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Biomedical subjects

C M Butler

Publications and source records attributed to C M Butler.

23 records · Page 2Linked to original sources

An investigation of recurrent pine oil poisoning in an infant by the use of gas chromatographic-mass spectrometric methods.

An 18-month-old infant required six hospital admissions in a period of six months for episodes consisting of coughing, respiratory depression, hematemesis, coma, dehydration, and lesions about the mouth. A negative history of ingestion of toxins was repeatedly obtained from the family and two home inspection by the local Health Department failed to identify potential toxins. Metabolic work-up was entirely negative. Utilizing methods of GC-MS, metabolites of a-terpineol were isolated from infant urine on two admissions to the hospital. These metabolites were confirmed by mass spectrometry to be the same metabolites excreted by Sprague-Dawley rats injected with a-terpineol or pine oil. The child had no additional episodes after physical separation from the home environment.

Animals↗

Clinical applications of gas chromatograph/mass spectrometer/computer systems.

Gas chromatograph/mass spectrometer/computer systems can be used to quantify a wide variety of compounds of clinical interest. A quadrupole instrument operated in the chemical ionization (Cl) mode was used in these studies. Because of the sensitivity and specificity of selective ion detection, it is possible to make measurements routinely in the nanogram to picogram range, with 0.1-1.0 ml samples of plasma and 1-5 ml samples or urine. Internal standards, preferably stable-isotope-labeled compounds, were added to the biological samples before isolation was begun. We describe clinical applications of these procedures to problems in toxicology, pharmacokinetics, and perinatal pharmacology.

Autoanalysis↗

Comparative metabolism of four allylic barbiturates and hexobarbital by the rat and guinea pig.

A method for the extraction and identification of urinary metabolites of allylic barbiturates by gas chromatography and mass spectrometry is described. The metabolites from rat and guinea pig urine were extracted and separated into two fractions (an acidic and a nonacidic fraction) by chromatography on DEAE-Sephadex before converted into suitable derivatives for gas phase analysis. N,N'-dimethyl derivatives were used except in cases where metabolic N-demethylation was possible, in which case N-ethylation yielded more information. Hydroxyl, keto, and epoxy groups were converted into trimethylsilyl (TMS), alkyloxime, and chloro-TMS derivatives, respectively. This procedure was used to identify metabolites present in urine at concentrations as low as 0.1 microgram/ml. The allyl sidechains of secobarbital, alphenal, allobarbital, and aprobarbital were metabolized to epoxides, diols, and, in the case of secobarbital, to a ketol. Other sidechains were usually hydroxylated. Secobarbital was metabolized to compounds containing hydroxyl groups in both chains. Hexobarbital was metabolized by allylic hydroxylation, and no evidence of the epoxide-diol pathway was observed. The significance of the detection of epoxides of the four allylic barbiturates is discussed.

Animals↗

Effects of a 5 alpha-reductase inhibitor, finasteride, on the developing prostate and testis of a marsupial.

This study examines the role of dihydrotestosterone in virilization of the developing male tammar. The onset of prostate differentiation in this marsupial species normally occurs around 25 days postpartum, long after the onset of testicular testosterone production immediately after birth and the appearance of 5 alpha-reductase in the urogenital sinus before day 10. Males treated with the 5 alpha-reductase inhibitor Finasteride had reduced prostatic growth and development, and their testicular structure was disorganized. Exogenous testosterone in males enhanced the development of prostatic buds but also caused damage to the testis structure. Treatment of female tammars with testosterone between days 20-30 postpartum stimulated prostatic tissue formation and Wolffian duct development, confirming that prostatic differentiation is initiated by androgens and occurs over a relatively narrow window of time. Testosterone had a deleterious effect on the ovary, destroying the germ cells. Although treatment with testosterone damaged gonadal cellular structure in both male and female tammar young, dihydrotestosterone is apparently necessary for stability of the seminiferous tubules in the testis. Taken together, these results suggest that dihydrotostesterone initiates prostatic development between days 20 and 25 after birth in this marsupial.

5-alpha Reductase Inhibitors↗