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Biomedical subjects

R C Dart

Publications and source records attributed to R C Dart.

At least 55 records · Page 3Linked to original sources
PubMed1997

Tylenol Extended Relief overdose.

In this report we describe the toxicokinetics of the Tylenol Extended Relief (TER) preparation of acetaminophen in human overdose. We collected 41 cases of TER overdose from five regional poison centers. Patients who met the following criteria were studied: a single ingestion of TER alone; confirmed time of ingestion; at least four acetaminophen determinations; and normal concentrations of liver function enzymes. With the exception of standard decontamination measures, treatment with N-acetylcysteine (NAC) if any acetaminophen level was above the treatment line of the Rumack-Matthew nomogram, and additional acetaminophen determinations, no interventions were recommended. Our study group comprised 13 patients, 12 female and 1 male, with single overdoses of 10.4 to 65 g TER. The acetaminophen elimination half-life was 3.1 +/- .8 hours (mean +/- SD; range, 1.3 to 4.0 hours; n = 12). The elimination phase for patients 2, 3, 4, 6, 8, 9, 11, 13 was delayed until 8.0 +/- 2.8 hours (range, 5 to 14 hours) after ingestion. Patients 3, 8, and 11--who had initial acetaminophen levels below the "possible toxicity" line of the Rumack-Matthew nomogram--later had acetaminophen levels above this line. No patient demonstrated a late or second acetaminophen peak. We conclude that the elimination half-life of TER acetaminophen is similar to that reported in overdose of immediate-release acetaminophen overdose. In a subgroup of patients, drug absorption continued beyond the 2 to 4 hours previously reported in immediate-release acetaminophen overdose. On the basis of our data, the use of a single 4-hour acetaminophen determination may lead to failure to recognize patients with potentially toxic TER ingestion. Until more toxicokinetic data are available, a reasonable approach would be to obtain at least one additional acetaminophen determination at least 4 to 6 hours after the first, if the first is obtained 4 to 8 hours after ingestion. NAC treatment should be initiated if either level is above the nomogram line but not if both levels fall below the nomogram line.

Acetaminophen↗
PubMed1997

Placental transfer of N-acetylcysteine following human maternal acetaminophen toxicity.

OBJECTIVE: To determine whether the antidote for acetaminophen poisoning, N-acetylcysteine, administered to pregnant women with acetaminophen toxicity, crosses the placenta and can be measured in the newborn circulation following delivery. DESIGN: Over a 15-month period, four pregnant women with acetaminophen toxicity, who delivered their infants while receiving the antidote N-acetylcysteine, were studied. Maternal and cord blood from three viable infants, and cardiac blood sampled during an autopsy on the fourth, were analyzed for the presence of N-acetylcysteine using high-performance liquid chromatography. Maternal and cord blood aminotransferase activities, and autopsy findings on the nonviable infant were used to assess hepatic injury. RESULTS: N-Acetylcysteine was detected in the cord blood of three viable infants and in cardiac blood of a fourth, sampled at the time of autopsy. The mean N-acetylcysteine concentration in cord blood was 9.4 micrograms/mL (+/-1.3). This is well within the range associated with therapeutic doses of N-acetylcysteine typically administered to adults with acetaminophen poisoning. No adverse sequelae developed in the three viable infants. The fourth infant, delivered at 22 weeks gestational age died 3 h after birth. All mothers recovered and none of the four infants had evidence of acetaminophen-related toxicity. CONCLUSIONS: This is the first study documenting placental transfer of N-acetylcysteine in humans and provides impetus for research establishing a direct antidotal effect of N-acetylcysteine in the fetus.

Acetaminophen↗
PubMed1997

DMPS-arsenic challenge test. I: Increased urinary excretion of monomethylarsonic acid in humans given dimercaptopropane sulfonate.

The purpose of the present study was to evaluate in a novel manner the arsenic exposure of humans living in two towns in Northeastern Chile. Residents of one town drink water containing 593 microg As/l. Those in the control town drink water containing 21 microg As/l. Our hypothesis was that the administration of the chelating agent, 2,3-dimercaptopropane-1-sulfonic acid, Na salt (DMPS, DIMAVAL) would increase the urinary excretion of arsenic, alter the urinary profile of arsenic species and thus result in a better indication of the body load of arsenic and a better biomarker for arsenic exposure. The method used to evaluate these subjects was to give them 300 mg DMPS by mouth, after an overnight fast, and collect urine at specified time periods. The urine samples were analyzed for inorganic arsenic, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and total arsenic by hydride generation and atomic absorption spectrophotometry. The results indicated that: 1) During the 2-hr period after DMPS administration, MMA represented 42%, inorganic As, 20 to 22% and DMA, 37 to 38% of the total urinary arsenic. The usual range of the MMA percentage in human urine has been 10 to 20%. The % MMA increased almost equally for both the arsenic-exposed and control subjects. 2) The exposed subjects had a greater urinary excretion of total arsenic, before and after DMPS administration, than the control subjects. 3) Although buccal cells were obtained only from a few subjects, the prevalence of mononucleated buccal cells, an indication of genotoxicity, was 5-fold greater for those who consumed drinking water with the higher arsenic content than among control subjects. Our conclusions are that 1) DMPS has a highly specific effect in humans on MMA metabolism and/or urinary excretion; 2) the human body stores substantial amounts of arsenic; and 3) the urinary arsenic concentration after DMPS administration may be more indicative of the body burden of arsenic because it was greater than that found before DMPS was given.

