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Muen W.J.,Royal London Hospital | Muen W.J.,Moorfields Eye Hospital | Kingston J.E.,Royal London Hospital | Kingston J.E.,Great Ormond Street Childrens Hospital | And 7 more authors.
Ophthalmology | Year: 2012

Purpose: To report the efficacy of super-selective intra-ophthalmic artery melphalan (IAM) for the treatment of refractory retinoblastoma and any associated complications of this treatment. Design: A prospective case series. Participants: Eyes with retinoblastoma that had been treated with systemic chemotherapy or local therapy and had a relapse of their condition. Methods: All patients receiving IAM between May 2009 and September 2010 were included in the study. Intra-ophthalmic artery melphalan was offered to patients who had failed to respond adequately to systemic chemotherapy and local treatment where appropriate or because of a new recurrence of retinoblastoma that could not be treated with local therapies. None of the patients were excluded because of central nervous system abnormalities. Patients received 2 treatments of IAM given 4 weeks apart. All patients received an orthoptic assessment 3 weeks after each treatment and an examination under anesthesia (EUA). A third treatment was given if an unsatisfactory response was observed on EUA after 2 treatments. Main Outcome Measures: The response of the retinoblastoma tumor(s) and any associated local side effects from the treatment. Results: A total of 15 eyes in 14 patients were treated with IAM during the study period. The mean age at the time of IAM was 31.5 months (median 17.3, range 11.2150.7 months), and the mean follow-up was 8.7 months (316.3 months). Tumor control was achieved in 12 eyes (80%), and 12 eyes (80%) had local side effects that included third cranial nerve palsy in 6 (40%), orbital edema in 3 (20%), permanent retinal detachment in 1 (7%), and vitreous hemorrhage in 4 (27%). Seven eyes (47%) developed significant retinal pigment epithelium changes. Conclusions: Intra-ophthalmic artery melphalan is an effective treatment for retinoblastoma, achieving a high level of remission in refractory tumors. It can be associated with significant local side effects that can result in loss of vision and possible amblyogenesis. Clinicians and parents need to consider the benefits and potential local side effects before embarking on treatment. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2012 American Academy of Ophthalmology.


Deep A.,King's College | Goonasekera C.D.A.,King's College | Wang Y.,King's College London | Brierley J.,Great Ormond Street Childrens Hospital
Intensive Care Medicine | Year: 2013

Background: Maintaining threshold values of cardiac output (CO) and systemic vascular resistance (SVR) when used as part of the American College of Critical Care Medicine (ACCM) haemodynamic protocol improves the outcomes in paediatric septic shock. Objective: We observed the evolution of CO and SVR during the intensive care admission of children with fluid-refractory septic shock and report this together with the eventual outcomes. Design: Prospective observational study. Setting: Tertiary care Paediatric Intensive Care Unit (PICU) in London. Methods: Children admitted in fluid refractory septic shock to the Intensive Care Unit over a period of 36 months were studied. Post liver re-transplant children and delayed septic shock admissions were excluded. A non-invasive ultrasound cardiac output monitor device (USCOM) was used to measure serial haemodynamics. Children were allocated at presentation into one of two categories: (1) hospital-acquired infection and (2) community-acquired infection. Vasopressor, inotrope or inodilator therapies were titrated to maintain threshold cardiovascular parameters as per the ACCM guidelines. Results: Thirty-six children [19 male, mean age (SD) 6.78 (5.86) years] were admitted with fluid-refractory septic shock and studied. At presentation, all 18 children with hospital-acquired (HA) sepsis and 3 from among the community-acquired (CA) sepsis group were in 'warm shock' (SVRI < 800 dyne s/cm5/m2) whereas 15 of the 18 children with community-acquired sepsis and none in the hospital-acquired group were in 'cold shock' [cardiac index (CI) < 3.3 l/min/m2]. All 21 children in 'warm shock' were initially commenced on a vasopressor (noradrenaline). Despite an initial good response, four patients developed low CI and needed adrenaline. Similarly, all 15 children in cold shock were initially commenced on adrenaline. However, two of them subsequently required noradrenaline. Five others needed milrinone as an inodilator. In general, both groups of children had normalised SVRI and CI within 42 h of therapy but required variable doses of vasopressors, inotropes or inodilators in a heterogeneous manner. The overall 28-day survival rate was 88.9 % in both groups. Central venous oxygen saturation (ScvO2) was significantly (p = 0.003) lower in the community-acquired group (mean 51.72 % ± 4.26) when compared to the hospital-acquired group (mean 58.72 % ± 1.36) at presentation but showed steady improvement during therapy. Gram-positive organisms were predominant in blood cultures, 61 % in HA and 56 % in CA groups. Conclusions: In general, we found children with community-acquired septic shock presented in cold shock whereas hospital-acquired septic shock children manifested warm shock. Both types evolved in a heterogeneous manner needing frequent revision of cardiovascular support therapy. However the 28-day survival in both groups was the same at 89 %. Frequent measurements of haemodynamics using non-invasive ultrasound helped in fine tuning cardiovascular therapies. © 2013 Springer-Verlag Berlin Heidelberg and ESICM.


