Aeromedical Evacuation, the Expeditionary Medicine Learning Curve, and the Peacetime Effect.

INTRODUCTION: Organizational proficiency increases with experience, which is known as a learning curve. A theoretical peacetime effect occurs when knowledge and skills degrade during peacetime. In this study, the intertheater evacuation system was examined for evidence of a military learning curve and peacetime effect. MATERIALS AND METHODS: Data on medical evacuations from U.S. Central Command occurring between January 1, 2003, and December 31, 2022, were acquired from the TRANSCOM Regulating and Command & Control Evacuation System. Priority mission evacuation time corresponding to peak periods of activity in Iraq and Afghanistan and minimal activity in Afghanistan was analyzed. Any reduction or increase in the delivery time of casualties would be considered a change in proficiency. RESULTS: There was a marginal monthly decline of 0.019 days (27.4 min) to perform a priority evacuation from Iraq (95% confidence interval [CI], 0.009 to 0.028 days, P < .001) and a decline of 0.010 days (14.4 min) from Afghanistan (95% CI, 0.003 to 0.016 days, P = .004) over 40 months from peak monthly average times. There was a monthly marginal increase in priority evacuation average time from Afghanistan of 0.008 days (11.5 min) (95% CI, 0.005 to 0.011, P < .001) between January 2013 and December 2020. The number of monthly evacuations estimated to maintain or improve monthly average evacuation time is approximately 50. CONCLUSIONS: An intertheater aeromedical evacuation system increased in proficiency during periods of conflict and declined during relative peacetime. There is evidence of a peacetime effect on intertheater aeromedical evacuation.

In the adult CNS, ethanol prevents rather than produces NMDA antagonist-induced neurotoxicity.

Single doses of an NMDA antagonist cause an adult or a prepubertal form of neurodegeneration, depending on the age of the animal. Single doses of ethanol (EtOH) by blocking NMDA receptors produce apoptotic neurodegeneration in young animals. This capability could account, in part, for the ability of EtOH to produce the fetal alcohol syndrome. We investigated whether EtOH could produce NMDA antagonist-induced neurotoxicity (NAN), a different neurotoxicity that is seen only in adult animals. In spite of producing blood EtOH levels (30 to 600 mg/dl) known to block NMDA receptors, EtOH was unable to produce neurotoxicity in the adult central nervous system (CNS). Moreover, EtOH in a dose-dependent fashion (ED(50)=138 mg/dl) prevented the selective and powerful NMDA antagonist, MK-801, from producing NAN in adult animals, suggesting that activity at another site might be negating the neurotoxic effect of EtOH's inherent NMDA antagonistic activity. Because GABA(A) agonism and non-NMDA glutamate antagonism, properties which EtOH possesses, can prevent NAN, we proceeded to study whether GABA(A) antagonists (or agents capable of reversing EtOH's GABAergic effects) and non-NMDA agonists could reverse EtOH's protective effect. Bicuculline, Ro15-4513, finasteride, kainic acid or AMPA, alone or in combination, did not significantly reverse EtOH's protective effect. Given that EtOH has effects on a wide range of ion channels and receptors, determining the precise mechanism of EtOH's protective effect will take additional effort. The inability of EtOH to acutely produce NAN in the adult CNS indicates that, in contrast to fetuses, brief exposure of the adult CNS to EtOH is non-toxic for neurons.

Sudden unexplained hemolysis occurring in an infant due to presumed Loxosceles envenomation.

We report the case of a 3-week-old infant referred for evaluation of sudden onset jaundice and unexplained hemolysis. After an exhaustive workup, the most likely etiology was found to be envenomation by a brown recluse spider, Loxosceles reclusa. This case underscores the fact that severe loxoscelism may occur in the absence of the classically described necrotic cutaneous lesion, and represents one of the youngest presumed cases of loxoscelism. We present the case to illustrate the importance of considering loxoscelism in the differential diagnosis of sudden massive hemolysis in children, particularly in endemic areas of the midwestern and southern United States.

