Timing of antenatal steroids exposure and its effects on neonates.

OBJECTIVE: Antenatal corticosteroid (ACS) has long been regarded as the standard of care for women at risk of preterm labour. There are, however, varying practices and regimes in ACS administration. It is unclear if "a window of efficacy" truly exists and if the benefits of ACS would diminish after 7 days from the first dose. The objective of this study is to determine if the time interval between antenatal corticosteroids and delivery influences the neonatal outcomes in preterm deliveries from 23+5 to 36+6 weeks' gestation. METHODS: This is a retrospective analysis of 302 women and 352 infants who delivered from 23+5 to 36+6 weeks' gestation in KK Women's and Children's Hospital from 1st November 2014 to 31st January 2015. The timings of the first two doses of corticosteroids and the delivery were retrieved. Neonatal outcomes were compared between those delivering within 7 days and those delivering beyond 7 days of first dose of ACS. RESULTS: 61.2% of preterm infants received at least one dose of antenatal corticosteroids, of which 23.6% received it within the window of efficacy. Overall incidence of respiratory distress asyndrome in our study is 17.6%. Significantly, neonates with ACS exposure beyond 7 days were seven times more likely to have RDS as compared to those exposed to ACS within the window of efficacy (RR 0.535, 95% CI 0.166-1.72), after adjusting for potential confounders. CONCLUSION: The results of this study support the current practice among obstetricians to aim to administer ACS within 7 days of delivery.

A single-center experience of cytomegalovirus infections in Asian pediatric patients undergoing allogeneic hematopoietic stem cell transplant for leukemia in Singapore.

INTRODUCTION: Cytomegalovirus (CMV) infection remains a significant cause of morbidity and mortality in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) despite improved surveillance and the current preemptive approach. Few data on its prevalence in the Asian pediatric population exist. METHODS: We retrospectively reviewed the prevalence of CMV infections in 33 patients with 37 transplants who received HSCT for leukemia from 1998 to 2008, and who were managed preemptively for infections. RESULTS: In the 37 transplants, 16 patients (43%) had CMV DNAemia. Of the patients who were CMV seropositive before transplant and received stem cells from seropositive donors (R+/D+), 69% had DNAemia; of those who received stem cells from seronegative donors (R+/D-), 36% had CMV DNAemia. Of the patients who were CMV naïve before transplant and received stem cells from seropositive donors (R-/D+), 25% had CMV DNAemia. In CMV-seronegative donor-recipient transplants (R-/D-), 20% of patients had CMV DNAemia. The median time to the first episode of CMV DNAemia was 21 (range: 10-107) days after the transplants, and the median duration of CMV DNAemia was 22 (range: 2-315) days. CMV DNAemia recurred in 44% (7 of 16) of these patients. Only 1 patient developed CMV disease (retinitis). No deaths were related to CMV infections. CONCLUSIONS: CMV infection manifesting as DNAemia is a common complication in pediatric patients undergoing allogeneic HSCT for leukemia. Pre-transplant serostatus predicts reactivation risks; invasive CMV disease is rare using the preemptive approach in our patient population.

Mn(2+) and Mg(2+) synergistically enhanced lactic acid production by Lactobacillus rhamnosus FTDC 8313 via affecting different stages of the hexose monophosphate pathway.

AIMS: The study aimed to evaluate the effects of Mn(2+) and Mg(2+) on lactic acid production using response surface methodology and to further study their effects on interactions between the enzymes and substrates along the hexose monophosphate pathway using a molecular modelling approach. METHODS AND RESULTS: A rotatable central composite design matrix for lactic acid production was generated with two independent factors namely, manganese sulfate and magnesium sulfate. The second-order regression model indicated that the quadratic model was significant (P < 0·05), suggesting that the model accurately represented the data in the experimental region. Three-dimensional response surface showed that lactic acid production was high along the region where the ratio of MnSO4 to MgSO4 was almost 1 : 1, justifying the need for both Mg(2+) and Mn(2+) to be present simultaneously in stimulating the production of lactic acid. Molecular docking simulation was performed on a total of 13 essential enzymes involved in the hexose monophosphate pathway for the production of lactic acid with four different conditions namely in the presence of Mg(2+) , Mn(2+) , both Mg(2+) and Mn(2+) and in the absence of metal ions. Results showed that the presence of both Mg(2+) and Mn(2+) within the binding site improved the binding affinity for substrates in five enzymes namely, glucose-6-phosphate dehydrogenase, phosphogluconate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, phosphopyruvate hydratase and pyruvate kinase. CONCLUSIONS: Using response surface methodology and molecular modelling approach, we illustrated that Mg(2+) and Mn(2+) synergistically enhanced lactic acid production by Lactobacillus rhamnosus FTDC 8313 via affecting different stages of the hexose monophosphate pathway. SIGNIFICANCE AND IMPACTS OF THE STUDY: Mg(2+) and Mn(2+) synergistically improved lactic acid production of Lact. rhamnosus via improved binding affinity of the enzyme-substrate along the hexose monophosphate pathway, instead of purely affecting growth as previously understood.

