Somatic mutation screening: identification of individuals harboring K-ras mutations with the use of plasma DNA.

BACKGROUND: Many cancers are attributed to somatic mutation of DNA. We investigated whether it is feasible to detect cancer-associated somatic mutations in patients with neoplasms by using plasma DNA. METHODS: Plasma samples were prospectively collected from 240 patients undergoing colonoscopy. Colorectal biopsies were performed as clinically indicated in 135 patients, and risk factor information was available from 232 patients. DNA was extracted from plasma and colorectal tissue and was amplified by use of a polymerase chain reaction method that enriches for mutations in codon 12 of the K-ras oncogene. Molecular, histologic, and clinical data were compared by use of two-sided Fisher's exact test. RESULTS: Mutations in the K-ras gene detected in the plasma of 64 (28%) of 232 patients were statistically significantly associated with colorectal cancer risk factors (P =.0002). Of those patients having tissue available for comparison (n = 135), mutations in the K-ras gene were found in the tissues of 35 patients, and 29 (83%) of these 35 showed mutations in plasma samples. In contrast, the plasma assay was negative in 93 of the 100 patients whose tissue K-ras was wild-type. Among patients without biopsies (n = 105), 28 had mutated K-ras in their plasma DNA, despite the absence of remarkable colonoscopy findings; 24 of these 28 patients had risk factors for colorectal cancer. Overall, 25 (39%) of 64 patients showing mutations in plasma DNA had colorectal neoplasms with K-ras mutations compared with five (3%) of 176 patients without K-ras mutations in plasma DNA. CONCLUSION: Plasma DNA assays for the detection of mutations in K-ras codon 12 may provide a feasible method to screen populations for somatic mutations frequently found in neoplasms. The clinical utility of using this test in screening populations requires further study.

A retrospective analysis of 96 "asp" (Megalopyge opercularis) envenomations in Central Texas during 1996.

BACKGROUND: The most frequently reported caterpillar envenomation in Central Texas is by the puss caterpillar or "asp," Megalopyge opercularis. This caterpillar is described by patients and physicians as inflicting intense radiating pain. The intensity of symptoms may be underestimated leading to undertreatment. Adequate treatment protocols have been lacking and those in use are not very successful. We present a retrospective study of patients who were stung and contacted the Central Texas Poison Center. METHODS: All human exposures to asp stings reported to the Central Texas Poison Center during 1996 were included. Inclusion criteria consisted of all cases documented as an asp envenomation by the specialists in poison information. Characterization of symptoms and treatment used were evaluated. RESULTS: There were 96 exposures to asps reported. Ninety-five of the patients experienced local pain with 26 of these reporting intense radiating pain. Forty developed erythema, 27 described edema, and 9 complained of welts/hives. Other symptoms reported included white spots (4), pruritus (3), red streak (2), numbness (2), and individual accounts of chest pain, rash, ecchymosis, tingling, blister, and muscle spasm. There was no treatment modality that promptly relieved pain. DISCUSSION: Although asp envenomations appear to be very common, clinical cases have rarely been documented. This may be due to physicians not recognizing the etiological agent. Pain may be very intense and standard pain management appears to be unsuccessful. CONCLUSION: This study suggests that further examination of treatment modalities may be beneficial in addressing the morbidity of Megalopyge opercularis envenomations.

Five-year multicenter retrospective review of cyclobenzaprine toxicity.

Cyclobenzaprine (CBP) has a cyclic structure similar to amitriptyline. In overdose, CBP has been suggested to produce the cardiovascular and neurologic toxicity found with the cyclic antidepressants. To examine this possibility, a retrospective chart review of all cases of CBP exposure reported to five regional poison centers was performed for the years 1989-93. There were a total of 750 charts identified for CBP exposure, of which 523 had data sufficient for evaluation. There were 121 polydrug ingestions leaving 402 pure CBP ingestions. Ages ranged from 7 mo to 77 yrs, with a mean of 20 yrs; 26% were 6 yrs or less. Females comprised 63% of the patient group. No deaths occurred. Dysrhythmias beyond sinus tachycardia were infrequent, and none were life-threatening. No seizures occurred. Common effects were lethargy, sinus tachycardia, and agitation, and both hypertension and hypotension were seen. All symptomatic cases with a known time of ingestion were symptomatic within 4 h of ingestion. Doses ingested ranged from 5-1000 mg, with a mean of 133 mg. Asymptomatic and symptomatic patients had a mean dose ingested of 45 mg and 183 mg, respectively. Treatment was primarily gastrointestinal (GI) decontamination and supportive care. Other therapies required were mechanical ventilation, dopamine, fluid bolus, sedation, and foley catheter. Symptoms requiring treatment beyond GI decontamination did not occur with ingestions less than 100 mg. In conclusion, cyclobenzaprine does not appear to produce the life-threatening cardiovascular or neurologic effects of the cyclic antidepressants in doses less than 1 g. Lethargy and anticholinergic effects are prominent, though serious toxicity is infrequent.

Unintentional albuterol ingestion in children.

