Age exaggerates proinflammatory cytokine signaling and truncates signal transducers and activators of transcription 3 signaling following ischemic stroke in the rat.

Neuroinflammation is associated with glial activation following a variety of brain injuries, including stroke. While activation of perilesional astrocytes and microglia following ischemic brain injury is well documented, the influence of age on these cellular responses after stroke is unclear. This study investigated the influence of advanced age on neuronal degeneration, neuroinflammation, and glial activation in female Sprague-Dawley rats after reversible embolic occlusion of the middle cerebral artery (MCAO). Results indicate that in comparison to young adult rats (3 months), aged rats (18 months) showed enhanced neuronal degeneration, altered microglial response, and a markedly increased expression of proinflammatory cytokines/chemokines following MCAO. In addition, the time-course for activation of signal transducers and activators of transcription 3 (STAT3), the signaling mechanism that regulates astrocyte reactivity, was truncated in the aged rats after MCAO. Moreover, the expression of suppressor of cytokine signaling 3 (SOCS3), which is associated with termination of astrogliosis, was enhanced as a function of age after MCAO. These findings are suggestive of an enhanced proinflammatory response and a truncated astroglial response as a function of advanced age following MCAO. These data provide further evidence of the prominent role played by age in the molecular and cellular responses to ischemic stroke and suggest that astrocytes may represent targets for future therapies aimed at improving stroke outcome.

Pathophysiology of the vascular wall and its relevance for cerebrovascular disorders in aged rodents.

Chronic hypertension and cerebral amyloid angiopathy (CAA) are the main pathologies which can induce the rupture of cerebral vessels and intracerebral hemorrhages, as a result of degenerative changes in the vascular wall. A lot of progress has been made in this direction since the successful creation of the first mouse model for the study of Alzheimer's disease (AD), as the spectrum of AD pathology includes a plethora of changes found in pure cerebrovascular diseases. We describe here some of these mouse models having important vascular changes that parallel human AD pathology, and more importantly, we show how these models have helped us understand more about the mechanisms that lead to CAA formation. An important cellular event associated with reduced structural and functional recovery after stroke in aged animals is the early formation of a scar in the infarcted region that impairs subsequent neural recovery and repair. We review recent evidence showing that the rapid formation of the glial scar following stroke in aged rats is associated with premature cellular proliferation that originates primarily from the walls of capillaries in the corpus callosum adjacent to the infarcted region. After stroke several vascular mechanisms are turned-on immediately to protect the brain from further damage and help subsequent neuroregeneration and functional recovery. Although does occur after stroke, vasculogenesis is overshadowed in its protective/restorative role by the angiogenesis and arteriogenesis. Understanding the basic mechanisms underlying functional recovery after cerebral stroke in aging subjects is likely to yield new insights into the treatment of brain injury in the clinic.

Potential pharmacokinetic basis for zolpidem dosing in children with sleep difficulties.

The pharmacokinetics of zolpidem was assessed in this open-label, dose-escalation study in children with insomnia. Twenty-one children, seven per age group (2-6, >6 to 12, >12 to 18 years), received a single dose of zolpidem at one of the three dose levels (0.125, 0.25, or 0.50 mg/kg (20 mg maximum dose)). Multiple pharmacokinetic measures were assessed at nine post-dose intervals and pharmacodynamics was assessed by polysomnography and actigraphy. Significant pharmacokinetic effects by dose were observed only as linear increases in maximum concentration (C(max), P<0.001) and area under the plasma concentration-time curve (AUC, P<0.001). Significant pharmacokinetic effects by age group included an increase in AUC (P=0.02), half-life (P=0.04), and mean residence time (P=0.01), whereas total body clearance decreased (P=0.01) and steady-state volume of distribution was variable. Pharmacodynamic measures were independent of the pharmacokinetic estimates. Overall, zolpidem was well tolerated and a pediatric dose of 0.25 mg/kg is recommended for future efficacy studies.

Outcome analysis of preoperative embolization in cranial base surgery.

