Robust neurite extension following exogenous electrical stimulation within single walled carbon nanotube-composite hydrogels.

UNLABELLED: The use of exogenous electrical stimulation to promote nerve regeneration has achieved only limited success. Conditions impeding optimized outgrowth may arise from inadequate stimulus presentation due to differences in injury geometry or signal attenuation. Implantation of an electrically-conductive biomaterial may mitigate this attenuation and provide a more reproducible signal. In this study, a conductive nanofiller (single-walled carbon nanotubes [SWCNT]) was selected as one possible material to manipulate the bulk electrical properties of a collagen type I-10% Matrigel™ composite hydrogel. Neurite outgrowth within hydrogels (SWCNT or nanofiller-free controls) was characterized to determine if: (1) nanofillers influence neurite extension and (2) electrical stimulation of the nanofiller composite hydrogel enhances neurite outgrowth. Increased SWCNT loading (10-100-µg/mL) resulted in greater bulk conductivity (up to 1.7-fold) with no significant changes to elastic modulus. Neurite outgrowth increased 3.3-fold in 20-µg/mL SWCNT loaded biomaterials relative to the nanofiller-free control. Electrical stimulation promoted greater outgrowth (2.9-fold) within SWCNT-free control. The concurrent presentation of electrical stimulation and SWCNT-loaded biomaterials resulted in a 7.0-fold increase in outgrowth relative to the unstimulated, nanofiller-free controls. Local glia residing within the DRG likely contribute, in part, to the observed increases in outgrowth; but it is unknown which specific nanofiller properties influence neurite extension. Characterization of neuronal behavior in model systems, such as those described here, will aid the rational development of biomaterials as well as the appropriate delivery of electrical stimuli to support nerve repair. STATEMENT OF SIGNIFICANCE: Novel biomedical devices delivering electrical stimulation are being developed to mitigate symptoms of Parkinson's, treat drug-resistant depression, control movement or enhance verve regeneration. Carbon nanotubes and other novel materials are being explored for novel nano-neuro devices based on their unique properties. Neuronal growth on carbon nanotubes has been studied in 2D since the early 2000s demonstrating increased outgrowth, synapse formation and network activity. In this work, single-walled carbon nanotubes were selected as one possible electrically-conductive material, dispersed within a 3D hydrogel containing primary neurons; extending previous 2D work to 3D to evaluate outgrowth within nanomaterial composites with electrical stimulation. This is the first study to our knowledge that stimulates neurons in 3D composite nanomaterial-laden hydrogels. Examination of electrically conductive biomaterials may serve to promote regrowth following injury or in long term stimulation.

A comparison of two bedside tests for the detection of salicylates in urine.

OBJECTIVE: Ferric chloride (FC) and Trinder reagent (TR) have both been used to identify salicylates (ASA) in the urine of patients presenting with possible drug overdose. The authors sought to compare the sensitivities and specificities of these two reagents in detecting ASA in the urine of patients presenting to an emergency department (ED) with suspected drug overdose. METHODS: Patients were eligible for inclusion in this study if they presented to the ED with either suspected overdose or unexplained metabolic acidosis. One milliliter of the patient's urine was added to 1 mL of each of the two reagents. A positive test was defined as any darkening of the color of the reagent. Each patient had a quantitative serum ASA measured. RESULTS: Twenty of 180 patients (11%) had quantitative serum ASA levels above 5 mg/dL. Both reagents were 100% sensitive in identifying these patients. The specificity of FC was 71% compared with 73% for TR. The two reagents gave similar results in 91% of cases. CONCLUSION: Both FC and TR are reliable in detecting ASA in the urine of patients presenting with suspected drug overdose. A negative result with either test eliminates the need for a quantitative serum ASA level. Because FC has a longer shelf life than TR, it is the more practical reagent for use in the ED.

Ketamine abusers presenting to the emergency department: a case series.

