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Biomedical subjects

W Kerns

Publications and source records attributed to W Kerns.

14 recordsLinked to original sources
PubMed2001

Airway obstruction following canebrake rattlesnake envenomation.

We report an unusual case of canebrake rattlesnake (Crotalus horridus atricaudatus) envenomation whose major manifestation was orolingual edema and airway compromise. The likely source of swelling was mucosal absorption of venom following the first aid technique of cutting and sucking the bite site. Except for airway compromise, the patient had mild local bite site effects (swelling) and mild systemic findings (depressed fibrinogen and elevated creatinine phosphokinase). He was managed with fiberoptic nasotracheal intubation and Crotalid antivenin with good outcome.

Administration, Oral↗
PubMed1998

Altered hemostasis in male rats following administration of the ACAT inhibitor SKF-99085.

SKF-99085, an acyl-CoA:cholesterol acyltransferase (ACAT) was evaluated in male and female Sprague-Dawley rats at oral doses of 0, 10, 100, or 400 mg/kg/day for 6 months as part of the preclinical safety assessment of this drug candidate. In male rats given 400 mg/kg/day SKF-99085, hemorrhage and death were observed in males during the first month of the study, prompting collection of blood samples at weeks 6, 17, and 24 to monitor coagulation parameters. A dose-related increase in activated partial thromboplastin time (APTT) and Thrombotest clotting time (TCT) was observed in all male drug-treated groups. Mean APTT values for male rats given 10, 100, or 400 mg/kg/day were increased maximally to 17.5, 20.8, and 34.7 s (control, 15.4-16.0 s), and mean TCT values were increased to 86, 100, and >300 s (control, 71-74 s), respectively. Mean prothrombin times (PT) for male rats given 400 mg/kg/day were increased to 16.5 s (control, 12.9-13.1 s). Activities of factors II, VII, IX, and X were decreased in males at dosages of 10, 100, or 400 mg/kg/day. Factor V and VIII activities were unaffected. In summary, the drug-related hemorrhagic disorder observed in male rats given high doses of the ACAT inhibitor SKF 99085 was attributed to a reduction in the activity of vitamin-K-dependent coagulation factors. In contrast to humans and some other species, the APTT and TCT were more sensitive than the PT in detecting this effect.

Acetyl-CoA C-Acyltransferase↗
PubMed1998

Glycolate kinetics and hemodialysis clearance in ethylene glycol poisoning. META Study Group.

OBJECTIVE: Toxic manifestations following ethylene glycol exposure are due to accumulation of metabolites, particularly glycolate. We characterized glycolate elimination kinetics and dialysis properties in a series of ethylene glycol poisonings. METHODS: Patients who ingested ethylene glycol and received fomepizole (4-methylpyrazole; 4-MP) +/- hemodialysis were prospectively evaluated. Serial blood samples for ethylene glycol, glycolate, pH, and bicarbonate were drawn to determine glycolate elimination rate, t1/2, and correlations between initial glycolate and initial markers of acidosis. Dialyzer inlet and outlet samples were obtained to measure hemodialysis glycolate clearance. Plasma ethylene glycol and glycolate were determined by gas chromatography. RESULTS: Ten patients, mean age 49 years (range 28-73 years), presented a mean of 10.5 hours (range 3.5-21.5 hours) after ethylene glycol ingestion. Mean initial ethylene glycol was 18.5 mmol/L (range 0.8-62.2 mmol/L) (115 mg/dL; range 5-386 mg/dL) and glycolate was 17.0 mmol/L (range 10.0-23.7 mmol/L). Nine of 10 underwent hemodialysis. Nonhemodialysis (n = 4) elimination rate was 1.08 +/- 0.67 mmol/L/h (mean +/- SD) and t1/2 was 626 +/- 474 minutes. Elimination t1/2 during hemodialysis (n = 8) was 155 +/- 42 minutes. Hemodialysis clearance (n = 5) was 170 +/- 23 mL/min with flow rates 250-400 mL/min. Pearson correlation coefficients were: anion gap vs glycolate r2 = 0.65 (p = 0.005), bicarbonate vs glycolate r2 = 0.10 (NS) and pH vs glycolate r2 = 0.06 (NS). CONCLUSION: Glycolate has a slow elimination rate and long half-life. Hemodialysis effectively clears glycolate. An increased anion gap correlates with the presence of glycolate. Hemodialysis is projected as useful for ethylene glycol-poisoned patients with anion gap acidosis and low ethylene glycol blood levels.

