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Objective: To establish whether the timing of delivery between 37 and 42 weeks gestation influences neonatal respiratory outcome and thus provide information which can be used to aid planning of elective delivery at term., Design: All cases of respiratory distress syndrome or transient tachypnoea at term requiring admission to the neonatal intensive care unit were recorded prospectively for nine years., Setting: Rosie Maternity Hospital, Cambridge., Subjects: During this time 33,289 deliveries occurred at or after 37 weeks of gestation., Main Outcome Measures: This information enabled calculation of the relative risk of respiratory morbidity for respiratory distress syndrome or transient tachypnoea in relation to mode of delivery and onset of parturition for each week of gestation at term., Results: The incidence of respiratory distress syndrome at term was 2.2/1000 deliveries (95% CI; 1.7-2.7). The incidence of transient tachypnoea was 5.7/1000 deliveries (95% CI; 4.9-6.5). The incidence of respiratory morbidity was significantly higher for the group delivered by caesarean section before the onset of labour (35.5/1000) compared with caesarean section during labour (12.2/1000) (odds ratio, 2.9; 95% CI 1.9-4.4; P < 0.001), and compared with vaginal delivery (5.3/1000) (odds ratio, 6.8; 95% CI 5.2-8.9; P < 0.001). The relative risk of neonatal respiratory morbidity for delivery by caesarean section before the onset of labour during the week 37+0 to 37+6 compared with the week 38+0 to 38+6 was 1.74 (95% CI 1.1-2.8; P < 0.02) and during the week 38+0 to 38+6 compared with the week 39+0 to 39+6 was 2.4 (95% CI 1.2-4.8; P < 0.02)., Conclusions: A significant reduction in neonatal respiratory morbidity would be obtained if elective caesarean section was performed in the week 39+0 to 39+6 of pregnancy.

The incidence of triplet pregnancies is increasing due to the widespread use of ovulation induction agents and assisted conception treatments. The aim of this study was to acertain the normal ultrasonographic measurements for fetal growth parameters in triplet pregnancies. The ultrasonographic measurements of all triplet pregnancies managed in two major hospital centres were reviewed retrospectively and those in which there was less than 25% discordance in birth weight were included in the study. Triplet 50th centile for fetal biparietal diameter, whilst falling through the normal singleton centile range from 27 weeks gestation, did not fall below the 10th centile value of singletons. Triplet 50th centile for head circumference was equivalent to the singleton 10th centile from 23 weeks gestation. Triplet 50th centile for abdominal curcumference was persistently below that of the singleton 50th centile, falling below the singleton 10th centile from 29 weeks gestation. Normal growth rate of triplet gestations in the third trimester of pregnancy varies from that of singletons. An awareness of this altered growth rate is necessary to avoid the inappropriate diagnosis of asymmetrical triplet fetal growth retardation. We suggest that the growth curves presented here may be used to monitor triplet fetal growth.

ETA selective (BQ123, FR139317, PD151242) and ETB selective (BQ3020) ligands were used to define the binding characteristics and contractile function of endothelin receptor subtypes in human myometrium. In saturation binding assays with 10 microns-thick tissue sections [125I]endothelin-1 (ET-1) bound with a single affinity to receptors in the myometrium (Kd, 1.19 +/- 0.17 nM) and adjacent endometrium (Kd, 1.39 +/- 0.51 nM). Competition binding assays in myometrium revealed a heterogeneous population of receptors with BQ123 (Kd ETA, 1.43 +/- 0.33 nM; Kd ETB, 39.91 +/- 9.06 microM), FR139317 (Kd ETA, 2.54 +/- 0.87 nM; Kd ETB, 89.79 +/- 24.34 microM) and BQ3020 (Kd ETA, 4.57 +/- 0.58 microM; Kd ETB, 90.07 +/- 19.53 nM). The presence of these receptors in myometrium was confirmed by saturation assays with the new ETA selective ligand [125I]PD151242 (Kd, 0.93 +/- 0.08 nM; Bmax 138.7 +/- 1.0 fmol/mg protein) and the ETB selective [125I]BQ3020 (Kd, 0.62 +/- 0.07; Bmax 44.5 +/- 1.1 fmol/mg protein). Reverse-transcriptase PCR assays detected mRNA encoding both receptor subtypes in myometrium. Autoradiography with radiolabelled PD151242 and BQ3020 demonstrated that ETA receptors were the predominant subtype in the myometrium and identified a population of ETB receptors in the endometrium. In tissue bath experiments, an ET-1-induced increase in contractility of myometrial strips was antagonized by 10 microM FR139317 but not by BQ123 at the same concentration. The ETB agonist BQ3020, which is a potent agonist in animal tissue, did not increase contractility when tested at concentrations up to 2 microM.

