Termination of Pregnancy with Intra-amniotic Hypertonic Saline

Successful therapeutic abortion was performed consecutively by an intra-amniotic injection of hypertonic saline in 102 out of 110 patients in whom the size of the uterus corresponded with a pregnancy of 16 weeks or more.A spontaneous abortion of the fetus followed the injection alone in 92 of the cases, and the overall injection-delivery interval was 39·75 (range 11-98) hours. In 10 women intravenous oxytocin injection was used as an additional uterine stimulant because contractions were not established after 48 hours. Complete spontaneous expulsion of the placenta occurred in 71 cases, and evacuation of the placenta under general anaesthesia was required in the other 31.No major complication occurred among the 110 patients.     

Release of prostaglandin F2α during the bovine peripartal period

Progesterone, estrone and 15-keto-13,14-dihydro-PGF_2α levels were determined in the peripheral blood circulation during the peripartal period in 12 cows. Plasma concentrations of progesterone showed a gradual and continuous decrease during the last 60 days before parturition. This gradual decrease was followed by an abrupt decline in the progesterone concentration occurring 24–48 hours before delivery. The plasma levels of estrone started to increase about 30 days prior to parturition with high concentrations attained during the last days of pregnancy. After delivery the estrone content decreased to baseline levels. Increased levels of the PGF_2α metabolite were recorded 24–48 hours before parturition. These increased PGF_2α metabolite levels occurred before or in conjunction with prepartum luteolysis. Prostaglandin metabolite levels remained high during parturition and returned to baseline 10–20 days after delivery.     

Intra-amniotic LPS and antenatal betamethasone: inflammation and maturation in preterm lamb lungs

The proinflammatory stimulus of chorioamnionitis is commonly associated with preterm delivery. Women at risk of preterm delivery receive antenatal glucocorticoids to functionally mature the fetal lung. However, the effects of the combined exposures of chorioamnionitis and antenatal glucocorticoids on the fetus are poorly understood. Time-mated ewes with singleton fetuses received an intra-amniotic injection of lipopolysaccharide (LPS) either preceding or following maternal intramuscular betamethasone 7 or 14 days before delivery, and the fetuses were delivered at 120 days gestational age (GA) (term = 150 days GA). Gestation matched controls received intra-amniotic and maternal intramuscular saline. Compared with saline controls, intra-amniotic LPS increased inflammatory cells in the bronchoalveolar lavage and myeloperoxidase, Toll-like receptor 2 and 4 mRNA, PU.1, CD3, and Foxp3-positive cells in the fetal lung. LPS-induced lung maturation measured as increased airway surfactant and improved lung gas volumes. Intra-amniotic LPS-induced inflammation persisted until 14 days after exposure. Betamethasone treatment alone induced modest lung maturation but, when administered before intra-amniotic LPS, suppressed lung inflammation. Interestingly, betamethasone treatment after LPS did not counteract inflammation but enhanced lung maturation. We conclude that the order of exposures of intra-amniotic LPS or maternal betamethasone had large effects on fetal lung inflammation and maturation.     

Release of prostaglandin F, regression of corpora lutea and induction of premature parturition in goats treated with estradiol-17β

Premature parturition was induced in five pregnant goats infused intravenously with 4.65–8.4 mg estradiol-17β but not in one treated with 5.85 mg estradiol-17α. A single intramuscular injection of 12 mg estradiol benzoate (8.8 mg estradiol-17β equivalents) was also effective. These doses were estimated to provide plasma concentrations of estradiol-17β in the physiological range for animals at spontaneous parturition. Circulating plasma concentrations of progesterone decreased and lactogenesis occurred before all instances of induced parturition but no such changes resulted from infusion of estradiol-17α. Placental delivery was normal in all animals but neonates of more than 10 days prematurity were non-viable.In three of the five goats infused with estradiol-17β, evidence was obtained for release of F-group prostaglandins from the uterus at the time of onset of the decline in progesterone.     

Pharmacological Studies with Lincomycin in Late Pregnancy

The placental transmission of lincomycin was studied in 60 patients in late pregnancy. A peak maternal blood level of 12·5 μg/ml was recorded 45 minutes after injection, and detectable levels were still present up to 42 hours after a single injection. A peak cord blood level of 2·7 μg/ml was recorded 55 minutes after injection; cord blood levels were about a quarter of the maternal blood levels, and in most cases no levels were detectable 24 hours after a single injection. The passage of lincomycin into and out of the liquor was slower and more variable, but some hours after injection the liquor levels were always higher than the maternal or cord blood levels, and detectable levels were still present in the liquor 52 hours after a single injection. Repeated injections did not lead to any significant accumulation of lincomycin. The only side effect was a possible case of neuromuscular block in a mother delivered by caesarean section. No infant was adversely affected.     