OBJECTIVE: Management of cranial base tumors requires an interdisciplinary approach. Supraselective angiography and embolization is an important adjunct to cranial base surgery. Though successful embolization facilitates resection, the morbidity of this procedure remains poorly defined. Therefore, we set out to define the morbidity associated with embolization of skull base meningiomas, thus allowing for informed decision making when considering this adjunct to tumor resection. METHODS: A retrospective analysis was performed on our experience with embolization of 167 cranial base meningiomas. Cranial base meningiomas were defined as tumors originating from the olfactory groove, tuberculum sella, medial sphenoid wing, petro-clival region or foramen magnum. RESULTS: 280 feeding vessels were embolized with an average of 1.7 vessels per lesion. In 91% of patients embolized, good to excellent embolization was achieved without permanent neurological sequelae. In 20 patients no embolization was attempted due to the risk of new neurologic deficits or lack of an appropriate vessel for embolization. Twenty-one patients (12.6%) had transient worsening of their neurologic exam or a medical complication requiring hospitalization. Fifteen patients (9%) experienced permanent neurologic deficits or medical morbidity as a result of embolization. Four of the patients who experienced major complications had a decline in previously compromised cranial nerve function. CONCLUSIONS: Embolization of cranial base tumors is an important part of the therapeutic armamentarium for the treatment of cranial base lesions. Recognition of the morbidity of this procedure will allow for the most appropriate use of this powerful adjunct to cranial base surgery.

Ultrasonography by emergency physicians in patients with suspected cholecystitis.

This article investigates the use of bedside abdominal ultrasonography (BAU) performed by emergency physicians (EPs) to screen patients for cholelithiasis and cholecystitis. In this prospective study EPs performed BAU on 116 patients. Agreement between BAU and formal abdominal ultrasound (FUS) performed in the radiology department for detecting cholelithiasis and cholecystitis was determined using Kappa statistics. Test characteristics of BAU for detecting cholelithiasis and acute cholecystitis were calculated. Agreement between BAU and FUS was 0.71 for cholelithiasis and 0.46 for acute cholecystitis. Test characteristics of BAU for cholelithiasis were sensitivity 92%, specificity 78%, positive predictive value (PPV) 86%, negative predictive value (NPV) 88%. Test characteristics of BAU for acute cholecystitis compared with clinical follow-up were sensitivity 91%, specificity 66%, PPV 70%, NPV 90%. BAU may be used to exclude cholelithiasis and is sensitive for cholecystitis. However, when EPs with limited experience identify cholecystitis a confirmatory test is warranted before cholecystectomy.

The diagnosis of lower extremity deep venous thrombosis.

The diagnosis of lower extremity deep venous thrombosis (DVT) is critical to emergency physicians because of the risk of pulmonary embolism. This article reviews the diagnostic modalities available for patients with suspected lower extremity DVT. The use of compression ultrasonography and the recent advances in the D-dimer assays are emphasized. A clinical algorithm that utilizes a non invasive approach to this potentially life threatening disease is presented.

Treatment of sleep-disordered breathing in children with myelomeningocele.

The prevalence of moderate to severe sleep-disordered breathing (SDB) in patients with myelomeningocele may be as high as 20%, but little information is available regarding treatment of these patients. To assess the efficacy and complications of treatments for these children, we collected data on 73 patients from seven pediatric sleep laboratories. Obstructive sleep apnea (OSA, n = 30) and central apnea (n = 25) occurred more frequently than central hypoventilation (n = 12). We also describe a sleep-exacerbated restrictive lung disease type of SDB in 6 patients who had hypoxemia during sleep without apnea or central hypoventilation. For each type of SDB, effective treatments were identified in a stepwise process, moving towards more complex and invasive therapies. For OSA, adenotonsillectomy was often ineffective (10/14), whereas nasal continuous positive airway pressure (CPAP) was usually successful (18/21). For central apnea, methylxanthines and/or supplemental oxygen proved sufficient in 2 of 9 and 3 of 6, respectively, but noninvasive positive pressure ventilation was required in 7 children. For central hypoventilation, supplemental oxygen (alone or with methylxanthines), noninvasive positive pressure ventilation, and tracheostomy with positive pressure ventilation were effective in 3, 2, and 2 patients, respectively. Sleep-exacerbated restrictive lung disease always required supplemental oxygen treatment, but in 2 cases also required noninvasive positive pressure ventilation; nutritional and orthopedic procedures also were helpful. Posterior fossa decompression was used for the first three types of SDB, but data were insufficient to delineate specific recommendations for or against its use. In summary, evaluation by an experienced, multidisciplinary team can establish an effective treatment regime for a child with myelomeningocele and SDB.

