PubMed Health⌕ Search

Biomedical subjects

T E Stacey

Publications and source records attributed to T E Stacey.

At least 37 records · Page 2Linked to original sources
PubMed1985

Dizygotic twins with 3-hydroxy-3-methylglutaric aciduria; unusual presentation, family studies and dietary management.

A 4-month-old infant with hypotonia and macrocephaly was diagnosed as having 3-hydroxy-3-methylglutaric aciduria, using gas chromatography and mass spectrometry and confirmatory enzyme studies. The same diagnosis was made on his asymptomatic non-identical twin. Examination of the pedigree is consistent with an autosomal recessive mode of inheritance. Dietary treatment improved the symptoms of the propositus, but did not prevent episodes similar to Reye's syndrome in both twins. One such episode closely followed immunisation and our experience suggests that children with this disorder should be observed carefully following immunisation. These episodes were accompanied by an overflow of a wide range of abnormal metabolites. Examination of the urine for organic acids should be considered in infants with unexplained hypotonia and macrocephaly, especially if accompanied by abnormal biochemical indices.

Acidosis↗
PubMed1984

Urinary excretion of l-carnitine and acylcarnitines by patients with disorders of organic acid metabolism: evidence for secondary insufficiency of l-carnitine.

Concentrations of l-carnitine and acylcarnitines have been determined in urine from patients with disorders of organic acid metabolism associated with an intramitochondrial accumulation of acyl-CoA intermediates. These included propionic acidemia, methylmalonic aciduria, isovaleric acidemia, multicarboxylase deficiency, 3-hydroxy-3-methylglutaric aciduria, methylacetoacetyl-CoA thiolase deficiency, and various dicarboxylic acidurias including glutaric aciduria, medium-chain acyl-CoA dehydrogenase deficiency, and multiple acyl-CoA dehydrogenase deficiency. In all cases, concentrations of acylcarnitines were greatly increased above normal with free carnitine concentrations ranging from undetectable to supranormal values. The ratios of acylcarnitine/carnitine were elevated above the normal value of 2.0 +/- 1.1. l-Carnitine was given to three of these patients; in each case, concentrations of plasma and urine carnitines increased accompanied by a marked increase in concentrations of short-chain acylcarnitines. These acylcarnitines have been examined using fast atom bombardment mass spectrometry in some of these diseases and have been shown to be propionylcarnitine in methylmalonic aciduria and propionic acidemia, isovalerylcarnitine in isovaleric acidemia, and hexanoylcarnitine and octanoylcarnitine in medium-chain acyl-CoA dehydrogenase deficiency. The excretion of these acylcarnitines is compatible with the known accumulation of the corresponding acyl-CoA esters in these diseases. In this group of disorders, the increased acylcarnitine/carnitine ratio in urine and plasma indicates an imbalance of mitochondrial mass action homeostasis and, hence, of acyl-CoA/CoA ratios. Despite naturally occurring attempts to increase endogeneous l-carnitine biosynthesis, there is insufficient carnitine available to restore the mass action ratio as demonstrated by the further increase in acylcarnitine excretion when patients were given oral l-carnitine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyl-CoA Dehydrogenases↗
PubMed1983

Volumes of distribution of sodium and albumin in the sheep placenta.

