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Biomedical subjects

W Dunlop

Publications and source records attributed to W Dunlop.

At least 19 recordsLinked to original sources
PubMed1992

Is fetal heart rate monitoring sufficiently sensitive to detect changes during labour?

Although fetal monitoring is a common clinical procedure, there is little quantitative evidence that it can detect changes occurring during labour. We present quantitative data comparing the first and second stage of labour, from 21 labours resulting in a normal fetal outcome. A range of fetal heart rate variables was calculated from the output of a fetal heart rate monitor. Significant changes were detected in baseline fetal heart rate (P less than 0.005), heart rate variability (P less than 0.05), number of dips (P less than 0.01) and their depth (P less than 0.01). The results encourage confidence in the sensitivity of fetal monitoring for the detection of changes in a number of fetal heart rate variables during the course of labour.

Electrocardiography↗
PubMed1992

Pregnancy induced hypertension and sodium pump function in erythrocytes.

OBJECTIVE: To determine if erythrocyte sodium pump function is altered with the onset of pregnancy induced hypertension. DESIGN: A prospective descriptive study. SUBJECTS: Thirty-two primigravid women with pregnancy-induced hypertension (17 had proteinuria) and 32 gestation-matched normotensive primigravid pregnant women were studied and measurements repeated 20 weeks after delivery. INTERVENTION: Erythrocyte sodium, ouabain-sensitive sodium flux and the sodium pump rate constant were measured in whole blood and the maximum velocity and sodium affinity of the sodium pump were measured in vitro. RESULTS: Blood pressure remained higher after delivery in the women who had been hypertensive during pregnancy. In normal pregnancy erythrocyte sodium was decreased, and ouabain-sensitive sodium flux, the sodium pump rate constant and maximum velocity (Vmax) were increased compared with 20 weeks after delivery. In pregnancy-induced hypertension erythrocyte sodium and sodium pump changes were the same as in normal pregnancy. The possibility of a positive association between changes in erythrocyte sodium and in blood pressure was excluded. The rate constant of the sodium pump in blood was related to its Vmax measured in vitro but the relation had greater variance in the hypertensives with 7 of the 32 women having rate constants greater than expected from their Vmax. CONCLUSION: There was no evidence of sodium pump inhibition or a rise in intracellular sodium associated with increased blood pressure in pregnancy. There may have been stimulation of the sodium pump by a plasma factor in some hypertensive women.

Adult↗
PubMed1992

Evidence for Na(+)-Ca2+ exchange and Ca(2+)-induced Ca2+ release in a cultured vascular smooth muscle cell line from the rat.

Measurements of intracellular calcium (Cai2+) and sodium (Nai+) have been made in single smooth muscle cells from the rat aortic cell line (A10) using the Ca(2+)- and Na(+)-sensitive dyes Fura-2 and SBFI (sodium-binding benzofuran isophthalate). The effects of manipulation of intracellular and extracellular Na+ on Cai2+ have been investigated. Reversal of the Na+ gradient in control cells does not result in any measurable increase in Cai2+ or change in the rate of recovery of the cells from agonist stimulation, suggesting that there is little functional Na(+)-Ca2+ exchange. In ouabain-pre-treated cells however, the recovery from agonist stimulation is significantly slowed, suggesting that in the presence of an elevated intracellular Na+ concentration there is an alteration in the Ca(2+)-handling mechanisms. Reversal of the Na+ gradient in ouabain-pre-treated cells results in a transient increase in Cai2+ followed by a slow secondary rise. The transient component of this rise is absent on a second activation of the cell or by prior mobilization of the intracellular stores of Ca2+ by agonist. Data presented in this paper suggest the possibility that the transient component is due to a Ca(2+)-induced Ca(2+)-release mechanism triggered by an initial influx of Ca2+. The mechanism underlying this influx is not known but may involve the Na(+)-Ca2+ exchanger operating in reverse. The possible modulation of the Na(+)-Ca2+ exchanger and Ca(2+)-induced Ca2+ release by internal Na+ is discussed.

Animals↗
PubMed1992

Calcium oscillations in single isolated human vascular smooth muscle cells.

When cultured human vascular smooth muscle cells are exposed to sodium-free solutions oscillations in intracellular calcium concentration are observed. In some cells the oscillations are maintained at constant amplitude throughout the exposure to Na(+)-free solution, in others the amplitude of the oscillations falls to a lower, steady-state level. The oscillations are also activated and maintained in isotonic, Na(+)-free, K+ solutions suggesting that the underlying mechanism does not involve the opening and closing of voltage-dependent channels. The possible mechanisms responsible for this behaviour are discussed.

Calcium↗
PubMed1992

Mobilization of calcium by the brief application of oxytocin and prostaglandin E2 in single cultured human myometrial cells.

