Biomedical subjects
L R Goldfrank
Publications and source records attributed to L R Goldfrank.
Herbal preparation use among urban emergency department patients.
OBJECTIVE: To determine the prevalence of herbal preparation use among patients presenting to an urban teaching hospital ED. METHODS: A prospective anonymous survey on herbal preparation use was performed. Consecutive, acutely ill or injured adult (> or = 18 years old) ED patients were offered the survey over a 1-month period. The survey also asked for information related to patient age, ethnicity, gender, employment, education, cigarette smoking history, ethanol consumption, use of illicit drugs, chief complaint, and HIV status. RESULTS: Of 2,473 eligible subjects, 623 (25%) participated. The overall reported prevalence of herbal preparation use among the participants was 21.7%. Women were more likely to use herbal preparations than men (28.5% vs 17.2%, p = 0.013). Prevalence rates in different ethnic populations were: whites, 18.2%; Hispanics, 13.9%; blacks, 26.4%; and Asians, 36.8%. Asians had a significantly higher use rate than the other ethnic groups (p = 0.039). Neither HIV positivity, educational level, employment status, nor age was significantly associated with herbal preparation use. The most commonly reported herbal preparations were goldenseal tea, garlic, and ginger. Several of the herbal preparations reported as used by patients in this study have been associated with severe systemic toxicity in the medical literature. CONCLUSION: Although the survey response rate was low, the prevalence of herbal preparation use among acutely ill or injured patients presenting to this urban ED remains significant. A directed history toward specific herbal preparation use may provide relevant pharmacologic information and uncover cases of herbal-preparation-induced toxicity.
Poison center data and the Pollyanna phenomenon.
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Effects of Prussian blue and N-acetylcysteine on thallium toxicity in mice.
BACKGROUND: Thallium poisoning is now rare but still occurs as a result of homicide attempts. Prussian blue's efficacy in the treatment of experimental thallium poisoning has been demonstrated in animal models, and its use in humans is supported by anecdotal data. Since thallium binds sulfhydryl groups, the use of N-acetylcysteine is also considered as a potential antidote. STUDY OBJECTIVE: To compare the efficacy of Prussian blue and N-acetylcysteine in a murine model of thallium poisoning. METHODS: Female Swiss albino mice with free access to food and water were used. Two study doses of thallium, given as a subcutaneous injection of thallium acetate dissolved in sterile water, were chosen: 70 mg/kg (LD90) and 85 mg/kg (> LD100). A randomized, placebo controlled study was conducted with survival at 120 h chosen as the outcome measure. Four treatment groups were studied: control, Prussian blue, N-acetylcysteine, and the combination of Prussian blue and N-acetylcysteine. Prussian blue was dissolved in water and given by oral gavage at a dose of 50 mg/kg. N-acetylcysteine was diluted in normal saline and given as intraperitoneal injections of 200 mg/kg. Sterile water by gavage and normal saline by peritoneal injection were given as control treatments whenever an active agent was not given. Survival was recorded over a 120 h study period and compared at 120 h by a Fisher's exact test. RESULTS: At 120 h following subcutaneous injection of thallium 70 mg/kg, only 10% of the control animals survived. Treatment with N-acetylcysteine or Prussian blue increased survival to 35% (p = 0.13) and 50% (p = 0.014), respectively. The addition of N-acetylcysteine to Prussian blue offered no benefit over Prussian blue therapy alone. CONCLUSIONS: Prussian blue was found to decrease mortality from thallium poisoning at a dose equal to the LD90 in this model, but not a dose greater than the LD100. No role for N-acetylcysteine in the treatment of thallium poisoning was demonstrated by this study.
Antidotal efficacy of glutamate and aspartate for colchicine toxicity.
Glutamic and aspartic acids were evaluated for their antidotal efficacy in colchicine toxicity. Female adult inbred mice were treated with ip doses of either 1000 mg glutamic acid (GA) or aspartic acid (AA)/kg bw by various treatment schedules relative to the administration of an ip LD5n of 7.8 mg colchicine/kg bw. Mice were observed for survival and changes in body weight. Pretreatment with AA increased survival by 42% (p = 0.01). Concurrent AA treatment improved survival non-significantly (p = 0.07). With post-exposure AA therapy, however, mortality was increased (p = 0.005). No significant beneficial effects of GA occurred. Early AA therapy improves survival in colchicine poisoned mice, but as delay in treatment is increased, AA efficacy is lost.
Research directions in emergency medicine.
