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R Causon

Publications and source records attributed to R Causon.

18 recordsLinked to original sources
PubMed1998

The electroanalysis of mannitol, xylose and lactulose at copper electrodes: voltammetric studies and bioanalysis in human urine by means of HPLC with electrochemical detection.

The electrochemical behavior of mannitol, xylose and lactulose has been investigated at a copper working electrode. A sensitive, accurate and precise method employing HPLC with electrochemical detection in the d.c. amperometric mode, has been developed and validated for the determination of mannitol and lactulose in human urine. The ratio of these probe carbohydrates is altered in conditions that cause damage to the intestinal mucosal barrier. Systematic studies employing cyclic voltammetry indicate that the electrode reaction involves an electrocatalytic oxidation of each carbohydrate in a process yielding a single irreversible anodic wave that is dependent on the ionic strength of the sodium hydroxide supporting electrolyte solution. High performance liquid chromatography with electrochemical detection was performed using a thin-layer cell housing a custom manufactured copper working electrode. The optimized HPLC method can detect 72, 57 and 419 pg of mannitol, xylose and lactulose injected on column, respectively. The corresponding linear calibration ranges are 359 pg-2.24 microgram, 57.4 pg-896 ng and 419 pg-262 ng, respectively. Solid-phase extraction of human urine on polar sorbents, and direct injection after simple 1 + 99 dilution in 0.025 M NaOH were compared for bioanalysis. Direct injection was selected for further method developed as the technique proved robust and simple. The optimized method was validated for the determination of mannitol and lactulose in human urine over the concentration ranges predicted when assessing intestinal permeability (0.25-2.5 mg ml-1 mannitol and 0.05-1.0 mg ml-1 lactulose). Over these ranges intra- and inter-assay bias is < +/- 6.5%, and imprecision (coefficient of variation) is < 9% for each carbohydrate. The validated method provides a useful alternative to HPLC with pulsed-amperometric detection at gold electrodes.

Chromatography, High Pressure Liquid↗
PubMed1997

Validation of chromatographic methods in biomedical analysis. Viewpoint and discussion.

Bioanalytical method validation is the process used to establish that a quantitative analytical method is suitable for biomedical applications. Reassurances as to the quality of the method and its reliability come from adopting a minimum series of validation experiments and obtaining satisfactory results. Consistent evaluation of the key analytical parameters: recovery, response function, sensitivity, precision, accuracy, selectivity and stability, is discussed with a view to improving scientific standards in manuscripts submitted for publication.

Chromatography↗
PubMed1990

DOPA decarboxylase inhibition does not influence the diuretic and natriuretic response to exogenous alpha-atrial natriuretic peptide in man.

The role of dopamine synthesis in the renal actions of human alpha-atrial natriuretic peptide (alpha ANP) was investigated in six dehydrated volunteers using the DOPA decarboxylase inhibitor carbidopa. Each subject received oral placebo or carbidopa (100 mg) followed by an infusion of alpha ANP 10 pmol.kg-1.min-1 for 1 h. The responses to placebo alone and to carbidopa alone were investigated on separate occasions. alpha ANP produced a similar increase in plasma immunoreactive alpha ANP whether placebo or carbidopa pretreatment had been given. Urinary dopamine excretion was increased by alpha ANP. Carbidopa pretreatment substantially attenuated this increase without affecting the natriuretic or water-diuretic response to alpha ANP. Carbidopa also failed to alter the change in filtration fraction produced by alpha ANP. The results suggest that increased synthesis of intrarenal dopamine is not required for the renal effects of alpha ANP in man.

Adult↗
PubMed1989

Differential effect of high-dose naloxone on the plasma adrenaline response to the cold-pressor test.

1. Although the opiate antagonist naloxone has been shown to affect sympathoadrenomedullary function in some studies, this has not been a uniform finding in all investigations, using different doses of naloxone. We have therefore investigated the actions of saline placebo and increasing bolus doses of intravenous naloxone (25, 100 and 250 micrograms/kg) on the plasma noradrenaline, adrenaline, adrenocorticotrophin (ACTH) and cortisol responses to a cold-pressor test in six males and two females in a double-blind randomized study. 2. Basal levels of adrenaline did not differ on any of the study occasions: the cold-pressor stimulus produced a significant rise in mean plasma adrenaline to a peak of 0.16 nmol/l, with a peak incremental rise of 0.08 nmol/l. In the presence of the two higher doses of naloxone, the incremental rise in the mean adrenaline level was significantly enhanced, reaching 0.30 nmol/l at 100 micrograms of naloxone/kg and 0.29 nmol/l at 250 micrograms of naloxone/kg, with no significant enhancement observed at the lowest dose of naloxone. The rise in plasma noradrenaline, systolic and diastolic blood pressure and pulse rate during the cold-pressor test was not consistently altered by any dose of naloxone, but there was a significant trend for the degree of discomfort to increase with the dose of naloxone. 3. Neither plasma ACTH nor serum cortisol rose in response to the cold-pressor stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1987

Bio-medical applications of high performance liquid chromatography (HPLC) with amperometric detection.

