Association between maternal blood lipids during pregnancy and offspring growth trajectories in a predominantly macrosomic cohort: findings from the ROLO longitudinal birth cohort study.

The purpose of this study is to examine associations between maternal lipid profiles in pregnancy and offspring growth trajectories in a largely macrosomic cohort. This is a secondary analysis of the ROLO birth cohort (n = 293), which took place in the National Maternity Hospital, Dublin, Ireland. Infants were mostly macrosomic, with 55% having a birthweight > 4 kg. Maternal mean age was 32.4 years (SD 3.9 years), mean BMI was 26.1 kg/m2 (SD 4.4 kg/m2) and 48% of children born were males. Total cholesterol, high density lipoprotein cholesterol (HDL-cholesterol), low density lipoprotein cholesterol (LDL-cholesterol) and triglycerides were measured from fasting blood samples of mothers at 14 and 28 week gestation. The change in maternal lipid levels from early to late pregnancy was also examined. Offspring abdominal circumference and weight were measured at 20- and 34-week gestation, birth, 6 months, 2 years and 5 years postnatal. Linear spline multilevel models examined associations between maternal blood lipid profiles and offspring growth. We found some weak, significant associations between maternal blood lipids and trajectories of offspring growth. Significant findings were close to the null, providing limited evidence. For instance, 1 mmol/L increase in maternal triglycerides was associated with faster infant weight growth from 20- to 34-week gestation (0.01 kg/week, 95% CI - 0.02, - 0.001) and slower abdominal circumference from 2 to 5 years (0.01 cm/week, 95% CI - 0.02, - 0.001). These findings do not provide evidence of a clinically meaningful effect.    Conclusion: These findings raise questions about the efficacy of interventions targeting maternal blood lipid profiles in pregnancies at risk of macrosomia. New studies on this topic are needed. What is Known: • Maternal fat accumulation during early pregnancy may potentially support fetal growth in the third trimester by providing a reserve of lipids that are broken down and transferred to the infant across the placental barrier. • There are limited studies exploring the impact of maternal lipid profiles on infant and child health using growth trajectories spanning prenatal to postnatal life. What is New: • Maternal blood lipid profiles were not associated with offspring growth trajectories of weight and abdominal circumference during pregnancy up to 5 years of age in a largely macrosomic cohort, as significant findings were close to the null, providing limited evidence for a clinically meaningful relationship. • Strengths of this work include the use of infant growth trajectories that span prenatal to postnatal life and inclusion of analyses of the change of maternal lipid levels from early to late pregnancy and their associations with offspring growth trajectories from 20-week gestation to 5 years of age.

Randomized preclinical study of machine perfusion in vascularized composite allografts.

BACKGROUND: Attempts to improve limb preservation for transplantation using ex vivo perfusion have yielded promising results. However, metabolic acidosis, aberrant perfusate biochemistry and significant perfusion-induced oedema are reported universally. Optimizing perfusion protocols is therefore essential for maintaining tissue health. METHODS: A randomized, two-stage open preclinical trial design was used to determine the optimal temperature and mean arterial pressure for machine perfusion. Conditions compared were: normothermic machine perfusion at 70 mmHg (NMP-70); subnormothermic perfusion (28°C) at 70 mmHg; subnormothermic (28°C) perfusion at 50 mmHg; and hypothermic perfusion (10°C) at 30 mmHg. Following this, a head-to-head experiment was undertaken comparing the optimal machine perfusion with static cold storage. Paired bilateral limbs (10 in total) were randomized to either 8 h of static cold storage, or 2 h of static cold storage and 6 h of optimal machine perfusion. Both groups of limbs were then reperfused on a circuit primed with matched blood from unrelated donors for 4 h without immunosuppression. RESULTS: NMP-70 resulted in less tissue injury and stable perfusion biochemistry. Assessing reperfusion outcomes, static cold storage resulted in acidosis with increased lactate and a worsening electrolyte profile, necessitating bolus infusions of bicarbonate to prevent graft loss. Conversely, NMP-70 was associated with haemodynamic and biochemical stability. Histologically, on reperfusion with allogeneic whole blood, limbs subjected to static cold storage exhibited multifocal ischaemic injury and increased inflammation, which was absent with NMP-70. Static cold storage also resulted in significant oedema compared with NMP-70. CONCLUSION: Normothermic perfusion resulted in superior graft preservation and less reperfusion injury compared with the current static cold storage protocol.

