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Biomedical subjects

K M Hurlbut

Publications and source records attributed to K M Hurlbut.

14 recordsLinked to original sources
PubMed1998

Intravenous administration of oral N-acetylcysteine.

OBJECTIVE: To report the indications and adverse events associated with administration of the oral N-acetylcysteine preparation by the intravenous route. DESIGN: Retrospective consecutive case series analysis of 226,720 Toxic Exposure Surveillance System data sheets from a certified regional poison center during the period January 1, 1992 through December 31, 1993. SETTING: A regional poison center certified by the American Association of Poison Control Centers. PATIENTS: Seventy-six patients treated with the oral N-acetylcysteine solution by the intravenous route. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We report the indications and adverse events associated with the intravenous administration of the oral N-acetylcysteine preparation. Four (4/76, 5.3%) patients developed adverse events attributable to N-acetylcysteine. None of these events involved hemodynamic, cardiovascular, or pulmonary effects. All reactions occurred during infusion of the initial N-acetylcysteine dose. There were three (3/76, 3.9%) deaths overall; however, they were not attributable to the intravenous administration of the oral N-acetylcysteine preparation. CONCLUSIONS: Intravenous administration of the oral N-acetylcysteine preparation appears to have limited adverse effects and offers another mechanism of delivery of the potentially lifesaving N-acetylcysteine when oral administration is not possible.

Acetaminophen↗
PubMed1998

DMPS (2,3-dimercaptopropane-1-sulfonate, dimaval) decreases the body burden of mercury in humans exposed to mercurous chloride.

DMPS (2,3-dimercaptopropane-1-sulfonate, Na salt), when used as a challenge test for mercury in workers involved in the production of a calomel skin-bleaching lotion and in direct contact with mercurous chloride, elevated urine levels of mercury. A DMPS treatment regimen was devised and initiated. Three days after the challenge test, DMPS was administered p.o. (400 mg per day) for 8 days, followed by a no-treatment period of five days. A new cycle of DMPS treatment for 7 days was initiated and followed by 5 days without treatment. A third period of treatment was begun for 6 days, followed by a 5-day no-treatment period. The urinary mercury greatly increased during those periods when DMPS was administered (1754, 314, and 173 microgram/24 h for the periods 1, 2 and 3, compared with 106, 48 and 53 microgram/24 h on the corresponding no-treatment periods). One of the workers presented signs of drug intolerance and was discharged after receiving the first cycle of treatment. DMPS treatment was effective in lowering the body burden of mercury and in decreasing the urinary mercury concentration to normal levels.

Adult↗
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

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

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

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↗
PubMed1992

Urinary mercury after administration of 2,3-dimercaptopropane-1-sulfonic acid: correlation with dental amalgam score.

There is considerable controversy as to whether dental amalgams may cause systemic health effects in humans because they liberate elemental mercury. Most such amalgams contain as much as 50% metallic mercury. To determine the influence of dental amalgams on the mercury body burden of humans, we have given volunteers, with and without amalgams in their mouth, the sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS), a chelating agent safely used in the Soviet Union and West Germany for a number of years. The diameters of dental amalgams of the subjects were determined to obtain the amalgam score. Administration of 300 mg DMPS by mouth increased the mean urinary mercury excretion of the amalgam group from 0.70 to 17.2 micrograms and that of the nonamalgam group from 0.27 to 5.1 micrograms over a 9-h period. Two-thirds of the mercury excreted in the urine of those with dental amalgams appears to be derived originally from the mercury vapor released from their amalgams. Linear regression analysis indicated a highly significant positive correlation between the mercury excreted in the urine 2 h after DMPS administration and the dental amalgam scores. DMPS can be used to increase the urinary excretion of mercury and thus increase the significance and reliability of this measure of mercury exposure or burden, especially in cases of micromercurialism.

Adolescent↗
PubMed1992

Human studies with the chelating agents, DMPS and DMSA.

Meso-2,3-dimercaptosuccinic acid (DMSA) is bound to plasma albumin in humans and appears to be excreted in the urine as the DMSA-cysteine mixed disulfide. The pharmacokinetics of DMSA have been determined after its administration to humans po. For the blood, the tmax and t1/2 were 3.0 h + 0.45 SE and 3.2 h + 0.56 SE, respectively. The Cmax was 26.2 microM + 4.7 SE. To determine whether dental amalgams influence the human body burden of mercury, we gave volunteers the sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS). The diameters of dental amalgams of the subjects were determined to obtain the amalgam score. Administration of 300 mg DMPS by mouth increased the mean urinary mercury excretion of subjects over a 9 h period. There was a positive correlation between the amount of mercury excreted and the amalgam score. DMPS might be useful for increasing the urinary excretion of mercury and thus increasing the significance and reliability of this measure of mercury exposure. DMSA analogs have been designed and synthesized in attempts to increase the uptake by cell membranes of the DMSA prototype chelating agents. The i.v. administration of the monomethyl ester of DMSA, the dimethyl ester of DMSA or the zinc chelate of dimethyl DMSA increases the biliary excretion of platinum and cadmium in rats.

Adult↗
PubMed1991

Drug-induced psychoses.

Major causes of drug-induced psychoses include cocaine, amphetamines, phencyclidine, cannabinoids, LSD, mescaline, the so-called designer drugs, anticholinergic compounds, and steroids. Most drug-induced psychoses are managed with general supportive measures, reassurance, minimizing patient stimulation, and benzodiazepines as needed; however, specific antidotes such as physostigmine for anticholinergic poisoning or urinary acidification to enhance excretion of amphetamines or phencyclidine may be indicated in some patients. Any patient with a drug-induced psychosis must be evaluated carefully for evidence of other toxic effects of the drug in question.

Designer Drugs↗