Ketamine hydrochloride, familiar to emergency physicians as a dissociative anesthetic, has been abused as a hallucinogen for almost 30 years. The drug produces effects similar to those of phencyclidine but with a much shorter duration of effect. Since 1996, an increasing number of patients have presented to Connecticut Emergency Departments (EDs) after the intentional abuse of ketamine. Because the medical literature contains almost no information on the consequences of ketamine abuse, we have compiled a series of ketamine abusers presenting to the ED. Among the 20 patients in this series, common presenting complaints included anxiety, chest pain, and palpitations. Tachycardia was the most common physical examination finding. Nystagmus, a common finding after phencyclidine use, was seen in only three cases. The most frequent complications after ketamine abuse were severe agitation and rhabdomyolysis. The symptoms of ketamine intoxication appear to be short-lived, with 18 of the 20 patients discharged from the ED within 5 h of presentation. Emergency physicians should include ketamine in the differential diagnosis of drug- or toxin-induced hallucinations. Methods for detecting this drug in biologic fluids are reviewed as are treatment recommendations for managing the patient who presents to the ED after abusing ketamine.

Anticholinergic poisoning with adulterated intranasal cocaine.

In recent years, emergency physicians have encountered a growing number of patients who present with anticholinergic toxicity after using adulterated heroin. Anticholinergic poisoning caused by adulterated cocaine is far less common. This report describes the case of a 39-year-old man who arrived in the emergency department several hours after the nasal insufflation of cocaine. Classic symptoms of anticholinergic toxicity were evident on examination, including dry, flushed skin, agitation, tachycardia, mydriasis, and absence of bowel sounds. Treatment included intravenous fluids and lorazepam, with resolution of symptoms over several hours. Urine samples revealed the presence of cocaine metabolites as well as the anticholinergic drug atropine, and infrequently encountered adulterant of cocaine. Anticholinergic poisoning is reviewed, and the physical examination findings that distinguish this syndrome from the closely related sympathomimetic syndrome typical of cocaine are detailed. Current treatment recommendations for anticholinergic poisoning are summarized.

Noxious fumes in a medical center: chemical and psychological aspects.

A group of operating room personnel at a medical center in Connecticut reported severe respiratory irritation manifested by either proxysmal cough or throat irritation suggestive of a noxious fume exposure, 13 April 1994. However, persistent complaints on 14 April 1994 were significantly different and more suggestive of a psychological reaction. By careful interviewing, physical examination, toxicological assays, and epidemiological investigation, the true nature of a mixed physiological and psychological episode was delineated. Enlightened management policy enabled rapid restoration of return to work with minimal economic loss.

Differential developmental effects of acute hypoxia on the rabbit atrioventricular conduction axis.

The differential developmental effects of hypoxia on antegrade fast and slow and retrograde conduction through the atrioventricular junction are unknown. This study describes the effects of hypoxia on fast and slow antegrade atrioventricular node, infra-Hisian and retrograde conduction in immature and mature hearts during premature pacing protocols in excise, perfused adult and neonatal rabbits. The results are: (1) antegrade conduction delay through the atrioventricular node is the same developmentally, but delay through the His-Purkinje system is greater in adults; (2) hypoxia reduces the extra delay in the His-Purkinje system in adults; (3) fast atrioventricular node conduction is more sensitive to hypoxia in neonates than in adults, and slow atrioventricular node conduction is more sensitive to hypoxia in adults than in neonates, and (4) retrograde atrioventricular node conduction is more resistant to hypoxia in neonates than in adults.

Different effects of flecainide on atrioventricular conduction properties in the adult and immature rabbit heart.

