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Biomedical subjects

J M Davison

Publications and source records attributed to J M Davison.

At least 55 records · Page 3Linked to original sources

Erythrocyte sodium lithium countertransport in normal and hypertensive pregnancy: relation to haemodynamic changes.

OBJECTIVE: To establish the changes in erythrocyte sodium lithium countertransport (SLC) with advancing normal pregnancy and to determine if these changes were different in pregnancy induced hypertension (PIH). The changes in both groups were assessed in relation to haemodynamic changes. DESIGN: SLC, mean arterial pressure (MAP), cardiac output (CO) and total peripheral vascular resistance (TPVR) were determined serially during normal pregnancy and cross-sectionally in PIH. Women were studied again 20 weeks after delivery where possible. SETTING: Routine antenatal clinic and antenatal ward of a regional reference centre. SUBJECTS: Fifty-one normal primigravid women were studied serially and 41 primigravid women with PIH were studied at time of diagnosis. RESULTS: During normal pregnancy SLC (mmol Li/h/l cells) increased from a nonpregnant value of 0.24 +/- 0.02 (mean +/- SEM) to 0.32 +/- 0.02 at 14 weeks, and 0.37 +/- 0.02 at 20 weeks gestation. This was maintained until 38 weeks (0.40 +/- 0.02). The increase until 20 weeks occurred at the time of greatest change in CO (5.10 +/- 0.18 to 6.79 +/- 0.20 l/min) and TPVR (1327 +/- 58 to 969 +/- 33 dyn/s/cm-5). The decrease in TPVR with a rise in SLC is opposite to the relation reported in essential hypertension so that a functional relation is unlikely. However, the changes within pregnancy were positively correlated (r = 0.43, P < 0.01). In hypertensive pregnancies TPVR was elevated compared with normotensive pregnancies (1543 +/- 100 vs 1090 +/- 37) but the SLC was not different from that found in normotensive pregnancies (0.43 +/- 0.02 vs 0.40 +/- 0.02). CONCLUSIONS: The changes in SLC activity suggest dynamic effects on erythrocyte membrane function during pregnancy. However, no differences could be found between normal and hypertensive pregnancy and SLC is unlikely to be of value as a marker of hypertensive risk during pregnancy.

Adult↗

Alterations in erythrocyte chloride content accompanying the changes in erythrocyte hydration and potassium content in normal human pregnancy: a comparison with pregnancy induced hypertension.

OBJECTIVES: To determine whether the change in erythrocyte potassium content in normal human pregnancy is accompanied by a similar change in erythrocyte chloride content. To assess erythrocyte hydration and potassium and chloride content in pregnancies complicated by proteinuric pregnancy induced hypertension. DESIGN: A serial study during and after normal pregnancy. A comparative study during and after pregnancies complicated by proteinuric pregnancy induced hypertension (PIH). Erythrocyte hydration, total osmoles, potassium and chloride and plasma osmolality were determined. SETTING: University teaching hospital, UK. SUBJECTS: Twenty-eight women studied at 14, 28 and 36 weeks of normal pregnancy and ten women with PIH studied during the third trimester of pregnancy. All women were reinvestigated 20 weeks after delivery. RESULTS: The fall of erythrocyte potassium early in normal pregnancy (277.4 vs 265.2 mmol/kg; P < 0.02) and its rise between 28 and 36 weeks (272.3 vs 288.0 mmol/kg; P < 0.005) were accompanied by similar changes in erythrocyte chloride content (151.9 vs 131.1 mmol/kg; P < 0.001 and 129.4 vs 141.3 mmol/kg; P < 0.001, respectively). Plasma osmolality in PIH was raised above that normal in pregnancy (287.2 vs 283.0 mosm/kg; P < 0.005). In PIH, compared to normal pregnancy, erythrocyte hydration (2.00 vs 1.89 l/kg dry weight cells), total osmoles (573.0 vs 534.2 mosm/kg), potassium (303.0 vs 288.0 mmol/kg) and chloride (154.9 vs 141.3 mmol/kg) were greater. CONCLUSIONS: These findings further support the hypothesis that changes in plasma osmolality in pregnancy are secondary to alterations in cell osmoles and serve to limit changes in cell hydration. Erythrocyte composition and plasma osmolality are altered in PIH.

Chlorides↗

The effect of early labour, maternal analgesia and fetal acidosis on fetal plasma oxytocin concentrations.

