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Biomedical subjects

M Silver

Publications and source records attributed to M Silver.

At least 19 recordsLinked to original sources
PubMed1992

The effects of glycemia on breathing movements and plasma prostaglandin E concentrations in the sheep fetus.

OBJECTIVE: The purpose of this study was to determine the roles of fetal plasma glucose and prostaglandin E in controlling fetal breathing movements. STUDY DESIGN: Five late pregnant ewes with catheterized twin fetuses were fasted for 48 hours; one fetus was kept normoglycemic (by glucose infusion) and the other allowed to become hypoglycemic during this period. Fetal breathing movement and fetal and maternal plasma prostaglandin E and glucose concentrations were measured throughout. Data were analyzed by paired and unpaired t tests. RESULTS: The mean incidence of fetal breathing movement was significantly greater in the normoglycemic fetuses that in the hypoglycemic twins at the end of the fast (p less than 0.05), whereas plasma prostaglandin E levels increased significantly (p less than 0.05) and to the same extent in both groups of fetuses. CONCLUSION: The reduced incidence of ovine fetal breathing movement that occurs during maternal fasting appears to be primarily caused by fetal hypoglycemia and does not directly involve changes in fetal plasma prostaglandin E.

Animals↗
PubMed1992

Intravenous catheterisation of foetus and mare in late pregnancy: management and respiratory, circulatory and metabolic effects.

The uterine and umbilical vessels of 12 pregnant ponies were catheterised to study foetal metabolism. The effects of this procedure on maternal and foetal cardiovascular, respiratory, metabolic and adrenocortical activity were monitored during and after surgery. Premedication with acepromazine-butorphanol-detomidine was followed by induction of anaesthesia with detomidine and ketamine and maintenance, using mechanical ventilation, with halothane in oxygen and nitrous oxide. Mean maternal arterial blood pressure was greater than 70 mmHg during anaesthesia and arterial oxygen tension remained over 100 mmHg. The foetuses were adequately oxygenated but were hypercapnic and lactic acidaemic. Most maternal and foetal blood gases and metabolites had returned to normal by 24 h, although foetal plasma lactate fell more slowly. The maternal adrenocortical discharge was less severe than reported previously and plasma cortisol had fallen to basal levels by 48 h after surgery. Foetal plasma cortisol remained low and did not change during or after surgery. Arterio-venous metabolite and gas tension differences across the uterine and umbilical circulations were slightly greater at operation than in the recovery period, suggesting that uteroplacental perfusion may have been impaired during surgery. Post-operative recovery of the mare and foetus was satisfactory and subsequent problems associated with the foetal catheters were not related to the anaesthesia or surgery.

Acid-Base Equilibrium↗
PubMed1992

Effect of cortisol infusion on the pituitary-adrenal axis of the hypothalamo-pituitary-disconnected fetal sheep.

In order to determine whether cortisol acts directly at the level of the fetal pituitary to promote pars distalis corticotroph maturation, we have infused cortisol into the hypothalamo-pituitary-disconnected (HPD) fetal sheep from 111 to 117 days of gestation. In this study we have measured fetal plasma cortisol and immunoreactive adrenocorticotrophic hormone (ir-ACTH) concentrations between 105 and 116 days of gestation, and we have determined the proportions of adult- and fetal-type corticotrophs in the pars distalis of catheter control fetuses and in HPD fetuses infused with either saline (HPD+SAL) or cortisol (2 mg/day; HPD+F). The fetal plasma cortisol concentrations did not change significantly following HPD. The mean fetal plasma cortisol concentration between 113 and 116 days was threefold higher in the HPD+F fetuses than that measured in HPD fetuses. Following HPD, fetal plasma ir-ACTH concentrations were significantly higher than in catheter control fetuses. Despite the significant elevation in plasma cortisol concentrations in HPD+F fetuses between 113 and 116 days, plasma ir-ACTH concentrations were not different in these fetuses from HPD fetuses infused with saline. At 117 days of gestation in HPD+F fetuses, the proportion of fetal-type corticotrophs in the pars distalis was significantly less than in the HPD+SAL fetuses; however, there was no significant change in the proportion of adult-type corticotrophs in the pars distalis following cortisol infusion. We have shown that cortisol has a direct trophic effect on the maturation of the pars distalis corticotrophs; however, the full maturation of these cells requires an intact hypothalamo-pituitary axis. These findings demonstrate the importance of the fetal hypothalamus in anterior pituitary corticotroph maturation during the last third of gestation.