Electrochemical detection of eluted solutes in HPLC is now well established as a selective and highly sensitive technique. Measurement of catecholamines and metabolites has been the most popular application with an exponential increase in literature. Recent improvements include the use of diphenylborate for extractions, the introduction of smaller diameter HPLC materials which improve resolution and sensitivity, and the replacement of carbon paste with glassy carbon which now gives a more stable electrode with similar sensitivity. Applications of HPLC with amperometric detection to the determination of drugs, amino acids and peptides are discussed.

Animals↗
PubMed1987

Location of extra-adrenal catecholamine secreting tumours by selective venous sampling and nuclear magnetic resonance scanning.

Iodinated meta-iodobenzylguanidine (MIBG) scanning is a safe non-invasive method for locating extra-adrenal paragangliomas. However, a positive result is dependent on the presence of an uptake mechanism in the tumour. We report two cases of MIBG negative intracranial catecholamine secreting tumours successfully located by selective venous sampling and nuclear magnetic resonance scanning.

3-Iodobenzylguanidine↗
PubMed1987

Neuropeptide Y and its flanking peptide in human endocrine tumors and plasma.

Neuropeptide Y (NPY) and its flanking peptide (CPON) were measured in extracts of pheochromocytomas (n = 26), ganglioneuroblastomas (n = 8), and other tumors (n = 95) and plasma (n = 38). NPY was present in high concentrations in the majority of the pheochromocytomas, but was absent in 3 tumors. Similar concentrations of NPY were measured using N- and C-terminal-directed antisera, and there was a good correlation between the concentrations of NPY immunoreactivity and CPON immunoreactivity in the same extracts. Gel permeation chromatography revealed that the separate peptides NPY and CPON were the major products. No significant amounts of a large mol wt precursor containing both immunoreactivities was found. Among the other tumors, 6 of 22 carcinoid tumors, 2 of 2 somatostatinomas, and 3 of 18 insulinomas contained detectable amounts of NPY. Plasma NPY concentrations were very low in normal subjects, and extraction and a 10-fold concentration step were necessary to establish the normal range (0.35-1.25 pmol/L). Plasma NPY concentrations were detectable in unextracted plasma (10 pmol/L) in 50% of patients with pheochromocytomas, but no correlation was found between plasma NPY concentrations and either plasma norepinephrine or epinephrine concentrations. These results indicate that 1) NPY and CPON are present in most, but not all, pheochromocytomas and ganglioneuroblastomas; 2) secretion of NPY immunoreactivity may be independent of that of catecholamines; 3) CPON immunoreactivity is present in plasma of patients with pheochromocytoma; 4) the majority of NPY and CPON immunoreactivities appears to be in the form of the separate free peptide, and there is very little precursor containing both immunoreactivities expressed in these tumors; and 5) NPY immunoreactivity is present in a variety of other endocrine tumors.

Chromatography, Gel↗
PubMed1985

The effects of L-DOPA on regional cerebral blood flow and oxygen metabolism in patients with Parkinson's disease.

Studies performed on 18 patients with Parkinson's disease and 6 control subjects have shown that acute administration of L-DOPA in clinically effective doses gives rise to a diffuse increase in regional cerebral blood flow without accompanying stimulation of regional oxygen utilization. The data suggest that this rise in rCBF is caused by vasodilatation due to a direct action of the drug on the cerebral blood vessels. The effect of L-DOPA on rCBF did not correlate with the degree of clinical improvement seen in each patient after treatment. The therapeutic effect of L-DOPA in the brain was not reflected in any change of regional cerebral oxygen utilization as measured by our technique. We suggest that the pharmacological actions of L-DOPA in the brain take place on at least two different levels.

Adult↗
PubMed1984

Neutrophil chemotactic activity and histamine in atopic and nonatopic subjects after exercise-induced asthma.

Seven atopic and 6 nonatopic asthmatics with exercise-induced asthma were subjected to a treadmill exercise task. After this procedure, both groups had elevations in the concentrations of plasma histamine and serum high molecular weight neutrophil chemotactic activity (as assessed by Sephadex G-200 chromatography). These findings support the view that the release of mast-cell-associated mediators can be independent of the atopic state.

Adolescent↗
PubMed1983

Plasma amine and hormone changes in 'post-partum blues'.

The relationship between hormone levels, plasma catecholamines, and mood disturbances has been investigated in 44 patients during days 2 to 5 of the immediate post-partum period. Fifty-two per cent of the mothers showed periods of emotional lability although there was no significant correlation between plasma concentrations of FSH, prolactin, oestrone, oestradiol, cortisol, or progesterone and the incidence of post-partum blues. In contrast there was a significant reduction of circulating catecholamines which correlated with mood disturbances. Women who experienced only a single day of post-partum blues had significantly lower levels of noradrenaline and adrenaline on that day compared with preceding or subsequent days.