Bone resorption and dietary calcium in pregnancy-a window to future maternal bone health.

BACKGROUND: Pregnancy is characterized by increased bone turnover and reversible loss of bone mineral density (BMD) to meet fetal calcium demands. The long-term effect of bone turnover and maternal diet in pregnancy on maternal bone is not well established. OBJECTIVE: We aimed to determine if an association exists between [1] bone resorption, [2] dietary calcium, and [3] serum 25-hydroxyvitamin D in pregnancy with maternal BMD 5-year postpartum. DESIGN: This is a prospective, longitudinal study of 107 women recruited to the ROLO low glycemic index dietary intervention trial in pregnancy and followed-up at 13, 28, and 34 weeks' gestation and 5 years' postpartum. At 13 and 28 weeks' gestation, a biomarker of bone resorption, urine cross-linked N-telopeptide of type I collagen (uNTX), was measured. At the 5-year follow-up BMD was measured using dual-energy X-ray absorptiometry. Anthropometry, dietary intakes, and serum 25-hydroxyvitamin D were measured in pregnancy and at 5 years. Multiple linear regression, controlling for confounders, was used for analysis. RESULTS: Mean BMD at 5 years was 1.208 g/cm2. In pregnancy, 24-34% reported dietary calcium intakes <800 mg/day. Vitamin D deficiency (< 30 nmol/L) was observed in 38-41% of women in pregnancy and in 29% of women at the 5-year follow-up. At 13 and 28 weeks' gestation, uNTX levels greater than the median were associated with 0.060 and 0.050 g/cm2 lower BMD 5 years later, respectively. Dietary calcium <800 mg/day in trimester 3 was associated with 0.072 g/cm2 lower BMD 5 years later. Vitamin D deficiency at 5 years, but not in pregnancy, was associated with lower BMD. CONCLUSION: Higher bone resorption and low dietary calcium in pregnancy were associated with lower BMD 5 years later. These findings could enable the identification of women at risk of declining of BMD in later life, but further research is needed. Adequate dietary calcium should be advised in the antenatal setting to promote lifelong maternal bone health.

Fetal Growth Trajectories and Their Association with Maternal, Cord Blood, and 5-year Child Adipokines.

BACKGROUND: The growth of the fetus is a complex process influenced by multiple factors. Studies have highlighted the important role of biochemical growth markers such as leptin and adiponectin on fetal growth. OBJECTIVE: To compare fetal growth trajectories with biochemical growth markers from maternal blood samples at 28 weeks' gestation, cord blood samples at birth, and in child blood samples at 5 years of age from mother-infant pairs who were part of the longitudinal ROLO study. METHODS: 781 mother-infant pairs from the ROLO and ROLO Kids study were included. Ultrasound measurements and birth weight were used to develop fetal growth trajectory groups for estimated abdominal circumference and estimated weight. Blood serum levels of leptin, adiponectin, insulin, TNF-alpha, and IL-6 from maternal, cord, and 5-year child samples were recorded. ANOVA and chi-square tests were applied to test the associations between fetal growth trajectory membership and maternal and child biochemical growth indicators. The influence of child sex was also investigated. RESULTS: Male sex was associated with a faster weight trajectory compared to females (p=0.001). At 28 weeks' gestation, maternal leptin levels were significantly higher in mothers with a fetus on a slower estimated abdominal circumference trajectory compared to fast (25616 [IQR: 11656.0 to 35341.0] vs. 14753.8 [IQR: 8565.4 to 24308.1], p < 0.001) and maternal adiponectin levels were lower in fetuses on a slower estimated abdominal circumference trajectory compared to a fast trajectory (22.4 [IQR: 13.6 to 35.9] vs. 27.6 [IQR: 17.6 to 46.3], p=0.027). No associations were noted with inflammatory markers. No associations were identified between fetal growth trajectories and growth markers at 5 years of age. CONCLUSIONS: This study shows that male sex is associated with an accelerated estimated weight trajectory. Furthermore, high leptin and low adiponectin in maternal serum in late gestation are associated with a slower fetal growth trajectory. No associations were identified with blood growth markers after pregnancy.

