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Biomedical subjects

R M Thompson

Publications and source records attributed to R M Thompson.

At least 37 records · Page 2Linked to original sources

Does the conventional cystogram exaggerate reflux?

We studied 35 patients with anterograde and retrograde cystography. Many patients who had reflux on retrograde cystography either did not have reflux or the reflux was reduced significantly on anterograde cystography. Furthermore, when reflux was seen on anterograde cystography it appeared to have more prognostic value than when seen on retrograde cystography. The question is raised of whether much reflex seen on retrograde cystography is not actually an artifact of the examination and does not exist beyond circumstances of the test.

Adolescent↗

Evidence for the epoxide-diol pathway in the biotransformation of mephenytoin.

A dihydrodiol metabolite of mephenytoin (5-dihydroxycyclohexadienyl)-5-ethyl-3-methylhydantoin and other mono- and dihydroxylated and N-demethylated metabolites were identified in urine from a male epileptic patient receiving therapy with mephenytoin (300 mg/day). Metabolites, extracted from urine before and after enzymatic hydrolysis, were derivatized with a trimethylsilyl reagent and analyzed by combined gas chromatography and mass spectrometry. Two previously unreported metabolites were characterized: 5-ethyl-5-(di-hydroxyphenyl)-3-methylhydantoin and 5-ethyl-5-(hydroxy-methoxy-phenyl)-3-methylhydantoin. The structures of several other metabolites were confirmed: N-demethylmephenytoin, 5-ethyl-5-hydroxyphenylhydantoin, 5-ethyl-5-hydroxyphenyl-3-methylhydantoin and mephenytoin dihyrodiol. The dihydrodiol metabolite was of special interest since it was probably produced via an epoxide intermediate, 5-(epoxy-cyclohexadienyl)-5-ethyl-3-methylhydantoin. Previous reports have demonstrated that epoxides of this structural class are extremely reactive compounds, capable of alkylating biologic macromolecules. Covalent binding of the mephenytoin epoxide to macromolecules may be an important factor in the production of adverse and sometimes fatal side effects observed in patients receiving long-term therapy with mephenytoin.

Adult↗

Analysis of mono- and disaccharides by high-performance liquid chromatography of the benzyloxime-perbenzoyl derivatives.

A group of biologically important mono- and disaccharides are separated by high-performance liquid chromatography of the benzyloxime-perbenzoyl derivatives on a normal-phase microparticulate column with a hexane-dioxane mixture as the eluting solvent. A single, quantifiable derivative of each sugar is formed easily. These derivatives are detected by UV absorption at either 230 or 254 nm, with a sensitivity in the picomole range at the former wavelength. The sugars in the residues from the evaporation of small aliquots of biologic fluids (10-100 microliter) are derivatized without prior isolation and are determined quantitatively by the use of appropriate internal standards. The analyses could be performed routinely with a simple, inexpensive instrument.

Benzoates↗

Determination of disaccharides in feces by permethylation and gas chromatography: rapid screening for carbohydrate intolerance in children.

Disaccharides can be identified and determined quantitatively in fecal specimens by permethylation of the components in crude supernatants followed by isothermal gas chromatographic separation on OV-17 columns. The method provides a rapid screening procedure for detecting patients suspected of having a carbohydrate intolerance secondary to intestinal disaccharidase deficiency.

Carbohydrate Metabolism, Inborn Errors↗

Mass spectrometry of some permethylated apiosyl nucleosides.

The mass spectra of the permethyl derivatives of a group of synthetic D-apio-L-furanosyl nucleosides were collected and compared with those of their ribosyl analogs. While most of the m/e values are the same between analogous spectra, some of the relative intensities differ markedly. Each spectrum contains characteristics ions which are probably due to fragmentation of the dissimilar sugar moieties.

Mass Spectrometry↗

Identification of drugs, drug metabolites, and other compounds in urine by permethylation and gas-phase analysis.

A small aliquot of urine (50-200 mul) is evaporated to dryness, the residue permethylated with the methylsulfinylmethide carbanion and methyl iodide, and the product mixture separated and analyzed by GC and GC-MS. Certain drugs (especially the anticonvulsants), drug metabolites, mono-, di-, and trisaccharides, and organic acids, including fatty acids and glucuronides, can be identified in the mixture. The technique is probably useful mainly as a screening method for the detection of any of these types of compounds in urine.

Adolescent↗

Separation of permethylated isomeric glucuronides by gas chromatography and analysis of the mass spectra.

Glucuronic acid conjugates of several foreign compounds (1- and 2-naphthols, 2-, 3-, and 4-hydroxybiphenyls, m- and p-hydroxyphenylphenylhydantoins) were produced in the isolated perfused rat liver and identified in the bile as the permethyl derivatives. Permethylated glucuronide isomers were easily separated by gas chromatography on SE-30 and OV-17 columns. The mass spectra of permethylated glucuronide isomers were very similar. Gas chromatography proved to be most useful for the separation and identification of isomeric glucuronides.

Animals↗

Permethylation of barbiturates: variation in product ratios with varying methylsulfinylmethide carbanion.

Permethylation of a barbiturate with the methylsulfinylmethide carbanion and methyl iodide gave three products clearly separable by GLC. Alteration of the reaction conditions by varying the barbiturate to carbanion ratio or the barbiturate to carbanion exposure time resulted in a single product for only one examined barbiturate, secobarbital. This derivatization technique is useful for the GLC analysis of polar barbiturate metabolites, such as glucuronides, in biological fluids but is of limited value for the analysis of the parent compounds.

Barbiturates↗

Metabolism of 5-(p-toluyl)-5-ethylbarbituric acid and 5-(p-toluyl)-5-phenylhydantoin in the isolated perfused rat liver.

The primary route of metabolism of 5-(p-toluyl)-5-ethylbarbituric acid (TEBA) and 5-(p-toluyl)-5-phenylhydantoin (MPPH) in the isolated perfused rat liver is oxidation of the aromatic methyl group either to a primary alcohol which is then conjugated with glucuronic acid and excreted in the bile (MPPH only) or to the carboxylic acid which is excreted free in the bile (both TEBA and MPPH). All metabolites were identified by previously described permethylation and GC-MS techniques.

Animals↗

An artifact in the gas chromatographic analysis of urinary organic acids from phenylketonuric children: decarboxylation of the phenylpyruvic acid during extraction.

Phenylpyruvic acid is converted at least partially to phenylacetic acid during the normal extraction procedure used to obtain urinary organic acid profiles of phenylketonuric children by gas chromatography. This decarboxylation reaction can be reduced or completely eliminated by forming oxime derivatives prior to extraction.

Child↗

Metabolism of methocarbamol (robaxin) in the isolated perfused rat liver and identification of glucuronides.

1. Permethylation and g.l.c.-mass spectrometric analysis of bile from an isolated rat liver perfusion to which methocarmol was added showed seven components not present in control bile: methocarbamol, glucuronides of methocarbamol and desmethyl-methocarbamol, and four glucuronides of hydroxylated methocarbamol metabolites. 2. An interesting rearrangement of a methyl group has been found in the mass spectrum of 3-(2-methoxyphenyloxy)-1,2-dimethoxypropane, the permethylation product from methocarbamol.

Animals↗