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Biomedical subjects

Mark A Helfaer

Publications and source records attributed to Mark A Helfaer.

At least 19 recordsLinked to original sources
PubMed2006

Neurobehavioral functional deficits following closed head injury in the neonatal pig.

Neurobehavioral deficits in higher cortical systems have not been described previously in a large animal model of diffuse brain injury. Anesthetized 3-5 day old piglets were subjected to either mild (142 rad/s) or moderate (188 rad/s) rapid non-impact axial rotations of the head. Multiple domains of cortical function were evaluated 5 times during the 12 day post-injury period using tests of neurobehavioral function devised for piglets. There were no observed differences in neurobehavioral outcomes between mild injury pigs (N=8) and instrumented shams (N=4). Moderately injured piglets (N=7) had significantly lower interest in exploring their environment and had higher failure rates in visual-based problem solving compared to instrumented shams (N=5) on days 1 and 4 after injury. Neurobehavioral functional deficits correlated with neuropathologic damage in the neonatal pigs after inertial head injury. Injured axons detected by immunohistochemistry (beta-APP) were absent in mild injury and sham piglets, but were observed in moderately injured piglet brains. In summary, we have developed a quantitative battery of neurobehavioral functional assessments for large animals that correlate with neuropathologic axonal damage and may have wide applications in the fields of cardiac resuscitation, stroke, and hypoxic-ischemic brain injury.

Amyloid beta-Protein Precursor↗
PubMed2006

Shaken baby syndrome.

Unfortunately, head trauma caused by shaken baby syndrome is a common occurrence in infants and young children. The proper treatment and safety of these children can be enhanced by the nurse's ability to recognize features characteristic of this syndrome. If abuse is suspected, appropriate physicians, child-protective, and law-enforcement agencies should be notified immediately. Further research must be done to improve the understanding of the mechanisms associated with this disorder in the ultimate hope of improving the lives and outcome of infants and children.

Child, Preschool↗
PubMed2006

Sepsis-induced lung injury in rats increases alveolar epithelial vulnerability to stretch.

OBJECTIVE: Previous in vitro models have shown that cellular deformation causes dose-dependent injury and death in healthy rat alveolar epithelial cells (AECs). We compared the viability of AECs from septic rats with those from nonseptic rats after 1 hr of cyclic equibiaxial stretch. We hypothesized that sepsis would increase stretch-induced cell death. DESIGN: Laboratory investigation. SETTING: University research laboratory. SUBJECTS: Thirty-seven male Sprague-Dawley rats weighing 240-260 g. INTERVENTIONS: Anesthetized rats were subjected to cecal ligation and double puncture (2CLP) or sham laparotomy without cecal ligation or puncture (sham). After 24 or 48 hrs, AECs were isolated, seeded in custom wells, and maintained in culture for 48 hrs before study. AECs were stretched cyclically (15/min) to a 0%, 12%, 25%, or 37% change in surface area (DeltaSA) for 1 hr. Cell viability, phenotypic markers, and nuclear factor-kappaB intracellular localization were assessed using fluorescent immunocytochemistry. MEASUREMENTS AND MAIN RESULTS: Phase and fluorescent images were evaluated for all studies. Response to stretch was the same at 24 and 48 hrs after 2CLP. Relative to sham, 2CLP significantly increased cell death at 25 and 37% DeltaSA (p<.003, analysis of variance). Relative to sham, 2CLP did not alter expression of type I or type II phenotypic markers. Nuclear factor-kappaB within the nuclear compartment was observed after 2CLP in unstretched cells and after 1 hr of cyclic stretch at 37% DeltaSA. In sham, nuclear factor-kappaB within the nuclear compartment was seen only after stretch. CONCLUSIONS: AECs isolated from septic rats are more vulnerable to mechanical deformation injury than AECs from nonseptic animals.

Animals↗
PubMed2006

Challenges of electronic medical record implementation in the emergency department.

