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The use of transabdominal cervico-isthmic cerclage is described in 13 patients with a diagnosis of cervical incompetence. The patients were recruited from seven Scottish Maternity Units over a period of 10 years. The 13 patients have had a successful pregnancy in 86.6% of pregnancies with this procedure compared with a success rate of 16% in their previous pregnancies. In carefully selected cases transabdominal cervico-isthmic cerclage is a worthwhile procedure in patients with cervical incompetence when the cervix is so damaged that it would be impossible to insert a vaginal suture or when a vaginal suture has previously failed.

The endothelins (ETs) are potent vasoconstrictor peptides that bind to two distinct receptors, ETA and ETB. This study compares the localization of ETA and ETB receptors in placentae complicated by intrauterine growth retardation (IUGR) and abnormal umbilical Doppler waveform, gestationally matched controls, fetuses that were small for gestational age (SGA), and normal term placentae. Quantitative autoradiography was performed using ETA and ETB subtype-selective ligands. Both ETA and ETB receptors were expressed in the human placenta. Gestational and fetal size effects on the receptor density within stem villi were found, but no effect of abnormal placental blood flow could be demonstrated. A distinct spatial distribution of receptor subtypes within the placenta was observed. Smooth muscle cells expressed both receptors with ETA expression predominant in the proximal regions of the villous tree and ETB abundant in the periphery and decidua. Both receptors were also expressed at lower density on paravascular stromal cells in stem villi. Although these data do not demonstrate aberrant localization of ET receptors in IUGR and SGA placentae, the spatially distinct distribution of ET receptors in the human placenta suggests that ETs play a role in modulation of placental blood flow.

Fetal electrocardiogram waveform analysis was used to assess the effect of epidural bupivacaine on the fetal myocardial conducting system by evaluating its effect on the PR interval, RR interval, T/QRS ratio and the PR-RR correlation coefficient. There were no significant changes in either the PR interval or the PR-RR correlation coefficient. There was a significant increase in the fetal heart rate and a significant fall in the T/QRS ratio. Epidural bupivacaine does not alter fetal myocardial conduction as measured by the PR interval and it does not induce ischaemic cardiac changes as assessed by the T/QRS ratio.

Background: Glutathione transferases (GSTs) constitute a family of isoenzymes that catalyze the conjugation of the tripeptide glutathione with a wide variety of hydrophobic compounds bearing an electrophilic functional group. Recently, a number of X-ray structures have been reported which have defined both the glutathione- and the substrate-binding sites in these enzymes. The structure of the glutathione-free enzyme from a mammalian source has not, however, been reported previously., Results: We have solved structures of a human alpha-class GST, isoenzyme A1-1, both in the unliganded form and in complexes with the inhibitor ethacrynic acid and its glutathione conjugate. These structures have been refined to resolutions of 2.5 A, 2.7 A and 2.0 A respectively. Both forms of the inhibitor are clearly present in the associated electron density., Conclusions: The major differences among the three structures reported here involve the C-terminal alpha-helix, which is a characteristic of the alpha-class enzyme. This helix forms a lid over the active site when the hydrophobic substrate binding site (H-site) is occupied but it is otherwise disordered. Ethacrynic acid appears to bind in a non-productive mode in the absence of the coenzyme glutathione.

Objective: Our purpose was to audit midtrimester chorionic villus sampling after a positive maternal serum screening test for autosomal trisomy., Study Design: From January 1990 until July 1993 chorionic villus sampling was offered to all screened positive women., Results: Five hundred fifty-one mothers had chorionic villus sampling. The mean age was 31.7 years. The mean gestational age was 18.2 weeks. The mean time for direct karyotyping was 4.4 days and for culture results 20.2 days. Results were obtained in 99.6% of samples: direct plus culture results in 94%, direct results alone in 2.3%, and culture results alone in 3.3%. Fourteen pregnancies had abnormal karyotypes. There were five cases of placental mosaicism and one false-positive result. The loss rate was 0.4%., Conclusion: Midtrimester chorionic villus sampling, which is easier to perform than cordocentesis, provides a rapid and reliable karyotype. The complication rate is comparable to that of other invasive procedures.

The crystal structure of a mutant Bacillus stearothermophilus lactate dehydrogenase, into which an additional loop has been engineered in order to prevent tetramerization of the enzyme, has been solved and refined at 2.4 A. The minimal repeat unit in the crystal is a dimer and the tetramer cannot be generated by any of the crystallographic symmetry operations in P2(1). The loop protrudes out into the solvent, stabilized by a good hydrogen bonding arrangement, and clearly sterically hinders tetramer formation. This is the first structure of B. stearothermophilus lactate dehydrogenase (bsLDH) in which the allosteric activator fructose, 1,6-bisphosphate (FBP) is not present. To investigate the mechanism of allosteric activation in this enzyme we have compared the structure with a ternary complex of B. stearothermophilus lactate dehydrogenase. Many of our observations confirm those reported from a comparison of FBP-bound ternary bsLDH complex with an FBP free LDH from another bacterial source, Bifidobacterium longum. Our results suggest that quaternary structural alterations may have less influence on the mechanism than previously reported. The differences in the quaternary structural behaviour of these two enzymes is discussed.

