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Biomedical subjects

G C Liggins

Publications and source records attributed to G C Liggins.

At least 19 recordsLinked to original sources

The influence of oligohydramnios on thoracic dimensions of fetal sheep.

Oligohydramnios frequently leads to lung hypoplasia in the fetus, but the underlying mechanisms are incompletely understood. Our aim was to determine the effects of oligohydramnios on the dimensions of the fetal thorax. Using pairs of implanted ultrasound transducers in 6 fetal sheep, we measured 4 thoracic dimensions (transverse, anterior-posterior, manubrium to left and right hand sides of the diaphragmatic dome) for 2 control days, 3 days of amniotic and allantoic fluid drainage (oligohydramnios), and 2 days after the return of drained fluids. The effect of oligohydramnios, which began at 121-2 days of gestation (term being c.145 days), on each dimension was quantified daily as the difference between the measured value and the value predicted from the growth of that dimension over the study period. Oligohydramnios led, within 48 hours, to significant reductions in the transverse dimension (5.9-6.1%) and in the distance between the manubrium and the dome of the diaphragm (1.7-2.2%). There was no change in the anterior-posterior dimension. We conclude that oligohydramnios causes alterations, within 48 hours, in the dimensions of the fetal thorax which can be reversed, at least partially, by re-expansion of the fluid sacs. These changes, which are expected to produce reductions in thoracic volume, may, if prolonged, lead to lung hypoplasia.

Animals

Oral prostaglandin E2 for induction of labour at term.

A low dose regimen of prostaglandin E2 tablets, 0.5 mg hourly for up to 10 doses, was used in an attempt to induce labour without prior amniotomy in 69 patients between 35 and 44 weeks gestation. The induction was considered successful if the patient delivered within 36 hours after therapy began. The success rate was 62 percent. The incidence of undesirable side effects was low and no serious fetal complications were related to treatment.

Administration, Oral

Controlled trial of induction of labor by vaginal suppositories containing prostaglandin E2.

A group of 84 women at 39-43 weeks of pregnancy were randomly allocated to a blind trial of induction of labor with vaginal suppositories containing inert material or either 0.2 mg or 0.4 mg of prostaglandin E2. The suppositories were self-administered every two hours during waking hours on two successive days until labor started or 15 had been used. Side-effects were absent. Labor was established within 48 hr of insertion of the first suppository in 9.3% of control patients, 65.4% of those treated with 0.2 mg PGE2 and 85.7% of those treated with 0.4 mg PGE2. The mean Apgar scores in the three groups were the same. The mean total dose of PGE2 were 2.0 mg (0.2 mg group) and 2.3 mg (0.4 mg group). It is concluded that vaginal PGE2 is an effective and acceptable method of inducing labor at term.

Clinical Trials as Topic

Somatomedin-like activity, prolactin, growth hormone and insulin in human cord blood.

In order to assess the possible influence of fetal polypeptide hormones on birth size, somatomedin-like receptor activity (SmLRA) (n = 281), prolactin (n = 158), growth hormone (n = 133) and insulin (n = 108) concentrations were measured in the cord blood of 281 singleton infants born after different complications of pregnancy. Infant sex did not significantly affect the concentration of any hormone. SmLRA concentrations appeared to rise from 25 to 38 weeks of gestation, but thereafter fell. Concentrations of prolactin, growth hormone and insulin correlated negatively with gestational age. Insulin emerged as the hormone most clearly related to fetal growth, since concentrations were high (mean +/- SD = 20.6 +/- 11.5 uU/ml) in serum from infants of diabetic mothers (IDM) and other large-for-dates infants (10.1 +/- 4.8 uU/ml), but low (5.3 +/- 0.5 uU/ml) in infants who were small-for-dates (SFD). In contrast, SmLRA concentrations were high in serum from SFD infants (0.63 +/- 0.29 U/ml) and low in IDM (0.43 +/- 0.16 U/ml). Prolactin concentrations were higher in serum from SFD infants (212 +/- 101 ng/ml) and from IDM (237 +/- 182 ng/ml) than from normal infants born at term (139 +/- 68 ng/ml). Administration of intramuscular betamethasone to pregnant women in premature labour resulted in significant elevations in the concentrations of prolactin and insulin in cord blood.

