Publications
378 results found
Nicol MP, Gnanashanmugam D, Browning R, et al., 2015, A Blueprint to Address Research Gaps in the Development of Biomarkers for Pediatric Tuberculosis, CLINICAL INFECTIOUS DISEASES, Vol: 61, Pages: S164-S172, ISSN: 1058-4838
- Author Web Link
- Cite
- Citations: 22
Shah V, Christov G, Mukasa T, et al., 2015, Cardiovascular status after Kawasaki disease in the UK, Heart, Vol: 101, Pages: 1646-1655, ISSN: 1468-201X
Objective Kawasaki disease (KD) is an acute vasculitis that causes coronary artery aneurysms (CAA) in young children. Previous studies have emphasised poor long-term outcomes for those with severe CAA. Little is known about the fate of those without CAA or patients with regressed CAA. We aimed to study long-term cardiovascular status after KD by examining the relationship between coronary artery (CA) status, endothelial injury, systemic inflammatory markers, cardiovascular risk factors (CRF), pulse-wave velocity (PWV) and carotid intima media thickness (cIMT) after KD.Methods Circulating endothelial cells (CECs), endothelial microparticles (EMPs), soluble cell-adhesion molecules cytokines, CRF, PWV and cIMT were compared between patients with KD and healthy controls (HC). CA status of the patients with KD was classified as CAA present (CAA+) or absent (CAA−) according to their worst-ever CA status. Data are median (range).Results Ninety-two KD subjects were studied, aged 11.9 years (4.3–32.2), 8.3 years (1.0–30.7) from KD diagnosis. 54 (59%) were CAA−, and 38 (41%) were CAA+. There were 51 demographically similar HC. Patients with KD had higher CECs than HC (p=0.00003), most evident in the CAA+ group (p=0.00009), but also higher in the CAA− group than HC (p=0.0010). Patients with persistent CAA had the highest CECs, but even those with regressed CAA had higher CECs than HC (p=0.011). CD105 EMPs were also higher in the KD group versus HC (p=0.04), particularly in the CAA+ group (p=0.02), with similar findings for soluble vascular cell adhesion molecule 1 and soluble intercellular adhesion molecule 1. There was no difference in PWV, cIMT, CRF or in markers of systemic inflammation in the patients with KD (CAA+ or CAA−) compared with HC.Conclusions Markers of endothelial injury persist for years after KD, including in a subset of patients without CAA.
Evans C, Orf K, Horvath E, et al., 2015, Impairment of neutrophil oxidative burst in children with sickle cell disease is associated with heme oxygenase-1, Haematologica - the Hematology Journal, Vol: 100, Pages: 1508-1516, ISSN: 0390-6078
Sickle cell disease is a risk factor for invasive bacterial infections, and splenic dysfunction is believed to be the main underlying cause. We have previously shown that the liberation of heme in acute hemolysis can induce heme oxygenase-1 during granulopoiesis, impairing the ability of developing neutrophils to mount a bactericidal oxidative burst, and increasing susceptibility to bacterial infection. We hypothesised that this may also occur with the chronic hemolysis of sickle cell disease, potentially contributing to susceptibility to infections. We found that neutrophil oxidative burst activity was significantly lower in treatment-naive children with sickle cell disease compared to age-, gender- and ethnicity-matched controls, whilst degranulation was similar. The defect in neutrophil oxidative burst was quantitatively related to both systemic heme oxygenase-1 activity (assessed by carboxyhemoglobin concentration) and neutrophil mobilization. A distinct population of heme oxygenase-1-expressing cells was present in the bone marrow of children with sickle cell disease, but not in healthy children, with a surface marker profile consistent with neutrophil progenitors (CD49dHi CD24Lo CD15Int CD16Int CD11b+/-). Incubation of promyelocytic HL-60 cells with the heme oxygenase-1 substrate and inducer, hemin, demonstrated that heme oxygenase-1 induction during neutrophilic differentiation could reduce oxidative burst capacity. These findings indicate that impairment of neutrophil oxidative burst activity in sickle cell disease is associated with hemolysis and heme oxygenase-1 expression. Neutrophil dysfunction might contribute to risk of infection in sickle cell disease, and measurement of neutrophil oxidative burst might be used to identify patients at greatest risk of infection, who might benefit from enhanced prophylaxis.