The volumes of distribution of 22Na and 24Na, 51Cr-EDTA and albumin labelled with 131I and 125I were measured in cotyledons and skeletal muscle taken from pregnant sheep and the fetuses near term. Radiolabelled substances were injected through chronically implanted catheters 0.5-3.2 hr before removal of tissues in 'short-term' experiments and 24-26 hr before in 'long-term' experiments. Volumes of distribution were expressed as percentages of tissue weights. Cotyledonary water content was 81.5 +/- 0.6% (S.E. of mean) of wet weight (n = 10 sheep). Sodium content was 76.0 +/- 4.0 m-mole kg-1 wet weight (n = 4) and potassium content was 58.8 +/- 2.4 m-mole kg-1 wet weight (n = 4). In short-term studies cotyledonary spaces following injection into the fetal circulation were: Na, 20.5 +/- 0.9% (n = 10 sheep); Cr-EDTA, 19.5 +/- 1.2% (n = 3); and albumin, 2.8 +/- 0.3% (n = 11). The equivalent maternal cotyledonary spaces were: Na, 23.5 +/- 1.6%, or 22.1 +/- 1.6% when 'corrected' for fetal radioactivity (n = 8); and albumin, 4.7 +/- 0.8% (n = 8). Maternal and fetal cotyledonary sodium spaces were additive. Larger cotyledons had larger fetal sodium spaces. In long-term studies, the value for maternal albumin spaces was considerably higher 12.3 +/- 3.2% (n = 3), whereas that for fetal albumin spaces was only 3.9 +/- 0.4% (n = 4). The higher fetal sodium space of 24.9 +/- 1.0% (n = 4) in the long-term experiments was attributable to rising sodium counts in the maternal circulation. In the short-term experiments maternal skeletal muscle spaces were Na, 13.5 +/- 1.3% (n = 7) and albumin, 1.7 +/- 0.3% (n = 7), with higher values of 22.0% (n = 2) and 3.8 +/- 0.2% (n = 3) respectively in long-term experiments. In the short-term experiments fetal skeletal muscle spaces were Na, 32.8 +/- 3.2% (n = 7) and albumin, 2.5 +/- 0.3% (n = 10), with higher values of 39.7 +/- 7.4% (n = 4) and 16.2 +/- 0.6% (n = 4) respectively in long-term experiments.

Animals↗
PubMed1983

Metabolic response to carnitine in methylmalonic aciduria. An effective strategy for elimination of propionyl groups.

Patients with methylmalonic aciduria have an excessive intramitochondrial accumulation of acylcoenzyme A compounds that may reduce the availability of free coenzyme A (CoA) for normal metabolic requirements, producing profound metabolic disturbances. Giving carnitine to a patient with methylmalonic aciduria produced an increase in hippurate excretion (an index of intramitochondrial adenosine triphosphate (ATP) and CoA availability), a large increase in short chain urinary acylcarnitines, and a reduction in excretion of methylmalonate and methylcitrate. These acylcarnitines were shown by fast atom bombardment and B/E linked scan mass spectrometry to be propionylcarnitine and acetylcarnitine. Carnitine acts by removing (detoxifying) propionyl groups, thereby releasing CoA and restoring ATP biosynthesis and concentrations towards normal. L-carnitine may play a central role in maintenance of mitochondrial and cellular homoeostasis in methylmalonic aciduria and propionic acidaemia. These principles may provide an approach to the treatment of this and other disorders, inherited and acquired, in which accumulation of acyl CoA metabolites results in sequestration of free CoA, thereby perturbing metabolic homoeostasis.

Acetylcarnitine↗
PubMed1980

Maternofetal electrical potential difference in conscious sheep: effect of fetal death or acidosis.

Maternofetal electrical potential difference (pd) was measured in conscious pregnant ewes during the last 40 days of gestation. Recordings were made via catheters filled with saline solution and chronically implanted in at least two blood vessels on either side of the placenta. The pd ranged between -14 and 93 mV, mother positive. The mean potential declined from 54 +/- 8 mV (n = 5) immediately after operation to 28 +/- 7 mV after 48 hours and did not alter significantly thereafter. The pd increased with fetal acidosis induced by infusion of acid. The mean slope was 54 +/- 11 mV per pH unit (n = eight infusions). The pd rose when the fetus died, but was abolished by killing the ewe. The pd 1 day postoperatively fell with increasing gestational age (pd = 164 - 1.00 x days; p < 0.05, n = 41 sheep).

Allantois↗
PubMed1978

Fetomaternal transfer of glucose analogues by sheep placenta.

The steady-state permeability of the placenta to radiolabeled 3-O-methyl--D-glucopyranose (3MeG), alpha-methyl-D-glucopyranoside (AMG), and D-xylose was measured in chronically catheterized conscious sheep near term. Fetomaternal flux was calculated by application of Fick's principle to the uterine circulation after injection to the fetus. At a fetal glucose concentration of 10.2 +/- 1.25 mM, the permeability of 3MeG was half the maximal value of 59.5 +/- 11.2 ml/min found by extrapolation to zero glucose concentration. The permeability to 3MeG is considerably greater than is compatible with restricted diffusion, which together with the competitive effect of D-glucose suggests a carrier-mediated transfer mechanism. The permeability to AMG was less than 0.1 ml/min. The specificity pattern of sugar transport from the fetal side of the sheep placenta is different from that reported for gut lumen or kidney tubule in other species. D-Xylose is not metabolically inert after its injection into the fetal lamb.

