ORCID Profile
0000-0002-9097-6028
Current Organisations
Osaka Metropolitan University
,
Izumiotsu Shiritsu Byoin
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Publications
Mesenchymal Stromal Cell Delivery Via Cardiopulmonary Bypass Provides Neuroprotection in a Juvenile Porcine Model
Publisher: Elsevier BV
Date: 09-2023
Predictors of neurological outcome in cooled neonates
Publisher: Wiley
Date: 27-02-2013
DOI: 10.1111/PED.12008
Abstract: We define clinical predictors of neurological outcome in neonates with hypoxic-ischemic encephalopathy undergoing hypothermia therapy. Twenty-one neonates who underwent selective head cooling between 2004 and 2010 and were followed neurologically for ≥ 24 months were investigated retrospectively. Patients were ided according to the neurological outcome at 2 years of age into group A (n = 11), patients with normal neurological function, and group B (n = 10), patients with neurological disabilities (n = 9) or those who died (n = 1). Predictors were determined by χ(2) and Mann-Whitney U-tests, anova, Spearman rank correlations and receiver-operator curves. Group B showed higher average blood lactate levels during the first day, particularly at 24 h of life lower day-3 cerebral blood flow resistance index higher maximum dobutamine dose used higher rate of thiamylal sodium used more severe background electroencephalogram suppression during the first week (group A: 11/11 cases ≤ grade 3 group B: 7/9 cases at grade 4-5) and higher rate of cerebral lesions on magnetic resonance imaging in the second week (group A: 1/11 case group B: 9/10 cases) than group A. The most useful predictor of poor prognosis was cerebral parenchymal lesions on magnetic resonance imaging with 90%, 90% and 90% of sensitivity, specificity and accuracy, followed by week-1 background electroencephalogram ≥ grade 4 with 70%, 100% and 85% and day-3 cerebral blood flow resistance index < 0.46 with 71%, 88% and 80%, respectively. Prediction of post-cooling neurological outcome could be improved substantially by evaluating multiple factors.
Preterm white matter brain injury is prevented by early administration of umbilical cord blood cells.
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.EXPNEUROL.2016.06.017
Abstract: Infants born very preterm are at high risk for neurological deficits including cerebral palsy. In this study we assessed the neuroprotective effects of umbilical cord blood cells (UCBCs) and optimal administration timing in a fetal sheep model of preterm brain injury. 50 million allogeneic UCBCs were intravenously administered to fetal sheep (0.7 gestation) at 12h or 5d after acute hypoxia-ischemia (HI) induced by umbilical cord occlusion. The fetal brains were collected at 10d after HI. HI (n=7) was associated with reduced number of oligodendrocytes (Olig2+) and myelin density (CNPase+), and increased density of activated microglia (Iba-1+) in cerebral white matter compared to control fetuses (P<0.05). UCBCs administered at 12h, but not 5d after HI, significantly protected white matter structures and suppressed cerebral inflammation. Activated microglial density showed a correlation with decreasing oligodendrocyte number (P<0.001). HI caused cell death (TUNEL+) in the internal capsule and cell proliferation (Ki-67+) in the subventricular zone compared to control (P<0.05), while UCBCs at 12h or 5d ameliorated these effects. Additionally, UCBCs at 12h induced a significant systemic increase in interleukin-10 at 10d, and reduced oxidative stress (malondialdehyde) following HI (P<0.05). UCBC administration at 12h after HI reduces preterm white matter injury, via anti-inflammatory and antioxidant actions.
Adalimumab originator versus adalimumab biosimilars in inflammatory bowel disease in Australia
Publisher: Informa UK Limited
Date: 19-04-2023
Could cord blood cell therapy reduce preterm brain injury?
