Biomedical subjects
Publications and source records attributed to W L Hearn.
A tank truck containing bulk pool chlorinating solution overturned. A man was trapped beneath the truck, and a ruptured seam in the tank released a continuous flow of sodium hypochlorite over him. He survived for 10 min as the caustic solution extensively eroded soft tissue exposed to the chemical flow.
The glucuronic acid conjugate of N-hydroxy-4-aminobiphenyl was tested for carcinogenicity using a heterotopically transplanted rat urinary bladder (HTB) diverted from urine flow. A low-grade transitional cell carcinoma developed in 1 of 16 HTB and sarcoma surrounding the Ommaya reservoir connected to HTB in 8 of 16 rats. This unexpected high incidence of sarcomas, not previously observed in HTB-carcinogenesis model, suggested that the glucuronide conjugate of N-hydroxy-4-aminobiphenyl is a locally active carcinogen to mesenchymal cells.
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Dimethylnitrosamine, a powerful carcinogen, is produced in the urine of patients with urinary tract infections of Proteus mirabilis and Escherichia coli when nitrite is present. Treatment with tetracycline antibiotics does not enhance the concentration of this carcinogen but, rather, sharply reduces it. The results emphasize the importance of proper antibiotic therapy for the infections to reduce the possibility of the subsequent development of bladder cancer.
The glucuronic acid conjugate of N-hydroxy-4-aminobiphenyl (NOH-4-ABP) has been isolated in relatively pure form from the urine of dogs given 4-aminobiphenyl, utilizing molecular size, ion exchange, adsorption, and partition chromatography. This conjugate is an active mutagen in Salmonella typhimurium strains TA1538 and TA98 but not in TA1535 or TA1537. NOH-4-ABP and 4-nitrosobiphenyl are also highly active in TA1538 and TA98 and inactive in TA1535 and TA1537. These observations support the concept that this conjugate is the water-soluble carrier that delivers the active metabolite to the bladder. A substance of identical chromatographic and spectral properties to the conjugate isolated from dog urine has been synthesized in low yield by the direct condensation of NOH-4-ABP with glucuronic acid. This substance yields NOH-4-ABP on dilute acid hydrolysis. Sodium (N-4-biphenylhydroxylamino-beta-D-glucopyranosid) uronate, the N-O-C isomer, was also synthesized. It was found to have differing chromatographic and chemical properties to the natural conjugate. This evidence suggests that the urinary conjugate is the compound in which conjugation has occurred with the nitrogen atom of the hydroxylamine group rather than the oxygen atom.
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Cocaethylene, the ethyl homolog of cocaine, is an active cocaine metabolite found in cocaine users who simultaneously consume cocaine and ethanol. To study the combined incidence of cocaine and cocaethylene, an analytical method was devised that would simultaneously quantify both drugs in whole blood or tissues. The method includes a quantitative procedure by GC-NPD with a confirmation by ion trap mass spectrometry. Propylbenzoylecgonine, the propyl homolog of cocaine, was used as the internal standard. The quantitative method was linear from 0.05 to 10.0 mg/L with a limit of detection of 0.02 mg/L. Cocaethylene and propylbenzoylecgonine were synthesized in the laboratory. The complete analytical procedure and the method of synthesis are presented, along with brief descriptions of medical examiner cases where both cocaine and cocaethylene were quantified and where cocaethylene may have played a part in the cause of death. In the five cases presented, the cocaine concentration ranged from 0.03 to 1.4 mg/L and cocaethylene ranged from 0.03 to 0.53 mg/L in the blood.
Hair analysis for cocaine was used in the investigation of a case of accidental cocaine poisoning. A 25-year-old man consumed an entire bottle of Pony Malta, an imported Colombian soft drink. Unbeknownst to him, the 6.2-oz bottle contained a large quantity of cocaine. It was subsequently discovered that this bottle was one of 45 recovered that contained cocaine as part of a smuggling scheme. The subject was hospitalized for acute cocaine intoxication but died 24 days later. The admission blood contained 2.3 mg/L of cocaine and 4.5 mg/L of benzoylecgonine. Subsequent segmental analysis by MS/MS of hair samples taken at the autopsy revealed a peak cocaine concentration in the segment corresponding to the time he ingested the tainted beverage. The use of hair analysis as an adjunct to traditional analytical techniques may help document drug use history and is especially useful in situations have blood and urine specimens have not been collected in a timely fashion.
A quantitative method was developed for the simultaneous analysis of morphine, codeine, hydromorphone, hydrocodone, and oxycodone in urine by gas chromatography/mass spectrometry. Samples were hydrolyzed with beta-glucuronidase and then extracted by solid phase extraction on Bond Elute Certify cartridges at pH 6.8. Nalorphine was used as the internal standard. The opiates were analyzed by full-scan electron impact GC/MS after derivatization with acetic anhydride-pyridine. The standard curves for all five drugs were linear between 50 and 1000 ng/mL, with correlation coefficients exceeding 0.99. Coefficients of variation were less than 7%. The method was applied to the analysis of postmortem urines positive by EMIT opiate assay, and the effect of the hydrolysis procedure on recovery of each drug was measured. The results indicate that the hydrolysis procedure is effective in increasing the recovery of all five drugs from urine. The described method enables the laboratory to identify the five opiates most commonly encountered in forensic and clinical laboratories. Its sensitivity for all five drugs is well below GC/MS cutoffs for codeine and morphine employed in NIDA laboratories, and it provides for conclusive full-scan drug identification.
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