George EC, Walker AS, Kiguli S, et al., 2015, Predicting mortality in sick African children: the FEAST Paediatric Emergency Triage (PET) Score., BMC Medicine, Vol: 13, ISSN: 1741-7015
BACKGROUND: Mortality in paediatric emergency care units in Africa often occurs within the first 24 h of admission and remains high. Alongside effective triage systems, a practical clinical bedside risk score to identify those at greatest risk could contribute to reducing mortality. METHODS: Data collected during the Fluid As Expansive Supportive Therapy (FEAST) trial, a multi-centre trial involving 3,170 severely ill African children, were analysed to identify clinical and laboratory prognostic factors for mortality. Multivariable Cox regression was used to build a model in this derivation dataset based on clinical parameters that could be quickly and easily assessed at the bedside. A score developed from the model coefficients was externally validated in two admissions datasets from Kilifi District Hospital, Kenya, and compared to published risk scores using Area Under the Receiver Operating Curve (AUROC) and Hosmer-Lemeshow tests. The Net Reclassification Index (NRI) was used to identify additional laboratory prognostic factors. RESULTS: A risk score using 8 clinical variables (temperature, heart rate, capillary refill time, conscious level, severe pallor, respiratory distress, lung crepitations, and weak pulse volume) was developed. The score ranged from 0-10 and had an AUROC of 0.82 (95 % CI, 0.77-0.87) in the FEAST trial derivation set. In the independent validation datasets, the score had an AUROC of 0.77 (95 % CI, 0.72-0.82) amongst admissions to a paediatric high dependency ward and 0.86 (95 % CI, 0.82-0.89) amongst general paediatric admissions. This discriminative ability was similar to, or better than other risk scores in the validation datasets. NRI identified lactate, blood urea nitrogen, and pH to be important prognostic laboratory variables that could add information to the clinical score. CONCLUSIONS: Eight clinical prognostic factors that could be rapidly assessed by healthcare staff for triage were combined to create the FEAST Paediatric Emergency
von Both U, Levin M, Kaforou M, et al., 2015, Understanding immune protection against tuberculosis using RNA expression profiling., Vaccine, Vol: 33, Pages: 5289-5293, ISSN: 1873-2518
A major limitation in the development and testing of new tuberculosis (TB) vaccines is the current inadequate understanding of the nature of the immune response required for protection against either infection with Mycobacterium tuberculosis (MTB) or progression to disease. Genome wide RNA expression analysis has provided a new tool with which to study the inflammatory and immunological response to mycobacteria. To explore how currently available transcriptomic data might be used to understand the basis of protective immunity to MTB, we analysed and reviewed published RNA expression studies to (1) identify a “susceptible” immune response in patients with acquired defects in the interferon gamma pathway; (2) identify the “failing” transcriptomic response in patients with TB as compared with latent TB infection (LTBI); and (3) identify elements of the “protective” response in healthy latently infected and healthy uninfected individuals.Abbreviations TB, tuberculosis; MTB, Mycobacterium tuberculosis; IFN-γ, interferon-gamma; PBMC, peripheral blood mononuclear cells; MSMD, Mendelian susceptibility to mycobacterial disease; BCG, bacille Calmette–Guerin; LTBI, latent tuberculosis infectionKeywords Transcriptomics; RNA expression profiling; Tuberculosis; Vaccines; Interferon-γ; Type I interferon
Davies S, Sutton N, Blackstock S, et al., 2015, Predicting IVIG resistance in UK Kawasaki disease, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 100, Pages: 366-368, ISSN: 0003-9888
- Author Web Link
- Open Access Link
- Cite
- Citations: 85
Eleftheriou D, Levin M, Shingadia D, et al., 2015, Authors' response to 'Aspirin dose for treatment of Kawasaki disease', ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 100, ISSN: 0003-9888
- Author Web Link
- Cite
- Citations: 1
Stevens J, Herberg JA, Levin M, 2015, Infectious diseases and the kidney in children, Pediatric Nephrology, Seventh Edition, Pages: 1609-1654, ISBN: 9783662435953
