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Biomedical subjects

S M Pond

Publications and source records attributed to S M Pond.

At least 127 records · Page 7Linked to original sources
PubMed1984

Two fatalities after acute occupational exposure to ethylene dibromide.

A worker collapsed while working inside a tank that was later found to contain residues of ethylene dibromide. He died 12 hours later with metabolic acidosis, depression of the CNS, and laboratory evidence of liver damage. A supervisor attempting to rescue the first victim also collapsed inside the tank and died 64 hours later with intractable metabolic acidosis and hepatic and renal failure. The clinical, pathological, and toxicological findings, as well as results of industrial hygiene sampling, are reported. Pathophysiological mechanisms and possible therapeutic interventions are discussed. The cases demonstrate the extreme hazards of exposure to the highly toxic chemical. The importance of protective work practices wherever there is potential exposure to ethylene dibromide is emphasized.

Adult↗
PubMed1984

Randomized study of the treatment of phenobarbital overdose with repeated doses of activated charcoal.

We performed a prospective randomized study of the effectiveness of repeated oral doses of activated charcoal in the treatment of phenobarbital overdose. Ten comatose patients who required intubation and mechanical ventilation completed the protocol. Five patients received repeated doses of activated charcoal and sorbitol. Five other patients who received a single dose of charcoal and cathartic served as control subjects. The serum half-life of phenobarbital (mean +/- SD, 36 +/- 13 hours) during repeated administration of charcoal and sorbitol was significantly shorter than that after charcoal administration was discontinued (93 +/- 7 hours) and shorter than the half-life in the single-dose group (93 +/- 52 hours). The length of time that patients in each group required mechanical ventilation, 39 +/- 24 hours (single-dose group) and 48 +/- 8 hours (repeated-dose group), did not differ significantly, nor did the time spent in the hospital. Although administration of repeated doses of activated charcoal to patients with phenobarbital overdose significantly increased the elimination of phenobarbital, it had no clear effects on the patients' clinical course.

Administration, Oral↗
PubMed1984

Nonlinear formation of propranolol metabolites in dogs after portacaval transpositions.

The formation of four major metabolites of propranolol by the liver was examined at steady state in three dogs that had undergone surgical portacaval transposition, following which injection of drug into the hindlimb delivers the total dose to the liver. Propranolol was infused directly into the liver via a hindlimb vein at dose rates ranging from 1.01 to 6.3 mg/min. In all dogs the formation of 4-hydroxypropranolol, alpha-naphthoxylactic acid, and propranolol glycol was saturable. Vmax and Km values were determined at steady state by relating the rate of excretion of each metabolite into bile and urine to the blood concentration of propranolol. The formation of propranolol glucuronide was a first order process. The use of a dog with a portacaval transposition has permitted development of a method to estimate, in vivo, the kinetic properties of enzymes responsible for hepatic first-pass metabolism of drugs.

Animals↗
PubMed1984

Benefit of hemoperfusion in acute theophylline intoxication.

Charcoal and resin hemoperfusion or hemodialysis can accelerate theophylline elimination. Their benefit in the treatment of poisoned patients has been accepted on the basis of case reports. We reviewed the treatment of 26 patients with acute theophylline intoxication to determine how much of an effect hemoperfusion or hemodialysis had on the hospital course and outcome of the overdose. Eighteen patients received supportive care and eight patients hemoperfusion (HP) or hemodialysis (HD). The HP/HD patients had more severe theophylline intoxication on the basis of admission and peak theophylline levels, degree of hypotension and occurrence of arrhythmias. During HP/HD, theophylline concentrations decreased, heart rate slowed, blood pressure increased and evidence of central nervous system effects diminished. Despite the severe intoxication in the HP/HD groups, duration of clinical toxicity was shorter (13.5 +/- 7.1 vs. 21.6 +/- 14.1 hr) than in the control group. Seizures occurred in patients in both groups, but there was higher mortality or neurological morbidity in the supportive care (3/4) than in the HP/HD (1/5) group. Our study provides evidence that HP/HD can reduce the duration of clinical intoxication and probably reduces mortality and morbidity in patients with severe theophylline intoxication.

Adolescent↗
PubMed1984

Diuresis, dialysis, and hemoperfusion. Indications and benefits.

The author discusses the clinical indications for therapy to enhance removal of toxins; the methods available to enhance removal of toxins, including forced diuresis and control of urine pH, peritoneal dialysis, hemodialysis, and hemoperfusion; the kinetics of hemodialysis and hemoperfusion; and the pharmacokinetic prediction of the efficacy of hemodialysis and hemoperfusion.

Adult↗
PubMed1984

Intestinal infarction complicating phenobarbital overdose.

