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Biomedical subjects

M D Mitchell

Publications and source records attributed to M D Mitchell.

At least 289 records · Page 16Linked to original sources

In-vitro venous prostacyclin production, plasma 6-keto-prostaglandin F1 alpha concentrations, and diabetic retinopathy.

Previous studies have shown that vessels from diabetics produce less prostacyclin in vitro than those from normal controls. To determine whether this decreased production is related to complications elective biopsy of a superficial forearm vein was performed on 12 insulin-dependent male diabetics, six with nil or minimal and six with proliferative retinopathy, and seven male controls. Vein segments from the diabetics and controls produced similar amounts of prostacyclin in vitro (medians 0.11 and 0.19 ng/mg tissue respectively), but the segments from the diabetics with nil or minimal retinopathy produced less than those from the diabetics with proliferative retinopathy (medians 0.09 and 0.18 ng/mg respectively). Preoperative plasma immunoreactive concentrations of 6-keto-prostaglandin F1 alpha were not significantly different between the controls and the diabetics (medians 101 and 116 pg/ml respectively). In a separate study, however, 11 diabetics with duration of disease of over 10 years and nil or minimal retinopathy had significantly lower concentrations than a matched group of 16 with background or proliferative retinopathy (medians 79 and 121 pg/ml respectively). These results do not support an association between reduced prostacyclin production and diabetic retinopathy.

6-Ketoprostaglandin F1 alpha↗

Plasma oxytocin concentrations during the menstrual cycle.

Concentrations of oxytocin have been measured in plasma samples obtained daily from 6 women throughout complete menstrual cycles. Measurements of menstrual blood loss and plasma levels of luteinizing hormone (LH), progesterone and 17beta-oestradiol suggested that normal ovulatory cycles were studied. A significant elevation in the circulating concentration of oxytocin was found in association with peak levels of LH. It is suggested that oxytocin may have a role in the process of ovulation in the human female.

Adult↗

Temporal relationships between peripheral plasma concentrations of oxytocin, progesterone and 13,14-dihydro-15-keto-prostaglandin F2 alpha during the oestrous cycle and early pregnancy in the ewe.

Peripheral plasma concentrations of oxytocin, 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM), progesterone and LH were determined at 3 hourly intervals during the oestrous cycle (n = 3) and in early pregnancy (n = 4) in sheep. The progesterone and LH concentrations showed that the cycling ewes were sampled during the periods of luteal regression (decreasing progesterone concentrations), the preovulatory gonadotrophin surge and the beginning of the next luteal phase (increasing progesterone concentrations). The pregnant ewes had basal LH concentrations and luteal phase concentrations of progesterone (greater than 1ng/ml after day 5 following mating) throughout the whole of the sampling period. Oxytocin concentrations in the non-pregnant ewes decreased around the time of luteal regression to reach low concentrations (mean concentrations of approximately 18pg/ml) during the preovulatory period and then increased after the preovulatory surge. PGFM concentrations exhibited a pulsatile pattern with increasing concentrations as progesterone levels fell. In the pregnant ewes oxytocin concentrations gradually fell until approximately 16 days post-mating (approximately 7-8pg/ml). The magnitude of the pulses in PGFM concentrations were also lower than in the cycling ewes. These results demonstrate that the increased concentrations of PGFM which are found during the period of luteal regression are not caused by increased peripheral concentrations of oxytocin.

Animals↗

Serial determinations of prostaglandin E levels in amniotic fluid following the vaginal administration of a prostaglandin E2 gel.

To determine the release and absorption of prostaglandin E2 from a viscous gel instilled into the vagina for clinical purposes, serial measurements of prostaglandins E and F in amniotic fluid have been made. The results obtained suggest that the exogenous prostaglandins reach the amniotic fluid four hours after administration and following the onset of uterine stimulation. The findings are in agreement with previous clinical observations and indicate that the technique could be used to make further improvements in the prostaglandin carrier vehicles used in clinical practice.

Amniotic Fluid↗

Prostaglandin synthesis inhibition by maternal and fetal sheep plasma and its relation to haptoglobin and albumin levels.

Mammalian plasmas and sera have been reported to contain endogenous inhibitors of prostaglandin synthesis (EIPS), but the identity and role of these suggested inhibitors is as yet undetermined. Albumin and haptoglobin have been proposed as possible inhibitors, and it has been suggested that EPIS may have a part to play in the control of PG production during pregnancy and in the neonatal period. As part of a series of studies aimed at elucidating the identity and role of EIPS, maternal and fetal blood samples were collected from chronically catheterized pregnant ewes, and plasma levels of albumin, haptoglobin and EIPS activity determined. Pregnant ewe plasma possessed high EIPS activity and fetal lamb plasma little or no EIPS activity. Levels of albumin and/or haptoglobin did not consistently parallel that of EIPS activity. A post-operative rise (4 sheep studied) and a pre-parturition nadir (1 sheep studied) in maternal plasma EIPS activity were also noted. The possible physiological significance of these results is discussed.

Animals↗

Comparisons between the abilities of various human and ovine plasmas to inhibit prostaglandin synthesis.

