in which the American Academy of Pediatrics recommends competence for pediatric emergency physicians. RESULTS: Sixty (51%) physicians completed the survey. Residency training included internal medicine, family practice, surgery, general practice, pediatrics, and emergency medicine, while only 32 (53%) were Board certified in emergency medicine. All respondents treated pediatric patients. Over 25% were uncomfortable (level 3 or 4) with performing certain potentially life-saving pediatric procedures. These included cardioversion, defibrillation, external pacing, nasal intubation, needle cricothyrotomy, rapid sequence intubation, laryngoscopy, tracheostomy replacement, chest tube placement, vascular cutdowns, emergency childbirth, pericardiocentesis, intraosseous line placement, infant subdural and ventriculoperitoneal (V-P) shunt taps, and upper airway foreign body removal. Over 25% of respondents were also uncomfortable with non-life-saving procedures such as temperomandibular joint (TMJ) reductions, tooth reinsertions, rape evaluations, suprapubic taps, tympanocentesis, retrograde urethrograms, thoracentesis, paraphimosis reduction, ear foreign body removal, and pain management. CONCLUSION: While emergency physicians within the catchment area of a tertiary care children's hospital feel comfortable with most pediatric procedures, they express a significant degree of discomfort with many potentially life-saving skills. Because of the infrequent need for many of these interventions in children, the high levels of discomfort are not surprising. These procedures may most comfortably be performed at pediatric centers but can be accomplished well at all EDs if personnel are adequately trained. A strong working relationship with pediatric emergency centers and an enhanced teaching of these procedures may increase comfort levels with these potentially life-saving measures.

Varicella: pediatric genital/rectal vesicular lesions of unclear origin.

Three children who presented with localized vesicular rash in the diaper area were found to have primary varicella-zoster infections. Primary varicella can closely mimic genital herpes simplex virus (HSV 1 or 2), which may be an indicator of sexual abuse. To avoid unfounded investigation for sexual abuse, primary varicella-zoster infection must be included in the differential diagnosis. Direct fluorescent antibody testing is a sensitive and specific diagnostic test that can be used to distinguish HSV 1 or 2 from varicella-zoster.

T-independent form of azophenylarsonate fails to reveal "silent" idiotype-positive B cells in idiotype-suppressed mice.

In three distinct chronic Ig-specific suppression systems in which suppression was initiated by injection of mice with anti-idiotype (Id) or anti-allotype sera, evidence has been presented by others that the differentiation of B cells bearing surface Ig with a target marker (Id or allotype) need not be totally disrupted. Normally "silent" Id+ B cells from Id-suppressed mice could be revealed by certain procedures, one of these being to make use of the powerful stimulatory properties of bacterial lipopolysaccharide. We have employed a similar strategy to determine whether cryptic CRIA+ B cells exist in significant numbers in hyperimmune, CRI-suppressed (HIS) A/J mice. Thus, following T cell removal, the Ar-specific B cell repertoire from HIS mice was probed using Ar- Brucella abortus as a T-independent Ag. No evidence for "silent" CRIA+ B cells was found. The results, taken in conjunction with those of others, suggests that there may exist multiple forms of long-term Ig-specific suppression.

Utility of comprehensive toxicologic screens in children.

This study was undertaken to evaluate the clinical utility and cost-effectiveness of the limited component versus the high performance liquid chromatography (HPLC) component of comprehensive toxicologic screens in children. A retrospective patient series was studied at the emergency department (ED) of Hughes Spalding Children's Hospital, an urban, tertiary-care ED, consisting of all patients younger than 19 years of age who had a comprehensive toxicologic screen between January 1994 and July 1995. The comprehensive test included a broad-spectrum HPLC component as well as a limited component that examined serum for ethanol, aspirin, and acetaminophen and urine for benzodiazepines, barbiturates, amphetamines, cocaine, phencyclidine, and opiates. All toxicologic screens were reviewed for the presence of exogenous toxins, followed by a chart review of all patients with positive screens and a selection of negative screens. Toxins were categorized as (1) iatrogenic or noniatrogenic, (2) clinically or nonclinically suspected by history and physical, and (3) clinically or nonclinically significant. Comprehensive toxicology screens were performed in 463 cases during the study period; 234 (51%) were positive for exogenous toxins. In 227 of 234 positive screens (97%), toxins were either suspected by history and/or physical, were present on the limited portion of the toxicology screen, or were clinically insignificant. The remaining 7 of the 234 positive screens (3%) were clinically significant and detected solely by the broad-spectrum HPLC portion of the comprehensive screen. However, in none of these 7 cases was patient management clinically altered as a result of the positive screen. The total additional cost for the HPLC component was $16,205 ($35x463), an average distributive charge of $2,315 per patient in whom the HPLC portion provided additional clinical information ($16,205/7). Although adding significant charges to the evaluation of suspected toxic exposures in children, the HPLC component of the comprehensive drug screen was of no additional clinical benefit compared with its limited component alone.

Societal savings by "fast tracking" lower acuity patients in an urban pediatric emergency department.

