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Biomedical subjects

A A Calder

Publications and source records attributed to A A Calder.

At least 55 records · Page 3Linked to original sources

Correlation between umbilical artery resistance index, 6 ketoprostaglandin F1 alpha and thromboxane B2 in the fetoplacental compartment in patients with pregnancy induced hypertension.

Umbilical artery flow velocity waveforms (UAFVW's) were measured by Doppler ultrasound in 35 pregnant women with pregnancy induced hypertension. The stable hydration products of the vasoconstrictor and proaggregatory thromboxane A2 and vasodilatory and anti-aggregatory prostacyclin (i.e. thromboxane B2 (TxB2) and 6 ketoprostaglandin F1 alpha (6 keto PGF1 alpha) respectively) were measured in blood obtained from the umbilical vein and were assayed by radioimmunoassay. Abnormal umbilical artery Resistance Index (UARI) was associated with higher thromboxane B2 levels, lower 6-ketoprostaglandin F1 alpha levels and lower 6-keto PGF1 alpha/TxB2 ratio. Moreover, the umbilical artery Resistance Index was significantly correlated with the 6-keto PGF1 alpha/thromboxane B2 ratio suggesting an association between abnormal umbilical artery blood flow and altered prostacyclin/thromboxane balance in the fetoplacental compartment in patients with pregnancy induced hypertension (PIH).

6-Ketoprostaglandin F1 alpha↗

Plasma prostaglandin metabolite concentrations in normal and dysfunctional labour.

OBJECTIVE: To determine the concentrations of the metabolites of prostaglandin E2 (PGEM) and of prostaglandin F2 alpha (PGFM) prior to the onset of labour and during spontaneous labour, and to correlate the changes in concentrations of these metabolites with labour outcome. DESIGN: Longitudinal study throughout labour. SETTING: Labour ward of a large maternity unit. SUBJECTS: Seven primigravid and 11 parous women in the late third trimester with no signs of labour, and 17 primigravid and 11 parous women in spontaneous labour. INTERVENTIONS: Six of the primigravid women required augmentation with oxytocin because of dysfunctional labour. RESULTS: Before labour, parous women had significantly higher concentrations of both PGEM (P < 0.007) and PGFM (P < 0.006) compared with primigravid women. During labour, PGFM concentrations were significantly higher in both primigravid (P < 0.0002) and parous (P < 0.0001) women compared with the concentrations of these metabolites in women not in labour; the same was true for PGEM in primigravid (P < 0.003) but not in parous (P = 0.1) women. There was a small but significant increase (P < 0.02) in PGEM as labour progressed in both the normal groups. Amniotomy was associated with a significant increase in PGFM in primigravid and parous women (P < 0.002 and P < 0.009, respectively). The concentration of PGFM one hour following amniotomy correlated inversely with the amniotomy to delivery interval in both the normal primigravid (r = -0.624; P = 0.04) and the parous (r = 0.745; P = 0.021) groups. Women with dysfunctional labour showed no significant rise in PGEM or PGFM. Their PGFM concentrations were significantly lower than those seen in normal labour (P < 0.05). The concentration of PGFM in cord blood was significantly higher (P < 0.0001) in the parous women who laboured than in women delivered by elective caesarean section. There was no difference in the corresponding concentrations of PGEM (P = 0.9). CONCLUSIONS: These data show that spontaneous labour is associated with increased concentrations of prostaglandin metabolites in the maternal plasma, and are consistent with PGF2 alpha being an important stimulator of uterine contractility, with a relative deficiency of PGF2 alpha being associated with dysfunctional labour.

Adult↗

Gemeprost-induced cervical ripening: histological and biophysical effects.

The mechanism of prostaglandin-induced cervical ripening is not clear. The aim of this study was to measure the biophysical and histological effects of gemeprost on the cervix. Thirty-four women admitted for surgical termination of pregnancy in the first trimester were randomised in a double-blind manner to receive either gemeprost or placebo prior to surgery. In 20 (10 active, 10 placebo) a needle biopsy was taken from the anterior lip of the cervix prior to cervical dilatation for histology. The forces required to dilate the cervix from 3 mm to 10 mm were measured. A group of seventeen parous women undergoing surgical termination who did not receive gemeprost were also studied as a parous control group. A needle biopsy was obtained in eight of them and also in six non-pregnant parous women undergoing hysterectomy for benign conditions, the latter acting as a non-pregnant control group. Polymerised collagen was stained with Picrosirius red and glycosaminoglycans with alcian blue using a MgCl2 gradient. Optical densitometry was used as an objective measure of staining. Neutrophil concentration was assessed immunohistochemically. Gemeprost treatment increased free passibility (the size of the largest dilator which could be passed without encountering resistance) (P < 0.01), reduced the forces required to dilate the cervix (P < 0.01) reduced blood loss (P < 0.05), reduced the collagen concentration (P < 0.01) and was associated with a modest neutrophil influx (P < 0.02) as compared to placebo. The pregnant parous group had a significantly lower collagen concentration than the non-pregnant parous group (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Induced↗

Choriodecidual production of interleukin-8 and mechanism of parturition.