Intracellular calcium ([Ca2+]i) mobilization was studied in single cultured human myometrial cells in response to the agonists oxytocin and prostaglandin E2 (PGE2) using the fluorescent dye Fura-2. Oxytocin and PGE2 applications were associated with an increase in [Ca2+]i, although there was a marked intercell variation in the amplitude of the agonist-induced response. Removal of extracellular calcium ([Ca2+]o) reduced the oxytocin-induced rise and abolished the PGE2-induced rise in [Ca2+]i, thereby demonstrating that oxytocin but not PGE2 can mobilize intracellular stores of calcium. In nominally calcium-free medium, [Ca2+]i was not increased by PGE2 but subsequent application of oxytocin increased [Ca2+]i, thereby demonstrating that, within a single cell, calcium stores were mobilized by oxytocin and not PGE2. The intracellular calcium stores were completely depleted by a single application of oxytocin and not replenished in the absence of [Ca2+]o. Perfusion with calcium-containing medium for 100 s enabled store refilling. Cell depolarization by 140 mM-K+ caused a transient increase followed by a sustained elevation of [Ca2+]i on which were superimposed small fluctuations. Oxytocin caused an influx of calcium in cells depolarized by K+. This was more marked than that obtained with PGE2.

Calcium↗
PubMed1992

Oxytocin-evoked repetitive rises of intracellular calcium in single cultured human myometrial cells.

Repetitive transient increases in intracellular calcium were recorded in single cultured human myometrial cells exposed continuously to oxytocin (1 pM-1 nM). Each transient was preceded by a pacemaker-like gradual increase in baseline [Ca2+]i. Removal of extracellular Ca2+ reversibly stopped the transients although small fluctuations in [Ca2+]i were observed in seven out of eleven cells studied. In a proportion of cells (1-2%) repetitive Ca2+ transients were observed in the absence of exogenous oxytocin. The pattern of activity was similar to that seen in cells exposed to oxytocin. These spontaneous elevations in [Ca2+]i were reversibly inhibited by removing extracellular calcium. These experiments demonstrate for the first time repetitive agonist-induced and spontaneous transient increases in [Ca2+]i in single cultured human myometrial cells.

Calcium↗
PubMed1992

The effect of [Na+]i and [Na+]o on Ca2+ mobilization in the rat aortic smooth muscle cell line A7r5.

Measurements of intracellular calcium (Ca2+i) and sodium (Na+i) have been made in single smooth muscle cells in confluent cultures of the A7r5 cell line using the Ca(2+)- and Na(+)-sensitive dyes Fura-2 and sodium-binding benzofuran isophthalate (SBFI). Reversal of the Na+ gradient in control cells results in a small increase in Ca2+i and slows the rate of recovery in Ca2+i following agonist stimulation. This suggests that a Na(+)-Ca2+ exchange mechanism may be functioning in these cells. In ouabain-pretreated cells, Na+i is elevated and the recovery from agonist stimulation is significantly slowed. This suggests that the elevation of Na+i alters Ca2+ homeostasis. Reversal of the Na+ gradient in ouabain-pretreated cells results in a transient increase in Ca2+i which was larger than in control cells. This response is reduced during a second or third exposure to zero Na+o.NA+i, in Na(+)-loaded cells, falls in the absence of external Na+. This fall is slowed in the absence of external Ca2+ supporting the idea that the Na+ loss is via Na(+)-Ca2+ exchange. The possible modulation of the Na(+)-Ca2+ exchanger and Ca2+ mobilization by internal Na+ is discussed.

Animals↗
PubMed1992

Transients in intracellular free calcium in subconfluent and confluent cultures of a rat smooth muscle cell line.

The Ca2+ mobilizing mechanisms in the smooth muscle cell line A7r5 were found to undergo changes related to the degree of confluence of the cultures. In sparse cultures resting calcium was stable and exposure to arginine vasopressin (AVP) resulted in a single transient increase in intracellular free calcium (Ca2+i). In confluent cultures the cells could be divided into two general groups, those with a stable resting Ca2+i and those which demonstrated spontaneous brief elevations in Ca2+i of variable frequency. Application of AVP elevated Ca2+i, induced oscillations in quiescent confluent cells, increased the frequency of oscillatory activity in cells which were already active and, in cells which exhibited high frequency spontaneous fluctuations, inhibited this activity. Isotonic K+ depolarizing solution and normal solutions containing Co2+ inhibited Ca2+ spikes. These data suggest that the mechanism underlying the transients involves cyclical electrical phenomena at the cell membrane possibly utilizing calcium channels. There is no indication that the mechanism involves cytoplasmic oscillators.

Action Potentials↗
PubMed1992

Repetitive transients in intracellular Ca2+ in cultured human vascular smooth muscle cells.