Abbasi-Moheb L.,Max Planck Institute for Molecular Genetics | Abbasi-Moheb L.,University of Social Welfare and Rehabilitation Sciences | Mertel S.,Free University of Berlin | Gonsior M.,Free University of Berlin | And 20 more authors.
American Journal of Human Genetics | Year: 2012

With a prevalence between 1 and 3%, hereditary forms of intellectual disability (ID) are among the most important problems in health care. Particularly, autosomal-recessive forms of the disorder have a very heterogeneous molecular basis, and genes with an increased number of disease-causing mutations are not common. Here, we report on three different mutations (two nonsense mutations, c.679C>T [p.Gln227*] and c.1114C>T [p.Gln372*], as well as one splicing mutation, g.6622224A>C [p.Ile179Argfs*192]) that cause a loss of the tRNA-methyltransferase-encoding NSUN2 main transcript in homozygotes. We identified the mutations by sequencing exons and exon-intron boundaries within the genomic region where the linkage intervals of three independent consanguineous families of Iranian and Kurdish origin overlapped with the previously described MRT5 locus. In order to gain further evidence concerning the effect of a loss of NSUN2 on memory and learning, we constructed a Drosophila model by deleting the NSUN2 ortholog, CG6133, and investigated the mutants by using molecular and behavioral approaches. When the Drosophila melanogaster NSUN2 ortholog was deleted, severe short-term-memory (STM) deficits were observed; STM could be rescued by re-expression of the wild-type protein in the nervous system. The humans homozygous for NSUN2 mutations showed an overlapping phenotype consisting of moderate to severe ID and facial dysmorphism (which includes a long face, characteristic eyebrows, a long nose, and a small chin), suggesting that mutations in this gene might even induce a syndromic form of ID. Moreover, our observations from the Drosophila model point toward an evolutionarily conserved role of RNA methylation in normal cognitive development. © 2012 by The American Society of Human Genetics. All rights reserved.


Sklia D.,City University London | Kyriacou P.A.,City University London | Petros A.J.,Great Ormond Street Childrens Hospital
IFMBE Proceedings | Year: 2016

Sidestream dark field (SDF) spectral imaging has been used to take pictures of capillaries within the skin. The most common location to place the SDF is the mucosa area in the mouth. However, in neonates the sublingual area is not easily accessible, thus an optimal location on the skin should be found. This feasibility study aims to determine the optimal site, out of five body areas on the neonate from which to obtain image of capillary microcirculation. These preliminary results indicate that the chest wall can be considered as the optimal measurement location on the skin when using the SDF modality. © Springer International Publishing Switzerland 2016.


O'Connor G.,Great Ormond Street Childrens Hospital | O'Connor G.,University College London | Nicholls D.,Foundation Medicine
Nutrition in Clinical Practice | Year: 2013

The rate of adolescents presenting with anorexia nervosa (AN) is increasing. Medically unstable adolescents are admitted to the hospital for nutrition restoration. A lack of global consensus on appropriate refeeding practices of malnourished patients has resulted in inconsistent refeeding practices. Refeeding hypophosphatemia (RH) is the most common complication associated with refeeding the malnourished patient. This review sought to identify the range of refeeding rates adopted globally and the implication that total energy intake and malnutrition may have on RH while refeeding adolescents with anorexia nervosa. Studies were identified by a systematic electronic search of medical databases from 1980 to September 2012. Seventeen publications were identified, including 6 chart reviews, 1 observational study, and 10 case reports, with a total of 1039 subjects. The average refeeding energy intake was 1186 kcal/d, ranging from 125-1900 kcal/d, with a mean percentage median body mass index (% mBMI) of 78%. The average incidence rate of RH was 14%. A significant correlation between malnutrition (% mBMI) and post-refeeding phosphate was identified (R2 = 0.6, P =.01). This review highlights the disparity in refeeding rates adopted internationally in treating malnourished adolescents with anorexia nervosa. Based on this review, the severity of malnutrition seems to be a marker for the development of RH more so than total energy intake. © 2013 American Society for Parenteral and Enteral Nutrition.