Publisher: Frontiers Media SA
Date: 09-10-2014
Nucleated red blood cell counts: An early predictor of brain injury and 2-year outcome in neonates with hypoxic-ischemic encephalopathy in the era of cooling-based treatment
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.BRAINDEV.2013.06.012
Abstract: Raised nucleated red blood cell (NRBC) counts in neonates may indicate in utero hypoxia and brain damage. The study aimed to examine the use of NRBC counts as a predictor of brain injury and neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy (HIE) treated under current cooling-based strategy. Forty-three neonates with asphyxia between 2004 and 2010 were retrospectively investigated. Twenty neonates with moderate/severe HIE underwent hypothermia (HT), and 23 with mild HIE were treated in normothermia (NT). Neonates were ided into groups according to the presence of cerebral parenchymal lesions on magnetic resonance imaging (MRI) at 2 weeks after birth. All patients were followed-up neurologically for ⩾ 24 months. NRBC counts during the first 3 days were compared between groups. Eleven HT (HT-N) and 21 NT (NT-N) neonates had normal MRI, and 9 HT (HT-L) and 2 NT (NT-L) neonates had parenchymal lesions. NRBC counts, both absolute and /100 white blood cells (WBC) counts, during the first 3 days in HT-L and NT-L were significantly higher than those in HT-N and NT-N, particularly within 6 hours after birth (HT-N: 502 [0-3060]/mm(3) vs HT-L: 2765 [496-6192] 0 [0-3417] vs NT-L: 4384 [3978-4789], median [range]). Neonates with /100 white blood cells ⩾ 6/mm(3) and absolute NRBC counts ⩾ 1324/mm(3) within 6 hours of birth had high risks of abnormal MRIs and 2-year outcomes. NRBC counts can predict brain injury and neurological outcomes in cooled and non-cooled asphyxiated neonates.
Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial
Publisher: Elsevier BV
Date: 03-2017
Safety of drugs used for the treatment of Crohn’s disease
Publisher: Informa UK Limited
Date: 04-05-2019
DOI: 10.1080/14740338.2019.1612874
Abstract: Medications in treating Crohn's disease (CD) have evolved over the last two decades, particularly with the use of biologic agents. There are, however, concerns about the safety and adverse events associated with these medications. The authors review the safety profile of immunosuppressive medications used in Crohn's disease in adult patients. The authors performed a literature search until October 2018 to examine safety data on thiopurines, methotrexate, anti-TNFα agents, vedolizumab and ustekinumab. The authors focused on 'trial' and 'real-world' data for the biologic agents. Safety in pregnancy and the elderly are also presented. Available data in CD suggest that immunosuppressive medications are relatively safe, although there are concerns about an elevated risk of serious infections, skin cancer and lymphoma particularly with thiopurines and anti-TNFα agents. Data on vedolizumab and ustekinumab suggest these newer biologic agents are well tolerated however, longer term data in CD are required to identify risks with extended use. Apart from methotrexate, there appear to be no adverse congenital outcomes with exposure of drugs during pregnancy.
Key metabolomic alterations are associated with ulcerative colitis disease state and activity: a validation analysis
Publisher: BMJ
Date: 17-08-2023
Human Umbilical Cord Blood Therapy Protects Cerebral White Matter from Systemic LPS Exposure in Preterm Fetal Sheep
Publisher: S. Karger AG
Date: 2018
DOI: 10.1159/000490943
Abstract: b i Background: /i /b Infants born preterm following exposure to in utero inflammation/chorioamnionitis are at high risk of brain injury and life-long neurological deficits. In this study, we assessed the efficacy of early intervention umbilical cord blood (UCB) cell therapy in a large animal model of preterm brain inflammation and injury. We hypothesised that UCB treatment would be neuroprotective for the preterm brain following subclinical fetal inflammation. b i Methods: /i /b Chronically instrumented fetal sheep at 0.65 gestation were administered lipopolysaccharide (LPS, 150 ng, 055:B5) intravenously over 3 consecutive days, followed by 100 million human UCB mononuclear cells 6 h after the final LPS dose. Controls were administered saline instead of LPS and cells. Ten days after the first LPS dose, the fetal brain and cerebrospinal fluid were collected for analysis of subcortical and periventricular white matter injury and inflammation. b i Results: /i /b LPS administration increased microglial aggregate size, neutrophil recruitment, astrogliosis and cell death compared with controls. LPS also reduced total oligodendrocyte count and decreased mature myelinating oligodendrocytes. UCB cell therapy attenuated cell death and inflammation, and recovered total and mature oligodendrocytes, compared with LPS. b i Conclusions: /i /b UCB cell treatment following inflammation reduces preterm white matter brain injury, likely mediated via anti-inflammatory actions.