Nonocclusive intestinal infarction developed in a 29-year-old man after phenobarbital overdose. He was found 72 hours after the overdose, at which time examination of the abdomen disclosed no abnormalities and he was not hypotensive. During the next ten hours, abdominal distention, ileus, and gas within the intestinal wall and portal venous system developed. Laparotomy disclosed ischemic intestinal infarction of the right colon and distal ileum with no evidence of thrombosis of the mesenteric vessels. The patient recovered fully after ileostomy with subsequent reanastomosis. To our knowledge, ischemic intestinal infarction after drug overdose has not been reported previously.

Adult↗
PubMed1984

Dose-dependent bioavailability and metabolism of salicylamide in dogs.

The dose-dependent first-pass metabolism and pharmacokinetics of salicylamide (SAM) were studied at four dose levels in six dogs. Four minutes after each oral dose, a tracer dose of [14C]SAM was given i.v. to determine clearance and bioavailability. Over the dosage range studied, 5 to 40 mg/kg, bioavailability increased from 0.24 +/- 0.14 (mean +/- S.D.) to 0.76 +/- 0.20 (P less than .05). Clearance decreased from 3.4 +/- 1.0 to 0.60 +/- 0.11 liters/min (P less than .01) and half-life increased from 5.0 +/- 1.2 to 23.5 +/- 6.1 min (P less than .01). Measurement of SAM clearance to individual metabolites indicated that the sulfoconjugation and not the glucuronidation pathway was responsible for the dose-dependent effects observed. These effects occurred even at doses not expected to have caused significant depletion of body stores of inorganic sulfate; the plasma concentration of inorganic sulfate decreased by only a maximum of 13 and 26% after the 5- and 10-mg/kg SAM doses, respectively. When [14C]SAM was given alone in tracer amounts, clearance values greatly exceeded cardiac output. This suggests that SAM undergoes sulfation in organs other than the liver and intestinal wall.

Animals↗
PubMed1983

Hemoperfusion in a child who ingested diquat and died from pontine infarction and hemorrhage.

A 2 1/2 year old boy accidentally ingested the herbicide diquat. Progressive neurologic dysfunction preceded his death 143 hours after poisoning. Brain stem infarction and purpura were noted at post mortem and closely resembled the brain stem pathology in 3 of 7 adults who died after diquat ingestion. Renal, gastrointestinal and pulmonary involvement in this child also resembled that seen in adults after ingestion of diquat. Hemoperfusion was performed six times in an effort to lower the body diquat burden. Cellulose-coated, activated charcoal was first employed 40 hours postingestion and removed diquat from serum with clearances of 104 and 39 ml/minute at the initiation of hemoperfusion and 6 hours later, respectively. Serum diquat concentrations decreased rapidly during charcoal hemoperfusion. However, marked rebound in serum diquat concentrations were noted between charcoal treatments, indicating extensive sequestration of diquat by tissues. Thrombocytopenia and hypocalcemia, the major complications of charcoal hemoperfusion, were easily treated. Unlike charcoal, Amberlite XAD-4 resin hemoperfusion did not remove diquat from serum. Charcoal hemoperfusion may temporarily reduce serum diquat concentrations. Whether the early institution and daily performance of charcoal hemoperfusion will minimize diquat-induced damage to brain and other organs is not clear from this case and will only be determined in future studies.

Adolescent↗
PubMed1982

Gas chromatographic analysis of meperidine and normeperidine: determination in blood after a single dose of meperidine.

A method is described for the determination of meperidine and its pharmacologically active metabolite, normeperidine, in blood, plasma, and urine using gas chromatography with nitrogen-phosphorus detection. Structural analogs of both meperidine and normeperidine were used as internal standards. Unlike previously reported assays, this procedure was sensitive and convenient enough for use in pharmacokinetic studies of both meperidine and normeperidine following single doses of meperidine. The assay was sensitive to 5 ng of meperidine/ml and 2.5 ng of normeperidine/ml extracted from a 1-ml biological sample. The between-assay coefficients of variation at these concentrations were 9.4 and 10.4%, respectively.

Adult↗
PubMed1982

Massive intoxication with acetaminophen and propoxyphene: unexpected survival and unusual pharmacokinetics of acetaminophen.

A 28-year-old woman ingested an estimated 58 g acetaminophen and 9 g propoxyphene 20 h before hospitalization. Her serum acetaminophen concentration at 22 h was 485 micrograms/mL and declined with an unusually long half-life of 14 h. Hemodialysis for 4 h (started at 36 h) reduced the acetaminophen concentration from 250 to 32 micrograms/mL. The patient's complete recovery was remarkable because of the large amounts of drugs ingested, the delayed treatment, and prior exposure to enzyme inducers (known to increase acetaminophen hepatotoxicity). Administration of N-acetylcysteine prevented inorganic sulfate depletion usually caused by acetaminophen and may have increased the formation of acetaminophen sulfate. Some patients eliminate large overdoses of acetaminophen very slowly. Measures to enhance the elimination of this drug and its toxic metabolite by these individuals may be useful even when diagnosis or hospitalization is delayed.