TARGET AUDIENCE: Physicians, nurse practitioners and physician assistants who care for infants and children in the emergency department or in other ambulatory and acute care settings. In particular, physicians with administrative responsibilities will find this information useful. OBJECTIVES: 1. Describe the purpose and scope of an electronic medical record. 2. Point out the unique demands that the emergency department places upon an EMR. 3. List the advantages and disadvantages of computerized charting.

Emergency Service, Hospital↗
PubMed2005

Kinetic therapy improves oxygenation in critically ill pediatric patients.

OBJECTIVE: To compare changes in oxygenation after manual turning and percussion (standard therapy) and after automated rotation and percussion (kinetic therapy). DESIGN: Randomized crossover trial. SETTING: General and cardiac pediatric intensive care units. PATIENTS: Intubated and mechanically ventilated pediatric patients who had an arterial catheter and no contraindications to using a PediDyne bed. INTERVENTIONS: Patients were placed on a PediDyne bed (Kinetic Concepts) and received 18 hrs blocks of standard and kinetic therapy in an order determined by randomization. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases were measured every 2 hrs during each phase of therapy. Oxygenation index and arterial-alveolar oxygen tension difference [P(A-a)O(2)] were calculated. Indexes calculated at baseline and after each 18-hr phase of therapy were analyzed. Fifty patients were enrolled. Data from 15 patients were either not collected or not used due to reasons that included violation of protocol and inability to tolerate the therapies in the study. Indexes of oxygenation were not normally distributed and were compared using Wilcoxon signed rank testing. Both therapies led to improvements in oxygenation, but only those from kinetic therapy achieved statistical significance. In patients receiving kinetic therapy first, median oxygenation index decreased from 7.4 to 6.19 (p = .015). The median P(A-a)O(2) decreased from 165.2 to 126.4 (p = .023). There were continued improvements in oxygenation after the subsequent period of standard therapy, with the median oxygenation index decreasing to 5.52 and median P(A-a)O(2) decreasing to 116.0, but these changes were not significant (p = .365 and .121, respectively). When standard therapy was first, the median oxygenation index decreased from 8.83 to 8.71 and the median P(a-a)o(2) decreased from 195.4 to 186.6. Neither change was significant. Median oxygenation index after the subsequent period of kinetic therapy was significantly lower (7.91, p = .044) and median P(A-a)O(2) trended lower (143.4, p = .077). CONCLUSIONS: Kinetic therapy is more efficient than standard therapy at improving oxygenation and produces improvements in oxygenation that are more persistent.

Analysis of Variance↗
PubMed2005

Trends in operative management of pediatric splenic injury in a regional trauma system.

OBJECTIVE: Selective nonoperative management of pediatric blunt splenic injury became the standard of care in the late 1980s. The extent to which this practice has been adopted in both trauma centers and nontrauma hospitals has been investigated sporadically. Several studies have demonstrated significant variations in practice patterns; however, most published studies capture only a selective population over a relatively short time interval, often without simultaneous adjustment for confounding variables. The objective of this study was to characterize the variation in operative versus nonoperative management of blunt splenic injury in children in nontrauma hospitals and in trauma centers with varying resources for pediatric care within a regionalized trauma system in the past decade. METHODS: The study population included all children who were younger than 19 years and had a diagnosis of blunt injury to the spleen (International Classification of Diseases code 865.00-865.09) and were admitted to each of the 175 acute care hospitals in Pennsylvania between 1991 and 2000. The proportion of patients who were treated operatively was stratified by trauma-level certification and adjusted for age and splenic injury severity. Multivariable logistic regression models were used to generate probabilities of splenectomy by age, injury severity, and hospital type. RESULTS: From 1991 through 2000 in Pennsylvania, 3245 children sustained blunt splenic injury that required hospitalization; 752 (23.2%) were treated operatively. Generally, as age and splenic injury severity increased, the proportion of patients who were treated operatively increased. Compared with pediatric trauma centers, the relative risk (with associated 95% confidence interval) of splenectomy was 4.4 (3.0-6.3) for level 1 trauma centers with additional qualifications in pediatrics; 6.2 (4.4-8.7) for level 1 trauma centers, 6.3 (5.3-7.4) for level 2 trauma centers, and 5.0 (4.2-5.9) for nontrauma centers. Significant variation in practice pattern was seen among hospital types and over time even after adjustment for age and injury severity. CONCLUSIONS: The operative management of splenic injury in children varied significantly by hospital trauma status and over time during the past decade in Pennsylvania. Given the relative benefits of nonoperative treatment for children with blunt splenic injury, these results highlight the need for more widespread and standardized adoption of this treatment, particularly in hospitals without a large volume of pediatric trauma patients.