Taking guidance from parents involved in a longitudinal birth cohort - the ROLO family advisory committee.

BACKGROUND: The ROLO Study (Randomised cOntrol trial of a Low glycaemic index diet in pregnancy to prevent macrosomia) was a randomised control trial conducted between 2007 and 2011 to examine if a low glycaemic index (GI) diet could reduce the incidence of macrosomia. The ROLO Family Advisory Committee is a self-selected group of parents who are involved in the longitudinal follow-up of the ROLO Study. The committee was established in 2017 and the goal is to achieve a partnership between ROLO families and researchers, leading to improved research quality, relevance, and outcomes. This research method is termed "Public and patient involvement (PPI)" and describes how researchers collaborate and engage with the public in order to make research more relevant to them. METHODS: The ROLO study mothers and children have been prospectively followed-up at multiple time points post-pregnancy. In October 2017, all women were invited to join the ROLO Family Advisory Committee via email or via advertisement on the ROLO Study Facebook page. Fathers and other guardians of the study children were also invited to join. Two annual meetings with the research team and parents were held in 2018 and 2019. The meetings were recorded, transcribed verbatim by researchers, and thematically analysed. RESULTS: Parents provided opinions on the areas they felt should be explored within the ROLO study using information that was collected up to the current follow-up point. They also shared views on research interests which were of importance to them. These topics included; child mental health, fussy eating in childhood and healthy eating policies in schools. Mothers were much more concerned about factors which influenced their child's health rather than their own. Incorporating an element of PPI to this study was found to be a positive learning experience for participants and researchers. CONCLUSION: The involvement of parents has enriched the research agenda at the UCD Perinatal Research Centre. We will continue to engage with the parents of the ROLO Study and plan to involve the children to explore their opinions at the next opportunity.

DASH (Dietary Approaches to Stop Hypertension) dietary pattern and maternal blood pressure in pregnancy.

BACKGROUND: High blood pressure (BP) in pregnancy is associated with significant adverse outcomes. In nonpregnant populations, the DASH (Dietary Approaches to Stop Hypertension) diet is associated with reductions in blood pressure. The present study investigated the relationship between the DASH dietary pattern and maternal BP in pregnancy. METHODS: This is an observational study of 511 women who participated in the ROLO study (Randomized cOntrol trial of LOw glycaemic index diet for the prevention of recurrence of macrosomia), 2007-2011, Dublin, Ireland. Auscultatory blood pressure, systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements were taken. Mean arterial pressure (MAP) was calculated. Dietary intakes were recorded using 3-day food diaries in each trimester. DASH scoring criteria were used to score and rank participants from low to high intakes of foods recommended in the DASH diet. Statistical analysis using analysis of variance and multiple linear regression were used to determine the relationship between maternal BP and DASH scores. RESULTS: Dietary intake more closely resembling the DASH dietary recommendations throughout pregnancy was associated with a lower DBP (mmHg) in trimesters 1 [B: -0.70; 95% confidence interval (CI) = -1.21 to -0.18] and 3 (B: -0.68; 95% CI = -1.19 to -0.17), as well as lower MAP (mmHg) in trimesters 1 (B: -0.78; 95% CI = -1.33 to -0.25) and 3 (B: -0.54; 95% CI = -1.04 to -0.04), controlling for body mass index, age, education, energy intake and intervention grouping. CONCLUSIONS: The DASH dietary pattern was associated with lower maternal BP in pregnancy among healthy women without hypertensive disorders of pregnancy. Despite the observational nature of these findings, the results demonstrate the potential for healthcare professionals to intervene to promote cardiovascular health in pregnancy.

