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Biomedical subjects

L S Nelson

Publications and source records attributed to L S Nelson.

At least 19 recordsLinked to original sources

A case of levetiracetam (Keppra) poisoning with clinical and toxicokinetic data.

BACKGROUND: Levetiracetam (Keppra) is a new anticonvulsant used to treat partial complex seizures that is also being investigated for its mood-stabilizing properties. Although its precise mechanism of action is unknown, levetiracetam does not appear to directly interact with the GABA system. We report the first intentional overdose with levetiracetam including clinical effects and serial serum concentrations. CASE REPORT: A 38-year-old woman reportedly ingested 60 (500 mg) tablets of levetiracetam that she used as a mood-stabilizing medication for bipolar disorder. She had no other prescription medications available and no other medical history. She vomited 4 hours after ingestion and presented to the ED 2 hours later. In the ED, the patient was obtunded and was intubated secondary to respiratory depression. Her only other significant clinical finding was diminished deep tendon reflexes. Serum ethanol, lithium, carbamazepine, phenytoin, and valproic acid levels were all negative as was a subsequent urine screen for drugs of abuse. Her levetiracetam serum concentration was 400 microg/mL at 6 hours, 72 microg/mL at 18 hours, and 60 microg/mL at 20.5 hours (therapeutic serum concentration is 10-37 microg/mL). The elimination half-life was calculated to be 5.14 hours. She was extubated the next hospital day and recovered without sequelae. CONCLUSION: In overdose, levetiracetam is sedating and causes respiratory depression, however, recovery is rapid with supportive care. This is the first reported case of levetiracetam overdose; serial serum concentrations suggest first-order elimination even at concentrations 10-40 fold higher than therapeutic.

Adult↗

Clenbuterol ingestion causing prolonged tachycardia, hypokalemia, and hypophosphatemia with confirmation by quantitative levels.

BACKGROUND: Clenbuterol is a long acting beta2-adrenergic agonist used in the treatment of pulmonary disorders. Acute clenbuterol toxicity resembles that of other beta2-adrenergic agonists. Most previously reported cases of clenbuterol toxicity describe patients who ate livestock illicitly treated with clenbuterol. CASE REPORT: We report a case of human clenbuterol toxicity confirmed and correlated with qualitative and quantitative serum clenbuterol assays. This poisoned patient, a 28-year-old woman, developed sustained sinus tachycardia at 140/min, hypokalemia (2.4 mEq/L, 2.4 mmol/L), hypophosphatemia (0.9 mg/dL, 0.29 mmol/L), and hypomagnesemia (1.52 mg/dL, 0.76 mmol/L) after ingesting a reportedly small quantity of clenbuterol. The patient received repeated doses of metoprolol to treat her cardiovascular stimulation and potassium chloride to treat her hypokalemia. She remained symptomatic for more than 20 hours after the ingestion. Analysis by enzyme-linked immunosorbent assay and liquid chromatography/mass spectrometry revealed a serum clenbuterol concentration of 2.93 mcg/L 3 hours after the ingestion and an undetectable serum concentration 20 hours after ingestion. It is noteworthy that at a serum concentration below the limit of detection by liquid chromatography/mass spectrometry, the patient remained symptomatic. Acute clenbuterol toxicity is rarely reported following illicit use in humans, and this is the first such case to provide confirmatory toxicological analysis.

Adrenergic beta-Agonists↗

Aldicarb poisoning by an illicit rodenticide imported into the United States: Tres Pasitos.

OBJECTIVE: Although intentional and unintentional rodenticide poisoning is common, most readily available agents are of relatively low acute toxicity. A four-year long epidemic of severe toxicity from rodenticide exposure continues among patients predominantly of Dominican descent living in New York City. This study characterizes the ongoing epidemic of acute cholinesterase inhibitor poisoning due to an illicit rodenticide and identifies its etiology. METHODS: A prospectively collected case series of poisoned patients referred to the New York City Poison Control Center. The main outcome measures include the clinical characteristics upon presentation, antidotal and other therapeutic requirements, and patient outcome. Product analysis was performed with paper chromatography, gas chromatography/mass spectrometry, and high-performance liquid chromatography. A murine model assessing both clinical effect and cholinesterase activity was also performed. RESULTS: Thirty-five patients were referred following exposure to Tres Pasitos. Patients developed signs of cholinergic hyperactivity and many required high doses of atropine (>10 mg) to control these symptoms. The source was identified as a rodenticidal compound sold illicitly in local groceries primarily within the Dominican community. Murine cholinesterase activity fell significantly following exposure to the rodenticide. High-performance liquid chromatography identified aldicarb, an extremely potent carbamate-type cholinesterase inhibitor, not licensed for rodenticidal use in this country. CONCLUSION: Illicit sale of undocumented compounds poses a substantial public health threat. Despite several public health interventions, the epidemic continues.

Adolescent↗

Sustained-release potassium chloride overdose.

BACKGROUND: Although ingestion of sustained-release potassium supplements can cause life-threatening hyperkalemia in patients with abnormal renal function, only a few previous reports suggest that this may occur in patients with normal renal function. We report 2 cases of hyperkalemia in patients with normal renal function who developed hyperkalemia after ingesting sustained-release potassium preparations and describe the use of radiography and whole-bowel irrigation in their care. CASE REPORTS: The first patient is a 50-year-old woman who ingested 100 K-Dur tablets (each tablet containing 750 mg KCl or 10 mEq potassium) in a suicide attempt 1 hour prior to presenting to the emergency department. She developed a peak serum potassium level of 9.7 mEq/L and had transient, potentially life-threatening electrocardiographic changes. The second patient was a 17-year-old man who ingested 20 to 30 Klor-Con tablets (each tablet containing 750 mg KCl or 10 mEq potassium) in a suicide attempt 10 hours prior to presentation. Although he developed a peak serum potassium level of 6.1 mEq/L, he had a persistently normal electrocardiogram. In both patients, the tablets were visualized on abdominal radiographs and the gastrointestinal tracts of both were successfully decontaminated using whole-bowel irrigation. DISCUSSION: Although the sensitivity and specificity are unknown, the abdominal radiograph appears to be useful in detecting sustained-release potassium tablets. Whole-bowel irrigation as a primary method of gastrointestinal decontamination also appears to be effective although its use is not previously reported for sustained-release potassium overdoses.

