Newcastle upon Tyne, United Kingdom
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Kang E.,National Institute of Allergy and Infectious Diseases | Gennery A.,Great North Childrens Hospital
Hematology/Oncology Clinics of North America | Year: 2014

Allogeneic hematopoietic stem cell transplantation has been shown to be curative for well-described as well as newly discovered immunodeficiencies. However, it is difficulty to define a universal transplant regimen given the rarity of these disorders and the varied pathophysiology these disorders encompass. This article discusses those primary immunodeficiencies most commonly treated by hematopoietic stem cell transplant and describes the transplant issues specific to these disorders. © 2014.


Cowan M.J.,University of California at San Francisco | Gennery A.R.,Great North Childrens Hospital
Journal of Allergy and Clinical Immunology | Year: 2015

Defects in DNA cross-link repair 1C (DCLRE1C), protein kinase DNA activated catalytic polypeptide (PRKDC), ligase 4 (LIG4), NHEJ1, and NBS1 involving the nonhomologous end-joining (NHEJ) DNA repair pathway result in radiation-sensitive severe combined immunodeficiency (SCID). Results of hematopoietic cell transplantation for radiation-sensitive SCID suggest that minimizing exposure to alkylating agents and ionizing radiation is important for optimizing survival and minimizing late effects. However, use of preconditioning with alkylating agents is associated with a greater likelihood of full T- and B-cell reconstitution compared with no conditioning or immunosuppression alone. Areduced-intensity regimen using fludarabine and low-dose cyclophosphamide might be effective for patients with LIG4, NHEJ1, and NBS1 defects, although more data are needed to confirm these findings and characterize late effects. For patients with mutations in DCLRE1C (Artemis-deficient SCID), there is no optimal approach that uses standard dose-alkylating agents without significant late effects. Until nonchemotherapy agents, such as anti-CD45 or anti-CD117, become available, options include minimizing exposure to alkylators, such as single-agent low-dose targeted busulfan, or achieving T-cell reconstitution, followed several years later with a conditioning regimen to restore B-cell immunity. Gene therapy for these disorders will eventually remove the issues of rejection and graft-versus-host disease. Prospective multicenter studies are needed to evaluate these approaches in this rare but highly vulnerable patient population. © 2015 American Academy of Allergy, Asthma & Immunology.


Bailey S.,Great North Childrens Hospital | Parkes J.,University of Cape Town
Clinical Endocrinology | Year: 2015

A 13-year-old male presents with fluctuating visual disturbance and headaches. Imaging reveals a significant predominantly cystic suprasellar tumour, typical of a craniopharyngioma. The patient has growth hormone deficiency but the rest of the hypothalamic/ pituitary axis is intact. What are the options for therapy in 2014? Specifically, is there a role for local treatment with interferon injected into the cyst cavity? The aim of management in children with craniopharyngiomas is to reduce the impact of the tumour as much as possible, while minimising the morbidity associated with treatment. There are a number of therapeutic options available: surgery, radiotherapy and the insertion of therapeutic agents directly into the tumour cyst. The role of intracystic therapy in the form of interferon is discussed; including when to use this therapeutic option and practical details of its use. © 2014 John Wiley & Sons Ltd.


Johnson S.,Great North Childrens Hospital | Waters A.,University College London
Immunobiology | Year: 2012

Haemolytic uraemic syndrome (HUS) accounts for the most common cause of childhood acute renal failure. Characterized by the classical triad of a microangiopathic haemolytic anaemia, thrombocytopaenia and acute renal failure, HUS occurs as a result of Shiga-toxin producing microbes in 90% of cases. The remaining 10% of cases represent a heterogeneous subgroup in which inherited and acquired forms of complement dysregulation have been described in up to 60%. Emerging evidence suggests that microbes associated with HUS exhibit interaction with the complement system. With the advent of improved genetic diagnosis, it is likely that certain cases of infection-induced HUS may be attributed to underlying defects in complement components. This review summarises the interplay between complement and infection in the pathogenesis of HUS. © 2011 Elsevier GmbH.