Variation in a range of mTOR-related genes associates with intracranial volume and intellectual disability.

De novo mutations in specific mTOR pathway genes cause brain overgrowth in the context of intellectual disability (ID). By analyzing 101 mMTOR-related genes in a large ID patient cohort and two independent population cohorts, we show that these genes modulate brain growth in health and disease. We report the mTOR activator gene RHEB as an ID gene that is associated with megalencephaly when mutated. Functional testing of mutant RHEB in vertebrate animal models indicates pathway hyperactivation with a concomitant increase in cell and head size, aberrant neuronal migration, and induction of seizures, concordant with the human phenotype. This study reveals that tight control of brain volume is exerted through a large community of mTOR-related genes. Human brain volume can be altered, by either rare disruptive events causing hyperactivation of the pathway, or through the collective effects of common alleles.

Diffusion weighted magnetic resonance imaging for acute stroke: practical and popular.

AIM: To evaluate the feasibility and impact of diffusion weighted magnetic resonance imaging (DW MRI) as the first line neuroimaging of stroke at a district general hospital. METHODS: Prospective audit of all in-patients admitted with clinically suspected acute stroke and referred for imaging over a consecutive 17 week period. The data collected included scan type, time from cerebral event to imaging request, and time from formal radiological request to neuroimaging. Clinicians' (general physicians, neurologists, and radiologists) perceptions were assessed by a questionnaire. RESULTS: 148 patients had neuroimaging for clinically suspected stroke during this period. Eighty one per cent of patients (120 of 148) had DW MRI as first line. Ninety two per cent of these patients had DW MRI within 24 hours of the formal radiological request. Twenty eight patients did not undergo DW MRI because lack of MRI safety, clinical state, unavailability because of maintenance service or lack of trained staff. Clinicians found the introduction of the DW MRI based service a significant improvement on computed tomography, especially for equivocal cases. CONCLUSION: DW based MRI service is both feasible and sustainable in the setting of a district general hospital and most clinicians feel that this is a significant improvement to stroke services.

Cerclage-wiring-assisted fixation of difficult hand fractures.

Difficult hand fractures with multiple butterfly fragments, multiple cortical splits or intraarticular extension continue to pose a challenge for optimal stable fixation that allows early postoperative mobilisation. In this study, we describe the use of cerclage-wire-assisted fixation of 17 difficult hand fractures in 16 patients. The cerclage wires helped to maintain the reduction, so providing sufficient initial stability for placement of a plate and screws. Stable fixation of the fracture was then accomplished without losing the reduction. One to three cerclages of stainless-steel wires were used for the preliminary fixation. Stable fixation was then accomplished by a bridging or neutralising plate technique. Postoperatively, the fixation was sufficiently stable to allow immediate mobilisation. With an average follow up of 44.5 months, all 17 fractures united without loss of reduction. At final follow-up, the average total active range of motion was 247 degrees (range 220-260 degrees ).

Intraperitoneal alginate-encapsulated neonatal porcine islets in a placebo-controlled study with 16 diabetic cynomolgus primates.

BACKGROUND: A nonhuman primate model of diabetes is valuable for assessing porcine pancreatic islet transplants that might have clinical benefits in humans. METHODS: Neonatal porcine islets, microencapsulated in alginate-polyornithine-alginate, were injected intraperitoneally (10,000 IEQs/kg islets) into eight adult male cynomolgus monkeys rendered diabetic with streptozotocin. Eight diabetic controls were given an equivalent dose of empty placebo capsules. All subjects received a repeat transplant 3 months after the first. RESULTS: The transplant was well tolerated and no adverse or hypoglycemic events occurred. There were two deaths from nontransplant treatment or diabetic complications unrelated to the transplants. After transplantation, the average insulin dose was reduced in the islet-treated group and increased in the control group. At 12 weeks after the first transplant there was a mean 36% (95% CI: 6% to 65%, P = .02) drop in daily insulin dose compared with the control group. After 24 weeks the difference increased to a mean of 43% (95% CI: 12% to 75%, P = .01) without significant differences in blood glucose values between the two groups. Individual responses after islet transplant varied and one monkey was weaned off insulin by 36 weeks. At terminal autopsy, organs appeared normal and there was no visible peritoneal reaction. No animal had polymerase chain reaction (PCR)-amplified signals of porcine endogenous retrovirus or exogenous virus infections in blood or tissues. CONCLUSION: Repeated intraperitoneal transplantation of microencapsulated neonatal porcine islets is a safe procedure in diabetic primates. It was shown to result in a significant reduction in insulin dose requirement in the majority of animals studied, whereas insulin requirement increased in controls.

Genetic predisposition to two rheumatic diseases.

The co-existence of ankylosing spondylitis and rheumatoid arthritis is uncommon and usually occurs in a male with a long history of back pain followed by the appearance of clinical features of ankylosing spondylitis, while features of rheumatoid arthritis develop in the third or fourth decade of life. Recently, histocompatibility (HLA) antigens have partially elucidated the genetic factors predisposing to both diseases. We report a patient with ankylosing spondylitis and rheumatoid arthritis who had the associated HLA genes.

