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Biomedical subjects

G M Stirrat

Publications and source records attributed to G M Stirrat.

At least 55 records · Page 3Linked to original sources

Prescribing for labour.

Prostaglandins, particularly PGE2 vaginally, can be valuable for cervical ripening or induction of labour in some women. Ease of use must not be allowed to result in unjustified intervention. Amniotomy followed by oxytocin infusion are the methods of choice for induction of labour. Careful monitoring of the maternal and fetal condition are vital, especially if an epidural block is in place. Augmentation of labour is only appropriate for inefficient primigravid labour. Failure to progress in a multiparous woman is more likely to be due to obstruction. Low residue, easily digested foodstuffs are not necessarily contraindicated during normal labour. When properly used, Entonox can provide analgesia equivalent to 75-100 mg pethidine. Sodium citrate is the antacid of choice during labour and should be combined with an H2-receptor blocking agent for caesarean section, or other procedure involving anaesthesia. The routine injection of Syntometrine at delivery of the anterior shoulder to prevent PPH is widespread in the UK but has not been properly tested. Oxytocics are invaluable in the treatment of PPH.

Anesthesia, General↗

Characterization and localization of HLA antigens on hydatidiform mole.

Frozen sections of three specimens of hydatidiform mole were stained with monoclonal antibodies to HLA Class I and Class II antigens by means of an indirect immunoperoxidase technique. Class I (HLA A, B, C) antigens were detected on proliferating extravillous trophoblast and on villous stromal cells but not on quiescent villous trophoblast. Trophoblast Class I antigen was detected with four different antibodies to monomorphic determinants but not with antibodies to the appropriate polymorphic HLA A or B type. Stromal cells were reactive with all Class I antibodies. Class II (HLA DR) antigens were not detected on any molar tissue. The expression of HLA antigens by molar tissue is similar to that of the normal first-trimester human placenta.

Antibodies, Monoclonal↗

Radionuclide imaging of ovarian tumours with a radiolabelled (123I) monoclonal antibody (NDOG2).

The biodistribution of a radiolabelled monoclonal antibody (123I-NDOG2) was studied in patients with ovarian tumour. It was found that the uptake patterns in known tumour sites was variable and that the clearance of the agent from the vascular pool was due to renal excretion of the radionuclide and the redistribution of the radioactively labelled compound into other compartments. The mean (+/- SD) plasma clearance time was 20.8 (+/- 2.3) h and the ratios of target (tumour) to background (thigh) ranged between 1.4 and 4.8. The ratio between the plasma radioactivity at either 3.5 or 20 h after administration was calculated relative to the initial plasma radioactivity. These values (0.79 and 0.48, respectively) were incorporated into an image-subtraction technique that allowed for redistribution outside the vascular pool. A whole-body dose equivalent to 16.3 mu Sv MBq-1 (60.4 mrem.mCi-1) was calculated.

Antibodies, Monoclonal↗

Placental alkaline phosphatase in benign and malignant endometrium.

The presence of placental alkaline phosphatase has been demonstrated immunohistochemically using a monoclonal antibody, in frozen sections of human endometrium. The enzyme is present in glandular epithelium, but is found most commonly in the surface epithelial layer throughout the menstrual cycle. It has also been demonstrated in malignant endometrial epithelium in eight out of twelve patients.

Alkaline Phosphatase↗

Immunohistological and biochemical evidence for a role for hyaluronic acid in the growth and development of the placenta.

A monoclonal antibody, designated NDOG1, has been used to stain a series of human and monkey placentae as well as several adult human tissues using immunoperoxidase techniques. In early placentae, NDOG1 was found to stain extracellular material associated with proliferating, extravillous cytotrophoblast cell columns and with the cytotrophoblast shell at the feto-maternal junction. The immunohistology suggests that NDOG1 antigen may be secreted by the anchoring cytotrophoblast into the immediately adjacent maternal tissues. NDOG1 antibody also shows extracellular staining in the stroma of early human placentae and reacted with the apical villous syncytiotrophoblast plasma membrane throughout pregnancy. Biochemical experiments demonstrated that extracts of this latter membrane contained NDOG1 antigenic activity which was susceptible to digestion with bovine testicular hyaluronidase. Hyaluronic acid was the only glycosaminoglycan found in this membrane, thereby implying a reaction between NDOG1 antibody and hyaluronic acid. Whilst no such direct interaction could be demonstrated in vitro, NDOG1 was shown to compete with two other antibodies which themselves demonstrated specificity for hyaluronic acid. The proposed identity between the NDOG1 antigen and hyaluronic acid is discussed particularly in terms of placentation where the distribution of NDOG1 staining may confirm the role of hyaluronic acid in providing an open matrix structure during stages of cell proliferation, migration and invasion.

