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Biomedical subjects

J Falconer

Publications and source records attributed to J Falconer.

At least 55 records · Page 3Linked to original sources

The effect of prolonged hypobaric hypoxia on growth of fetal sheep.

The effect of prolonged hypobaric hypoxia on fetal sheep was studied. Pregnant ewes were subjected to an atmospheric pressure of 429 torr from 30 days to 135 days gestation (long-term study). Average fetal weight for the hypoxaemic group (3.35 +/- 0.53 kg; n = 4; mean +/- SD) was significantly lower than for the controls (4.23 +/- 0.29 kg; n = 7; P less than 0.05). A short-term study was undertaken with fetuses (n = 8) which were catheterized at 110 days gestation and whose dams were subjected to hypobaric hypoxia from 120 to 141 days gestation. The mean carotid PO2 of fetuses in the hypoxic group was 12.7 +/- 0.7 torr compared to 22.7 +/- 0.7 torr for the control group (n = 9; P less than 0.001) throughout the period of treatment. Fetal arterial oxygen content fell from 6.5 +/- 1.7 to 4.9 +/- 0.4 ml/dl (P less than 0.05), but rose to control values after 7 days due to an increase in fetal haemoglobin concentration (9.6 +/- 1.1 to 13.0 +/- 1.9 g/dl, P less than 0.001) and packed cell volume (33 +/- 3 to 45 +/- 4%, P less than 0.001). In the hypoxaemic fetuses, pH fell initially from 7.34 +/- 0.02 to 7.28 +/- 0.03 (P less than 0.05) and then recovered to 7.32 +/- 0.03 within 24 h. Mean fetal weight of the short-term hypoxic group was 3.46 +/- 0.72 kg compared to 4.15 +/- 0.51 for the control group (P less than 0.05). Both long- and short-term hypoxia produced a similar reduction in fetal body weight. The adrenal glands were significantly heavier in the hypoxic fetuses than in controls. Placental weight was not effected by hypoxia, but exposure from 30 days gestation reduced the average size of cotyledons (P less than 0.05). It is concluded that the fetal sheep increases its ability to acquire and transport oxygen in response to chronic hypoxia, but this compensation is not sufficient to prevent growth retardation or changes to the pattern of tissue growth.

Altitude Sickness↗

Changes to metabolite concentration in fetal sheep subjected to prolonged hypobaric hypoxia.

The effect of hypobaric hypoxaemia on the concentration of metabolic substrates in the ovine fetus and pregnant ewe with implanted vascular catheters, was investigated. At 120 to 141 days of gestation sheep were subjected to hypobaria (mean fetal carotid PO2 12.7 +/- 0.7 torr; n = 9) or normobaria (mean fetal carotid PO2 22.7 +/- 0.7 torr; n = 11; P less than 0.001). At 141 days gestation mean fetal weight was 3.46 +/- 0.72 kg in the hypobaric group compared to 4.15 +/- 0.51 in the normobaric group (P less than 0.05). Concentrations of glucose in maternal and fetal plasma and fructose in fetal plasma were similar in hypobaric and normobaric fetuses. The concentration of lactate in fetal plasma rose from 1.68 +/- 1.34 to 8.79 +/- 5.8 mmol/l (P less than 0.001) within 24 h of onset of hypoxia, but fell to 3.36 +/- 1.13 mmol/l by day 3 of treatment, though still significantly above the concentration of lactate in the control fetuses (1.47 +/- 0.47; P less than 0.001). There was no significant effect of hypoxia on the concentration of lactate or alanine in maternal plasma. Alanine concentration in the plasma of fetuses subjected to hypoxia significantly increased within 24 h of exposure (0.28 +/- 0.10 vs 0.58 +/- 0.39 mmol/l; P less than 0.01) and remained elevated for the duration of the study. There was no significant effect of gestational age on the concentration of metabolic substrates in either the control or experimental groups. Hypoxia is associated with a sustained rise in the concentration of plasma lactate and alanine in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗

Essential thrombocythemia associated with recurrent abortions and fetal growth retardation.