This study was designed to determine the threshold dose for toxicity, the potential for serious medical complications, and the medical care required after unintentional albuterol ingestion in children. This study was prospective and descriptive. Data were obtained on pediatric albuterol ingestions evaluated emergently as reported to three regional poison control centers. Data elements included dose ingested, physical findings, medical treatment, and outcome. During 18 months, 78 patients who ingested albuterol and who received urgent medical evaluation were identified. Mean age was 2.8 years. The amount ingested ranged from 0.2 to 8.8 mg/kg. The most commonly reported signs of toxicity were tachycardia (57%, 44/78), widened pulse pressure (50%, 27/54), hyperglycemia (50%, 12/24), agitation (45%, 35/78), low serum carbon dioxide (42%, 10/24), vomiting (26%, 20/78), and hypokalemia (26%, 9/35). We found a threshold dose o 1 mg/kg for three or more signs of toxicity (P < 0.01). No patient required any specific treatment for toxicity. Seventy-two percent of patients were discharged from medical care within six hours of ingestion. Albuterol overdose in children causes a variety of cardiovascular, neuromuscular, and metabolic effects that are usually benign. The threshold dose for the development of three or more signs of toxicity is 1 mg/kg or three to 10 times the recommended daily dose. Toxicity is short-lived and does not require specific therapy or hospital admission in most cases.

Bupropion overdose: a 3-year multi-center retrospective analysis.

Bupropion (Wellbutrin; Burroughs Welcome Co, Research Triangle Park, NC) is a unique monocyclic antidepressant about which there is limited overdose information. A retrospective analysis of all bupropion ingestions reported to five regional poison control centers from 1989 through 1991 was conducted. There were 58 cases of bupropion ingestion and nine cases of combined bupropion and benzodiazepine ingestion. Sinus tachycardia was the only toxic cardiovascular effect noted, except for one case of hypotension in the bupropioin and benzodiazepine group. Neurological toxicity was commonly encountered and included lethargy, tremors, and seizures. Both benzodiazepines and phenytoin were efficacious in controlling seizures. Five cases of pure bupropion overdose had electrolytes reported. Serum potassium ranged from 2.6 to 4.2 mEq/L (mean, 3.3 mEq/L). In overdose, bupropion seems to lack major cardiovascular toxicity; however, it does manifest significant neurological toxicity.

Acute fluoxetine overdose: a report of 234 cases.

Limited toxicity information is available in the medical literature on the antidepressant fluoxetine (Prozac, Dista Products Co, Indianapolis, IN). The goal of this prospective multicenter study was to develop a toxicity profile of initial signs and symptoms observed in an acute fluoxetine overdose. A prospective study was made of patients reported to one of four American Association of Poison Control Centers' regional poison control centers after ingesting an acute overdose of fluoxetine. A standard data collection form was used on all patients ingesting fluoxetine. Information obtained included age, current medications, dose, coingested drugs, presenting symptoms, vital signs, electrocardiogram abnormalities, outcome, and fluoxetine levels. The authors collected 272 cases; 234 cases met the criteria of the study. Fluoxetine was ingested alone in 87 cases and with ethanol or other drugs in the remaining 147 cases. Of the 87 cases where fluoxetine was ingested alone, 67 patients were adults and 20 were children. Symptoms that were seen in the adult group included: tachycardia (15/67), drowsiness (14/67), tremor (five/67), vomiting (four/67), or nausea (four/67). Thirty patients did not develop symptoms. Twelve of the adult overdose patients had total fluoxetine levels ranging from 232 to 1390 ng/mL. The authors conclude that symptoms that develop after an acute overdose of fluoxetine appear minor and of short duration. Aggressive supportive care is the only intervention necessary.

The effects of fluoxetine in the overdose patient.

Fluoxetine (Prozac) is a new antidepressant, first marketed in the United States in January 1988. Only limited toxicologic information during a fluoxetine overdose is available. The goal of this prospective multi-center study was to develop a toxicity profile of initial signs and symptoms observed in fluoxetine overdose. A standardized data collection form was used on all patients ingesting fluoxetine as reported to four poison centers. Information obtained included age, dose, co-ingested drugs, presenting symptoms, vital signs, EKG abnormalities and lab values. Of the 127 cases of acute fluoxetine overdose collected, 106 cases met the criteria of the study. Of these, 69/106 ingested other drugs, including ethanol and 37/106 ingested fluoxetine alone. Of the latter group, the amounts ingested ranged from 20 to 1500 mg. It was observed that 48.6% (18/37) remained asymptomatic, 16.2% (7/37) were sleepy, 24.3% (9/37) had a sinus tachycardia (of 100 beats per minute or greater), and 8.1% (3/37) had a diastolic pressure over 100 mm Hg. Data collection is ongoing. Based upon our initial experience, fluoxetine in overdose appears to be relatively benign.

CNS depression in an infant after the ingestion of tobacco: a case report.

An 8-month-old female infant was brought in after ingesting cigarette butts. Upon presentation to the ED approximately 2.5 hr post-ingestion, the child was very lethargic and respirations were depressed. She was intubated and a NG tube was placed. Gastric lavage was performed, after which activated charcoal and sorbitol were given. Atropine was administered to treat excessive secretions. The patient became progressively more obtunded throughout the emergency department stay. Upon admission to the PICU she was minimally responsive. The urine tox screen was positive only for nicotine. The patient gradually improved with supportive care and was sent home on the third hospital day. Although the effects of Nicotine are well documented, few cases have been reported of severe toxicity in pediatric patients. We believe this to be the only reported case of severe CNS depression secondary to the ingestion of cigarette butts in a pediatric patient.

Review of veterinary cases received by the Hennepin Poison Center in 1984.

During 1984 the Hennepin Poison Center documented 28, 141 poison exposures. Of these, 1,092 or 3.88% were veterinary exposures. In this study we review those animal cases and present data on the relative number of species involved, the nature of the contaminants, frequency of calls during different times of the day and different times of year. We also report on the number of symptomatic animals, routes of exposure and referral patterns. We will also give brief reports on veterinary cases of particular interest.