Objective: To determine the levels in serum of tissue inhibitor of metalloproteinases (TIMP) in pregnancy and to examine the possibility of a time course in relation to parturition, both term and preterm., Methods: Serum tissue inhibitor of metalloproteinases was measured using an enzyme-linked immunosorbent assay. A cross-sectional study was conducted in 333 women during pregnancy, labor, and the postpartum period and in 27 nonpregnant volunteers. Longitudinal data were obtained from 22 women who provided a sample at term, during labor, and in the postpartum period., Results: In uncomplicated pregnancies, serum TIMP levels were low from the onset of pregnancy until 37 weeks' gestation, in comparison to levels in nonpregnant women (P < .001). During the final weeks of pregnancy, levels rose and at 37-42 weeks were similar to nonpregnant levels. The levels did not change with the onset of labor. Serum concentrations of TIMP obtained during preterm labor were elevated compared to a control group of patients at a similar gestation who subsequently delivered at term (P < .01). Serum TIMP levels were significantly higher during the postpartum period than at all other times (P < .001)., Conclusions: Changes in serum TIMP levels during and after pregnancy may parallel the remodeling of the extracellular matrix that takes place throughout this period. Further work is necessary to evaluate the prognostic value of TIMP for preterm labor.

Serum levels of tissue collagenase, matrix metalloproteinase-1, were measured in both longitudinal and cross-sectional studies, in 332 pregnant women and 27 non-pregnant volunteers. The enzyme-linked immunosorbent assay (ELISA) used is the first described to measure collagenase in serum directly, is specific, and is rapid and reproducible. Levels were determined throughout pregnancy, during term and preterm labour, and in the post-partum period. Serum tissue collagenase levels were elevated in pregnancy (P < 0.001). There was no difference between levels of serum collagenase prior to labour at term and those observed during labour. Similarly, there was no significant difference in levels obtained during preterm labour and those at a similar gestation in women who subsequently delivered at term. No significant decrease in levels had occurred by the 4th post-partum day. In view of these findings of unaltered matrix metalloproteinase-1 levels in association with labour, previous reports of raised serum collagenase activity in association with the onset of spontaneous labour, at term and preterm gestation periods, may be due to increased neutrophil collagenase activity.

Objective: Our purpose was to investigate the effects and pharmacologic properties of potassium channel openers in isolated pregnant human myometrium., Study Design: Biopsy specimens of myometrium obtained from 67 women during pregnancy and labor were used for isometric recording under physiologic conditions., Results: Levcromakalim and pinacidil, two prototype potassium channel openers, are potent inhibitors of spontaneous and induced (0.5 nmol/L oxytocin and 10 mumol/L phenylephrine) contractions in isolated human pregnant myometrium, obtained before and after the onset of labor. The sulfonylurea glibenclamide is an apparent competitive antagonist of this inhibition. No antagonism was observed with the sulfonylurea tolbutamide. Both potassium channel openers significantly inhibited contractility evoked by low (10 and 20 mmol/L) but not high (40 and 80 mmol/L) concentrations of extracellular potassium chloride., Conclusion: These findings suggest that the relaxant ability of levcromakalim and pinacidil in human pregnant myometrium is because of potassium channel activation. This introduces a potential new approach for tocolysis.

The cDNA for Endothelin-2 (ET-2) has been previously cloned and characterised; however, ET-2 remains the least studied of the endothelin isopeptides and little is known of its function and location. In the present study reverse transcriptase-polymerase chain reaction revealed the presence of seven alternatively spliced mRNA variants encoding ET-2, with a specific pattern of distribution in various human tissues. Computer alignment and analysis of the DNA sequences demonstrated alternative splicing of five exons of 52, 169, 123, 99 and 174 base pairs, in the carboxy terminal region of the mRNA encoding preproET-2. This region contains sites for the post-transcriptional processing of preproET-2 into mature ET-2, therefore we postulate that post-transcriptional processing may be disrupted or altered in these variants.

The conversion of the electrically silent pregnant uterus to highly excitable at term represents a dramatic physiological event which is poorly understood. Here we provide the first description, from single-channel recordings, of a large conductance (212 pS) calcium-activated potassium channel (BKCa) in human pregnant myometrium which, in labour tissue, is either absent or has been considerably altered in its physiological and pharmacological properties. In the latter, the K+ channels have an identical conductance (221 pS) and K+ selectivity to BKCa channels but exhibit no Ca2+ or voltage sensitivity. We have termed these BK channels. Furthermore, the activity of the BKCa channel from pregnant tissue is inhibited by internal application of Ba2+ but not tetraethylammonium (TEA), whereas the activity of the BK channel is sensitive to internal TEA but not Ba2+. The role of the BKCa channel may be to suppress myometrial activity during gestation whereas BK channel activity may be important in providing a Ca(2+)-independent K+ conductance which would allow cytoplasmic Ca2+ levels to rise without activating a counteracting Ca(2+)-dependent outward current, normally provided by the BKCa channels which, by its very nature, would tend to oppose depolarization. The findings suggest that K+ channels may have an important role in determining the functional activity of the myometrium.