Small-intestinal Cell Turnover in Patients with Parasitic Infections

Small-intestinal deoxyribonucleic acid (DNA) loss rates were measured in six patients with Strongyloides stercoralis hyperinfestation, in four patients with hookworm disease, and in eight normal controls. In the four patients with strongyloidiasis having weight loss, hypoproteinaemia, and oedema the mean DNA loss rates were 73·9, 51·6, 58·0, and 62·2 ng atoms DNA-P/min respectively, which was significantly higher than that of patients with hookworm disease (mean 17·3, S.D. 6·6) or in eight control subjects (mean 14·5, S.D. 7·5). In two of three patients with strongyloidiasis the high DNA loss rates fell to normal after treatment, and in two others investigated only after treatment the rates were normal. It is suggested that the high epithelial cell turnover in these patients may result in excessive loss of endogenous substances and that this may be an important mechanism in causing malnutrition and hypoproteinaemia in patients with S. stercoralis hyperinfestation.     

Measles Virus-Specific IgG in Cerebrospinal Fluid in Multiple Sclerosis

The prevalence of measles virus-specific IgG in cerebrospinal fluid (C.S.F.) of patients with multiple sclerosis (M.S.) has been compared with that in fluids from patients with other neurological diseases and from normal control subjects. The prevalence in the three groups was 58·1%, 24·1%, and 0% respectively. Fivefold concentration of the specimens increased the prevalence in the first two groups to 80·6% and 34·5% respectively, while measles IgG was not detected in any fluids of the normal control group, even after concentration.     

Serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2α in the induction of abortion

Abortion was successfully induced in 62 of 68 patients in the 9th to the 26th week of pregnancy by serial intramuscular administration of 15(S)-15-methyl-prostaglandin F_2α (15-ME-PGF_2α). In 6 patients who failed to abort after 24 hours of prostaglandin administration, a concomitant infusion of oxytocin was initiated; 5 of these patients aborted within 12 hours of the combined therapy. A single patient failed to abort, even with the combined therapy, and underwent surgical evacuation. The mean abortion time in the 67 successful inductions was 14.56 hours. Parous patients aborted somewhat faster, mean 13.98 hours, as compared to nulliparous patients, mean 15.02 hours, but this difference was not statistically significant. In this study initial intramuscular injection of 100 μg 15-ME-PGF_2α was followed in 1 hour by 250 μg and then 250 μg every 2 hours with concomitant oxytocin therapy initiated after 24 hours. The results with this dose schedule were compared to the results obtained in a previous study with a higher dose schedule, an initial dose of 100 μg 15-ME-PGF_2α, followed in 1 hour by 250 μg then 500 μg every 2 hours. There was no significant difference in the mean abortion time and the incidence of side effects between the 2 dose schedules. The mean abortion time for patients with gestational ages of 16 weeks and less was the same with both dose schedules, however patients with gestational ages of 17 weeks and higher aborted somewhat faster with the higher dose schedule. It might therefore be advisable for patients with gestations of 17 weeks and higher to be treated with the higher dose schedule. In earlier gestations patients could be started on the lower schedule, and if abortion had not occurred within 15 hours the dose of 15-ME-PGF_2α could then be increased to 500 μg every 2 hours.     

Fibrin Degradation Products in Normal and Abnormal Pregnancy and Parturition

The levels of fibrin, fibrinogen degradation products (F.D.P.) in the serum were investigated in normal pregnancy and parturition, after caesarean section, and in patients with abruptio placentae, eclampsia, intrauterine death, and post-partum haemorrhage. No significant change occurred during normal pregnancy, but a highly significant increase was found during labour and again during the first week after normal delivery. After caesarean section the levels of F.D.P. were increased two to four hours after operation, and substantially higher levels were found three to eight days after operation than after normal delivery. High levels of F.D.P. were associated with abruptio placentae and eclampsia, and increased levels after intrauterine death and post-partum haemorrhage.An excess of F.D.P. with diminished or normal systemic fibrinolytic activity suggests that local intravascular fibrin deposition and fibrinolysis occur in normal parturition and in these complications of pregnancy. The very high levels of F.D.P. found in abruptio placentae will be important in the pathogenesis of the defective haemostasis that may accompany this complication.     