To evaluate the cost-effectiveness of a "fast track" system for diverting lower acuity patients away from the pediatric emergency department (ED), 4,060 patients triaged to the fast track area of an urban pediatric ED with the 10 most common discharge diagnoses from 1/1/94 through 12/31/94 were retrospectively evaluated. Patients triaged as having nonurgent concerns qualified for treatment in a separate fast track area for 8 hours per day (fast track patients). These patients were compared with 5,199 seen in the main pediatric ED for the same concerns during the remaining hours when the fast track was not in operation (ED patients). Computer records were reviewed for demographics, acuity levels, diagnosis, and collection ratios (revenues/charges). The societal savings was calculated as sigma $ [(delta mean revenue of diagnosis1-10 in the main ED - mean revenue of diagnosis1-10 in the fast track) x the number of patients seen in fast track for diagnosis1-10] stratified by acuity. Collection ratios were comparable between groups (57% v 62%), but the average charges (physician and facility) were significantly less for patients seen in the fast track by a ratio of 1:2.4 (P < .0001). The average net revenue was also significantly less for all patients seen in the fast track by a ratio of 1:2.6 (P < .0001). When stratified by diagnosis and acuity, the savings to society was $101,313, or an average of $25/patient seen in the fast track ($101,313 per 4,060). A fast track is an effective system for maintaining patient flow at a cost savings to society. It can help the hospital in its negotiations with payors because it curtails charges. It is also a potential means for maintaining overall departmental revenues as payors increasingly deny traditional pediatric ED visits for patients with lower acuity concerns.

Serum amylase determinations in pediatric patients presenting to the ED with acute abdominal pain or trauma.

The objective of this study was to evaluate the overall impact of serum amylase determinations in the initial management of patients presenting to the pediatric emergency department (ED) with the acute onset of abdominal pain or trauma. All cases of patients younger than 18 years of age who presented to the pediatric ED for whom a serum amylase value was determined during an 18-month period were reviewed. Data were collected retrospectively, including serum amylase concentration, age, gender, presenting complaint, discharge/admission status, diagnosis, and discharge plans or inpatient management to evaluate the impact of serum amylase determinations. Seven hundred twenty-three cases were reviewed during the study period. Six hundred fifty-six patients met study criteria, with 385 serum amylase determinations performed for the evaluation of acute abdominal pain and 271 for acute trauma. Sixty-seven serum amylase determinations were also sent for other reasons. Overall, 12 of 656 study patients had elevated amylase levels (1.8%) during the study period (range, 130 to 2318 U/L). Eight of 271 amylase levels sent to the laboratory for trauma (3.0%), and 4 of 385 sent for abdominal pain (1.0%) were elevated. Overall, serum amylase concentration had no influence on whether or not the patient was admitted to the hospital. Of the 12 patients with elevated amylase levels sent for abdominal pain or trauma, only 2 had their clinical management affected by the serum amylase concentration. In both cases, the patient presented with subacute abdominal pain related to significant abdominal trauma that had occurred 2 to 3 weeks earlier. Both patients showed evidence of pancreatic insult with diagnostic imaging studies.(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective evaluation of pediatric emergency care during the 1996 Summer Olympic Games in Atlanta, Georgia.

OBJECTIVES: To explore the impact that a temporary influx of millions of people can make on the local pediatric emergent and urgent care systems. The spectrum of illness was also explored. DESIGN/METHODS: Prospective cohort of patients from outside the usual catchment area presenting at two children's emergency departments and their satellite urgent care centers during the 1996 Summer Olympics. A 13-point survey was completed on each which included general demographics, transportation, language, time in the area, chief complaint, past medical conditions, diagnosis, and medical complications or problems related to their visit. RESULTS: A total of 263 patients met criteria, mean age 6.7 years. Twenty-four percent were seen in the tertiary care centers and 76% in urgent care. Twenty-three countries with 15 primary languages were represented. Fifty-one percent were in Atlanta for less than seven days, and 44% were uninsured. Most presented with common concerns including; fevers, rashes, respiratory difficulty, and minor trauma. Children were sicker than our typical emergency department patients, with hospital admission rates two times the usual for the tertiary care children's hospital (27% vs 13%) and the county children's hospital (7% vs 3%). Nineteen (7.2%) had unusual presentations or difficulty with care. Notably, five had language barriers; three had serious chronic conditions of unknown detail to the temporary caregiver; two did not bring vital medical supplies (ie, spare tracheotomy tube); one mislabeled medications, causing an overdose; one had leukemia, needed transfusion, but did not know of the regional centers; and one required helicopter transport secondary to traffic. CONCLUSION: A large influx of people resulted in a relatively minor impact on the emergent care system for children. Care could have been improved if those with chronic illnesses were better informed of regional health care centers, essential medical needs for travel, and if travel included a physician's medical summary. In addition, anticipation of the Olympic Games helped the pediatric emergency medicine community improve disaster preparedness, and enhance its working relationship with the adult emergency medicine community and the regional poison center. Ongoing efforts for disaster preparedness with periodic reevaluation have also been established.