Keith K. Burkhart

Alterations in tau phosphorylation in rat and human neocortical brain slices following hypoxia and glucose deprivation.

Tau is a microtubule-associated protein which is regulated by phosphorylation. Highly phosphorylated tau does not bind microtubules and is the main component of the paired helical filaments seen in Alzheimers and related neurodegenerative diseases. Recent reports suggested that patterns of tau phosphorylation changed following ischemia and/or reperfusion in vivo. We used an in vitro model employing rat and human neocortical slices to investigate changes in tau phosphorylation which accompany oxygen and glucose deprivation. Western blotting with polyclonal and phosphorylation-sensitive Tau-1 monoclonal antisera was used to monitor changes in tau which accompanied conditions of oxygen and glucose deprivation and reestablishment of these nutrients. In vitro hypoglycemia/hypoxia caused tau to undergo significant dephosphorylation in both rat and human neocortical slices after 30 and 60 min of deprivation. This dephosphorylation was confirmed using immunoprecipitation experiments after radiolabeling tau and other proteins with 32Pi. Okadaic acid, a phosphatase inhibitor, was able to prevent tau dephosphorylation in both control and ischemic slices. Lubeluzole, a benzothiazole derivative with in vivo neuroprotective activity, did not significantly alter patterns of tau phosphorylation. Restoration of oxygen and glucose following varied periods of in vitro hypoxia/hypoglycemia (15-60 min) led to an apparent recovery in phosphorylated tau. These data suggest that tau undergoes a rapid, but reversible dephosphorylation following brief periods of in vitro hypoxia/hypoglycemia in brain slices and that changes in tau phosphorylation help determine the extent of recovery following oxygen and glucose deprivation.

Pulmonary Toxicity Following Exposure to an Aerosolized Leather Protector

BACKGROUND An aerosol spray for leather protection was reformulated to remove trichloroethane. The new formulation contained isobutane, n-heptane, ethyl acetate and fluoroaliphatics. RETROSPECTIVE REVIEW Thirty-nine patients reported symptoms to the regional poison center. Respiratory symptoms developed within hours of exposure. Most symptoms resolved within two days. Abnormal pulmonary function tests, including obstructive disease or diminished diffusing capacity, were demonstrated in three of the four tested patients. CONCLUSIONS The mechanism for the pulmonary toxicity has not been determined.

Respiratory failure following adenosine administration

Adenosine is frequently administered to convert the rhythm of patients with paroxysmal supraventricular tachycardia to sinus rhythm. Adverse reactions are common after its administration, but these have been short-lived because adenosine has a half-life of less than 10 seconds. This report describes a 54-year-old male patient with chronic obstructive pulmonary disease who presented with paroxysmal supraventricular tachycardia at 200 beats/min. A 12-mg bolus injection of adenosine aggravated mild bronchospasm and produced respiratory failure. The patient subsequently required ventilatory support for 9 days. The presence of bronchoconstriction should be considered as a possible contraindication to the administration of intravenous adenosine.

Comparison of Topical Magnesium and Calcium Treatment for Dermal Hydrofluoric Acid Burns

STUDY OBJECTIVE To compare topical preparations of magnesium and calcium in the treatment of dermal hydrofluoric acid burns. DESIGN A randomized, blinded, controlled animal model study. SETTING Animal care facility. TYPE OF PARTICIPANTS New Zealand rabbits. INTERVENTIONS Each rabbit was burned with hydrofluoric acid at four sites along the thoracolumbar spine. Equimolar amounts of calcium gluconate, magnesium gluconate, and a magnesium hydroxide antacid were added into a lubricating jelly. The jelly alone was a control preparation. After a water rinse, the burns were massaged with the gels for 1 minute five times; at 4 and 20 minutes and at 1, 4, and 24 hours. Each rabbit served as its own control by receiving all four treatments. MEASUREMENTS AND MAIN RESULTS Burn diameter and burn surface area diminished over time, but there were no statistically significantly differences among the treatments. Burn ranking and burn rating of severity also did not demonstrate differences. The histologic analysis of the burns, however, demonstrated that calcium gluconate-treated burns were less severe and more superficial than the control and magnesium gluconate-treated burns; the magnesium hydroxide antacid-treated burns were not statistically different compared to the calcium gluconate-treated burns. CONCLUSION Topical calcium gluconate is an efficacious treatment for dermal hydrofluoric acid burns. Further research is needed to determine the role of magnesium-containing antacids in the treatment of hydrofluoric acid burns.

Thrombocytopenia Following Timber Rattlesnake Envenomation

STUDY OBJECTIVE To better characterize timer rattlesnake venom--induced thrombocytopenia and coagulopathy and the response to therapy with Antivenin (Crotalidae) Polyvalent. METHODS We conducted a retrospective multicenter review of timber rattlesnake envenomation. RESULTS We reviewed 18 cases at two institutions. Restoration of normal prothrombin time and partial thromboplastin time was achieved in all cases with antivenom therapy. In contrast, complete reversal of thrombocytopenia was not achieved, despite antivenom therapy. CONCLUSION Antivenom (Crotalidae) Polyvalent was less effective in reversing thrombocytopenia than coagulopathy after timber rattlesnake envenomation, suggesting that a component of timber rattlesnake venom persists in the blood despite antivenom therapy. Persistent thrombocytopenia may be due to a venom factor that the antivenom does not neutralize or to inadequate dosing of antivenom. Prompt reversal of thrombocytopenia following treatment of timber rattlesnake envenomation with this antivenom appears unlikely.