The goal of emergency medicine is to improve health while preventing and treating disease and illness in patients seeking emergency medical care. Improvements in emergency medical care and the delivery of this care can be achieved through credible and meaningful research efforts. Improved delivery of emergency medical care through research requires careful planning and the wise use of limited resources. To achieve this goal, emergency medicine must provide appropriate training of young investigators and attract support for their work. Promotion of multidisciplinary research teams will help the specialty fulfill its goals. The result will be the improvement of emergency medical care which will benefit not only the patients emergency physicians serve but also, ultimately, the nation's health.
Assessment of visual acuity in the supine position.
OBJECTIVE: To determine whether a modified Snellen eye chart could be used to accurately assess visual acuity (VA) in the supine position. METHOD: This was a prospective study involving ED staff volunteers comparing VA on a standard Snellen eye chart with VA on a size-reduced ceiling-mounted modified Snellen eye chart. RESULTS: Fifty-six volunteers participated. VA ranged from 20/10 to 20/200 on both of the charts, but 87% of the volunteers had VA of 20/50 or better. The VA results for the 2 charts were highly correlated; right eye r = 0.931 and left eye r = 0.953. Weighted ks showed substantial agreement for both eyes; kappa = 0.63 and 0.79 for the right and left eyes, respectively. In only 4 of 112 paired measurements did the VA recorded with the ceiling chart differ by > 1 line from that recorded on the Snellen chart. CONCLUSION: There is an excellent correlation between VAs determined in the erect and the supine positions using the standard Snellen eye chart and the modified ceiling-mounted version. Substantial agreement exists between readings using the 2 charts. Although additional testing is warranted in an ophthalmologically diverse patient population, use of this chart for the assessment of VA in the supine ED patient may allow for earlier VA evaluation.
Administration of purified human plasma cholinesterase protects against cocaine toxicity in mice.
BACKGROUND: Cocaine is metabolized in part by plasma cholinesterase to form ecgonine methyl ester. Decreased plasma cholinesterase activity is associated with enhanced cocaine toxicity in both humans and animals. This study was designed to determine whether the administration of exogenous plasma cholinesterase is protective against cocaine toxicity. METHODS: Using a blinded protocol, female Swiss albino mice were randomized to receive an intraperitoneal injection of either 13.7 mg/kg of purified human plasma cholinesterase dissolved in phosphate buffered saline, or an equal volume of phosphate buffered saline as a control. One hour later, all animals received an intraperitoneal injection of either 100 or 125 mg/kg of cocaine, and the incidence of seizures and death was recorded. In a similar fashion, another group of animals was randomized to receive a human plasma cholinesterase dose of either 13.7 or 27.4 mg/kg, followed by 150 mg/kg of cocaine. RESULTS: Administration of 13.7 mg/kg of human plasma cholinesterase increased plasma cholinesterase activity by a mean of 63 +/- 13 fold, with a Tmax of 90 minutes and a Vd of 85 +/- 13 mL/kg. Cocaine's effects on seizures and death were attenuated by human plasma cholinesterase. A cocaine dose of 150 mg/kg represents an ED100 for seizures and an LD100. At this dose, lethality was reduced to 30% (p < 0.001) and seizures were reduced to 40% (p < 0.001) by administration of 27.4 mg/kg of human plasma cholinesterase. CONCLUSIONS: Pretreatment with purified human plasma cholinesterase protects mice against the convulsive and lethal effects of cocaine.
Pharmacokinetics following a loading plus a continuous infusion of pralidoxime compared with the traditional short infusion regimen in human volunteers.
BACKGROUND: Many authors currently recommend infusing the adult dose (1 g) of pralidoxime over a 15-30 minute period. When administered in this manner, computer simulations predict that plasma pralidoxime concentrations will fall below 4 mg/L as early as one and one half hours after administration. The objective of this study was to assess whether a loading dose followed by a continuous infusion would maintain therapeutic levels longer than the traditional short infusion regimen of pralidoxime if the same total dose was administered. METHODS: Utilizing a randomized, crossover design, healthy volunteers were administered either 16 mg/kg of pralidoxime intravenous over 30 minutes or 4 mg/kg of pralidoxime intravenous over 15 minutes followed by 3.2 mg/kg/h for 3.75 h (for a total dose of 16 mg/kg). Pralidoxime levels were obtained at 0, 10, 20, 30, 60, 120, 180, 240, 300, and 390 minutes and patients were observed for vital sign changes and adverse effects. RESULTS: Seven subjects completed both arms of the study. One subject's data were excluded from pharmacokinetic analysis due to aberrant plasma pralidoxime analysis. The loading dose followed by the continuous infusion maintained therapeutic levels for 257.3 +/- 50.5 minutes whereas the short infusion maintained therapeutic levels for 118.1 +/- 52.1 (p < 0.001). Adverse effects were encountered during the short infusion regimen which did not occur during the continuous infusion. Dizziness or blurred vision occurred in all subjects during the short infusion regimen. Additionally, statistically significant increases in diastolic blood pressure occurred during the short infusion regimen. CONCLUSIONS: The results of this study indicate that a loading dose followed by a continuous infusion of pralidoxime maintains therapeutic concentrations for a longer period of time than the currently recommended short infusion regimen in healthy volunteers.