Abdominal Injuries↗
PubMed2004

Traumatic axonal injury is exacerbated following repetitive closed head injury in the neonatal pig.

Inflicted brain injury is associated with widespread traumatic axonal injury (TAI) and subdural hematoma and is the leading cause of death in infants and children. Anesthetized 3-5-day-old piglets were subjected to either a single (n = 5) or double (n = 6, 15 min apart) rapid (<15 msec), non-impact, axial rotations of the head. Peak rotational velocities (averaging 172 rad/sec for single and 138 rad/sec for double loads) were lower than those utilized to induce severe injuries (240-260 rad/sec; Raghupathi and Margulies, 2002). At 6 h post-injury, brains were evaluated for the presence TAI using immunohistochemistry for the 200-kDa neurofilament protein (NF200). Accumulation of NF200 was observed in both contiguous (swellings) and in disconnected axons (axon bulbs) predominantly in central deep and peripheral subcortical white matter regions in the frontal, temporal, and parietal lobes of all injured piglets. Although the density of injured axons did not significantly increase after two rotational loads, the distribution of injured axons shifted from a few foci (2.2 +/- 2.3 per animal) with 1-2 swellings/bulbs following a single rotation to significantly more foci (14.7 +/- 11.9), and additional foci (2.5 +/- 1.9) containing 3 or more axon swellings/bulbs following two rotational loads. The density and distribution of injured axons following a single mild rotation were significantly reduced compared with those obtained previously following a single more severe rotational load. Collectively, these data are indicative of the graded response of the immature brain to rotational load magnitude, and importantly, the vulnerability to repeated, mild, non-impact loading conditions.

Animals↗
PubMed2004

Guidelines for critical care medicine training and continuing medical education.

OBJECTIVE: Critical care medicine trainees and faculty must acquire and maintain the skills necessary to provide state-of-the art clinical care to critically ill patients, to improve patient outcomes, optimize intensive care unit utilization, and continue to advance the theory and practice of critical care medicine. This should be accomplished in an environment dedicated to compassionate and ethical care. PARTICIPANTS: A multidisciplinary panel of professionals with expertise in critical care education and the practice of critical care medicine under the direction of the American College of Critical Care Medicine. SCOPE: Physician education in critical care medicine in the United States should encompass all disciplines that provide care in the intensive care unit and all levels of training: from medical students through all levels of postgraduate training and continuing medical education for all providers of clinical critical care. The scope of this guideline includes physician education in the United States from residency through ongoing practice after subspecialization. DATA SOURCES AND SYNTHESIS: Relevant literature was accessed via a systematic Medline search as well as by requesting references from all panel members. Subsequently, the bibliographies of obtained literature were reviewed for additional references. In addition, a search of organization-based published material was conducted via the Internet. This included but was not limited to material published by the American College of Critical Care Medicine, Accreditation Council for Graduate Medical Education, Accreditation Council for Continuing Medical Education, and other primary and specialty organizations. Collaboratively and iteratively, the task force met, by conference call and in person, to construct the tenets and ultimately the substance of this guideline. CONCLUSIONS: Guidelines for the continuum of education in critical care medicine from residency through specialty training and ongoing throughout practice will facilitate standardization of physician education in critical care medicine.

Clinical Competence↗
PubMed2004

Risk factors for mortality in 137 pediatric cardiac intensive care unit patients managed with extracorporeal membrane oxygenation.