Essential thrombocythemia (ET) is one of the myeloproliferative disorders characterized by an elevated platelet count, usually greater than 1,000 X 10(9)/L. It may be associated with either hemorrhagic or thrombotic tendencies. Although it usually affects older people, we have recently encountered two young women with ET who had a total of six spontaneous abortions before the end of the first trimester. During her most recent pregnancy, one of the patients underwent plateletpheresis on four separate occasions before the 12th week. She reached 34 weeks but demonstrated evidence of fetal growth retardation and pre-eclampsia. At delivery there were scattered villus infarcts in the placenta. Based on this patient and previous reports in the literature, we postulate that the spontaneous abortions, fetal growth retardation, and pre-eclampsia may be related to the thrombocytosis and suggest that the use of antiplatelet agents throughout pregnancy should be seriously considered in such cases.

Abortion, Habitual↗

Oral epidermal growth factor is trophic for the stomach in the neonatal rat.

The stomach of the naturally suckled rat pup was shown to grow rapidly during the first 24 h following delivery. Both absolute weight (p less than 0.001) and weight in proportion to body weight (p less than 0.001) increased. The stomachs of pups fed formula containing epidermal growth factor (EGF) were larger than those of their control littermates (p less than 0.05). These data support a role for milk EGF in the regulation of neonatal gut growth.

Administration, Oral↗

Effect of restriction of placental growth on oxygen delivery to and consumption by the pregnant uterus and fetus.

Endometrial caruncles were excised from 13 sheep (caruncle sheep) before pregnancy to restrict placental growth. In subsequent pregnancies, half the caruncle fetuses were growth retarded or small (weight more than 2 SD below mean weight for control fetuses) with the remainder, normal-sized (weight within 2 SD of mean weight for control fetuses). The caruncle and 16 control sheep, each with indwelling vascular catheters, were studied between 121 and 130 days of pregnancy. Oxygen delivery to and consumption by the pregnant uterus in caruncle sheep with small fetuses was significantly reduced compared to controls while oxygen extraction was significantly increased. Oxygen tension (P02) and content in the common umbilical vein and in the descending aorta were significantly lower in small caruncle fetuses compared to controls but only P02 was lower in normal-sized caruncle fetuses. Oxygen delivery to, and consumption by, the fetus was significantly reduced in normal-sized and in small caruncle sheep compared to controls while oxygen extraction was increased in small caruncle sheep. Utero-placental oxygen consumption was significantly lower in caruncle sheep with small fetuses compared to that in controls. Despite these changes, oxygen consumption by the gravid uterus and fetus, per kg of tissue mass, was similar in both groups of caruncle and in control sheep. Utero-placental oxygen consumption per kg of utero-placental mass in caruncle sheep with small fetuses was not significantly different to that in sheep with normal-sized caruncle or control fetuses, although it averaged only 25% of that in controls. It is concluded that intrauterine growth retardation following restriction of placental growth is associated with a reduced supply of oxygen to both the pregnant uterus and fetus and a redistribution of oxygen to the fetus. This is due to the disproportionate maintenance of fetal growth relative to that of the placenta, since oxygen consumption by either, in terms of tissue mass, was not altered. Further, the greater uterine and fetal extraction of oxygen suggests that a smaller margin of safety may exist between supply and demand in intrauterine growth retardation.

Animals↗

Effect of restriction of placental growth on fetal and utero-placental metabolism.

The effect of restriction of placental growth on the supply of glucose to the gravid uterus and fetus and on fetal and utero-placental metabolism of glucose and lactate was examined in this study. Endometrial caruncles were removed from 13 sheep (caruncle sheep) prior to mating, which restricted placental growth in the subsequent pregnancy. Half the fetuses of caruncle sheep were small or growth retarded, with the remainder normal in size. After insertion of vascular catheters at 110 days gestation, the caruncle sheep, together with 16 control sheep, were studied between 121 and 130 days of gestation. Glucose delivery to and consumption by the gravid uterus and its contents, both as a total and per kg of tissue mass, was significantly lower in caruncle ewes with small fetuses, although glucose extraction was similar to that in controls. Utero-placental glucose consumption was significantly lower in caruncle ewes carrying small fetuses compared to that in control ewes, both as a total and per kg of placenta. Small caruncle fetuses were hypoxaemic and hypoglycaemic and the lactate concentration in the common umbilical vein was significantly higher than in control sheep. Glucose delivery to and consumption by the fetus was significantly lower in normal-sized and in small caruncle fetuses compared to controls. Fetal glucose consumption per kg of fetus was similar in control and caruncle sheep. Fetal glucose extraction increased as fetal weight decreased. Utero-placental production of lactate was similar in control and caruncle ewes. However, uterine output of lactate decreased as placental weight fell. Utero-placental production of lactate per kg of placenta was significantly higher in caruncle ewes compared to controls and increased as oxygen content in blood from the fetal femoral artery decreased. Fetal lactate consumption per kg of fetus increased as the concentration of lactate in blood from the common umbilical vein increased. It is concluded that intrauterine growth retardation due to restriction of placental growth is associated with a reduced supply of glucose to both the pregnant uterus and fetus and a redistribution of glucose therein to the fetus, both directly as glucose and indirectly as lactate. This reflects the disproportionate maintenance of fetal weight relative to that of the placenta, reduced utero-placental consumption of glucose per kg of placenta, conversion of a greater proportion of that glucose or other substrate(s) to lactate by the placenta and an increase in the fraction of the lactate produced by utero-placental tissues that is secreted into the fetal circulation.

