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Biomedical subjects

W Snedden

Publications and source records attributed to W Snedden.

51 records · Page 3Linked to original sources
PubMed1976

The direct determination of oestrogen and progesterone in human ovarian tissue by quantitative high resolution mass spectrometry.

The concentration of oestrone, oestradiol and progesterone in ovarian tissue have been determined directly by quantitative high resolution mass fragmentography without the necessity of extraction or purification. The changes in the levels of these steroids in the ovary throughout a 28 day period correlate well with those measured in plasma and also with those of the corresponding metabolites excreted in urine. Some benign ovarian tumours (cysts) have been shown to contain abnormally large amounts of progesterone.

Corpus Luteum↗
PubMed1976

A method for the measurement of ultra-low amounts of prostaglandins in inflammatory exudates using gas chromatography and mass spectrometry.

A GC-MS assay for PGE2 and PGF2alpha has been described. The method is highly specific and sensitive down to the sub-picogram level. The assay has been used to measure the time dependence of PG concentration in carrageenan-induced inflammatory exudates and the results compared with a bioassay. Estimates of the extraction and purification yield of PGs from exudates have also been obtained.

Animals↗
PubMed1976

Massive excretion of 2-oxoglutaric acid and 3-hydroxyisovaleric acid in a patient with a deficiency of 3-methylcrotonyl-CoA carboxylase.

A three-month old child, presenting with a history of feeding problems, suspected respiratory infection and failure to thrive, later developed fits and a profound irreversible metabolic acidosis. Chromatographic investigation of the urine revealed a gross excretion of 2-oxoglutaric and 3-hydroxyisovaleric acids. The identity of these two acids was confirmed by mass spectrometry. Enzyme studies on liver obtained at post-mortem demonstrated a deficiency of 3-methylcrotonyl-CoA:carbon dioxide ligase (ADP) (EC 6.4.1.4).

Crotonates↗
PubMed1975

The measurement of urinary digoxin and dihydrodigoxin by radioimmunoassay and by mass spectroscopy.

A radioimmunoassay for urinary digoxin is described which includes an initial solvent extraction to remove factors in urine which cause non-specific interference in the assay. The recoveries obtained using different solvents are compared and the non-specific factors influencing the assay investigated further. These effects were overcome by the use of a small urine volume (10 mul) in a direct, unextracted, urine assay and the results obtained correlated closely with those from the assay using prior extraction (r=0.99). No false positive results were obtained with unextracted urine samples from hospitalised patients not receiving digoxin. The specificity was also determined with regard to the natural steroids, spironolactone and the metabolites of digoxin including dihydrodigoxin. The metabolite dihydrodigoxin, with a saturated lactone ring, was not detected whereas the mono-, and bis-digitoxo-sides and digoxigenin metabolites did cross react in the assay. It was not possible to separate dihydrodigoxin and digoxin by thin-layer chromatography or solvent extraction due to their similar structures, however, mass spectroscopy was successful in this respect and was employed to obtain the ratio of dihydrodigoxin to digoxin in extracted urine samples. Levels of urinary digoxin excreted by patients maintained on different oral doses of the drug were measured. The percentage excreted in the urine as digoxin correlated closely with the oral dose (r = 0.96) but was found to be lower than that reported in most previous studies. Mass spectroscopy measurements showed that an average of 16.4% (range 12.2-19.7%) of the total oral dose was excreted as dihydrodigoxin in the urine of nine patients investigated.

Animals↗
PubMed1975

Ammonia and urea transport by the excluded human colon.

1. Ammonia and urea transport across the colonic mucosa was studied by a perfusion technique in four subjects with colonic exclusion for chronic hepatic encephalopathy. 2. Reduction of luminal pH inhibited net and unidirectional transport of ammonia from lumen to plasma, but net absorption from high luminal concentrations persisted at low pH. 3. Neither addition of urea to the perfusate nor intravenous infusion of urea produced a consistent increase in the colonic excretion of ammonia when ammonia-free solutions were perfused. 4. In one subject intravenous infusion of (15N)-ammonium chloride produced rapid labelling of colonic effluent ammonia and within 60 min the specific enrichments of ammonia in effluent and in arterial plasma were approximately equal. 5. During perfusion of nitrogen-free solutions, only small amounts of urea appeared in the effluent, suggesing limited permeability of the colonic mucosa to urea. 6. These results are discussed in relation to the equilibration of ammonia across the colonic mucosa by both ionic and non-ionic diffusion. The lack of evidence of 'juxtamucosal' (as opposed to luminal) ureolysis is in contrast to other observations on the intact colon. The possible reasons for and implications of this discrepancy are discussed.

Ammonia↗
PubMed1969

The conversion of 4-hydroxypyrazolo[3,4-d]pyrimidine (allopurinol) into 4,6-dihroxypyrazolo[3,4-d]pyrimidine (Oxipurinol) in vivo in the absence of xanthine-oxen oxidoreductase.