Primary angiitis of the central nervous system as a first presentation in Hodgkin's disease: a case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Granulomatous angiitis of the central nervous system is a rare cause of neurological deterioration. It is often diagnosed posthumously, and a high index of suspicion is necessary to make the correct diagnosis on a timely basis. CLINICAL PRESENTATION: A 27-year-old woman presented to the emergency room with complaints of worsening headache, nausea, and vomiting for 10 days, which were preceded by swelling of her tongue. At the examination, she had mild ocular tenderness, but no cranial nerve abnormalities. Radiographic examination revealed a right temporal lobe area with edema, and mild contrast enhancement was noted on computed tomography and magnetic resonance imaging. A similar but smaller region was present in the left frontal lobe. INTERVENTION: Stereotactic biopsy of the left temporal lobe revealed granulomatous angiitis. Further workup revealed Hodgkin's disease in the mediastinum. Dexamethasone as well as chemotherapy for Hodgkin's disease was initiated. The patient's symptoms resolved, and she returned to work with her disease in remission. CONCLUSION: Previous reports of central nervous system angiitis have shown an association with Sjogren's syndrome, herpes zoster infection, human immunodeficiency virus, and Hodgkin's disease. A review of the literature revealed a total of 12 patients with central nervous system angiitis and Hodgkin's disease. As a group, these patients had very poor outcomes. However, of six patients who presented with central nervous system angiitis and concurrent Hodgkin's disease and who underwent aggressive treatment for both conditions, three had a full recovery, two had a partial recovery, and one died.

Use of intra-aortic balloon pump counterpulsation for refractory symptomatic vasospasm.

Delayed neurologic deficits secondary to vasospasm remain a vexing problem. Current treatments include: hypertensive hypervolemic hemodilution (Triple-H) therapy, angioplasty, and intra-arterial papaverine administration. Significant morbidity and mortality still result from vasospasm despite these therapies. We present two patients with symptomatic vasospasm who received intra-aortic balloon pump counterpulsation (IABP) to improve cerebral blood flow when they were unable to tolerate Triple-H therapy. One patient (L.T.) developed vasospasm after resection of a meningioma that encased the carotid and middle cerebral artery. The other patient (D.F.) suffered a subarachnoid hemorrhage (Fisher Grade III, Hunt/Hess Grade III) from a basilar tip aneurysm. Postoperatively, both patients developed vasospasm. Treatment with Triple-H therapy, angioplasty, and papaverine yielded modest results. When they experienced cardiac ischemia, Triple-H therapy was stopped, but their neurologic condition deteriorated markedly. Because of this, IABP was started. Both patients had an immediate improvement in cardiac function. IABP was able to reverse some of the neurologic deficits, and was weaned off after several days of support. Both patients had a substantial improvement in function, and are now capable of caring for themselves. We conclude that IABP may play an important role for improving cerebral blood flow in patients with vasospasm. It may be particularly useful in those patients with limited cardiac reserve.

Early predictors of myoglobinuria and acute renal failure following electrical injury.

