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Biomedical subjects

W A Walters

Publications and source records attributed to W A Walters.

At least 37 records · Page 2Linked to original sources

Effect of inhibition of nitric oxide synthase and guanylate cyclase on hydralazine-induced vasodilatation of the human fetal placental circulation.

1. The vasodilator effects of hydralazine in vitro, using the Krebs' perfused human placental lobule was studied. Single placental lobules were bilaterally perfused (maternal and fetal sides 5 mL/min each, 95% O2, 5% CO2, 37 degrees C) and changes in fetal arterial pressure (FAP) and venous outflow (VO) were recorded. 2. Submaximal vasoconstriction was induced by KCl (20-50 mmol/L), which increased basal FAP from 22.8 +/- 1.7 to 91.3 +/- 3.9 mmHg (n = 9, P < 0.001), and decreased VO from 4.1 +/- 0.6 to 0.2 +/- 0.1 mL/min (n = 6, P < 0.01). 3. Hydralazine caused vasodilatation (IC50 1.9 mmol/L, n = 9) and increased VO in the presence of KCl-induced vasoconstriction. 4. Infusion of N omega-nitro-L-arginine (100 mumol/L) to block nitric oxide synthase caused the basal FAP to increase from 30.9 +/- 5.9 to 47.4 +/- 6.7 (n = 6, P < 0.05) and significantly potentiated hydralazine-induced vasodilatation (n = 7, P < 0.05). 5. The soluble guanylate cyclase inhibitor LY 83583 (6-anilino-5,8-quinolinedione) (1 mumol/L) significantly antagonized the vasodilatation produced by hydralazine (n = 5, P < 0.05). 6. Thus, Hydralazine appears to activate guanylate cyclase, leading to increased cyclic GMP in fetal arterial vascular smooth muscle to cause vasorelaxation. No evidence was obtained to suggest that hydralazine exerted its action by either releasing nitric oxide from endothelial cells in the placenta or acting as a nitric oxide donor.

Adolescent↗

Modulation by adenosine of thromboxane A2 receptor-mediated constriction in the human umbilical artery.

The powerful vasoconstrictor autacoid thromboxane A2 (TxA2) has pathological roles in many diseases including pre-eclampsia or pregnancy induced hypertension (PIH). Adenosine and other purines are released by tissues during ischemia as occurs in the utero-placental circulation during PIH. These substances, particularly adenosine, may modulate TxA2 constrictor responses. We therefore characterized TxA2 receptors in the umbilical artery in vitro using the competitive antagonist GR32191. Also examined was the Ca2+ channels' involvement in adenosine-induced inhibition of TxA2 vasoconstriction. Results showed that TxA2 receptors on umbilical arteries are identical to those present in platelets, the placenta and umbilical vein. Adenosine was found to inhibit equally constriction involving either voltage or receptor operated Ca2+ channels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Release of a substance from the human placenta having digoxin-like immunoreactivity.

1. The human placental lobule, perfused with a constant flow (5 mL/min) of Krebs' solution after delivery at term, released into the fetal perfusate a digoxin-like substance, as measured by a fluorescence polarization immunoassay. 2. Initially the venous concentration was 360 +/- 66.7 pmol/L digoxin equivalents. This level did not change significantly during fetal vasoconstriction induced by prostaglandin F2 alpha infusion and persisted for the duration of the experiment (1.5-2 h). 3. Infusion into the fetal circulation of Fab fragments of sheep antibodies to digoxin caused vasodilatation, indicated by a fall in perfusion pressure. 4. Thus a digoxin-like immunoreactive substance, previously reported to be present in the placenta, is released into the fetal circulation and may play a role in placental control of fetal vascular tone.

Adolescent↗

Vascular actions of purines in the foetal circulation of the human placenta.