Exploration of Factors Associated with Intention, Initiation and Duration of Breastfeeding.

Aim To assess breastfeeding intention, initiation and duration up to three months postnatal and associated factors. Methods Secondary data from 131 healthy pregnant women participating in an RCT in a Dublin hospital who recorded intention to breastfeed were included. Demographic and breastfeeding data were collected. Results Of the 131 women, 91.6% (n=120) reported intending to breastfeed. 91.7% of those subsequently initiated breastfeeding (n=110/120). Of those intending to breastfeed, 78.9% (n=86/109) and 68.9% (n=73/106) remained breastfeeding at one and three months postnatal respectively. Higher education (p<0.05) and lower BMI (p<0.05) were significantly associated with initiation and duration of breastfeeding. Ethnicity, age, parity or mode of delivery were not significantly associated with breastfeeding. Conclusion Many factors are associated with breastfeeding intention and duration including education and BMI. It is important to develop tailored support measures to encourage initiation and continuation of breastfeeding.

Young people's perceptions of acne and acne treatments: secondary analysis of qualitative interview data.

BACKGROUND: Acne vulgaris is a common skin condition affecting approximately 95% of adolescents to some extent. First-line treatments are topical preparations but nonadherence is common. A substantial proportion of patients take long courses of oral antibiotics, associated with antibiotic resistance. OBJECTIVES: This study aimed to explore young people's views and experiences of acne and its treatments. METHODS: We report a secondary thematic analysis of interview data collected by researchers in the Health Experiences Research Group (HERG), University of Oxford. A total of 25 transcripts from young people aged 13-24 years with acne were included. RESULTS: Acne is often perceived as a short-term self-limiting condition of adolescence and this appears to have implications for seeking treatment or advice. Participants widely perceived topical treatments as being ineffective, which seemed related to unrealistic expectations around speed of onset of action. Many participants felt they had tried all available topical treatments, although were unsure what was in them or unaware of differences between cosmetic and pharmaceutical treatments. They had concerns around how to use topicals 'properly' and how to avoid side-effects. They were also concerned about the side-effects or necessity of oral treatments, although few seemed aware of antibiotic resistance. CONCLUSIONS: People with acne need support to manage their condition effectively, particularly a better understanding of different topicals, how to use them and how to avoid side-effects. Unrealistic expectations about the onset of action of treatments appears to be a common cause of frustration and nonadherence. Directing people towards accessible evidence-based information is crucial. What's already known about this topic? There is a common perception that acne is a short-term condition that will resolve without treatment. Previous research has shown that nonadherence to topical treatments is common and that oral antibiotics are the most commonly prescribed treatment for acne in the U.K. Further research is needed to understand how young people perceive acne treatments and the implications of this for treatment adherence and self-management. What does this study add? People often said they had tried all available topical preparations for acne, but seemed confused between cosmetic and pharmaceutical treatments. People seemed unsure how to use topical treatments 'properly' or how to avoid side-effects. This was rarely discussed with health professionals. People's perception of acne as a short-term condition appeared to influence their expectations around onset of action of treatment and their views about its effectiveness and necessity. What are the clinical implications of the work? The perception of acne as a short-term condition has implications for self-management and motivation to seek and adhere to treatments. Providing advice about onset of action of treatments and how to prevent side-effects is crucial, including directing people towards accessible, written, evidence-based information. People's confusion about the different topical treatments available may be alleviated by such information, or by encouraging photos or other recordings of treatments tried and for how long. Linked Comment: Prior. Br J Dermatol 2020; 183:208-209. Plain language summary available online.

Five-year follow up of a low glycaemic index dietary randomised controlled trial in pregnancy-no long-term maternal effects of a dietary intervention.