Adult↗
PubMed1996

Insufficient stocking of poisoning antidotes in hospital pharmacies.

OBJECTIVE: To determine whether antidotes for poisoning and overdose are available in hospitals that provide emergency department care. DESIGN: Written survey of hospital pharmacy directors, each of whom reported the amount currently in stock of 8 different antidotes: antivenin (Crotalidae) polyvalent, cyanide kit, deferoxamine mesylate, digoxin immune Fab, ethanol, naloxone hydrochloride, pralidoxime chloride, and pyridoxine hydrochloride. PARTICIPANTS: Pharmacy directors of all hospitals with emergency departments in Colorado, Montana, and Nevada. MAIN OUTCOME MEASURES: Proportions of hospitals with insufficient stocking of each antidote, defined as complete lack of the antidote or an amount inadequate to initiate treatment of 1 seriously poisoned 70-kg patient. RESULTS: Questionnaires were mailed to 137 hospital pharmacy directors and 108 (79%) responded. Only 1 (0.9%) of the 108 hospitals stocked all 8 antidotes in adequate amounts. The rate of insufficient stocking for individual antidotes ranged from 2% (for naloxone) to 98% (for digoxin immune Fab). In a multiple regression analysis, smaller hospital size and lack of a formal review of antidote stocking were independent predictors of the number of antidotes stocked insufficiently. CONCLUSIONS: Insufficient stocking of antidotes is a widespread problem in Colorado, Montana, and Nevada. Although these states are served by a certified regional poison center, potentially lifesaving antidotes are frequently not available when and where they might be needed to treat a single poisoned patient.

Analysis of Variance↗
PubMed1996

The clinical spectrum of Jin Bu Huan toxicity.

Herbal medications and other nontraditional medical therapies are becoming increasingly popular in the United States. We describe three children and three adults in whom severe toxic effects developed after ingestion of a Chinese herbal medication, jin bu huan, which is sold as Jin Bu Huan Anodyne Tablets. Jin bu huan produced distinct clinical syndromes after acute ingestion in children and long-term use in adults. A single, acute ingestion in children rapidly produced life-threatening neurologic and cardiovascular manifestations, while long-term jin bu huan use in adults was associated with hepatitis. Jin bu huan contains levo-tetrahydropalmatine, a potent neuroactive substance. The constituents of jin bu huan are misidentified on the package, resulting in significant delay in identifying the plant alkaloid responsible for its toxicity. Although perceived as innocuous, jin bu huan may produce major health effects. The highly concentrated formulation, the lack of childproof packaging, and the product insert listing indications for the treatment of serious medical conditions may all contribute to the development of toxic reactions.

Aged↗
PubMed1996

Clinical ergotism with lingual ischemia induced by clarithromycin-ergotamine interaction.

The macrolide class of antibiotics, including erythromycin and troleandomycin, is associated with clinically significant adverse drug interactions. This results from macrolide inhibition of cytochrome P-450 metabolism of numerous xenobiotics, resulting in elevated serum drug levels and clinical intoxication. Animal studies, however, suggest that clarithromycin, the newest approved macrolide antibiotic, has has less potential for adverse drug reactions. We describe a patient who, on her fifth day of clarithromycin therapy, developed clinical ergotism (i.e., hypertension, lingual ischemia, and peripheral cyanosis) several hours after administration of her usual 2-mg dose of ergotamine tartrate. To our knowledge, this is the first report of clinical ergotism precipitated by clarithromycin-ergotamine interaction and suggests that, like other macrolide antibiotics, ergot preparations should be avoided in patients who are taking clarithromycin.

Clarithromycin↗
PubMed1996

Ovine desipramine antibody fragments reverse desipramine cardiovascular toxicity in the rat.