Human uterine vascular smooth muscle cells have been isolated and maintained in culture. When these cells are exposed to bathing solutions with nominally zero sodium, using potassium, N-methyl-D-glucamine or Tris as substitutes, repetitive transient increases in intracellular calcium are observed. These transients are abolished when the calcium concentration of the bathing solution is reduced to nominally zero suggesting a role for extracellular calcium in the activation or maintenance of the transients. The hypothesis is proposed that the underlying mechanism involves a calcium influx through the reversed operation of a sodium-calcium exchange mechanism and the cyclical activation of calcium-induced calcium release from the sarcoplasmic reticulum. Noradrenaline (10(-6) M) and caffeine (20-30 mM) reversibly inhibited the transients. The inhibitory action of these agents could not be mimicked by dibutyryl cAMP suggesting that cAMP does not mediate the inhibition. Caffeine alone had no effect on resting calcium. Thimerosal (1-100 microM), an agent thought to activate a second type of calcium-induced calcium release mechanism activated repetitive transient increases in intracellular calcium which behave in a similar manner to those activated by sodium removal. These data are consistent with the presence of a thimerosal-activated calcium-induced calcium release mechanism in these cultured human cells. It is proposed that this mechanism is different from the calcium-induced calcium release mechanism, described in other cell types, which is activated by caffeine.

Bucladesine↗
PubMed1991

Properties of fetal heartbeat intervals during labour.

This study was designed to investigate the range of beat-to-beat changes in fetal inter-beat (RR) intervals during routine clinical monitoring in labour. Fetal RR intervals were automatically measured and collected from 10 fetuses. Intervals which were incorrectly measured were excluded, and the remaining 23,510 intervals were used to compile the distribution of beat-to-beat changes. The inter-quartile range of this distribution was 23 ms and the 99th centile fell at approximately 50 ms. No relationship could be established between beat-to-beat changes and the absolute RR interval. These findings differ from the results published by other workers on the basis of data obtained antenatally or during early labour. In addition, the results suggest possibilities for improving algorithms designed to enhance data quality in fetal heart rate monitoring.

Algorithms↗
PubMed1991

Serial changes in pulmonary haemodynamics during human pregnancy: a non-invasive study using Doppler echocardiography.

1. Serial pulmonary haemodynamic investigations were performed in 13 women before conception, at monthly intervals throughout pregnancy, and then at 6 months after delivery. 2. Mean pulmonary artery pressure was calculated from pulsed Doppler pulmonary velocities. Pulmonary flow was measured by Doppler and cross-sectional echocardiography. These two measurements were used to calculate pulmonary vascular resistance. 3. Mean non-pregnant pulmonary artery pressure was 13.8 mmHg and no significant change was demonstrated during pregnancy. 4. Pulmonary flow increased from 4.88 to 7.19 litres/min during pregnancy. 5. Pulmonary vascular resistance decreased from 2.85 resistance units before pregnancy to 2.17 resistance units at 8 weeks gestation. Thereafter there was no further significant change, values returning to pre-pregnant levels by 6 months after delivery.

Adult↗
PubMed1991

Is GIFT (gamete intrafallopian transfer) the best treatment for unexplained infertility?

OBJECTIVE: To compare the cumulative pregnancy rates after gamete intrafallopian transfer (GIFT) with the cumulative spontaneous pregnancy rates in couples with unexplained infertility. DESIGN: A contemporaneous study in a single group of patients. SETTING: Northern Regional Fertility Centre. SUBJECTS: 76 couples with unexplained infertility of more than 3 years duration. INTERVENTIONS: Successful pregnancies were recorded during at least 3 months before GIFT and up to 21 months after a maximum of three cycles of GIFT treatment. MAIN OUTCOME MEASURES: Pregnancy resulting in a live birth. RESULTS: Average monthly fecundability without treatment was 0.021 and after GIFT was 0.14 (P less than 0.001). This was reflected as a cumulative pregnancy rate of 52% after three cycles of GIFT and 30% after 24 months without treatment. CONCLUSIONS: The chance of having a baby after one cycle of GIFT is significantly greater than the chance in a spontaneous cycle. However, considering the cumulative pregnancy rates, we suggest that if GIFT is to be a realistic treatment option, it should be offered for more than one cycle.

Adult↗
PubMed1991

Reproducibility of ultrasonic measurement of fetal cardiac haemodynamics.

Two observers made independent estimates of volume flow across all four heart valves in 27 fetuses using a combination of cross-sectional and Doppler echocardiography. There were considerable discrepancies between observers in volume flow estimation arising from inconsistency both in cross-sectional and in Doppler measurements. One observer also produced a second estimate by making new measurements from the original recordings. There was considerable within-observer variability which was mainly due to errors in cross-sectional measurements. The problems of applying this technique to fetal cardiac haemodynamics are discussed.