Animals↗

Restriction of placental size in sheep enhances efficiency of placental transfer of antipyrine, 3-O-methyl-D-glucose but not of urea.

When placental growth is restricted, fetal growth is reduced but the fetal to placental weight ratio increases, suggesting that the efficiency of placental transfer may have increased. Therefore, placental transfer of antipyrine, 3-O-methyl-D-glucose and urea was measured in control pregnant sheep and in sheep with restricted placental growth (pre-pregnancy excision of endometrial caruncles). Clearance of each decreased with placental weight but clearance of antipyrine and of 3-O-methyl-D-glucose per kg of placenta increased as placental weight decreased. The small placenta exhibited increased efficiency of flow-determined transfer of antipyrine and of facilitated-diffusion transfer of glucose but not of passive transfer of the hydrophilic substance, urea. These compensatory changes should help to maintain oxygen and glucose to the fetus when the growth of the placenta has been limited by reduction of the number of placental attachment sites.

3-O-Methylglucose↗

Effect of restriction of placental growth on umbilical and uterine blood flows.

Endometrial caruncles were excised from sheep (caruncle sheep) before pregnancy. The effect of this on umbilical and uterine blood flows in a subsequent pregnancy was examined. Thirteen caruncle and twelve control sheep with indwelling vascular catheters were studied at 121 and 130 days pregnancy. In caruncle sheep, fetal, placental, and total uterine content weights were significantly lower than in control sheep. Six caruncle sheep carried normal-sized fetuses (weight within +/- 2 SD of mean weight for control fetuses) and seven carried small fetuses (weight greater than +/- 2 SD below mean weight for control fetuses). Mean weights of placentas in these groups were 0.290 +/- 0.067 and 0.156 +/- 0.069 kg, respectively, compared with 0.459 +/- 0.157 kg in control sheep. In small caruncle fetuses, umbilical and uterine blood flows and placental antipyrine clearance were significantly lower than in controls at 121 and 130 days gestation. Only umbilical blood flow was reduced in normal-sized caruncle fetuses. Umbilical blood flow and placental antipyrine clearance increased with gestational age in control sheep but not in sheep with normal-sized or small caruncle fetuses. In all sheep, umbilical and uterine blood flows and antipyrine clearance correlated with placental weight. Umbilical blood flow per kilogram of placenta but not uterine blood flow per kilogram of placenta correlated inversely with placental weight. Fetal weight at 130 days generally correlated with placental weight, umbilical and uterine blood flows, and antipyrine clearance in a curvilinear fashion such that fetal weight was not greatly restricted until these variables were less than or equal to 65% of control values.

Animals↗

Acute hemorrhagic stress in conscious sheep elevates immunoreactive beta-endorphin in plasma but not in cerebrospinal fluid.

The effects of acute hemorrhagic stress on the concentrations of immunoreactive beta-endorphin (IR beta EP) in cerebrospinal fluid (CSF) and blood plasma were investigated in conscious sheep in which the cisterna magna, a carotid artery, and a jugular vein were chronically cannulated. Serial samples of CSF and jugular venous blood were collected before and after acute arterial hemorrhage and in control experiments. Basal concentrations of IR beta EP were higher in plasma than in CSF. Plasma concentrations of cortisol and IR beta EP increased within 45 min of the commencement of hemorrhage and returned to near baseline levels within 2.25 h. The concentrations of cortisol and IR beta EP in plasma observed after hemorrhage were significantly different from those observed in controls (analysis of variance). Neither the molar nor the relative changes from initial concentrations of IR beta EP in CSF were significantly different between hemorrhage-stressed and controls by analysis of variance. These results show that hemorrhagic stress in conscious sheep elevates concentrations of IR beta EP in plasma but not in CSF, indicating that pituitary beta EP secreted into blood does not enter CSF in significant amounts.