Adult↗

An immunohistological study of HLA antigen expression by gestational choriocarcinoma.

Two cases of gestational choriocarcinoma have been examined for the expression of HLA and trophoblast antigens using the indirect immunoperoxidase technique on frozen tissue sections. Approximately 40-70% of tumour cells express MHC Class I antigen as detected by a panel of antibodies to monomorphic, or framework, MHC Class I antigenic determinants. Evidence in one case suggests that most of these cells may not express the paternal, polymorphic HLA antigenic determinants but that a small subpopulation do carry the fully antigenically active molecule. These latter may give rise to patient anti-paternal HLA antibodies. Class II (HLA DR or DC) antigens are expressed by none, or very few, tumour cells.

Choriocarcinoma↗

Radionuclide imaging of ovarian tumours with 123I-labelled monoclonal antibody (NDOG2) directed against placental alkaline phosphatase.

A radiolabelled monoclonal antibody (NDOG2) directed against placental alkaline phosphatase (PLAP) was used in the radio-immunodetection of ovarian carcinoma. Tumour deposits were successfully visualized in 11 of 15 patients and the abnormalities demonstrated were classified as focal or diffuse. Of the 11 patients, eight showed focal abnormalities alone and three had a diffuse abnormality, of which two also showed a focal abnormality. False-positive results may occur not only due to uptake of 123I by gut mucosa and an inadequately blocked thyroid gland but also from activity in an incompletely emptied bladder. A false-negative result occurred due to high background activity in the liver masking a known, discrete tumour deposit.

Alkaline Phosphatase↗

Practical applications of a monoclonal antibody (NDOG2) against placental alkaline phosphatase in ovarian cancer.

A monoclonal antibody (NDOG2) against placental alkaline phosphatase (PLAP) in ovarian cancer has been used in three ways by the Bristol University Department of Obstetrics & Gynaecology. First, in an indirect immunoperoxidase technique, NDOG2 demonstrated positive standing in 64% of 56 ovarian carcinomas as well as in 25% of 44 benign tumours. The majority of these positive tumours were serous cystadenocarcinomas or serous cystadenomas and there was considerable variation in the expression of this antigen from tumour to tumour. NDOG2 was also used as the basis of two serum assays and, when labelled with 123-iodine (123I), in radioimmunoscintigraphy (RIS) to monitor patients' response to therapy. The first serum assay measures the enzymic activity of PLAP and the second recognizes the antigenicity of the molecules. Assay 2 proved more useful in that it predicted the course of the disease in 45% of patients followed up, whereas Assay 1 was only of use in 25% of cases. RIS proved to be a useful imaging technique and was at least as sensitive as conventional imaging techniques. The common causes of false-positive and false-negative results are described.

Alkaline Phosphatase↗

Management of spontaneous rupture of the membranes in the absence of labor in primigravid women at term.

One hundred and thirty-five healthy primigravid women at or near term with spontaneous rupture of the membranes without uterine contractions were submitted to a prospective trial of management. Rupture of the membranes was diagnosed by speculum examination. If labor did not commence, induction was performed by oxytocin infusion starting at 9 AM following admission. One hundred and five women went into labor spontaneously before induction became necessary. Sixty-three of these women required augmentation with oxytocin. Twenty-seven percent of the induced group required cesarean section delivery compared to 10% of those in spontaneous labor augmented by oxytocin and to none of those who did not require oxytocin (p less than 0.01). Ninety-four percent of those in spontaneous labor were delivered vaginally compared to 73% of the induced group (p less than 0.01). Forty-one percent of the augmented group were delivered by forceps. Awaiting the spontaneous onset of labor for 24 hours or less did not result in clinical maternal or neonatal infection. We would therefore advocate awaiting the spontaneous onset of labor after spontaneous rupture of membranes without contractions at or near term in healthy primigravid women for up to 24 hours because it seems to confer significant advantages without producing any additional hazard.