Low-level lead exposure triggers neuronal apoptosis in the developing mouse brain.

While the toxic effects of lead have been recognized for millennia, it has remained a significant public health concern due to its continued use and toxicological potential. Of particular interest is the increased susceptibility of young children to the toxic effects of lead. Although the exact mechanism(s) for lead toxicity is currently not well understood, research has established that it can be a potent NMDA antagonist. Previous research has established that exposure to NMDA antagonists during the brain growth spurt period (first 2 weeks of life in mice) can produce apoptotic neurodegeneration throughout the brain. Based on this information, the ability of lead exposure (two injections of 350 mg/kg lead 4h apart) to produce apoptosis in the neonatal mouse brain was assessed histologically 8-24h after treatment using activated caspase-3 immunohistochemistry, De Olmos silver technique, Nissl staining, and electron microscopy. Lead exposure produced significant neurodegeneration in the caudate/putamen, hippocampus, subiculum, and superficial and deep cortical layers of the frontal cortical regions. Further ultrastructural examination revealed cellular profiles consistent with apoptotic cell death. Statistical results showed that lead exposure significantly increased apoptotic neurodegeneration above that seen in normal controls in animals treated at postnatal day 7, but not on day 14. The results of this study may provide a basis for further elucidation of mechanisms through which the immature nervous system may be particularly susceptible to lead exposure.

Post-cervical decompression parsonage-turner syndrome represents a subset of C5 palsy: six cases and a review of the literature: case report.

BACKGROUND: Approximately 5% of cervical decompression cases are complicated by postoperative weakness. Parsonage-Turner syndrome (PTS) or neuralgic amyotrophy is known to be precipitated by surgery and unrelated to technical or structural issues. Our practice has seen a number of cases of PTS after cervical decompression surgery. In this case report, we discuss a series of such patients, highlighting the commonalities with the more frequently diagnosed C5 palsy. We conclude with our management algorithm. CLINICAL PRESENTATION: Six patients with post-cervical decompression PTS were referred to our institution during a 32-month period. All patients were examined physically, radiographically, and electromyographically and were followed for up to 2 years or until symptoms resolved. Conservative management was the rule, and surgical intervention, including nerve releases and nerve reconstruction, was undertaken in select circumstances. In the majority of patients (4 of 6 patients), pain management and physical therapy alone were used and achieved eventual resolution of pain and recovery of motor strength. The other 2 patients required adjunctive surgical procedures to maximize their outcomes. CONCLUSION: PTS accounts for a subset of patients experiencing postoperative weakness after cervical decompression operations. Although it is at times difficult to arrive at this diagnosis, an understanding of the history of PTS, among other causes of postoperative weakness, allows a structured approach to these patients. An evidence-based approach to management helps provide the best outcome for a given patient.

High dose magnesium sulfate exposure induces apoptotic cell death in the developing neonatal mouse brain.

BACKGROUND: Magnesium sulfate (MgSO4) is often used as a treatment for pre-eclampsia/eclampsia and preterm labor, resulting in the exposure of a significant number of neonates to this drug despite a lack of evidence suggesting that it is safe, or effective as a tocolytic. While there is evidence that MgSO4 may be neuroprotective in perinatal brain injury, recent reviews have suggested that the effects are dependent upon dose, and that higher doses may actually increase neonatal morbidity and mortality. There is a lack of evidence investigating the neurotoxic effects of neonatal magnesium (Mg) exposure on the developing brain, specifically in terms of neurodevelopmental apoptosis, a cell-killing phenomenon known to be potentiated by other drugs with mechanisms of action at Mg-binding sites (i.e. NMDA receptor antagonists such as MK-801, ketamine, and PCP). OBJECTIVE: To investigate the effects of Mg exposure on the neonatal mouse brain at different postnatal ages to determine whether MgSO4 treatment causes significant cell death in the developing mouse brain. METHODS: C57Bl/6 mice were treated with four doses of MgSO4 (250 mg/kg) on postnatal days 3 (P3), 7 (P7) or 14 (P14). Caspase-3 immunohistochemistry, cupric silver staining, and electron microscopy techniques were used to examine Mg-treated brains for neurotoxic effects. RESULTS: Qualitative evaluation using cupric silver staining revealed widespread damage throughout the brain in P7 animals. Results of electron microscopy confirmed that the cell death process was apoptotic in nature. Quantitative evaluation of damage to the cortex, caudate-putamen, hippocampus, thalamus, and cerebellum showed that Mg treatment caused significant brain damage in animals treated on P3 and P7, but not P14. CONCLUSIONS: Administration of high doses of Mg may be detrimental to the fetal brain, particularly if exposure occurs during critical periods of neurodevelopment.

