%0 Journal Article %~ PubMed %A Hsu, Peter %A Santner Nanan, Brigitte %A Dahlstrom, Jane E %A Fadia, Mitali %A Chandra, Arin %A Peek, Michael %A Nanan, Ralph %T Altered Decidual DC-SIGN(+) Antigen-Presenting Cells and Impaired Regulatory T-Cell Induction in Preeclampsia. %B American Journal of Pathology %D 2012 %C United States %I American Society for Investigative Pathology %V 181 %N 6 %P 2149-2160 %@ 0002-9440 %X %Z FOR Codes: 111401 %0 Journal Article %~ PubMed %A Poulton, Alison %A Liu, Anthony %A Nanan, Ralph %T Budesonide in preschool-age children with recurrent wheezing. %B The New England Journal of Medicine %D 2012 %C United States %I Massachusetts Medical Society %V 366 %N 6 %P 570 %@ 1533-4406 %X %Z FOR Codes: 110203 111403 %0 Journal Article %~ PubMed %A Nanan, Ralph K %A Poulton, Alison S %A Champion, Bernard L %T Clinical pathways: a departure from the art of medicine. %B The Medical Journal of Australia %D 2012 %C Australia %I Australasian Medical Publishing Company Pty. Ltd. %V 196 %N %P 96 %@ 1326-5377 %X Is canonical thinking inhibiting the flexibility and innovation required for expert clinical reasoning? %Z FOR Codes: 111709 111717 %0 Journal Article %~ PubMed %A Suresh, Ashwin %A Liu, Anthony %A Poulton, Alison %A Quinton, Ann %A Amer, Zara %A Mongelli, Max %A Martin, Andrew %A Benzie, Ronald %A Peek, Michael %A Nanan, Ralph %T Comparison of maternal abdominal subcutaneous fat thickness and body mass index as markers for pregnancy outcomes: A stratified cohort study. %B The Australian & New Zealand Journal of Obstetrics & Gynaecology %D 2012 %C Australia %I Wiley-Blackwell Publishing Asia %V 52 %N 5 %P 420-426 %@ 1479-828X %X %Z FOR Codes: 111402 %0 Journal Article %~ PubMed %A Nalos, Marek %A Santner-Nanan, Brigitte %A Parnell, Grant %A Tang, Benjamin %A McLean, Anthony S %A Nanan, Ralph %T Immune effects of interferon gamma in persistent staphylococcal sepsis. %B American journal of respiratory and critical care medicine %D 2012 %C United States %I American Thoracic Society %V 185 %N 1 %P 110-112 %@ 1073-449X %X %Z FOR Codes: 110203 110703 %0 Journal Article %~ PubMed %A Eviston, David P %A Quinton, Ann E %A Benzie, Ron J %A Peek, Michael J %A Martin, Andrew %A Nanan, Ralph K %T Impaired fetal thymic growth precedes clinical preeclampsia: a case-control study. %B Journal of Reproductive Immunology %D 2012 %C Ireland %I Elsevier Ireland Ltd %V 94 %N 2 %P 183-189 %@ 1872-7603 %X In preeclampsia the maternal adaptive immune system undergoes specific changes, which are different from the physiological processes associated with healthy pregnancy. Whether preeclampsia also affects the fetal immune system is difficult to investigate, due to limited access to the fetus. We hypothesized that if preeclampsia affects the fetal adaptive immune system this might be associated with early changes in thymic growth. In this case-control study, 53 preeclamptic and 120 healthy control pregnancies were matched for maternal age, gestational age and smoking. Fetal thymus diameter was measured as the greatest width perpendicular to a line connecting sternum and spine based on ultrasound images taken at 17-21 weeks gestation. Independent of fetal and maternal anthropometric measures, thymuses were found to be smaller in preeclamptic pregnancies than healthy controls (16.2mm versus 18.3mm, respectively, mean difference=2.1mm, 95% CI: 0.8-3.3, p<0.001), and the odds of developing preeclampsia was estimated to be 0.72 (95% CI: 0.60-0.86, p<0.001) lower for each 1mm increase in thymus diameter. There was no correlation between the onset of preeclampsia and fetal thymus size. This is the first study to suggest that fetal thymus growth is reduced before the clinical onset of preeclampsia and precedes any described fetal anomalies or maternal immunological changes associated with preeclampsia. We propose that the fetal adaptive immune system is either passively affected by maternal processes preceding clinical preeclampsia or is actively involved in initiating preeclampsia in later pregnancy. %Z FOR Codes: 110399 110799 %0 Journal Article %~ PubMed %A Liu, Anthony %A Björkman, Tracey %A Stewart, Caroline %A Nanan, Ralph %T Pharmacological treatment of neonatal opiate withdrawal: between the devil and the deep blue sea. %B International Journal of Pediatrics %D 2011 %C United States %I Hindawi Publishing Corporation %V 2011 %N %P 935631 %@ 1687-9759 %X Illicit drug use with opiates in pregnancy is a major global health issue with neonatal withdrawal being a common complication. Morphine is the main pharmacological agent administered for the treatment of neonatal withdrawal. In the past, morphine has been considered by and large inert in terms of its long-term effects on the central nervous system. However, recent animal and clinical studies have demonstrated that opiates exhibit significant effects on the growing brain. This includes direct dose-dependent effects on reduction in brain size and weight, protein, DNA, RNA, and neurotransmitters-possibly as a direct consequence of a number of opiate-mediated systems that influence neural cell differentiation, proliferation, and