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Biomedical subjects

M Silver

Publications and source records attributed to M Silver.

At least 127 records · Page 7Linked to original sources
PubMed1989

Tricuspid and pulmonary atresia with coarctation of the aorta: a rare combination possibly explained by persistence of the fifth aortic arch with a systemic-to-pulmonary arterial connection.

A ten-day old baby was found to have tricuspid and pulmonary atresia, and a "ductal-dependent" pulmonary circulation that was prostaglandin-sensitive. An unusual coarctation of the aorta was not recognised until an autopsy was performed, some 11 days after construction of an aortopulmonary shunt. A previously undefined anomaly in this neonate was persistence of the fifth aortic arch with a systemic-to-pulmonary artery connection on the same side as the definitive aorta. The histology of the fifth aortic arch is consistent with the pattern of an arterial duct.

Aorta, Thoracic↗
PubMed1989

Cardiac and neurological abnormalities in v-fps transgenic mice.

Transgenic mice that widely express the v-fps protein-tyrosine kinase develop several independent pathological conditions, in addition to a high tumor incidence. v-fps expression and protein-tyrosine kinase activity in the heart were directly correlated with cardiac enlargement. This cardiomegaly was accompanied by severe myocardial and endocardial damage, which was concentrated in the left ventricular wall, and characterized by a progressive atrophy and necrosis of cardiac muscle fibers with concomitant fibrosis. This pathology was associated with congestive heart failure. Mice from five lines developed a marked trembling, correlated with expression of the v-fps transgene in the brain, and two lines showed a striking bilateral enlargement of the trigeminal nerves. Unlike tumor formation, these cardiac and neurological phenotypes were evident shortly after birth and showed 100% penetrance. The pleiotropic effects of the v-fps transgene suggest the involvement of protein-tyrosine kinases in mammalian neural development and cardiac function.

Animals↗
PubMed1989

Pituitary-adrenocortical activity in the fetal pig in the last third of gestation.

The responsiveness of the fetal adrenal to a rise in either endogenous or exogenous ACTH (adrenocorticotrophic hormone) was examined acutely in piglets between 70 and 105 days gestation (term, 115 days). In addition the pre-partum changes in plasma ACTH and cortisol were followed in chronically catheterized fetuses and the effect of a continuous intrafetal ACTH infusion on the time of delivery was also investigated. The acute experiments on ten sows were carried out (under sodium pentobarbitone) on twenty-five fetuses, sampled from a branch of the umbilical artery with minimal disturbance. A second sample was taken 10-20 min later after exteriorization or surgery (catheterization). Such fetal manipulation resulted in significant increases in plasma ACTH and cortisol from 70 days gestation and the responses increased with fetal age. No corresponding changes were seen in the controls or in the sow over the same period. An exogenous bolus of ACTH (200 ng ml-1 I.V.) evoked rises in fetal plasma cortisol comparable with the endogenous changes (+11 +/- 2 ng ml-1, n = 4). Chronic experiments were carried out on fourteen sows catheterized under sodium pentobarbitone anaesthesia at 95-100 days gestation; in fetuses sampled until delivery (at 111-114 days) gradual rises in both fetal plasma cortisol and ACTH were observed. There was a highly significant positive correlation between plasma cortisol and log plasma ACTH (r = 0.81, n = 52, P less than 0.001). Analysis of the basal values from the 70-100 day fetuses also showed a positive correlation (r = 0.47, n = 23, P less than 0.05) but the slope of the regression line was significantly less than that for the older fetuses indicating a greater adrenocortical response to a given level of ACTH nearer term. In five sows a continuous infusion of ACTH (0.125 mg day-1 for 4-5 days from about 100 days) was given to one or two fetuses per litter (total size, 7-12). This treatment resulted in a rise in fetal plasma cortisol to 85.4 +/- 8.9 ng ml-1, which was equivalent to that found during labour, but did not induce premature parturition.

Adrenocorticotropic Hormone↗
PubMed1989

The development of corticotrophs in the fetal sheep pars distalis: the effect of adrenalectomy or cortisol infusion.