An update on fecal microbiota transplantation for the treatment of gastrointestinal diseases
Publisher: Wiley
Date: 12-11-2022
DOI: 10.1111/JGH.15731
Abstract: Our understanding of the microbiome and its implications for human health and disease continues to develop. Fecal microbiota transplantation (FMT) is now an established treatment for recurrent Clostridioides difficile infection. There is also increasing evidence for the efficacy of FMT in inducing remission for mild–moderate ulcerative colitis. However, for other indications, data for FMT are limited, with randomized controlled trials rare, typically small and often conflicting. Studies are continuing to explore the role of FMT for many other conditions, including Crohn's disease, functional gut disorders, metabolic syndrome, modulating responses to chemotherapy, eradication of multidrug resistant organisms, and the gut–brain axis. In light of safety, logistical, and regulatory challenges, there is a move to standardized products including narrow spectrum consortia. However, the mechanisms underpinning FMT remain incompletely understood, including the role of non‐bacterial components, which may limit success of novel microbial approaches.
Preterm umbilical cord blood derived mesenchymal stem/stromal cells protect preterm white matter brain development against hypoxia-ischemia
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.EXPNEUROL.2018.07.006
Abstract: Preterm infants are at high risk for white matter injury and subsequent neurodevelopmental impairments. Mesenchymal stem/stromal cells (MSC) have anti-inflammatory/immunomodulatory actions and are of interest for neural repair in adults and newborns. This study examined the neuroprotective effects of allogeneic MSC, derived from preterm umbilical cord blood (UCB), in a preterm sheep model of white matter injury. Quad-lineage differentiation, clonogenicity and self-renewal ability of UCB-derived MSC were confirmed. Chronically instrumented fetal sheep (0.7 gestation) received either 25 min hypoxia-ischemia (HI) to induce preterm brain injury, or sham-HI. Ten million MSC, or saline, were administered iv to fetuses at 12 h after HI. Fetal brains were collected 10d after HI for histopathology and immunocytochemistry. HI induced white matter injury, as indicated by a reduction in CNPase-positive myelin fiber density. HI also induced microglial activation (Iba-1) in the periventricular white matter and internal capsule (P < .05 vs control). MSC administration following HI preserved myelination (P < .05), modified microglial activation, and promoted macrophage migration (CD163) and cell proliferation (Ki-67) within cerebral white matter (P < .05). Cerebral CXCL10 concentration was increased following MSC administration (P < .05), which was likely associated with macrophage migration and cell proliferation within the preterm brain. Additionally, MSC administration reduced systemic pro-inflammatory cytokine TNFα at 3d post-HI (P < .05). UCB-derived MSC therapy preserved white matter brain structure following preterm HI, mediated by a suppression of microglial activation, promotion of macrophage migration and acceleration of self-repair within the preterm brain. UCB-derived MSC are neuroprotective, acting via peripheral and cerebral anti-inflammatory and immunomodulatory mechanisms.