Both prostaglandins and antiprogestagens can induce labour and ripen the cervix, but the mechanisms are unclear. The collagenases that bring about cervical ripening are neutrophil derived. We examined the potential of uterine tissues to control neutrophil attraction by measuring interleukin-8 production. Choriodecidual cells in culture produced substantial amounts of interleukin-8; release was inhibited by progesterone and stimulated by the antiprogestagen mifepristone. Interleukin-8 production was similar in cells from spontaneously delivered placentas and from those obtained at caesarean section. Since prostaglandin E and interleukin-8 have synergistic effects, we suggest that interleukin-8 activity is the final common step of prostaglandin and antiprogestagen action in parturition.

Cells, Cultured↗

Prostaglandins and the cervix.

The dramatic capabilities of prostaglandins to modify the condition of the uterine cervix have been exploited to the considerable benefit of patients who require therapeutic interventions for labour induction and termination of pregnancy. This will continue to be an important facet of clinical obstetric and gynaecologic practice, although further refinements and improvements in techniques seem certain to continue.

Abortion, Therapeutic↗

The effect of pH on release of PGE2 from vaginal and endocervical preparations for induction of labour: an in-vitro study.

OBJECTIVE: To study the effect of pH and precoating with obstetric cream on the release of prostaglandin E2 (PGE2) from commercially available triacetin and starch based gels, lactose based vaginal tablets and sustained release hydrogel polymer pessaries in-vitro. DESIGN: A prospective observational study. METHODS: PGE2 preparations held in dialysis bags were placed in Ringers lactate buffer and release of PGE2 into the buffer was measured over 8-12 h by radioimmunoassay. The hydrogel polymer pessary was also assessed after precoating with obstetric cream. MAIN OUTCOME MEASURES: In-vitro PGE2 release at pH 7.4, pH 5.4 and pH 3.4. RESULTS The gel preparations provided rapid and reliable release, while the lactose based vaginal tablet provided much lower release of PGE2 with sudden and variable release occurring after 5-8 h, an effect which was enhanced at low pH. With the triacetin gel preparation, release of PGE2 was reduced at lower pH, while the starch based gel appeared to provide optimal release at pH 5.4. The hydrogel polymer pessaries provided linear release in-vitro and this was reduced at pH 3.4. In addition, precoating the sustained release hydrogel polymer pessaries with obstetric cream virtually abolished release of PGE2. CONCLUSIONS: As the vagina is normally acid, these results suggest that vaginal pH could influence PGE2 release and this may result in variable clinical responses. In view of this, pH should be taken into account in the development of preparations for clinical use. Furthermore, the use of obstetric cream should be avoided when administering PGE2 preparations for induction of labour.

Cells↗

A comparative study of danazol and norethisterone in dysfunctional uterine bleeding presenting as menorrhagia.

This randomized open study compared the efficacy and safety of norethisterone, 5 mg three times a day from day 19 to 26, and danazol, 200 mg daily, in the treatment of dysfunctional uterine bleeding presenting as menorrhagia. Clinical criteria were employed to confirm the diagnosis, and subjective assessment of the condition was performed during one pre-treatment and three treatment cycles. Fourteen patients commenced norethisterone and 10 danazol. Bleeding intensity scores were significantly lower with danazol than with norethisterone, and patients assessed their blood loss to be significantly less with danazol than with norethisterone. Associated symptoms of backache and abdominal pain were improved to a similar degree by both treatments. Adverse reactions were reported with similar frequency and were of a similar nature in both treatment groups.

Abdominal Pain↗

Labor and normal delivery: induction of labor.

The continuing search for improvements in the methods of labor induction has seen the development of techniques that are more efficient, more reliable, safer, and more acceptable to the patient. Ultimately, these objectives will be best served by striving to mimic the normal physiology of parturition as closely as possible. Attention must be paid to the control of cervical ripening as well as myometrial contractility. Refinements in the use of oxytocin and prostaglandins continue to produce better results and the dawning of the era of progesterone receptor blockers gives hope of further significant advances.

Cervix Uteri↗

Neutrophil activation is confined to the maternal circulation in pregnancy-induced hypertension.