Patterns of shoot growth and branching were studied over two growing seasons in rooted cuttings collected from both epicormic shoots and seedlings of Betula pendula Roth. Epicormic shoots were induced to sprout on stumps and small logs of 5-, 10- and 30-year-old trees. The use of epicormic shoots enhanced the rooting capacity of stem cuttings collected from these shoots but did not appear to reverse the process of maturation. In this study, maturation was based on characteristics typical of mature trees but not necessarily those of the mother plant, because it was not possible to root cuttings, for comparison, from 5-, 10- and 30-year-old ortets, other than from epicormic shoots. There was evidence of the persistence of mature characteristics through an increase in shoot plagiotropism with increasing ortet age. Rooted cuttings from both seedlings and epicormic shoots, however, assumed an increasingly orthotropic habit with a smaller shoot angle at the end of the first growing season than at the beginning and this continued into the second growing season. Other indications of maturation, such as delayed bud flushing and the incidence of flowering with increasing ortet age, were also evident in rooted cuttings from epicormic shoots. There was a clear difference in branching habit depending on cutting source. Rooted cuttings derived from epicormic shoots produced nearly twice as many lateral branches compared with rooted cuttings collected from seedlings, but this was not an effect of maturation. There was some evidence that rooted cuttings derived from seedlings grew taller than rooted cuttings from epicormic shoots.

The crystal structures of the deoxy and carbonmonoxy forms of a distal pocket myoglobin mutant in which valine68(E11) is replaced by threonine have been solved to 2.1- and 2.2-A resolution, respectively. This substitution has been shown previously to cause large decreases in the rate of oxygen binding and to lower the equilibrium association constants for O2 and CO. The synchrotron Laue method was used for the rapid acquisition of X-ray diffraction data to overcome problems caused by the very rapid rate of autooxidation of the mutant protein. The refined deoxy structure shows that the noncoordinated water molecule in the distal pocket is in a position to form strong hydrogen bonds with both the N epsilon-H of the distal histidine64 and O gamma of threonine68 with no other unexpected alterations in the protein structure. In the carbonmonoxy form, the bound ligand is well-defined and inclined away from the two hydrogen-bonding groups, refining to a position in which the Fe-C-O angle is 162 degrees. This value is very close to that previously observed in recombinant wild-type and position-64 (E7) mutants of sperm whale myoglobin (160-170 degrees). The similarity of the CO conformations contrasts with the 150-fold range in equilibrium binding constants (KCO) among the distal pocket myoglobin mutants and indicates that CO affinities cannot be predicted from the coordination geometry of the bound ligand. Furthermore, a comparison of the infrared stretching frequencies of CO in wild-type, valine64 and threonine68 single mutant, and valine64-threonine68 double mutant pig carbonmonoxymyoglobins shows a lack of correlation between KCO and vCO. These effects can be understood in terms of the stability of noncovalently bound water in deoxymyoglobin and electrostatic interactions between bound ligands and the distal pocket residues.

Maternal and feto-placental Doppler flow velocity waveforms were studied during acute and chronic antihypertensive therapy in patients with pregnancy-induced hypertension. Eight primigravidae were acutely treated with oral nicardipine. Diastolic blood pressure fell at 30, 45 and 60 min after nicardipine. The uteroplacental systolic/diastolic ratio rose significantly at 30 min, but this change was no longer apparent at 60 min. Umbilical artery and maternal brachial artery systolic/diastolic ratios were unchanged. Fifteen patients with mild pre-eclampsia were chronically treated with oral pindolol. Diastolic blood pressure fell significantly within 24 h. The uteroplacental systolic/diastolic ratio rose 3 days after pindolol. Brachial artery or umbilical artery systolic/diastolic ratios were unchanged. A control group of 15 patients with untreated mild pre-eclampsia showed a significant rise in uteroplacental and umbilical artery systolic/diastolic ratios within 7 days of starting recordings. In patients with pregnancy-induced hypertension, acute and chronic blood pressure reduction was associated with no change in umbilical artery or maternal brachial artery Doppler systolic/diastolic ratios and a transient rise in the uteroplacental systolic/diastolic ratio.