Animals↗

Effect of hypoxia on the initiation of secondary wool follicles in the fetus.

The development of secondary wool follicles in single fetal sheep subjected to hypobaric hypoxaemia was studied. One group of pregnant ewes were exposed to 57.1 kPa from 30 to 135 days gestation. Fetal weights (mean +/- s.d.) for the hypoxaemic group (3.35 +/- 0.53 kg; n = 4) were significantly lower than for the controls (4.19 +/- 0.31 kg; n = 3, P less than 0.05). At 110 days gestation, a second group had arterial and venous catheters surgically implanted into the ewe and fetus and skin samples were taken from the fetus. At 120 days gestation (10 days after surgery) these animals were subjected to hypoxia for 20 days, at a level to maintain fetal carotid pO2 between 1.47 and 1.87 kPa (mean carotid pO2 for the control fetuses was 2.84 +/- 0.28 kPa). Fetal weight at 140 days was not significantly different in the hypoxaemic and control groups. Morphometric analysis revealed that the secondary to primary follicle ratio (S:P) was less in both groups of hypoxaemic fetuses than in their respective controls. Although hypoxia for 20 days did not significantly alter fetal weight, it produced a low S:P ratio similar to the longer-term hypoxaemic animals. It is concluded that hypoxia has a marked effect in reducing the initiation of secondary follicles in the last third of gestation.

Animals↗

Secretion of N-terminal pro-opiomelanocortin-derived peptides in response to acute haemorrhagic stress in conscious sheep.

To determine whether peptides derived from the N-terminus of the corticotropin/melanotropin/endorphin precursor, pro-opiomelanocortin, are released into blood in response to acute haemorrhagic stress, we examined the effect of haemorrhage on plasma concentrations of immunoreactive gamma 3-melanotropin, beta-endorphin and cortisol. Plasma concentrations of immunoreactive gamma 3-melanotropin (mean +/- SEM) increased within 30 min of haemorrhage from 71.1 +/- 10.4 to 106.8 +/- 6.3 fmol/mL (p less than 0.01) and plasma cortisol increased from 16.2 +/- 3.8 to 85.9 +/- 22.4 pmol/mL (p less than 0.025). The changes in plasma immunoreactive gamma 3-melanotropin and beta-endorphin were positively correlated (p less than 0.025). This study shows that peptides derived from the N-terminus of pro-opiomelanocortin are co-secreted with the C-terminal peptide beta-endorphin during acute haemorrhagic stress in sheep.

Animals↗

Cannulation of the cisterna magna in sheep: a method for chronic studies of cerebrospinal fluid.

A method of cannulating the cisterna magna of sheep is described. Successful cannulations were achieved in 15 of 17 attempts (88%). Mean cannula patency was 13.9 days (range 7-20). Using these cannulas, it was possible to obtain samples of cerebrospinal fluid (CSF) in large volumes (4-8 ml) and remove 20-30 ml of CSF over a 5 h period. This technique allows access to the CSF of an animal large enough for the removal of samples of CSF of sufficient size to detect materials present at very low concentrations.

Animals↗

Intrauterine growth retardation: clinical and experimental.

Intrauterine growth retardation is a common and potentially hazardous problem for the fetus. Despite this, the obstetric factors associated with growth retardation have changed little in the last twenty years. Some of the other factors, the so-called behavioural factors should be amenable to correction through education or changing social circumstances. Experimental studies presented here support the clinical observations that the growth retarded fetus is often malnourished and/or hypoxaemic. Restriction of placental growth results in fetal growth failure and these fetuses are chronically hypoxaemic and hypoglycaemic. Furthermore the apparent margin of safety between the delivery to and consumption by the fetus is less for the small fetuses. We suggest that this reduction in supply results in the endocrine changes and that these in turn, modulate the pattern of fetal growth.

Animals↗

Effect of restriction of placental growth on the concentrations of insulin, glucose and placental lactogen in the plasma of sheep.

