Search PubMed⌕ Search

Biomedical subjects

R C Dart

Publications and source records attributed to R C Dart.

At least 19 recordsLinked to original sources
PubMed2003

Rethinking the toxic methanol level.

INTRODUCTION: Treatment thresholds for methanol poisoning are based on case reports and published opinion. Most guidelines recommend treatment for a methanol level > or = 20 mg/dL in a nonacidotic patient. No supportive data have been offered nor has the time of the exposure been addressed. For instance, no distinction has been drawn between a methanol level drawn 1 hr vs. 24 hr from ingestion. We analyzed all published cases of methanol poisoning to determine the applicability of the 20 mg/dL threshold in a nonacidotic patient, specifically those arriving early for care (within 6 hr) with a peak or near-peak blood methanol concentration. METHODS: Using predefined search criteria, a systematic review of the world literature was performed using MEDLINE and EMBASE. In addition, each article's references were hand searched for pre-1966 articles, as were fatality abstracts from all U.S. poison centers. Human cases were included if they reported a known time of a single methanol exposure, acid-base data, blood methanol, and blood ethanol (if not acidotic). RESULTS: Dating to 1879, 372 articles in 18 languages were abstracted using a standard format; 329 articles (2433 patients) involved methanol poisoning, and 70 articles (173 patients) met inclusion criteria. Only 22 of these patients presented for care within 6hr of ingestion with an early methanol level. All but 1 patient was treated with an inhibitor of alcohol dehydrogenase (ADH). A clear acidosis developed only with a methanol level > or = 126 mg/dL. The patient that did not receive an ADH inhibitor was an infant with an elevated early methanol level (46 mg/dL) that was given folate alone and never became acidotic. Intra and inter-rater reliability were 0.95. CONCLUSIONS: Nearly all reports of methanol poisoning involve acidotic patients far removed from ingestion. The small amount of data regarding patients arriving early show that 126 mg/dL is the lowest early blood methanol level ever clearly associated with acidosis. Contrary to conventional teaching, there are case reports of acidosis after only a few hours of ingestion. The data are insufficient to apply 20 mg/dL as a treatment threshold in a nonacidotic patient arriving early for care. Prospective studies are necessary to determine if such patients may be managed without antidotal therapy or dialysis.

Acidosis↗
PubMed2001

Effect of maximal daily doses of acetaminophen on the liver of alcoholic patients: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Retrospective reports suggest that therapeutic doses of acetaminophen may be associated with fulminant hepatic failure and death in alcoholic patients. Millions of patients use acetaminophen; the prevalence of alcoholism in the United States is 5% to 10%. OBJECTIVE: To determine if hepatic injury was associated with maximal therapeutic dosing of acetaminophen to chronic alcohol abuse patients immediately following cessation of alcohol intake (the presumed time of maximal vulnerability). METHODS: Patients entering an alcohol detoxification center were enrolled in a randomized, double-blind, placebo-controlled trial. Exclusion criteria were baseline values of aspartate or alanine aminotransferase greater than 120 U/L, international normalized ratio greater than 1.5, serum acetaminophen level greater than 20 mg/L, or a history of ingesting more than 4 g/d of acetaminophen. Acetaminophen, 1000 mg, or placebo was administered orally 4 times daily for 2 consecutive days and liver test results were monitored for 2 more days. Acetaminophen was not administered until the alcohol had been eliminated. RESULTS: There were 102 patients in the acetaminophen-treated group and 99 patients in the placebo-treated (control) group. Demographic data, alcohol history, and baseline blood test results were similar in both groups. The mean (SD) aspartate aminotransferase level on day 4 was 38.0 +/- 26.7 U/L in the acetaminophen-treated group and 37.5 +/- 27.6 U/L in the placebo-treated group. There were 4 patients in the acetaminophen-treated group and 5 in the placebo-treated group who developed an increase in their serum aspartate aminotransferase level to greater than 120 U/L; it did not exceed 200 U/L in any patient. The mean (SD) international normalized ratio on day 4 was 0.96 +/- 0.09 in the acetaminophen-treated group and 0.98 +/- 0.11 in the placebo-treated group. CONCLUSION: Repeated administration of the maximum recommended daily doses of acetaminophen to long-term alcoholic patients was not associated with evidence of liver injury.