Adolescent↗

Chlamydial serology in fertile and infertile women.

Species-specific circulating antibodies to Chlamydia trachomatis were found in 75% of 48 infertile women with damaged fallopian tubes, 47.5% of 40 parous women seeking sterilisation, 46% of 63 women seeking termination of pregnancy, 31% of 75 infertile women with normal fallopian tubes, and 24% of 72 women using barrier contraception. High titres of antibody (greater than or equal to 1/1024) were found in 46%, 15%, 16%, 8%, and 7% of these groups, respectively, and were common in those women with a history of pelvic inflammatory disease or use of an intrauterine device. Thus, although the presence of antibody to C trachomatis was correlated with tubal damage, it was not diagnostic of tubal disease, since a substantial number of pregnant or potentially fertile women also had serological evidence of chlamydial infection. However, the results show that high titres of chlamydial antibodies in infertile women indicate the need for early laparoscopy to assess tubal status.

Adult↗

Class 1 major histocompatibility complex antigens on human extra-villous trophoblast.

Using immunohistological techniques, class 1 products of the major histocompatibility complex (MHC) have been demonstrated on various forms of human extra-villous trophoblast in placental tissues taken from first, second and third trimester pregnancies. This contrasts with the absence of class 1 MHC antigens on all forms of villous trophoblast. The extra-villous trophoblast which reacted with antibodies to monomorphic class 1 MHC antigens consistently failed to bind HLA-A or HLA-B antibodies specific for the foetal phenotype. This suggests, but does not prove, that the MHC antigen expression of trophoblast may be restricted to HLA-C or some other undefined class 1 antigen.

Antibody Specificity↗

Immunohistology of normal and ovarian cancer tissue with a monoclonal antibody to placental alkaline phosphatase.

A monoclonal antibody, designated NDOG2, has been shown to react with placental alkaline phosphatase. It does not bind to liver, kidney, bone, or intestinal alkaline phosphatase enzymes and has shown a positive reaction with all of over 50 placentae. Immunohistological studies have shown (a) a reaction with respiratory bronchiolar epithelium of lung, endocervical gland epithelium, the epithelium of fallopian tube, and certain reticular cells in the thymic medulla; (b) no detectable staining with ten other normal tissues including testis and tonsil; and (c) a significant reaction with nine of 13 ovarian cystadenocarcinomas and little or no staining with four malignant ovarian tumors of other histopathological types. The NDOG2 antibody may be of value as a marker in patients with ovarian cystadenocarcinoma.

Adult↗

Fetal distress and the condition of newborn infants.

In a prospective audit of the obstetric management of 1210 consecutive deliveries the association was investigated between the need for operative delivery for fetal distress during labour and the condition of the newborn infant. Operative delivery was performed for only 11.5% of the newborn infants with severe acidosis at birth (umbilical artery pH less than 7.12, base deficit greater than 12 mmol (mEq)/1), 24.1% of those with an Apgar score less than 7 at one minute, and 15.8% of those with both severe acidosis and a one minute Apgar score less than 7. Most of the infants delivered operatively were in a vigorous condition at birth and did not have severe acidosis. Fetal blood sampling was done in 4.0% of labours. As none of the fetal blood values were less than 7.20 and only three of the infants sampled in utero suffered severe acidosis at birth, fetal blood sampling would have had to be performed much more often to provide a useful guide to metabolic state at birth. While the large majority of "at risk" fetuses had continuous fetal heart rate monitoring in labour, this had not been provided in 48.7% of the labours of infants with severe acidosis, 38.7% of infants with a one minute Apgar score less than 7, and 47.4% of infants with both severe acidosis and a one minute Apgar score less than 7. Continuous fetal heart rate monitoring was associated with a much higher incidence of operative delivery for fetal distress than was intermittent fetal heart rate auscultation. These results suggest an urgent need to review present methods for assessing the intrapartum condition of the fetus, making the diagnosis of fetal distress, and assessing the condition of the infant at birth.

Acidosis↗