Adult↗
PubMed1997

Insulin improves survival in a canine model of acute beta-blocker toxicity.

STUDY OBJECTIVE: To compare the efficacy of a novel antidote, insulin, with standard treatments, glucagon and epinephrine, in a canine model of acute beta-blocker toxicity. METHODS: Anesthetized dogs were fitted with instruments by means of thoracotomy and vascular cutdown for multiple cardiodynamic, hemodynamic, metabolic, and electrical measures. After basal measurements were taken, animals received intravenous propranolol (.25 mg/kg/minute) continuously for the remainder of the experiment. Toxicity was defined as a 25% decrease in the product of heart rate times mean blood pressure. Thirty minutes after the development of toxicity, toxic measures were taken (treatment 0 minutes), and then the animals (n = 6 each group) received either sham (saline solution), insulin (4 IU/minute with glucose clamped), glucagon (50 micrograms/kg bolus, then 150 micrograms/kg/hour infusion), or epinephrine (1 microgram/kg/minute). Animals were monitored until death or for 240 minutes. RESULTS: Propranolol decreased contractility, left ventricular pressure, and systemic blood pressure, and resulted in death of all sham-treated animals by 150 minutes. Six of six insulin-treated, four of six glucagon-treated, and one of six epinephrine-treated animals survived. Survival was greater for insulin-treated animals, compared with either glucagon-treated (P < .05) or epinephrine-treated animals (P < .02) by the log-rank test. Insulin-treated animals were characterized by improved cardiodynamics and hemodynamics, increased myocardial glucose uptake, and decreased serum potassium. CONCLUSION: Insulin is a superior antidote compared with glucagon or epinephrine in an anesthetized canine model of acute beta-blocker toxicity.

Acute Disease↗
PubMed1997

The effect of hypertonic sodium and dantrolene on propranolol cardiotoxicity.

OBJECTIVE: To evaluate whether measures that lower cytosolic calcium (Ca) can reverse propranolol (PROP) toxicity in the isolated, perfused rat heart. METHODS: Isolated rat hearts were perfused on a Langendorff apparatus with Krebs-Henseleit-bicarbonate (KHB) buffer solution. Toxicity was produced by perfusing the hearts with PROP (5 micrograms/mL) for 30 minutes. Subsequently, the hearts were treated for 30 minutes with buffer containing PROP plus experimental treatment. Three treatments were chosen: hypertonic sodium (Na) (160 mmol), to stimulate Na-Ca exchange, dantrolene (DAN) (10 mumol), to inhibit Ca release from sarcoplasmic reticulum, and combined hypertonic Na and DAN. The hearts were paced after 20 minutes of treatment. Heart rate (HR), left ventricular peak systolic pressure (LVP), the first derivative of LVP (dP/dt), and coronary flow were measured. RESULTS: PROP decreased HR and rendered the hearts refractory to pacing. PROP did not alter dP/dt. PROP increased LVP consistent with increased cytosolic Ca. Combined hypertonic Na and DAN treatment restored the ability to pace PROP-toxic hearts to the basal HR. Individually, hypertonic Na or DAN treatment partially restored the ability to pace toxic hearts. As experimental treatments increased HR, dP/dt and LVP decreased, consistent with decreased cytosolic Ca availability. CONCLUSION: These data are consistent with the hypothesis that bradycardia during beta-blocker cardiotoxicity is mediated by altered Ca homeostasis.

