Magnesium induces neuronal apoptosis by suppressing excitability.

In clinical obstetrics, magnesium sulfate (MgSO(4)) use is widespread, but effects on brain development are unknown. Many agents that depress neuronal excitability increase developmental neuroapoptosis. In this study, we used dissociated cultures of rodent hippocampus to examine the effects of Mg(++) on excitability and survival. Mg(++)-induced caspase-3-associated cell loss at clinically relevant concentrations. Whole-cell patch-clamp techniques measured Mg(++) effects on action potential threshold, action potential peak amplitude, spike number and changes in resting membrane potential. Mg(++) depolarized action potential threshold, presumably from surface charge screening effects on voltage-gated sodium channels. Mg(++) also decreased the number of action potentials in response to fixed current injection without affecting action potential peak amplitude. Surprisingly, Mg(++) also depolarized neuronal resting potential in a concentration-dependent manner with a +5.2 mV shift at 10 mM. Voltage ramps suggested that Mg(++) blocked a potassium conductance contributing to the resting potential. In spite of this depolarizing effect of Mg(++), the net inhibitory effect of Mg(++) nearly completely silenced neuronal network activity measured with multielectrode array recordings. We conclude that although Mg(++) has complex effects on cellular excitability, the overall inhibitory influence of Mg(++) decreases neuronal survival. Taken together with recent in vivo evidence, our results suggest that caution may be warranted in the use of Mg(++) in clinical obstetrics and neonatology.

A pilot study to assess the safety of dobutamine stress echocardiography in the emergency department evaluation of cocaine-associated chest pain.

STUDY OBJECTIVE: Chest pain in the setting of cocaine use poses a diagnostic dilemma. Dobutamine stress echocardiography (DSE) is a widely available and sensitive test for evaluating cardiac ischemia. Because of the theoretical concern regarding administration of dobutamine in the setting of cocaine use, we conducted a pilot study to assess the safety of DSE in emergency department patients with cocaine-associated chest pain. METHODS: A prospective case series was conducted in the intensive diagnostic and treatment unit in the ED of an urban tertiary-care teaching hospital. Patients were eligible for DSE if they had used cocaine within 24 hours preceding the onset of chest pain and had a normal ECG and tropinin I level. Patients exhibiting signs of continuing cocaine toxicity were excluded from the study. All patients were admitted to the hospital for serial testing after the DSE testing in the intensive diagnostic and treatment unit. RESULTS: Twenty-four patients were enrolled. Two patients had inadequate resting images, one DSE was terminated because of inferior hypokinesis, another DSE was terminated because of a rate-related atrial conduction deficit, and 1 patient did not reach the target heart rate. Thus, 19 patients completed a DSE and reached their target heart rates. None of the patients experienced signs of exaggerated adrenergic response, which was defined as a systolic blood pressure of greater than 200 mm Hg or the occurrence of tachydysrhythmias (excluding sinus tachycardia). Further suggesting lack of exaggerated adrenergic response, 13 (65%) of 20 patients required supplemental atropine to reach their target heart rates. CONCLUSION: No exaggerated adrenergic response was detected when dobutamine was administered to patients with cocaine-related chest pain.

Organ procurement and successful transplantation after malathion poisoning.

BACKGROUND: One of the major limitations to organ procurement and donation is the lack of suitable donors. As the demand for suitable organs exceeds the supply, identification of potential donors continues to evolve. Due to perceived risks of transmittable toxins and insufficient understanding of toxicological fate, poisoned patients are often overlooked as organ donors. CASE REPORT: A 17-year-old white male was found by his mother having a seizure in bed. A strong odor of pesticides was noted and an empty container of malathion was found. He was transported to an outlying hospital and underwent prolonged cardiopulmonary resuscitation. The patient exhibited symptoms consistent with cholinergic poisoning and received a total of 12 mg of atropine and a pralidoxime bolus of 1 g followed by an infusion at 500 mg/h. Initial plasma cholinesterase was 1433 IU/L (normal 7500-14,600). The patient developed aspiration pneumonia and remained comatose. No further treatment for cholinergic toxicity was needed 5 days after admission and a cerebral blood flow scan confirmed brain death. After review of the available literature on the disposition andfate of malathion in human tissues, the patient's liver and kidneys were harvested for transplantation. The recipients were all doing well 1 year posttransplantation. CONCLUSIONS: This case of successful transplantation after organophosphate exposure underscores the fact that poisoned patients should not be overlooked as transplant candidates. Decisions should be based on the clinical presentation and knowledge of the properties of the toxin.