The poisoned patient with altered consciousness. Controversies in the use of a 'coma cocktail'.
OBJECTIVE: In the assessment and management of the potentially poisoned patient with altered consciousness, the most consequential and controversial interventions occur during the first 5 minutes of care. In this review article, the risks and benefits of standard diagnostic and therapeutic interventions are presented to guide clinicians through this critical period of decision making. DATA SOURCES: Data for discussion were obtained from a search of English-language publications referenced on MEDLINE for the years 1966 to 1994. Older literature was included when pertinent. Search terms included poisoning, overdose, toxicity, naloxone, glucose, thiamine, and flumazenil. STUDY SELECTION: Only large trials were used for determinations of diagnostic utility and efficacy. Small trials, case series, and case reports were reviewed extensively for adverse effects. DATA EXTRACTION AND SYNTHESIS: Trials were reviewed for overall methodology, inclusion and exclusion criteria, sources of bias, and outcome. CONCLUSION: Analysis favors empirical administration of hypertonic dextrose and thiamine hydrochloride to patients with altered consciousness. Although rapid reagent test strips can be used to guide this therapy, they are not infallible, and they fail to recognize clinical hypoglycemia that may occur without numerical hypoglycemia. Administration of naloxone hydrochloride should be reserved for patients with signs and symptoms of opioid intoxication. Flumazenil is best left for reversal of therapeutic conscious sedation and rare select cases of benzodiazepine overdose.
Emergency medicine.
A survey determined that Medicaid recipients had limited access to outpatient care other than the care received at emergency departments. Recent advances in our understanding of trauma call into question how fluid resuscitation should be performed in the field.
Health care reform or a return to social darwinism?
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Role of emergency medicine residency programs in determining emergency medicine career choice among medical students.
STUDY OBJECTIVE: To characterize the role of emergency medicine residency programs in determining emergency medicine career choice among medical students. DESIGN: Observational, cross-sectional, descriptive study. Information on student career choice was obtained through a targeted query of the National Resident Matching Program data base, simultaneously stratified by specialty and school, and adjusted for class size. PARTICIPANTS: All accredited emergency medicine residency programs and four-year allopathic medical schools. RESULTS: Fifty-two schools (42%) had a closely affiliated emergency medicine residency program, ie, one based primarily at the institution's main teaching hospital(s). This configuration was associated with a 70% increase in the median proportion of students choosing emergency medicine as a career when compared to the 73 schools with no closely affiliated emergency medicine residency (5.1% vs 3.0%, P < .0001). When institutions were stratified by overall commitment to emergency medicine, the median proportion of students choosing emergency medicine as a career was 2.9% for institutions with a minimal commitment to emergency medicine (neither an academic department of emergency medicine nor a closely affiliated emergency medicine residency), 4.1% for institutions with a moderate commitment to emergency medicine (either a department of emergency medicine or an emergency medicine residency, but not both), and 5.7% for institutions with a substantial commitment to emergency medicine (a department of emergency medicine and an emergency medicine residency) (P < .0001). When institutional commitment to emergency medicine was examined in a simple multivariate model, only the presence of an emergency medicine residency was associated independently with student career choice (P < .001). CONCLUSION: An emergency medicine residency program that is closely affiliated with a medical school is strongly and independently associated with a quantitatively and statistically significant increase in the proportion of students from that school who choose a career in emergency medicine. These data support the proposition that, if emergency medicine is to meet national manpower shortage needs by attracting students to the specialty, it must establish residency programs within the primary teaching hospital(s) of medical schools. Such a configuration does not currently exist in the majority of schools.
Thallium poisoning from maliciously contaminated food.
