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Type 1 diabetes mellitus (T1D) is an autoimmune disorder where T lymphocytes damage the islet beta cells but B lymphocytes also play an important role. Although changes in peripheral B cell phenotype have been observed, little is known about the B cells that secrete the autoantibodies. We developed a sensitive B cell enzyme-linked immunospot assay (ELISpot assay) to detect individual B cell antibody responses to glutamic acid decarboxylase (GAD) and islet antigen-2 (IA-2). We found that even healthy donors have B cells that secrete antibodies in response to GAD and IA-2 in the ELISpot. There was increased B cell reactivity to autoantigens in the peripheral blood of individuals with newly-diagnosed, but not long-standing, type 1 diabetes. However, no correlation with serum autoantibody levels was found, indicating that additional factors such as antigen affinity or exposure to antigens in vivo are required for antibody secretion, and that even healthy donors have potentially autoreactive B cells.

Aims/hypothesis Islet-specific autoantibodies can predict the development of type 1 diabetes. However, it remains unclear if B cells, per se, contribute to the causal pancreatic immunopathology. We aimed to identify phenotypic signatures of disease progression among naive and memory B cell subsets in the peripheral blood of individuals with type 1 diabetes. Methods A total of 69 participants were recruited across two separate cohorts, one for discovery purposes and the other for validation purposes. Each cohort comprised two groups of individuals with type 1 diabetes (one with newly diagnosed type 1 diabetes and the other with long-standing type 1 diabetes) and one group of age- and sex-matched healthy donors. The phenotypic characteristics of circulating naive and memory B cells were investigated using polychromatic flow cytometry, and serum concentrations of various chemokines and cytokines were measured using immunoassays. Results A disease-linked phenotype was detected in individuals with long-standing type 1 diabetes, characterised by reduced C-X-C motif chemokine receptor 3 (CXCR3) expression on switched (CD27+IgD−) and unswitched (CD27intermediateIgD+) memory B cells. These changes were associated with raised serum concentrations of B cell activating factor and of the CXCR3 ligands, chemokine (C-X-C motif) ligand (CXCL)10 and CXCL11. A concomitant reduction in CXCR3 expression was also identified on T cells. Conclusions/interpretation Our data reveal a statistically robust set of abnormalities that indicate an association between type 1 diabetes and long-term dysregulation of a chemokine ligand/receptor system that controls B cell migration. Electronic supplementary material The online version of this article (10.1007/s00125-018-4651-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

We consider systems of companies which have financial interests in each other and develop principles by which the real interest of one company in another can be determined. The paper develops an algorithm to calculate true interests from a weighted digraph that encodes the direct and indirect mutual holdings of the companies.

OBJECTIVE: To assess if exposure to repeat dose(s) of antenatal corticosteroids has beneficial effects on neurodevelopment and general health in mid-childhood, at 6 to 8 years’ corrected age. METHODS: Women at risk for very preterm birth, who had received a course of corticosteroids ≥7 days previously, were randomized to intramuscular betamethasone (11.4 mg Celestone Chronodose) or saline placebo, repeated weekly if risk of very preterm birth remained. Mid-childhood assessments included neurocognitive function, behavior, growth, lung function, blood pressure, health-related quality of life, and health service utilization. The primary outcome was survival free of neurosensory disability. RESULTS: Of the 1059 eligible long-term survivors, 963 (91%) were included in the primary outcome; 479 (91%) in the repeat corticosteroid group and 484 (91%) in the placebo group. The rate of survival free of neurosensory disability was similar in both groups (78.3% repeat versus 77.3% placebo; risk ratio 1.00, 95% confidence interval, 0.94–1.08). Neurodevelopment, including cognitive function, and behavior, body size, blood pressure, spirometry, and health-related quality of life were similar in both groups, as was the use of health services. CONCLUSIONS: Treatment with repeat dose(s) of antenatal corticosteroids was associated with neither benefit nor harm in mid-childhood. Our finding of long-term safety supports the use of repeat dose(s) of antenatal corticosteroids, in view of the related neonatal benefits. For women at risk for preterm birth before 32 weeks’ gestation, ≥7 days after an initial course of antenatal corticosteroids, clinicians could consider using a single injection of betamethasone, repeated weekly if risk remains.