Adrenal Cortex Hormones

Regional blood flow during simulated diving in the conscious Weddell seal.

Changes in regional blood flow during simulated normobaric diving were studied in the conscious Antarctic Weddell seal (Leptonychotes weddelli) by injecting 25-microns radioactive microspheres into the left ventricle. Injections were performed before and 8--12 min after submersion of the head in iced seawater. Diving was associated with a fall in cardiac output from a mean control value of 39.8 +/- 10.2 to 5.6 +/- 3.4 l/min (mean +/- SD) and in heart rate from 52 +/- 15 to 15 +/- 4 beats/min. Blood flow to the splanchnic and peripheral vascular bed was reduced by more than 90%, cerebral blood flow was unchanged, right and left ventricular blood flow decreased by 85%, and adrenal blood flow decreased by 39%. The pulmonary fraction of the injected microsphere dose increased from 7.9 to 29.9% during diving. This may signify a large increase of peripheral arteriovenous shunting during the dive and/or increased bronchial artery blood flow. It is concluded that blood flow during diving is directed to organs and tissues according to their metabolic requirements.

Animals

High corticosteroid levels in plasma of adult and foetal Weddell seals (Leptonychotes weddelli).

Pregnant and non-pregnant Weddell seals and foetuses were found to have very high plasma concentrations of corticosteroids (1--7 mumol/l) that were unaffected by stress. Cortisol comprised most of the corticosteroid in the adult but only 50% of that in the foetus. The affinity constant (4.30-5.53 x 10(7) l/mol) and specificity of CBG and the MCR (4.5 l/d/kg lean body mass) in adult seals were similar to those of Man. The binding capacity of CBG (1.48--1.86 mumol/l) which is approximately three times that of Man contributed to the high plasma corticosteroid concentrations but the main factor was the cortisol turnover rate of 3670 mumol/d (1.3 g/d) which is the highest value reported in any species.

Adrenal Cortex Hormones

Stimulation of breathing movements in fetal sheep by inhibitors of prostaglandin synthesis.

We studied the effects of inhibitors of prostaglandin synthesis on fetal breathing movements on 17 occasions in 11 lambs (gestational age 125-141 days). We gave 12 h infusions of sodium mechlofenamate (8.6-22.2 mg.kg-1) in 13 studies and indomethacin (21.8-38.8 mg.kg-1) in four studies. Results were similar with both agents and did not correlate with drug dosage. There were no changes in fetal arterial blood pressure, pH or blood gas tensions. We assessed fetal breathing movements by measurements of tracheal pressure for a control period of 224 h prior to and 208 h during the infusion of inhibitors of prostaglandin synthesis; their administration caused a marked stimulation of fetal breathing movements judged from the following four variables: (1) incidence of fetal breathing movements increased from 38.4 to 69.2% of the time (P < 0.001); (2) average amplitude of change in tracheal pressure during fetal breathing movements increased from 4.1 to 6.0 torr (P < 0.01); (3) maximal amplitude of change in tracheal pressure during fetal breathing movements increased from 8.8 to 13.4 torr (P < 0.01); and (4) the duration of the longest continuous episode of fetal breathing movements increased from 37 to 229 min (P < 0.05). Two fetuses had electrocorticogram (ECoG) recordings. In control periods, fetal breathing movements occurred only during low voltage, high frequency ECoG activity; however, during infusions of inhibitors of prostaglandin synthesis, fetal breathing movements occurred also during high voltage, low frequency ECoG activity. We conclude that inhibitors of prostaglandin synthesis stimulate fetal breathing movement in fetal sheep. These results suggest that a component of the prostaglandin system is a factor which inhibits breathing movements during fetal life.

Animals

Prolactin in umbilical cord blood and the respiratory distress syndrome.