Adrenocorticotropic Hormone↗
PubMed1992

The development of gluconeogenic enzymes in the liver and kidney of fetal and newborn foals.

The activities of glucose-6-phosphatase (G6P), fructose diphosphatase, phosphoenolpyruvate carboxykinase (PEPCK), aspartate and alanine transferases were measured in liver and kidney of fetal foals between 100-318 days of gestation (term approximately 335 days) and during the immediate postnatal period (0-48 h after birth). All 5 enzymes could be detected in the fetal liver and kidney at the youngest gestational age studied. Mean fetal activities were lower than those observed in their mothers and showed no change with gestational age for the majority of enzymes studied. However, renal PEPCK and renal and hepatic G6P did increase towards term. At birth, hepatic and renal activities of these two enzymes were higher than those found in late gestation or in the adult animals. There was no apparent change in the activities of any of the other enzymes at birth. In late gestation (80-90% gestation), the activities of G6P and PEPCK in the foal were low compared to those in other species at the same stage of gestation. Similarly, the perinatal increase in enzyme activity occurred closer to term in the foal than in most other species. These observations indicate that maturation of glucogenic capacity occurs relatively late in the fetal foal and suggests that this process may be dependent on the prepartum rise in fetal cortisol as occurs in other species.

Aging↗
PubMed1991

Physiological and pathological influences on sheep blood plasma amine oxidase: effect of pregnancy and experimental alloxan-induced diabetes mellitus.

A copper-containing amine oxidase is present in sheep blood plasma and has a high capacity to deaminate spermine and spermidine. The physiological function of this enzyme remains to be determined. Sheep blood plasma amine oxidase (SPAO) was measured by its ability to deaminate spermidine (700 microM) using a peroxidase-linked colorimetric assay developed for microtitre plates. SPAO activity has been studied in a group of Welsh Mountain sheep with experimental alloxan-induced diabetes. This resulted in an increase in SPAO activity which reached a peak of 70 days after alloxan treatment (60 per cent increase). This change could be seen in both pregnant and non-pregnant diabetic sheep. In normal pregnant ewes, SPAO activity remained stable for the first 100 days of pregnancy but declined by 50 per cent in the last month of pregnancy. Together, these findings suggest that SPAO activity is controlled by hormonal influences. This sensitive and convenient assay method could provide clues as to the physiological significance of SPAO and may be a useful clinical chemical indicator in the sheep.

Amine Oxidase (Copper-Containing)↗
PubMed1991

Postoperative course after sufentanil or fentanyl anesthesia for coronary artery surgery.

Postoperative hemodynamic effects were compared in 50 patients randomly selected to receive either sufentanil, 25 micrograms/kg, or fentanyl, 100 micrograms/kg, anesthesia for coronary artery bypass grafting. The two groups exhibited similar patient demographics; dose of premedicants and muscle relaxants; and use of inhalation agents. Values for 15 hemodynamic variables were recorded at baseline and at six postoperative times. The times to awakening, response to verbal commands, and extubation were also noted. Patients who received sufentanil had a more stable course, with higher cardiac outputs, lower systemic vascular resistances, and a lower incidence of hypertension. Postoperatively, the two groups had similar values for time to awakening, response to verbal commands, and extubation. Elimination half-lives differed significantly: 554 +/- 91 minutes (fentanyl) versus 277 +/- 60 minutes (sufentanil). Serum concentrations of both decreased linearly. The added advantages of postoperative hemodynamic stability could be important in the choice of anesthetic.

Anesthesia Recovery Period↗
PubMed1991

Effects of tutors with subject expertise on the problem-based tutorial process.