Acetaminophen↗
PubMed2001

A randomized multicenter trial of crotalinae polyvalent immune Fab (ovine) antivenom for the treatment for crotaline snakebite in the United States.

BACKGROUND: Current therapy for crotaline snakebite includes antivenin (Crotalidae) polyvalent, an antivenom with numerous adverse effects. We compared the efficacy and safety of 2 dosing regimens with a new antivenom, Crotalinae polyvalent immune Fab (Fab AV). METHODS: A single dose of Fab AV alone (as-needed [PRN] group) was compared with an initial dose plus repeated treatments during 18 hours (scheduled group) in a multicenter randomized trial. The study included patients with minimal or moderate envenomation by a crotaline snake within the preceding 6 hours, aged 10 years or older, in whom worsening of the envenomation syndrome was observed before Fab AV treatment. After treatment with Fab AV to achieve initial control, patients were randomized to the scheduled or PRN treatment group. Scheduled group patients received additional doses of Fab AV every 6 hours for 3 doses. The PRN group received no planned additional doses of antivenom. RESULTS: The mean severity score of the 31 patients decreased from 4.35 to 2.39 points (P<.001); there was no difference between scheduled and PRN groups. No patient in the scheduled group received unplanned Fab AV doses, but 8 of 16 patients in the PRN group received unplanned doses (P =.002). Acute reactions occurred in 6 patients (19%), and serum sickness occurred in 6 (23%) of 26 patients who returned for follow-up. CONCLUSIONS: In the first randomized trial of antivenom in the United States, Fab AV effectively terminated venom effects. Since the unplanned use of Fab AV in the PRN group was common, the treatment regimen may require more than 1 initial dose.

Adolescent↗
PubMed2001

Time to reconstitution: purified Fab antivenom vs. unpurified IgG antivenom.

We conducted prospective, randomized analytical and observational trials to assess reconstitution times of two lyophilized crotaline snake antivenoms, Antivenin (Crotalidae) Polyvalent [Wyeth-Ayerst] (ACP) and affinity-purified, mixed monospecific crotalid antivenom ovine Fab (CroTAb) (Fab antivenom). The analytical experiment indicated Fab antivenom and ACP reached their maximum protein concentration at 25 and 45min, respectively. In the observational experiment, Fab antivenom (median 40min) had a shorter reconstitution time than ACP (>90min, p<0.008).

Antivenins↗
PubMed2001

Efficacy, safety, and use of snake antivenoms in the United States.

The mainstay of hospital treatment for venomous snakebite is antivenom. There is currently only one antivenom available in the United States for the treatment of pit viper envenomation, Antivenin (Crotalidae) Polyvalent (ACP). The general indication for the administration of antivenom is presence of progressive venom injury. Progressive injury is defined as worsening local injury (eg, swelling, ecchymosis), a clinically important coagulation abnormality, or systemic effects (eg, hypotension, altered mental status). Unfortunately, there are no prospective data available regarding the efficacy of ACP. The efficacy of a new antivenom (CroFab; FabAV) composed of purified Fab specific to indigenous snake species has been demonstrated in prospective trials. FabAV appears as effective as IgG antivenoms. However, Fab molecules have a shorter half-life than IgG molecules and may allow recurrence of venom effects, if additional doses are not administered. It has also been found that other antivenoms, including ACP, also allow recurrence of venom effects. The Fab preparation has produced fewer acute or delayed (serum sickness) allergic reactions; however, further experience is needed to confirm this observation. Evaluation of this new antivenom has led to advances in our understanding of antivenoms in terms of solubility and durability. Fab fragments enter solution quickly, thereby shortening the time to antivenom administration and are remarkably stable under extreme conditions of heat and handling.

Animals↗
PubMed2001

Neutralization of Latrodectus mactans and L. hesperus venom by redback spider (L. hasseltii) antivenom.

