Biomedical subjects
Publications and source records attributed to S C Curry.
1. Glycol ethers and their alkoxyacetic acid metabolites produce a linear increase in plasma osmolality with increasing plasma concentration. 2. This change in osmolality may be too small to be clinically useful at concentrations expected in cases of acute human glycol ether poisoning.
STUDY OBJECTIVE: Acetaminophen freely crosses the placenta, and acetaminophen ingestion is the most frequent intentional overdose in pregnancy. Although most patients do well after maternal treatment with the antidote N-acetylcysteine (NAC), fetal death with massive hepatic necrosis has occurred. It has never been shown whether NAC crosses the placenta to yield fetal plasma levels equal to those associated with hepatoprotective effects in human beings. Our study objective was to evaluate this in a widely accepted large animal model for maternal-fetal research. DESIGN AND TYPE OF PARTICIPANTS: A nonblinded experiment was performed using four domestic sheep at near-term gestation. INTERVENTIONS: NAC 150 mg/kg IV was administered to the ewe over 15 minutes. After induction of anesthesia, the fetal head was delivered surgically and a neck vein cannulated for blood sampling. Maternal and fetal blood samples were obtained at the end of NAC infusion, at 30- and then at 60-minute intervals for four hours. Plasma NAC levels were determined by gas chromatography/mass spectroscopy (detection limit, 2 micrograms/mL; quantification limit, 5 micrograms/mL). RESULTS: Maternal peak plasma NAC levels were 619, 631, 1,757, and 2,512, micrograms/mL, respectively, within 30 minutes of infusion. However, NAC was only minimally detectable in plasma of two fetal animals and transiently reached quantifiable levels in two others. None of the fetal animals attained serial plasma NAC levels that equalled those associated with therapeutic dosing or hepatoprotective effects in human beings. CONCLUSION: Transplacental transport of NAC is clinically insignificant in a mammalian model resembling the human being. These findings suggest that the human fetal liver is not protected from acetaminophen toxicity by maternal NAC therapy.
STUDY OBJECTIVE: To examine the efficacy of digoxin-specific Fab fragments (dsFab) in the treatment of experimentally induced Nerium oleander cardiac glycoside toxicity in a dog model. DESIGN: A nonblined, placebo-controlled experiment. SUBJECTS: Ten adult greyhound dogs of either sex divided into treatment and control groups of five dogs each. INTERVENTIONS: A tincture of oleander was prepared and administered intravenously to each animal. After the onset of cardiotoxicity, the treatment group received 60 mg/kg dsFab IV. MEASUREMENTS AND MAIN RESULTS: All dogs exhibited dysrhythmias meeting our criteria for cardiac glycoside cardiotoxicity within 27 minutes of beginning the infusion. Three of five control dogs had lethal dysrhythmias during the three-hour observation period. The remaining two control dogs exhibited dysrhythmias throughout the three-hour experiment. All five of the dsFab-treated dogs survived and converted to normal sinus rhythm within eight minutes of dsFab infusion. Three treatment animals reverted back to nonlethal and hemodynamically stable dysrhythmias after a mean of 107 minutes. CONCLUSION: Large doses of dsFab are efficacious in the treatment of dysrhythmias in this canine model of N oleander cardiac glycoside poisoning.
STUDY OBJECTIVES: To determine if toxic concentrations of cyanide in blood result in a difference between calculated and measured percent hemoglobin oxygen saturation (percent saturation gap). DESIGN: An in vitro laboratory study. SETTING: Hospital laboratory. TYPE OF PARTICIPANTS: Arterial blood from five stable patients residing in a tertiary hospital ICU. Venous blood samples obtained from five healthy volunteers. INTERVENTIONS: Two-mL aliquots from each blood sample were placed into four test tubes and mixed with phosphate buffer. Cyanide was added to three of the tubes so that the four tubes contained 0, 6, 12, and 25 mg/L cyanide. MEASUREMENTS AND MAIN RESULTS: The percent saturation gap was calculated by subtracting the percent oxyhemoglobin measured on an oximeter from the percent saturation calculated by a blood gas analyzer. Using two-tailed, paired t tests, we could not demonstrate a difference in mean percent saturation gaps between arterial samples or venous samples with and without cyanide. All blood samples had a normal percent saturation gap (P greater than .99 by Fisher's exact test). We had greater than a 95% chance of demonstrating a difference in mean percent saturation gaps of only 0.46% in arterial blood and of 3.3% in venous blood if such a difference existed. CONCLUSIONS: Our results, as well as a review of the literature, indicate that there are no data supporting the suggestion that a percent saturation gap should imply the diagnosis of poisoning by inorganic cyanide.
