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Biomedical subjects

E Watson

Publications and source records attributed to E Watson.

At least 109 records · Page 6Linked to original sources
PubMed1976

Rapid analytic method for adriamycin and metabolites in human plasma by a thin-film fluorescence scanner.

A rapid and highly sensitive method is described for the quantitative determination of adriamycin and metabolites in plasma. Adriamycin (Ad) with daunorubicin added as the internal standard was extracted from plasma with chloroform-isopropanol (1:1), separated by thin-layer chromatography (TLC), and quantitated in situ via a fluorescence scanning technique. This method represents one of the very few reliable quantitative TLC methods and is suitable for the routine determination of Ad in plasma in amounts as low as 2 ng/ml. Plasma Ad levels at 24 hours in rabbits and in patients both given a 1-mg/kg dose, previously regarded as difficult to be measured, are now easily measurable using as little as 0.5 ml of plasma. Multiple samples (ten to 15) can be analyzed by this method within a day.

Animals↗
PubMed1975

Assessment of cerebrospinal fluid levels of dopamine metabolites by gas chromatography.

The acid metabolites of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined in lumbar cerebrospinal fluid (CSF) by a new procedure. After gas chromatographic separation, the pentafluoroprionyl 2,2,3,3,3-pentafluoro-1-propionyl esters of DOPAC and HVA were analyzed by electron capture detection. Normal HVA levels were quantitated in as little as 0.1 ml CSF. No significant amounts of DOPAC (less than 1 ng/ml) were found in any of the drug-free samples analyzed. Levels of DOPAC increased only marginally in the CSF of patients receiving acute or chronic doses of L-Dopa. Baseline HVA levels ranged from 4.5--50 ng/ml with a mean value of 23 ng/ml. These studies demonstrate that HVA is the major dopamine metabolite in human CSF.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1975

Sudden death in infancy in Inner North London.

All cases of sudden infant death occurring over a 2-yr period in Inner North London were subjected to pathological and sociological analysis, using detailed expert interviewing of the mother soon after the event by doctors and Health Visitors. Of the cases showing no cause of death at autopsy (Cot Death) the great majority were found subsequently to have microscopic pathology sufficient to cause death, mainly respiratory tract inflammation. In addition, the majority of the "Cot Death" group had a clinical history of illness and in many of these cases hindsight suggested that the quality of health care could have been improved. Only a small minority of sudden infant deaths were found to have no history of illness and no microscope pathology. The results suggest that most cases of sudden infant death may result from a combination of respiratory infection with either special physiological or special sociological factors.

Age Factors↗
PubMed1975

Evaluation of dopamine metabolism in rat striatum by a gas chromatographic technique.

Dopamine metabolism in rat striatum was evaluated by gas chromatographic quantitation of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). The level of DOPAC (5.21 nmoles/g plus or minus 0.40 S.E.M., n equals 12) exceeded that HVA (3.63 nmoles/g plus or minus 0.25 S.E.M., n equals 12). 2 hr following administration of probenecid (200 mg/kg i.p.) the level of striatal HVA was approximately doubled whereas the level of DOPAC was not significantly elevated. Pargyline (75 mg/kg i.p.) poduced a rapid depletion of DOPAC and HVA. the rate of disappearance of DOPAC (t1/2 equals 10 min) exceeded that of HVA (t1/2 equals 18 min). Rates of metabolite formation were computed assuming steady state kinetics. The rate formation of DOPA (20.5 nmoles/g/hr) was much greater than that of HVA (10.1 nmoles/g/hr). We conclude that DOPAC is the major dopamine metabolite in rat striatum and that its measurement may provide the best index of functional neuronal activity in this species.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1975

Dopamine metabolism in the tuberculum olfactorium.

The occurrence of the major dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the tuberculum olfactorium of the rat was demonstrated by gas chromatography. The ratio of DOPAC to HVA in the tuberculum olfactorium was greater than the ratio of these metabolites in the striatum. The effect of pargyline and probenecid on dopamine metabolite levels was similar for both the tuberculum olfactorium and striatum.

Animals↗
PubMed1975

Urinary metabolites of halothane in man.

The urinary metabolites of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) were investigated in five individuals given trace doses (25 muCi), and in three individuals given large doses (1 mCi) of radioactively labeled 14C-halothane. The latter were donor subjects for heart transplant operations. Separation of the nonvolatile urinary metabolites of halothane was accomplished by chemical extraction, electrophoresis, ion-exchange and high-pressure liquid chromatography, and gas chromatography. Identification of the individual metabolites was by nuclear magnetic resonance and mass spectrometry. Three major metabolites were identified: trifluoroacetic acid, N-trifluoroacetyl-2-aminoethanol, and N-acetyl-S-(2-bromo-2-chloro-1,1-difluoroethyl)-L-cysteine. Smaller unidentified radioactive peaks were also found. The presence of both ethanolamide and cysteine conjugates of halothane is of concern. These urinary products imply the presence of reactive intermediates. The conjugation of such intermediates to proteins and phospholipids may give rise to the high-molecular-weight covalently bound metabolites demonstrated to be present in the liver following halothane anesthesia. Elucidation of the structures of the urinary metabolites provides information important to an understanding of halothane metabolism and its potential hepatotoxicity.

Binding Sites↗
PubMed1975

Differential sensitivity of two dopaminergic structures in rat brain to haloperidol and to clozapine.

The mechanisms underlying the dissociation of the extrapyramidal and antipsychotic properties of haloperidol as compared to clozapine were explored by studying the effects of these drugs on dopamine metabolism in the straitum and tuberculum olfactorium (TO) of the rat. Homovanillic acid and 3,4-dihydroxyphenylacetic acid were simutaneously measured in these regions by a gas chromatographic techinque after treating the rats with different doses of the drugs. Dose-response curves and time-action curves were generated. For both drugs, a higher dose was required to achieve half-maximal metabolite elevation in the TO as compared to the striatum. The apparent differential sensitivity to haloperidol was attributed to differences in time to peak response. The time to peak response to clozapine was similar in both structures. Thus, the striatum appears to be more sensitive to clozapine than the TO with respect to elevation of dopamine metabolites. The effect of haloperidol on dopamine metabolism in the striatum was more persistent than that in the TO. After 4 hours, metabolite levels were still elevated in the striatum, whereas after 2 hours they returned to base line in the TO. The extrapyramidal effects of haloperidol may be due to the persistent action of this drug on dopamine metabolism in the striatum, and the lack of extrapyramidal effects of clozapine may be due to its brief action on dopamine metabolism in the striatum.

3,4-Dihydroxyphenylacetic Acid↗