OBJECTIVE: To determine whether a dietary intervention in pregnancy had a lasting effect on maternal outcomes of diet, HbA1c and weight retention 5 years post-intervention; and to establish whether modifiable maternal behaviours were associated with these outcomes. DESIGN: Randomised control trial of low glycaemic index (GI) diet in pregnancy with longitudinal follow up to 5 years post-intervention. SETTING: Dublin, Ireland (2007-2016). POPULATION: In all, 403 women of 759 (53.1%) were followed up at 5 years. A total of 370 (intervention n = 188; control n = 182) were included in this analysis. METHODS: Fasting glucose was measured at 13 and 28 weeks' gestation and HbA1c (mmol/mol) at 5-year follow up. Weight retention (kg) from early pregnancy to 5 years post-intervention was calculated. Dietary intakes, anthropometry, and lifestyle factors were measured in pregnancy and 5 years post-intervention. Multiple linear regression models, controlling for confounders, were used for analysis. OUTCOME: Maternal diet, HbA1c, and weight retention at 5 years post-intervention. RESULTS: There was no difference between the intervention and control at 5 years post-intervention for any long-term maternal outcomes measured. HbA1c at 5 years post-intervention was associated with early-pregnancy fasting glucose (B 1.70, 95% CI 0.36-3.04) and parity ≥3 (B 1.04, 95% CI 0.09-1.99). Weight retention was associated with change in well-being from pregnancy to 5 years (B -0.06, 95% CI -0.11 to -0.02), gestational weight gain (B 0.19, 95% CI 0.00-0.38), and GI (B 0.26, 95% CI 0.06-0.46) at 5 years. CONCLUSIONS: The ROLO low-GI dietary intervention in pregnancy had no impact on maternal dietary intakes, HbA1c or body composition 5 years post-intervention. Maternal factors and lifestyle behaviours in pregnancy have long-term effects on glucose metabolism and weight retention up to 5 years later. TWEETABLE ABSTRACT: Pregnancy factors are associated with maternal glucose metabolism and weight retention 5 years later-findings from the ROLO Study.

Construct and criterion validity testing of the Non-Technical Skills for Surgeons (NOTSS) behaviour assessment tool using videos of simulated operations.

BACKGROUND: Surgeons' non-technical skills are an important part of surgical performance and surgical education. The most widely adopted assessment tool is the Non-Technical Skills for Surgeons (NOTSS) behaviour rating system. Psychometric analysis of this tool to date has focused on inter-rater reliability and feasibility rather than validation. METHODS: NOTSS assessments were collected from two groups of consultant/attending surgeons in the UK and USA, who rated behaviours of the lead surgeon during a video-based simulated crisis scenario after either online or classroom instruction. The process of validation consisted of assessing construct validity, scale reliability and concurrent criterion validity, and undertaking a sensitivity analysis. Central to this was confirmatory factor analysis to evaluate the structure of the NOTSS taxonomy. RESULTS: Some 255 consultant surgeons participated in the study. The four-category NOTSS model was found to have robust construct validity evidence, and a superior fit compared with alternative models. Logistic regression and sensitivity analysis revealed that, after adjusting for technical skills, for every 1-point increase in NOTSS score of the lead surgeon, the odds of having a higher versus lower patient safety score was 2·29 times. The same pattern of results was obtained for a broad mix of surgical specialties (UK) as well as a single discipline (cardiothoracic, USA). CONCLUSION: The NOTSS tool can be applied in research and education settings to measure non-technical skills in a valid and efficient manner.

Patterns of hypothalamic GnIH change over the reproductive period in starlings and rats.