The kidney is involved in a wide range of bacterial, viral, fungal, and parasitic diseases. In most systemic infections, renal involvement is a minor component of the illness, but in some, renal failure may be the presenting feature and the major problem in management. Although individual infectious processes may have a predilection to involve the renal vasculature, glomeruli, interstitium, or collecting systems, a purely anatomic approach to the classification of infectious diseases affecting the kidney is rarely helpful because most infections may involve several different aspects of renal function. In this chapter, a microbiological classification of the organisms affecting the kidney is adopted. Although they are important causes of renal dysfunction in infectious diseases, urinary tract infections and hemolytic uremic syndrome (HUS) are not discussed in detail because they are considered separately in chapters XX and XX, respectively. The kidney is involved in a wide range of bacterial, viral, fungal, and parasitic diseases. In most systemic infections, renal involvement is a minor component of the illness, but in some, renal failure may be the presenting feature and the major problem in management. Although individual infectious processes may have a predilection to involve the renal vasculature, glomeruli, interstitium, or collecting systems, a purely anatomic approach to the classification of infectious diseases affecting the kidney is rarely helpful because most infections may involve several different aspects of renal function. In this chapter, a microbiological classification of the organisms affecting the kidney is adopted. Although they are important causes of renal dysfunction in infectious diseases, urinary tract infections and hemolytic uremic syndrome (HUS) are not discussed in detail because they are considered separately in Chaps. 47, “Renal Involvement in Children with HUS,” and 53, “Urinary Tract Infections in Children,”
Kiguli J, 2015, Anaemia and blood transfusion in African children presenting to hospital with severe febrile illness, BMC Medicine, Vol: 13
Zenz W, Klobassa DS, Sonnleitner A, et al., 2014, Genetic research in Austrian children. Balancing act between milestones in medicine and millstones in bureaucracy, MONATSSCHRIFT KINDERHEILKUNDE, Vol: 162, Pages: 1110-1116, ISSN: 0026-9298
Hoang LT, Shimizu C, Ling L, et al., 2014, Global gene expression profiling identifies new therapeutic targets in acute Kawasaki disease, GENOME MEDICINE, Vol: 6, ISSN: 1756-994X
- Author Web Link
- Open Access Link
- Cite
- Citations: 96
Kaforou M, Wright VJ, Levin M, 2014, Host RNA signatures for diagnostics: An example from paediatric tuberculosis in Africa, JOURNAL OF INFECTION, Vol: 69, Pages: S28-S31, ISSN: 0163-4453
- Author Web Link
- Cite
- Citations: 15
Levin M, Burgner D, 2014, Treatment of Kawasaki disease with anti-TNF antibodies, LANCET, Vol: 383, Pages: 1700-1703, ISSN: 0140-6736
- Author Web Link
- Cite
- Citations: 7
Anderson ST, Kaforou M, Brent AJ, et al., 2014, Diagnosis of Childhood Tuberculosis and Host RNA Expression in Africa, New England Journal of Medicine, Vol: 370, Pages: 1712-1723, ISSN: 1533-4406
Kiguli S, Akech SO, Mtove G, et al., 2014, WHO GUIDELINES ON FLUID RESUSCITATION IN CHILDREN Concerns about intravenous fluids given to critically ill children Reply, BMJ-BRITISH MEDICAL JOURNAL, Vol: 348, ISSN: 1756-1833
- Author Web Link
- Open Access Link
- Cite
- Citations: 1
Kiguli S, Akech SO, Mtove G, et al., 2014, WHO guidelines on fluid resuscitation in children: missing the FEAST data, BMJ-BRITISH MEDICAL JOURNAL, Vol: 348, ISSN: 0959-535X
- Author Web Link
- Open Access Link
- Cite
- Citations: 14
Carpenter D, Taype C, Goulding J, et al., 2014, <i>CCL3L1</i> copy number, <i>CCR5</i> genotype and susceptibility to tuberculosis, BMC MEDICAL GENETICS, Vol: 15
- Author Web Link
- Cite
- Citations: 14
Eleftheriou D, Levin M, Shingadia D, et al., 2014, Management of Kawasaki disease, ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION, Vol: 99, Pages: 74-83, ISSN: 1359-2998
- Author Web Link
- Cite
- Citations: 2
Eleftheriou D, Levin M, Shingadia D, et al., 2014, Management of Kawasaki disease, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 99, Pages: 74-83, ISSN: 0003-9888
- Author Web Link
- Cite
- Citations: 154
Levin M, Burns JC, Gordon JB, 2014, Warfarin plus Aspirin or Aspirin Alone for with Giant Coronary Artery Aneurysms Secondary to Kawasaki Disease?, CARDIOLOGY, Vol: 129, Pages: 174-177, ISSN: 0008-6312
- Author Web Link
- Cite
- Citations: 6
Herberg JA, Kaforou M, Gormley S, et al., 2013, Transcriptomic Profiling in Childhood H1N1/09 Influenza Reveals Reduced Expression of Protein Synthesis Genes, Journal of Infectious Diseases, Vol: 208, Pages: 1664-1668, ISSN: 1537-6613
We compared the blood RNA transcriptome of children hospitalized with influenza A H1N1/09, respiratory syncytial virus (RSV) or bacterial infection, and healthy controls. Compared to controls, H1N1/09 patients showed increased expression of inflammatory pathway genes and reduced expression of adaptive immune pathway genes. This was validated on an independent cohort. The most significant function distinguishing H1N1/09 patients from controls was protein synthesis, with reduced gene expression. Reduced expression of protein synthesis genes also characterized the H1N1/09 expression profile compared to children with RSV and bacterial infection, suggesting that this is a key component of the pathophysiological response in children hospitalized with H1N1/09 infection.