Reference values for 75 g oral glucose tolerance test in pregnancy

A 75 g oral glucose tolerance test was performed in 212 pregnant women with no predisposing factors suggesting glucose intolerance to establish the normal pattern of glucose metabolism in pregnancy. Reference values for the test were established for the middle of pregnancy (14-20 weeks, n=43) and late pregnancy (28-37 weeks, n=168). One woman was excluded because she had diabetes that required treatment with insulin. There were statistically significant differences between the two groups for samples taken both one and two hours after the glucose load. Reference ranges for the interpretation of the glucose tolerance test in pregnancy should therefore take account of the period of gestation.Arbitrary upper limits of normal (represented by the 97·5 centile) two hours after a 75 g oral glucose load are proposed at 7·5 and 9·6 mmol/l for the second and third trimesters, respectively.     

Post-partum Hypercalcaemia in Treated Hypoparathyroidism

Two patients with post-thyroidectomy hypoparathyroidism were observed throughout three pregnancies. Their normal maintenance treatment with vitamin D remained unaltered. Serum calcium levels remained normal until shortly before delivery but rose rapidly in the immediate postpartum period to peak levels of 7·8, 6·0, and 6·8 mEq/l. while still on normal or reduced maintenance treatment. This apparent increased sensitivity to vitamin D after delivery persisted for as long as three months.     

Exchangeable and Total Body Potassium in Patients with Chronic Renal Failure

Total body potassium determined by whole-body monitoring and exchangeable body potassium estimated with ⁴³K were measured simultaneously in 12 patients with stable chronic renal failure. Values for the exchangeable potassium were obtained after equilibration periods of 24, 48, and 64 hours. The exchangeable body potassium, expressed as a percentage of the total body potassium (mean ± S.E. of mean), gave values of 60·7 ± 3·3%, 83·6 ± 2·7%, and 85·9 ± 2·7% at 24, 48, and 64 hours respectively. It seems that the equilibration between radioactive and native potassium is incomplete after 24 hours; and that exchangeable potassium measured at this time is not an accurate index of the status of total body potassium in such patients. Furthermore, the finding that the value at 64 hours is significantly less than found in healthy subjects suggests that the exchangeable potassium is a smaller fraction of the total body potassium in patients with chronic renal failure.     

Prolonged Corticotrophic Action of a Synthetic Substituted α1-18 ACTH

The adrenocorticotrophic effects of a synthetic corticotrophin analogue, α^1-18 ACTH with D-serine¹, lysine¹⁷, and lysine amide¹⁸ substitutions has been studied. It is effective after both intramuscular and subcutaneous administration and compared with tetracosactrin depot (Synacthen depot, Cortrosyn depot) it has a similarly prolonged time course of action—about 24 hours after 0·5 mg and 30 hours after 1 mg. Unlike tetracosactrin depot, however, it is well absorbed when given intranasally and does not produce painful reactions at the site of injection. Its prolonged time course of action does not depend on a formulation designed to delay its release from the injection site but most probably on a decreased rate of degradation in the circulation.     

Streptokinase in Recent Myocardial Infarction: A Controlled Multicentre Trial

In this controlled multicentre trial treatment with either streptokinase or heparin was allocated at random to patients suffering from myocardial infarction of less than 24 hours'' duration. Treatment with either drug was standardized and lasted for 24 hours. A total of 764 patients entered the trial; 34 patient charts were rejected (including all 28 charts from one centre) because of data failure. On retrospective analysis of the 730 remaining patients the two groups were found to have been comparable at the start.The total hospital mortality was 18·5% of 373 patients allotted to streptokinase treatment and 26·3% of 357 given herapin. The mortality after infusion (24 hours) was 10·6% of 340 patients treated with streptokinase and 17·8% of 320 given herapin (P=0·011). Reinfarction in hospital after the 24-hour period of infusion occurred significantly less often in patients treated with streptokinase (P=0·036). Bleeding from puncture sites and pyrexia occurred more frequently during streptokinase treatment.After exclusion of those patients whose diagnosis was unconfirmed on retrospective assessment, the total hospital mortality rate was 19·0% of 357 patients treated with streptokinase and 27·4% of 339 treated with heparin (P=0·011). These results indicate that in recent myocardial infarction streptokinase was superior to heparin in reducing mortality and reinfarction rate during an average period of six weeks in hospital.     

Vasopressin Analogue DDAVP in Diabetes Insipidus: Clinical and Laboratory Studies

In seven patients with cranial diabetes insipidus an analogue of vasopressin, DDAVP, produced an antidiuresis lasting up to 20 hours after a single intranasal dose. Lysine vasopressin (LVP) in the same dose produced a less potent antidiuresis which lasted for only three to four hours. The plasma half life of DDAVP was 7·8 and 75·5 min for the fast and slow phases, compared with 2·5 and 14·5 min for LVP. Radioiodine-labelled DDAVP was not destroyed by incubation with late pregnancy plasma, which contains an enzyme that inactivates vasopressin. The slow metabolic clearance of DDAVP, its absorption through the nasal mucosa, and its lack of side effects make this the ideal drug for the treatment of vasopressin-sensitive diabetes insipidus. Patients usually require 10 to 20 μg DDAVP given intranasally twice daily for good clinical control of their diabetes insipidus.     