Please cite this paper as: Dodd J, Grivell R, Crowther C, Robinson J. Antenatal interventions for overweight or obese pregnant women: a systematic review of randomised trials. BJOG 2010;117:1316–1326. Background Overweight and obesity during pregnancy is an increasing health problem. Objective A systematic review to assess the benefits and harms of antenatal dietary or lifestyle interventions for pregnant women who are overweight or obese. Search strategy The Cochrane Controlled Trials Register (CENTRAL) was searched (last search January 2010). Reference lists of retrieved studies were searched by hand. No date or language restrictions were used. Selection criteria Randomised controlled trials comparing antenatal dietary and/or lifestyle or other interventions with no treatment for overweight or obese women were considered. Studies were evaluated independently for appropriateness for inclusion and methodological quality. The primary outcome was large-for-gestational-age infants. Data collection and analysis Nine randomised controlled trials were included involving 743 women who were overweight or obese during pregnancy. Seven trials compared a dietary intervention with standard antenatal care. Main results There were no statistically significant differences identified between women who received an antenatal intervention and those who did not for the large-for-gestational-age infant outcome (three studies; 366 women; risk ratio 2.02; 95% CI 0.84, 4.86) or mean gestational weight gain [four studies; 416 women; weighted mean difference −3.10 kg; 95% CI −8.32, 2.13 (random-effects model)]. There were no statistically significant differences identified for other reported outcomes. Author’s conclusions The effect of providing an antenatal dietary intervention for overweight or obese pregnant women on maternal and infant health outcomes remains unclear.

Objective To evaluate the effect of providing antenatal dietary and lifestyle advice on neonatal anthropometry, and to determine the inter-observer variability in obtaining anthropometric measurements. Design Randomised controlled trial. Setting Public maternity hospitals across metropolitan Adelaide, South Australia. Population Pregnant women with a singleton gestation between 10+0 and 20+0 weeks, and body mass index (BMI) ≥25 kg/m2. Methods Women were randomised to either Lifestyle Advice (comprehensive dietary and lifestyle intervention over the course of pregnancy including dietary, exercise and behavioural strategies, delivered by a research dietician and research assistants) or continued Standard Care. Analyses were conducted using intention-to-treat principles. Main outcome measures Secondary outcome measures for the trial included assessment of infant body composition using body circumference and skinfold thickness measurements (SFTM), percentage body fat, and bio-impedance analysis of fat-free mass. Results Anthropometric measurements were obtained from 970 neonates (488 Lifestyle Advice Group, and 482 Standard Care Group). In 394 of these neonates (215 Lifestyle Advice Group, and 179 Standard Care Group) bio-impedance analysis was also obtained. There were no statistically significant differences identified between those neonates born to women receiving Lifestyle Advice and those receiving Standard Care, in terms of body circumference measures, SFTM, percentage body fat, fat mass, or fat-free mass. The intra-class correlation coefficient for SFTM was moderate to excellent (0.55–0.88). Conclusions Among neonates born to women who are overweight or obese, anthropometric measures of body composition were not modified by an antenatal dietary and lifestyle intervention. Tweetable abstract Lifestyle advice in pregnancy does not modify body composition of infants of overweight and obese women.

In recent years the use of high-order harmonic radiation to create and control events on attosecond timescales has grown at a phenomenal rate. With the use of carrier-envelope phase (CEP) stabilization and few-cycle laser systems it is possible to probe physical processes on unprecedented timescales. Here, we report the first experimental observation of high-harmonic emission at individual half-cycles of a laser pulse. We show that these half-cycle emissions are extremely sensitive to the CEP, providing a route to a new single-shot measurement technique of the CEP. We use this technique to measure the CEP of an 8.5 fs pulse at a centre wavelength of 800 nm with an accuracy of 20 as (1 as=1×10−18 s). With appropriate spatio-spectral filtering of the harmonic spectra, our calculations show that we can isolate emission from an individual half-cycle cutoff, which corresponds to a single isolated attosecond pulse of duration

We have investigated experimentally the energy transmission and spectral broadening of 30-fs, 700-μJ laser pulses in a neon-filled, 250-μm inner diameter hollow fibre. We implement a differentially pumped fibre, where a vacuum is maintained at the fibre entrance, and compare this to a statically filled fibre. We obtain significantly higher transmission and increased spectral broadening in the differentially pumped case due to a reduction of ionisation defocusing at the fibre entrance. This arrangement provides a method for the generation of near-transform- limited pulses with smoothly varying pulse duration whilst maintaining constant pulse energy, by simple adjustment of the gas pressure. Compression of ∼450-μJ pulses from the differentially pumped fibre to a duration of 6.5 fs has been achieved for pulses with spectra spanning 650–900 nm, by use of negatively dispersive chirped mirrors.