Discordant fetal growth, as defined by an intertwin weight difference (calculated as a percentage of the weight of the larger twin) of 20% or more, is associated with an increased perinatal mortality and morbidity. In this study, the accuracy of ultrasound estimation of fetal weight by abdominal circumference and biparietal diameter measurements in 107 twin pregnancies was assessed. Discordant growth greater than 20% as measured by ultrasound was found to have a sensitivity of 5-25%, a specificity of 87-95%, a positive predictive value of 12-43% and a negative predictive value of 80-85% at gestations ranging from 28 weeks to term. ROC calculations showed that changes in the discordance level used did not improve the value of the test. These results indicate that ultrasound measurement of fetal weight alone cannot be used accurately to assess discordant growth in twin pregnancies., (Copyright 1992 International Society of Ultrasound in Obstetrics and Gynecology)

The purpose of this study was to investigate the influence of postnatal x-ray pelvimetry after caesarean section on the management of the subsequent pregnancy. The case records of 331 women delivered by casearean section in their first pregnancy were reviewed. By standard radiological criteria, the pelvis was considered to be inadequate in 248 (75%) of them and adequate in 83 (25%). Of the women with a radiologically inadequate pelvis, 172 underwent an elective caesarean section. Seventy-six were allowed vaginal delivery: 51 of these women delivered vaginally and 25 required an emergency caesarean section. Of the women with a radiologically adequate pelvis, 61 achieved a vaginal delivery and 22 were delivered by caesarean section. All of the three cases of uterine rupture occurred in women with a radiologically adequate pelvis. This study suggests that x-ray pelvimetry is not a good predictor of the outcome of a trial of vaginal delivery. We conclude that the practice of routine postnatal pelvimetry should be abandoned.

The prenatal diagnosis of a presacral (type IV) sacrococcygeal teratoma (SCT) is described. The initial ultrasound appearance was suggestive of a lower urinary tract obstruction, but further ultrasonic examination and radiological imaging using contrast medium led to the diagnosis of SCT. This is the first prenatal diagnosis of a totally intra-abdominal SCT.

Since January 1988 the technique of first-trimester chorionic villus sampling (placental biopsy) has been extended to include cases in the second trimester. To date, 40 procedures have been performed. The main indication for the late chorionic villus sampling was a low serum alpha-fetoprotein value in association with an increased risk for Down syndrome (n = 28), abnormal ultrasonographic finding (n = 7), and failed amniotic cell culture (n = 3). Successful karyotype results were achieved in all but two cases. Most results were obtained within 48 hours with direct cytogenetic techniques. No cases of mosaicism were found. The highest yield of abnormal karyotypes was obtained from the cases with abnormal ultrasonographic findings (one trisomy 21, two 45,X). One case of trisomy 21 was identified in the 28 cases of low serum alpha-fetoprotein. No spontaneous losses have occurred. The technique is easy to learn, does not differ from first-trimester procedures, and may have a lower complication rate than cordocentesis. The reporting of cases to the CVS Newsletter should help evaluate late chorionic villus sampling as another method for rapid fetal karyotyping.

Autotetraploid plants with 2n = 56 chromosomes were found in a population of plants derived from callus cultures of stem internodes of silver birch (Betula pendula Roth) with 2n = 28 chromosomes. These plants were readily identified by their twisted, pubescent foliage and slow rate of growth, and by cytological examination. The frequency of autotetraploidy varied with the auxin used in the culture medium. When indole-3-butyric acid was used, autotetraploids accounted for 3.8% of the total study population, whereas when naphthaleneacetic acid was used, the frequency of autotetraploidy increased to 11.0%. The remainder of the plants in the study population were morphologically normal with 2n = 28 chromosomes. The autotetraploids have potential value as breeding material for the production of triploid birches (2n = 42), which are known to be fast growing, through crosses with diploid silver birch.

Increase in platelet size has been found in conditions with increased platelet destruction and use. This increase in platelet size can be found in patients with moderate or severe hypertension in pregnancy, even in the presence of a normal platelet count. The goal of this study was to investigate whether an increase in platelet size was present before the manifestation of the disease and therefore could be used to predict the progression of the disease before it is clinically apparent. Three hundred normal primigravid pregnancies were studied between 28 and 30 weeks' gestation, and blood was taken to assess platelet count and mean platelet volume. Two hundred sixteen patients had no hypertensive problems during their pregnancy, 84 developed hypertension, 62 had mild hypertension only with diastolic blood pressures between 90 and 99 mm Hg, 13 had moderate hypertension with diastolic blood pressures between 100 and 109, and nine had severe hypertension with diastolic blood pressure above 110. No difference was found between these groups in the parameters measured. Therefore it was felt that platelet volume may not be a useful screening test in a low-risk population. A second study was carried out to investigate the serial changes in these parameters in patients at risk of progressive disease. Thirty-four patients with essential hypertension were followed from 24 weeks with serial blood sampling to study changes in platelet size. An additional 40 patients with mild pregnancy-induced hypertension were also studied. From these patient groups, 20 patients developed severe hypertension. The mean platelet volume increased significantly at least 1 week before the hypertension became clinically apparent. There was no change in platelet count at this time. It is concluded that increasing platelet size can predict which patients are likely to progress to severe disease before it becomes clinically obvious.