In vitro activity of moxifloxacin against local bacterial isolates.

INTRODUCTION: The emergence of resistance to common antimicrobials in bacteria has been increasingly reported in various countries. Empirical antimicrobial therapy of various infections would therefore need to be reviewed. The introduction of new fluoroquinolones has created an interest in the use of these as possible agents in the empirical treatment of respiratory tract infections. MATERIALS AND METHODS: The minimum inhibitory concentration (MIC) of the new fluoroquinolone, moxifloxacin, against 400 clinical bacterial isolates was determined by the E-test method. RESULTS: All Streptococcus pneumoniae isolates (penicillin sensitive or resistant) were susceptible to moxifloxacin. Similarly, both beta-lactamase and non beta-lactamase producing Haemophilus influenzae and Moraxella catarrhalis isolates were susceptible to moxifloxacin. As for Enterobacteriaceae, 88.6% of the isolates tested were susceptible to moxifloxacin with MIC < 8 mg/L, but resistance was noted for some of Proteus mirabilis, Klebsiella spp. and Escherichia coli. Enterococci and Acinetobacter baumannii were resistant to moxifloxacin, whilst the anaerobes tested were susceptible to moxifloxacin. CONCLUSION: Moxifloxacin has good in vitro activity against common organisms associated with community and nosocomial infections, with the exception of enterococci, methicillin-resistant Staphylococcus aureus and ciprofloxacin-resistant gram-negative bacteria. There was good anti-anaerobic activity against Bacteroides fragilis and Clostridum spp. Results of this study are consistent with other similar published in vitro studies.

Caries, bitewings, and treatment decisions.

BACKGROUND: The most common adjunct to the visual and tactile clinical examination for dental caries is the bitewing radiograph. The aim of this study was to report on treatment planning decisions made by Victorian dentists when given a range of predetermined radiographic scenarios. METHODS: A postal survey was conducted to obtain data from 550 dentists selected systematically (every fourth dentist) from the register of the Dental Board of Victoria (1996). RESULTS: The survey response rate was 64 per cent. Fifty per cent of responding dentists selected an operative intervention for radiographic lesions confined to enamel. CONCLUSIONS: A review of current dental literature does not support this approach because a large proportion of proximal tooth surfaces that have associated radiolucencies confined to enamel are not cavitated. This study supports the need for continuing education programmes on the management of dental caries; such programmes should follow an evidence-based model.

The Community Family Case Studies Programme at the University of Malaya.

The New Integrated Curriculum at the Faculty of Medicine, University of Malaya, Which comprises three major longitudinal strands, was first implemented in 1998 to provide better integration of clinical and basic medical sciences. One of these longitudinal strands, the Doctor, Patients, Health and Society (DPHS) module, emphasizes the importance of developing good communication skills as well as introducing students to behavioural sciences, public health medicine, statistics and epidemiology. Community Family Case Studies (CFCS), within this module, have been used as a means for students to focus on these aspects, as the students are introduced to patients, their families and their community in Year 1 of the medical course and are required to follow them up throughout their five-year training period.

Severe Kikuchi's disease responsive to immune modulation.

Kikuchi's disease, although an uncommon entity, has been increasingly reported since it was first discovered in 1972. The most common manifestation of Kikuchi's disease, cervical lymphadenopathy, has no clinically distinguishable features. Therefore, a diagnosis of Kikuchi's disease has largely been based on clinical suspicion and histopathological confirmation. We present a 15-year-old Chinese girl with severe Kikuchi's disease, whose relapsing course was only responsive to highdose steroid and intravenous immunoglobulin therapy.

Hematopoietic SCT activity in Asia: a report from the Asia-Pacific Blood and Marrow Transplantation Group.

The hematopoietic SCT (HSCT) activity in nine Asian countries/regions was surveyed to overview the current situation. Data of 58 113 HSCTs (allogeneic: 63% vs autologous: 37%) performed between 1986 and 2006 by 432 transplant teams were collected. The number of HSCTs has been increasing in the past two decades in most countries/regions. The increase in allogeneic HSCTs is greater than in autologous HSCTs. The proportion of unrelated donors among allogeneic HSCTs in 2006 varied widely from <1% (Iran and Vietnam) to 62% (Japan). The use of each stem cell source, that is, BM, PBSC, cord blood and others (including co-infusion of BM and PBSC), also varied widely (36, 58, 0.1 and 6% in HSCT from related donors, respectively, and 53, 11, 35 and 1% in HSCT from unrelated donors, respectively). HSCTs have been continuously increasing for all indications except for chronic myelogenous leukemia and solid tumors. Hemoglobinopathy is a common indication among non-malignant diseases in many Asian countries/regions except for China, Japan and Korea. This survey clearly shows the recent progress of HSCTs in Asia and also some differences in donor and stem cell selection and disease application among countries/regions.