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Biomedical subjects

R Burton

Publications and source records attributed to R Burton.

At least 55 records · Page 3Linked to original sources

Identification of valproic acid metabolites in human serum and urine using hexadeuterated valproic acid and gas chromatographic mass spectrometric analysis.

Valproic acid, an antiepileptic drug, is extensively metabolized in humans. A hexadeuterated valproic acid was used in this study to aid the identification of metabolites and their artifacts in serum and urine extracts. A 600 mg oral dose of hexadeuterated valproic acid was administered to a human volunteer at steady state serum concentrations of unlabelled valproic acid. By using gas chromatography mass spectrometry, metabolites were characterized as their methyl, tert-butyldimethylsilyl, or trimethylsilyl derivatives. A di-unsaturated metabolite with concentrations comparable to 2-ene valproic acid was identified in serum and urine. The presence of a molecular ion doublet in the mass spectrum corresponding to the unlabelled and hexadeuterated dienes reduces the possible structures for this metabolite. A new metabolite, 2-propyl-4-ketopentanoic acid was also identified in serum and in urine. The dicarboxylic acids, 2-propylsuccinic and 2-propylmalonic were identified in the urine extract as metabolites. Identification of isolated metabolites was aided by comparison of the retention times and mass spectra to those of synthesized reference compounds. Diagnostic fragment ions and ion doublets in the mass spectra of the derivatives of newly identified metabolites were compared to those of known metabolites.

Biotransformation↗

Valproic acid analysis in saliva and serum using selected ion monitoring (electron ionization) of the tert.-butyldimethylsilyl derivatives.

A highly sensitive ion monitoring method for the determination of valproic acid in saliva and in serum has been developed based on the gas chromatographic--mass spectrometric analysis of the tert.-butyldimethylsilyl derivatives. Extraction methods are simple and the techniques for derivatization are rapid and convenient. Selected ion monitoring was carried out using electron ionization conditions and a common ion m/z 201 (M+--57) present in valproic acid and the internal standard octanoic acid. The lower limit of sensitivity that has acceptable precision for assay purposes is 0.1 mg/l based on a 200-microliter sample size. The ion monitoring method (derivatized) was compared to a gas chromatographic method (underivatized) for serum valproate assays and found to be essentially identical. The assay methodology was used in a kinetic study of valproic acid in two normal subjects. Saliva levels of drug were found to give reasonably good correlations with serum total and with serum free concentrations of drug in both individuals.U

Administration, Oral↗

Methods and validity of dietary assessments in four Scandinavian populations.

Average intakes of nonstarch polysaccharides (dietary fiber), foods, and nutrients were measured in representative samples of 30 men aged 50-59 in 4 Scandinavian populations with a 3-4 fold difference in risk for large bowel cancer. The assessment technique, a 4-day weighed record of food consumed and duplicate collections of all food eaten, was validated by chemical analysis of the duplicates, by measuring 24-hour urine and fecal nitrogen excretion, and by comparing the constituents of the urine samples collected during the survey with similar collections 1-2 weeks later. There were good agreements between estimates of fat and protein intake obtained by food-table calculations of the 4-day weighed record and the chemically analyzed duplicates. Urinary plus fecal nitrogen excretion was equal to estimated nitrogen intake during the survey, and no discernable changes in urinary output occurred after the survey, thereby implying that dietary habits had not changed as a result of the investigative technique. It is concluded that the dietary data are indicative of current patterns of food consumption and are sufficiently valid for comparison with data on cancer risk in the 4 areas.

Colonic Neoplasms↗

Colon cancer and large bowel function in Denmark and Finland.

Stool weight and transit time through the gut were measured in 4 groups of 30 men, aged 50-59 years, randomly selected from populations in urban (Copenhagen) and rural (Them) Denmark and urban (Helsinki) and rural (Parikkala) Finland. These populations exhibited a 3-4 fold difference in risk for large bowel cancer. Mean transit time (37 +/- 1 hours, Copenhagen; 43 +/- 1 hours, Helsinki; 40 +/- 1 hours, Them; 37 +/- 1 hours, Parikkala) was not significantly different among populations, but average 24-hour stool weights (136 +/- 13 g, Copenhagen; 176 +/- 17 g, Helsinki; 169 +/- 16 g, Them; 196 +/- 15 g, Parikkala) were different and had a significant inverse relationship to total large bowel cancer incidence, with larger stool weights being found in the low-risk population. A high proportion of study subjects, especially in Finland, were found to be taking medication or to have a history of gastrointestinal illness, but neither of these variables related to bowel habit.

Colon↗

Influence of a psyllium-based fibre preparation on faecal and serum parameters.