The effect of restricting placental growth on maternal glucose, insulin and placental lactogen was investigated in 16 ewes carrying singleton lambs. Uterine caruncles were removed from seven ewes (caruncle ewes) before pregnancy, resulting in reduced placental size and retarded intra-uterine fetal growth. The concentration of insulin in maternal plasma was similar in both control and caruncle ewes. The concentration of glucose was significantly higher in the caruncle than in the control ewes (3.26 +/- 0.15 (S.E.M.) mmol/l, number of observations (n) = 9, vs 2.75 +/- 0.1, n = 9, P less than 0.02, and 3.27 +/- 0.16, n = 7, vs 2.46 +/- 0.11, n = 12, P less than 0.001, for the carotid artery and utero-ovarian vein respectively). The concentration of ovine placental lactogen (oPL) in the utero-ovarian vein was reduced in the caruncle compared with the control ewes (283 +/- 65 micrograms/l, n = 8, and 705 +/- 106 micrograms/l, n = 18, P less than 0.02, respectively). Restriction of placental growth by removal of endometrial caruncles similarly reduced the concentrations of oPL in maternal arterial plasma (231 +/- 54 micrograms/l, n = 9, and 621 +/- 96 micrograms/l, n = 18, P less than 0.002). Production of oPL by the placenta was also reduced by limiting placental growth to 30 +/- 11 micrograms/min, n = 8, compared with 133 +/- 43 micrograms/min, n = 15, P less than 0.05, for the controls. Production of oPL per gram of placenta in the caruncle group, although only 34% of the control value, was not reduced significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Normal sister chromatid exchange levels in hospital sterilization employees exposed to ethylene oxide.

This study was undertaken to determine whether a specific group of hospital workers exposed to ethylene oxide (ETO) in sterilizing areas showed evidence of increased levels of sister chromatid exchange (SCE) formation. SCE frequencies were determined for 14 sterilizer workers and 14 matched controls. Time-weighted average (TWA) and peak ambient levels of ETO were measured in the sterilizing areas. Results indicated that all sterilizer workers were exposed to less than 5 parts per million TWA of ETO and that there were no statistically significant differences in SCE levels between sterilizer workers and controls. Smoking habits did appear to be associated with increased SCE levels. In this particular hospital setting no evidence of genetic effects stemming from employees' exposure to low levels of ETO was found.

Adult↗

Clinical exercise trial for stroke patients.

This investigation evaluated the effectiveness of the traditional and facilitation approaches to therapeutic exercise in stroke patients. A total of 42 adults (24 men and 18 women) with a mean age of 61.6 years (SD = 21) were selected from a larger population of hospitalized stroke victims. Stroke patients were classified by CT scan information and judged medically fit to participate in a nonrestrictive program by neurologic examinations and laboratory tests. The Barthel Index and the manual muscle test were administered at admission and discharge. Both facilitation and traditional exercise therapies improved functional and motor performance, but there were no significant differences between these approaches. The lack of differences between the facilitation and traditional exercise therapies may be due to heterogeneity of the stroke population, the small sample size, and the measurements used. The study demonstrates the need for a measurement instrument capable of reliably assessing the facilitation approach. Future investigations should incorporate lesion type, site, and side along with global measurements in evaluating differences among motor remediation approaches.

Activities of Daily Living↗

The relationship of body and placental weight to plasma levels of insulin and other hormones during development in fetal rabbits.

The relationship of body and placental weight with plasma levels of insulin, glucose, glucagon, glucocorticoids and somatomedins in fetal rabbits between 22 days of gestation and term has been investigated. At 22, 24, 26, 28 and 30 days gestation, body and placental weights were strongly correlated and were also significantly correlated with log transformed plasma insulin concentrations in individual fetuses from nulliparous does. At 30 days gestation, mean plasma insulin levels, as well as body and placental weights, were significantly elevated in fetuses from multiparous does (p less than 0.05) and in fetuses whose growth had been increased by surgical reduction in litter size on day 9 of pregnancy (p less than 0.001). Log insulin concentrations in fetuses from multiparous does and in litter-reduced fetuses were also significantly correlated with bodyweight. The correlation coefficient for log insulin and bodyweight in all individual rabbit fetuses at 30 days gestation was 0.69 (p less than 0.001, n = 116). Fetal log plasma glucagon concentrations at 26 and 28 days gestation were negatively correlated with body weight, but were not significantly related at 30 days gestation. Neither glucose nor glucocorticoid concentrations were significantly related to bodyweight in individual fetuses. Plasma somatomedin activity in litter-reduced fetuses at 30 days gestation, was significantly higher (p less than 0.02) than in normal fetuses, but was not significantly correlated with fetal body weight. The observation of strong positive correlation between insulin and bodyweight throughout the last third of gestation reinforces the belief that fetal insulin plays an important role in the regulation of both placental and fetal growth.

Animals↗