Acetaminophen↗
PubMed1982

Potential pitfalls in the evaluation of the usefulness of hemodialysis for the removal of lithium.

A 50-year old female who was comatose from an overdose of lithium was treated with hemodialysis. Serum lithium concentrations declined 47% during a 3-h hemodialysis but increased afterwards, peaking 8 h after hemodialysis was stopped. Hemodialysis clearances were estimated by equations using extraction ratios of lithium from whole blood, serum, and red cells, and flows of whole blood, serum or red cells. The amount of lithium removed was calculated from these clearances as well as measured directly in the dialysate. Errors were introduced into the calculation of the amount of lithium removed by hemodialysis unless whole blood concentrations of lithium and whole blood flows were used. These arose because extraction of lithium from serum (0.7 +/- 0.3, mean +/- SD) was greater than that from whole blood (0.49 +/- 0.06) or from red blood cells (0.18 +/- 0.12). Despite the rapid decrease in serum concentrations of lithium during hemodialysis and rebound afterwards, the patient's neurologic status did not change concurrently. The patient did not regain consciousness until lithium concentrations fell to less than 0.4 meq/L in serum and 0.1 meq/L in cerebrospinal fluid. The lack of parallel change in serum concentrations and coma probably reflects the lag time in equilibration between lithium concentrations in serum and brain.

Female↗
PubMed1982

Effects on the liver of chemicals encountered in the workplace.

The liver plays a central role in toxicology. It is the primary organ of detoxification and elimination by metabolism of many chemicals. Many workplace chemicals can affect the liver in animals; fewer have been proved to do so in humans. The diverse hepatic effects observed in humans from occupational exposure to chemicals range from fatty infiltration, acute hepatitis and cholestasis to cirrhosis and angiosarcoma. Three important workplace chemicals, prototypes for the toxicities of many others, are carbon tetrachloride, vinyl chloride and the polychlorinated biphenyls (PCB's). These three are described in some detail to highlight principles of occupational toxicology. Most of the hepatic effects produced by chemicals in the workplace have clinical, laboratory and morphological features common to many other forms of liver disease. Therefore, only an astute physician who takes an occupational history will recognize the association between a patient's workplace and liver disease.

Carbon Tetrachloride Poisoning↗
PubMed1982

A technique to study hepatic and intestinal drug metabolism separately in the dog.

A model to study hepatic and intestinal drug metabolism in the dog has been evaluated. The model is made by performing a portacaval transposition, cholecystectomy and inserting a Thomas cannula into the duodenum. The result is a healthy animal in which drugs can be infused either in a normal i.v. (forelimb) fashion, directly into the liver (hindlimb) or given orally. Blood can be sampled from a peripheral vein, peripheral artery or hepatic vein. Bile and urine can be collected continuously. Pharmacokinetics can be studied in awake, unmedicated animals. The model can be used to assess oral, i.v. or hepatic infusion of drugs and their hepatic, intestinal or pulmonary metabolism.

Animals↗
PubMed1982

Lack of gastrointestinal metabolism of propranolol in dogs after portacaval transposition.

We studied whether or not propranolol underwent presystemic metabolism in the gastrointestinal wall in five dogs. The dogs were studied before and four weeks after creation of a portacaval transposition. Before surgery, systemic bioavailability of the oral dose was 8 +/- 8% (mean +/- S.D.), whereas after transposition the bioavailability was 102 +/- 9%. The systemic plasma clearance increased from 766 +/- 192 to 976 +/- 280 ml/min. The terminal half life and apparent volume of distribution after transposition were not significantly different from those obtained preoperatively. Our results indicate that there is complete absorption but no metabolism of propranolol by the gastrointestinal wall.

Administration, Oral↗
PubMed1982

Amanita phalloides-type mushroom poisoning.

In the fall of 1981 the San Francisco Bay Area Regional Poison Control Center received more than 100 calls regarding wild mushroom ingestion. Ten cases, including three fatalities, had all the features of Amanita phalloides poisoning. Encephalopathy, coma and renal insufficiency occurred in all three patients who died, but did not occur in those who survived. Two of the three patients who died arrived at the hospital late in the course of their illness, and severe gastroenteritis with accompanying dehydration probably contributed to their deaths. The poison control center promoted public awareness of the mushroom hazard through newspaper and television stories and by notifying local health departments. It also has devised a simple form to improve the quality of data collection and to assist in later verification of suspected A phalloides poisoning.

Adolescent↗