Adult↗
PubMed1982

The effects of nifedipine and hydralazine induced hypotension on sympathetic activity.

To determine whether inhibition of sympathetic activity is a factor in calcium antagonist induced hypotension, plasma noradrenaline was measured after intravenous infusion of hydralazine (25 mg) and the calcium antagonist nifedipine (4 mg) in 6 hypertensive males. The resultant reduction in mean blood pressure (12.4% and 14.2% respectively) was accompanied by similar increases in heart rate and plasma noradrenaline concentration. These results suggest that calcium slow channel blockade does not inhibit noradrenaline release from sympathetic nerves and that nifedipine induced hypotension is independent of such a mechanism.

Adult↗
PubMed1982

A novel double-isotope technique for the enzymatic assay of plasma histamine: application to estimation of mast cell activation assessed by antigen challenge in asthmatics.

The concentration of plasma histamine may provide an index of mast cell activation (degranulation) and can be measured by a sensitive radioenzymatic assay based on its specific conversion to (3H)-methylhistamine in the presence of histamine-N-methyltransferase and (3H)-S-adenosyl-L-methionine. In this assay, the separation of excess (3H)-S-adenosyl-L-methionine from (3H)-methylhistamine requires several steps, for which a correction factors is necessary to maintain precision. In the present modification, duplicate 50-microliters aliquots of each plasma sample were incubated with histamine-N-methyltransferase and (3H)-S-adenosyl-L-methionine. A further aliquot, with an added standard of 200 ng/ml histamine, was incubated with histamine-N-methyl-transferase and (14C)-S-adenosyl-L-methionine. This standard was converted to (14C)-methylhistamine, and its recovery at the end of the assay corrected both for varying efficiency of methylation among plasma samples and for losses during the subsequent extraction and separation stages. The sensitivity of the assay was 25 pg/ml. The intra-assay and interassay coefficients of variation were 7.2% and 11.6%, respectively. In five asthmatics, antigen challenge caused a 28% fall in FEV1, and this was associated with a twofold to threefold rise in plasma histamine concentration. This assay may thus prove a useful method for assessing the role of mast cell release of mediators in vivo.

Adult↗
PubMed1982

Exercise-induced release of histamine and neutrophil chemotactic factor in atopic asthmatics.

Concentrations of plasma histamine and serum neutrophil chemotactic factor (NCF) were measured in seven atopic asthmatics who developed exercise-induced asthma (EIA) after a treadmill task. The results were compared with those obtained after inhalation of specific antigen or methacholine. Plasma histamine concentrations were measured with a novel double-isotope radiometric assay, and NCF was identified by its elution in the void volume fractions of Sephadex G-200 and as a single peak of activity at approximately 0.20 molar NaCl after anion exchange chromatography on diethylaminoethyl-Sephacel (pH 7.8). After exercise or antigen challenge, the time courses of appearance of both mediators were virtually identical and accompanied the increase in airways obstruction. There was a statistically significant correlation between the concentrations of histamine or NCF and the magnitude of airflow obstruction after exercise and antigen challenge. This suggested that there may be a direct association between mediator release and EIA or antigen-induced bronchoconstriction. In contrast, there were no significant elevations in circulating histamine and NCF after inhalation of methacholine, at concentrations giving a fall in FEV1 comparable to that induced by exercise or antigen. The prior administration of cromolyn to three asthmatics inhibited both their EIA and the release of histamine and NCF. When four asthmatics were exercised for periods of 1, 3, and 6 min, the release of NCF and fall in peak expiratory flow rate were directly related to the duration of the exercise. The rise of NCF activity in subjects with EIA was fivefold greater than that observed in asthmatics who did not experience airways obstruction when subjected to the same exercise task. These results provide further evidence that mediators of hypersensitivity are released during EIA.

Adolescent↗
PubMed1982

The effect of disodium cromoglycate on rectal mucosal histamine release, eosinophil exudation and disease activity in active ulcerative colitis.

Disodium cromoglycate has been reported to benefit some patients with active ulcerative colitis. We have investigated the effect of cromoglycate in high dose on rectal mucosal mast cell degranulation (assessed indirectly by measurement of mucosal histamine release, using in vivo rectal dialysis, and the eosinophil content of the rectal inflammatory exudate) and on disease activity in eight patients in relapse. Although cromoglycate (1600 mg by mouth daily for 2 weeks) did not affect histamine release, it reduced (P less than 0.05) the eosinophil content of the exudate towards normal. Stool frequency also fell (P less than 0.05) but other aspects of bowel habit, sigmoidoscopic appearance, rectal mucosal potential difference and electrolyte transport were unaltered. Pre-treatment values of histamine release and eosinophil exudation could not be used to predict the response to cromoglycate. The reduction in eosinophil exudation produced by the drug could be due to inhibition of mast cell release of chemotactic factors other than histamine; the therapeutic effect of cromoglycate was unimpressive.

Adult↗