Adrenergic beta-Antagonists↗
PubMed1996

The effects of extracellular ions on beta-blocker cardiotoxicity.

The mechanism of beta-blocker induced cardiotoxicity is poorly understood. One possible explanation is that beta-blockers induce ion dyshomeostasis, resulting in cardiac hyperpolarization. The intent of this study was to determine if modifying extracellular ions would reverse cardiotoxicity from two beta-blockers: propranolol (PROP) and atenolol (ATEN). Two treatments were studied: low extracellular K+ and high extracellular Na+. Isolated rat hearts were perfused on a Langendorff apparatus with Krebs-Henseleit- Bicarbonate buffer (KHB) solution. Toxicity (Tox) was induced by perfusing hearts for 30 min with KHB + PROP [5 microgram/ml] or KHB + ATEN [2.5 mg/ml]. Subsequently, hearts were perfused with KHB containing either PROP or ATEN, but modified by lowering K+ [2.3 mM] or raising Na+ [160 mM] for a 30-min treatment (Tx) period. Hearts were paced near the end of treatment. Cardiodynamics were monitored via a balloon-tipped catheter in the left ventricle. The first derivative of LV pressure (dP/dt) with respect to time served as our index of myocardial performance. Tx groups were as follows: (1) KHB only, (2) PROP only, (3) PROP + K, (4) PROP + Na, (5) ATEN only, (6) ATEN 4 K, and (7) ATEN + Na. PROP induced negative chronotropic effects and rendered the hearts refractory to pacing. ATEN demonstrated similar chronotropic toxicity plus decreased myocardial contractility. Tx with low extracellular K+ and high extracellular Na+ increased HR and restored the ability to pace, thereby reversing toxicity. These data suggest that beta-blocker toxicity is mediated via hyperpolarization.

Adrenergic beta-Antagonists↗
PubMed1994

Propafenone overdose.

Propafenone is an infrequently used class IC antiarrhythmic drug. We report our experience with a patient who overdosed with propafenone and developed coma, seizures, bradycardia, hypotension, and conduction delay. The clinical manifestations and management of this patient are discussed in light of the known pharmacology of propafenone and compared with the limited number of cases that appear in the literature.

Adult↗
PubMed1994

Beta-blocker and calcium channel blocker toxicity.

Toxicity from beta-blocker and calcium channel blocker drugs is a challenging medical emergency with steadily increasing incidence. Clinical manifestations of intoxication with these drugs are presented in light of known pharmacologic and pharmacokinetic properties, as well as the physiology of the beta-adrenoreceptor and calcium channel. Review of clinical and basic science literature provides the basis for specific management guidelines for beta-blocker and calcium channel blocker toxicity.

Adrenergic beta-Antagonists↗
PubMed1990

Reduction of factor VII coagulant activity (VIIC), a risk factor for ischaemic heart disease, by fixed dose warfarin: a double blind crossover study.

An increase in factor VII coagulant activity is known to be an important risk factor for ischaemic heart disease. Four hundred and eight healthy male Post Office workers were screened in an occupational survey. Sixty eight (16.5%) of these had values of factor VII coagulant activity greater than 1.0 SD above the age related mean. A randomised double-blind crossover study was undertaken to investigate the effect of a fixed daily minidose of warfarin (1 mg) on the high activities of factor VII in these men. Forty two agreed to enter the study and 40 completed it. Their mean factor VII coagulant activity before warfarin treatment was 135.9%. Treatment with a fixed minidose of warfarin significantly reduced factor VII coagulant activity to 124.6%; there was no change on placebo. The prothrombin time was also significantly prolonged on active treatment although all the results remained within the normal range. These findings suggested a fixed minidose warfarin regime might be useful in the primary prevention of ischaemic heart disease by reducing high activities of factor VII.

Adolescent↗
PubMed1988

In vivo inhibition of oxidative drug metabolism by, and acute toxicity of, 1-aminobenzotriazole (ABT). A tool for biochemical toxicology.