Animals↗
PubMed1978

Bidirectional sodium fluxes across the placenta of conscious sheep.

Conscious pregnant sheep in the last 3 wk of gestation were studied 1--3 days after surgery. Fetal plasma sodium concentration was significantly lower than maternal. A mean electrical potential difference (PD) of 34 +/- 4 (SE) mV (n = 24) was recorded between maternal and fetal intravascular catheters, the mother being positive with reference to fetus. Unidirectional fetomaternal (Jf leads to m) and maternofetal (Jm leads to f) sodium fluxes were determined by application of Fick's principle to uterine and umbilical circulations following injection of 22NaCl or 24NaCl to fetus or mother, respectively. Blood flows were measured by an antipyrine technique. Jm leads to f = 0.142 +/- 0.029 mmol/min (n = 10); Jf leads to m =0.137 +/- 0.015 mmol/min (n = 21). Jm leads to f increased as a linear function of calculated fetal weight. In seven sheep both Jm leads to f and Jf leads to m were measured in a single experiment. The measured ratio Jm leads to f/Jf leads to m was significantly different from the ratio predicted using Ussing's flux ratio equation. There is probably a transplacental sodium pump active in the direction fetus to mother.

Animals↗
PubMed1977

Placental permeability in the sheep.

The transplacental flux of different radiolabelled substances was measured, according to Fick's principle, in chronically catheterised pregnant sheep (124 to 143 days of gestation). Knowing the uterine blood flow, it was possible to calculate the net flux and derive a permeability coefficient, K. With 14C erythritol, K soon reaches its ultimate value, thus suggesting there is only one rate-limiting step to transfer and no significant middle compartment in the sheep placenta. The comparison of feto-maternal fluxes of different metabolically inert, lipid insoluble molecules (urea, erythritol, mannitol and Cr-EDTA) demonstrates a very sharp decrease in permeability as molecular size increases. The membrane behaves like a tight epithelium, with pores of of an approximate radius of 0.45 nm which allow but a poor passive diffusion. On the contrary, permeability to 3 methylglucose and 2 deoxyglucose is much too high for passive diffusion. Transfer competition between D-glucose and 3 methylglucose affords other evidence for a stereospecific monosaccharide carrier. The relationship between the presumably "active" sodium flux out of the fetus and the electrical potential difference across the placenta is discussed. The fetus is usually negative to the mother but the potential difference changes from day to day, and in twin gestation, the respective fetomaternal potentials seem to be independent. Acid infusion to the fetus increases the potential difference. The maintenance of this electrical or chemical gradients is taken as a consequence of the low passive permeability of the placenta.

Animals↗
PubMed1976

Permeability of the sheep placenta to unmetabolized polar non-electrolytes.

1. The rate of appearance in uterine venous blood of radioactively labelled, polar, non-electrolytes has been measured following their injection into the foetal circulation in the chronically catheterized sheep near term. Uterine blood flow was measured by an antipyrine technique. 2. Estimates of a placental permeability constant not corrected for area were 61-2 +/- 5-5 ml. min-1 (mean +/- S.E. of mean) for [14C] urea, 1-85 +/- 0-16 for [14C]erythritol and 0-21 +/- 0-03 for [3H]mannitol. Results are also presented for [14C]ethylene glycol, [14C]L-glucose, [14C]mannitol, [51Cr] EDTA and [3H] and [14C]sucrose. 3. In four sheep, permeability measurements for several solutes were made and the results were analysed in terms of restricted diffusion via cylindrical, water-filled pores. Calculation of pore radius was made by a minimum variance method and values ranging from 0-43 to 0-45 nm were obtained. 4. Stability and absence of protein binding of probe molecules was investigated by gel permeation on Sephadex columns.

Animals↗