Prolactin was measured in umbilical cord serum obtained from 77 newborn infants of gestational age 28 to 40 weeks. A positive correlation with gestational age was demonstrated. Between 30 and 36 weeks of gestation the elevation of the regression line of the concentration of cord PRL versus gestation age was significantly lower (P less than 0.05) for those infants who developed respiratory distress syndrome compared to the regression line for infants who did not develop RDS. Between 32 and 33.5 weeks, the mean +/- SEM cord PRL concentration in infants who developed RDS (101.7 +/- 9.5 ng/ml) was significantly less (P less than 0.025) than the PRL concentration in those who did not develop RDS (161.8 +/- 18.9 ng/ml). Cord PRL did not correlate with cord cortisol or dehydroepiandrosterone sulfate concentrations. Cord growth hormone concentrations did not show any relationship to the occurrence of RDS. Serum PRL was not suppressed in a further 114 infants whose mothers were treated prenatally with betamethasone. These findings raise the possibility of a role of PRL in fetal lung maturation.

Betamethasone

A receptor assay for somatomedin-like activity using multiplication-stimulating activity (MSA) as radioligand.

Multiplication-stimulating activity (MSA) in the medium of cultured rat liver cells was purified 120-fold by chromatography on Dowex 50W and Sephadex G 50. MSA was labelled with 125I-iodine and bound to a human placental membrane receptor. An assay for somatomedin-like receptor activity (SmLRA) in unextracted serum was based on the displacement of 125I-MSA from the placental receptor. The mean lambda (precision) was 0.063, sensitivity was less than 0.006 SmLRA units and interassay variation was 18%. The mean (+/- S.D.) SmLRA concentrations in 13 normal subjects, 7 growth hormone deficient patients and 8 patients with active acromegaly were 0.86 +/- 0.19, 0.34 +/- 0.08 and 2.34 +/- 0.82 U/ml, respectively. This assay may have potential clinical application in disorders of growth hormone secretion.

Acromegaly

The binding of rat liver cell multiplication-stimulating activity (MSA) to human placenta and serum proteins.

Multiplication-stimulation activity (MSA) from the medium of BRL-3A rat liver cells in culture binds to cell membrane and cytosol receptors from human placenta and to serum proteins. The binding of MSA to placental cell membranes is dependent on time, temperature, pH and divalent ion concentration. MSA bound to placental cytosol receptor and serum is not displaced by insulin, whereas that bound to placental cell membranes is displaced by insulin and insulin-like peptides. The affinity of the three receptors for MSA is similar [approximately 10(8) M(-1)]. An assay using 125I-MSA and placental membrane receptor detects somatomedin-like receoptor activity (SmLRA) in unextracted sera from man and animals. A binding protein in serum that competes for 125I-MSA with receptor could not be completely separated from SmLRA by heating, acidification, charcoal treatment and gel chromatography of the serum. The relative activities of SmLRA and serum binding protein remained constant in three disorders of human growth (acromegaly, growth hormone deficiency and Laron's dwarfism) in which values of SmLRA varied widely. However, the binding protein is only partly responsible for the apparent SmLRA of unextracted serum. It is concluded that MSA is a suitable radioligand for the investigation of somatomedin disorders in man either by receptor assays or by studies of tissue receptors.

Animals

Pituitary stalk-section and some of its effects on endocrine function in the fetal lamb.

A detailed description is given of a method to section the pituitary stalk of the fetal lamb after 105 days gestational age. The approach to the stalk is made through a window in the frontal bone. In order to prevent regeneration of the hypothalamo-pituitary connections a silicone plate is introduced through the probe used to fracture the stalk. The surgical outcome and viability of 11 pituitary stalk sectioned fetuses is described over periods of up to 23 days. The presence of pituitary infarction following stalk section was related to damage of the anterior hypophysial vesssels if the probe was deviated from the mid-line at any time in its course. The effect of this procedure on fetal plasma T4 and PRL concentrations and the initiation of premature labour by the continuous infusion of cortisol into the fetus is described.

Animals