OBJECTIVE: To identify factors associated with mortality in children with heart disease managed with extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective chart review. SETTING: Tertiary care university-affiliated children's hospital. PATIENTS: All pediatric cardiac intensive care unit patients managed with ECMO between January 1, 1995, and June 30, 2001. INTERVENTIONS: None. RESULTS: During the study period, 137 patients were managed with ECMO in the pediatric cardiac intensive care unit. Of the 137 patients, 80 (58%) survived > or =24 hrs after decannulation, and 53 (39%) survived to hospital discharge. Patients managed with ECMO following cardiac surgery were analyzed separately from patients not in the postoperative period. Factors associated with an increased probability of mortality in the postoperative patients were age <1 month, male gender, longer duration of mechanical ventilation before ECMO, and development of renal or hepatic dysfunction while on ECMO. Single ventricle physiology and failure to separate from cardiopulmonary bypass were not associated with an increased risk of mortality. Cardiac physiology and indication for ECMO were not associated with mortality rate. Although longer duration of ECMO was not associated with increased mortality risk, patients with longer duration of ECMO were less likely to survive without heart transplantation. CONCLUSIONS: In a series of 137 patients managed with ECMO in a pediatric cardiac intensive care unit, survival to hospital discharge was 39%. In postoperative patients only, mortality risk was increased in males, patients <1 month old, patients with a longer duration of mechanical ventilation before initiation of ECMO, and patients who developed renal or hepatic failure while on ECMO.

Adolescent↗
PubMed2004

The effect of a thyroid hormone infusion on vasopressor support in critically ill children with cessation of neurologic function.

OBJECTIVE: To determine the impact of a thyroid hormone infusion (T4) on the vasopressor requirements in children with cessation of neurologic function (i.e., brain death) during evaluation for organ recovery DESIGN: Retrospective cohort study. SETTING: The 1998-2002 database of a regional organ recovery program. PATIENTS: Children </=18 yrs with cessation of neurologic function during evaluation for organ recovery (n = 171) were included. The treated group (n = 91) received a weight-based bolus and continuous infusion of T4 according to the organ procurement agency protocol. All other children (n = 80) were considered untreated. INTERVENTIONS: T4 was administered at the clinician's discretion. All children (treated and untreated) had identical goals for fluids, blood pressure, and organ function criteria. Vasopressor score ([dopamine x 1] + [dobutamine x 1] + [epinephrine x 100] + [norepinephrine x 100] + [phenylephrine x 100]) at the time of the program's involvement (T0) and at organ recovery (TOR) were recorded. The Wilcoxon rank sum and Student's two-sample t-test were used to compare the average vasopressor score at T0 vs. TOR. The Wilcoxon signed rank test was used to analyze the difference in median vasopressor score at T0 vs. TOR. Multivariable linear regression was used to assess the impact of T4 on the ability to wean vasopressor support while accounting for the effects of several potential confounders. MEASUREMENTS AND MAIN RESULTS: One hundred seventy-one subjects were included in the final analysis. T4 administration was associated with an unadjusted decrease in the vasopressor score of 32 (95% confidence interval, 12-53; p = .002). After adjusting for steroid administration, fluid balance, and baseline vasopressor score, T4 administration was associated with a decrease in vasopressor score of 24 (95% confidence interval, 6-43; p = .011). CONCLUSIONS: T4 reduced vasopressor needs in children with cessation of neurologic function and hemodynamic instability. A prospective study of T4 in critically ill and hemodynamically unstable children appears warranted.

Adolescent↗
PubMed2004

Approaches in the management of acute respiratory failure in children.