1. A patient with congenital deficiency of xanthine oxidase (EC 1.2.3.2) (xanthinuria) excreted the xanthine isomer 4,6-dihydroxypyrazolo[3,4-d]pyrimidine (oxipurinol) in his urine when the hypoxanthine isomer 4-hydroxypyrazolo[3,4-d]pyrimidine (allopurinol) was given by mouth. 2. The identity of the oxipurinol that the patient excreted was established by mass spectrometry. 3. The mass spectra and infrared spectra of allopurinol, oxipurinol, hypoxanthine and xanthine are compared. 4. A mechanism for the fragmentation of these compounds that occurs during their mass-spectrometric investigation is proposed. 5. A possible metabolic pathway for the oxidation of allopurinol to oxipurinol in the absence of xanthine oxidase is discussed.

Adult↗
PubMed1969

The mass-spectrometirc identification of hypoxanthine and xanthine ('oxypurines') in skeletal musce from two patients with congenital xanthine oxidase deficiency (xanthinuria).

1. The presence of hypoxanthine and xanthine in the skeletal muscle of two patients with congenital xanthine oxidase deficiency (xanthinuria) was demonstrated by high-resolution mass spectrometry. 2. Evidence was obtained for the presence of a trace of hypoxanthine only in normal muscle. 3. Dry pulverized tissue was introduced directly into the mass spectrometer and preliminary chemical processing of the tissue was therefore unnecessary. 4. The criteria for the mass-spectrometric identification of hypoxanthine and xanthine in the tissue and the significance of the observations are discussed.

Adult↗
PubMedDate not supplied

Hemodynamic and adrenergic responses of bevantolol and propranolol in hypertensives.

The hemodynamic and neurohumoral responses of 21 thiazide-resistant hypertensives receiving sequential chronic therapy with propranolol and bevantolol, a new cardioselective beta-1 blocker, were studied and compared with their responses to placebo. The objective was to determine to what extent decreased circulation levels of catecholamines and renin activity contributed to the hypotensive action of bevantolol and whether it demonstrated a significant sparing effect on vascular resistance. Both propranolol and bevantolol lowered supine and erect blood pressures to a comparable extent but the response of diastolic pressure to upright posture was maintained. Resting heart rates were lowered and postural tachycardia was attenuated. Propranolol induced a greater decrease in forearm blood flow and greater increase in vascular resistance than bevantolol. Both drug therapies were associated with lowered plasma concentrations of noradrenaline and adrenaline, while the decrease in noradrenaline levels was linearly related to the fall of mean arterial pressure for both drugs. Plasma renin activity was lowered only to a marginal extent by either drug but aldosterone concentrations were significantly reduced to a comparable extent by both drugs. The results suggest that a negative chronotropic action on the heart and an overall reduction in sympathetic nervous tone both contribute to the hypotensive effects of bevantolol and propranolol, but reduction of plasma renin activity may be of lesser importance. Bevantolol demonstrated a significant vascular sparing effect in this patient group compared with propranolol.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Cardiac hypertrophy in experimental hypertension: interaction of the sodium ion, blood pressure and lisinopril.

The interaction of blood pressure, salt intake and the inhibition of angiotensin converting enzyme activity with cardiac hypertrophy were examined in the Dahl rat model. Eight-week-old salt sensitive and salt resistant rats were each separated into two colonies, one of which was maintained on a low salt and the other on a high salt diet for three weeks, at the end of which time both salt sensitive colonies were hypertensive. Each colony was then separated into two groups, one received no medication the other was given lisinopril until normotension was achieved. After 11 weeks of therapy, intra-arterial blood pressures and heart rates were recorded. The rats were sacrificed and heart weight to body weight ratios were determined. Both untreated salt sensitive groups displayed marked cardiac hypertrophy which correlated well with diastolic blood pressure irrespective of salt intake. Lisinopril therapy lowered blood pressures to normotensive levels in all groups except for salt sensitive rats ingesting a high salt diet where, despite a 10-fold increase in drug dose, normotension was not achieved. Significant cardiac regression accompanied lisinopril therapy in rats receiving low salt diets but high salt intake severely attenuated regression in both strains. There was no significant correlation between heart weight and blood pressure in the treated groups. The results suggest that cardiac regression appears to be mediated by other factors besides ventricular afterload pressure and that high salt intake adversely affects blood pressure and heart weight response to lisinopril therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Correlation of left ventricular hypertrophy and its regression by lisinopril with salt-induced hypertension.

The interaction of salt with hypertension-induced left ventricular hypertrophy and its reversal by inhibition of angiotensin converting enzyme were studied in salt sensitive and salt resistant Dahl rats. Eight-week-old rats were fed either a low or high salt diet for three weeks. The colonies were then further divided and either treated with lisinopril or given no treatment for 11 weeks. Untreated salt sensitive rats had higher blood pressures than salt resistant animals. Left ventricular weight and wall thickness in both untreated salt sensitive groups was higher than in the resistant groups. Therapy lowered blood pressures in all groups but those of the high salt group remained higher than the low salt group. Reduction of left ventricular weight and wall thickness took place in either strain only when salt intake was low. Right ventricular and atrial weights were largely unaffected either by salt intake or drug therapy. Plasma renin activity increased and aldosterone levels decreased with lisinopril therapy in all groups except the salt sensitive, high salt group where both remained unchanged at low levels. Lisinopril was effective in reducing blood pressure and left ventricular hypertrophy, but both effects were severely impaired by high salt intake. The major determinant of left ventricular hypertrophy appeared to be afterload, as shown by a good correlation between left ventricular mass and systolic blood pressure, but there was some indication of a possible independent hypertrophic action of salt.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