Reliable and sensitive analysis of occult bone marrow metastases using automated cellular imaging.

The presence of occult bone marrow metastases (OM) has been reported to represent an important prognostic indicator for patients with operable breast cancer and other malignancies. Assaying for OM most commonly involves labor-intensive manual microscopic analysis. The present report examines the performance of a recently developed automated cellular image analysis system (ACIS; ChromaVision Medical Systems, Inc.) for identifying and enumerating OM in human breast cancer specimens. OM analysis was performed after immunocytochemical staining. Specimens used in this study consisted of normal bone marrow (n = 10), bone marrow spiked with carcinoma cells (n = 20), and bone marrow obtained from breast cancer patients (n = 39). The reproducibility of ACIS-assisted analysis for tumor cell detection was examined by having a pathologist evaluate montage images generated from multiple ACIS runs of five specimens. Independent ACIS-assisted analysis resulted in the detection of an identical number of tumor cells for each specimen in all instrument runs. Additional studies were performed to analyze OM from 39 breast cancer patients with two pathologists performing parallel analysis using either manual microscopy or ACIS-assisted analysis. In 17 of the 39 cases (44%), specimens were classified by the pathologist as positive for tumor cells after ACIS-assisted analysis, whereas the same pathologist failed to identify tumor cells on the same slides after analysis by manual microscopy. These studies indicate that the ACIS-assisted analysis provides excellent sensitivity and reproducibility for OM detection, relative to manual microscopy. Such performance may enable an improved approach for disease staging and stratifying patients for therapeutic intervention.

Toxicological information series, IV. Information resources for chemical emergency response.

The need for rapidly available information by community agencies responding to chemical emergencies (leaks, spills, releases, fires, explosions, etc.) can be met by a number of resources. These resources include local poison control centers, the Toxicology Data Network (National Library of Medicine), the Agency for Toxic Substances and Disease Registry, ATSDR/NLM's ANSWER, the National Chemical Response and Information Center, the National Pesticide Telecommunications Network, The National Response Center (U.S. Coast Guard), the Federal Emergency Management Agency, the U.S. Environmental Protection Agency, the National Safety Council, private-sector database vendors, and textbooks addressing hazardous substances.

Chlorine poisoning at the swimming pool revisited: anatomy of two minidisasters.

A case of acute chlorine gas exposure in a swimming pool attendant was previously reported (Clin Tox 13:377-381, 1978). In April 1986, approximately 30 people, including a swimming coach, lifeguards, and competitive swimmers ranging in age from 5 to 12 years old, were exposed to heavy concentrations of chlorine gas at a large indoor swimming pool. The coach, one lifeguard, and 18 of the children were hospitalized. In June 1988, a similar exposure occurred at the same swimming pool, and 11 persons were affected. Information from these 2 incidents illustrates 4 important factors in disaster prevention and management: proper training of equipment operators, effectiveness of triage, information flow to relatives of the afflicted, and requisite posthospitalization followup to detect possible long-term adverse effects.

Toxicology of fires: an emerging clinical concern.

As a wider variety of synthetic materials is used in buildings, the potential for poisoning from inhalation of products of combustion is increasing greatly. Research during the past few years has shown that the burning of plastics (insulation, furniture, carpeting, electric wiring covering, decorative items) results in the formation of large amounts of highly toxic chemicals. Clinicians treating victims of fires should be aware of the toxicological ramifications of combustion, including delayed pathophysiological sequellae. A case report and a review of some current hypotheses of fire-induced toxicity illustrate the current state of knowledge, as well as some uncertainties and controversies in fire toxicology.

Effect of orally administered magnesium hydroxide in experimental iron intoxication.

We have previously shown that ferrous and ferric ions readily for complexes with magnesium hydroxide [Mg(OH)2] thus reducing the absorption of iron salts from the gastrointestinal tract. The present study answers the following question: what is the optimal dose, time of administration, optimal limit of effectiveness, and potential hazard of this form of therapy. Adult mongrel dogs were administered ferrous sulfate [FeSO4] tablets at a dosage of 650 mg/lb of body weight. Either 30 or 60 minutes later, the dogs were given Mg(OH)2 at either 5 or l0 times the dose of elemental iron. Serum iron concentrations in all animals given Mg(OH)2 were significantly lower (p less than 0.05) than those of control animals. No significant differences were observed regardless of dose or time of administration of Mg(OH)2. Although serum Mg++ concentrations were significantly elevated (p less than 0.05) om all treated animals 4 and 6 hr post iron, no clinical manifestations of hypermagnesemia were observed. These studies demonstrate the effectiveness of Mg(OH)2 in the management of experimental iron intoxication and warrant a controlled clinical trial in humans.

Tissue injuries associated with parenteral propylhexedrine abuse.

Propylhexedrine, the active ingredient in Benzedrex Inhalers, is extracted from the wicks of the inhalers by drug abusers for intravenous injection to provide a "desirable high." Six representative cases treated over a one-year period are presented to exemplify the potential for soft tissue injury. Because the actual constituents of the injected material prepared from the inhalers were not established, solutions were prepared from Benzedrex Inhalers according to the formula provided by one of the patients. The extract was then subjected to vigorous qualitative and quantitative analyses; the presence of essentially pure propylhexedrine hydrochloride was confirmed in varying concentrations. To examine the progression of injury following injection of the prepared extract, the ears of 12 New Zealand white rabbits were injected either intra-arterially or subcutaneously. The opposite ear of each rabbit served as a control. Both clinical and pathologic observations demonstrated injury consistent with intense local vasoconstriction. Injury did not appear to relate to impurities in the solution or other embolic phenomena. Finally, the laboratory findings are discussed with regard to the clinical examples. In sum, the insult to tissue from intravascular or local injection with propylhexedrine appears to respond, although poorly, to efforts to reverse the intense pharmacologic vasoconstriction.