Donor Recruitment for Fecal Microbiota Transplantation
Publisher: Oxford University Press (OUP)
Date: 07-2015
Preterm Hypoxic–Ischemic Encephalopathy
Publisher: Frontiers Media SA
Date: 20-10-2016
Impact of intra- and extrauterine growth on bone mineral density and content in the neonatal period of very-low-birth-weight infants
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.EARLHUMDEV.2015.10.020
Abstract: Very-low-birthweight infants (VLBWIs) are at high risk for suboptimal bone mineral density (BMD) and bone mineral content (BMC). Small-for-gestational-age (SGA) status also causes reduced bone mineralization in full-term infants. However, the impact of intrauterine and postnatal extrauterine growth on BMD and BMC in VLBWIs is inconclusive. We retrospectively investigated n=68 VLBWIs, comprising 45 appropriate-for-gestational-age (AGA) and 23 SGA infants who underwent lumbar spine dual-energy X-ray absorptiometry at term-equivalent age. BMD and BMC did not differ between AGA and SGA VLBWIs. Subgroup analyses of infants with birthweight<1000 g vs 1000-1500 g, and GA<27 weeks vs ≥ 27 weeks also showed no differences in BMD and BMC between AGA and SGA infants. In contrast, infants with extrauterine growth restriction (EUGR) showed significantly lower values than those without (BMD: 0.124 ± 0.023 vs 0.141 ± 0.032 g/cm(2), P=0.02 BMC: 0.80 ± 0.26 vs 0.94 ± 0.23 g, P=0.04). There were no differences between AGA and SGA infants with EUGR. However, in the AGA cohort, infants with EUGR showed significantly lower values than those without (BMD: 0.121 ± 0.022 0.141 ± 0.03 g/cm(2), P=0.02 BMC: 0.73 ± 0.23 vs 0.94 ± 0.23 g, P=0.005). Multiple regression analyses showed GA, weight and head circumference at birth, and weight percentile at term correlated with term BMD. Conversely, only weight percentile at term significantly correlated with term BMC. EUGR, rather than IUGR, is a risk factor for reduced BMD and BMC in the neonatal period in VLBWIs.
Response to faecal microbiota transplantation in ulcerative colitis is not sustained long term following induction therapy
Publisher: BMJ
Date: 10-12-2021
Umbilical cord blood versus mesenchymal stem cells for inflammation-induced preterm brain injury in fetal sheep
Publisher: Springer Science and Business Media LLC
Date: 11-03-2019
DOI: 10.1038/S41390-019-0366-Z
Abstract: Chorioamnionitis and fetal inflammation are principal causes of neuropathology detected after birth, particularly in very preterm infants. Preclinical studies show that umbilical cord blood (UCB) cells are neuroprotective, but it is uncertain if allogeneic UCB cells are a feasible early intervention for preterm infants. In contrast, mesenchymal stem cells (MSCs) are more readily accessible and show strong anti-inflammatory benefits. We aimed to compare the neuroprotective benefits of UCB versus MSCs in a large animal model of inflammation-induced preterm brain injury. We hypothesized that MSCs would afford greater neuroprotection. Chronically instrumented fetal sheep at 0.65 gestation received intravenous lipopolysaccharide (150 ng 055:B5, n = 8) over 3 consecutive days or saline for controls (n = 8). Cell-treated animals received 10 Lipopolysaccharide induced neuroinflammation and apoptosis, and reduced the number of mature oligodendrocytes. MSCs reduced astrogliosis, but UCB did not have the same effect. UCB significantly decreased cerebral apoptosis and protected mature myelinating oligodendrocytes, but MSCs did not. UCB appears to better protect white matter development in the preterm brain in response to inflammation-induced brain injury in fetal sheep.