Anatomical hemispherectomy is frequently employed in the surgical management of pediatric patients with medically refractory epilepsy.In this chapter, we review the historical evolution of this surgical procedure, outline the indications and the criteria for selecting surgical candidates and describe the important pre-operative evaluation of the surgical candidates.We provide a detailed description of our surgical technique, anesthesiological considerations, and post-operative care plan. Ultimately we analyze the most common complications associated with this procedure.Anatomical hemispherectomy performed in carefully selected pediatric patients with medically intractable epilepsy can be a safe and efficacious surgical procedure.

Evidence is accumulating that the risk of osteoporosis in later life may be determined in part by environmental influences on bone development during intrauterine and early postnatal life. A potential role for fetal leptin in mediating these effects is suggested by animal studies showing that leptin influences prenatal osteoblast growth and development, and that fetal leptin concentrations are altered by changes in maternal nutrition. In a group of term human infants we reported previously that maternal birthweight, smoking, fat mass, and exercise during late pregnancy independently predict neonatal bone mass. To investigate the potential role of leptin in mediating these effects, we now relate leptin concentrations in umbilical venous serum to neonatal bone mass and body composition in 117 infants. There were strong positive associations between umbilical venous leptin concentration and each of whole body bone mineral contents (BMC) (r = 0.42, P < or = 0.001) and estimated volumetric bone density (r = 0.21, P = 0.02); whole body lean mass (r = 0.21, P < or = 0.024); and whole body fat mass (r = 0.60, P < 0.001). The associations with neonatal BMC and fat mass, but not with lean mass, were independent of associations that we have reported previously between cord serum insulin-like growth factor 1 (IGF-1) concentrations and neonatal body composition. Among the maternal determinants of neonatal bone mass, cord leptin explained the relationship with maternal fat stores, but not those with the mother's own birthweight, smoking, or physical activity. We conclude that umbilical venous leptin predicts both the size of the neonatal skeleton and its estimated volumetric mineral density. In addition, among previously documented maternal determinants of neonatal bone mass in healthy pregnancies, maternal fat stores may mediate their effect on fetal bone accrual through variation in fetal leptin concentrations.

Objective To determine the use of pharmacologic analgesia during childbirth when antenatal hypnosis is added to standard care. Design Randomised controlled clinical trial, conducted from December 2005 to December 2010. Setting The largest tertiary referral centre for maternity care in South Australia. Population A cohort of 448 women at >34 weeks of gestation, with a singleton pregnancy and cephalic presentation, planning a vaginal birth. Exclusions were: the need for an interpreter; pre-existing pain; psychiatric illness; younger than 18 years; and previous experience of hypnosis for childbirth. Methods All participants received usual care. The group of women termed Hypnosis + CD (hypnotherapist guided) were offered three antenatal live hypnosis sessions plus each session's corresponding audio CD for further practise, as well as a final fourth CD to listen to during labour. The group of women termed CD only (nurse administered) were played the same antenatal hypnosis CDs as group 1, but did not receive live hypnosis training. The control group participants were given no additional intervention or CDs. Main outcome measure Use of pharmacological analgesia during labour and childbirth. Results No difference in the use of pharmacological analgesia during labour and childbirth was found comparing hypnosis + CD with control (81.2 versus 76.2%; relative risk, RR 1.07; 95% confidence interval, 95% CI 0.95–1.20), or comparing CD only with control (76.9 versus 76.2%, RR 1.01, 95% CI 0.89–1.15). Conclusions Antenatal group hypnosis using the Hypnosis Antenatal Training for Childbirth (HATCh) intervention in late pregnancy does not reduce the use of pharmacological analgesia during labour and childbirth.

The epidemiological observations that prenatal and perinatal events lead to adult disease are now well supported by animal data. The events in the periconceptual period, in early and late pregnancy and in infancy can effect programming of cardiovascular, endocrine and metabolic regulatory systems. However, the mechanisms underlying these pathological changes remain to be elucidated. Until this is addressed in experimental animals, clinical trials in human pregnancy are premature.