At 90 days gestation a uniquely fetal-type and an adult-type corticotroph have been observed in the fetal sheep pars distalis (term approximately 147 days). Between 90 and 130 days gestation the fetal type is predominant, and its numbers decline toward term. In this study the effect of the endogenous cortisol surge on the change in the population of corticotrophs in the pars distalis was investigated in sheep fetuses after bilateral adrenalectomy at 120 days gestation or after an infusion of 2 mg cortisol/day between 109 and 115 days gestation. The total proportion of corticotrophs, expressed as a percentage, decreased significantly (P less than 0.01) from 115 days in saline-infused controls (21.09 +/- 1.10%) and 135 days in intact controls (14.59 +/- 1.12%). The percentage of adult-type corticotrophs increased significantly (P less than 0.01) from 5.65 +/- 0.77 at 115 days, to 11.93 +/- 1.41 at 135 days. The percentage of fetal-type corticotrophs decreased significantly (P less than 0.001) from 14.91 +/- 0.35 at 115 days to 2.33 +/- 0.48 at 135 days. A small proportion of ACTH-immunoreactive cells could not be defined as either adult- or fetal-type corticotrophs. These changes in the corticotroph population had not occurred at 135 days in fetuses that had been adrenalectomized at 120 days; the percentage of corticotrophs relative to unstained cells (21.70 +/- 0.46%), the percentage of adult-type corticotrophs (6.42 +/- 0.29%), and the percentage of fetal-type corticotrophs (14.65 +/- 0.49%) were similar to those in 115-day-old fetuses, indicating that the normal change in the corticotroph population between 115 and 135 days gestation was dependent upon the presence of the fetal adrenal. In fetuses exposed to exogenous cortisol between 109 and 115 days gestation, the percentage of corticotrophs relative to unstained cells (16.53 +/- 1.68%), the percentage of adult-type corticotrophs (12.40 +/- 1.34%), and the percentage of fetal-type corticotrophs (3.78 +/- 0.58%) were similar to those at 135 days. This indicates that a short period of increased fetal plasma cortisol can bring about premature maturation of the corticotrophs in the fetal sheep pars distalis. We have also described an ACTH-immunoreactive cell which has characteristics of both an adult- and a fetal-type corticotroph. Its morphological appearance suggests that it may be a transitional stage from the fetal- to the adult-type corticotroph.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗
PubMed1988

Preferential oxygen supply to the brain and upper body in the fetal pig.

In the fetal pig over 50% of the oxgenated umbilical venous blood bypasses the liver via vascular channels of over 100mu diameter which appear to act as a ductus venosus (DV). In the present experiments the oxygen levels (pO2, SO2 and O2 content) in the fetal carotid (CA) and femoral (FA) arteries were measured to determine whether preferential streaming of the oxygenated blood is maintained from the bypass to the foramen ovale and thence through the left heart to the upper body, as in other species. The results were obtained from 12 piglets catheterized and maintained in utero under sodium pentobarbitone anaesthesia. Significant CA-FA differences in pO2, SO2 and O2 content were observed in these fetuses during both normoxaemia and hypoxaemia showing that a higher level of oxygen can be maintained to the fetal head and brain over a wide range of oxygenation. These results confirm that the hepatic channels in the fetal piglet act as a fully functional DV.

Animals↗
PubMed1988

Demonstration of residual bone marrow effect in mice exposed to ethylene glycol monomethyl ether.

Ethylene glycol monomethyl ether (EGMME) has been reported to cause hematopoietic abnormalities in man. We have shown that mice exposed to EGMME post-natally have suppressed bone marrow cellularity and progenitor cells 8 weeks post-exposure which returns to normal values by 16 weeks. Studies were designed to determine whether EGMME exposed mice that recovered had evidence of residual marrow stem cell injury. B6C3F1 mice were injected subcutaneously with EGMME on days 1-5 after birth at doses of 0, 100, 200 and 400 mg/kg per day, allowed to recover, and stressed with 200 rads whole body irradiation at 15 and 21 weeks post-exposure. Bone marrow functions were examined during the recovery period. Mice that had been exposed to EGMME were more sensitive to irradiation and recovery of marrow cellularity and progenitor cell numbers occurred more slowly than in unexposed controls. This indicates that EGMME can cause persistent residual damage of bone marrow progenitor cells in mice, an effect that would not be apparent with routine hematological techniques.

Animals↗
PubMed1988

The foramen ovale of the foetal and neonatal foal.

Hearts from 24 foals were studied; 10 were from foetuses ranging in gestational age from 230 to 322 days and 14 were from newborn and young foals aged between birth and 17 days. The foramen ovale and associated vena caval and atrial structures were examined by scanning electron microscopy. Additional observations were made by light and transmission electron microscopy. A tube-like flap of tissue was observed, extending from the aperture in the caudal vena cava to the lumen of the left atrium. In the younger foetuses, the distal end of this tube was covered with a thread-like network of tissue. In animals nearer to term, the network was replaced by distal fenestrations. Protrusions were seen on the rim of the opening of the tube as it entered the atrium. The role that these may play, together with the significance of cardiac muscle and non-elastic connective tissue in the wall of the tube, were discussed with respect to possible mechanisms of closure of the foramen ovale.

Animals↗
PubMed1988

Inhibition of 3 beta-hydroxysteroid dehydrogenase in the sow near term: effects on fetal and maternal steroids and on delivery.