Sodium nitroprusside causes cyanide poisoning at currently recommended infusion rates. Serum thiocyanate concentrations are of no value in detecting cyanide poisoning caused by nitroprusside. Methemoglobinemia in those patients receiving intravenous nitroglycerin may seriously impair oxygen delivery and is not always accompanied by cyanosis in anemic patients. Angiotensin-converting enzyme inhibitors are responsible for a plethora of adverse effects, including renal insufficiency, hypotension, angioedema, cough, and increased insulin sensitivity.
We describe a case of severe refractory hypoglycemia secondary to topical salicylate intoxication. A 72-year-old man with psoriasis and end-stage renal disease was treated with a topical cream containing 10% salicylic acid. The patient presented with encephalopathy and subsequently developed hypoglycemia refractory to infusions of large amounts of glucose. A serum salicylate concentration was elevated at 3.2 mmol/L. Emergent hemodialysis was accompanied by rapid lowering of serum salicylate concentration and resolution of refractory hypoglycemia. Salicylate is well absorbed across normal and diseased skin. Salicylate markedly impairs gluconeogenesis and increases glucose utilization, resulting in hypoglycemia. To our knowledge, this is the first article on hypoglycemia due to the application of topical salicylate.
We did a double-blind, placebo-controlled crossover study of 10 healthy young men taking no medications to determine if ingesting lovastatin is associated with more severe muscle damage after exercise. Five men in the first group took 40 mg of lovastatin daily for 30 days while those in the second group took an identical-appearing placebo. Each volunteer then walked downhill on a -14-degree incline on a treadmill at 3 km per hour for an hour. After a 2-week rest, the subjects were crossed over. Serial serum creatine kinase activity was measured immediately before and 8, 24, 48, 72, 120, and 144 hours after each treadmill session. With each subject serving as his own control, peak mean serum creatine kinase activity (/+- SEM) following treadmill after lovastatin therapy was similar to that following placebo (168.4 +/- 25.8 U per liter versus 146.7 +/- 14.7 U per liter, respectively [P = .9]). With an alpha value of .05, we had greater than a 99% chance of detecting a difference in the rise of serum creatine kinase activity of 200 U per liter between groups. Our data suggest that lovastatin is not an independent risk factor for developing exercise-induced muscle damage using this model of exercise in our study population.
An ovine model of maternal iron poisoning in pregnancy was used to examine the placental transport of deferoxamine and ferrioxamine and to follow maternal and fetal serum iron concentrations when maternal serum iron levels exceeded total iron-binding capacity. Ewes in the third stage of gestation underwent hysterotomy and delivery of the fetal head through an abdominal incision while under ketamine and halothane anesthesia. The fetal external jugular vein was catheterized for sampling of venous blood while the fetus remained in utero. Administration of deferoxamine mesylate or ferrioxamine mesylate IV to ewes was not accompanied by measurable deferoxamine or ferrioxamine in fetal blood. In a final experiment, four gravid ewes in a control group received 2 mg/kg maternal body wt iron IV over 60 minutes. An experimental group comprising another four ewes received similar doses of iron but then received 50 mg/kg deferoxamine mesylate IV over 15 minutes. Control and deferoxamine ewes reached similar peak maternal serum iron concentrations (2,479 +/- 266 and 2,121 +/- 343 micrograms/dL, respectively). The markedly elevated maternal serum iron concentrations were not accompanied by meaningful elevations in fetal serum iron levels over baseline values. Maternal deferoxamine infusion resulted in a more rapid fall in maternal serum iron concentrations but had no effect on fetal serum iron levels. The ovine fetus appears to be protected from elevated maternal serum iron concentrations in the last trimester of pregnancy. It could not be demonstrated that meaningful quantities of deferoxamine or ferrioxamine cross the placenta in the last trimester.(ABSTRACT TRUNCATED AT 250 WORDS)
Marijuana remains a complex, poorly understood drug with many effects. Although its acute psychological effects are well described, data linking cannabis use to chronic psychiatric or social problems and decreased driving or workplace safety are much less clear. Current laboratory procedures have not yet been shown useful to demonstrate acute intoxication, so they remain screening instruments for those interested in detecting cannabis use for other reasons. Although both acute and chronic effects of marijuana use have been described, they appear to be less than other commonly abused substances, including tobacco and alcohol. The rare acute complications that present to the Emergency Department can be managed with conservative measures.