PURPOSE OF REVIEW: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are conditions that are associated with significant morbidity and mortality in children. There have been no advances in preventing ARDS, but this review highlights strategies directed at minimizing ventilator-induced lung injury and other new adjunctive therapies in the care of these patients. RECENT FINDINGS: High-frequency oscillatory ventilation, airway pressure release ventilation, and partial liquid ventilation are potential protective ventilatory modes for children with ALI or ARDS. Recruitment maneuvers, prone positioning, and kinetic therapy are all reported to improve oxygenation by opening the lung while positive end-expiratory pressure maintains functional residual capacity. Inhaled nitric oxide and surfactant are used to reduce inspired oxygen concentration and facilitate gas exchange, but their efficacy in ARDS continues to be investigated. Also, early investigations suggest that a specialized enteral formula can be a useful adjunctive therapy by reducing lung inflammation and improving oxygenation. When mechanical ventilation and adjunctive therapies fail, extracorporeal life support continues to be used as a rescue therapy. SUMMARY: It is likely that a combination of these therapies will maximize treatment and clinical outcomes in the future, but the only way that will be proven is through large controlled clinical trials in pediatric patients.

Child↗
PubMed2004

Association of timing, duration, and intensity of hyperglycemia with intensive care unit mortality in critically ill children.

OBJECTIVE: To study the association of timing, duration, and intensity of hyperglycemia with pediatric intensive care unit (PICU) mortality in critically ill children. DESIGN: Retrospective cohort study. SETTING: PICU of a university-affiliated, tertiary care, children's hospital. PATIENTS: A total of 152 critically ill children receiving vasoactive infusions or mechanical ventilation. INTERVENTIONS: None. METHODS: With institutional review board approval, we reviewed a cohort of 179 consecutive children, 1 mo to 21 yrs of age, treated with mechanical ventilation or vasoactive infusions. We excluded 18 with <3 microg.kg(-1).min(-1) dopamine only, diabetes, or solid organ transplant and nine who died within 24 hrs of PICU admission. Peak blood glucose (BG) and time to peak BG during PICU admission, duration of hyperglycemia (percentage of PICU days with any BG of >126 mg/dL), and intensity of hyperglycemia (median BG during first 48 PICU hours) were analyzed for association with PICU mortality using chi-square, Student's t-test, and logistic regression. MEASUREMENTS AND MAIN RESULTS: Peak BG of >126 mg/dL occurred in 86% of patients. Compared with survivors, nonsurvivors had higher peak BG (311 +/- 115 vs. 205 +/- 80 mg/dL, p <.001). Median time to peak BG was similar in nonsurvivors (23.5 hrs; interquartile ratio, 5-236 hrs) and survivors (19 hrs; interquartile ratio, 6-113 hrs). Duration of hyperglycemia was longer in nonsurvivors (71% +/- 14% of PICU days) vs. survivors (37% +/- 5% of PICU days, p <.001). Nonsurvivors had more intense hyperglycemia during the first 48 hrs in the PICU (126 +/- 38 mg/dL) vs. survivors (116 +/- 34 mg/dL, p <.05). Univariate logistic regression analysis showed that peak BG and the duration and intensity of hyperglycemia were each associated with PICU mortality (p <.05). Multivariate modeling controlling for age and Pediatric Risk of Mortality scores showed independent association of peak BG and duration of hyperglycemia with PICU mortality (p <.05). CONCLUSIONS: Hyperglycemia is common in critically ill children. Peak BG and duration of hyperglycemia are independently associated with mortality in our PICU. A prospective, randomized trial of strict glycemic control in this subset of critically ill children who are at high risk of mortality is both warranted and feasible.

Adolescent↗
PubMed2004

An evaluation of a noninvasive cardiac output measurement using partial carbon dioxide rebreathing in children.

Cardiac output (CO) is an important hemodynamic measure that helps to guide the therapy of critically ill patients. Invasive CO assessment in infants and children is often avoided because of the inherent risks. A noninvasive CO monitor that uses partial rebreathing has been recently developed to determine CO via the Fick principle for carbon dioxide. There have been no clinical studies confirming its accuracy in pediatric patients. This is a prospective observational study of 37 children <12 yr of age who underwent cardiac catheterization. Under general anesthesia via an endotracheal tube without a leak, we made multiple CO measurements using thermodilution and compared them with noninvasively determined CO measurements. Paired measurements were analyzed for bias, precision, and correlation via Bland-Altman plot and linear regression. Noninvasive measurements showed a linear correlation with thermodilution CO assessment with an r value of 0.83 (P < 0.03). Bland-Altman analysis yielded a bias of -0.27 L/min and a precision +/-1.49 L/min. Cardiac index measurements demonstrated a decreased r value of 0.67 (P = 0.15) and a bias of -0.18 L . min(-1) . m(-2) and precision of +/-2.13 L . min(-1) . m(-2). Differences between partial rebreathing measurements and thermodilution measurements were largest in children with a body surface area of </=0.6 m(2) ventilated with tidal volumes <300 mL. Based on these findings, noninvasive CO measurement using partial rebreathing may be clinically acceptable in children with >0.6 m(2) body surface area and >300 mL tidal volume.