Kaforou M, Wright VJ, Oni T, et al., 2013, Detection of Tuberculosis in HIV-Infected and -Uninfected African Adults Using Whole Blood RNA Expression Signatures: A Case-Control Study., Plos Medicine, Vol: 10
Background: A major impediment to tuberculosis control in Africa is the difficulty in diagnosing active tuberculosis (TB),particularly in the context of HIV infection. We hypothesized that a unique host blood RNA transcriptional signature woulddistinguish TB from other diseases (OD) in HIV-infected and -uninfected patients, and that this could be the basis of a simplediagnostic test.Methods and Findings: Adult case-control cohorts were established in South Africa and Malawi of HIV-infected or -uninfected individuals consisting of 584 patients with either TB (confirmed by culture of Mycobacterium tuberculosis [M.TB]from sputum or tissue sample in a patient under investigation for TB), OD (i.e., TB was considered in the differentialdiagnosis but then excluded), or healthy individuals with latent TB infection (LTBI). Individuals were randomized intotraining (80%) and test (20%) cohorts. Blood transcriptional profiles were assessed and minimal sets of significantlydifferentially expressed transcripts distinguishing TB from LTBI and OD were identified in the training cohort. A 27 transcriptsignature distinguished TB from LTBI and a 44 transcript signature distinguished TB from OD. To evaluate our signatures, weused a novel computational method to calculate a disease risk score (DRS) for each patient. The classification based on thisscore was first evaluated in the test cohort, and then validated in an independent publically available dataset(GSE19491). In our test cohort, the DRS classified TB from LTBI (sensitivity 95%, 95% CI [87–100]; specificity 90%, 95% CI[80–97]) and TB from OD (sensitivity 93%, 95% CI [83–100]; specificity 88%, 95% CI [74–97]). In the independent validationcohort, TB patients were distinguished both from LTBI individuals (sensitivity 95%, 95% CI [85–100]; specificity 94%, 95% CI[84–100]) and OD patients (sensitivity 100%, 95% CI [100–100]; specificity 96%, 95% CI [93–100]). Limitations of our studyin
Tacke CE, Breunis WB, Hoang LT, et al., 2013, Fc-Gamma Receptor Genetic Variation In Kawasaki Disease, 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals, Publisher: WILEY-BLACKWELL, Pages: S71-S71, ISSN: 0004-3591
- Author Web Link
- Cite
- Citations: 1
Chang C-J, Kuo H-C, Chang J-S, et al., 2013, Replication and Meta-Analysis of GWAS Identified Susceptibility Loci in Kawasaki Disease Confirm the Importance of B Lymphoid Tyrosine Kinase (<i>BLK</i>) in Disease Susceptibility, PLOS ONE, Vol: 8, ISSN: 1932-6203
- Author Web Link
- Cite
- Citations: 38
Levin M, Kaforou M, Herberg J, et al., 2013, METHOD FOR CALCULATING A DISEASE RISK SCORE, PCT/GB2013/050225
The present disclosure relates to a general method for converting complex gene expression data into a simple, composite disease risk score which can be used for the development of rapid diagnostic tests suitable for clinical use for the determination of the presence of an infection or disease in a host.
Levin M, 2013, Steroids for Kawasaki disease: the devil is in the detail, HEART, Vol: 99, Pages: 69-70, ISSN: 1355-6037
- Author Web Link
- Cite
- Citations: 9
Maitland DM, 2013, Exploring mechanisms of excess mortality with early fluid resuscitation: Insights from the FEAST trial, BMC Medicine, Vol: 11
Couto-Alves A, Wright VJ, Perumal K, et al., 2013, A new scoring system derived from base excess and platelet count at presentation predicts mortality in paediatric meningococcal sepsis, CRITICAL CARE, Vol: 17, ISSN: 1466-609X
- Author Web Link
- Cite
- Citations: 19
Binder A, Martinon-Torres F, Levin M, et al., 2012, A genome-wide association study of meningococcal disease identifies novel susceptibility and severity genes in a paediatric meningococcal patient cohort, EUROPEAN JOURNAL OF PEDIATRICS, Vol: 171, Pages: 1426-1426, ISSN: 0340-6199
Renner P, Roger T, Bochud P-Y, et al., 2012, A functional microsatellite of the <i>macrophage migration inhibitory factor</i> gene associated with meningococcal disease, FASEB JOURNAL, Vol: 26, Pages: 907-916, ISSN: 0892-6638
- Author Web Link
- Cite
- Citations: 42
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.