Myoglobinuria-induced acute renal failure (ARF) is a potentially lethal consequence of electrical injury. We describe clinical variables that can predict the risk of myoglobinuria and ARF following electrical injury. This was a retrospective multivariate analysis of risk factors among electrically injured patients over a 26-year period. Urine myoglobin status was documented in 162 patients; 14% had myoglobinuria. No patient developed ARF. Multivariate modeling revealed that high-voltage exposure, prehospital cardiac arrest, full-thickness burns, and compartment syndrome were associated with myoglobinuria. Using a prediction rule defined as positive when a patient had > or = 2 risk factors yielded a sensitivity of 96% and negative predictive value of 99%. Electrical injury patients with myoglobinuria have little risk of developing ARF. A prediction rule can be used to screen out patients at low risk for myoglobinuria and identify high-risk patients who warrant early aggressive treatment and a more definitive myoglobin test.

Proposed grading system to predict the extent of resection and outcomes for cranial base meningiomas.

OBJECTIVE: This investigation was performed to construct a grading system for cranial base meningiomas that augments the current system of topographic labeling. This new system classifies cranial base meningiomas based on predicted surgical resection and patient outcomes. METHODS: Two hundred thirty-two consecutive patients with cranial base meningiomas were surgically treated by the two senior authors between April 1993 and August 1997. Using standard statistical tests, a large number of preoperative, intraoperative, and follow-up findings were analyzed for correlation with the extent of resection. These included the presence of previous radiotherapy, Cranial Nerve III, V, and VI palsies, multiple fossa involvement, and vessel encasement. RESULTS: Analysis revealed that each variable tested was independently and inversely correlated with total tumor resection (P < 0.002). We were able to construct a grading system based on these variables; when more variables are present, the grade is higher. With the grading system, lower-grade tumors were correlated with increased probabilities of total resection (r2 = 0.9947) and better patient outcomes, as measured by Karnofsky performance scale scores (r = 0.9291). We also found that, as a group, patients who underwent subtotal resection exhibited worse Karnofsky performance scale scores and had longer hospital stays. CONCLUSION: The current system of classifying cranial base meningiomas provides no information regarding the tumor except location and no information concerning patient prognosis. We present a more useful system to categorize these tumors. Our scheme must be tested at other centers to corroborate our findings. This new grading system should serve to guide surgical treatment, inform patients, and improve communication among surgeons.

Clinical features of obstructive sleep apnea hypoventilation syndrome in otherwise healthy children.

Obstructive sleep apnea hypoventilation syndrome (OSAHS) is an important public health problem. However, major gaps exist in our knowledge about the clinical features of this disorder in the pediatric age group. The purpose of this study was to examine clinical features of OSAHS diagnosed by polysomnography in otherwise healthy children. In this cross-sectional study, 326 children without underlying medical conditions (5.8+/-3.0 years, range 1-12 years; 56% male) were recruited from patients referred by primary care and otorhinolaryngology physicians for evaluation of snoring and difficulty breathing. Ethnic group distribution was African-American (38%), Caucasian (30%), and Hispanic (31%). Complaints of daytime tiredness or sleepiness were reported in 29% of the children. All children underwent overnight polysomnography (N = 330 studies). OSAHS was diagnosed in 59% of the children, based on polysomnographic criteria. The remaining children had either primary snoring (25%); no snoring (10%), or upper airway resistance syndrome (6%). Neither male gender nor obesity increased the likelihood for the diagnosis of OSAHS. However, the incidence of obesity in the study population (28%) was more than twice that of the general pediatric population. African-American children had a greater likelihood for OSAHS diagnosis compared to Hispanic or Caucasian children. Daytime complaints of sleepiness or tiredness were not more common in children diagnosed with OSAHS than in the children without OSAHS. As expected, tonsillar hypertrophy increased the likelihood of OSAHS diagnosis. In summary, many of the clinical features of childhood OSAHS are in marked contrast to those in adults.

Evaluation of the patient with blunt chest trauma: an evidence based approach.

The patient who has sustained blunt trauma to the chest can present a diagnostic challenge to the emergency physician. There are several diagnostic modalities available for treating life-threatening injuries to these patients. The authors review published studies to support the use of these tests in diagnosing injuries from blunt thoracic trauma. The article focuses chiefly on two current areas of controversy, the diagnosis of blunt aortic and blunt myocardial injury. Finally, the authors make recommendations for the use of various tests based on the available evidence.