Pulsed Doppler ultrasound assessment of blood flow was performed in the fetal aorta and umbilical arteries of 41 patients with hypertension in pregnancy. Patients were grouped according to severity of the hypertension and the presence or absence of chronic hypertension. Doppler abnormalities were seen in two patients with chronic hypertension, both of whom delivered small for gestational age infants. Only one patient with mild to moderate preeclampsia had abnormal aortic Doppler assessment and was also delivered of a small for gestational age infant. The highest number of abnormal Doppler waveforms in both fetal aorta and umbilical artery were found in patients with severe preeclampsia. Abnormalities were detected more frequently in the fetal aorta than in the umbilical artery. Doppler assessment was often abnormal before a nonstress test or biophysical profile. The number of abnormal Doppler values correlated with perinatal outcome in patients with severe preeclampsia.

The interactions of serum levels of magnesium and parathyroid hormone (PTH) have been studied in a patient with hypomagnesemia and hypocalcemia following intestinal bypass surgery for obesity. When serum magnesium was low serum PTH was not stimulated by hypocalcemia. With correction of magnesium deficiency hypocalcemia was associated with elevation of serum PTH levels. Infusion of exogenous PTH induced a clearly detectable renal response in the presence of hypomagnesemia but the response was diminished when serum magnesium was elevated. In this patient it appears that hypomagnesemia suppressed parathyroid gland activity, leaving the renal action of PTH intact.

A double-blind randomised controlled trial, comparing pramoxine hydrochloride 1 per cent and hydrocortisone acetate 1 per cent in a mucoadhesive foam base, with simple aqueous foam (B.P.), in relieving episiotomy discomfort and episiotomy healing in 40 patients was carried out. Simple aqueous foam was more effective with regard to wound healing and episiotomy discomfort as measured by analgesic consumption. Pramoxine and hydrocortisone foam offers no advantage over simple aqueous foam in the treatment of post partum episiotomy discomfort.

Prostacyclin and thromboxane have been implicated in the pathophysiology of several disorders of pregnancy, but there is little information on concentrations of these prostaglandins in normal pregnancy. The aim of our study was to determine the range of values throughout normal pregnancy and the puerperium and to compare this with concentrations in normal non-pregnant women. Measurement was by radioimmunoassay of prostacyclin and thromboxane metabolites. We observed a significant difference in prostacyclin metabolites in the first trimester, (mean 19.9, SEM 0.96 pg/ml) compared with the normal non-pregnant group (mean 15.9, SEM 0.68 pg/ml). There were no significant differences between values in the normal non-pregnant group and those in the second and third trimester or postnatally. The increase in prostacyclin in the first trimester may be associated with placentation and physiological vasodilation, and insensitivity to angiotensin II seen in early pregnancy. We noted a significant reduction in thromboxane metabolites in the second (mean 133, SEM 14.9 pg/ml) and third (mean 123, SEM 10.7 pg/ml) trimesters and the puerperium (mean 119, SEM 6.3 pg/ml) compared with the values in the normal non-pregnant group (mean 142, SEM 4.9 pg/ml). This may be due to increased platelet stability or decreased thromboxane synthesis.

A new technique is described for the measurement of blood loss in the faeces of patients labelled with radioactive chromium ((51)Cr). The method is simple and is probably more accurate at low levels of faecal radioactivity than those previously described. The method will measure as little as 0.02muC of (51)Cr in whole blood in a 24-hour stool. The apparent average daily blood loss in a series of 10 normal people averaged 0.6 ml., with a range of 0.3 to 1.3 ml. Estimations of plasma and salivary radioactivity have been made in an attempt to assess the importance of contamination from eluted (51)Cr. Minor radioactivity in plasma but none in saliva was recorded. Stool contamination from such sources is thought to be insignificant. No significant correlation existed between chemical occult blood tests and isotope measurements, where there was less than 10 ml. of whole blood in a 24-hour stool.

Most series of haematemesis or melaena present data about the clinical problems in relation to the final diagnosis. When a patient is admitted there is the problem of management which depends to a considerable extent on the diagnosis. This paper demonstrates that it is possible to achieve an accurate diagnosis in 80% during the first 24 hours.

Two patients are described with chronic liver disease and portal hypertension in association with ulcerative colitis for which colectomy and ileostomy had been performed. Both patients developed bleeding from the varices situated around the ileostomy stoma and one also bled from the oesophageal varices. Each had a successful portacaval shunt performed because of this bleeding. The occurrence of such ileal varices is uncommon, but is important as a manifestation of portal hypertension. Although it can usually be easily controlled by local measures, portal-systemic shunt should always be considered, particularly as such patients are also very likely to bleed from oesophageal varices.