E. Malcolm Symonds

Platelet angiotensin II binding sites in normotensive and hypertensive women

Summary. Specific binding of angiotensin II (AII) to platelets was measured in 89 women, 25 nulliparous non‐pregnant women and 64 primigravida in the third trimester of pregnancy. There was significantly lower binding in the 25 pregnant women who were normotensive (2.3 fmol/109 cells) when compared with the non‐pregnant women (9.0 fmol/109 cells P<0.001). Significantly higher platelet AII binding levels were found in the 39 women who had pregnancy induced hypertension (PIH) (5.5 fmol/109 cells) when compared with the 25 normotensive pregnant women (P<0.001). Of the 39 women with PIH, platelet AII binding was higher in the 23 women who had pre‐eclampsia (7.0 fmol/109 cells), when compared with the 16 who had non‐proteinuric PIH, (4.6 fmol/109 cells) although the difference was not statistically significant (P<0.04). The pressor response to AII is also diminished in pregnancy, yet less so if pregnancy induced hypertension develops. Platelets may provide a readily accessible tissue with which to study AII responsiveness in pregnancy.

Renin and reproduction

I should state at the outset that this article is not about hypertension, although that subject is inevitably part of any review of the renin-angiotensin system. Nevertheless, a hormone system that plays a major role in the regulation of sodium excretion and produces a very potent vasoconstrictor with a majorfunctional base in the genital tract must be of considerble interest and importance in any studies on volume homeostasis and the regulation of blood pressure in pregnancy. The system shows significant activation at various stages of the menstrual cycle and is one of‘ the first hormones to increase in activity in the peripheral circulation in response to pregnancy. Furthermore, the multifocal sources of renin production in the genital tract raise very important issues about the role of’ renin in these sites. There is no doubt that renin acts as a circulatory hormone, but the function of the system in the genital tract suggests a predominant role as a tissue hormone with a tnodification or stimulation of locally acting vasoconstrictor atld vasodilator hormones.

Biodistribution of 111In-labelled engineered human antibody CTM01 (hCTM01) in ovarian cancer patients: influence of prior administration of unlabelled hCTM01

Abstract mAb hCTM01 binds a carcinoma-associated antigen, the MUC1 gene product. The antigen is also present in the circulation, and administration of 111In-labelled hCTM01 results in the formation of immune complexes with enhanced accumulation in the liver. To avoid the unwanted effect of circulating radioactive immune complexes, a strategy to remove the circulating antigen was investigated using a split-dosage schedule. Eleven patients suspected of having ovarian carcinoma were injected with 1u2009mg/kg unlabelled hCTM01, 1u2009h before receiving 0.1u2009mg/kg 111In-labelled hCTM01 (100u2009MBq). The amount of radioactivity was determined in resected tumour tissue, various normal tissues and blood samples obtained at laparotomy 6 days postinjection (p.i.). In all patients, the circulating antigen decreased to its nadir after the unlabelled antibody infusion and immune complex formation was demonstrated. Uptake in tumour deposits 6 days p.i. was 11.1 times higher than in normal tissues (P<0.0001) and 5.9 times higher than in blood (P<0.0001). 111In activity in liver tissue was comparable to 111In uptake in tumour tissue, and considerably lower than previously reported in patients not pretreated with unlabelled antibody. The split-dosing strategy would appear to be advantageous for use of hCTM01 as a specific carrier for the delivery of cytotoxic agents to patients with ovarian cancer.

Intrapartum fetal monitoring - basic knowledge

recognise cardiotocographic (CTG) trace ahnorin:ilities. delay in coinmunication and friilure to take tiinely action. Tlie speed with which hypoxia can develop ,aries witli differing clinical situations and specific abnormali- ties of the fetal lieart rate (FHK). It is also influenced by delay CTG traces are :ibnorinal in those who develop Iiypoxia and acidosis in labour and subseqiient hypoxic ischriemic encepli:ilopathy,