Ultrasonography by emergency physicians in patients with suspected ureteral colic.

We performed a prospective study of patients with suspected ureteral colic to evaluate the test characteristics of bedside renal ultrasonography (US) performed by emergency physicians (EPs) for detecting hydronephrosis, and to evaluate how US can be used to predict the likelihood of nephrolithiasis. Thirteen EPs performed US, recorded the presence of hydronephrosis, and made an assessment of the likelihood of nephrolithiasis. All patients underwent i.v. pyelography (IVP) or unenhanced helical computed tomography (CT). There were 126 patients in the study: 84 underwent IVP; 42 underwent helical CT. Test characteristics of bedside US for detecting hydronephrosis were: sensitivity 72%, specificity 73%, positive predictive value (PPV) 85%, negative predictive value (NPV) 54%, accuracy 72%. The PPV and NPV for the ability of the EP to predict nephrolithiasis after performing US were 86% and 75%, respectively. We conclude that bedside US performed by EPs may be used to detect hydronephrosis and help predict the presence of nephrolithiasis.

Sleep disorders in infancy, childhood, and adolescence.

Sleep disorders cause substantial problems during infancy, toddlerhood, preschool ages, school ages, and adolescence. They represent the most common behavioral problems facing most parents, as well as some of the most unusual and fascinating disorders known to medicine. Sleep disorders can result from pulmonary problems, neurologic problems, family problems, or psychologic or psychiatric problems. The majority of these disorders can be diagnosed by a comprehensive sleep and medical assessment, but special studies such as polysomnography, multiple sleep latency testing, or video electroencephalographic monitoring are necessary for certain diagnoses. Pediatric sleep disorders represent a true interdisciplinary and developmental field, richly connected with many aspects of health care and medical science. Physicians and other pediatric care providers must become increasingly knowledgeable about sleep disorders to offer the best care to their patients.

Renal ultrasonography.

Renal US is one of several imaging modalities available to the emergency physician in the evaluation of patients with acute urologic disorders. It offers excellent anatomic detail without exposure to radiation or contrast agents but does not assess renal function. It is particularly useful in the evaluation of renal colic, although its role here may decrease with increasing availability of helical CT. It also has an important role in excluding bilateral renal obstruction as the cause of acute renal failure. Doppler renal US is likely to take on a more prominent role in the evaluation of renal trauma and is the diagnostic study of choice to rule out renal vein thrombosis. Bedside emergency renal US performed and interpreted by emergency physicians with limited training and experience is gaining in use and acceptance. Its role at present is primarily to identify unilateral hydronephrosis in patients with suspected renal colic. This role is likely to expand in the future as emergency US use grows and technology advances. Bedside emergency renal US may eventually be used in the evaluation of patients with acute renal failure, suspected renal vein thrombosis, and renal trauma.

Mechanisms of pediatric electrical injury. New implications for product safety and injury prevention.

OBJECTIVES: To determine age-specific mechanisms of electrical injury in children, to examine product safety regulation of the major sources of electrical injury hazard, and to assess the adequacy of current prevention strategies. DESIGN: Case series of 144 pediatric and adolescent electrical injuries in patients seen in the specialized burn center and tertiary care hospital between 1970 and 1995, examination of Consumer Product Safety Commission product recall reports for electrical injury hazards between 1973 and 1995, and review of the National Electric Code. RESULTS: Eighty-six cases of electrical injuries resulted from low-voltage (< 1000-V) exposures, all occurring within the home. In children aged 12 years and younger, household appliance electrical cords and extension cords caused more than 64 (63%) of 102 injuries, whereas wall outlets were responsible for only 14 (15%) of injuries. Fifty-eight cases resulted from high-voltage exposures, accounting for 38 (90%) of 42 injuries in children older than 12 years. No federal safety regulations for electrical cords exist, although voluntary standards have been adopted by many manufacturers. Among 383 consumer products identified by the Consumer Product Safety Commission to be electrical injury hazards, 119 were appliance cords, extension cords, or holiday stringed light sets. Several products numbered more than 1.5 million units in US household distribution prior to the investigation by the Consumer Product Safety Commission. CONCLUSIONS: Household electrical cords are the major electrocution hazard for children younger than 12 years, yet no federal safety mandates exist. Despite voluntary standards, noncompliant manufacturers can introduce vast numbers of unsafe cords onto the US household market every year. Conversion of existing voluntary safety guidelines into federally legislated standards may be the most effective intervention against pediatric electrocutions.