The influence of flecainide (0.1, 0.5, 1.0, and 2.0 micrograms/mL) on atrioventricular (AV) conduction was studied in neonatal and adult perfused rabbit hearts using extracellular bipolar surface electrograms and premature atrial and ventricular pacing. Flecainide produced a concentration and rate-related increase in the steady-state nodal conduction (AHmin) and an increase in slow AH conduction (AHmax) in both age groups. The drug produced significant increases in the refractory periods of the atrium, AV node, His-Purkinje system, and ventricular myocardium. The neonatal refractory periods were significantly greater at lower or the same drug concentrations than those of the adult. The neonatal Wenckebach cycle length was significantly greater with a lower concentration of drug (0.5 microgram/mL) than was the adult Wenckebach cycle length. The His-Purkinje system steady-state conduction time (HVmin) was increased by a lower concentration of drug in the neonate (0.5 microgram/mL) as compared with 2.0 micrograms/mL in the adult. These data show that across a wide range of AV conduction parameters, the neonatal preparations responded to a lower concentration of flecainide than did the adult preparations. These findings may, in part, be the basis for the reported greater efficacy of the drug in children than in adults.

Serotonin syndrome: case report and review of the literature.

We present the case of a 35-year-old woman who developed serotonin syndrome after receiving a single dose of the cyclic antidepressant imipramine (Tofranil). She was already being treated for depression with paroxetine (Paxil), a selective serotonin reuptake inhibitor. Two hours after receiving imipramine, the patient developed tachycardia, delirium, bizarre movements, and myoclonus, all classic findings of serotonin syndrome. Her antidepressants were discontinued and she was treated with intravenous fluids, sedation, and a short course of cyproheptadine, a serotonin receptor antagonist. All symptoms resolved completely within 24 hours. In this case report, we review the drug interactions that can precipitate serotonin syndrome, and give recommendations for the diagnosis and treatment of this potentially fatal disorder.

Lack of proarrhythmia as assessed by Holter monitor after atrial radiofrequency ablation of supraventricular tachycardia in children.

The purpose of this study was to assess the short-term arrhythmogenicity of atrial radiofrequency (RF) ablation lesions in children. Patients with the greatest exposure to RF energy comprised the study group. Holter data on 35 RF ablation procedures in 31 patients with a median age of 13.2 years (range 3 months to 20 years) was retrospectively analyzed. Patients received an average of 19.9 (SD = 13.6) RF lesions, all delivered by an atrial approach. Supraventricular ectopy and ventricular ectopy were compared immediately before and after and 4 to 9 weeks after RF ablation by serial Holter monitoring. Factors thought to possibly predispose patients to a proarrhythmic effect were used to define subgroups for separate analysis. No increase in ambient supraventricular ectopy or ventricular ectopy was observed either immediately after or 4 to 9 weeks after RF ablation compared with the baseline Holter recordings. Children exposed to relatively large doses of RF energy may demonstrate transient and asymptomatic nonsustained tachycardias in the short term. However, no new sustained tachycardias and no increase in supraventricular or ventricular ambient ectopy are detected by short-term Holter monitoring.

Developmental effects of d-sotalol on anterograde and retrograde atrioventricular conduction in the rabbit.

INTRODUCTION: These experiments investigate the developmental effects of d-sotalol on standard electrophysiologic parameters of anterograde and retrograde AV conduction in the rabbit. METHODS AND RESULTS: Using bipolar electrograms and standard pacing techniques, the effects of graded concentrations of d-sotalol on anterograde and retrograde conduction in mature and immature perfused rabbit hearts were compared. Also, a quantitative assessment of the drug's effects on a rate-dependent property of anterograde AV node (AVN) conduction, termed the "recovery process," was compared in mature and immature rabbit hearts. The main developmental electrophysiologic findings of this investigation are: (1) in both the mature and immature rabbit heart, d-sotalol increases the anterograde conduction time and prolongs refractoriness of the AVN, yet the minimal concentrations of d-sotalol that produce these changes are lower in the neonate; (2) d-sotalol increases the anterograde refractory period of the His-Purkinje system in both age groups, but increases anterograde infra-Hisian conduction only in the neonate; (3) 1 x 10-4 M d-sotalol significantly changes the time constant of the AVN recovery process in the neonate, but not in the adult; (4) for retrograde conduction, slow conduction through the AVN (HAmax) and infra-Hisian region (VHmax) are increased by d-sotalol in the neonate, but not in the adult. CONCLUSIONS: The findings of this study illustrate that d-sotalol has different effects on parameters of the developing AV conduction system. This implies that there may be maturational changes in the ionic currents that are responsible for anterograde and retrograde AVN and His-Purkinje conduction.