The beneficial effects of melatonin administration following hypoxia-ischemia in preterm fetal sheep
Publisher: Frontiers Media SA
Date: 22-09-2017
Superior treatment persistence with ustekinumab in Crohn’s disease and vedolizumab in ulcerative colitis compared with anti‐TNF biological agents: real‐world registry data from the Persistence Australian National IBD Cohort (PANIC) study
Publisher: Wiley
Date: 20-06-2021
DOI: 10.1111/APT.16436
Abstract: Medication persistence contributes real‐world evidence about treatment effectiveness, tolerability and prescriber and patient acceptability. To evaluate persistence of biological agents in Crohn's disease (CD) and ulcerative colitis (UC) and the effects of immunomodulator use and treatment lines. Retrospective national population‐based data on treatment persistence for adalimumab, infliximab vedolizumab and ustekinumab for CD and UC were analysed from the Australian Pharmaceutical Benefits Scheme using Kaplan‐Meier analysis and Cox proportional hazards models. There were 2499 patients included with 8219 person‐years of follow‐up. In CD patients ustekinumab had increased persistence compared to anti‐TNF agents (HR: 1.79, 95%CI: 1.32‐2.38, P 0.01). Twelve‐month CD persistence rates were ustekinumab 80.0%, vedolizumab 73.5%, infliximab 68.1% and adalimumab 64.2% ( P = 0.01). In moderate‐severe UC vedolizumab had increased persistence compared to anti‐TNF agents (HR: 1.67, 95% CI: 1.27‐2.18 P 0.001). Twelve‐month UC persistence rates were vedolizumab 73.4%, infliximab 61.1% and adalimumab 45.5% ( P 0.001). Immunomodulator co‐therapy did not significantly increase persistence in non‐anti‐TNF therapy ( P 0.05). Thiopurines increased persistence of anti‐TNF agents in CD ( P 0.001) and UC ( P = 0.03). Methotrexate co‐therapy increased persistence of anti‐TNF agents in CD ( P = 0.001) only. First‐line therapy was superior to non‐first line in persistence ( P 0.001). In fistulising CD, the persistence of infliximab and adalimumab was not significantly different ( P = 0.11). Persistence was highest in ustekinumab in CD and vedolizumab in UC. Factors which increased the persistence of biological agents are first‐line therapy, and immunomodulator co‐therapy in anti‐TNF agent use.
Controlling the Effective Oxygen Tension Experienced by Cells Using a Dynamic Culture Technique for Hematopoietic Ex Vivo Expansion
Publisher: Wiley
Date: 02-2018
DOI: 10.1002/CPSC.42
Abstract: Clinical hematopoietic stem rogenitor cell (HSPC) transplantation outcomes are strongly correlated with the number of cells infused. Hence, to generate sufficient HSPCs for transplantation, the best culture parameters for expansion are critical. It is generally assumed that the defined oxygen (O
Endoscopy
Publisher: Springer Science and Business Media LLC
Date: 07-2010
Human Amnion Epithelial Cells Protect Against White Matter Brain Injury After Repeated Endotoxin Exposure in the Preterm Ovine Fetus.
Publisher: SAGE Publications
Date: 04-2017
Abstract: Intrauterine inflammation is a significant cause of injury to the developing fetal brain. Using a preterm fetal sheep model of in utero infection, we asked whether human amnion epithelial cells (hAECs) were able to reduce inflammation-induced fetal brain injury. Surgery was undertaken on pregnant sheep at ~105 days gestation (term is 147 days) for implantation of vascular catheters. Lipopolysaccharide (LPS 150 ng/kg bolus) or saline was administered IV at 109, 110, and 111 days. Sixty million fluorescent-labeled hAECs were administered at 110, 111, and 112 days gestation via the brachial artery catheter. Brains were collected at 114 days for histological assessment. hAECs were observed within the cortex, white matter, and hippoc us. Compared to control lambs, LPS administration was associated with significant and widespread fetal brain inflammation and injury as evidenced by increased number of activated microglia in the periventricular white matter ( p = 0.02), increased pyknosis, cell degeneration ( p = 0.01), and a nonsignificant trend of fewer oligodendrocytes in the subcortical and periventricular white matter. Administration of hAECs to LPS-treated animals was associated with a significant mitigation in both inflammation and injury as evidenced by fewer activated microglia ( p = 0.03) and pyknotic cells ( p = 0.03), significantly more oligodendrocytes in the subcortical and periventricular white matter ( p = 0.01 and 0.02, respectively), and more myelin basic protein-positive cells within the periventricular white matter ( p = 0.02). hAEC administration to fetal sheep exposed to multiple doses of LPS d ens the resultant fetal inflammatory response and mitigates associated brain injury.