Stability and microbiology of inhalant N-acetylcysteine used as an intravenous solution for the treatment of acetaminophen poisoning.

STUDY OBJECTIVE: Intravenous N-acetylcysteine has been used as an antidote for acetaminophen poisoning for more than 25 years in Europe and Canada. In the United States, only the oral administration of N-acetylcysteine is approved by the US Food and Drug Administration. Many physicians routinely use the inhalant preparation as an intravenous formulation; however, no stability, microbiology, or pyrogen studies have been performed. In this study, we evaluate the stability and microbiology of inhalational N-acetylcysteine compounded as an intravenous formulation. METHODS: A total of 8 N-acetylcysteine solutions (solution A through H) were prepared by injecting 150 mL of 20% solution through a 22-microm filter to 1 L of 5% dextrose (D(5)W; 2.6% solution). Solutions A through C were prepared at ambient conditions (25 degrees C [77 degrees F], 65% relative humidity), and solution D was prepared at accelerated conditions (40 degrees C [104 degrees F], 75% relative humidity) for stability testing. The assays were performed by means of high-performance liquid chromatography at 0, 4, 8, 12, 24, 36, 48, 60, and 72 hours according to US Pharmacopeia XXIV methodology. Solutions E through G were assessed for bacterial growth, and solution H underwent pyrogen testing by using a Limulus amebocyte lysate method. RESULTS: Solutions A through C remained stable for at least 60 hours (<10% decomposition), but at 72 hours, there was a 10.3%, 14.9%, and 13.4% degradation, respectively. Under accelerated conditions (solution D), stability lasted for more than 72 hours. Solutions E through G remained free from bacterial growth at 72 hours, and solution H tested negative for endotoxins-pyrogens. CONCLUSION: Inhalational N-acetylcysteine prepared as an intravenous solution meets US Pharmacopeia standards for stability up to 60 hours and is free from bacteria and their byproducts, offering a viable alternative to the traditional use of oral N-acetylcysteine.

Chronic but not acute estradiol treatment protects against the neurodegenerative effects of N-methyl-D-aspartate receptor antagonists.

Drugs that block NMDA receptors, thereby inducing an NMDA receptor hypofunctional (NRHypo) state, can cause a disseminated pattern of irreversible neurodegeneration. Based on several lines of evidence, an N-methyl-D-aspartate receptor hypofunction (NRHypo) mechanism has been postulated to contribute to neurodegenerative changes in Alzheimer disease (AD). Because estrogen putatively exerts a neuroprotective effect in AD, we examined whether estrogen protects against NRHypo-induced neurodegeneration. We administered estradiol benzoate in three separate experiments to adult female rats: (1) 100 microg subcutaneously as a onetime dose, (2) 100 microg bid twice daily for 4.5 or 14 d, and 3) 300 microg twice daily for 4.5 d. Two hours after the last estradiol dose, MK-801 was administered (0.5 mg/kg subcutaneously) to produce a robust neurotoxic injury. Controls received MK-801, but no estradiol. Four hours after administration of MK-801, the severity of injury was evaluated histologically by quantitative methods previously described. Compared to controls, a single dose of estradiol produced no change in the severity of injury (p = 0.24). Chronic treatment with estradiol was associated with a 25-35% reduction in the number of injured neurons (p < 0.05 in all cases). We conclude that chronic but not acute estradiol treatment reduces the severity of NRHypo-induced neurodegeneration.