Alder Hey Childrens NHS Trust

Liverpool, United Kingdom

Alder Hey Childrens NHS Trust

Liverpool, United Kingdom
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Ranghini E.,University of Liverpool | Mora C.F.,University of Liverpool | Edgar D.,University of Liverpool | Kenny S.E.,Alder Hey Childrens NHS Trust | And 2 more authors.
PLoS ONE | Year: 2013

We have recently shown that kidney-derived stem cells (KSCs) isolated from the mouse newborn kidney differentiate into a range of kidney-specific cell types. However, the functionality and integration capacity of these mouse KSCs remain unknown. Therefore, the main objectives of this study were (1) to determine if proximal tubule-like cells, generated in vitro from KSCs, displayed absorptive function typical of proximal tubule cells in vivo, and (2) to establish whether the ability of KSCs to integrate into developing nephrons was comparable with that of metanephric mesenchyme (MM), a transient population of progenitor cells that gives rise to the nephrons during kidney organogenesis. We found that proximal tubule-like cells generated in vitro from mouse KSCs displayed megalin-dependent absorptive function. Subsequently, we used a chimeric kidney rudiment culture system to show that the KSCs could generate proximal tubule cells and podocytes that were appropriately located within the developing nephrons. Finally, we compared the ability of KSCs to integrate into developing kidneys ex vivo with that of metanephric mesenchyme cells. We found that KSCs integrated into nascent nephrons to a similar extent as metanephric mesenchyme cells while both were excluded from ureteric bud branches. Our analysis of the behavior of the two cell types shows that some, but not all KSC characteristics are similar to those of the MM. © 2013 Ranghini et al.


Michael B.,Walton Center for Neurology and Neurosurgery Trust | Michael B.,University of Liverpool | Menezes B.F.,Walton Center for Neurology and Neurosurgery Trust | Cunniffe J.,Arrowe Park Hospital | And 6 more authors.
Emergency Medicine Journal | Year: 2010

Introduction: Bacterial meningitis is a medical emergency, the outcome of which is improved by prompt antibiotic treatment. For patients with suspected meningitis and no features of severe disease, the British Infection Society recommends immediate lumbar puncture (LP) before antibiotics, to maximise the chance of a positive cerebrospinal (CSF) culture. In such patients, CT scanning before LP is not needed. Methods: The case notes of adults with meningitis admitted to a large district general hospital over 3 years were reviewed. Patients were classified as Likely Bacterial Meningitis or Likely Viral Meningitis based on their CSF and peripheral blood results using the Meningitest Criteria, with microbiological and virological confirmation. Results: Of 92 patients studied, 24 had Likely Bacterial Meningitis, including 16 with microbiologically confirmed disease (none had PCR tests for bacteria). Sixty-eight had Likely Viral Meningitis, four of whom had viral PCR, including one with herpes simplex virus. No patient had an LP before antibiotics. CSF culture was positive for eight (73%) of the 11 patients who had an LP up to 4 h after starting antibiotics, compared with eight (11%) of 71 patients with a later LP (p<0.001). None of the 34 LPs performed more than 8 h after antibiotics was culture-positive. For 62 (67%) of the 92 patients, the delay was due to a CT scan, although only 20 of these patients had a contraindication to an immediate LP. Conclusions: Too many patients with acute bacterial meningitis are being sent for unnecessary CT scans, causing delays in the LP, and reducing the chances of a positive CSF culture after starting antibiotics. However, even if antibiotics have been started, an LP within 4 h is still likely to be positive. Molecular tests for diagnosis should also be requested.


Fuente Mora C.,University of Liverpool | Ranghini E.,University of Liverpool | Bruno S.,University of Turin | Bussolati B.,University of Turin | And 5 more authors.
Stem Cells and Development | Year: 2012

In this study we have shown that the papilla of the mouse kidney contains a population of Pax2+ cells that are detectable from the early postnatal period through to adulthood. Lineage analysis suggests that some of these Pax2+ cells are derived from the metanephric mesenchyme, a population of progenitor cells that gives rise to the nephrons during kidney organogenesis. Here we describe a method for isolating and culturing the Pax2+ population, and demonstrate that some cells within this population are multipotent stem cells, as they are clonogenic and appear to undergo unlimited self-renewal. Further, under appropriate culture conditions, these stem cells can differentiate to generate renal cell types, such as podocyte- and proximal tubule-like cells, and are also able to generate nonrenal cell types, such as adipocytes and osteocytes. The availability of a kidney-derived multipotent stem cell line with the potential to generate podocytes and proximal tubule cells in culture will expedite progress in understanding the biology of these important renal cell types, and will be a useful tool in toxicological studies and drug discovery. © Copyright 2012, Mary Ann Liebert, Inc.