apoptosis. At this stage, we are stuck between the devil and the deep blue sea. There are no real alternatives to pharmacological treatment with opiates and other drugs for neonatal opiate withdrawal and opiate addiction in pregnant women. However, pending further rigorous studies examining the potential harmful effects of opiate exposure in utero and the perinatal period, prolonged use of these agents in the neonatal period should be used judiciously, with caution, and avoided where possible. %Z FOR Codes: 111403 %0 Journal Article %~ PubMed %A Poulton, Alison Sally %A Babajanyan, Arman %A Nanan, Ralph %T Restricted elimination diet for ADHD. %B Lancet %D 2011 %C United Kingdom %I The Lancet Publishing Group %V 377 %N 9777 %P 1567-1568 %@ 0140-6736 %X %Z FOR Codes: 111104 111403 %0 Journal Article %~ PubMed %A Mohamed, N %A Eviston, D P %A Quinton, A E %A Benzie, R J %A Kirby, A C %A Peek, M J %A Nanan, R K %T Smaller fetal thymuses in pre-eclampsia: a prospective cross-sectional study. %B Ultrasound in Obstetrics and Gynecology %D 2011 %C United Kingdom %I John Wiley & Sons Ltd. %V 37 %N 4 %P 410-415 %@ 1469-0705 %X To determine whether the thymus is smaller in fetuses of pre-eclamptic mothers than in those of normal controls. %Z FOR Codes: 110320 111401 111403 %0 Journal Article %~ PubMed %A Delsing, Corinne %A Van Den Wittenboer, Ellen %A Liu, Anthony J W %A Peek, Michael John %A Quinton, Ann %A Mongelli, Max %A Poulton, Alison %A Nanan, Ralph %T The relationship between maternal opiate use, amphetamine use and smoking on fetal growth. %B The Australian & New Zealand Journal of Obstetrics & Gynaecology %D 2011 %C Australia %I Wiley-Blackwell Publishing Asia %V 51 %N 5 %P 446-451 %@ 1479-828X %X Opiate and amphetamine use during pregnancy is frequently associated with cigarette smoking. The negative effects on fetal growth from nicotine combined with opiates or amphetamines during pregnancy are not well documented. %Z FOR Codes: 111401 %0 Journal Article %~ PubMed %A Suryani, Santi %A Fulcher, David A %A Santner-Nanan, Brigitte %A Nanan, Ralph %A Wong, Melanie %A Shaw, Peter J %A Gibson, John %A Williams, Andrew %A Tangye, Stuart G %T Differential expression of CD21 identifies developmentally and functionally distinct subsets of human transitional B cells. %B Blood %D 2010 %C United States %I American Society of Hematology %V 115 %N 3 %P 519-529 %@ 0006-4971 %X The transitional stage of B-cell development represents an important step where autoreactive cells are deleted, allowing the generation of a mature functional B-cell repertoire. In mice, 3 subsets of transitional B cells have been identified. In contrast, most studies of human transitional B cells have focused on a single subset defined as CD24(hi)CD38(hi) B cells. Here, we have identified 2 subsets of human transitional B cells based on the differential expression of CD21. CD21(hi) transitional cells displayed higher expression of CD23, CD44, and IgD, and exhibited greater proliferation and Ig secretion in vitro than CD21(lo) transitional B cells. In contrast, the CD21(lo) subset expressed elevated levels of LEF1, a transcription factor highly expressed by immature lymphocytes, and produced higher amounts of autoreactive Ab. These phenotypic, functional, and molecular features suggest that CD21(lo) transitional B cells are less mature than the CD21(hi) subset. This was confirmed by analyzing X-linked agammaglobulinemia patients and the kinetics of B-cell reconstitution after stem cell transplantation, which revealed that the development of CD21(lo) transitional B cells preceded that of CD21(hi) transitional cells. These findings provide important insights into the process of human B-cell development and have implications for understanding the processes underlying perturbed B-cell maturation in autoimmune and immunodeficient conditions. %Z FOR Codes: 110202 %0 Journal Article %~ PubMed %A Marceau, James R %A Murray, Henry %A Nanan, Ralph K H %T Efficacy of Oral Sucrose in Infants of Methadone-Maintained Mothers. %B Neonatology %D 2010 %C Switzerland %I S. Karger AG %V 97 %N 1 %P 67-70 %@ 1661-7819 %X Background: One report indicated that taste-induced analgesia was sub-optimal in methadone-exposed (ME) infants. Objectives: The purpose of this work was to compare the effects of oral sucrose in infants born to methadone-maintained mothers with control infants. Methods: The aim was to compare the effects of an oral sucrose solution in infants scheduled to have a heel lance procedure for routine newborn screening. Infants received 0.05 ml (one drop) of a 24% sucrose solution by mouth 2 min before a heel lance procedure, then a further 0.05 ml of sucrose at the time of the heel lance; this was repeated every 1-2 min until 30 s after the completion of the procedure. The primary outcome measure was pain. We assessed pain using the Premature Infant Pain Profile (PIPP), which is a validated composite pain assessment tool. Results: PIPP scores were similar in both infant groups. Median PIPP scores of the ME infant group versus the control infant group were 2.0 (interquartile range (IQR) 0-7) versus 2.0 (IQR 