A fibre made of psyllium husk was given to 12 elderly patients for 4 months in order to investigate their faecal output and selected serum parameters. The fibre significantly improved bowel function and faecal output confirming its value as a non-irritant, harmless bulk-forming laxative. Serum cholesterol was decreased by 20% while triglycerides remained unchanged. There was a significant reduction in serum calcium after withdrawal of the fibre supplement. There were no significant changes in serum iron, total iron binding capacity, fibrinogen, or in the haematological parameters (ESR, haemoglobin, leucocyte count) attributable to the fibre. The high phytate content of the fibre does not appear to have any clinically significant effect on mineral absorption. It is suggested that dietary fibre (at least psyllium-based fibre preparations) may have significant cholesterol lowering capacity due to the binding of bile-acids in the intestine.

Aged↗

The use of ophthalmosonometry in the diagnosis of carotid artery stenosis.

One hundred and fifty-two patients underwent supraorbital Doppler studies of 304 carotid arteries to determine the presence or absence of hemodynamically significant lesions. Subsequent carotid arteriography was used to validate the accuracy of the test. Of 124 patients having abnormal Doppler examinations, 107 (86%) were angiographically proved to have lesions of the internal carotid artery that produced a stenosis of 50% or more. In the last 80 patients, the accuracy was increased to 94%. Of 115 proved stenoses or occlusions, the supraorbital Doppler examination correctly identified 99, for a diagnostic accuracy of 86%. In the last 50 patients, this accuracy was increased to 93%. Since only 58% of the patients with lesions had a bruit, the Doppler study was of particular value in identifying the patients with significant lesions in the absence of a bruit. Likewise, since only 61% of carotid arteries with bruits had lesions of hemodynamic significance, a normal Doppler examination could have been used to avoid angiographic screening of those arteries with bruits in the absence of major lesions, providing those hemodynamically insignificant lesions were not producing symptoms related to emboli. The technique of ophthalmosonometry and the significance of the test in clinical evaluation is discussed.

Blood Flow Velocity↗

Latency of some glycosidases of rat liver lysosomes.

The latency of the alpha-glucosidase activity of intact rat liver lysosomes was studied by using four substrates (glycogen, maltose, p-nitrophenyl, alpha-glucoside, alpha-fluoroglucoside) at a range of substrate concentrations. The results indicate that the entire lysosome population is impermeable to glycogen and maltose, but a proportion of lysosomes are permeable to alpha-fluoroglucoside and a still higher proportion permeable to p-nitrophenyl alpha-glucoside. Incubation at 37 degrees C in an osmotically protected buffer of of pH 5.0 caused lysosomes to become permeable to previously impermeant substrates and ultimately to release their alpha-glucosidase into the medium. The latencies of lysosomal beta-glucosidase and beta-galactosidase were examined by using p-nitrophenyl beta-glucoside and beta-galactoside as substrates. The results indicate permeability properties to these substrates similar to that to p-nitrophenyl alpha-glucoside. On incubation in an osmotically protected buffer of pH 5, lysosomes progressively released their beta-galactosidase in soluble form, but beta-glucosidase remained attached to sedimentable material. Lysosomal beta-glucosidase was inhibited by 0.1% Triton X-100; alpha-glucosidase and beta-galactosidase were not inhibited.

Animals↗

Correlative assay of computerized cranial tomography CCT, water content and specific gravity in normal and pathological postmortem brain.

An assay of water content and specific gravity in normal and pathological autopsy brain has been correlated with CCT attenuation values obtained just prior to brain cutting. Formalin fixation does not alter normal values so that fixed brain appears to be suitable for this type of study. Low attenuation values in CCT correlate better with changes in specific gravity, rather than water in infarcts, but they have a close relationship to water content in edema. The high water content in infarcts of the white matter reveals a striking disparity in fluid control between cortex and white matter, which has not been emphasized in experimental studies. Water movement within and around blood clots has been discussed.

Body Water↗

Use of the Doppler flowmeter in stroke prevention.

The directional Doppler flowmeter can be used to identify collateral patterns of extracanial arterial blood flow that are associated with hemodynamically significant lesions of the internal carotid artery. The use of this non-invasive technique can identify accurately those patients who are candidates for angiographic confirmation.

Carotid Arteries↗

In vitro induction of tumour-specific immunity. I. Development of optimal conditions for induction and assay of cytotoxic lymphocytes.

A microculture system for in vitro induction of tumour-specific immunity with syngeneic spleen cells and plasma-cell tumours is described. The system generates cytoxic lymphocytes assessed by their ability to lyse 51Cr-labelled target cells in a microcytotoxicity assay. Both the inductive and effector phases are subject to many variables in material and methodology and the optimal conditions are defined in this study. Of particular importance are the responder- to stimulator-cell ratios, the presence of 2-mercaptoethanol, the day of harvest, the method of target-cell 51Cr labelling, and preincubation of the cytotoxic lymphocytes prior to assay.

Animals↗

Atypical fibromuscular hyperplasia involving the carotid artery.

A case of atypical fibromuscular hyperplasia involving the carotid artery in a 38-year-old male is described. The lesion, with associated intimal disruption and subintimal hematoma, caused cerebral embolus and transient neurologic dysfunction. Segmental resection and autogenous graft reconstruction of the carotid artery were successful in removing the lesion and preventing subsequent symptoms.

Adult↗