OBJECTIVE: To test the effectiveness of L. hasseltii (redback spider) antivenom in neutralizing the lethal effects of L. hesperus and L. mactans (North American black widow) venoms. METHODS: LD50 values for the L. hesperus and L. mactans venom preparations were determined. A prospective, randomized, double-blind antivenom efficacy experiment was then performed for each venom using a mouse envenomation model. The following treatments were premixed and incubated at 25 degrees C for 1 hour prior to intraperitoneal injection: 1) saline control + protein control, 2) saline control + L. hasseltii antivenom, 3) L. hesperus or L. mactans venom + protein control, and 4) L. hesperus or L. mactans venom + L. hasseltii antivenom. The study endpoints were time elapsed until death and survival at 24 hours. RESULTS: The mouse LD50 values for L. hesperus and L. mactans venoms were 0.64 mg/kg and 0.26 mg/kg, respectively. In the efficacy trial, all mice in group 3 (L. hesperus or L. mactans venom and protein control) died. In both experiments, all mice in group 4 (L. hesperus or L. mactans venom + antivenom) survived (p < 0.0001). CONCLUSION: This is the first study to derive mouse LD50 values for L. hesperus and L. mactans venom obtained by electrical stimulation of live adult spiders. Redback spider antivenom is effective in neutralizing the lethal effects of L. hesperus and L. mactans venoms in a mouse envenomation model. While this study is limited by the optimized premixing of antigen with antibody, it generates the hypothesis that redback antivenom would be effective in the treatment of latrodectism in humans caused by the two clinically relevant species of North American widow spiders.

Animals↗
PubMed2001

Calcium neutralizes fluoride bioavailability in a lethal model of fluoride poisoning.

OBJECTIVES: Acute systemic fluoride poisoning can result in systemic hypocalcemia, cardiac dysrhythmias, and cardiovascular collapse. Topical and intraarterial therapy with calcium or magnesium salts reduces dermal injury from fluoride burns. The mechanism of these therapies is to bind and inactivate the fluoride ion. The purpose of this study is to evaluate the effect of calcium and magnesium to decrease the bioavailability of fluoride in a lethal model of fluoride poisoning. METHODS: In preliminary studies, we determined that fluoride 3.6 mM/kg intraperitoneally in the form of sodium fluoride was uniformly and rapidly fatal in a mouse model. Using this fluoride dose, we performed a controlled, randomized, blinded study of low- and high-dose calcium chloride (1.8 and 3.6 mM/kg intraperitoneally, respectively) and magnesium sulfate (3.6 mM/kg intraperitoneally) to decrease the bioavailability of the fluoride ion. After injection with sodium fluoride, animals were immediately treated with injections of sodium chloride (control), calcium chloride (low- or high-dose), or magnesium sulfate. The major outcome was 6-hour survival using a Cox Proportional Hazard model. RESULTS: All untreated animals died within 60 minutes. Using a Cox Proportional Hazard model, each 1.8 mM/kg dose of calcium chloride administered reduced the risk of death by 33%. Magnesium sulfate treatment was not associated with a hazard reduction. CONCLUSION: Calcium chloride administered simultaneously with sodium fluoride reduces the bioavailability of fluoride poisoning in a mouse model. The equivalent dose of magnesium sulfate does not significantly decrease fluoride bioavailability.

Animals↗
PubMed2001

Attenuation of verapamil-induced myocardial toxicity in an ex-vivo rat model using a verapamil-specific ovine immunoglobin.