A case of a full-term newborn with severe craniotabes due to insufficient maternal sunlight exposure during the COVID-19 pandemic
Publisher: Elsevier BV
Date: 09-2023
A neonate of coronary artery fistula from left circumflex to coronary sinus
Publisher: Springer Science and Business Media LLC
Date: 22-04-2011
DOI: 10.1007/S00246-011-9976-X
Abstract: The patient was a neonate with a large coronary artery fistula (CAF) between the left circumflex artery and coronary sinus in whom an intractable progressive heart failure with myocardial ischemia developed within 24 h after birth. He survived the surgical intervention and is doing well. This is the first report of coronary fistula presenting with cardiogenic shock on the first day of life. Additionally, this is the fourth case of the CAF between the left circumflex artery and coronary sinus in children, and the first case in a newborn.
Specific Bacteria and Metabolites Associated With Response to Fecal Microbiota Transplantation in Patients With Ulcerative Colitis
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1053/J.GASTRO.2018.12.001
Abstract: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis (UC). In a randomized controlled trial of FMT in patients with active UC, we aimed to identify bacterial taxonomic and functional factors associated with response to therapy. We performed a double-blind trial of 81 patients with active UC randomly assigned to groups that received an initial colonoscopic infusion and then intensive multidonor FMT or placebo enemas, 5 d/wk for 8 weeks. Patients in the FMT group received blended homogenized stool from 3-7 unrelated donors. Patients in the placebo group were eligible to receive open-label FMT after the double-blind study period. We collected 314 fecal s les from the patients at screening, every 4 weeks during treatment, and 8 weeks after the blinded or open-label FMT therapy. We also collected 160 large-bowel biopsy s les from the patients at study entry, at completion of 8 weeks of blinded therapy, and at the end of open-label FMT, if applicable. We analyzed 105 fecal s les from the 14 in idual donors (n = 55), who in turn contributed to 21 multidonor batches (n = 50). Bacteria in colonic and fecal s les were analyzed by both 16S ribosomal RNA gene and transcript licon sequencing 285 fecal s les were analyzed by shotgun metagenomics, and 60 fecal s les were analyzed for metabolome features. FMT increased microbial ersity and altered composition, based on analyses of colon and fecal s les collected before vs after FMT. Diversity was greater in fecal and colon s les collected before and after FMT treatment from patients who achieved remission compared with patients who did not. Patients in remission after FMT had enrichment of Eubacterium hallii and Roseburia inulivorans compared with patients who did not achieve remission after FMT and had increased levels of short-chain fatty acid biosynthesis and secondary bile acids. Patients who did not achieve remission had enrichment of Fusobacterium gonidiaformans, Sutterella wadsworthensis, and Escherichia species and increased levels of heme and lipopolysaccharide biosynthesis. Bacteroides in donor stool were associated with remission in patients receiving FMT, and Streptococcus species in donor stool was associated with no response to FMT. In an analysis of fecal and colonic mucosa s les from patients receiving FMT for active UC and stool s les from donors, we associated specific bacteria and metabolic pathways with induction of remission. These findings may be of value in the design of microbe-based therapies for UC. ClinicalTrials.gov, Number NCT01896635.
Australian consensus statements for the regulation, production and use of faecal microbiota transplantation in clinical practice.