0-9) at the time of the heel lance (p = 0.99) and 2.0 (IQR 0-4) versus 1.0 (IQR 0-4) 30 s after the completion of the heel lance procedure (p = 0.28). Conclusions: This study found no differences in the pain responses of ME infants and non-exposed infants when given sucrose during heel lance procedures. %Z FOR Codes: 111403 %0 Journal Article %~ PubMed %A Liu, A J W %A Sithamparanathan, S %A Jones, M P %A Cook, C-M %A Nanan, R %T Growth restriction in pregnancies of opioid-dependent mothers. %B Archives of disease in childhood. Fetal and neonatal edition %D 2010 %C United Kingdom %I BMJ Group %V 95 %N 4 %P F258-62 %@ 1468-2052 %X Intrauterine growth restriction (IUGR) can lead to significant intellectual and behavioural problems in later life. IUGR represents a frequent feature of pregnancies of opioid-dependent mothers (ODMs), the causes of which are largely unknown. The objective of this study was to determine the independent risk factors for IUGR in ODMs. %Z FOR Codes: 110399 111403 111402 %0 Journal Article %~ PubMed %A Liu, Anthony J W %A Nanan, Ralph %T Maternal methadone dose at delivery and neonatal abstinence syndrome. %B The Journal of pediatrics %D 2010 %C United States %I Mosby, Inc %V 157 %N 6 %P 1044; author reply 1044-5 %@ 0022-3476 %X %Z FOR Codes: 110399 %0 Journal Article %~ PubMed %A Liu, Anthony J W %A Jones, Michael P %A Murray, Henry %A Cook, Colleen-Maree %A Nanan, Ralph %T Perinatal risk factors for the neonatal abstinence syndrome in infants born to women on methadone maintenance therapy. %B The Australian and New Zealand Journal of Obstetrics and Gynecology %D 2010 %C Australia %I Wiley-Blackwell Publishing Asia %V 50 %N 3 %P 253-258 %@ 1479-828X %X Background: Neonatal abstinence syndrome (NAS) occurs in more than 50% of infants exposed to intrauterine opiates. Maternal opiate dosing has been investigated with conflicting results. Aims: The aims of this study were to correlate maternal methadone dose and other risk factors with the development of NAS requiring pharmacological treatment by using easily accessible clinical parameters. Methods: Retrospective medical record review of data from 228 opioid dependent pregnant women who delivered 232 live-born infants. Logistic regression analysis was performed on maternal, perinatal and neonatal parameters to identify risk factors for NAS requiring treatment. A prediction model was developed and validated on a separate independent cohort of 188 infants. Results: Of the 232 infants, 172 (74%) infants were treated for NAS. The risk of withdrawal increased by 17% per 5 mg increment of the last maternal methadone dose. The risk was lower for younger gestational ages and for those delivered by Caesarean section compared to those delivered by normal vaginal delivery. Through predictive modeling, gestational age, mode of delivery and last methadone dose were established as risk factors for withdrawal. The model was validated by other statistical measures and its diagnostic performance confirmed on the separate independent cohort. Conclusions: Our data suggests that timing and mode of delivery as well as last maternal methadone dose are significant risk factors for the development of NAS requiring treatment. Based on these clinical parameters, risk stratification for perinatal management of pregnancies associated with opioid dependency and risk prediction for the neonate might now be possible. %Z FOR Codes: 111403 %0 Journal Article %~ PubMed %A Nanan, Ralph %A Wall, Jack R %T Remission of Hashimoto's Thyroiditis in a Twelve-Year-Old Girl with Thyroid Changes Documented by Ultrasonography. %B Thyroid %D 2010 %C United States %I Mary Ann Liebert, Inc. Publishers %V 20 %N 10 %P 1187-1190 %@ 1557-9077 %X Background: Although it is known that Hashimoto''s thyroiditis in children and adolescents can go into long-term remission, and that treatment with thyroxine (T4) may not be necessary, it is difficult to quantify changes in the degree of autoimmune destruction of the thyroid. Here we report a patient in whom there was a relationship between functional and anatomical changes as assessed by hormone measurements and ultrasonography. Summary: The patient was a 12-year-old girl with Hashimoto''s thyroiditis who was initially euthyroid and later treated with 50 μg levo-T4 when her free T4 (fT4) had declined from 17 to 7 pmol/L (normal range, 8–22 pmol/L). At this time her thyroid-stimulating hormone (TSH) was 4.1 mIU/L (normal range, 0.30–4.0 mIU/L) and thyroid ultrasonography demonstrated features of early inflammation. Two years later, while on the same dose of T4, ultrasound examination revealed severe end-stage Hashimoto''s thyroiditis and thyroid function tests showed a T4 of 14.0 pmol/L and TSH of 0.81 mIU/L. Twelve months later, however, the thyroid ultrasound had returned to almost normal with only minimal features of inflammation. Thyroid function tests showed a fT4 of 12.8 pmol/L and TSH of 0.75 mIU/L. Her T4 treatment was then stopped. Eight, 17, and 30 weeks after this, her fT4 was 16.8, 9.7, and 13.9 pmol/L, respectively, and her respective TSH values at the same times were 0.10, 2.24, and 0.75 