1. The vasoactive effects of adenosine triphosphate (ATP), adenosine and other purines in the foetal circulation of the human placenta were examined. Single lobules of the placenta were bilaterally perfused in vitro with Krebs buffer (maternal and foetal sides 5 ml min-1 each, 95% O2:5% CO2, 37 degrees C). Changes in foetal vascular tone were assessed by recording perfusion pressure during constant infusion of each purine. To allow recording of the vasodilator effects, submaximal vasoconstriction was induced by concomitant infusion of prostaglandin F2 alpha (0.7-2.0 mumol l-1). 2. ATP (1.0-100 mumol l-1) usually caused concentration-dependent reductions in perfusion pressure. However, biphasic with initial transient increases, or only increases in pressure were sometimes observed. Falls in pressure caused by ATP were significantly reduced by addition to the perfusate of NG-nitro-L-arginine (L-NOARG) (100 mumol l-1) but not NG-nitro-D-arginine (D-NOARG) (100 mumol l-1). They were not influenced by addition of indomethacin (10 mumol l-1) or L-arginine (100 mumol l-1). 3. Adenosine (0.01-1.0 mmol l-1) consistently caused concentration-dependent reductions in perfusion pressure, this effect not being influenced by indomethacin. L-NOARG, but not D-NOARG, reduced the potency of adenosine approximately three fold. L-Arginine, but not D-arginine enhanced its potency by a similar amount. 4. 2-Methylthio-ATP, a selective P2 gamma agonist was approximately 50 times more potent than ATP as a vasodilator agent, always causing decreases in perfusion pressure. 5. Beta-gamma-Methylene ATP, a selective P20 agonist, was approximately 100 times more potent than ATP as a vasoconstrictor, but only caused transient increases in perfusion pressure.6. The rank order of vasodilator potencies of a selection of adenosine receptor agonists was, 2-chloroadenosine>>5-(N-cyclopropyl)-carboxamidoadenosine, >5-N-ethylcarboxamidoadenosine, >2-chloro-N6-cyclopentyladenosine, >CGS-21680 > N6-cyclohexyladenosine = adenosine. Vasodilatation due to adenosine was inhibited by the PI-A2 receptor antagonist 3,7-dimethyl-l-propargylxanthine(DMPX).7. These results suggest that ATP may cause an endothelium-dependent vasodilatation in the foetal vessels of the human placenta via activation of a P2y receptor linked to the formation of nitric oxide(NO). Vasodilatation caused by ATP may mask an accompanying vasoconstrictor effect mediated, via a P2X receptor, in the villous vascular smooth muscle. Adenosine acting on P1-A2 receptors, which are also present in the foetal vasculature, may require synergistic interaction with NO to achieve a maximal vasodilator response.

Adenosine↗

Autacoids affecting vascular tone in the human fetal extracorporeal circulation.

1. The human fetal extracorporeal circulation is normally a vasodilated, low pressure system. 2. As this vasculature lacks innervation, autacoids have been postulated as being of great importance in controlling its tone. 3. This has now been confirmed by pharmacological in vitro techniques, particularly utilizing perfusion of the isolated umbilical cord and placental lobule. 4. The fetal umbilical-placental vessels are sensitive to a wide range of vasoconstrictor autacoids, some of which can cause intense vasospasm. 5. Thromboxane A2 receptors have been identified in both umbilical vein and placental villous vessels. 6. Prostacyclin and endothelial cell-derived relaxing factor (or nitric oxide) may be largely responsible for the low vascular resistance normally found in the fetal extracorporeal circulation. 7. Immediately after birth it is likely that stimuli such as cooling, stretching and handling of the umbilical cord cause release of eicosanoids and other autacoids from the vessels, leading to their complete closure.

Autacoids↗

The effects of chronic maternal hypotension during pregnancy.

The relationship between chronic maternal hypotension and obstetric outcome was examined retrospectively in a group of 134 pregnant women and compared with a normotensive control group. The hypotensive women had significantly increased risks of delivery before the 38th week of gestation, lower birth-weight of babies for gestational age, and postpartum complications. In addition, the rates of preterm delivery before 37 weeks' gestation, birth-weight less than 2,500 g and significant meconium-staining of the amniotic fluid were higher in the hypotensive group, although these results did not reach statistical significance. These data support the need for a prospective study of the effects of chronic hypotension during pregnancy.

Adult↗

Medical audit of hysterectomy in the Hunter Area of New South Wales.

A computer search in the New South Wales (NSW) Department of Health statistical data base was made to obtain the medical record numbers of patients who had had hysterectomies in the public or private hospitals of the Hunter Area of the State during the years 1987-89. The medical records of patients so identified were then extracted and reviewed by a medical team. The age at and the principal indication for hysterectomy were noted in each case and these data were then compared with those for the rest of NSW. The hysterectomy rate in the Hunter Area was 66.5 per 10,000 women aged 15 years or more, compared with a rate of 33.8 per 10,000 in the rest of NSW. When the 9.04% of hysterectomies performed on patients whose domicile was outside the Hunter Area were excluded, the corrected hysterectomy rate for the area was 57.46 per 10,000 women. The commonest indications for hysterectomy were menorrhagia (25.4%) and fibroids (15.32%). The limitations of this kind of retrospective study are discussed and suggestions are made for an improved methodology to be used in a future study.

Adolescent↗

Regulation of fetal vascular tone in the human placenta.

Using an in vitro placental lobule perfusion technique, the human fetal placental vasculature has been found to respond vigorously with high sensitivity to various vasoconstrictor substances, including angiotensin II, endothelins 1 and 3, prostaglandins F2 alpha, E2 and D2 and the thromboxane A2 agonist U46619. Thromboxane A2 receptors mediating vasoconstriction have been characterized in fetal placental vessels and appear to be identical to those on human platelets and pulmonary blood vessels. Although the isolated fetal placental vessels are largely unresponsive to exogenous vasodilatory stimuli, when preconstricted they respond by vasodilatation to several vasodilator substances, including arachidonate, prostacyclin, prostaglandin E1, theophylline and nitroglycerine. The resistance offered to flow in vitro by the villous vasculature is therefore low, as it is in vivo. Both intrinsic and extrinsic mechanisms probably operate to cause relaxation of the vascular smooth muscle with the vasodilatory effects of locally released autacoids dominating the effects of those having vasoconstrictor actions.