Anesthesia, General↗
PubMed2003

Transient loss of microtubule-associated protein 2 immunoreactivity after moderate brain injury in mice.

Microtubule-associated protein 2 (MAP2) is important for microtubule stability and neural plasticity and appears to be among the most vulnerable of the cytoskeletal proteins under conditions of neuronal injury. To evaluate the acute effects of moderate severity traumatic brain injury on MAP2, anesthetized, adult male C57BL/6 mice were subjected to controlled cortical impact brain injury. At 5 min, 15 min, 90 min, 4 h, and 24 h following brain injury (n = 4 injured and n = 1 sham-injured per time point), mice were sacrificed and immunohistochemistry was performed on coronal brain sections. Profound decreases in MAP2 immunolabeling were observed in the ipsilateral cortex and hippocampal dentate hilus at 5 min postinjury and in the ipsilateral hippocampal CA3 area by 4 h postinjury. Decreases in MAP2 labeling occurred prior to notable neuronal cell loss. Interestingly, cortical MAP2 immunoreactivity returned by 90 min postinjury, but the recovery was short-lived within the core in comparison to the periphery of the impact site. Partial restoration of MAP2 immunoreactivity was also observed in the ipsilateral CA3 and dentate hilus by 24 h postinjury. Our data corroborate that MAP2 is an early and sensitive marker for neuronal damage following traumatic brain injury. Acute MAP2 loss, however, may not necessarily presage neuronal death, even following moderate severity traumatic brain injury. Rather, to the best of our knowledge, our data are the first to suggest an intrinsic ability of the traumatized brain for MAP2 recovery after injury of moderate severity.

Animals↗
PubMed2002

Rapid loss and partial recovery of neurofilament immunostaining following focal brain injury in mice.

Neurofilaments (NF), the intermediate filaments of the neuronal cytoskeleton, provide mechanical stability to the cell. High-molecular-weight NF (NFH) comprises a heavily phosphorylated carboxyl terminal ("sidearm") domain which helps determine interfilament spacing distances. Experimental evidence suggests that dephosphorylation greatly increases the rate and extent of proteolysis of NFH. Because NF proteolysis has been implicated as one pathogenic mechanism underlying cell death following traumatic brain injury (TBI), we analyzed the patterns of acute NFH damage in relation to phosphorylation state following focal, concussive, controlled cortical impact (CCI) brain injury in mice. Brains from C57BL/6 male mice (n = 4 injured and n = 1 sham per time point) were evaluated 5 min, 15 min, 90 min, 4 h, and 24 h following CCI injury (1 mm depth, 5 m/s). Immunohistochemistry was performed using antibodies that recognize epitopes on either dephosphorylated (d-NFH) or phosphorylated (p-NFH) sidearms or on the core (c-NFH) domain. As early as 5-15 min postinjury, immunoreactivity for d-, p-, and c-NFH decreased in the ipsilateral cortex, and hippocampal CA3, CA1, and dentate areas. This marked decrease of NFH labeling occurred in the absence of notable cell loss. Furthermore, partial recovery of NFH labeling was observed as early as 90 min postinjury in the cortex and by 24 h postinjury in hippocampal CA3 and dentate. The results of this study suggest that both phosphorylated and dephosphorylated NFH are vulnerable almost immediately following focal brain injury in mice, but that injured neurons may have an adaptive capability to partially restore this important cytoskeletal protein.

Animals↗