Learning curve for radiofrequency catheter ablation in pediatrics at a single institution.

We examined the learning curve for radiofrequency ablation in pediatrics at a single institution. The first 146 cases were retrospectively reviewed, including patients < or = 21 years old with a single tachycardia diagnosis who were undergoing radiofrequency ablation for the first time. Data regarding demographics, electrophysiologic properties of the tachycardia, and procedural characteristics were tabulated. Data were then analyzed for evidence of association between these characteristics, success, and experience. Results revealed that success rates improved significantly with experience, reaching 85% success for all cases after < 100 cases attempted. Success for accessory pathway tachycardias alone reached > 93%. The number of cases of nonpathway tachycardias undertaken significantly increased as experience was gained. Fluoroscopy time improved to 34 +/- 27 minutes after < 100 cases. In conclusion, as experience was gained, (1) success rates showed a steep improvement; (2) the population undergoing radiofrequency ablation clearly shifted to include more difficult diagnoses; and (3) fluoroscopy time significantly decreased.

Correlation of pediatric echocardiographic Doppler and catheter-derived valvar aortic stenosis gradients and the influence of aortic regurgitation.

This report suggests that in the absence of aortic regurgitation, Doppler peak and mean gradients are useful predictors of catheter peak-to-peak aortic stenosis gradients >50 mm Hg; however, in the presence of aortic regurgitation, the predictive value diminishes dramatically, but improves when electrographic data are incorporated. We present potentially useful equations to help predict the need for interventional catheterization for valvar aortic stenosis.

Right ventricular outflow reconstruction with cryopreserved homografts in pediatric patients: intermediate-term follow-up with serial echocardiographic assessment.

OBJECTIVES: This study was performed to assess by echocardiography the intermediate-term outcome of cryopreserved homografts employed in pulmonary outflow reconstruction in children and to validate the reliability of Doppler echocardiography in their evaluation. BACKGROUND: Cryopreserved homografts have become the most widely used pulmonary conduits. Previous reports have shown the occurrence of homograft regurgitation in the immediate postoperative period and the propensity of regurgitation to progress. Although Doppler echocardiography has been useful in assessing extracardiac valved conduit stenosis, its reliability in assessing a large series of cryopreserved homografts has not been documented. METHODS: Echocardiograms of 41 patients (43 homografts) who underwent operations between December 1986 and October 1992 were retrospectively reviewed. The median age of patients at operation was 37.5 months (range 3 to 333), and the median duration of follow-up was 28.5 months (range 1 to 68). Homograft regurgitation was classified on a scale of 0 to 4+. Pressure gradients across the homografts measured in 23 catheterizations were correlated with corresponding echocardiographic gradients. RESULTS: Regurgitation: Homograft regurgitation occurred in 100% of patients at follow-up. Progression of severity > 2 grades occurred during follow-up in 35% and was associated with operation before age 18 months (p < 0.002) and stenosis progression (p < 0.05) but not with homograft type (aortic or pulmonary). These data predict that 50% of patients operated on before 18 months of age will have severe regurgitation by 15 months postoperatively compared with only 15% operated on after 18 months. Stenosis: At follow-up, 51% of homografts had a stenotic gradient > or = 25 mm Hg predominantly at the distal anastomosis, and stenosis progression was related to young age at operation (< 18 months, p < 0.005) and small conduit size (p < 0.01). Fifty percent of conduits implanted before age 18 months could be predicted to stenose by 21.8 months compared with only 5% of those implanted after age 18 months. The gradient measured from Doppler echocardiography correlated well with the catheterization gradient (r = 0.86). CONCLUSIONS: Cryopreserved homograft dysfunction is frequent and progressive. Young age at operation (< 18 months) predicts more rapid deterioration. Doppler echocardiography is reliable in assessing the systolic gradients across homografts. Serial echocardiographic assessment in the follow-up of these patients accurately characterizes these problems.