Blind nasotracheal intubation in the presence of facial trauma.

Blind nasotracheal intubation (BNTI) is an effective procedure for the intubation of trauma patients. The presence of major facial trauma has been considered a relative contraindication due to the perceived risk of intracranial placement. The purpose of the present study was to assess the risk of intracranial placement in patients with facial fractures who undergo BNTI. The records of 311 patients with facial fractures were reviewed for methods of intubation and complications. Eighty-two patients underwent BNTI. There were no cases of intracranial placement, significant epistaxis requiring nasal packing, esophageal intubation, or osteomyelitis. Three patients (4%) developed sinusitis and eight (10%) developed aspiration pneumonia. We conclude that the presence of facial trauma does not appear to be a contraindication to BNTI.

Rhinovirus infection associated with serious lower respiratory illness in patients with bronchopulmonary dysplasia.

OBJECTIVE: To determine the characteristics of rhinovirus infection in patients with bronchopulmonary dysplasia. SUBJECTS AND METHODS: Between July 1, 1993, and July 1, 1995, 40 patients with bronchopulmonary dysplasia were identified. Viral cultures were obtained in ambulatory patients presenting with an acute respiratory illness requiring hospitalization or in hospitalized patients with a respiratory deterioration. When rhinovirus was isolated epidemiologic data were collected, and the characteristics of the illness, its severity and outcome were noted. Key features of rhinovirus and respiratory syncytial virus (RSV) bronchiolitis were compared. RESULTS: There were 8 cases of lower respiratory tract illness associated with rhinovirus infection in 6 infants (mean age, 7.1 +/- 4.1 months) and 1 child (age, 40 months), an incidence of 0.15 infection/patient year. The mean gestational age and birth weight of these patients were 27.3 (+/- 2.75) weeks and 853 (+/-341) g, respectively. There were 5 males. Four patients needed intensive care unit admission and 1 required mechanical ventilation. By comparison there were 13 cases of RSV bronchiolitis, an incidence of 0.25 infection/patient year. The 2 groups were similar epidemiologically and an equal proportion of patients with rhinovirus and RSV needed intensive care unit admission. A greater percentage of patients with RSV required mechanical ventilation (50% vs. 14%), but this difference was not statistically significant. Three cases of rhinovirus were nosocomial, and 1 infant had a second infection. Four patients required 5 hospitalizations caused by rhinovirus infection, and the mean duration of hospital stay was 11 days. All children had sustained worsening in their respiratory status after rhinoviral illness requiring additional therapy. CONCLUSIONS: Rhinovirus is a common and potentially serious lower respiratory pathogen in bronchopulmonary dysplasia patients. Rhinovirus infection has lasting pulmonary sequelae in these children.

The efficacy of intravenous droperidol in the prehospital setting.

Droperidol is used for sedating combative patients in the emergency department (ED). We performed a randomized, prospective, double-blind study to evaluate the efficacy of droperidol in the management of combative patients in the prehospital setting. Forty-six patients intravenously received the contents of 2-cc vials of saline or droperidol (5 mg). Paramedics used a 5-point scale to quantify agitation levels prior to and 5 and 10 min after administration of the vials. Twenty-three patients received droperidol and 23 received saline. At 5 min, patients in the droperidol group were significantly less agitated than were patients in the saline group. At 10 min, this difference was highly significant. Eleven patients in the saline group (48%) required more sedation after arrival in the ED versus 3 patients (13%) in the droperidol group. We conclude that droperidol is effective in sedating combative patients in the prehospital setting.