STUDY OBJECTIVE: To develop a model of severe desipramine cardiovascular toxicity and to determine whether partial neutralization of the antigen by desipramine-specific Fab antibody fragments ameliorates its cardiovascular effects. METHODS: We administered desipramine to rats until the QRS interval tripled in duration and mean arterial pressure (MAP) was less than 100 mm Hg. Animals were then assigned to one of six groups: (1) no treatment, (2) normal saline solution control treatment (.9% NaCl infusion equal to the volume of Fab infusion), (3) nonimmune Fab control treatment (infusion of Fab equal to that in the 9.6% neutralization treatment), (4) 9.6% desipramine Fab (infusion of ovine desipramine Fab equal to 9.6% of an equimolar neutralization), (5) 19.2% desipramine Fab, and (6) 30.0% desipramine Fab. RESULTS: QRS-interval duration, heart rate, and MAP were recorded for 60 minutes. Animals in groups 1 through 3 demonstrated slow and incomplete improvement. Animals in groups 4 through 6 showed improvement in QRS-interval duration and heart rate within 4 minutes (P<.05) compared with untreated animals. A dose-response relationship was evident; animals given the highest dose of desipramine-specific Fab showed the greatest improvement. CONCLUSION: Partial neutralization of desipramine by specific Fab fragments produces rapid improvement of QRS-interval duration and heart rate in a rat model of severe desipramine toxicity.

Animals↗
PubMed1996

Validation of a severity score for the assessment of crotalid snakebite.

STUDY OBJECTIVE: No research tool exists for the clinical evaluation of crotalid snakebite. We sought to determine the correlation of the snakebite severity score (SSS) with the clinical assessment of physicians experienced in the management of crotalid snakebite. METHODS: We retrospectively used the SSS to quantify the severity of envenomation in 108 patients with crotalid snakebite. Two physicians experienced in the management of venomous snakebite independently and blindly assessed the severity of envenomation as detailed in medical records with the use of accepted clinical criteria. The correlation of the SSS and the physicians' consensus was determined with pointbiserial correlation. RESULTS: The SSS correlated well with the physicians' consensus at presentation (r=+.63, z score=6.52, P<.000001) and at the point at which the patient's condition was worst (r=+.70, z score=7.24, P<.000001). The SSS also correlated highly with the physicians' assessment of change in the patient's condition (r=+.51, z score=6.10, P<.000001). With the physicians' consensus as the gold standard, the sensitivity of a change in the SSS of 1 point in detecting clinically significant worsening of the envenomation syndrome was .97; specificity was .81. CONCLUSION: The SSS correlated well with the clinical condition of patients bitten by crotalid snakes as represented by the medical record. It provides a more objective instrument for the evaluation of severity and progression of envenomation in patients with crotalid snakebite.

Animals↗
PubMed1996

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.

Emergency Medicine↗
PubMed1996

Sodium 2,3-dimercaptopropane-1-sulfonate challenge test for mercury in humans. III. Urinary mercury after exposure to mercurous chloride.

The sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (Dimaval; DMPS) challenge test has been given previously to humans exposed to elemental mercury (vapor) or mercuric salts, but not mercurous salts. The test (300 mg p.o., after an 11-hr fast) was given to 11 factory workers who make a skin lotion that contains mercurous chloride, eight users of the skin lotion and nine controls. Urines were analyzed for total mercury by using cold vapor atomic absorption spectrophotometry. The mercury excreted for 6 hr before and 6 hr after DMPS treatment was 113 micrograms +/- 26 and 5037 micrograms +/- 682 S.E.M. for the skin lotion makers; 16.2 micrograms +/- 3.4 and 1410 micrograms +/- 346 S.E.M. for the skin lotions users; and 0.49 micrograms +/- 0.11 and 18.4 micrograms +/- 7.1 S.E.M. for the controls, respectively. The increases in urinary mercury resulting from the DMPS challenge test were 45-, 87- and 38-fold, respectively. The results demonstrate that, in humans exposed to mercurous chloride, DMPS increases the urinary excretion of mercury and that the DMPS/mercury challenge test is of value for a more realistic estimation of mobilizable mercury. An attempt to associate genotoxicity, as indicated by micronuclei content in buccal cells, with mercury exposure was inconclusive, perhaps because of the small number of subjects.

Adult↗
PubMed1995

Mobilization of heavy metals by newer, therapeutically useful chelating agents.

Four chelating agents that have been used most commonly for the treatment of humans intoxicated with lead, mercury, arsenic or other heavy metals and metalloids are reviewed as to their advantages, disadvantages, metabolism and specificity. Of these, CaNa2EDTA and dimercaprol (British anti-lewisite, BAL) are becoming outmoded and can be expected to be replaced by meso-2,3-dimercaptosuccinic acid (DMSA, succimer) for treatment of lead intoxication and by the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS, Dimaval) for treating lead, mercury or arsenic intoxication. Meso-2,3-DMSA and DMPS are biotransformed differently in humans. More than 90% of the DMSA excreted in the urine is found in the form of a mixed disulfide in which each of the sulfur atoms of DMSA is in disulfide linkage with an L-cysteine molecule. After DMPS administration, however, acyclic and cyclic disulfides of DMPS are found in the urine. The Dimaval-mercury challenge test holds great promise as a diagnostic test for mercury exposure, especially for low level mercurialism. Urinary mercury after Dimaval challenge may be a better biomarker of low level mercurialism than unchallenged urinary mercury excretion.