Female↗

Self-reported long-term outcomes of hysterectomy.

OBJECTIVES: To investigate women's perceptions of and satisfaction with the long-term outcomes from a hysterectomy performed between 2 and 10 years ago and to determine whether satisfaction is related to demographic factors, factors associated with the hysterectomy, and the number or type of perceived benefits and problems associated with the hysterectomy. DESIGN: Retrospective survey by telephone interview and postal questionnaire of 236 women who had a hysterectomy between 2 and 10 years ago. SETTING: Women who had had a hysterectomy were identified from a community survey in the Hunter Region of NSW, Australia. SUBJECTS: Two hundred and thirty-six women who self-reported having had a hysterectomy between 2 and 10 years ago. MAIN OUTCOME MEASURES: Perceived benefits resulting from the hysterectomy; perceived physical and psychological problems caused by the hysterectomy; satisfaction with care. RESULTS: Relief from heavy bleeding was the most frequent benefit (57%) and the most important benefit (32%). Most of the women reported improvements in symptoms experienced before hysterectomy but more than half the women had symptoms which they believed had been worsened or caused by the hysterectomy. Despite this, high levels of satisfaction with the operation were reported. CONCLUSION: The results highlight the need to examine more closely decision-making about treatment for menstrual symptoms such as heavy bleeding.

Adult↗

Ethical aspects of surrogacy.

Ethical issues related to surrogacy are explored and an argument made for its ethical approval in circumstances where the particularities of the case warrant this approach to reproduction. Despite recent and impending legislation to prohibit commercial surrogacy in some States of Australia, although data are difficult to obtain, unofficial and anecdotal reports from medical practitioners specializing in the management of infertility throughout the country indicate an increasing number of requests for surrogacy and increasing referral of infertile couples to the USA for commercial surrogacy arrangements.

Ethics, Medical↗

Changes in the biological activity of autacoids during passage through the human perfused fetoplacental lobule.

Changes in the biological activities of a number of autacoids after a single passage through the human perfused fetoplacental lobule have been assessed by bioassay, whilst recording fetal vascular resistance. Bradykinin did not affect vascular resistance, but its biological activity on the superfused bioassay tissues fell by approximately 98%, whereas des-Asp1-angiotensin I activity increased at least 80-fold and the vascular resistance rose. All these effects were inhibited by captopril. Angiotensin II increased vascular resistance but its activity on the bioassay tissues was not changed. 5-Hydroxytryptamine activity was reduced by 67-90% and resistance to flow was not affected. The activities of prostaglandins D2, E2, and F2 alpha were slightly reduced. Prostaglandins D2 and F2 alpha caused vasoconstriction, their maximum effects being greater than those of either of the angiotensins. The TxA2-mimetic U46619 was approximately 90 times more potent than PGF2 alpha, as a vasoconstrictor, but the maximal effects were comparable. Thus, autacoid activity can be reduced, augmented or not affected during passage through the human perfused fetal placental vasculature.

Angiotensin I↗

Ovarian stromal and luteal tissue prostaglandins, 17 beta-estradiol, and progesterone in relation to the phases of the menstrual cycle in women.

The concentrations of prostaglandin F2 alpha, prostaglandin E2, the 15-keto-13, 14-dihydro-metabolite of prostaglandin F2 alpha, progesterone, and 17 beta-estradiol were measured in 31 ovarian stromal tissue and 18 luteal tissues. Tissue samples were obtained during abdominal hysterectomy. The ovarian stromal tissue prostaglandin F2 alpha content during the late secretory and early proliferative phases was significantly higher (p less than 0.001) than in tissues obtained during any other phases of the menstrual cycle. The ovarian stromal tissue prostaglandin E2 content was significantly elevated (p less than 0.01) during the late proliferative and early secretory phases. The content of the prostaglandin F2 alpha metabolite also was elevated (p less than 0.001) in ovarian stromal tissues obtained during the late proliferative and early secretory phases. Comparison of the concentrations of prostaglandins and sex steroids in ovarian stromal and luteal tissues indicate the latter to be far more active in terms of steroid and arachidonate metabolism. During the early luteal phase, when the luteal progesterone content was at its highest, both luteal and ovarian stromal tissue contents of prostaglandin E2 were also elevated. The late secretory phase of the menstrual cycle was characterized by lowered luteal progesterone content and a markedly elevated level of prostaglandin F2 alpha in luteal and ovarian stromal tissues. During cyclic ovarian activity in the woman, prostaglandin E2 predominated during the periovulatory phases while the period of luteal death was highlighted by the elevated prostaglandin F2 alpha content in ovarian stromal and luteal tissues.

Adult↗