OBJECTIVE: To determine whether an ovine verapamil-specific immunoglobin G (V-IgG) attenuates verapamil toxicity in an ex-vivo rat left ventricular papillary muscle model. METHODS: The authors dissected left ventricular papillary muscle strips from male Sprague-Dawley rats (350-410 g) and suspended them in an oxygen-perfused Tyrode buffer bath at 37.5 degrees C. Muscle strips equilibrated for 90 minutes under electrical stimulation of 1 Hz. Resting and developed tension (mg) were monitored continuously. A concentration-response trial was performed with verapamil concentrations ranging from 31 to 1,020 nM; 510 nM produced consistent reduction in developed tension. A trial of V-IgG was then conducted by administering the following treatments to papillary muscle strips in a randomized manner: V-IgG + 510 nM verapamil, nonspecific ovine IgG (N-IgG) + 510 nM verapamil (protein control), and 510 nM verapamil alone. Immunoglobin G was administered in equimolar concentrations to verapamil. Attenuation was expressed as inhibition of the verapamil-induced reduction of developed tension. RESULTS: The V-IgG comparative trial indicated the V-IgG + verapamil treatment had a mean reduction in developed tension of 14.1% (SD +/- 12.2) compared with 36.2% (SD +/- 14.9) for N-IgG + verapamil and 34.9% (SD +/- 8.1) for verapamil alone (p < 0.05). There was no difference between the two control groups. CONCLUSION: Verapamil-specific IgG attenuated verapamil-induced reduction of developed tension in an ex-vivo rat model.

Animals↗
PubMed2001

Tricyclic antidepressants directly depress human myocardial mechanical function independent of effects on the conduction system.

OBJECTIVES: To measure the effect of tricyclic antidepressant drugs (TCAs) on human myocardial contractility. METHODS: Human atrial tissue was obtained during cardiac bypass surgery. The tissue was harvested, suspended in a Tyrode buffer at 37 degrees C, and perfused with a 95%/5% oxygen-carbon dioxide mixture. Developed force was continuously measured using a force transducer and recorded by computer. After an equilibration period, escalating doses of amitriptyline or desipramine were added to the bath. All strips were exposed to the following five concentrations of each drug: 0 (control) 0.4, 4, 40, and 400 microM. The results for each experiment were expressed as the difference between the developed force measured prior to the addition of each concentration of drug and the developed force measured after a 30-minute exposure to the drug. RESULTS: Desipramine decreased the developed force by 27%, 49%, and 74% at concentrations of 0.4, 40, and 400 microM, respectively. Amitriptyline decreased the developed force by 38% at the 40-microM concentration and by 89% at the 400-microM concentration. Untreated strips retained 94% of baseline developed force at 150 minutes. CONCLUSIONS: Tricyclic antidepressants depress human myocardial function in a dose-dependent fashion independent of the effects on the cardiac conduction system. While previous work has demonstrated the effect of therapies for the reversal of impaired cardiac conduction following TCA poisoning, to the best of the authors' knowledge, no reports have documented the effects of therapy on direct myocardial depression. Additional therapies targeted at reversing the direct cardiodepressive effects of TCA may improve outcome following TCA poisoning.

Amitriptyline↗
PubMed2001

Acute myocardial infarction associated with amphetamine use.

Myocardial infarction is a rarely reported complication of amphetamine use. We report the case of a healthy 31-year-old man who presented to our emergency department with no clinical evidence of an acute coronary event after intravenous injection of amphetamines. However, he subsequently experienced a non-Q-wave anterior wall myocardial infarction associated with the use of amphetamines.

Adult↗
PubMed2001

Acetaminophen use in patients who drink alcohol: current study evidence.

Package labeling for all over-the-counter pain relievers and fever reducers warns patients who drink 3 or more alcoholic beverages daily to consult with a physician before using these products. In the absence of accurate, consistent data, physicians have relied on retrospective and anecdotal evidence, which has perhaps led to greater restrictions on acetaminophen use than necessary for patients who consume alcohol. Recently, a well-controlled clinical study was conducted to more rigorously characterize the risk to alcohol users taking acetaminophen. In this randomized, double-blind, placebo-controlled trial, patients enrolled in a drug detoxification facility received 1000 mg acetaminophen or placebo 4 times daily for 2 consecutive days immediately after discontinuing alcohol use. Serum aspartate aminotransferase and alanine aminotransferase levels, used to detect hepatic necrosis or liver disease, were monitored at baseline and again both during and after the study. Results for 201 patients completing the study showed no statistically significant difference in liver function tests for 102 patients receiving acetaminophen compared with 99 patients receiving placebo. Researchers concluded that there was no increase in liver toxicity among alcoholic patients given the maximal therapeutic dose (4 g/day) of acetaminophen and no clinical evidence of increased risk for these patients when acetaminophen is used within recommended doses.

