Modification of evoked hippocampal dentate inhibition by diazepam and three antagonists in urethane-anesthetized rats.

Urethane-anesthetized rats with perforant pathway stimulating electrodes and recording electrodes placed in the hippocampal dentate gyrus were exposed to increasing doses of either the benzodiazepine agonist diazepam or an antagonist (PK-11195, CGS-8216, and RO15-1788). Analysis of the monosynaptic evoked field potentials indicated that none of the four compounds altered the threshold for eliciting the excitatory postsynaptic potential (EPSP). Reductions in field population spike (PS) amplitudes were seen after exposure to RO15-1788, CGS-8216, and diazepam, but not PK-11195.

Potentiation of cocaine toxicity with calcium channel blockers.

Three calcium channel blockers were studied for efficacy in preventing seizures and death from cocaine intoxication. Rats were first pretreated with a test drug then subjected to high dose intraperitoneal cocaine. In this model, control animals developed seizures within six minutes, followed by death within ten minutes.

Diazepam in the prevention of seizures and death in cocaine-intoxicated rats.

Rats were exposed to high-dose intraperitoneal cocaine. Pretreatment with diazepam was found to be highly effective in reducing observed seizures from 90% to 0% and reducing the incidence of death from 85% to 10%. Furthermore, diazepam treatment after cocaine exposure was also effective in decreasing deaths, from 80% to 21%, even when given after the onset of seizures.

Type I and type II pyrethroids increase inhibition in the hippocampal dentate gyrus of the rat.

Urethane-anesthetized rats were prepared for stimulation of the perforant path and for recording from the granule cell region of the hippocampal dentate gyrus. Subjects were administered varying doses of allethrin (a prototype type I pyrethroid) or deltamethrin (a prototype type II pyrethroid), and the excitability of the perforant path and granule cells was tested. Both pyrethroids produced a dose-dependent decrease in the responsiveness of granule cells, following stimulation of the perforant path, that lasted up to 100 msec.

Selective left endobronchial suctioning in the intubated patient.

Suctioning of secretions from the left endobronchial tree is frequently necessary but often difficult in intubated patients. We examined the effectiveness of a catheter designed expressly for this purpose. Special curved tip (Bronchitrac-L) suction catheters were fitted with thin, radiopaque tubing to facilitate x-ray visualization.

Superiority of activated charcoal alone compared with ipecac and activated charcoal in the treatment of acute toxic ingestions.

A prospective, randomized clinical trial compared the clinical effectiveness of syrup of ipecac and activated charcoal to that of activated charcoal alone in the treatment of acute toxic ingestions. Two hundred adult patients with mild to moderate oral overdoses were entered into the trial. Patients receiving only activated charcoal were discharged from the emergency department in significantly (P less than or equal to .

Pressure controlled inverse ratio ventilation in severe adult respiratory failure.

Thirty-one patients with severe respiratory failure who were failing volume controlled conventional ratio ventilation were placed on pressure controlled inverse ratio ventilation (PC-IRV) for a total of 4,426 patient-hours. The PC-IRV resulted in a reduction of minute ventilation from 22 +/- 1.0 L/min (mean +/- SEM) to 15 +/- 0.

Convulsant-induced changes in perforant path-dentate gyrus excitability in urethane anesthetized rats.

The dentate gyrus of intact urethane-anesthetized rats was employed to evaluate the effects of different convulsive agents on granule cell excitability. One purpose of this study was to determine whether mechanisms of action suggested from in vitro studies of these compounds could be demonstrated over clinically relevant dose ranges in vivo. The data demonstrate that drugs capable of antagonizing gamma amino butyric acid (GABA)-mediated inhibition produced similar effects on the intact hippocampus.

Choreoathetoid disorder associated with amphetamine-like drugs.

Three cases of an acute choreoathetoid disorder that developed after the use of an amphetamine-like drug are reported. Because of the dramatic improvement in symptoms over a few hours in these cases, we recommend observation, supportive care, and the careful oral administration of activated charcoal.

The anticonvulsant action of nafimidone on kindled amygdaloid seizures in rats.

The anticonvulsant effectiveness of nafimidone (1-[2-naphthoylmethyl]imidazole hydrochloride) was evaluated in the kindled amygdaloid seizure model in rats. Nafimidone (3.1-120 mg/kg i.

Increased inhibition in dentate gyrus granule cells following exposure to GABA-uptake blockers.

Rats anesthetized with urethane had stimulating and recording electrodes placed in the perforant pathway and in the dentate gyrus. They were then exposed to increasing doses of either the vehicle control dimethylsulfoxide (DMSO) or one of two gamma-aminobutyric acid (GABA)-uptake blockers (SKF-100330A or SKF-89976A). Analysis of evoked field potentials from dentate granule cells indicated that the only effect of the GABA uptake blockers was to increase the threshold for evoking the field population spikes (PS).

Isoniazid overdose: pharmacokinetics and effects of oral charcoal in treatment.

The pharmacokinetics of isoniazid following overdose in two patients is described. One patient was treated with haemodialysis for seizures and persistent coma without obvious immediate clinical improvement. In addition, three volunteer subjects were given isoniazid orally on two separate occasions.