Publisher: BMJ
Date: 11-02-2020
DOI: 10.1136/GUTJNL-2019-320260
Abstract: Faecal microbiota transplantation (FMT) has proved to be an extremely effective treatment for recurrent Clostridioides difficile infection, and there is interest in its potential application in other gastrointestinal and systemic diseases. However, the recent death and episode of septicaemia following FMT highlights the need for further appraisal and guidelines on donor evaluation, production standards, treatment facilities and acceptable clinical indications. For these consensus statements, a 24-member multidisciplinary working group voted online and then convened in-person, using a modified Delphi approach to formulate and refine a series of recommendations based on best evidence and expert opinion. Invitations to participate were directed to Australian experts, with an international delegate assisting the development. The following issues regarding the use of FMT in clinical practice were addressed: donor selection and screening, clinical indications, requirements of FMT centres and future directions. Evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Consensus was reached on 27 statements to provide guidance on best practice in FMT. These include: (1) minimum standards for donor screening with recommended clinical selection criteria, blood and stool testing (2) accepted routes of administration (3) clinical indications (4) minimum standards for FMT production and requirements for treatment facilities acknowledging distinction between single-site centres (eg, hospital-based) and stool banks and (5) recommendations on future research and product development. These FMT consensus statements provide comprehensive recommendations around the production and use of FMT in clinical practice with relevance to clinicians, researchers and policy makers.
Resumption of oral intake following percutaneous endoscopic gastrostomy
Publisher: Wiley
Date: 27-05-2009
DOI: 10.1111/J.1440-1746.2009.05802.X
Abstract: Percutaneous endoscopic gastrostomy (PEG) provides enteral nutrition to patients who cannot swallow. Few studies have prospectively evaluated its long-term outcomes or eventual resumption of oral intake. Consecutive PEG patients were prospectively recruited from a tertiary hospital over 12 months and followed until all had met the primary endpoints of death or resumption of oral diet with PEG extubation. Data was collected by standardised periodic phone interview. Forty patients (24 males, median age 74 years) were followed for up to 8.4 years (median 5.3 months, interquartile range [IQR] 13.6 months). The end-of-study mortality rate was 70% (median 6.8 months, IQR 19.9 months) and the only predictor of mortality was head injury as the indication for PEG (Cox regression HR 5.90, 95% CI: 1.2-28.4). At two years following PEG, 30% of patients had resumed oral intake (median 2.9 months, IQR 7.2 months) and 19% remained on PEG-feeding. Predictors of resumption of oral intake were the ability to tolerate some oral intake at 3 months (HR: 248.5, 95% CI: 8.7-7065.3) and 6 months (HR: 6.3, 95% CI: 1.03-38.9) but not at 12 months. Cumulative survival was highest for ear nose and throat (ENT) tumour and worst for acute head injury (log rank P = 0.048). Half of all PEG patients remained alive at 2 years using PEG or have resumed full oral intake. A supervised trial of oral intake at 3 or 6 months may help predict eventual resumption of per oral diet.
Aristaless-related homeobox gene disruption leads to abnormal distribution of GABAergic interneurons in human neocortex: Evidence based on a case of X-linked lissencephaly with abnormal genitalia (XLAG)
Publisher: Springer Science and Business Media LLC
Date: 06-05-2008
DOI: 10.1007/S00401-008-0382-2
Abstract: X-linked lissencephaly with abnormal genitalia (XLAG) is a rare disorder caused by mutations in the aristaless-related homeobox (ARX) gene, located on Xp22.13. Arx-null mice show loss of tangential migration of GABAergic interneurons, presumably being related to caudal ganglionic eminence tangential migration. In the present study, we investigated a subpopulation of GABAergic interneurons in the brain of an infant with XLAG, who had a novel nonsense mutation of the ARX gene, compared with those of age-matched normal controls and Miller-Dieker syndrome. We performed immunocytochemistry for interneuron and migration markers. We found that glutamic acid decarboxylase (GAD)- and calretinin (CR)-containing cells were significantly reduced in the neocortex and located in the white matter and neocortical subventricular zone, while neuropeptide Y- or cholecystokinin-containing cells were normally distributed. Moreover, in the neocortical subventricular region, the GAD- and CR-containing cells expressed the radial migration marker Mash-1 as well as nestin. Our findings suggest that ARX protein controls not only the tangential migration of GABAergic interneurons from the ganglionic eminence, but also may serve to induce radial migration from the neocortical subventricular zone.