The effect of Epostane, a 3 beta-hydroxysteroid dehydrogenase inhibitor, on maternal and fetal plasma progesterone and other steroids has been investigated in chronically catheterized pregnant sows near term. Epostane (1-2 mg/kg) was given i.v. and samples withdrawn from the uterine vein and artery and a fetal artery. In seven sows tested at 106-110 d gestation (term 115 d) Epostane induced parturition 25 +/- 2.1 h later with the birth of live viable young (group 1). In four sows tested with the same dose of Epostane at 106-111 d gestation parturition was not induced (group 2). A rapid drop in maternal and fetal plasma progesterone occurred after Epostane; in group 1 maternal progesterone remained below 4 ng/ml until delivery whereas in group 2 the drop was temporary, as was the decrease in fetal progesterone in all animals. Epostane also resulted in a rapid fall in maternal and fetal plasma cortisol with a gradual recovery over the following 9-12 h which was accompanied by increased ACTH (adrenocorticotrophic hormone) levels in the fetus. In group 1 fetuses a further escalation in both cortisol and ACTH occurred up to and during delivery while in group 2 basal concentrations were restored after 24 h. Epostane also reduced maternal oestrone concentrations in both groups over the 6-9 h after drug treatment. In group 2 the basal oestrone concentrations and the oestrone/progesterone ratio before and after Epostane administration were lower than in group 1 which may in part explain the failure of Epostane to induce labour in the former despite their similar gestational age. It is concluded that Epostane is not a reliable inducing agent in the sow when infused within 5-10 d of term although enhanced adrenocortical activity probably ensures the viability of the piglets if delivered.

3-Hydroxysteroid Dehydrogenases↗
PubMed1988

Effects on maternal and fetal steroid concentrations of induction of parturition in the sheep by inhibition of 3 beta-hydroxysteroid dehydrogenase.

Changes in circulating steroid hormones, the incidence of myometrial contractions, and the onset of labour were all monitored after administration of the 3 beta-hydroxysteroid dehydrogenase inhibitor, epostane, to chronically catheterized ewes and fetuses near term. In all animals the drug induced delivery 33-36 h after injection or infusion into the ewe with the birth of live healthy lambs which showed normal subsequent development. Epostane induced immediate, permanent falls in both maternal and fetal plasma progesterone concentrations, accompanied by increased PGF metabolite concentrations in the uterine vein beginning 15 min after treatment. Of the other hormonal changes observed, the most striking was the pronounced drop in both maternal and fetal plasma cortisol. In the fetus this fall was followed by increasing concentrations of circulating ACTH which eventually restored the cortisol levels. By 12-24 h after epostane a substantial overshoot had occurred and at 27-30 h the fetal plasma cortisol concentrations were as high as those seen during normal parturition at term. No significant changes in maternal plasma oestradiol-17 beta could be detected after epostane treatment or during labour. The incidence of slow myometrial contractions increased significantly during the second 3-h period after epostane, although their duration did not change. Contraction patterns typical of first stage labour were seen from 20 to 24 h. These results show that epostane may be used as a safe, predictable inducing agent in sheep if given 6-10 days before term; the lambs showed no signs of prematurity despite their lowered plasma cortisol concentrations which persisted for some hours before labour was induced.

3-Hydroxysteroid Dehydrogenases↗
PubMed1987

Optimization of spoiler gradients in FLASH MRI.

The FLASH technique for fast magnetic resonance (MR) imaging often employs strong magnetic field gradients, called spoiler gradients, to dephase the transverse magnetization after it has been measured. Otherwise, image artifacts can develop. The effectiveness of spoiler gradients at suppressing these artifacts was evaluated experimentally on two-dimensional MR images of a uniform phantom and patients. It was informative to compare the magnetization immediately before the RF excitation in each phase encoding step. Only spoiler gradients in the slice selection direction were effective. Spoiler gradients that decreased steadily from a large amplitude in the first phase encoding step to zero in the last minimized the transverse magnetization and suppressed the image artifact, without changing the image contrast.

Humans↗
PubMed1987

Studies on the maturation of the small intestine of the fetal sheep. I. The effects of bilateral adrenalectomy.

The effect of bilateral adrenalectomy at 120 d gestation on subsequent maturation of proximal and distal small intestine was investigated in chronically catheterized fetal sheep. Ten adrenalectomized and fourteen controls were examined at 136 d; some following infusion of [3H]thymidine at 3-6 d or 4 h before termination of pregnancy. Mean plasma cortisol levels were 5.3 +/- 0.7 ng/ml in the adrenalectomized group; control values ranged from 14 to 39 ng/ml level during the 2-week experimental period. Fetal body growth was significantly increased following adrenalectomy. In the small intestine, growth of mucosal structures was reduced, especially in distal regions. Villus height was significantly reduced in both regions. External muscle thickness was significantly increased in both regions. Despite these changes there was no alteration in villus enterocyte morphology, nor were there any significant changes in villus or crypt densities. The proportion of crypt cells labelled with [3H]thymidine was unaffected by adrenalectomy. In proximal regions, migration rate of labelled enterocytes declined from 12.0 to 5.83% villus height/d (P less than 0.025) after adrenalectomy; there was no change in migration rate in distal regions. The estimated renewal time was greater in both proximal and distal regions in adrenalectomized compared with control fetuses.