The ability of various human and ovine blood plasmas to inhibit prostaglandin synthesis in vitro has been tested. Human plasmas were significantly more potent in their ability to inhibit prostaglandin synthesis than their counterpart ovine plasmas. In general, female plasma had greater inhibitory activities than male plasmas and adult plasmas were more active than fetal plasmas. There was no simple correlation between the activity of plasmas as inhibitors of prostaglandin synthesis and their respective albumin or haptoglobin contents.

Age Factors↗

A comparison of plasma prostaglandin levels in term and preterm labour.

Peripheral plasma levels of 13,14-dihydro-15-keto-prostaglandin F (PGFM) were determined in women during pregnancy and in term and preterm labour. The PGFM concentrations at term were not significantly different from the levels between 26 and 34 weeks gestation. In both term and preterm labour there was a rise in PGFM levels with increasing cervical dilatation although the mean values tended to be lower during preterm labour. These findings may provide an explanation for the effectiveness of prostaglandin synthetase inhibitors in suppressing myometrial activity in preterm labour.

Cervix Uteri↗

The relation between the release of prostaglandins at amniotomy and the subsequent onset of labour.

Maternal peripheral plasma levels of 13,14-dihydro-15-keto-prostaglandin F (PGFM) were measured in 16 women following amniotomy performed for the induction of labour at term. After 5 1/2 hours, seven patients were in established labour (Group I) but the remaining nine patients required an intravenous infusion of oxytocin (Group II). An initial rapid rise in PGFM concentrations within five minutes of amniotomy occurred in all women and, therefore, the onset of labour does not appear to be a direct consequence of this initial increase. In Group I there was a significant increase in PGFM concentrations between five and 30 minutes after amniotomy and from 30 minutes to the time at which the last sample was collected; these later rises were associated with the onset and progress of labour in these women. These increases in PGFM concentrations did not occur in patients in Group II. The reason for this difference in response to amniotomy is as yet unclear.

Dinoprost↗

Is oxytocin involved in parturition?

Peripheral plasma levels of oxytocin were determined in women during pregnancy and labour. There was a significant increase in maternal plasma oxytocin with advancing gestation but no significant change in levels at any stage of labour. Oxytocin concentrations in umbilical cord plasma were measured after spontaneous vaginal delivery and at elective caesarean section. A significant arteriovenous difference, with higher arterial levels, was found in both groups and the values after labour were significantly higher tha at elective caesarean section. These findings suggest that the fetus is able to produce oxytocin which may play a role in human parturition.

Female↗

Oral prostaglandin E2 in ductus-dependent pulmonary circulation.

Prostaglandin E2 (PGE2) was administered orally, in doses of 12-65 microgram/kg at intervals of 1-4 hours, to 12 neonates in whom the pulmonary circulation depended on patency of the ductus arteriosus. After an oral dose, both oxygen saturation (SaO2) and plasma PGE2 concentration increased consistently within 15-30 minutes, reaching values comparable to those during i.v. infusions. Treatment continued for 5 days to 4 months. In eight infants, PGE2 withdrawal resulted in a decrease of SaO2, from a mean of 75 +/- 7% to 57 +/- 10% (+/- SD). The ductus remained responsive for long periods--in four infants, for over 3 months. Consequently, surgery could be delayed until the infants and their pulmonary arteries had grown. Side effects during oral therapy were similar to those during i.v. infusion but were less severe in this series. The effectiveness and simplicity of oral PGE2 administration have advantages over i.v. administration, especially for long-term treatment.

Administration, Oral↗

Breast-feeding and plasma oxytocin concentrations.

The patterns of response of oxytocin to a breast feed were studied in 10 mothers in the first week post partum. The initiation of lactation did not appear to be related to release of oxytocin. In established lactation an oxytocin response did not appear to be essential for adequate milk flow and did not occur always at the time of peak milk flow. The only factor identified that positively correlated with release of oxytocin was multiparity. In those subjects who showed a response the hormone was released in surges, some of which persisted in the circulation for less than one minute. These findings cast some doubt on the conventional view that release of oxytocin is essential for satisfactory milk flow during breast-feeding.

Breast Feeding↗

Specific changes in the in vitro production of prostanoids by the ovine cervix at parturition.

A method of tissue superfusion has been used to measure in vitro prostanoid production by the ovine cervix during late pregnancy and at parturition. In late pregnancy (105-135 days of gestation) cervical tissue produced relatively large amounts of prostaglandin E (PGE); in comparison, the production rates of prostaglandin F (PGF), 13, 14-dihydro-15-oxo-prostaglandin F (PGFM) and 6-oxo-prostaglandin F1 alpha were generally low. Thromboxane B2 (TXB2) production was minimal and often unmeasurable. There were significant increases in the production rates of PGE and 6-oxo-PGF1 alpha by cervical tissue taken immediately after delivery, when compared to late pregnancy. Mean production rates of PGE increased from 19.8 +/- 4.1 to 43.8 +/- 7.4 ng/g. dry wt./min; 6-oxo-PGF1 alpha production rates increased more than three-fold from 10.0 +/- 2.7 to 34.6 +/- 9.8 ng/g. dry wt./min (means +/- S.E.M.). There were no significant differences in the rates of production of PGF, PGFM and TXB2 by the two groups.

Animals↗