OBJECTIVE: To determine the effect of early labour, maternal analgesia and fetal hypoxia on circulating fetal oxytocin concentrations. DESIGN: Prospective observational study. SETTING: Delivery suite in a District General Hospital. SUBJECTS: Fifty women at term who did not require oxytocin administration or more than one form of analgesia. Study groups: vaginal delivery with (1) no analgesia, (2) pethidine, or (3) epidural analgesia. Caesarean section under regional analgesia (4) prior to, and (5) after the onset of labour. INTERVENTIONS: Samples of blood were collected from the umbilical artery (UA) and umbilical vein (UV) immediately after fetal delivery prior to placental separation or oxytocic administration. MAIN OUTCOME MEASURES: Plasma oxytocin (OT) concentration, umbilical vein pH, cystine aminopeptidase activity. RESULTS: The geometric mean UA-OT was significantly greater than UV-OT in all groups and was not altered by pethidine; however, epidural administration increased the UA-UV difference. The UA-UV difference at caesarean section was not significantly altered by the onset of labour. There was no correlation between UV pH and UA-UV plasma oxytocin. Cystine aminopeptidase activity was not detectable in UA and UV plasma. CONCLUSIONS: Fetal OT production is increased by epidural but not by pethidine analgesia. It is not influenced by the onset of labour or fetal hypoxia.

Acidosis↗

Metabolic clearance of vasopressin and an analogue resistant to vasopressinase in human pregnancy.

The metabolic clearance rate (MCR) of arginine vasopressin (AVP) increases fourfold during human pregnancy. To explore whether circulating vasopressinase may play a role in this change, six women underwent a three-tier infusion clearance study, twice, in random order, to determine the MCRs of either AVP or 1-deamino-8-D-AVP (dDAVP, an analogue resistant to degradation by vasopressinase). Volunteers were tested in late pregnancy (LP), 24-48 h postdelivery (PD), and 5-6 (PP1) and 10-12 (PP2) wk postpartum, thus examining MCRs when vasopressinase levels were high, before and after removal of the placenta (LP and PD), and when plasma enzyme activity was becoming (PP1) and became (PP2) undetectable. Manipulation of infusate permitted comparison of MCRs at three plasma levels whose range was similar at each test period. PAVP and PdDAVP (2.2 and 10 pg/ml, respectively, during the initial infusion) increased to 8 and 31 pg/ml, stepwise increments that had no influence on respective MCRs (AVP: 3.4, 2.2, 0.77, and 0.67 l/min during LP, PD, PP1, and PP2 compared with 0.18, 0.21, 0.17, and 0.15 l/min for dDAVP). Comparison of similar and submaximal urinary osmolality revealed PdDAVP values three- to fourfold greater than PAVP. Von Willebrand factor (VWF) and factor VIIIc levels increased almost fourfold in response to dDAVP during pregnancy, but only doubled in the nonpregnant state; these differences did not reach significance. We conclude that although AVP disposal rates increase fourfold in pregnancy, those of dDAVP change little, suggesting a role of vasopressinase in the increased MCR of AVP in gestation (as well as in the genesis of certain polyuric disorders of pregnancy).(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine Vasopressin↗

Assessment of the renal circulation during pregnancy with color Doppler ultrasonography.

OBJECTIVES: A non-invasive method of assessing the renal vasculature during pregnancy would be useful in the management of patients with renal dysfunction resulting from preeclampsia or chronic renal disease. The objectives of this study were to determine (1) whether color ultrasonography during pregnancy facilitates Doppler interrogation of renal and intrarenal arteries, allowing (2) the assessment of differences between waveforms from nonpregnant and pregnant women and (3) the analysis of waveform variability throughout the kidney and between the right and left kidneys. STUDY DESIGN: In a cross-sectional study renal and intrarenal artery flow waveforms were obtained from women in early (12 to 19 weeks; n = 8), mid (20 to 29 weeks; n = 11), and late (30 to 37 weeks; n = 14) pregnancy with eight age-matched, nonpregnant women acting as controls. Waveforms were analyzed for pulsatility index, resistive index, and systolic/diastolic ratio. RESULTS: Left or right renal and upper- and lower-pole interlobar artery waveforms were obtained from all women. The mean pulsatility index values for the nonpregnant women were not significantly different from those women in early, mid, or late pregnancy. In the nonpregnant women, the left renal artery pulsatility index (1.13 +/- 0.13) was greater than the left lower interlobular artery pulsatility index (0.91 +/- 0.08; p < 0.05). During pregnancy renal and interlobar artery pulsatility index values were greater than those for the corresponding interlobular arteries, but the differences were not significant. Mean renal and intrarenal artery pulsatility index values were greater on the right, but the difference was significant only for the lower interlobular artery in midpregnancy. CONCLUSIONS: Pregnancy does not significantly affect renal and intrarenal artery flow waveforms, nor are there significant differences between waveforms from the renal and interlobar arteries.

Adult↗

Effect of pregnancy on long-term function of renal allografts.