mIU/L. Conclusions: This is the first recording of serial thyroid ultrasound changes in a patient with Hashimoto''s thyroiditis that paralleled changes in thyroid function. This indicates that thyroiditis can go into remission in some children. Thyroid ultrasound may be useful to make presumptive therapeutic decisions in children and adolescents with Hashimoto''s thyroiditis whose dose of thyroid hormone seems to be less than is full replacement. Thyroid function tests, however, should ultimately guide T4 dosage. %Z FOR Codes: 111403 %0 Journal Article %~ PubMed %A Maheshwari, Rajesh %A Liu, Anthony %A Nair, Ajitha %A Poulton, Alison %A Nanan, Ralph %T Smoking and brain development in preterm infants. %B Journal of Pediatrics %D 2010 %C United States %I Mosby, Inc %V 157 %N 2 %P 346-347 %@ 0022-3476 %X %Z FOR Codes: 111401 %0 Journal Article %~ PubMed %A Kwok, Samson Chi %A Bennetts, Bruce H %A Nanan, Ralph Kay %T A case of periodic fever and persistent splenomegaly in a 2-year-old boy. %B BMJ Case Reports %D 2009 %C United Kingdom %I BMJ Group %V 2009 %N %P bcr06.2008.0098 %@ 1757-790X %X We report an unusual case of periodic fever associated with persistent splenomegaly in a 2-year-old boy. Febrile episodes occurred at regular 2 weekly intervals and each lasted for 1-2 days. Following resolution of the fever on each occasion, the patient developed neck stiffness of 1-2 days duration. The periodic febrile episodes, as well as the splenomegaly, spontaneously resolved 9 months after the onset of disease. Infectious and malignant causes were ruled out as far as possible. This patient''s clinical features are unusual and do not match any known category of periodic fevers in childhood. We believe this case highlights the diagnostic challenges periodic fevers commonly represent. %Z FOR Codes: 110804 %0 Journal Article %~ PubMed %A Poulton, Alison %A Nanan, Ralph %T Age-related changes in motor subtle signs among girls and boys with ADHD. %B Neurology %D 2009 %C United States %I Lippincott Williams & Wilkins %V 73 %N 15 %P 1248 %@ 1526-632X %X %Z FOR Codes: 1114 %0 Journal Article %~ PubMed %A Peek, Michael %A Nanan, Ralph %T Comment on: Association of maternal pre-pregnancy weight with birth defects: Evidence from a case-control study in Western Australia. Aust N Z J Obstet Gynaecol 2009; 49: 11-15. %B The Australian & New Zealand journal of obstetrics & gynaecology %D 2009 %C Australia %I Wiley-Blackwell Publishing Asia %V 49 %N 5 %P 564-5 %@ 1479-828X %X %Z FOR Codes: 111402 %0 Journal Article %~ Isi %A Ma, C. S. %A Suryani, S. %A Avery, D. T. %A Chan, A. %A Nanan, R. %A Santner-Nanan, B. %A Deenick, E. K. %A Tangye, S. G. %T Early commitment of naive human CD4(+) T cells to the T follicular helper (T-FH) cell lineage is induced by IL-12 %B Immunology and Cell Biology %D 2009 %C United Kingdom, Australia %I Nature Publishing Group %V 87 %N 8 %P 590-600 %@ 0818-9641 %X %Z FOR Codes: 110701 110704 %0 Journal Article %~ PubMed %A Tetstall, Emma %A Liu, Anthony Jun Wing %A An, Ethan Ikhyun %A Canalese, Joe %A Nanan, Ralph %T Pregnancy and neonatal characteristics of opioid-dependent Indigenous Australians: a rural and metropolitan comparison. %B The Australian and New Zealand Journal of Obstetrics and Gynecology %D 2009 %C Australia %I Wiley-Blackwell Publishing Asia %V 49 %N 3 %P 279-284 %@ 1479-828X %X AIMS: To identify maternal, obstetric and neonatal characteristics of opioid-dependent Indigenous Australians in rural and metropolitan settings. METHODS: Retrospective cohort study of 232 metropolitan and 67 rural infants born to mothers maintained on methadone throughout pregnancy for the treatment of opiate dependency, between January 2000 and December 2006. Medical records of identified mother/infant dyads were reviewed by evaluating 20 different maternal, obstetric and neonatal parameters. RESULTS: The number of infants of opiate-dependent mothers (IODMs) identified to be of Aboriginal ethnicity was 47 in the rural and 50 in the metropolitan setting. This reflected a significantly higher proportion in the rural versus metropolitan areas (70.1% vs 21.6%, P < 0.05). The effect of rurality was independent of ethnicity with significantly lower rates of neonatal withdrawal requiring treatment (P < 0.001), antenatal consultations (P < 0.01), department of community services (DoCS) involvement (P < 0.001) and shorter infant lengths of stay (P < 0.001). There was a non-significant trend towards more intrauterine growth restriction in Aboriginal infants. There were no significant differences in parameters in rural Indigenous versus rural non-Indigenous infants. CONCLUSIONS: Significant differences exist between rural and metropolitan IODMs in terms of less attendance at antenatal consultations, less neonatal withdrawal requiring treatment, shorter average length of hospital stay for the infant and less documented DoCS involvement. These differences maybe a reflection of a different diagnostic and management approach. Ethnicity had no major clinical impact in either the rural or the metropolitan settings. Future research comparing the long-term outcomes would be of interest. %Z