One hour following intravenous pretreatment of rats with 50 mg/kg of the cytochrome P-450 suicide substrate 1-aminobenzotriazole (ABT), the metabolism of phenacetin to acetaminophen is inhibited completely [B. A. Mico et al., Drug Metab. Dispos. 15, 274 (1987)]. Here we report an examination of the time-course of inhibition of phenacetin elimination by ABT, a demonstration of dose-dependent inhibition of phenacetin and antipyrine clearances by ABT, and an examination of the acute toxicity of ABT in rats, as well as the effect of ABT on phenacetin metabolism in beagles. After a 1-, 12-, 24- or 36-hr pretreatment of rats with ABT (50 mg/kg, i.v.), the clearance of phenacetin was decreased 85, 88, 81 and 48%, respectively, from control values. Twelve hours after intraperitoneal pretreatment of rats with 0.3, 1.0, 5.0, 20, and 50 mg/kg of ABT, the total systemic clearance of phenacetin was suppressed 39, 47, 60, 75, and 79%, respectively, from control values. The clearance of intravenously administered antipyrine was decreased 38 and 66% after a 12-hr intraperitoneal pretreatment of rats with 10 or 50 mg/kg of ABT. In rats, no hematological, clinical chemistry, macroscopic, or microscopic abnormalities were detected 1, 2, 3, and 9 days after a single i.v. dose of ABT (50 mg/kg). A 1-hr pretreatment of beagles with ABT (20 mg/kg) decreased the clearance of intravenous phenacetin 50% and completely prevented the formation of acetaminophen. These results demonstrate that ABT pretreatment causes long-lasting inhibition of oxidative drug metabolism without disruption of normal physiological processes. Profound inhibition of oxidation in two species suggests that ABT may have general utility as an inhibitor of oxidative drug metabolism in biochemical pharmacology and toxicology studies.

Acetaminophen↗
PubMedDate not supplied

Cocaine-induced wide complex dysrhythmia.

Cocaine is a local anesthetic with the potential to induce dysrhythmia due to direct myocardial sodium channel antagonism similar to class I antidysrhythmic drugs. The hallmark of myocardial sodium channel poisoning is wide complex dysrhythmia, and the current accepted treatment is intravenous bicarbonate. Wide complex dysrhythmio due to cocaine in the absence of myocardial infarction is rare, and optimum management is undefined. We report three cases of acute cocaine intoxicating during which patients developed wide complex dysrhythmia consistent with sodium channel poisoning. In one case, wide complex tachycardia resolved without direct treatment. In the other cases, wide complex dysrhythmia resolved following intravenous bicarbonate therapy directed at reversing sodium channel blockade.

Adult↗
PubMedDate not supplied

Incidence of aspiration pneumonia in intubated patients receiving activated charcoal.

Several case reports and animal studies raise concerns over the risk of aspiration pneumonia when administering activated charcoal (AC) to intubated patients. Therefore, we sought to determine the incidence of aspiration pneumonia in intubated overdose patients who then received AC. We conducted a retrospective review from January 1994 to April 1997 of intubated patients who then received AC. Patients were transferred to, or primarily treated at, an 843-bed tertiary medical center with an annual emergency department volume of 100,000 patients. Objective evidence of infiltrate on chest radiograph during initial 48 h of hospitalization was used to determine the incidence of aspiration pneumonia. Patients with known preexisting pneumonia or with administration of AC before intubation were excluded. There were 64 patients identified. Fourteen were excluded for clinical aspiration before intubation, receiving activated charcoal before intubation, or abnormal immediate post-intubation chest radiographs. The remaining 50 patients, ages 1-64 years, 33% male, overdosing on a large variety of substances, required acute intubation and then received AC. Only two patients of these 50 (4%) with initial negative radiographs developed a new infiltrate after intubation and AC. Administration of AC to intubated overdose patients is associated with a low incidence of aspiration pneumonia.

Adolescent↗