With the increased interest in problem-based, small-group learning in medical education, a debate has arisen about whether the tutor should be an expert in the subject under discussion. This 1988 study at Harvard Medical School demonstrates that tutors' expertise has important effects on the process of discussion in a problem-based tutorial. In comparing discussions of subjects in which the tutors described themselves as expert with those in which they did not, the authors found that the tutors with expertise tended to take a more directive role in tutorials: they spoke more often and for longer periods, provided more direct answers to the students' questions, and suggested more of the topics for discussion. Tutor-to-student exchanges predominated, with less student-to-student discussion. These effects endanger an important goal of problem-based learning: the development of students' skills in active, self-directed learning.

Clinical Competence↗
PubMed1991

The effect of hypothalamo-pituitary disconnection on the functional and morphologic development of the pituitary-adrenal axis in the fetal sheep in the last third of gestation.

We have investigated the effect of hypothalamo-pituitary disconnection (HPD) on the maturation of basal ir-ACTH and cortisol concentrations in fetal sheep plasma, and on the development of the anterior pituitary corticotroph population in the last third of gestation. After HPD, fetal plasma ir-ACTH concentrations were significantly elevated, and continued to rise with increasing gestational age. However, despite elevated ir-ACTH concentrations, there was no increase in fetal plasma cortisol concentrations, and parturition was delayed for at least 8 days beyond normal term. Furthermore, HPD resulted in a significant disruption of the maturation of the pars distalis corticotrophs. We also examined the change in fetal plasma concentrations of ir-ACTH and cortisol to exogenous CRF after HPD. There was a significant increase in plasma ir-ACTH in response to CRF administration in the HPD fetuses, which was qualitatively similar to that observed in sham-operated fetuses. In contrast, the plasma cortisol response was less in HPD fetuses when compared to that in sham-operated fetuses. The results of this study demonstrate that ir-ACTH secretion is not maintained by the fetal hypothalamus in the last third of gestation, and that ir-ACTH secretion is tonically inhibited by the hypothalamus during this time. The disconnection of the pituitary from the hypothalamus disrupts the maturation of the pituitary-adrenal axis, thus demonstrating the fundamental importance of the hypothalamo-pituitary axis in the normal maturational cascade which culminates in birth in this species.

Adrenal Glands↗
PubMed1991

Effect of adrenalectomy or long term cortisol or adrenocorticotropin (ACTH)-releasing factor infusion on the concentration and molecular weight distribution of ACTH in fetal sheep plasma.

It is unclear whether the maturation of corticotrophs from the fetal to the adult type in the fetal sheep pituitary in late gestation is associated with changes in the sensitivity of the fetal pituitary to corticotrophic secretagogues and in the form of ACTH-containing peptides (IR-ACTH) secreted into the circulation. The maturation of the pituitary corticotroph population is known to be accelerated by intrafetal cortisol infusion and delayed by bilateral fetal adrenalectomy. We have therefore investigated the mol wt profile of IR-ACTH present in fetal sheep plasma from 110 days gestation until term (147 +/- 3 days) and determined whether intrafetal cortisol infusion between 105-117 days (2.5 mg cortisol/day), or bilateral fetal adrenalectomy can alter the mol wt profile of IR-ACTH in fetal sheep plasma. We have also investigated whether prior exposure to cortisol alters the subsequent responsiveness of the fetal pituitary to a long term infusion of ovine (o) CRF (10 micrograms oCRF/day). In the control group, the proportion of IR-ACTH which eluted in the low-mol wt (LMW) range (i.e. less than 12K) was significantly higher between 121-125 days (43.9 +/- 4.2%) than between 126-139 days (26.8 +/- 9.3%) but not different to that after 140 days gestation (29.9 +/- 5.5%). Between 110-117 days, cortisol infusion had no effect on the proportion of IR-ACTH in the LMW range (43.9 +/- 5.7%, saline infused; 44.1 +/- 2.4%, cortisol infused). Between 121-125 days, the proportion of IR-ACTH in the LMW range in the CRF-infused groups (with or without prior exposure to cortisol) was significantly lower (27.4 +/- 2.1%) than in the saline-infused control group. In contrast, after fetal adrenalectomy, the proportion of IR-ACTH in the LMW range between 126-139 days was significantly higher (48.0 +/- 6.7%) than in intact control animals (23.8 +/- 3.5%). We conclude that the change in the mol wt profile of IR-ACTH in fetal plasma after 125 days may be a consequence of changes in the morphological and/or functional characteristics of the corticotrophic cells in the fetal pituitary. Infusion of oCRF appears to accelerate the normal maturation of the fetal pituitary-adrenal relationship, and oCRF acting either directly or via secretion of cortisol may play a role in the posttranslational processing of POMC in the fetal sheep pituitary after 125 days gestation.