FOR Codes: 1114 1114 %0 Journal Article %~ PubMed %A Seddiki, Nabila %A Sasson, Sarah C %A Santner-Nanan, Brigitte %A Munier, Meeling %A van Bockel, David %A Ip, Susanna %A Marriott, Debbie %A Pett, Sarah %A Nanan, Ralph %A Cooper, David A %A Zaunders, John J %A Kelleher, Anthony D %T Proliferation of weakly suppressive regulatory CD4+ T cells is associated with over-active CD4+ T-cell responses in HIV-positive patients with mycobacterial immune restoration disease. %B European Journal of Immunology %D 2009 %C Germany %I Wiley - VCH Verlag GmbH & Co. KGaA %V 39 %N 2 %P 391-403 %@ 0014-2980 %X The role of Treg in patients with late-stage HIV disease, who commence combination antiretroviral therapy (cART) and develop pathogen-specific immunopathology manifesting as immune restoration disease (IRD) remains unclear. We hypothesised that Treg could be defective in either numbers and/or function and therefore unable to ensure the physiological equilibrium of the immune system in patients with IRD. Phenotypic and functional CD4(+) T-cell subsets of eight late-stage HIV patients with nadir CD4 count <50 cells/microL, who developed mycobacterial IRD upon commencing cART were compared with six therapy naive HIV(+) patients (nadir CD4 count <50 cells/microL), who did not develop an IRD after cART. Mycobacterium-avium-specific CD4(+) T cells from IRD patients produced high levels of IFN-gamma and IL-2 compared with controls (p<0.001). Surprisingly, we found a significant expansion of CD127(lo)Foxp3(+)CD25(+) Treg in IRD patients and a higher ratio of Treg to effector/memory subsets (p<0.001). In vitro suppression assays demonstrated reduced functional capacity of suppressor cells and diminished IL-10 secretion in IRD patients. Plasma levels of IL-7 were increased in patients and, interestingly, exogenous IL-7 and other cytokines strongly inhibited Treg suppression. These data suggest that despite substantial Treg expansion in IRD, their ability to induce suppression, and thereby downregulate aberrant immune responses, is compromised. %Z FOR Codes: 110701 %0 Journal Article %~ PubMed %A Liu, Anthony J W %A An, Ethan I %A Murray, Henry G %A Tetstall, Emma %A Leroi, Marcel J %A Nanan, Ralph K H %T Screening for hepatitis C virus infection in methadone-maintained mothers and their infants. %B The Medical Journal of Australia %D 2009 %C Australia %I Australasian Medical Publishing Company Pty. Ltd. %V 191 %N 10 %P 535-538 %@ 0025-729X %X OBJECTIVE: To describe the patterns of screening for hepatitis C virus (HCV) infection in methadone-maintained pregnant women and their infants. DESIGN, SETTING AND PATIENTS: Retrospective review of medical records from one rural and two metropolitan hospitals in New South Wales for pregnant women on methadone maintenance treatment and infants born to these women between 1 January 2000 and 31 December 2006, as well as records for pregnant women who were not on methadone treatment. MAIN OUTCOME MEASURES: Rates of anti-HCV antibody and HCV RNA testing for pregnant women and their infants, and ages at which infants attended follow-up appointments. RESULTS: Of 295 pregnant women on methadone maintenance treatment, 288 were tested for anti-HCV antibodies (98%), compared with 1995 of 9987 women who were not on methadone treatment (20%) (P < 0.001). Seropositive results were obtained for 243 women in the methadone group (84%) and 54 in the non-methadone group (3%) (P < 0.001), of whom 44 (18%) and 17 (31%), respectively, were subsequently tested for HCV RNA (P = 0.03). HCV RNA test results were positive for 31 (70%) and 10 (59%) seropositive women in the methadone and non-methadone groups, respectively (P = 0.39). Of infants of HCV-seropositive methadone-maintained mothers, 27% of those for whom we had follow-up attendance data received HCV screening, and one of these infants tested positive for anti-HCV antibodies and HCV RNA. CONCLUSIONS: Screening for HCV infection in the high-risk population of pregnant women on methadone maintenance treatment and their infants is inadequate. This could lead to significant underdetection of active HCV infection in this high-risk population, and their infants. Current screening guidelines may therefore need to be revised. %Z FOR Codes: 1114 %0 Journal Article %~ PubMed %A Poulton, Alison %A Nanan, Ralph %T Stimulant medications and growth. %B Journal of the American Academy of Child and Adolescent Psychiatry %D 2009 %C Netherlands, United %I Elsevier BV %V 48 %N 5 %P 574-576 %@ 1527-5418 %X %Z FOR Codes: 1114 %0 Journal Article %~ PubMed %A Santner-Nanan, Brigitte %A Peek, Michael John %A Khanam, Roma %A Richarts, Luise %A Zhu, Erhua %A Fazekas de St Groth, Barbara %A Nanan, Ralph %T Systemic increase in the ratio between Foxp3+ and IL-17-producing CD4+ T cells in healthy pregnancy but not in preeclampsia. %B Journal of Immunology %D 2009 %C United States %I American Association of Immunologists %V 183 %N 11 %P 7023-7030 %@ 1550-6606 %X Preeclampsia is the leading cause of morbidity and mortality in pregnancy. Although the etiology of preeclampsia is still unclear, it is believed to involve rejection of the