Pregnancy in renal allograft recipients is associated with hyperfiltration with the potential for glomerular damage and adverse effects on long-term graft prognosis. We have undertaken a case-controlled study of posttransplant follow-up for a mean of 12 years (range, 4 to 23) in 36 female renal allograft recipients, 18 who became pregnant and 18 controls (matched to underlying disease and renal function) who did not. Assessments included plasma creatinine (PCr), glomerular filtration rate (GFR) by infusion clearance of inulin (Cin), mean arterial pressure (MAP), and documentation of antihypertensive therapy. By the end of follow-up, PCr in the pregnancy group (112 +/- 73 mumol/L [1.26 +/- 0.83 mg/dL]) and controls (127 +/- 52 mumol/L [1.44 +/- 0.59 mg/dL]) had increased by 19% and 8%, respectively, and GFR in the pregnancy group (58 +/- 29 mL/min) and controls (56 +/- 32 mL/min) had decreased by 18% and 7%, respectively. Graft loss or chronic rejection occurred in two patients in each group and there was a death in the pregnancy group 9 years after the second of two successful pregnancies. MAP in the pregnancy group (96 +/- 12 mm Hg) had decreased by 1%, and in the controls (101 +/- 9 mm Hg) had increased by 5%. Two patients in the index group and three in the control group commenced antihypertensive therapy during follow-up. There was, therefore, no evidence of an adverse effect of pregnancy in renal allograft recipients on long-term renal function or development of hypertension.

Adult↗

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↗

Plasma oxytocin during the first and second stages of spontaneous human labour.

A technique for complete oxytocinase inhibition has been combined with a rapid serial sampling strategy to determine plasma oxytocin concentrations in twelve women during the early and late first stage and in eight women throughout the second stage of labour. The progress of labour is not related to an increase in oxytocin concentration, uterine contractions are not associated with changes in plasma oxytocin concentration and hypocontractile labour does not appear to be the result of a deficit of oxytocin. The majority of patients do not demonstrate an increase in plasma oxytocin concentration during the second stage of labour; however, a minority produce a large surge immediately before delivery. The results do not support a role for oxytocin during spontaneous labour unless uterine activity is controlled by extremely low plasma hormone concentrations or the uterus becomes sensitive to a constant oxytocin concentration.

Adult↗

Osmotic and volume control of vasopressin release in pregnancy.

This article, a review of factors controlling vasopressin (AVP) release in pregnancy, extends our contribution to a symposium in this journal published in 1987 (vol X, pp 270-275). Body tonicity decreases (approximately 10 mOsm/kg) very early in pregnancy due to decrements in the osmotic thresholds for AVP release and thirst. In addition, the metabolic clearance rate (MCR) of AVP markedly increases between gestational week 10 and midpregnancy, and is paralleled by the appearance and increase of circulating cystine aminopeptidase (vasopressinase), while the MCR of 1-deamino-8-D-AVP (DDAVP), an analogue resistant to inactivation by the enzyme, changes little in pregnancy. These increases (MCR of AVP and plasma vasopressinase) may explain certain syndromes of transient diabetes insipidus (DI) that complicate gestation. Finally, mechanisms responsible for the altered osmoregulation in pregnancy are obscure, but chorionic gonadotropin may be involved in the changes during human gestation.

Animals↗

Dialysis, transplantation, and pregnancy.

Women on regular dialysis are usually infertile, but contraception should not be neglected. Pregnancy is invariably complicated and poses excessive risks, with an uncertain and low chance of success. Even when therapeutic abortion is excluded, the live birth outcome at best is 19%. Renal transplantation usually reverses abnormal reproductive function and comprehensive pre-pregnancy counseling is essential, with discussion of all implications, including the harsh realities of long-term maternal survival. In this survey of 2,309 pregnancies in 1,594 women, therapeutic abortion was undertaken in 27% of conceptions and the spontaneous abortion rate was 13%. Of the conceptions that continued beyond the first trimester, 92% ended successfully. In most, renal function was augmented in pregnancy, with transient deterioration in late pregnancy (with or without proteinuria). Permanent renal impairment occurred in 15% of pregnancies. There was a 30% chance of developing hypertension, preeclampsia or both. Preterm delivery occurred in 50%, and intrauterine growth retardation in 25% of pregnancies. Despite its pelvic location, the transplanted kidney rarely produced dystocia and was not injured during vaginal delivery. Cesarean section should be reserved for obstetric reasons only. Neonatal complications include respiratory distress syndrome, leukopenia, thrombocytopenia, adrenocortical insufficiency, and infection. No predominant or frequent developmental abnormalities have been described and data on infancy and childhood are encouraging. For the future more work is needed to improve pre-pregnancy assessment criteria, to understand the mechanisms of gestational renal dysfunction and proteinuria, to assess the side effects and implications of immunosuppression in pregnancy, and to elucidate the remote effects of pregnancy on both renal prognosis and the offspring.