Adrenalectomy↗
PubMed1987

Studies on the maturation of the small intestine in the fetal sheep. II. The effects of exogenous cortisol.

The effect of cortisol on small intestinal maturation was investigated in catheterized fetal sheep by infusing 2 mg cortisol/d between 105 and 115 d gestation (term ca. 147 d). This treatment resulted in a fivefold increase in plasma cortisol compared with catheterized control fetuses of the same age. There were no detectable changes in enterocyte morphology after the cortisol infusion; the size and density of most intestinal components were largely unaffected by the treatment. By contrast, the kinetics of the enterocyte population were significantly altered by the raised cortisol levels. The proportion of crypt cells labelled was significantly increased from 0.20 +/- 0.04 to 0.33 +/- 0.03 in the proximal region (P less than 0.01) and from 0.22 +/- 0.03 to 0.31 +/- 0.02 in the distal region (P less than 0.01). The migration of enterocytes in both regions was significantly increased to nearly twice the control values (P less than 0.05). Correspondingly, renewal time was almost halved in both regions, while cell density was unchanged in distal and decreased in proximal regions. Hence cell loss appeared to have increased as a result of the cortisol infusion. The kinetic parameters for the villus enterocyte population of the fetuses receiving cortisol before 115 d were of similar magnitude to those previously seen in the normal near-term fetus. To this extent exogenous cortisol treatment given before a pre-partum surge mimicked the action of the endogenous hormone in late gestation.

Animals↗
PubMed1987

Effects of inhibiting 3 beta-hydroxysteroid dehydrogenase on plasma progesterone and other steroids in the pregnant mare near term.

Epostane, a competitive inhibitor of 3 beta-HSD was administered intravenously to a pregnant mare between 292 and 330 days of gestation at doses of 1-3 mg/kg/min. Plasma progesterone concentrations fell rapidly during epostane infusion in both the artery and uterine vein and remained significantly depressed for 4-5 h after the start of infusion. The venous arterial (V-A) plasma concentration difference in progesterone across the uterus also decreased significantly in response to epostane infusion. There were no significant changes in plasma progesterone or in the V-A concentration difference in control animals infused with vehicle alone. The plasma concentration of total unconjugated oestrogens in the uterine vein was reduced after administration of epostane but remained virtually unchanged in the control experiments. Uterine venous plasma concentrations of PGFM did not change significantly in the control or epostane-treated animals. Arterial plasma cortisol levels fell initially after epostane treatment but then rose to values significantly greater than before infusion. A similar increase in arterial plasma cortisol was observed in the control animals. None of the mares delivered after epostane treatment even at the highest dose. These observations demonstrate that inhibition of 3 beta-HSD alters steroidogenesis but has little effect on the length of gestation in the pregnant mare.

3-Hydroxysteroid Dehydrogenases↗
PubMed1987

Sympathoadrenal and other responses to hypoglycaemia in the young foal.

The effects of insulin-induced hypoglycaemia on plasma catecholamines, cortisol and metabolites have been examined in newborn and 7-14-day-old foals. The fall in plasma glucose elicited by the highest dose of insulin (1.0 i.u./kg) given to the neonates was slower in onset and less severe in effect than 0.5 i.u./kg in the older foals. There was a significant inverse correlation between the concentrations of glucose and adrenaline (but not noradrenaline) in plasma once the glucose level had fallen below 2 mmol/l; the adrenergic response to hypoglycaemia was greater in the 7-14-day-old foals than in the neonates. No significant changes in glucose or catecholamines were seen after fasting alone. The adrenocortical response to hypoglycaemia was poor after birth, but significant changes occurred in the older foals with a 3-fold increase in plasma cortisol at 60 min after 0.5 i.u. insulin/kg. There were significant increases in plasma FFA after hypoglycaemia in both groups of animals, but the rise was less pronounced in the neonates. A significant positive correlation was found between plasma adrenaline and FFA values. Hypoglycaemia also resulted in a significant rise in plasma lactate and a slow fall in alpha-amino nitrogen. These findings show that hypoglycaemia in the foal is followed by stimulation of the adrenal medullary component of the sympathetic system and by activation of the adrenal cortex with a number of consequent metabolic changes. The hypoglycaemic effects of insulin were more intense and the response more rapid in the older foals than in the neonates, which exhibited some degree of insulin resistance.

Animals↗
PubMed1987

Using restraint.

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Aged↗