Gonadotropin inhibitory hormone (GnIH) exerts powerful inhibitory effects on various levels of the vertebrate hypothalamic-pituitary-gonadal (reproductive) axis, yet little is known of how it might change naturally over the course of reproduction. We characterized patterns of hypothalamic GnIH cell abundance over the reproductive period in two popular models used for the study of reproductive endocrinology: European starlings (Sturnus vulgaris) and Sprague-Dawley rats (Rattus norvegicus). We also examined the effects on an unpredictable change in the environment on GnIH cell abundance during the reproductive period, specifically during the period of parental care, by simulating a nest predation event and removing eggs/pups. In both species, we report changes in GnIH cell abundance are occurring at similar reproductive time points but are not always directionally parallel; this may be due to a difference in life histories and physiology mediating parental care. We discovered that cells immunoreactive for the GnIH peptide in male and female starlings are most highly abundant on the first day of incubation and the first day after the first chick hatches. Conversely in rats, GnIH cell abundance decreases in dams on the first day after pups are born. In both male and female starlings and female rats, GnIH cell abundance increases in response to egg/pup loss, indicating that GnIH responds to an unpredictable change in the environment in a potentially conserved fashion. These changes in GnIH cell abundance during the reproductive period inspire further investigation of its adaptive role in reproductive physiological events and behaviors, especially parental care.

The vascular extracellular calcium-sensing receptor: an update.

The extracellular calcium-sensing receptor (CaR) was first described in the parathyroid gland. Recent studies have shown that the CaR is also expressed in blood vessels, especially in the endothelial and adventitial layers but its physiological function is still not clear. However, an understanding of its possible role(s) in the vasculature (perivascular-neurones, heart and blood vessels) is important because of the use of synthetic positive allosteric CaR modulators in hyperparathyroidism and the potential importance of negative modulators in the treatment of osteoporosis. In this review, the effects of CaR activation and inhibition are detailed and the possible role of the CaR as both an amplifier and attenuator of myo-endothelial coupling in the vasculature is described.

The expression and function of Ca(2+)-sensing receptors in rat mesenteric artery; comparative studies using a model of type II diabetes.

BACKGROUND AND PURPOSE: The extracellular calcium-sensing receptor (CaR) in vascular endothelial cells activates endothelial intermediate-conductance, calcium-sensitive K(+) channels (IK(Ca)) indirectly leading to myocyte hyperpolarization. We determined whether CaR expression and function was modified in a rat model of type II diabetes. EXPERIMENTAL APPROACH: Pressure myography, western blotting, sharp microelectrode and K(+)-selective electrode recordings were used to investigate the functional expression of the CaR and IK(Ca) in rat mesenteric arteries. KEY RESULTS: Myocyte hyperpolarization to the CaR activator calindol was inhibited by Calhex 231. U46619-induced vessel contraction elevated the extracellular [K(+)] around the myocytes, and inhibition of this 'K(+) cloud' by iberiotoxin was needed to reveal calindol-induced vasodilatations. These were antagonized by Calhex 231 and significantly smaller in Zucker diabetic fatty rat (ZDF) vessels than in Zucker lean (ZL) controls. Myocyte hyperpolarizations to calindol were also smaller in ZDF than in ZL arteries. In ZDF vessels, endothelial cell CaR protein expression was reduced; IK(Ca) expression was also diminished, but IK(Ca)-generated hyperpolarizations mediated by 1-EBIO were unaffected. CONCLUSIONS AND IMPLICATIONS: The reduced CaR-mediated hyperpolarizing and vasodilator responses in ZDF arteries result from a decrease in CaR expression, rather than from a modification of IK(Ca) channels. Detection of CaR-mediated vasodilatation required the presence of iberiotoxin, suggesting a CaR contribution to vascular diameter, that is, inversely related to the degree of vasoconstriction. Compromise of the CaR pathway would favour the long-term development of a higher basal vascular tone and could contribute to the vascular complications associated with type II diabetes.

Molecular and Structural Changes in Chlamydomonas under Limiting CO2 (A Possible Mitochondrial Role in Adaptation).