The aim of this study was to determine whether neutrophil activation occurs in the fetal circulation in pregnancy-induced hypertension and to correlate this with evidence of neutrophil activation in the maternal circulation. Twenty-one normal pregnancies and 23 complicated by pregnancy-induced hypertension were studied in the third trimester. The mean length of gestation at delivery was significantly shorter (P less than .01) and the mean birth weight percentile was significantly lower (P less than .05) in the hypertensive group; otherwise the groups were comparable. Blood was obtained before cesarean delivery or established labor in the mothers and immediately after delivery from the umbilical vein. Plasma neutrophil elastase, which is released after neutrophil activation, was measured by radioimmunoassay as a marker for neutrophil activation. The mean (+/- standard error) concentration of neutrophil elastase in maternal plasma in the hypertensive group (35.9 +/- 4.7 ng/mL) was significantly higher than in the normal group (20.8 +/- 0.87 ng/mL) (P less than .005). The concentration of neutrophil elastase in umbilical venous plasma was not significantly different between the normal and hypertensive groups. However, significantly higher concentrations of neutrophil elastase were found in the umbilical venous plasma of pregnancies delivered vaginally compared with those delivered by cesarean (P less than .05) regardless of diagnosis. There was no correlation between maternal venous and umbilical venous plasma neutrophil elastase concentrations, birth weight percentile, plasma urate, or platelet count. These data suggest that neutrophil activation is confined to the maternal circulation in pregnancy-induced hypertension where it may contribute to vascular damage and dysfunction in areas such as the placental bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Prostaglandins as therapy for labour induction or therapeutic abortion.

(a) Prostaglandins (especially PGE2) are highly effective for ripening the cervix and inducing labour. If the cervix is already ripe, a small dose of PGE2 may be all that is required to initiate a labour which resembles spontaneous labour as closely as possible. (b) Amniotomy is the central event. Although it is possible for an infant to be born in the caul, i.e. in intact membranes, it is the general rule for the membranes to rupture or to be ruptured during labour. Such rupture leads to heightened activity of endogenous prostaglandins. The timing of amniotomy is crucial. Performed too early, before the cervix is ripe, it may lead to complications. Delayed too late, we may lose the advantage of its uterine sensitizing. (c) Oxytocin is a potent myometrial stimulant if the uterus is primed to respond to it by prostaglandins, either endogenous or exogenous. It must be given intravenously and many mothers find this disagreeable. In most instances of labour induction, a proper combination of prostaglandin therapy and amniotomy may allow the use of oxytocin to be avoided, but it remains the therapy of final resort to carry labour through to delivery if required.

Abortion, Therapeutic↗

Vaginal administration of PGE2 for induction of labor stimulates endogenous PGF2 alpha production.

Prostaglandin E2 is effective for induction of labor but many preparations exist using a variety of vehicles from which the active ingredient may not be equally available. Plasma concentrations of bicyclic PGE2 metabolite (PGEM) and 13, 14-dihydro, 15-keto PGF2 alpha (PGFM) were measured following administration of a 3mg PGE2 vaginal tablet or 1mg PGE2 vaginal gel to twenty-four parous women with favorable induction features, randomly allocated to receive one or other preparation. PGEM increased rapidly following both administration of the 3mg PGE2 vaginal tablet and the 1mg PGE2 vaginal gel, reaching a peak within 40 minutes of PGE2 administration. The maximal rise in PGEM in the gel group correlated directly with the change in cervical score and inversely with the need for augmentation with oxytocin and the induction-delivery interval. A secondary rise in PGFM was noted in both groups 3-4 hours following PGE2 administration. The magnitude of the increase in PGE2 may be important in the clinical response to PGE2 administration, while PGE2 absorption may switch-on endogenous PGF2 alpha production, similar to what is seen in spontaneous labor.

Administration, Intravaginal↗

Neutrophil activation in pregnancy-induced hypertension.

Human neutrophil elastase may be a major mediator of vascular damage and could contribute to the vascular damage seen in women with pregnancy-induced hypertension (PIH). Elevated plasma levels of this substance will reflect neutrophil activation in vivo. To determine neutrophil activation in PIH, we studied 30 normal non-pregnant women, 32 women with normal pregnancies, 19 with mild/moderate PIH and 16 with severe PIH between 28 and 39 weeks gestation. Plasma neutrophil elastase was measured by radioimmunoassay. There was a significantly higher concentration of plasma neutrophil elastase in both mild/moderate and severe PIH than in normotensive pregnancies and this may contribute to the vascular lesion associated with PIH. Concentrations were also significantly higher in normal pregnancy than in non-pregnant women which suggests that neutrophil activation and degranulation are increased in normal pregnancy.

Adult↗

An analysis of uterine activity in spontaneous labour using a microcomputer.

A microcomputer was used to analyse uterine activity during spontaneous labour in 30 nulliparous and 30 parous patients. The intrauterine mean active pressure (MAP) in the nulliparous group was 1.51 kPa (SD 0.45) in the first stage and 2.71 kPa (SD 0.77) in the second stage. For the parous group, the MAP in the first stage was 1.22 kPa (SD 0.37) and in the second stage was 2.92 kPa (SD 0.98). A significant parity difference in MAP and contraction frequency was observed in the first stage but not in the second stage. Epidural analgesia did not appear to influence uterine activity in the first stage but was associated with a lower MAP, contraction frequency and intensity in the second stage. During the first stage, MAP increased by 21% in nulliparas and by 39% in multiparas. The rise in MAP was mainly due to an increase in contraction frequency.

Analgesics↗