Modification of amygdala-kindled postictal inhibition by pentylenetetrazol and diazepam.

When fully amygdala-kindled rats are electrically stimulated in grouped trials with intertrial stimulation intervals of less than 60 min, significant residual inhibition can be demonstrated. When these grouped trials of stimulation are repeated daily, additional cumulative inhibition is seen. The present study examined the effect of daily pretreatment with three doses of pentylenetetrazol (5, 10, and 20 mg/kg) and two doses of diazepam (0.

Interactions of aminophylline and three benzodiazepine compounds with amygdala-kindled seizures in rats.

Fully amygdala-kindled rats were used to study the effect of diazepam, RO 15-1788, and CGS-8216 on aminophylline-induced prolongation of elicited kindled afterdischarges. Similar proportional reductions in seizure afterdischarge durations were seen with diazepam and with RO 15-1788 after aminophylline although the absolute length of the afterdischarge durations were increased significantly with both drugs after aminophylline. The partial agonist effect of the benzodiazepine antagonist RO 15-1788 was demonstrated before and after aminophylline pretreatment.

Deterioration of conjunctival PO2 after CPR.

An 82-year-old man was resuscitated following cardiac arrest suffered outside the hospital. Conjunctival oxygenation (PcjO2), as measured by a conjunctival PO2 monitor, increased in the immediate post-resuscitation period (60 min) and neurologic status improved. The PcjO2 steadily declined over the next three hours.

The anticonvulsant action of AHR-11748 on kindled amygdaloid seizures in rats.

The anticonvulsant effectiveness of AHR-11748 (3-[3-(trifluoromethyl)phenoxy]-1-azetidinecarboxamide) was evaluated in the kindled amygdaloid seizure model in rats. Doses of AHR-11748 that did not cause prestimulation toxicity significantly attenuated elicited afterdischarge durations and the severity of the accompanying behavioral convulsive response in previously kindled rats. AHR-11748 (25-100 mg/kg i.

QRS interval in tricyclic antidepressant overdosage: inaccuracy as a toxicity indicator in emergency settings.

Emergency department treatment and disposition of tricyclic antidepressant (TCA)-overdose patients remains a common and difficult problem. Various clinical findings have been proposed as toxicity indicators. To study the performance of QRS duration as a predictor of toxicity in our patient population, we retrospectively reviewed the cases of all patients presenting to our ED with TCA overdosage.

The effect of exogenous GM1 ganglioside on kindled-amygdaloid seizures.

The effects of 12 daily doses of 30 mg/kg GM1 ganglioside i.p. on the acquisition of kindled-amygdaloid seizures in the rat was studied.

Interactions of lindane with synaptically mediated inhibition and facilitation in the dentate gyrus.

Rats were anesthetized with urethane and prepared with electrodes to stimulate the perforant path and to record extracellular field potentials from the dentate gyrus of the hippocampus. Pairs of stimuli were presented to the perforant path both at different stimulus intensities and at different time separations to evaluate the effects of exposure to lindane on inhibition and facilitation. Lindane appeared to produce a selective effect on early, GABA-mediated inhibition.

Factors responsible for increased excitability of dentate gyrus granule cells during exposure to lindane.

Rats were anesthetized with urethane, implanted with stimulating and recording electrodes in the perforant path and dentate gyrus, and exposed to different doses of lindane. Analysis of evoked field potential responses indicated that lindane exposure resulted in consistent, dose-dependent changes. Two separable effects were observed.

Tricyclic antidepressant overdose: emergency department findings as predictors of clinical course.

There is controversy regarding the appropriate utilization of health care resources in the management of tricyclic antidepressant overdosage. Antidepressant overdose patients presenting to the emergency department (ED) are routinely admitted to intensive care units, but only a small proportion develop cardiac arrhythmias or other complications requiring such an environment. The authors reviewed the findings in 165 patients presenting to an ED with antidepressant overdose.

Effects of the benzodiazepine antagonists RO 15-1788, CGS-8216 and PK-11195 on amygdaloid kindled seizures and the anticonvulsant efficacy of diazepam.

The anticonvulsant effectiveness of the benzodiazepine antagonists RO 15-1788, CGS-8216 and PK-11195 were evaluated against threshold and suprathreshold (400 microA) stimulation in fully amygdaloid-kindled rats. Pretreatment with either RO 15-1788 (3, 10 and 30 mg/kg), CGS-8216 (3, 10 and 30 mg/kg) or PK-11195 (10 and 60 mg/kg) failed in this study to modify consistently either the afterdischarge thresholds or elicited suprathreshold seizures or duration of afterdischarge. Using a double injection paradigm, the effectiveness of these three benzodiazepine antagonists to reverse the anti-convulsant and behavioral effects of diazepam were studied.

Activated charcoal--past, present and future.

Poisoned patients were first treated with charcoal more than 150 years ago. Despite its almost universal acceptance today, activated charcoal's role has been overshadowed by the emphasis on treating poisoned patients first with gastric emptying. We review the current use of activated charcoal and recent studies that suggest that activated charcoal may be the single most effective treatment in many types of poisoning.