When Chlamydomonas reinhardtii cells are transferred to limiting CO2, one response is the induction of a CO2-concentrating mechanism (CCM) with components that remain to be identified. Characterization of membrane-associated proteins induced by this transfer revealed that synthesis of the 21-kD protein (LIP-21) was regulated at the level of translatable message abundance and correlated well with the induction of CCM activity. Phase partitioning of LIP-21 and the previously characterized LIP-36 showed that both appeared to be peripherally associated with membranes, which limits their potential to function as transporters of inorganic carbon. Ultrastructural changes that occur when cells are transferred to limiting CO2 were also examined to help form a model for the CCM or other aspects of adaptation to limiting CO2. Changes were observed in vacuolization, starch distribution, and mitochondrial location. The mitochondria relocated from within the cup of the chloroplast to between the chloroplast envelope and the plasma membrane. In addition, immunogold labeling demonstrated that LIP-21 was localized specifically to the peripheral mitochondria. These data suggest that mitochondria, although not previously incorporated into models for the CCM, may play an important role in the cell's adaptation to limiting CO2.

The Low CO2-Inducible 36-Kilodalton Protein Is Localized to the Chloroplast Envelope of Chlamydomonas reinhardtii.

The localization of the 36-kD polypeptide of Chlamydomonas reinhardtii induced by photoautotrophic growth on low CO2 concentrations (0.03% in air [v/v], low CO2-grown cells) has been investigated. This polypeptide was specifically localized to the chloroplast envelope membranes isolated from low CO2-grown cells and was not present in the chloroplast envelopes isolated from high (5% CO2 in air [v/v]) CO2-grown cells. The 36-kD protein does not show carbonic anhydrase activity and was not present on the plasma membranes isolated from low CO2-grown cells. This protein may, in part, account for the different inorganic carbon uptake characteristics observed in chloroplasts isolated from high and low CO2-grown cells of C. reinhardtii.

A 36 Kilodalton Limiting-CO(2) Induced Polypeptide of Chlamydomonas Is Distinct from the 37 Kilodalton Periplasmic Carbonic Anhydrase.

Chlamydomonas reinhardtii possesses a CO(2)-concentrating mechanism, induced by limiting CO(2), which involves active transport and accumulation of inorganic carbon within the cell. Synthesis of several proteins is induced by limiting CO(2), but, of those, only periplasmic carbonic anhydrase has an identified function in the system. No proteins involved in active transport have yet been identified, but induced, membrane-associated polypeptides, such as the 36 kilodalton polypeptide focused on in this paper, would seem to be candidates for such involvement. The 36 kilodalton polypeptide was shown to be synthesized de novo upon transfer of cells to limiting CO(2). It was purified using SDS-PAGE and used to produce polyclonal antibodies. Antibodies were used to confirm the air-specific nature of the polypeptide, its strict association with membrane fractions, and the time course of its induction. Using the antibodies, a single, 36 kilodalton polypeptide was found to be specifically immunoprecipitated from in vitro translation products of poly(A(+)) RNA from cells only after exposure to limiting CO(2). The absence of translatable mRNA for this polypeptide in CO(2)-enriched cells indicated that regulation occurs at the level of message abundance. The antibodies were also used to demonstrate the distinction between the limiting-CO(2) induced 36 kilodalton polypeptide and the similarly sized, limiting-CO(2) induced periplasmic carbonic anhydrase.

Prenatal diagnosis of fetal glioblastoma multiforme.

Intracerebral tumours of the fetus are very rare conditions, most often presenting clinically as polyhydramnios and hydrocephalus. These conditions can be diagnosed with ultrasound and clearly differentiated from hydrocephalus and other intracranial lesions. The following report is of a case of an intracerebral tumour (glioblastoma multiforme) diagnosed at 33 weeks in utero using ultrasound. The prognosis for this condition is universally poor.

Pericervical intrafallopian bupivacaine instillation to reduce postoperative pain after laparoscopic tubal sterilisation.

In a double-blind comparative study of 46 women undergoing laparoscopic tubal sterilization under general anesthesia using Falope ring bands, the group of women (study group, n=22) having 0.5% bupivacaine instilled paracervically had less pain than women given normal saline (control group, n=24) at 1 and 2 hours. The trial group also required narcotic analgesia significantly less often (6/22 vs 19.24) than the control group. The reduction in postoperative pain afforded by this method of administration of bupivacaine allows day case laparoscopic sterilization to be performed with greater confidence.