fetus, possibly due to an imbalance between regulatory (Treg) and effector T cells. To test this, we compared the frequencies of circulating CD4(+) T cells expressing Foxp3, IFN-gamma, IL-10, or IL-17 at the end of the third trimester of healthy and preeclamptic pregnancies. The size of the Treg cell compartment, defined by the frequency of CD4(+)CD25(high), CD4(+)CD127(low)CD25(+), and CD4(+)Foxp3(+) cells was significantly higher in normal compared with preeclamptic pregnancies. CD4(+)CD25(high) and CD4(+)CD127(low)CD25(+) populations in preeclampsia were not significantly different from those in nonpregnant controls, whereas CD4(+)Foxp3(+) cells numbersre slightly lower in preeclampsia. The suppressive activity of ex vivo-sorted CD4(+)CD127(low)CD25(+) Treg cells was not significantly different between the three study groups. The percentage of CD4(+)IL-17-producing T cells decreased significantly in healthy compared with preeclamptic pregnancies and nonpregnant controls, whereas CD4(+)IL-10- and CD4(+)IFN-gamma-producing cells remained unchanged. Consequently, the ratio of Foxp3(+) Treg to IL-17-expressing CD4(+) T cells was significantly increased in healthy but not in preeclamptic pregnancies. Thus, preeclampsia is associated with the absence of normal systemic skewing away from IL-17 production toward Foxp3(+) expression. Finally, preeclamptic women had significantly higher levels of soluble endoglin, an inhibitor of TGF-beta receptor signaling, which may bias toward IL-17 production. These results suggest that homeostasis between regulatory and proinflammatory CD4(+) T cells might be pivotal for the semiallogeneic fetus to be tolerated within the maternal environment. %Z FOR Codes: 1107 1114 1107 1114 %0 Journal Article %~ PubMed %A Liu, Anthony J W %A Sy, Catherine %A Nanan, Ralph %T What's your diagnosis? Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). %B Journal of Pediatric Ophthalmology and Strabismus %D 2009 %C United States %I Slack, Inc. %V 46 %N 5 %P 264 %@ 0191-3913 %X %Z FOR Codes: 111301 111403 %0 Journal Article %~ PubMed %A Nalos, Marek %A Huang, Stephen %A Sluyter, Ronald %A Khan, Alamgir %A Santner-Nanan, Brigitte %A Nanan, Ralph %A McLean, Anthony %T "Host tissue damage" signal ATP impairs IL-12 and IFNgamma secretion in LPS stimulated whole human blood. %B Intensive care medicine %D 2008 %C Germany %I Springer %V 34 %N 10 %P 1891-7 %@ 0342-4642 %X Critical illness is associated with tissue damage, inflammation and the development of immune dysfunction. Leukocyte reprogramming occurs leading to insufficient production of pro-inflammatory cytokines upon subsequent stimulation. Cellular nucleotides released during tissue damage act via purinergic receptors to modulate immune function. We hypothesized that extracellular nucleotides in concentrations similar to those found near injured and ischemic tissues will modulate cytokine secretion. %Z FOR Codes: 110310 110309 %0 Journal Article %~ PubMed %A Santner-Nanan, Brigitte %A Seddiki, Nabila %A Zhu, Erhua %A Quent, Verena %A Kelleher, Anthony %A de St Groth, Barbara Fazekas %A Nanan, Ralph %T Accelerated age-dependent transition of human regulatory T cells to effector memory phenotype. %B International Immunology %D 2008 %C United Kingdom %I Oxford University Press %V 20 %N 3 %P 375-383 %@ 1460-2377 %X We and others recently described a method for isolating viable forkhead boxp3 (FoxP3(+)) T regulatory cells (Tregs) by means of the surface phenotype CD4(+)CD127(lo)CD25(+). In this study, we used the new strategy to measure Treg numbers, phenotype and function at different ages. Mean percentages of CD4(+)CD127(lo)CD25(+) Tregs increased only slightly throughout life, from 6.10% in cord blood to 7.22% in PBMC from adults between 20 and 25 years and 7.50% in PBMC from adults over the age of 60. In all age groups, a higher proportion of Tregs had acquired a CD45RA(-) memory phenotype compared with CD4(+)Foxp3(-) conventional T cells. This increase was entirely attributable to increased Tregs with an effector memory phenotype, whereas central memory phenotype cells were comparably represented within the Treg and conventional CD4(+) T-cell populations. Expression of CD95 also differed between Tregs and conventional CD4(+) T cells at all ages. However there was no difference in the suppressive capacity of the different naive and memory Treg subsets. These results suggest that, compared with their conventional CD4(+) T-cell counterparts, Tregs undergo preferential differentiation from a naive to an effector memory phenotype, driven by their specificity for self- rather than foreign antigen. However, number and function are remarkably stable throughout life. %Z FOR Codes: 111403 110308 110202 %0 Journal Article %~ PubMed %A Nanan, Ralph %A Liu, Anthony %A Fletcher, Jeffery T %T Ambulatory oral amoxicillin for severe pneumonia in children. %B Lancet %D 2008 %C United Kingdom %I Lancet Ltd. %V 371 %N 9621 %P 1333-4; author reply 1334 %@ 0140-6736 %X %Z FOR Codes: 111403 %0 Journal Article %~ PubMed %A Liu, Anthony J W %A Nanan, Ralph %T Bi-acromial dimples. %B International journal of dermatology %D 