Acetaminophen↗
PubMed2001

The use and effect of analgesics in patients who regularly drink alcohol.

Analgesic consumption poses special risks for regular users of alcohol. Among the numerous adverse health effects are acetaminophen toxicity and gastrointestinal (GI) bleeding associated with nonsteroidal anti-inflammatory drug (NSAID) use. An alcohol-acetaminophen hypothesis contends that alcohol enhances acetaminophen toxicity. Because 22% of adults use acetaminophen each week and 5% to 10% of the population is alcoholic, the healthcare implications of serious adverse interactions are considerable. However, such interactions are rare when NSAID doses remain in the therapeutic range. Although clinical studies fail to support anecdotal case reports of liver damage associated with consumption of therapeutic doses of acetaminophen by alcohol users, such reports are probably inaccurate because of the uncritical acceptance of patient history by the clinician and a lack of well-designed prospective trials. Over-the-counter (OTC) NSAIDs, such as aspirin, naproxen, and ketoprofen, are other analgesic options, but each carries the risk of GI bleeding. Unanswered questions about the newer "second-generation" NSAIDs, such as celecoxib and rofecoxib, make them less desirable than acetaminophen and OTC NSAIDs. Because the risk of GI bleeding or ulceration may be higher in alcoholic patients, the optimal strategy in prescribing pain relievers to those who consume alcohol is to use 1 drug at a time and to clearly communicate its generic name. Acetaminophen is the safest OTC analgesic and is recommended as first-line treatment for osteoarthritis. OTC NSAID users should be carefully advised as to recommended dose, and all patients should be reminded to stay within the dosing limits regardless which OTC analgesic is used.

Acetaminophen↗
PubMed2000

DMPS-arsenic challenge test. II. Modulation of arsenic species, including monomethylarsonous acid (MMA(III)), excreted in human urine.

The administration of sodium 2,3-dimercapto-1-propane sulfonate (DMPS) to humans chronically exposed to inorganic arsenic in their drinking water resulted in the increased urinary excretion of arsenic, the appearance and identification of monomethylarsonous acid (MMA(III)) in their urine, and a large decrease in the concentration and percentage of urinary dimethylarsinic acid (DMA). This is the first time that MMA(III) has been detected in the urine. In vitro biochemical experiments were then designed and performed to understand the urinary appearance of MMA(III) and decrease of DMA. The DMPS-MMA(III) complex was not active as a substrate for the MMA(III) methyltransferase. The experimental results support the hypothesis that DMPS competes with endogenous ligands for MMA(III), forming a DMPS-MMA complex that is readily excreted in the urine and points out the need for studying the biochemical toxicology of MMA(III). It should be emphasized that MMA(III) was excreted in the urine only after DMPS administration. The results of these studies raise many questions about the potential central role of MMA(III) in the toxicity of inorganic arsenic and to the potential involvement of MMA(III) in the little-understood etiology of hyperkeratosis, hyperpigmentation, and cancer that can result from chronic inorganic arsenic exposure.

Adult↗
PubMed2000

Occurrence of monomethylarsonous acid in urine of humans exposed to inorganic arsenic.

Monomethylarsonous acid (MMA(III)) has been detected for the first time in the urine of some humans exposed to inorganic arsenic in their drinking water. Our experiments have dealt with subjects in Romania who have been exposed to 2.8, 29, 84, or 161 microg of As/L in their drinking water. In the latter two groups, MMA(III) was 11 and 7% of the urinary arsenic while the monomethylarsonic acid (MMA(V)) was 14 and 13%, respectively. Of our 58 subjects, 17% had MMA(III) in their urine. MMA(III) was not found in urine of any members of the group with the lowest level of As exposure. If the lowest-level As exposure group is excluded, 23% of our subjects had MMA(III) in their urine. Our results indicate that (a) future studies concerning urinary arsenic profiles of arsenic-exposed humans must determine MMA(III) concentrations, (b) previous studies of urinary profiles dealing with humans exposed to arsenic need to be re-examined and re-evaluated, and (c) since MMA(III) is more toxic than inorganic arsenite, a re-examination is needed of the two hypotheses which hold that methylation is a detoxication process for inorganic arsenite and that inorganic arsenite is the major cause of the toxicity and carcinogenicity of inorganic arsenic.