Gastroenterologist perceptions of faecal microbiota transplantation
Publisher: Baishideng Publishing Group Inc.
Date: 2015
Faecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis
Publisher: Oxford University Press (OUP)
Date: 09-05-2017
Abstract: Faecal microbiota transplantation [FMT] has been investigated as a potential treatment for inflammatory bowel disease [IBD]. We thus performed a systematic review and meta-analysis assessing the effectiveness and safety of FMT in IBD. A systematic review was conducted until January 2017. Studies were excluded if patients had co-infection or data were pooled across disease subtypes (ulcerative colitis [UC], Crohn's disease [CD], pouchitis). Clinical remission was established as the primary outcome. Pooled effect sizes and 95% confidence intervals were obtained using the random effects model. In all, 53 studies were included [41 in UC, 11 in CD, 4 in pouchitis]. Overall, 36% [201/555] of UC, 50.5% [42/83] of CD, and 21.5% [5/23] of pouchitis patients achieved clinical remission. Among cohort studies, the pooled proportion achieving clinical remission was 33% (95% confidence interval [CI] = 23%-43%] for UC and 52% [95% CI = 31%-72%] for CD, both with moderate risk of heterogeneity. For four RCTs in UC, significant benefit in clinical remission (pooled odds ratios [[P-OR] = 2.89, 95% CI = 1.36-6.13, p = 0.006) with moderate heterogeneity [Cochran's Q, p = 0.188 I2 = 37%] was noted. Sub-analyses suggest remission in UC improved with increased number of FMT infusions and lower gastrointestinal tract administration. Most adverse events were transient gastrointestinal complaints. Microbiota analysis was performed in 24 studies, with many identifying increased ersity and a shift in recipient microbiota profile towards the donor post-FMT. FMT appears effective in UC remission induction, but long-term durability and safety remain unclear. Additional well-designed controlled studies of FMT in IBD are needed, especially in CD and pouchitis.
Term vs. preterm cord blood cells for the prevention of preterm brain injury.
Publisher: Springer Science and Business Media LLC
Date: 16-08-2017
DOI: 10.1038/PR.2017.170
Abstract: BACKGROUNDWhite matter brain injury in preterm infants can induce neurodevelopmental deficits. Umbilical cord blood (UCB) cells demonstrate neuroprotective properties, but it is unknown whether cells obtained from preterm cord blood (PCB) vs. term cord blood (TCB) have similar efficacy. This study compared the ability of TCB vs. PCB cells to reduce white matter injury in preterm fetal sheep.METHODSHypoxia-ischemia (HI) was induced in fetal sheep (0.7 gestation) by 25 min umbilical cord occlusion. Allogeneic UCB cells from term or preterm sheep, or saline, were administered to the fetus at 12 h after HI. The fetal brain was collected at 10-day post HI for assessment of white matter neuropathology.RESULTSHI (n=7) induced cell death and microglial activation and reduced total oligodendrocytes and CNPase+myelin protein in the periventricular white matter and internal capsule when compared with control (n=10). Administration of TCB or PCB cells normalized white matter density and reduced cell death and microgliosis (P<0.05). PCB prevented upregulation of plasma tumor necrosis factor (TNF)-a, whereas TCB increased anti-inflammatory interleukin (IL)-10 (P<0.05). TCB, but not PCB, reduced circulating oxidative stress.CONCLUSIONSTCB and PCB cells reduced preterm HI-induced white matter injury, primarily via anti-inflammatory actions. The secondary mechanisms of neuroprotection appear different following TCB vs. PCB administration.
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