2008 %C United Kingdom %I Wiley-Blackwell Publishing %V 47 %N 6 %P 594-595 %@ 1365-4632 %X %Z FOR Codes: 111403 %0 Journal Article %~ PubMed %A Poulton, Alison %A Nanan, Ralph Kay Heinrich %T Effects of prolonged and exclusive breastfeeding on childhood behavior and maternal adjustment: evidence from a large randomized trial. %B Pediatrics %D 2008 %C United States %I American Academy of Pediatrics %V 122 %N 2 %P 474 %@ 1098-4275 %X %Z FOR Codes: 1114 %0 Journal Article %~ PubMed %A Poulton, Alison %A Nanan, Ralph %T In the long run, skills are as good as pills for attention deficit hyperactivity disorder. %B The Medical Journal of Australia %D 2008 %C Australia %I Australasian Medical Publishing Company Pty. Ltd. %V 189 %N 5 %P 295-296 %@ 1326-5377 %X %Z FOR Codes: 111403 %0 Journal Article %~ PubMed %A Poulton, Alison %A Nanan, Ralph %T Measurement of growth in stimulant-naive children with attention-deficit/hyperactivity disorder by using cross-sectional and longitudinal approaches. %B Pediatrics %D 2008 %C United States %I American Academy of Pediatrics %V 122 %N 1 %P 221 %@ 1098-4275 %X %Z FOR Codes: 1114 %0 Journal Article %~ PubMed %A Liu, Anthony J W %A Nanan, Ralph %T Methadone maintenance and breastfeeding in the neonatal period. %B Pediatrics %D 2008 %C United States %I American Academy of Pediatrics %V 121 %N 4 %P 869; author reply 869-70 %@ 0031-4005 %X %Z FOR Codes: 111403 %0 Journal Article %~ PubMed %A Nanan, Ralph K H %A Liu, Anthony J W %A Poulton, Alison %T Nasal CPAP for very preterm infants. %B The New England Journal of Medicine %D 2008 %C United States %I Massachusetts Medical Society %V 358 %N 23 %P 2520-2521; author reply 2521 %@ 1533-4406 %X %Z FOR Codes: 1114 %0 Journal Article %~ PubMed %A Poulton, Alison %A Kwok, Samson %A Nanan, Ralph %T Overweight in children and adolescents in relation to attention-deficit/hyperactivity disorder. %B Pediatrics %D 2008 %C United States %I American Academy of Pediatrics %V 122 %N 4 %P 910 %@ 1098-4275 %X %Z FOR Codes: 1114 %0 Journal Article %~ PubMed %A Poulton, Alison S %A Nanan, Ralph %T Prior Treatment with Stimulant Medication: A Much Neglected Confounder of Studies of Growth in Children with Attention-Deficit/Hyperactivity Disorder. %B Journal of Child and Adolescent Psychopharmacology %D 2008 %C United States %I Mary Ann Liebert, Inc. Publishers %V 18 %N 4 %P 385-387 %@ 1557-8992 %X Abstract Evidence is provided that growth is an accurate indicator of prior treatment with stimulant medication. This is of utmost importance when interpreting clinical studies on attention-deficit/hyperactivity disorder (ADHD), as pretreated cohorts are likely to include fewer nonresponders and fewer individuals with intolerable side effects. In this respect, growth patterns are an excellent tool to identify pretreatment and thus address selection bias. %Z FOR Codes: 111403 %0 Journal Article %~ PubMed %A Nanan, Ralph K H %A Singh, Gurvinder %A Poulton, Alison %T Reductions in incidence of invasive group B streptococcal disease in the United States. %B JAMA : the journal of the American Medical Association %D 2008 %C United States %I American Medical Association %V 300 %N 14 %P 1649-1650 %@ 0098-7484 %X %Z FOR Codes: 1114 %0 Journal Article %~ PubMed %A Nanan, Ralph %A Poulton, Alison %T Routine measurement of head circumference as a tool for detecting intracranial expansion in infants. %B Pediatrics %D 2008 %C United States %I American Academy of Pediatrics %V 121 %N 6 %P 1298 %@ 1098-4275 %X %Z FOR Codes: 1114 %0 Journal Article %~ PubMed %A Avery, Danielle T %A Ma, Cindy S %A Bryant, Vanessa L %A Santner-Nanan, Brigitte %A Nanan, Ralph %A Wong, Melanie %A Fulcher, David A %A Cook, Matthew C %A Tangye, Stuart G %T STAT3 is required for IL-21-induced secretion of IgE from human naive B cells. %B Blood %D 2008 %C United States %I American Society of Hematology %V 112 %N 5 %P 1784-1793 %@ 1528-0020 %X The production of immunoglobulin E (IgE) is tightly regulated. This is evidenced by the fact that it comprises less than 0.0001% of serum Ig, and aberrant production causes atopic conditions, including allergy, rhinitis, and anaphylaxis. Interleukin-4 (IL-4) is a well-characterized inducer of IgE by human and murine B cells, whereas interferon-gamma can antagonize this effect. IL-21 has also been recognized for its ability to suppress IL-4-induced IgE production by murine B cells. Here, we identified IL-21 as an inducer of IgE production by CD40L-stimulated human naive B cells. Furthermore, there was a striking synergy between IL-4 and IL-21 on inducing IgE secretion by CD40L-stimulated human B cells, such that the levels detected under these conditions exceeded those induced by IL-4 or IL-21 alone by more than 10-fold. IL-21 induced activation of STAT3 and analysis of B cells from patients with loss-of-function STAT3 mutations revealed that the ability of IL-21 to induce IgE secretion, and augment that driven by IL-4, was STAT3-dependent. These findings highlight a fundamental difference between the regulation of IgE production by human and murine B cells and have implications for the dysregulated production of IgE