Babies who are small at birth or during infancy have increased rates of cardiovascular disease and non-insulin-dependent diabetes as adults. Some of these babies have low birthweights, some are small in relation to the size of their placentas, some are thin at birth, and some are short at birth and fail to gain weight in infancy. This paper shows how fetal undernutrition at different stages of gestation can be linked to these patterns of early growth. The fetuses' adaptations to undernutrition are associated with changes in the concentrations of fetal and placental hormones. Persisting changes in the levels of hormone secretion, and in the sensitivity of tissues to them, may link fetal undernutrition with abnormal structure, function, and disease in adult life.

We generate the 7th-13th harmonic of ≈800 nm by propagating 30-fs pulses at >1014W/cm2through a xenon-filled hollow-core PCF. The extremely low HHG threshold of 0.4 µJ would be achievable by multimegahertz solid-state lasers.

Applied Physics B, 97 (2), ISSN:0946-2171, ISSN:1432-0649, ISSN:0721-7269, ISSN:0340-3793

Establish an expert consensus for training in perioperative echocardiography in the province of Quebec.Cardiac anesthesiologists practicing in the province of Quebec with expertise in echocardiography were involved in the development of a multicentre expert consensus on training in perioperative echocardiography. Guidelines for training in adult echocardiography, transesophageal echocardiography and perioperative echocardiography by the American Society of Echocardiography (ASE), the American College of Cardiology (ACC) and/or the Society of Cardiovascular Anesthesiologists (SCA) were reviewed.A basic, advanced and director level of expertise were identified for training in perioperative echocardiography. The total number of echocardiographic examinations to achieve each of these levels of expertise remains unchanged from the 2002 ASE-SCA guidelines. However, the recommended proportion of examinations performed personally is increased in the Quebec expert consensus for both the basic and the advanced level of training to ensure proficiency in echocardiography while providing anesthesia care to the patient. A level of autonomy in perioperative echocardiography is also identified in the basic level of training as defined in the Quebec expert consensus. Maintenance of competence, certification in the perioperative transesophageal echocardiography (PTE) examination and duration of training are outlined for each of the three levels of training in the Quebec expert consensus but are not part of the recent 2002 ASE-SCA guidelines.Adequate perioperative echocardiographic training is an important aspect of cardiovascular anesthesia. The ACC, ASE and SCA guidelines for training in echocardiography were modified to reflect the expert consensus of anesthesiologists in the province of Quebec.

The majority of women with a twin pregnancy give birth preterm, but about 46% deliver after 37 weeks of gestation. Several population-based studies have reported that there is a higher risk of perinatal mortality and morbidity among women with a twin pregnancy continuing beyond 37 weeks of g

We aimed to determine whether our results were any better or worse than other published reports and to examine the efficacy of the West Midlands Ambulance Service (WMAS) policy of applying cardiopulmonary resuscitation (CPR) and manual ventilation to all unwitnessed cardiac arrests in preference to immediate defibrillation. All cardiac arrests were studied from October 1994 to September 1996. In all unwitnessed arrests, crews undertook CPR and manually ventilated the lungs via a mask or an endotracheal tube with a bag and valve or a mechanical resuscitator using an FIO2 of 1 or 0.21 for at least 2 min before defibrillation was attempted. There were 3403 diagnosed cardiac arrests but, in these, the diagnosis was not certain. CPR and advanced life support (ALS) were applied in 3380 patients and return of spontaneous circulation (ROSC) was obtained in 554, giving a success rate of 16.4%. A total of 364 patients were accepted into hospital, 90 patients died in A&E but 274 patients were admitted to ICU/CCU. Seventy died within 24 h, 69 died after 24 h and 135 were discharged alive and well without cerebral damage. The final success to discharge rate was 49.27%. Of those discharged, 69 had a circulatory arrest period of more than 4 min but in only 10 was a bystander available to start CPR. The European Resuscitation Council Guidelines recommending immediate defibrillation for unwitnessed arrests are not supported by these results. The apparent lack of cerebral damage and the percentage success suggests that resuscitation considerations should be as brain orientated as they are heart orientated. The elapsed time periods reported challenge several shibboleths.