We analysed 98 consecutive instrumental rotational deliveries of babies weighing > 2,500 grams in primiparae. Our aim was to compare the use of Kjelland's forceps with vacuum delivery with regard to efficacy and safety. The vaginal delivery rate was similar with Kjelland's forceps (96%) and vacuum (90%). The vacuum cup failed to effect rotation in 14% and 77% required forceps delivery after vacuum rotation. The vacuum took longer to effect delivery (P < 0.01). Women delivered with Kjelland's forceps had higher pain scores in the puerperium. There were no perinatal deaths. Low Apgar scores and cord arterial pH values of less than 7.20 were recorded more frequently after vacuum rotation (p < 0.05). Babies delivered with Kjelland's forceps sustained more physical trauma. The incidence of asphyxial encephalopathy was the same in both groups. We would recommend a more selective approach to the use of both rotational vacuum and Kjelland's forceps in primiparae.

The prevalence of premenstrual syndrome (PMS) was determined in 1600 women belonging to various socioeconomic groups in Karachi. Of the total, 33% had PMS, whose prevalence was high in lower socioeconomic group living in socially deprived areas. A direct association of PMS was noted with parity, being low in low parity group. Major complaints were pain in lower abdomen, cramps and backache with majority taking no treatment for their complaints.

Further experimental studies to determine the mass of venom injected by medically-significant Australian elapids are reported. The use of a modified enzyme immunoassay technique to measure venom injected during snake bite is presented. The feeding biting pattern of the Australian eastern brown snake (Pseudonaja textilis) is described. Using data from ten different snakes of this species, it is established that the mass of venom delivered in a first-bite is 4.69 +/- 0.85 mg (mean +/- S.E.) and a mean of 91% of the delivered venom is injected s.c. or into deeper tissues in a first-bite. For this species, the mass of venom delivered sequentially in a bite sequence falls to 1.32 +/- 0.94 mg in the third bite in such a sequence. For the Australian rough-scaled snake (Tropidechis carinatus), the mass of venom delivered in a first feeding bite is 6.15 +/- 2.23 mg, falling to a minimum of 1.92 +/- 0.61 mg in the third bite of a sequence. for the Australian death adder (Acanthophis antarcticus) the mass of venom delivered in a feeding bite is 41.95 +/- 16.13 mg for a first bite. Biting data is also presented for three species of the genus Pseudechis (the Australian mulga (king brown) and black snakes.

Ten experienced weight lifters were studied to determine the influence of strenuous, free-weight, squat lift exercise on changes in plasma volume, mean arterial pressure, and the rate pressure product. After a 40-min postural adjustment prior to upright exercise, each subject completed eight sets of eight repetitions of the squat exercise at 55% of the one-repetition maximum. Electrocardiogram heart rate was monitored throughout the test, and blood pressure was determined at the completion of each exercise set. Arterialized capillary blood was drawn during sitting and standing pre-exercise and at the end of the second, fourth, sixth, and eighth sets for the measurement of hemoglobin, hematocrit, and plasma protein concentration, and after the last set for blood lactate. Five additional subjects participated in a postural control comparison. The results of the ANOVA showed a significant loss in plasma volume over the trials which was 2 1/2 times greater than for the control subjects (17.9 vs 7.7% loss) over the same period of time. Exercise rate pressure product increased by 2.85 times resting while only 1.1 times resting for the control subjects. An elevation in mean arterial pressure was found to be correlated to changes in plasma volume, r = -0.98. This study found that plasma volume is reduced while the rate pressure product is increased during the squat lift exercise.

Antigenic stimulation of spleen mononuclear cells from contact-sensitized mice produced a soluble factor that enhanced the formation of E-rosettes by human lymphocytes in vitro. Production of this murine E-rosette augmenting factor (E-RAF) occurred over a narrow range of antigen concentrations, was hapten-specific, and depended on T-lymphocytes. The factor was not dialysable, in contrast to other substances extracted from normal leucocytes. Murine E-RAF is thus a lymphokine whose action is not species restricted. It was readily detected 30 min after contact of cells with antigen. E-RAF formation by spleen cells and delayed-type hypersensitivity reactions were elicited over a similar period after contact sensitization of mice.