in conditions characterized by extremely high levels of serum IgE. %Z FOR Codes: 110701 %0 Journal Article %~ PubMed %A Peek, Michael J %A Nanan, Ralph K %T The role of sepsis in the AMOR-IPAT Trial. %B American journal of obstetrics and gynecology %D 2008 %C United States %I Mosby %V 200 %N 0 %P e12; author reply e12-3 %@ 0002-9378 %X %Z FOR Codes: 111402 %0 Journal Article %~ PubMed %A Peek, Michael J %A Condous, George S %A Nanan, Ralph K H %T Fetal pulse oximetry and cesarean delivery. %B New England Journal of Medicine %D 2007 %C United States %I Massachusetts Medical Society %V 356 %N 13 %P 1377 %@ 1533-4406 %X %Z FOR Codes: 111402 %0 Journal Article %~ PubMed %A Liu, A J W %A Hogan, P %A Nanan, R %T Acute haemorrhagic oedema of infancy. %B Archives of disease in childhood %D 2006 %C United Kingdom %I BMJ Publishing Group %V 91 %N 5 %P 382 %@ 0003-9888 %X %Z FOR Codes: 110304 %0 Journal Article %~ PubMed %A Liu, Anthony J W %A Dao-Ung, Lan-Phuong %A McDonald, David %A Nanan, Ralph %T Chronic gingivitis in a new BTK mutation. %B European journal of haematology %D 2006 %C Denmark %I Blackwell Munksgaard %V 76 %N 2 %P 171-5 %@ 0902-4441 %X A 5-yr-old Caucasian boy with a new mutation in Bruton''s tyrosine kinase (BTK) is described. Full sequencing of the BTK gene revealed a point mutation in exon 17 resulting in an amino acid change from tryptophan to serine at location 581 of the tyrosine kinase domain. Clinically the child presented with chronic gingivitis and had no prior history of bacterial infections. Whereas serum immunoglobulin M (IgM) levels were undetectable, IgG levels were in the low normal range. The gingivitis completely resolved after intravenous immunoglobulin therapy. Lymphocyte phenotyping revealed 0.05% B cells in his peripheral blood, which were IgG(-), IgM(+), IgD(+), CD38(+), CD20(+), CD27(-). However, 40% of the B cells also expressed CD5. This subpopulation of B cells has not previously been described in X-linked agammaglobulinaemia (XLA) patients. We suggest that the occurrence of CD5(+) B cells could correlate with a late onset and mild clinical presentations of XLA. %Z FOR Codes: 110704 %0 Journal Article %~ Isi %A Fazekas de St Groth, B. %A Seddiki, N. %A Santner-Nanan, B. %A Martinson, J. %A Zaunders, J. %A Sasson, S. %A Landay, A. %A Nanan, R. %A Kelleher, A. %T Expression of IL-2 and IL-7 receptors discriminates between human regulatory and activated T-cells within CD45RA and CD45RO compartments. %B Clinical Immunology %D 2006 %C United States %I Academic Press %V 119 %N %P S7-S7 %@ 1521-6616 %X %Z FOR Codes: %0 Journal Article %~ PubMed %A Seddiki, Nabila %A Santner-Nanan, Brigitte %A Martinson, Jeff %A Zaunders, John %A Sasson, Sarah %A Landay, Alan %A Solomon, Michael %A Selby, Warwick %A Alexander, Stephen I %A Nanan, Ralph %A Kelleher, Anthony %A de St Groth, Barbara Fazekas %T Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. %B The Journal of experimental medicine %D 2006 %C United States %I Rockefeller University Press %V 203 %N 7 %P 1693-700 %@ 0022-1007 %X Abnormalities in CD4(+)CD25(+)Foxp3(+) regulatory T (T reg) cells have been implicated in susceptibility to allergic, autoimmune, and immunoinflammatory conditions. However, phenotypic and functional assessment of human T reg cells has been hampered by difficulty in distinguishing between CD25-expressing activated and regulatory T cells. Here, we show that expression of CD127, the alpha chain of the interleukin-7 receptor, allows an unambiguous flow cytometry-based distinction to be made between CD127(lo) T reg cells and CD127(hi) conventional T cells within the CD25(+)CD45RO(+)RA(-) effector/memory and CD45RA(+)RO(-) naive compartments in peripheral blood and lymph node. In healthy volunteers, peripheral blood CD25(+)CD127(lo) cells comprised 6.35 +/- 0.26% of CD4(+) T cells, of which 2.05 +/- 0.14% expressed the naive subset marker CD45RA. Expression of FoxP3 protein and the CD127(lo) phenotype were highly correlated within the CD4(+)CD25(+) population. Moreover, both effector/memory and naive CD25(+)CD127(lo) cells manifested suppressive activity in vitro, whereas CD25(+)CD127(hi) cells did not. Cell surface expression of CD127 therefore allows accurate estimation of T reg cell numbers and isolation of pure populations for in vitro studies and should contribute to our understanding of regulatory abnormalities in immunopathic diseases. %Z FOR Codes: 110704 %0 Journal Article %~ PubMed %A Adlington, Krista %A Liu, Anthony J W %A Nanan, Ralph %T Sleep disturbances in the disabled child--a case report and literature review. %B Australian family physician %D 2006 %C Australia %I Royal Australian College of General Practitioners %V 35 %N 9 %P 711-715 %@ 0300-8495 %X Sleep disturbances in children are common. In children with intellectual disabilities sleeping problems are more common. This may result in increased burden of illness, additional parental stress, and day time behavioural difficulties. This article illustrates the problems that sleep disturbances create for children with disabilities and discusses methods for managing sleep problems. %Z FOR Codes: 111403