Adrenalectomy↗
PubMed1991

Induction of labour in sheep by inhibition of 3-beta hydroxysteroid dehydrogenase: role of the fetal adrenal.

In sheep parturition may be induced within 33 h in late gestation by inhibiting progesterone production with the 3 beta hydroxysteroid dehydrogenase inhibitor Epostane. Its effect has now been investigated in ewes carrying adrenalectomised (n = 5), hypophysectomised (n = 4) or intact (n = 5) fetuses to determine the role of the fetal adrenal during this type of maternally-induced delivery. Epostane was infused i.v. (1.5 mg/kg) into each group of ewes at 137-156 days gestation. Fetus and mother were sampled from the time of administration until delivery. Measurements of plasma ACTH, cortisol, progesterone and PGF2 alpha metabolite (PGFM) were made and intrauterine pressure was monitored. Epostane induced delivery significantly later in the adrenalectomised (44 h) and hypophysectomised (52 h) animals compared with the controls (33 h). The drop in maternal plasma progesterone was similar in all 3 groups, but the subsequent increases in arterial and uterine venous PGFM were smaller in the adrenalectomised and hypophysectomised ewes than in the controls. The large escalation in fetal plasma cortisol before birth in controls was absent in adrenalectomised and hypophysectomised fetuses. The slight rises in plasma cortisol observed in the latter from about 24 h after Epostane, were related to the concomitant increases in maternal plasma levels (r = 0.76, P less than 0.01). No fetuses became hypoxic or acidotic during the period of induction despite the prolonged labour of hypophysectomised and adrenalectomised fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗
PubMed1991

Tissue glycogen and glucose 6-phosphatase levels in fetal and newborn foals.

Glycogen and glucose 6-phosphatase levels were measured in a variety of tissues from fetal, newborn and adult pregnant mares. Hepatic and renal glucose 6-phosphatase activities increased with increasing gestational age and rose further in the 24 h after birth to values similar to those observed in maternal tissues. The glycogen content of fetal liver and skeletal muscle also increased in late gestation, whereas that of fetal lung and cardiac muscle decreased toward term. No significant change in renal glycogen content with fetal age was observed. The values of hepatic glycogen and glucose 6-phosphatase found in the fetal foal near term were less than those observed previously in fetal sheep and pigs at a similar stage of gestation. These observations suggest that, in late gestation, the fetal foal has a limited glucogenic capacity compared with other domestic species and may have difficulty maintaining an adequate glucose supply during adverse conditions.

Animals↗
PubMed1991

Studies of bone marrow and leucocyte counts in peripheral blood in fetal and newborn foals.

Clinical and pathological records of 124 foals were studied. The foals were assigned to six groups; normal, premature, dysmature, bacterially infected, neonatal maladjustment syndrome and Equid herpesvirus type 1 (EHV-1) infected. Also, 6 pony fetuses were sampled via catheters in the umbilical vein and artery between 280 and 310 days gestation. Bone marrow aspiration was performed on a further 14 foals. Premature foals had significantly lower neutrophil counts than normal foals up to 5 h. Foals with bacterial infections had significantly lower neutrophil counts up to age 12 h. EHV-1 infected foals had significantly lower neutrophil counts up to age 24 h and significantly lower lymphocyte counts than all other groups up to age 12 h. Premature foals showed a higher neutrophil count and neutrophil/lymphocyte (N:L) ratio in survivors compared with non-survivors when all ages were considered, although the differences were not significant before 35 h. Discriminant analysis showed a 99% chance that the EHV-1 group could be identified from all other groups except dysmature foals, where discrimination between the two groups was about 90%. In catheterized fetuses, age-related increases in neutrophil counts and the N:L ratio occur from 280 to 310 days of gestation. In one preparation available for study leading up to parturition, the N:L ratio widened during the 3 days pre-partum. The bone marrow aspirates showed no significant changes in the myeloid:erythroid (M:E) ratio during the first 4 days post partum. The left shift (LS) index was significantly higher in foals suffering bacterial infection compared with normal or dysmature foals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Relationship between circulating tri-iodothyronine and cortisol in the perinatal period in the foal.