Vormoor B.,Northumbria University | Vormoor B.,Great North Childrens Hospital | Curtin N.J.,Northumbria University
Current Opinion in Oncology | Year: 2014

In 2012, two publications revealed a particular sensitivity of Ewing sarcoma cells to the inhibition of poly(ADP-ribose) polymerase (PARP). This review updates the reader on PARP function, the development of PARP inhibitors (PARPi) and the evidence for targeting PARP in Ewing sarcoma. It concludes with a description of ongoing/emerging PARPi clinical trials in patients with Ewing sarcoma. RECENT FINDINGS: PARP has a major role in DNA repair, and is a transcription regulator. The oncoprotein in Ewing sarcoma, EWS-FLI1, is proposed to interact with PARP-1, driving PARP-1 expression, which further promotes transcriptional activation by EWS-FLI1. Thus, there are two rationales for PARPi in the treatment of Ewing sarcoma: to disrupt the interaction between EWS-FLI1 and PARP, and for chemo-potentiation or radio-potentiation. The first clinical trial with a single agent PARPi failed to show significant responses, but preclinical evidence for combinations of PARPi with chemotherapy or radiotherapy is very promising. SUMMARY: Despite initial excitement for the potential of PARPi as single agent therapy in Ewing sarcoma, the emerging preclinical data now strongly support testing PARPi in combination with chemo/radiotherapy clinically. Copyright © Lippincott Williams & Wilkins.


Elemraid M.,Great North Childrens Hospital
Nursing children and young people | Year: 2013

To observe and report rates of, and reasons for, parents' refusal to consent to the participation of their children in appropriate clinical research. The parents of children admitted to hospital with a diagnosis of pneumonia or of empyema were asked for informed consent to research involving blood, urine and nasopharyngeal secretion samples from their child. Circumstances and numbers of agreements and refusals were compared and underlying reasons suggested. Of 144 consent requests, ten were refused, which appeared to be linked to: not wanting the child to undergo further tests, lack of interest in participating in studies, research possibly delaying discharge, and anxiety regarding written consent and the length of information sheets. Severity of the child's illness appeared to determine the parent's decision. Involvement and assistance of non-research nursing and medical staff and previous introductions to the researchers are helpful. The timing and setting for the consent process should be selected carefully. Adequate, accessible study information for parents and children contributes to successful recruitment of participants.


Reynolds B.C.,Great North Childrens Hospital | Cheetham T.D.,Great North Childrens Hospital
Archives of Disease in Childhood: Education and Practice Edition | Year: 2015

Disorders of calcium homeostasis are uncommon but important because of the broad spectrum of potential underlying causes that lie on a spectrum from the benign to the life-threatening. Paediatricians may find them challenging because they do not arise often enough for the investigative approach to be second nature. We report a 4-year-old with acute onset profound hypercalcaemia. We focus on an approach to the clinical problem that is based on the potential organ systems affected, namely the gut, bone and kidney. Key biochemical parameters that may help the paediatric team to reach a diagnosis are discussed, as well as important components of acute management.


Innes R.F.,Great North Childrens Hospital
Nursing children and young people | Year: 2015

The most common background to hyperpyrexia and convulsions is immaturity of the child's physiological reactions to infection, so an understanding of the pathophysiology of pyrexia and febrile convulsions in young children enables nurses to take appropriate action. Correct management involves prompt recognition of rising temperature, administration of antipyretic medication, use of other cooling strategies and careful monitoring. Diagnosis of the underlying cause occasionally requires laboratory investigation, if no focus for infection is found, most cases being viral.


Anderson M.,Great North Childrens Hospital
Patient Preference and Adherence | Year: 2013

Prolonged seizures and status epilepticus are a common acute neurological presentation in pediatric practice. As a result, there is a need for effective and safe medications that can be delivered to convulsing children to effect rapid seizure termination both in hospital and community settings. The challenges of achieving intravenous access, particularly in young children, mandate alternative routes of administration for these drugs. Over the last ten years, midazolam delivered via the buccal mucosa has been demonstrated to be efficacious, safe, and acceptable to children and their caregivers, and a formulation has recently been licensed for use in Europe. The aim of this article is to review the clinical pharmacology with respect to these issues. © 2013 Anderson, publisher and licensee Dove Medical Press Ltd.


Lamb W.H.,Great North Childrens Hospital
Practical Diabetes | Year: 2012

Given the enormous changes in physiology and neurobiology prevalent during adolescence, it is hardly surprising that this is also the time when metabolic control of diabetes is at its worst. Clinical teams are constantly looking for ways to improve diabetes control in youth and exploiting the perceived fascination of adolescents for new technology offers an attractive option. The management of type 1 diabetes has always been heavily influenced by new developments and this personal review, influenced by a long experience of working with adolescents, explores how some of the emerging technologies have been used in an attempt to influence diabetes control in this challenging age group. Copyright © 2012 John Wiley & Sons.

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