Adult↗
PubMed1991

Gamete intrafallopian transfer (GIFT) compared with intrauterine insemination in the treatment of unexplained infertility.

OBJECTIVE: To compare GIFT, intrauterine insemination (IUI) with, and without, ovarian hyperstimulation in the treatment of unexplained infertility. DESIGN: Women randomly allocated to one of three treatment protocols. SETTING: Northern Regional Fertility Centre. SUBJECTS: 59 couples with unexplained infertility of more than 3 years duration. INTERVENTIONS: Three cycles of either GIFT, IUI after ovarian hyperstimulation or IUI in a spontaneous cycle. MAIN OUTCOME MEASURES: Pregnancy resulting in a live birth. RESULTS: Fecundabilities were 0.12 after GIFT, 0.018 after ovarian hyperstimulation and IUI, and 0.018 after IUI in a spontaneous cycle. The fecundability after IUI was no different from that which would be expected without treatment in these couples but fecundability was significantly better (P greater than 0.02) after GIFT. CONCLUSIONS: This trial does not support the use of IUI in the treatment of unexplained infertility but confirms the value of GIFT.

Adult↗
PubMed1991

Erythrocyte hydration in normal human pregnancy.

OBJECTIVE: To determine whether the fall in plasma osmolality in normal human pregnancy resulted in cellular overhydration. DESIGN: The changes in erythrocyte hydration, potassium and total osmoles in response to a decrease in osmolality in vitro and associated with the fall in plasma osmolality in normal pregnancy were determined. SUBJECTS: Fifty-one women were studied serially during pregnancy and again 20 weeks after delivery. RESULTS: Erythrocytes from pregnant women exposed in vitro to a 29.9% osmolality decrement had a 28.5% increase in cell hydration. At 14 weeks gestation although plasma osmolality was lower than after delivery (281.1 vs 291.6 mosmol/kg; P less than 0.001) both erythrocyte hydration (1.83 l/kg dry weight cells) and potassium (264 mmol/kg) contents were reduced from the nonpregnant values (1.88 l/kg; P less than 0.01; 272 mmol/kg; P less than 0.001). For the remainder of pregnancy plasma osmolality remained at this lower level but cell hydration and potassium both increased to values at 38 weeks gestation that were greater than in the nonpregnant state (1.92 vs 1.88 l/kg; 287 vs 272 mmol/kg). CONCLUSIONS: These findings suggest that a loss of cell osmoles may be a primary event affecting cell hydration in pregnancy and plasma osmolality is then reduced to maintain normal cell hydration. Subsequent changes in cell hydration were led by changes in intracellular osmole content.

Erythrocytes↗
PubMed1991

Inhibition of Ca2+ mobilization by caffeine in a cultured vascular smooth muscle cell line (A7r5).

The effects of caffeine on the resting level and agonist-induced changes in intracellular calcium ([Ca2+]i) have been studied in the vascular smooth muscle cell line A7r5. Caffeine (1-30 mM) lowers the resting [Ca2+]i by reducing the entry of Ca2+ and inhibits completely the mobilization of Ca2+ by arginine vasopressin. Application of forskolin, to elevate cAMP, does not affect the resting level of Ca2+i but does abolish the agonist-induced rise. These data add to the complexity of caffeine-induced changes in [Ca2+]i and point to a possible interaction between cAMP and other second messenger systems mobilizing Ca2+i in this cell type.

Animals↗
PubMed1990

A serial study of erythrocyte sodium content and sodium pump kinetics in pregnancy.

1. Normotensive primigravid pregnant women were studied longitudinally during pregnancy and 20 weeks after delivery. 2. Erythrocyte sodium content, ouabain-sensitive sodium flux and sodium pump rate constant were measured in whole blood, and the maximum velocity and sodium affinity of the sodium pump were measured in vitro. 3. Erythrocyte sodium content decreased and the sodium pump rate constant increased up to 26 weeks gestation. The increase in rate constant was due to an increase in the affinity of the sodium pump for sodium up to 20 weeks gestation. After 20 weeks gestation there was an increase in maximum velocity and a decrease in sodium affinity of the sodium pump but no further change in the sodium pump rate constant. 4. At 14 weeks gestation the sodium pump rate constant was correlated with both the maximum velocity and sodium affinity constant. After this time the relationship was much more variable and there was no correlation with the sodium affinity constant. The comparison of measurements of the sodium pump in whole blood and in vitro gave no evidence of sodium pump inhibition. 5. The erythrocyte sodium pump changed throughout gestation with different components to the change, but, overall, available sodium pump activity in blood increased and sodium content decreased.

Biological Transport, Active↗