Animals↗
PubMed1995

Sodium 2,3-dimercaptopropane-1-sulfonate challenge test for mercury in humans: II. Urinary mercury, porphyrins and neurobehavioral changes of dental workers in Monterrey, Mexico.

The sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS) challenge test (300 mg p.o. after an 11-hr fast) was given in Monterrey, Mexico to dental and nondental personnel. Urine samples were collected and analyzed for total mercury. The mean mercury urinary excretion (+/- S.E.) for 6 hr before and 6 hr after DMPS administration for 10 dental technicians, who formulate amalgam, was 4.84 micrograms +/- 0.742 and 424.0 micrograms +/- 84.9; for 5 dentists, who use amalgam in their practice, 3.28 micrograms +/- 1.11 and 162.0 micrograms +/- 51.2; and for 13 nondental personnel, 0.783 microgram +/- 0.189 and 27.3 micrograms +/- 3.19. The urinary coproporphyrin levels before DMPS administration, which are indicative of renal mercury content, were quantitatively associated with the urinary mercury levels among the three study groups after DMPS administration. This was not so if the urinary mercury level before DMPS administration was compared with the urinary coproporphyrin concentration. The urinary mercury level after DMPS administration is a better indicator of exposure and renal mercury burden than is the mercury level measured in the urine before DMPS is given. Regression analysis showed that the coefficient of urinary mercury was statistically and adversely associated with complex attention (switching task), the perceptual motor task (symbol-digit substitution), symptoms and mood. The easily performed DMPS-mercury challenge test is useful for monitoring dental personnel for mercury vapor exposure.

Adult↗
PubMed1994

Pharmacokinetics of meso-2,3-dimercaptosuccinic acid in patients with lead poisoning and in healthy adults.

We compared the pharmacokinetics of meso-2,3-dimercaptosuccinic acid (DMSA) in three children with lead poisoning, three adults with lead poisoning, and five healthy adult volunteers. All subjects received DMSA orally. Maximum blood concentration and time to maximum blood concentration of total DMSA concentration were not statistically different among the groups. Unaltered DMSA was detected in the blood of all poisoned patients but in only one of five healthy volunteers. Elimination half-life of total DMSA (parent drug plus oxidized metabolites) was longer in children with lead poisoning (3.0 +/- 0.2 hours) than in adults with lead poisoning (1.9 +/- 0.4 hours) and healthy adults (2.0 +/- 0.2 hours). Renal clearance of total DMSA was greater in healthy adults (77.0 +/- 13.2 ml/min per square meter) than in either adults (24.7 +/- 3.3 ml/min per square meter) or children with lead poisoning (16.6 ml/min per square meter); renal clearance of the metabolites of DMSA was also greater in healthy adults (64.6 +/- 10.1 ml/min per square meter) than in either adults (35.4 +/- 8.4 ml/min per square meter) or children with lead poisoning (19.5 ml/min per square meter). The DMSA appeared to enter the erythrocytes of patients with lead poisoning to a greater extent than in healthy adults. We conclude that renal clearance of DMSA and its metabolites may be impaired and that the distribution of DMSA in children with lead poisoning may be different from that in adults.

Adult↗
PubMed1994

Determination and metabolism of dithiol chelating agents. XVI: Pharmacokinetics of 2,3-dimercapto-1-propanesulfonate after intravenous administration to human volunteers.

The pharmacokinetics of 2,3-dimercaptopropane-1-sulfonate (DMPS), an effective chelating agent for mercury, were determined in five healthy adults after i.v. administration of 3.0 mg/kg of DMPS. DMPS is rapidly transformed to disulfide forms; 15 min after administration, only 12% of the total DMPS detected in blood was present as the parent drug. DMPS and its metabolites were eliminated primarily by the kidneys. By 96 hr after administration, 12% of the total DMPS found in the urine was excreted as the parent drug (10% of the administered dose) and 88% was excreted as disulfide metabolites (74% of the administered dose). The disposition of parent drug was described by a biexponential equation with an elimination half-life of 1.8 hr. By contrast, the elimination half-life of total DMPS was 20 hr. The oral bioavailability of the parent drug was found in a separate study to be 39%. Mercury excretion in healthy volunteers correlated well with the urinary excretion of both the parent drug (r2 = .94) and the disulfide metabolites (r2 = .96).

Adult↗