Veal G.J.,Northumbria University | Errington J.,Northumbria University | Hayden J.,Alder Hey Childrens NHS Trust | Hobin D.,Birmingham Childrens Hospital | And 6 more authors.
European Journal of Cancer | Year: 2015

Introduction Administration of the most appropriate dose of chemotherapy to neonates is particularly challenging and frequently not standardised based on any scientific rationale. We report the clinical utility of carboplatin therapeutic drug monitoring in preterm and full-term neonates within the first month of life. Methods Carboplatin therapeutic monitoring was performed to achieve target drug exposures area under the plasma concentration-time curve (AUC values) in nine preterm and full-term neonates diagnosed with retinoblastoma or neuroblastoma treated over an 8 year period. Carboplatin was administered over 3 days with therapeutic drug monitoring utilised to target cumulative AUC values of 5.2-7.8 mg/ml min. Results AUC values achieved were within 15% of target values for the individual courses of treatment in all but one patient (12/13 courses of treatment), with dose modifications of up to 215% required to achieve target AUC values, based on initial mg/kg dosing schedules. Carboplatin clearance determined across three consecutive chemotherapy courses in two patients increased from 3.4 to 7.1 ml/min and from 7.2 to 16.5 ml/min, representing increases of 210-230% over several weeks of treatment. Complete remission was observed in 8/9 patients, with no renal toxicity reported and only one patient experiencing ototoxicity. Conclusion The study highlights the benefits of utilising therapeutic drug monitoring to achieve target carboplatin AUC values in preterm and full-term neonates treated within the first few weeks of life, particularly in view of marked increases in drug clearance observed over consecutive chemotherapy courses. In the absence of therapeutic drug monitoring, body-weight based dosing is recommended, with dosing guidance provided for both approaches to inform future treatment. © 2015 The Authors.


Murray P.,University of Liverpool | Vasilev K.,University of South Australia | Mora C.F.,University of Liverpool | Ranghini E.,University of Liverpool | And 6 more authors.
Biochemical Society Transactions | Year: 2010

In the future, stem-cell-based therapies could offer new approaches to treat kidney disease and reduce the incidence of ESRD (end-stage renal disease), but, as yet, research in this area is only being conducted in rodents and it is not clear whether or when it could be applied to human patients. Drug therapies, on the other hand, have been very effective at delaying the progression of kidney disease, but, for various reasons, current drug regimes are not suitable for all patients. A greater understanding of the molecular mechanisms that underlie disease progression in chronic kidney disease could help to identify novel drug targets. However, progress in this area is currently hindered due to the lack of appropriate in vitro culture systems for important renal cell types, such as proximal tubule cells and podocytes. This problem could be overcome if it were possible to direct the differentiation of kidney stem cells to renal cell types in vitro. In the present review, we highlight the potential of surface gradients of small chemical functional groups to direct the differentiation of kidney stem cells. ©The Authors.


Elsone L.,Walton Center Foundation Trust | Panicker J.,Walton Center Foundation Trust | Mutch K.,Walton Center Foundation Trust | Boggild M.,Townsville Hospital | And 2 more authors.
Multiple Sclerosis Journal | Year: 2014

Prompt treatment of neuromyelitis optica (NMO) relapses with steroids or plasma exchange (PLEX) often prevents irreversible disability. The objective of this study is to report the use of intravenous immunoglobulins (IVIG) as treatment for acute relapses in NMO. A retrospective review of 10 patients treated with IVIG for acute relapses was conducted. IVIG was used in the majority of cases because of lack of response to steroids with/without PLEX. Improvement was noted in five of 11 (45.5%) events; the remaining had no further worsening. One patient, a 79-year-old woman, had a myocardial infarction seven days after IVIG. IVIG may have a role in treating acute NMO relapses. © The Author(s) 2013.