A series of experiments to define the lethal potency (LD50) and electrophysiological properties of the venom of the Australian Rough-scaled Snake (Tropidechis carinatus) are described. Crude pooled venom contains at least five fractions which were separated using liquid chromatography and high pressure liquid chromatography techniques (Fractions I-V). LD50 studies are reported using each of these fractions, with data for both adult and neonatal mice. Fraction I (mol. wt greater than 100,000) was essentially non-toxic. Fraction IV (mol. wt less than or equal to 10,000) and Fraction V (mol. wt less than 1,000) were potent toxic components with LD50'S (s.c. injection; fraction in 0.1% bovine serum albumin and 0.85% saline; neonatal mice) of 0.04 mg/kg and 0.06 mg/kg respectively. LD50'S for the whole crude venom were similar in both adult and neonatal mice. Electrophysiological studies using a Bulbring preparation (rat isolated phrenic nerve-hemidiaphragm) indicated that Fractions I, IIa and IIb were inactive. Fraction IV (mol. wt less than or equal to 10,000) caused rapid neuromuscular blockade which appeared to be irreversible. Neurophysiological experiments with a rat isolated extensor digitorum longus muscle preparation suggested that the major toxic activity of the whole venom resides in Fractions III and IV, and that both of these fractions have presynaptic and postsynaptic action.

Plastic adherent and non-adherent mononuclear cells derived from synovial fluid were found to stimulate peripheral blood mononuclear cells of patients with rheumatoid arthritis (RA) in an autologous mixed lymphocyte reaction (AMLR). Stimulation produced by adherent cells was consistently greater than that produced by non-adherent mononuclear cells. CD11 enriched cells were not significant stimulators in the AMLR, however their presence was required for a significant reaction to occur. Limiting dilution studies revealed that the most plausible model involved two or more cells of the same type in each of the stimulator and responder populations for the AMLR to occur.

Using an enzyme immunoassay technique, a new method for measuring, in vivo, the mass of venom injected during snake bite, is presented. The venom injected into mice (as prey) and the venom left on the skin surface during bites by the two Australian Elapidae, the Taipan (Oxyuranus scutellatus) and the Tiger Snake (Notechus scutatus) has been measured. Venom delivery patterns vary significantly between these two species. In the case of the Tiger Snake (a total of 45 bites studied) the mean mass of venom injected in a first bite was 12.7 mg (S.E. 3.4 mg, median 8.1 mg); an average mass of 0.8 mg (S.E. 0.4 mg, median 0.17 mg) was left on the skin surface. A second bite delivered by the same snake yielded a mean venom mass only 27% of the first. In the case of the Taipan (a total of 24 bites) the mean venom mass injected in the first bite was 20.8 mg (S.E. 6.4 mg); with an average of 0.9 mg (S.E. 0.5 mg) left on the skin surface. In contrast to the situation observed with Tiger Snakes, second and third bites delivered in a rapid sequence yielded increasing masses of venom. The mean delivered in the third of a sequence of three bites was 48.8 mg (S.E. 23.8 mg). The ranges of venom mass, by species and by the sequence number of the bite, are also presented. In 66 of the 69 experimental bites studied in this report, venom could be easily detected, the species identified, and the absolute mass of venom measured.

Using immunological techniques, cases of human snake-bite can be proven and individual snake species identified. A series of experiments is described, to test the antigenic stability and physical properties of an Elapid venom, venom properties which will have implications in field use, transport, or the laboratory procedures relating to the immunological characterization of Australian snake venoms. Using venom from the Elapid, Tropidechis carinatus, we have demonstrated significant immunological stability at a temperature of 37 degrees for 48 h at least, and for 24 h at least when incubated continuously with skin, muscle, and fat homogenates; the venom is stable at 56 degrees for 2 h at least. No loss of venom occurs over the pH range 7-10; at pH ranges less than 4 and at ranges greater than 10 only 30% of venom is detected after 30 min incubation. Sonication (10 min at 100 watts) does not destroy immunological properties of the venom; 10 freeze-thaw cycles result in some 9% loss of immunologically detectable activity. Venom is adsorbed significantly on to dacron swabs, only 13% of the applied does being detected after 48 h incubation at 28 degrees. Sixty-seven percent of applied venom can be recovered from the skin of human volunteers 6 h after a simulated bite. The venom of this Elapid is antigenically robust. With the currently available sensitive assays, venom from human skin should still be detected in material kept without special preparation under field conditions for up to 2 days at least.

A study of the ability of Australians to identify snakes was undertaken, in which 558 volunteers (primary and secondary schoolchildren, doctors and university science and medical students) took part. Over all, subjects correctly identified an average of 19% of snakes; 28% of subjects could identify a taipan, 59% could identify a death adder, 18% a tiger snake, 23% an eastern (or common) brown snake, and 0.5% a rough-scaled snake. Eighty-six per cent of subjects who grew up in rural areas could identify a death adder; only 4% of those who grew up in an Australian capital city could identify a nonvenomous python. Male subjects identified snakes more accurately than did female subjects. Doctors and medical students correctly identified an average of 25% of snakes. The ability to identify medically significant Australian snakes was classified according to the observer's background, education, sex, and according to the individual snake species. Australians need to be better educated about snakes indigenous to this country.