Warne S.A.,Great Ormond Street Childrens Hospital | Hiorns M.P.,Great Ormond Street Childrens Hospital | Curry J.,Great Ormond Street Childrens Hospital | Mushtaq I.,Great Ormond Street Childrens Hospital
Archives of Disease in Childhood | Year: 2011

Persistent cloaco is the most severe type of anorectal malformation encountered in children. Patients with cloacal anomalies have a high incidence of associated anomalies most commonly: urinary tract and spinal. Persistent cloaca remains a difficult reconstructive challenge but it is now possible to anatomically correct the defect with surgery in the majority of patients. This review discusses embryology, prenatal diagnosis, neonatal physical and radiological findings. A summary of early management and investigation is provided and the commonest surgical reconstruction techniques are discussed. The main goals of surgical reconstruction are the achievement of bowel and bladder control for the child and normal sexual function in adult life. Although the majority of cloaca patients can achieve faecal and urinary continence with the surgical reconstructive procedures performed today, many require additional/ multiple urological procedures to achieve continence, treat bladder dysfunction and to protect renal function. One half of patients will develop renal failure, so regular and life long surveillance is mandatory. Due to the high number of associated gynaecological problems all patients should be assessed by a paediatric gynaecologist at puberty.


Bullock P.,King's College | Dunaway D.,Great Ormond Street Childrens Hospital | McGurk L.,Northumbria University | Richards R.,Cavendish Imaging
International Journal of Oral and Maxillofacial Surgery | Year: 2013

This technical note demonstrates the benefits of preoperative planning, involving the use of rapid prototype models and rehearsal of the surgical procedure, using image-guided navigational surgery. Optimum reconstruction of large defects can be achieved with this technique. © 2013 International Association of Oral and Maxillofacial Surgeons.


Muenzer J.,University of North Carolina at Chapel Hill | Beck M.,University Hospital Freiburg | Giugliani R.,Federal University of Rio Grande do Sul | Suzuki Y.,Gifu University | And 4 more authors.
Genetics in Medicine | Year: 2011

Purpose: To use the Hunter Outcome Survey, an international database, to assess the safety and effectiveness of enzyme replacement therapy with idursulfase in patients with Hunter syndrome who started treatment before 6 years of age. Methods: The study population included all patients enrolled in the Hunter Outcome Survey who started idursulfase infusions (0.5 mg/kg every other week) before 6 years of age and who had at least one follow-up examination recorded. Results: The study population included 124 patients, younger than 6 years, who had a mean age at start of idursulfase of 3.6 ± 1.6 years (mean ± SD). The mean duration of treatment was 22.9 ± 14.6 months. A total of 69 infusion-related reactions occurred in 33 (26.6%) patients, including three serious infusion-related reactions occurring in a single patient. After at least 6 months of idursulfase, urine glycosaminoglycan levels decreased from 592 ± 188 to 218 ± 115 μg/mg creatinine (P < 0.0001, n = 34). Liver size, estimated by palpation, was also significantly decreased (P = 0.005, n = 23). Similar safety and effectiveness results were seen in patients who were aged 6 years or older when initiating idursulfase. CONCLUSION:: No new safety concerns were identified in patients younger than 6 years, and clinical benefit was suggested by the reduction in liver size. © 2011 Lippincott Williams & Wilkins.


Yubero D.,Hospital Sant Joan Of Deu And Ciberer Isciii | Montero R.,Hospital Sant Joan Of Deu And Ciberer Isciii | Artuch R.,Hospital Sant Joan Of Deu And Ciberer Isciii | Land J.M.,National Hospital for Neurology and Neurosurgery | And 2 more authors.
Molecular Syndromology | Year: 2014

Coenzyme Q10 (CoQ10) deficiency appears to have a particularly heterogeneous clinical presentation. However, there appear to be 5 recognisable clinical phenotypes: encephalomyopathy, severe infantile multisystemic disease, nephropathy, cerebellar ataxia, and isolated myopathy. However, although useful, clinical symptoms alone are insufficient for the definitive diagnosis of CoQ10 deficiency which relies upon biochemical assessment of tissue CoQ10 status. In this article, we review the biochemical methods used in the diagnosis of human CoQ10 deficiency and indicate the most appropriate tissues for this evaluation. © 2014 S. Karger AG, Basel.


O'Connor G.,Great Ormond Street Childrens Hospital | Goldin J.,Great Ormond Street Childrens Hospital
International Journal of Eating Disorders | Year: 2011

Objective: A 10-year-old girl with anorexia nervosa developed the refeeding syndrome following cautious reintroduction of nutrition, emphasizing that even with cautious refeeding a shift in fluid, glucose, and electrolytes can still occur, increasing the risk of morbidity and mortality in this ever growing vulnerable group. Method: Biochemical, nutritional, and anthropometrical monitoring in the patient, who followed a conservative refeeding program after a prolonged period of nutritional inadequacy. Results: The refeeding syndrome presented itself with hypophosphatemia, hypotension, and cardiac abnormalities whilst refeeding at 25 kcal/kg (600 kcal/day). Discussion: Comprises of a literature review, highlighting this case as the youngest reported case of refeeding syndrome in anorexia nervosa. Discussion focuses on the possible deleterious affects that carbohydrates may have in exacerbating the refeeding syndrome. © 2010 by Wiley Periodicals, Inc. Copyright © 2009 Wiley Periodicals, Inc.

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