Pre- and post partum changes in plasma T3 have been examined in relation to plasma cortisol in 23 newborn foals (12 full term, 6 premature and 5 'twilight'), and in 5 fetuses catheterized in late gestation. Blood samples were collected daily from the fetuses and from the neonates at 30-min intervals for 2 h after birth; the plasma was assayed for T3 and cortisol by standard radioimmunoassay methods. In the full-term foals, plasma cortisol and T3 concentrations were high at birth (67.4 +/- 6.1 and 4.3 +/- 0.3 ng/ml respectively) and rose to a maximum during the following 2-h period to 141.0 +/- 8.8 ng/ml and 8.4 +/- 0.5 ng/ml. The corresponding changes in the premature foals over the same period were significantly lower (P less than 0.01; 17.2 +/- 2.2 to 27.0 +/- 4.3 ng cortisol/ml and 2.9 +/- 0.5 to 5.4 +/- 0.6 ng T3/ml). In the 'twilight' group, intermediate increases in both cortisol and T3 were observed. In the 5 chronically catheterized fetuses, both plasma cortisol and T3 were low in the last few weeks of gestation (7.0 +/- 1.1 ng/ml and 1.2 +/- 0.2 ng/ml respectively). In 2 fetuses there was little or no increase in plasma cortisol or T3 before induction of labour at about 320 days; one foal was premature and the other 'twilight'. Infusion of adrenocorticotrophic hormone for 4.5 days into the third fetus from 309 days led to an increase in both cortisol and T3 and the birth of a viable, full term foal. The 2 remaining fetuses were delivered spontaneously, one at term and one at 300 days (well before term). The latter was viable but dysmature; it showed a slight prenatal rise in plasma cortisol with little change in T3. When all the data were combined from both fetuses and neonates a significant positive correlation between plasma T3 and cortisol was found (P less than 0.001). These results demonstrate a relationship between circulating cortisol and T3 in the perinatal period and show that prematurity is associated with low concentrations of both hormones.

Adrenocorticotropic Hormone↗
PubMed1991

Respiratory and non-respiratory thoracic movements in the fetal pig.

The aim of this study was to characterize the pre-natal activity of the respiratory muscles in a non-ruminant, the pig. Tracheal pressure was recorded from 11 unanaesthetized fetal pigs in utero during late gestation in 9 sows. Two types of inspiratory effort occurred episodically in each fetus during each recording period. Episodes of breathing movements lasted 8.6 +/- 1.1 min and their overall incidence was 41.1 +/- 3.4% of recording time. The mean amplitude of the respiratory efforts was 7.6 +/- 1.1 mmHg and the mean inspiratory time was 0.8 +/- 0.1 s. Episodes of non-respiratory inspiratory efforts, considered to be fetal hiccups, lasted 5.6 +/- 0.8 min. Individual hiccups had a duration of 150-200 msec, a mean amplitude of 41.4 +/- 2.4 mmHg and a mean frequency, during episodes, of 21.9 +/- 2.0 min-1. In contrast to fetal breathing movements, hiccups appeared to be stereotyped events. It is concluded that, in common with other ruminant and non-ruminant species, two types of inspiratory effort occur in the fetal pig. Fetal hiccups, which have been observed in non-ruminant species, may be analogous to deep inspiratory efforts in the sheep fetus. The stimulus for, and function of, fetal hiccupping remain to be determined.

Animals↗
PubMed1991

Plasma progestagens in the mare, fetus and newborn foal.