Delivery, Obstetric↗

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↗

Perinatal outcome in renal allograft recipients: prognostic significance of hypertension and renal function before and during pregnancy.

With more renal allograft recipients becoming pregnant, it is important to refine existing pre-pregnancy assessment criteria and to identify other factors influencing perinatal outcome. We analyzed gestational renal response and acute or chronic hypertension in relation to perinatal outcome for 22 pregnancies that continued beyond 28 weeks' gestation in 17 allograft recipients (mean age 27 years, range 20-40) transplanted between 1967-1987. Before pregnancy, all had plasma creatinine of 1.62 mg/dL or less and 24-hour creatinine clearance of 39 mL/minute or greater. Six pregnancies were to four women on antihypertensive therapy. Mean arterial pressure (MAP), antihypertensive therapy, plasma creatinine, and 24-hour creatinine clearance were recorded before and during pregnancy. Perinatal outcome was adverse in ten pregnancies: five stillbirths, four growth-retarded infants, and one neonatal death, whereas 12 pregnancies had satisfactory perinatal outcome. Early-pregnancy increments and late-pregnancy decrements in renal function were identical in both groups. Mean arterial pressure was significantly higher at 16-28 weeks in women having adverse outcomes. Hypertension (MAP above 107 mmHg) occurred in 16 pregnancies (73%); it appeared before 28 weeks in seven and was invariably associated with adverse outcome. Hypertension appeared after 28 weeks in nine women and was associated with adverse outcome in only two cases. Five of six pregnancies in women who were on pre-pregnancy antihypertensive therapy ended in adverse outcome. It can be concluded that renal function was identical in pregnancies having adverse or satisfactory perinatal outcome, whereas hypertension before or during early pregnancy, albeit apparently satisfactorily controlled, appeared to be associated with adverse perinatal outcome.

Acute Disease↗

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↗

Effect of human pregnancy on metabolic clearance rate of oxytocin.

The metabolic clearance rate (MCR) of oxytocin (OT) was determined by use of constant infusion techniques to achieve low and high plasma OT concentrations in 10 women in late pregnancy and again 8-10 wk postpartum (mean plasma oxytocinase activity was 2.1 IU/ml plasma at term and less than 0.1 IU/ml plasma 8-10 wk postpartum). At the lower plasma OT concentrations (5.0 and 5.2 pg/ml, pregnant and postpartum, respectively) produced by infusion of 17.9 ng/min in pregnancy and 4.3 ng/min postpartum, mean MCR of OT was increased fourfold during pregnancy (5.7 +/- 0.6 and 1.3 +/- 0.1 l/min, pregnant and postpartum, respectively; P less than 0.001). At the higher plasma OT concentrations (8.0 and 8.0 pg/ml, pregnant and postpartum, respectively) produced by infusion of 35.7 ng/min in pregnancy and 8.5 ng/min postpartum, mean MCR of OT was likewise markedly increased during pregnancy compared with postpartum values (7.1 +/- 1.9 and 1.4 +/- 0.1 l/min, respectively; P less than 0.01). The MCR of OT was independent of plasma concentration (between 5 and 8 pg/ml) during pregnancy and in the postpartum period. It is concluded that the MCR of OT is increased markedly during human pregnancy. This may be due to concomitant increases in in vivo cystine aminopeptidase activity or other less specific pregnancy-associated metabolic changes.

Adult↗

Influence of humoral and volume factors on altered osmoregulation of normal human pregnancy.

These studies were designed to characterize mechanisms leading to decreased plasma osmolality (Posmol) and osmotic thresholds (T) for arginine vasopressin (AVP) release (TAVP) and thirst (Tthirst) in pregnancy. First, the influence of the pregnancy hormone, human chorionic gonadotrophin (hCG), was tested in six nonpregnant women who received hypertonic saline during the luteal phase of the menstrual cycle on two occasions (randomly allocated), once after 15,000 IU of hCG when Posmol, TAVP, and Tthirst decreased 6, 5, and 5 mosmol/kgH2O, respectively (P less than 0.01). In contrast, hCG pretreatment of males (n = 6) had no significant effect. Next, the role of decreased effective vascular volume (underfilling) was evaluated in seven women undergoing hypertonic saline infusion in the presence and absence of head-out water immersion (randomly allocated) during early and late pregnancy and postpartum. Posmol, TAVP, and Tthirst were not influenced by immersion and remained 10 mosmol/kgH2O lower in pregnancy (P less than 0.01). Central redistribution of intravascular volume consistently lowered hematocrit and rate of rise of PAVP per unit increment in Posmol (P less than 0.01). Although these data failed to support the hypothesis that the osmoregulatory change in human pregnancy is attributable to decrements in effective central volume (underfill), they do suggest that hCG may play a role.

Adult↗