White H.D.,University of Liverpool | Goenka N.,Countess of Chester NHS Trust | Furlong N.J.,St Helens and Knowsley NHS Trust | Saunders S.,Warrington and Halton Hospitals NHS Trust | And 5 more authors.
Diabetic Medicine | Year: 2014

Aims: The National Institute for Health and Clinical Excellence (NICE) published guidelines for the use of continuous subcutaneous insulin infusion in 2008 (technology appraisal 151). The first UK-wide insulin pump audit took place in 2012 with the aim of determining adherence to the guidance issued in NICE technology appraisal 151. The results of the adult service level audit are reported here. Methods: All centres providing continuous subcutaneous insulin infusion services to adults with diabetes in the UK were invited to participate. Audit metrics were aligned to technology appraisal 151. Data entry took place online using a DiabetesE formatted data collection tool. Results: One hundred and eighty-three centres were identified as delivering adult continuous subcutaneous insulin infusion services in the UK, of which 178 (97.3%) participated in the audit. At the time of the audit, 13 428 adults were using insulin pump therapy, giving an estimated prevalence of use of 6%. Ninety-three per cent of centres did not report any barriers in obtaining funding for patients who fulfilled NICE criteria. The mean number of consultant programmed activities dedicated to continuous subcutaneous insulin infusion services was 0.96 (range 0-8), mean whole-time equivalent diabetes specialist nurses was 0.62 (range 0-3) and mean whole-time equivalent dietitian services was 0.3 (range 0-2), of which 39, 61 and 60%, respectively, were not formally funded. Conclusions: The prevalence of continuous subcutaneous insulin infusion use in the UK falls well below the expectation of NICE (15-20%) and that of other European countries (> 15%) and the USA (40%). This may be attributable, in part, to lack of healthcare professional time needed for identification and training of new pump therapy users. © 2013 Diabetes UK.


PubMed | Bristol Royal Hospital for Children, Alder Hey Childrens NHS Trust, Royal Hospital for Sick Children, Northumbria University and 2 more.
Type: Journal Article | Journal: European journal of cancer (Oxford, England : 1990) | Year: 2015

Administration of the most appropriate dose of chemotherapy to neonates is particularly challenging and frequently not standardised based on any scientific rationale. We report the clinical utility of carboplatin therapeutic drug monitoring in preterm and full-term neonates within the first month of life.Carboplatin therapeutic monitoring was performed to achieve target drug exposures area under the plasma concentration-time curve (AUC values) in nine preterm and full-term neonates diagnosed with retinoblastoma or neuroblastoma treated over an 8 year period. Carboplatin was administered over 3 days with therapeutic drug monitoring utilised to target cumulative AUC values of 5.2-7.8 mg/ml min.AUC values achieved were within 15% of target values for the individual courses of treatment in all but one patient (12/13 courses of treatment), with dose modifications of up to 215% required to achieve target AUC values, based on initial mg/kg dosing schedules. Carboplatin clearance determined across three consecutive chemotherapy courses in two patients increased from 3.4 to 7.1 ml/min and from 7.2 to 16.5 ml/min, representing increases of 210-230% over several weeks of treatment. Complete remission was observed in 8/9 patients, with no renal toxicity reported and only one patient experiencing ototoxicity.The study highlights the benefits of utilising therapeutic drug monitoring to achieve target carboplatin AUC values in preterm and full-term neonates treated within the first few weeks of life, particularly in view of marked increases in drug clearance observed over consecutive chemotherapy courses. In the absence of therapeutic drug monitoring, body-weight based dosing is recommended, with dosing guidance provided for both approaches to inform future treatment.


PubMed | Alder Hey Childrens NHS Trust
Type: Journal Article | Journal: Journal of children's orthopaedics | Year: 2016

Congenital vertical talus (CVT) is a rare deformity. Traditionally, CVT correction involved extensive soft tissue releases, and this was associated with high complication rates. The Dobbs method is less invasive and comprises serial manipulation and casting, followed by minimally invasive reduction and K-wire fixation of the talonavicular joint and percutaneous Achilles tenotomy.The purpose of our study was to compare the outcomes of using the Dobbs method for CVT correction in idiopathic and teratological patients.A retrospective analysis of all patients treated with the Dobbs method for CVT between the years 2007 and 2012 was carried out. Notes, electronic records and radiographs were reviewed for every patient. The Oxford ankle foot score was obtained at follow-up.There was a total of ten children with 18 affected feet. Five children (ten feet) had teratological CVT. Recurrence was noted in six feet (two from the idiopathic group and four from the teratological group). The median age was 5months (range 2-8months). The mean follow-up was 53months (range 24-80months). There was a significant difference between pre-operative to initial post-operative and pre-operative to latest follow-up measurements for all angles in the successfully treated CVT group (p<0.000001). The mean Oxford ankle foot scores for each domain in all patients are 59.9 (physical), 88.8 (school and play) and 99.1 (emotional).The Dobbs method is a less invasive technique of CVT correction. It is an effective initial method of treatment in both teratological and idiopathic patients. A higher recurrence rate was observed in the teratological group, although this was not statistically significant.

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