Adolescent↗

The benefit of houseofficer education on proper medication dose calculation and ordering.

OBJECTIVES: Drug dosing errors commonly cause morbidity and mortality. This prospective controlled study was performed to determine: 1) residents' understanding of drug dose calculations and ordering; and 2) the short-term effect of a brief educational intervention on the skills required to properly calculate dosages and order medications. METHODS: The study was conducted at an urban public hospital with a four-year emergency medicine (EM) residency program. The EM residents served as the study group and were unaware of the study design. A written, eight-question test (T1) with clinical situations and factual questions was administered. Immediately following the test, correct answers were discussed for 30 minutes. Key concepts were emphasized. Six weeks later, a repeat test (T2a) with a similar format was administered to the study group. The same test (T2b) was simultaneously administered to a control group, residents of similar training who did not take T1, in order to determine test equivalency (T1 vs T2). Tests were graded using explicit criteria by a single investigator blinded to the order of administration. RESULTS: Twenty residents completed both tests T1 and T2a. Their mean scores were 48% and 70%, respectively (p < 0.001, paired t-test). The control group of ten residents had a mean score of 49% (T2b), similar to the study group's scores on T1 (T1 vs T2b, p = 0.40, unpaired t-test). CONCLUSION: Emergency medicine residents require specific training in calculating and executing drug ordering. A brief educational intervention significantly improved short-term performance when retested six weeks later. Long-term retention is unknown.

Adult↗

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Hazardous Substances↗

FMRFamide-related neuropeptide gene family in Caenorhabditis elegans.

Neuropeptides are used as signaling molecules in the nervous system of most organisms, including mammals. The family of FMRFamide (Phe-Met-Arg-Phe-NH2)-like neuropeptides (FaRPs) all share an RFamide sequence at their C-termini and have been shown to have diverse functions in the central and peripheral nervous systems. In the nematode Caenorhabditis elegans, FMRFamide-like peptides (FaRPs) are expressed in at least 10% of the neurons, including motor, sensory, and interneurons that are involved in movement, feeding, defecation, and reproduction. Twenty-two genes, designated flp-1 through flp-22, encode FaRPs in C. elegans, although there are likely to be additional flp genes to be identified. Each flp gene encodes a different set of FaRPs, yielding a predicted total of 59 distinct FaRPs; a few of the genes may also encode non-FaRPs. Inactivation of some of the flp genes indicates that at least one flp gene has unique functions, while at least two flp genes appear to have overlapping functions with other flp genes. These results suggest that a complex family of FaRPs have varied roles through all stages of development and in adulthood in C. elegans.

Animals↗

Isolation, pharmacology and gene organization of KPSFVRFamide: a neuropeptide from Caenorhabditis elegans.

To date, 53 peptides with C-terminal RFamides have been identified by the genome sequencing project in the nematode, Caenorhabditis elegans. In this study the FMRFamide-related peptide (FaRP) KPSFVRFamide (879.90 Da [MH]+) was structurally characterized from extracts of the nematode, Caenorhabditis elegans. Two copies of KPSFVRFamide are encoded by a gene designated flp-9. RT-PCR identified a single cDNA product which was confirmed as flp-9 by sequence determination. Flp-9 cDNA was isolated from larval stages of C. elegans but was not detected in adult worms, indicating that its expression is may be developmentally regulated. KPSFVRFamide displays sequence homology to the nematode peptide, KPNFIRFamide (PF4). The physiological effects of KPSFVRFamide, PF4 and the chimeras, KPNFVRFamide and KPSFIRFamide, were measured on body wall muscle and the vagina vera of the parasitic nematode, Ascaris suum. KPNFVRFamide and KPNFIRFamide had Cl--dependent inhibitory activity on innervated and denervated muscle-preparations, whereas KPSFVRFamide and KPSFIRFamide did not elicit a detectable physiological effect. Although all 4 peptides had inhibitory effects on the vagina vera, KPSFVRFamide and KPSFIRFamide (threshold, >/=0.1 microM) were less potent than KPNFVRFamide and KPNFIRFamide (threshold, >/=10 nM).

Amino Acid Sequence↗

Neuropeptide gene families in the nematode Caenorhabditis elegans.

Neuropeptides have diverse roles in the function and development of the nervous system. With the completion of the sequencing of the C. elegans genome, rapid identification of nematode neuropeptide genes is possible. To date, 41 C. elegans neuropeptide genes have been identified. Of these genes, 20 genes, named flp (FMRFamide-like peptide) genes, encode FMRFamide-related proteins (FaRPs). Deletion of one of the flp genes, flp-1, results in several behavioral defects, suggesting that at least one flp gene is not functionally redundant with other flp genes. Twenty-one genes, named neuropeptide-like protein (nlp) genes, encode peptides distinct from the FaRP family. The predicted nlp-1 and nlp-2 neuropeptides have modest similarity to buccalin and myomodulin, respectively. Cellular expression patterns and genetic analysis of flp and nlp genes suggest that neuropeptides in nematodes also have widespread and varied roles in nervous system function.

Amino Acid Sequence↗