Bed rest in pregnancy

Broughton Pipkin, F., Craven, D. J. & Symonds, E. M. (1 98 1) The uteroplacental renin-angiotensin system in normal and hypertensive pregnancy. Cunfrib Nephrol25,49-52. Cheslcy, L. C., Talledo, E., Bohler, C. S. & Zuspan, F. P. (1965) Vascular reactivity to angiotensin 11 and norepinephrine in pregnant and non-pregnant women. Am J Obstet Gynecol91,837-842. Davis, J. 0. & Freeman. R. H. (1976) Mechanisms regulating renin release. PhysiolRev 56, 1-56. Gant, N. F., Daley, G. L., Chand, S., Whalley, P. J. & MacDonald, P. C. ( IY73) A study of angiotensin I1 pressor response throughout primigravid pregnancy. J Clin Invest 52,2682-2689. Johnson, I. R. (1979) A study of the human endometrical isorenin-angiotensin system. MsUM, University of Nottingham. Kokot, F. & Czkanski, A. (1972) Plasma renin activity in peripheral and uterine vein blood in pregnant and non-pregnant women. J Obstet Gynaecol Br Cornmonw 79,72-76. Remuzzi, G., Marchesi, D., Zoja, C., Muratorc, D., Mecca, G., Misiani, K., Rossi E.. el al. (1980) Reduced umbilical and placental vascular prostacyclin in severe pre-eclampsia. Prostaglandins 20, 105-1 10. Symonds, E. M. & Broughton Pipkin, F. (1978) Pregnancy hypcrtension, parity and the renin-angiotensin system. Am J Obstet Gvnecol 132,473-479.

Five futures for academic medicine: future of academic medicine looks bleak.

EDITOR—Four factors are responsible for the failure of academic medicine. The first is the research assessment exercise, which, surprisingly, is not discussed in the ICRAM scenarios outlined by Clark for the International Campaign to Revitalise Academic Medicine.1 The second is the inhibition of clinical research by the draconian regulations often inflicted by ethics committees. The third is the formidable problems faced by people wishing to work with …

NUCLEAR PROGESTERONE UPTAKE BY ENDOMETRIAL TISSUE IN CASES OF SUBFERTILITY

To investigate the ability of steroid hormones to interact with endometrium, particularly in cases of unexplained subfertility, intact cells were incubated with tritiated progesterone and oestradiol and their uptake into the nuclei was measured. Samples were taken at dilatation and curettage from 23 fertile women, 14 women with unexplained primary subfertility, and 9 patients whose primary subfertility could be explained. Serum oestradiol and progesterone levels were not significantly different between the three groups, nor were values of 3H-oestradiol uptake. However, low (below 5 pmol/mg DNA) values for nuclear 3H-progesterone uptake were present in most samples from women with unexplained subfertility but in only about half of the women in the other two groups. This biochemical defect may be the cause of some cases of unexplained subfertility.

The Nottingham brush for chorion villus sampling

In the first trimester the embryo is enveloped in a dense coat of chorionic villi. This villus coat is maintained until after the 12th week when enlargement of the gestation sac and its approximation to the uterine wall results in attenuation of most of this material, apart from the chorion frondosum which develops to form the definitive placenta. Chorionic villi are filamentous in nature and access to it is readily available via the transcervical route. It is, therefore, conceivable that a small brush can be introduced through the cervix to entwine and subsequently retrieve chorionic villi for prenatal diagnosis. We describe our experience in advancing this concept to fashion an implement suitable for clinical application.

Medico-legal problems in obstetrics

Abstract Obstetric litigation has become a major issue in the practice and funding of obstetric care. Although litigation has led to some improvement in the quality of maternity services, it has also led to the complete breakdown in the provision of care where the costs of insurance for the practitioner have made obstetric practice uneconomic. Cerebral palsy and birth-related injuries are the major source of indemnity problems because of the high cost of settlements. In some countries, the impact on recruitment of staff and trainees has been profound. Shoulder dystocia and injuries to the brachial plexus are also a common source of litigation.

Intrapartum fetal monitoring ‐ medico‐legal implications

he contribution of birth asphyxia to cerebral palsy has tieen debated since 18621 and. Lvhile epideiniologists T and scientists continue the debate, there is a drainatic rise in claims for inedical negligence.’ Of the more than A.200 million paid out in ckiirns each year, 38% is for hypoxic brain injury or death of the fetus.’ There are many iiiore clainis for negligence that do not come to fruition but wliich incur considerable legal expense and mental agony for those involved. The main reasons for litigation are: o O to prevent recurrence o o parents want to know what happened and why