A Case Report of Venlafaxine Toxicity

Venlafaxine hydrochloride is a novel bicyclic antidepressant which inhibits the reuptake of serotonin, norepinephrine and, to a lesser extent, dopamine. A 41-year-old female ingested 4.5 g venlafaxine, 500 mg diphenhydramine, 50 mg thiothixene and subsequently experienced severe central nervous system depression requiring intubation. She also developed elevated systolic and diastolic blood pressures and sinus tachycardia. The patient was decontaminated with gastric lavage and activated charcoal. She regained consciousness within a few hours and was extubated nine hours after ingestion. This case demonstrates that severe central nervous system depression may follow venlafaxine overdose.

Attending supervision of nonemergency medicine residents in a university hospital ED

There have been a limited number of studies assessing the impact of attending physician supervision of residents in the emergency department (ED). The objective of this study is to describe the changes in patient care when attending emergency physicians (AEPs) supervise nonemergency medicine residents in a university hospital ED. This was a prospective study including 1,000 patients, 32 second- and third-year nonemergency medicine residents and eight AEPs. The AEPs classified changes in care for each case as major, minor, or none, according to a 40-item data sheet list. There were 153 major changes and 353 minor changes by the AEP. The most common major changes were ordering laboratory or x-ray tests that showed a clinically significant abnormality, and eliciting important physical exam findings. Potentially limb- or life-threatening errors were averted by the AEP in 17 patients. Supervision of nonemergency medicine residents in the ED resulted in frequent and clinically important changes in patient care.

Naja naja cobra bite

Most venomous snakes in the United States are of the Crotalidae family. Another family of snakes, the Elapidae, are not so common, but their bites may be a threat to zoo keepers and persons who have exotic snakes as pets. Because Elapidae envenomation is not common, signs and symptoms of such envenomation may not be recognized. Elapidae venom, because of a curare-like property, can produce respiratory compromise followed by death within 10 minutes. Antivenin, cholinesterase inhibitors, and mechanical ventilation are treatments to consider in such envenomations. Unlike Crotalidae antivenin, Elapidae antivenin may not confer protection against species not used in its preparation. Identification of the involved snake, by family and specie, should be an early priority. Correct management of the envenomated patient is dependent on the prompt administration of the most specific antivenin available when indicated.

Whole-bowel irrigation as adjunctive treatment for sustained-release theophylline overdose

STUDY OBJECTIVE To determine a therapeutic benefit for whole-bowel irrigation (with polyethylene glycol-electrolyte lavage solution) as adjunctive treatment to multiple doses of activated charcoal following an overdose of sustained-release theophylline. DESIGN Randomized crossover study. Three treatment arms were separated by one-week intervals. SETTING Animal care facility housing. TYPE OF PARTICIPANTS Eight female mongrel dogs. INTERVENTIONS Unanesthetized dogs were given approximately 75 mg/kg of sustained-release theophylline. In treatment arm 1, 1 g/kg activated charcoal was administered by nasogastric tube at two hours after ingestion followed by 0.5-g/kg doses at five and eight hours. During treatment arm 2, beginning two hours after theophylline ingestion, 25 mL/kg whole-bowel irrigation solution was administered every 45 minutes for four doses followed by activated charcoal. In treatment arm 3, the first dose of activated charcoal was given ten minutes before beginning the whole-bowel irrigation protocol. MEASUREMENTS AND MAIN RESULTS Serum theophylline levels were measured at zero, two, four, five, eight, 12, 16, and 24 hours after ingestion. Mean serum theophylline levels, area under the curve (P = .13), and terminal half-lives (P = .69) for each treatment group were not statistically different. This negative study had an 81% power to detect a 50% reduction in the area under the curve by whole-bowel irrigation treatment. CONCLUSION In this model, whole-bowel irrigation did not add to the therapeutic benefits of activated charcoal.

REVERSAL OF TOXICITY USING AVIDIN-BASED HEMOPERFUSION : A MODEL SYSTEM IN RATS USING BIOTINYLATED MELITTIN

The high-affinity interaction between avidin and biotin (Kd = 10(-15)M) can be exploited to develop specific protocols for retrieval of biotinylated drugs and toxicants from biological fluids. Melittin, the main toxic component of bee venom, was biotinylated and used as a model toxicant to determine whether avidin-based extracorporeal hemoperfusion could remove biotinylated melittin and thus alter the severity of the toxic response in rats. Melittin was biotinylated using N-hydroxysuccinimide-long-chain biotin. Biotinylated melittin produced 100% lethality in rats by 120 min following four sequential intravenous injections of 1.7 mg/kg biotinylated melittin (0, 5, 20, and 35 min). An avidin hemoperfusion column was constructed (10 mg avidin/1 ml gel) and connected via the femoral vasculature to rats intoxicated with biotinylated melittin. Controls rats were hemoperfused using avidin columns blocked with d-biotin. None of the 6 rats hemoperfused using the biotin-blocked avidin column control survived, whereas 5 of 9 of the experimental rats survived to 120 min. The difference between the two survival rates was statistically significant (p < 0.0048). Thus, avidin-based hemoperfusion improved survival following biotinylated melittin toxicity and strengthens the concept that avidin-based hemoperfusion can reverse the toxicity of biotinylated toxicants.