Four young adults presented two days after one of them had received marzipan balls packaged in a box from an expensive candy manufacturer. Two ate one candy ball, while two others shared a third. The next day, variable gastrointestinal symptoms developed. On the third day, two patients developed painful paresthesiae of the hands and feet, an early but nonspecific clinical marker of thallium poisoning. A tentative diagnosis of thallium poisoning was made based on symptoms, and treatment was initiated. The remaining candies were radiographed. Metallic densities in the candies supported the diagnosis, and atomic absorption spectroscopy was used to quantitate thallium content. Each candy contained a potentially fatal dose. Five to seven days later, hypertension and tachycardia developed in the two patients who had ingested an entire candy. All patients developed alopecia but recovered without overt neurologic or other sequelae. While the diagnosis of thallium poisoning is often delayed until alopecia develops, an early diagnosis favors an effective treatment strategy.
Special considerations in gastrointestinal decontamination.
Many considerations factor into selecting the most appropriate method of gastrointestinal decontamination used in the poisoned patient. A thorough knowledge of the indications and efficacy as well as contraindications and complications of each modality is critical to the clinician's assessment. This article examines the current utility of syrup of ipecac-induced emesis, orogastric lavage, activated charcoal, cathartics, and whole bowel irrigation. In addition, the role of multiple dose activated charcoal and the controversial issue of the N-acetylcysteine and activated charcoal interaction are discussed.
Concepts and controversies of bronchodilator overdose.
Beta-adrenergic agonists and theophylline are both capable of producing tremor, agitation, tachycardia, metabolic acidosis, hypokalemia, hyperglycemia, cardiac arrhythmias, and seizures. However, theophylline preparations, especially in the sustained-release formulations, are associated with a much higher incidence of morbidity and mortality secondary to status epilepticus and cardiovascular collapse. Overdoses of sustained-release preparations place patients at exceedingly high risk. This article describes the differentiation of the patient with acute and chronic theophylline overdoses and the implications for management of both clinical states.
Tetracaine protects against cocaine lethality in mice.
STUDY HYPOTHESIS: Tetracaine will enhance cocaine toxicity. STUDY POPULATION: Two hundred forty female Swiss albino mice weighing 27 to 45 g. METHODS: Intraperitoneal injections of tetracaine and cocaine were given to groups of ten mice each in a controlled, blinded fashion. Either tetracaine or an equal volume of normal saline was given five minutes before one of six incremental doses of cocaine, ranging from 60 to 110 mg/kg. The experiment was repeated twice using two different doses of tetracaine: either an LD10 (40 mg/kg determined from preliminary studies), or one-twentieth of the dose of cocaine (which approximates the ratio used in tetracaine, epinephrine, and cocaine). Lethality was recorded at 24 hours. Lethality between groups was compared with a Wilcoxon sign-rank test. RESULTS: Tetracaine reduced cocaine lethality at all doses. This reduction in lethality was statistically significant at both tetracaine doses (P < .05). CONCLUSION: In the mouse, pretreatment with tetracaine significantly decreases cocaine lethality.
Prevalence of sorbitol in multiple-dose activated charcoal regimens in emergency departments.
STUDY OBJECTIVES: To determine the availability and use of premixed activated charcoal in sorbitol preparations during multiple-dose activated charcoal therapy in the emergency department. DESIGN AND SETTING: A prospective telephone survey of all 911 receiving hospitals within the catchment area of one poison center. TYPE OF PARTICIPANTS: Hospital pharmacy supervisors and ED charge nurses. INTERVENTION: Hospital pharmacy supervisors were surveyed about the available preparations of activated charcoal on their hospital's formulary, and ED charge nurses in these same hospitals were surveyed about the prevalence of sorbitol use in multiple-dose activated charcoal regimens. MEASUREMENTS AND MAIN RESULTS: Eleven hospitals (16%) stocked only activated charcoal in sorbitol preparations. Twenty-one hospitals (31%) had both activated charcoal in sorbitol preparations and activated charcoal without sorbitol preparations, and 35 hospitals (52%) had only activated charcoal without sorbitol preparations. Repeat dosing of sorbitol during multiple-dose activated charcoal therapy occurred in 33 of 67 (49%) of the EDs surveyed. CONCLUSION: Sorbitol dosing is often repeated with activated charcoal during multiple-dose activated charcoal therapy in the ED because of the ready availability (and sometimes exclusive availability) of premixed activated charcoal in sorbitol preparations.