Adolescent↗
PubMed2000

Treatment of pain or fever with paracetamol (acetaminophen) in the alcoholic patient: a systematic review.

An unexpected clinical question has emerged in the treatment of pain or fever in the alcoholic patient: Is paracetamol a safe medication for the alcoholic patient? After decades of use in a variety of patients, sporadic reports suggest a relationship between liver injury and the use of paracetamol by alcoholic patients. We performed a systematic review of the medical literature to answer the question: Can administration of therapeutic doses of paracetamol cause hepatic injury in the alcoholic patient? After extensive data retrieval, each article in any language that involved the use of paracetamol by an alcoholic patient was abstracted and categorized for strength of evidence. Class I data (randomized, controlled trials) show that repeated ingestion of a therapeutic dose of paracetamol over 48 hours by patients with severe alcoholism did not produce an increase in hepatic aminotransferase enzyme levels nor any clinical manifestations compared with a placebo group. Class II data (prospective, nonrandomized trials) reveal that therapeutic doses of paracetamol have been administered to patients and an array of liver diseases (alcoholic, primary biliary, postnecrotic, or unspecified cirrhosis or alcoholic, acute viral, chronic active, or other infectious hepatitis) for periods up to 14 days without adverse effect. Finally, in several studies, a 1- to 2-g single dose of paracetamol was administered to alcoholic patients to study metabolism, again without adverse effect. In contrast, Class III data (retrospective case reviews and case reports) describe hepatic injury after repeated paracetamol ingestion with therapeutic intent, although usually not at therapeutic doses. Unfortunately, the information contained in Class III reports is often incomplete and contradictory. The history of ingestion is often unknown or contradicts other clinical information provided. For example, the history may indicate a therapeutic dose, but the serum paracetamol is elevated to levels only produced by ingestion much larger than the history indicates. In summary, all methodologically sound studies available indicate that therapeutic dosing of paracetamol to the alcoholic patient is not associated with hepatic injury. In fact, there is no change at all in hepatic aminotransferase enzymes, prothrombin time, or other biochemical parameters when compared with a placebo group in well-designed trials. Unless stronger evidence of a potentially dangerous interaction emerges, the use of paracetamol in the alcoholic patient is reasonable. During chronic treatment of pain, paracetamol may be preferred in the compliant alcoholic patients owing to the adverse effects associated with long-term use of nonsteroidal anti-inflammatory agents.

Acetaminophen↗
PubMed2000

Recurrent coagulopathy after antivenom treatment of crotalid snakebite.

BACKGROUND: We studied whether recurrence of coagulopathy, defined as the return of a coagulation abnormality after initial normalization, occurred after the use of antivenin (Crotalidae) polyvalent. METHODS: A retrospective, blinded, descriptive analysis of 354 consecutive cases of North American crotalid snake envenomation was done. Inclusion criteria were documented clinical evidence of crotalid snakebite, presence of a coagulopathy (platelet count <150,000/mm3, prothrombin time above normal, or fibrinogen level <150 mg/dL), and treatment with antivenin (Crotalidae) polyvalent. RESULTS: Of 112 cases with a coagulopathy extending beyond 6 hours after envenomation, 31 had sufficient coagulopathy testing to detect recurrence. Fourteen of these patients (45%) had recurrence of coagulopathy, and two cases were severe (fibrinogen level 29 mg/dL; platelet count 36,000/mm3). CONCLUSION: Recurrence of coagulopathy after envenomation by North American crotalid snakes may occur after use of antivenin (Crotalidae) polyvalent and can result in severe coagulation abnormalities.

Adult↗