This study used gas chromatography/mass spectrometry (GC/MS) to identify and measure plasma progestagens. The method included deuterated internal standards, e.g. [17,21,21,21-2H]-5 alpha-pregnane-3,20-dione, solid-phase extraction, derivatization (methoxime/t-butyldimethylsilyl) and GC/MS. Full-scan screening identified 3 5-pregnenes, 2 4-pregnenes and 7 5 alpha-pregnanes (no 5 beta-pregnanes). The selected ion mode was used for routine quantitation from calibration curves; response was linear (r greater than 0.98) from 2 to 2000 ng equivalents/ml (0.5 ng/ml method sensitivity) and intra- and inter-assay coefficients of variation were less than 20%. The predominant steroids in plasma from pregnant pony and light-horse mares near term were 20 alpha-hydroxy-5 alpha-pregnan-3-one (400-2100 ng/ml) and 5 alpha-pregnane-3 beta,20 alpha-diol (100-350 ng/ml). Four other mono- and dihydroxy-5 alpha-pregnanes were generally between 30 and 100 ng/ml. These pregnanes were detectable initially between 30 and 60 days gestation and increased gradually until a more rapid increase was observed 30 days pre-partum. Maximum concentrations occurred during the last 2-3 days, followed by a decline before parturition. The progesterone profile during early pregnancy was similar to that given in previous reports. However, progesterone was not detectable during mid- to late pregnancy, except in a few mares near term (0.5-1 ng/ml). 5 alpha-Pregnane-3,20-dione (5 alpha-DHP) concentrations were similar to those of progesterone during early pregnancy but remained elevated and relatively constant (30 ng/ml) to term. No 20 alpha- or 20 beta-hydroxy-4-pregnen-3-one was detected in mare plasma. In mares that aborted or delivered prematurely, these pregnanes showed a profile of decreasing concentrations. In the fetal artery (250-300 days) plasma concentrations (ng/ml) of the predominant steroids were: pregnenolone (422), 5-pregnene-3 beta,20 beta-diol (171), 3 beta-hydroxy-5 alpha-pregnan-20-one (277) and 5 alpha-pregnane-3 beta,20 beta-diol (221). In the fetal vein, the predominant steroid was 5 alpha-DHP (205); progesterone was low (12.7 ng/ml) but consistently found. Steroids in the uterine venous plasma were similar in type and concentrations to those found in the peripheral circulation; uterine arterial concentrations were generally 50% lower. These results suggest that fetal pregnenolone is converted rapidly to progesterone and/or 5 alpha-DHP by the placenta, with further 3 beta- and 20 beta-hydroxylation by the fetus. In contrast, 20 beta-hydroxylation predominated on the maternal side and so may not directly reflect the fetal-placental environment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Production of 5 alpha-dihydroprogesterone during late pregnancy in the mare.

Changes in the progesterone metabolite 5 alpha-dihydroprogesterone (5 alpha-DHP) in maternal plasma in late gestation, and possible sites of production of this steroid were studied in pony and Thoroughbred mares by an enzyme-linked immunosorbant assay for 5 alpha-DHP. In Thoroughbred mares, plasma 5 alpha-DHP increased from 63.7 +/- 10.5 ng/ml (27 days pre-partum) to 161.7 +/- 30.8 ng/ml (1 day pre-partum) falling to 90.2 +/- 16.1 ng/ml on the day of parturition. In pony mares, values rose from 30.8 +/- 8.1 ng/ml (27 days pre-partum) to 79.1 +/- 30.8 ng/ml (3 days pre-partum) and then decreased to 28.2 +/- 7.1 ng/ml on the day of parturition. Concentrations of 5 alpha-DHP were greater in the umbilical and uterine veins than in the corresponding umbilical and uterine artery samples. Tissues incubated with isotopically-labelled substrates showed that the fetal placenta converted pregnenolone to progesterone (47.5 +/- 9.0%). Endometrium metabolised [3H]pregnenolone to progesterone and 5 alpha-DHP (11.0 +/- 3.0% and 7.8 +/- 2.4%, respectively), and [14C]progesterone to 5 alpha-DHP (9.3 +/- 2.5%). Deuterium-labelled substrates were used to confirm the identity of these products by gas chromatography-mass spectrometry. Negligible amounts of 5 alpha-DHP were formed by other fetal tissues (adrenal, liver, kidney and testis). The results show that 5 alpha-DHP production in late pregnancy is derived primarily from endometrial metabolism of pregnenolone and/or progesterone.

5-alpha-Dihydroprogesterone↗