To our knowledge, acute inorganic lead poisoning from single ingestions of lead compounds has been only rarely reported. During a 14-month period, we were contacted regarding eight instances of acute ingestions of liquid lead-based ceramic glazes by mentally impaired residents of nursing homes or psychiatric facilities participating in ceramic arts programs. While some ingestions did not cause toxic effects, some patients developed acute lead poisoning characterized by abdominal pain, anemia, and basophilic stippling of red blood cells. In the blood of several patients, lead concentrations were far above normal (4 to 9.5 mumol/L). Urinary lead excretions were tremendously elevated during chelation therapy, with one patient excreting 535.9 mumol/L of lead during a 6-day period, the largest lead excretion ever reported in a patient suffering from acute lead poisoning, to our knowledge. All patients recovered following supportive care and appropriate use of chelating agents. Lead-based glazes are commonly found in nursing homes and psychiatric facilities. We suspect that acute or chronic lead poisoning from the ingestion(s) of lead-based ceramic glazes may be an unrecognized but not uncommon problem among such residents. We urge physicians to take ingestions of lead-based glazes seriously and to consider the diagnosis of lead poisoning in nursing home and psychiatric patients who have participated in ceramic crafts programs.
Explore the source record for details and available documents.
A 38-year-old man overdosed on benztropine mesylate (Cogentin; Merck Sharpe & Dohme, West Point, PA) and developed anticholinergic poisoning syndrome, which lasted nine days. Serial serum benztropine concentrations were obtained during his hospitalization. Fluctuating benztropine levels suggested that his lengthy intoxication may have been secondary to prolonged, intermittent absorption rather than from slow plasma clearance. This is believed to be the first report of serial serum benztropine concentrations after overdose.
Previous authors have classified poisonous snake bites as being legitimate or illegitimate, depending on whether the victim was taking unnecessary risks with a snake before being bitten. We reviewed medical records of 86 consecutive rattlesnake bite victims cared for at a single medical center to determine legitimacy of snake bites. A bite was considered illegitimate if, before being bitten, the victim recognized an encounter with a snake but did not attempt to move away from the snake. A legitimate bite was said to have occurred if a person was bitten before an encounter with a snake was recognized or was bitten while attempting to move away from a snake. The study group was made up of 75 male (87.2%) and 11 female (12.8%) victims. Seventy-four percent were 18 to 50 years old, and 15% had been bitten previously. Only 43.4% of all bites were considered legitimate, and pet (captive) snakes accounted for almost one third of all illegitimate bites. The ingestion of alcoholic beverages was associated with 56.5% of illegitimate bites versus 16.7% of legitimate bites (P less than .001). While 74.4% of bites were to upper extremities, only 27% of upper extremity bites were legitimate. All bites to the lower extremity were legitimate (P less than .001). Of 14 individuals bitten by pet snakes, all were men and 64.3% were under the influence of alcohol at the time of the bite.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
Phenytoin absorption is reportedly significantly altered in the presence of continuously administered enteral feedings, resulting in subtherapeutic serum phenytoin concentrations and loss of seizure control. We administered 500 mg of phenytoin as the suspension to five volunteers who were not receiving enteral feeding, again while they ingested protein hydrolysate enteral feedings hourly, and again during hourly ingestions of meat-base enteral feeding. Serum phenytoin concentrations, measured 3, 6, 9, 12, and 24 hours after phenytoin ingestion, were lowest with protein hydrolysate feedings. Mean serum phenytoin concentrations were consistently higher with the meat-base feeding than with the protein hydrolysate formula, although levels did not reach those of the control period. These data are in keeping with our previous observation that it is easier to attain therapeutic serum phenytoin concentrations in patients receiving a meat-base enteral feeding than in those receiving a protein hydrolysate formula.
A case of prolonged succinylcholine-induced paralysis in a child with organophosphate insecticide poisoning is presented. Three hours and 15 minutes of apnea after the administration of succinylcholine was attributed to a decreased rate of succinylcholine metabolism from inhibition of pseudocholinesterase by the insecticide. Only one similar case has been reported previously in the English medical literature. If succinylcholine is to be used in patients with organophosphate poisoning, a prolonged paralysis should be anticipated.
We cared for two rattlesnake bite victims who developed platelet counts of 21,000/mm3 and 22,000/mm3. Both had only mild defibrination without evidence of intravascular clotting. In both cases, the administration of antivenin was followed promptly by a sustained rise in platelet counts.