Neurocardiogenic syncope in children with a normal heart.

OBJECTIVES: The purpose of this study was to review the results of investigation and management of children with syncope and a structurally normal heart. BACKGROUND: Syncope is a common clinical problem and has many etiologies. Autonomic testing and, in particular, the tilt/orthostatic test have helped to positively diagnose neurocardiogenic syncope in a high proportion of such patients. METHODS: Patient case notes and autonomic test charts were reviewed in 162 children aged 1 to 20 years (mean age 12.8 years) with syncope. The autonomic test consisted of orthostatic maneuver, carotid sinus massage, diving reflex, Valsalva maneuver and dose response to intravenous boluses of isoproterenol and phenylephrine. Serum levels of epinephrine and norepinephrine were drawn during the orthostatic test. After confirmation of neurocardiogenic syncope, treatment was begun with fludrocortisone and salt, and beta-adrenergic blocking agents were used as a second line of therapy when indicated. RESULTS: The orthostatic test was positive for neurocardiogenic syncope in 100 patients (62%) and negative in 62 (38%). Patients in the former group were older, were more often female and had a diminished response to carotid sinus massage, a higher Valsalva ratio and a higher supine epinephrine level. Both groups showed an increase in epinephrine and norepinephrine levels at 5 min of standing. In the orthostatic positive group at the time of syncope, norepinephrine levels decreased, whereas epinephrine levels increased. Patients in this group were also more sensitive to the vasodilating effect of isoproterenol but not to its chronotropic effects. Eleven patients had cardioinhibitory syncope (asystole > or = 3 s). Of these, three had pacemaker implantation. Fludrocortisone and salt used in 84 patients in the orthostatic positive group produced resolution of symptoms in 55 patients (65%) and improvement in 14 (17%). Ten patients received beta-blockers, with resolution in four and improvement in four. CONCLUSIONS: Patients with orthostatic test-proved neurocardiogenic syncope show evidence of autonomic dysfunction. They also show beta-adrenergic hypersensitivity. Treatment initiated on the basis of the protocol was associated with amelioration of symptoms in the majority of patients.

Effect of beta-adrenergic stimulation on the QT interval of children with syncope.

The effect of intravenous bolus doses (0.25, 0.5, 1.0 microgram) of isoproterenol on the QT and RR intervals was reviewed in a group of 34 children undergoing autonomic testing for syncope. Twenty-one patients had a positive orthostatic test and 13 were negative. The two groups (positive and negative) were compared. Baseline QT and RR intervals were similar. The RR interval was shortened by isoproterenol in both groups. Isoproterenol shortened the QT interval in the negative group (as seen in normal persons), but produced QT prolongation in the positive group, although neither reached statistical significance when compared to baseline within the respective group. Comparing the values for RR and QT at each dose of isoproterenol (including baseline) between the two groups showed a significant difference in the QT interval after the 1.0-microgram dose of isoproterenol. Thus children with orthostatic positive neurocardiogenic syncope showed a different QT response to beta-adrenergic stimulation. This lends support to the theory of altered beta-adrenergic sensitivity being present in children with neurocardiogenic syncope.

Unusual pulmonary reaction to respiratory therapy in a premature newborn.

The case of an infant with the clinical features of bronchopulmonary dysplasia but with pathologic features unlike those usually associated with this condition is reported. The condition of this infant was probably related to respiratory therapy and may have been a variant of bronchopulmonary dysplasia.