Two deaths resulting from apparent parenteral injection of strychnine.

Large amounts of strychnine were found in the bodies of two drug abusers, presumable as a result of injection of "street drugs" adulterated with strychnine. Current therapeutic research with this drug, if widely accepted into medical practice, may lead to its greater availability and hence an increased poisoning incidence potential.

Decreased absorption of propoxyphene by activated charcoal.

In 1968 we first suggested that activated charcoal (AC) should be administered in the emergency treatment of propoxyphene overdosage. The dramatic increase in recent years of deaths involving propoxyphene has prompted us to again evaluate the efficacy of AC in preventing absorption of propoxyphene from the GI tract. Male rats (100-125 g) were administered propoxyphene hydrochloride (P-HCl, 350 mg/kg) or propoxyphene napsylate (P-N, 825 mg/kg) either dissolved or suspended in 5% acacia in H2O. After 30 min the rats were administered either AC at 10 times the drug dose or water. Surviving rats were sacrificed at 1, 2, 4, 8, 12, and 24 h; the brain, liver, and both kidneys were removed intact, weighed, and stored at -70 degrees C. After lyophilization, the tissues were analyzed for propoxyphene and its metabolite, norpropoxyphene, by GLC. There were significantly less deaths in rats that received P-HCl + AC or P-N + AC than rats that received either P-HCl or P-N alone (9 vs 19, p less than .01 and 5 vs 10, p less than .05 respectively). Tissue levels of propoxyphene and norpropoxyphene were similarly significantly reduced. These studies provide further evidence of the efficacy of AC in propoxyphene overdosage.

Intravenous self-administration of propoxyphene napsylate: case report and in-vitro studies.

A man who was prescribed propoxyphene napsylate (PN) for treatment of heroin addiction stated that he received no effect from the drug by the oral route. He then decided to administer the drug to himself intravenously in a manner identical to that used by most heroin addicts (heating the tablet with water in a spoon and drawing the liquid through a needle); this procedure brought him immediate subjective relief. Several reports have stated than PN is not efficacious via the intravenous route since it is relatively water insoluble and is therefore not likely to be abuse in this manner. However, in vitro experiments demonstrated that at least 1 mg of PN can be extracted by 10 mL of hot water from a tablet containing 100 mg of the drug. Assuming (as a conservative estimate) that the subject received a bolus injection of approximately 40 mg PN (he used four 100 mg tablets at once), his response may not have been entirely subjective. Moreover, severe cardiovascular and pulmonary complications may ensure as a result of the insoluble material injected.

A stable parenteral solution of apomorphine.

A sterile, stable apomorphine preparation suitable for parenteral use was prepared by dissolving 0.3% w/v powdered apomorphine hydrochloride in 1% reduced l-ascorbic acid. The solution was then sterilized by filtration through a 0.22 -micrometer Millipore filter, the air in the vial was replaced by nitrogen, and the vials were sealed and stored at 5 degrees C in the dark. Under these conditions the apomorphine solutions remained water-clear and retained their potency for at least 1 year following preparation.

Activated charcoal adsorbs aflatoxin B1.

Activated charcoal was demonstrated to adsorb aflatoxin B1 in an efficient manner in vitro at a neutral pH. One mg aflatoxin was adsorbed by 100mg activated charcoal. The complex appeared to be quite stable. Destruction of the aflatoxin by alkaline conditions was confirmed, and a large measure of destruction was also noted at acid pH. Implications of the adsorption phenomenon include prevention of systemic absorption.

NAGD regimen for the coma of drug-related overdose.

A specific arousal therapy with NAGD (Naloxone, Activated Charcoal, Glucagon, Doxapram) is outlined for victims of drug overdose in comatose and semi-comatose states. Several direct benefits accrue if early awakening or lightening of such patients is safely accomplished. There are: 1) elimination of need for prolonged intubation or tracheostomy; 2) patient's ability to tell which drug(s) were taken; 3) excessively frantic and vigorous supportive treatment is obviated; and 4) the overall hospital stay is shortened. The NAGD regimen has been found to effectively, safely, and predictably reverse coma. Therapy consists of: naloxone 0.8 mg to 1.6 mg intravenously; large-bore orogastric tube instillation of 100 gm to 120 gm activated charcoal slurry; glucagon 1 mg to 2 mg intravenously; and, in selected cases, doxapram 1 mg/kg to 2 mg/kg intravenously.

Rapid detection of amphetamine in urine by micro thin-layer chromatography and fluorescence.

A rapid, inexpensive, and simple screening procedure for the detection of amphetamine abuse was developed for use by laboratories without sophisticated equipment. A small volume of extract from a pH-adjusted urine specimen is used to spot a high-resolution micro TLC plate. The developed TLC plate is sprayed with a solution of fluorescamine in dry acetone. When viewed under ultraviolet illumination, amphetamines and other compounds with a primary amino group complexed with fluorescamine appear as greenish or bluish-white fluorescent spots. Secondary or tertiary amines do not react with fluorescamine. About 20 min is required to perform the procedure; the lower limit of detectability is approximately 100 ng/ml urine.