Growth of the placenta is influenced by events before and during early pregnancy. Some of these events set the growth trajectory of the placenta and the fetus for the remainder of the pregnancy. Maternal size and nutrition, and the local metabolic, cytokine and hormonal environment of the embryo all affect growth of the placenta. □ Placental growth, embryo development, maternal size, maternal nutrition, dietary intake

1. Foetal breathing movements, electrocortical activity, arterial pressure and heart rate were recorded continuously in chronically catheterized sheep, 97–145 days pregnant. 2. With increasing gestational age there was a fall in heart rate of 0·67 beats/day and a rise in arterial pressure of 0·46 mmHg/day. 3. Hypoxaemia in the foetus was induced by allowing the ewe to breathe low oxygen mixtures, 9% O2 with 3% CO2 in N2. In the younger foetuses there was an initial rise in heart rate whereas in the older foetuses there was a fall. After the end of hypoxia there was a persistent tachycardia in both groups. In the older foetuses there was a rise of arterial pressure. 4. Two vagotomized older foetuses showed cardiovascular responses similar to those of the younger foetuses. 5. Foetal breathing movements were abolished by hypoxaemia in twenty-two of twenty-five experiments. In the three exceptional experiments there was a small rise in Pa, CO2. 6. The proportion of time occupied by low voltage electrocortical activity in the foetus was reduced by hypoxaemia. 7. Hypercapnia was induced by giving the ewe 4-6% CO2 with 18% O2 in N2 to breathe. After an initial slight fall the foetal heart rate increased and there was a small rise in foetal arterial pressure. 8. The proportion of time occupied by low voltage electrocortical activity and breathing movements was increased by hypercapnia. 9. Maternal hyperoxia, induced by giving 50% O2 in N2, did not significantly increase foetal breathing movements unless the ewe was in labour. In labour the foetuses had lower Pa, O2 values initially and a reduced incidence of foetal breathing, both of which were increased by maternal hyperoxia.

SUMMARY The concentration of ovine placental lactogen (oPL) was measured by radioimmunoassay in plasma samples from chronically catheterized ewes and their fetuses from day 110 of gestation to term (about day 145). Concentrations of oPL in the plasma of the mother and fetus were raised after surgery, and remained raised for 3–5 days after the operation. Concentrations of oPL were greatest in the fetus at days 120–124 of gestation, and then declined until delivery. Mean concentrations of oPL in the fetus in late pregnancy for single, twin and triplet pregnancies were 101±6 (s.e.m.), 100±11 and 117±59 ng/ml respectively and were not significantly different. Mean concentrations of oPL in the mother in late pregnancy for single, twin and triplet pregnancies were 718±227, 1387±160 and 1510±459 ng/ml respectively; the difference between these means was significant (P P r = 0·624, P

SUMMARY The changes in plasma ACTH concentration of pregnant sheep and their foetuses during the latter half of pregnancy and during labour were studied. Before 140 days of gestation the mean concentration in foetal arterial plasma was 117 ± 19 (s.e.m.) pg/ml which rose to a mean of 286 ± 63 pg/ml. The rise in ACTH occurred at about the same time as, but not before, the rise in corticosteroid concentration in foetal plasma. The maternal plasma ACTH concentration did not change during the latter half of pregnancy and had a mean concentration of 64 ± 9 pg/ml. During labour there was a progressive rise in the ACTH concentration in foetal plasma which was not associated with any corticosteroid changes. Ethanol did not suppress labour but reduced the ACTH concentration in foetal plasma.

In a study of 56 patients undergoing simple surface surgery and simple light anaesthesia, 12 developed atelectasis in the postoperative period, and half of these also inhaled iodised oil fluid injection B.P. ('Neo-Hydriol Fluid ') on being asked to swallow the dye within two or more hours after the anaesthetic. It is suggested that keeping the pharynx dry and draining externally would reduce the incidence of these pulmonary complications. Patients at particular risk seem to be those who have operations on the chest and neck. The association between the length of time that the operations lasted and the incidence of atelectasis was suggestive, but not statistically conclusive. No single factor in the anaesthetic technique was specifically associated with the observed pulmonary complications.

In a consecutive series of 783 patients with acute myocardial infarction, 13 (1.7%) suffered a stroke. In all but one case the strokes occurred among the 255 patients whose peak creatine kinase (CK) concentrations fell in the upper third of the range of values (over 1160 IU/l, about eight times the upper limit of normal); the exception was a patient with a pre-existing ventricular aneurysm. The incidence of stroke in the patients with CK over 1160 IU/l was 4.7%, 24 times the incidence when peak CK was below this value (0.2%). Higher peak serum enzyme concentrations were associated with an even higher incidence of stroke. Comparison of peak enzyme concentrations with cumulated CK showed a close correlation (r = 0.90 with peak CK; r = 0.85 with peak aspartate transaminase), suggesting that the peak enzyme values reflected infarct size. Thus the risk of stroke after infarction was a function of the size of the myocardial infarct; two-thirds of the patients had negligible risk of stroke and did not need anticoagulant prophylaxis.