Response to Rimiterol and Salbutamol Aerosols Administered by Intermittent Positive-pressure Ventilation

The bronchodilator and cardiac effects produced by aerosols of 0·5% salbutamol and 0·5% and 1% rimiterol administered for three minutes in 40% oxygen by intermittent positive-pressure ventilation (I.P.P.V.) were compared in 15 asthmatic patients. Salbutamol and both the concentrations of rimiterol were equipotent in peak bronchodilator effect, but salbutamol had a significantly longer duration of bronchodilator action. There was significantly less increase in heart rate after rimiterol than after salbutamol. Aerosols of 0·5% rimiterol, 0·5% salbutamol, and saline were administered by I.P.P.V. to 10 normal volunteers. There was no difference between the mean heart rates after 0·5% rimiterol and saline but a highly significant increase in mean heart rate was observed after 0·5% salbutamol. It was concluded that 0·5% rimiterol was an effective short-acting bronchodilator drug with little or no cardiac beta₁-adrenergic activity when administered for three minutes by I.P.P.V. in 40% oxygen.     

Heat Inducible Expression of a Chimeric Maize hsp70CAT Gene in Maize Protoplasts

The response of maize (Zea mays L.) protoplasts to high temperature stress was investigated. After isolation and electroporation, protoplasts were preincubated for 12 hours at 26°C then incubated for 6 hours at elevated temperatures. The pattern of polypeptides synthesized by these protoplasts during the last hour was monitored by in vivo labeling with ³⁵S-methionine. Incubation at 40° and 42°C resulted in the synthesis of polypeptides not detectable at 26°C. Introduction of a chimeric maize heat shock protein 70 promoter-chloramphenicol acetyltransferase coding region gene into protoplasts via electroporation resulted in the temperature-dependent induction of chloramphenicol acetyltransferase activity with maximal activity at 40°C. In the same protoplasts, a second chimeric gene, in which the firefly luciferase coding region was under the control of the 35S promoter from cauliflower mosaic virus, did not show an increase in expression after incubation at higher temperatures. Maize protoplasts provide a system to study molecular responses to high temperature stress.     

Technetium-99m in the Diagnosis of Thyrotoxicosis

The thyroid uptake at 20 minutes of intravenously administered Technetium-99^m (^99mTc) was measured in 117 patients with a standard scintillation counter. Patients were divided into three groups on the basis of clinical assessment, four-hour ¹³¹I uptake, triiodothyronine (T-3) resin uptake, and protein-bound iodine measurements.In 31 patients with no evidence of thyroid disease the mean ^99m Tc uptake was 1·8% ±S.D. 1·1%. In 32 patients with thyroid enlargement who were euthyroid the mean uptake was 2·5% ±S.D. 2·2%. In 54 thyrotoxic patients the mean uptake was 17·7% with a range of 4·1 to 44%, all cases having an uptake above the upper limit of normal (4·0%). These results agree closely with reported uptake studies using scanning techniques. In seven patients the extrathyroidal neck activity was measured by using a scanner, and the mean was 6·3% of the extrathyroidal total body radioactivity comparing favourably with an assumed 6% used in our calculations.We have shown that the measurement of the thyroid uptake of ^99mTc with a scintillation counter is of value, and that it is not necessary to use scanning techniques in the diagnosis of thyrotoxicosis. Advantages of ^99m Tc are minimal radiation, reduction in patient and laboratory time, and low cost.     

Prostaglandins E and F in uterine venous plasma in relation to peripheral plasma levels of progesterone and 20α-hydroxyprogesterone in the rat throughout pregnancy and parturition

Prostaglandins E and F in uterine venous plasma and progesterone (P) and 20α-hydroxyprogesterone (20α-OH-P) in peripheral plasma were measured by radioimmunoassays throughout pregnancy and parturition in the rat. E Prostaglandins are low (approx. 2 ng/ml) and maintain a more or less constant level throughout most of the pregnancy except just before parturition when they rise to 3.8 ng/ml on day 20. F Prostaglandin levels are always higher than E prostaglandins and show distinct peaks around day 5 (5 ng/ml), day 11 (7 ng/ml), and before parturition (8.4 ng/ml).Progesterone levels are higher than 20α-OH-P levels throughout most of the pregnancy (day 6–20); however, during early pregnancy (day 1–5) and before parturition more 20α-OH-P than P is present in peripheral blood.The possible role of uterine venous prostaglandin levels in altering the 20α-OH-P/P ratio during pregnancy and parturition is discussed.