The use of epidural opiates, unlike the use of epidural local anaesthetics, is considered to have little, if any, effect on the cardiovascular system. A 76-year-old man with a flail chest injury was given a lumber epidural injection of meperidine. During the injection he suddenly complained of feeling cold, shivered vigorously and became tachypneic. His arterial blood pressure rose from 170/70 to 300/110; his pulse rate rose to 150/min. The patient was severely hypertensive for 40 minutes until treated with intravenous phentolamine. There is increasing evidence in the literature implicating the involvement of endogenous opiates in the central control mechanisms of blood pressure control.

Ultrasonographic evaluation of a suspected abdominal mass in children is becoming routine. Recognition of a rare congenital anomaly known as duplication of the gastrointestinal tract might aid in diagnosis and obviate the need for an extensive workup. Two cases are presented that clearly demonstrate the ultrasonographic spectrum of findings in this condition, ranging from a sonolucent cyst to an echogenic mass. An echogenic inner rim seen ultrasonographically is highly suggestive of the diagnosis.

SUMMARY The change in plasma ACTH and corticosteroid concentrations in response to a 60 min period of hypoxaemia were studied in foetal and adult sheep during the latter half of pregnancy. Hypoxaemia consistently caused large rises in the concentration of ACTH in foetal plasma, the magnitude of which did not change with gestational age but was related to the physiological state of the foetus. Before 139 days small and slow rises in corticosteroid (predominantly cortisol) concentration in foetal plasma were observed during hypoxaemia, and these may have been of maternal origin. After 139 days, hypoxaemia caused a rapid and large rise in the concentration of cortisol and corticosterone in foetal plasma, which was largely of foetal origin. Hypoxaemia caused no consistent change in maternal plasma ACTH concentration but was associated with progressive increases in plasma cortisol concentrations. The cortisol:corticosterone ratio in foetal plasma was 1·5 before 139 days and increased to 4·1 several days before term which was lower than the value of 9 in maternal plasma. Small concentrations of 11-deoxycortisol and cortisone were detected in maternal and foetal plasma, the changes of which were small during hypoxaemia. The results indicate that a maturational change in the sensitivity of the foetal adrenal to endogenous ACTH occurs several days before term.

N OREPINEPHRINE, a naturally occurring adrenergic transmitter, has both fl~-receptor and cq-receptor inotropic activity and has been used to treat the low cardiac output (CO) seen following cardiopulmonary bypass (CPB). 1 Its oq-receptor effect can produce increases in systemic vascular resistance (SVR), which can be modified by the concurrent use of a vasodilator. 2'3 Amrinone, a phosphodiesterase F-Ill inhibitor, is a potent vasodilator and a positive inotropic drug. 4 Its effects may counteract the vasoconstrictor effects of norepinephrine and may be synergistic or additive with its inotropic action. 5 Tolerance to the effects of norepinephrine may occur in the failing heart. This may be due to a decrease in the density of beta-receptors in the myocardium or secondary to an uncoupling of the beta-receptor from adenylate cyclase. 6'7 Amrinone exerts its effect independent of the beta-receptor, slowing breakdown of cyclic adenosine monophosphate (cAMP), and for a given degree of beta-adrenergic stimulation, it may increase the amount of intracellular calcium available to troponin-C. A case is reported of a patient, following aortocoronary bypass surgery, who was in severe biventricular failure, unresponsive to treatment with high doses of norepinephrine and phentolamine. The addition of amrinone to the patient's treatment resulted in marked improvement in his clinical condition, cardiac index (CI), and mixed venous oxygen saturation (SVO2).

The changes occurring in the plasma concentrations of ACTH and corticosteroids of maternal and fetal sheep, with chronically implanted catheters before, during and after hypoxia have been measured. During hypoxia there was a transient rise in maternal plasma ACTH which was associated with a large rise in plasma corticosteroids. In contrastfetal plasma ACTH showed a large and prolonged rise during hypoxia with little change (except in one case) in plasma corticosteroid levels. In the fetus, therefore, the adrenalappears to be far less sensitive to ACTH stimulation than in the mother. There was no consistent correlation between the pCO2, pH and ACTH changes observed.(Endocrinology 94: 588, 1974)