Complexation of ferrous ions by ferrozine, 2,2'-bipyridine and 1,10-phenanthroline: Implication for the quantification of iron in biological systems.

Iron is an essential nutrient for virtually all forms of life. Because of its redox properties and involvement in a wide range of biological processes, a number of qualitative and quantitative chemical tools have been developed to detect reduced (Fe2+) and oxidized (Fe3+) forms of iron in biomolecules. These types of measurements are not only important in detecting iron species in solution, but also in understanding iron distribution, accumulation, and role in physiological and pathological processes. Here, we use UV-vis spectrophotometry and three common chromogenic reagents, ferrozine, 2,2'-bipyridine, and 1,10-phenanthroline to detect and quantify the concentration of ferrous ions in aqueous solutions, owing to the unique absorption spectra, specific molar absorptivity, and characteristic colors of these Fe2+-chelator complexes. Our results show that the kinetics of the formation of the {Fe2+-(ferrozine)3} complex, but not the{Fe2+-(bipyridine)3} or the {Fe(II)-(phenanthroline)3} complexes depend on the concentration of the iron chelator, requiring up to 20 min to complete when close to stoichiometric ratios are employed. The molar absorptivity values of these complexes under excess chelator concentrations were ~ 10% to 15% higher than reported literature values (i.e. 31,500 ± 1500 M-1 cm-1 for ferrozine at 562 nm, 9950 ± 100 M-1 cm-1 for 2,2'-bipyridine at 522 nm, and 12,450 ± 370 M-1 cm-1 for 1,10-phenanthroline at 510 nm). Our results have important implications when quantifying iron in biological systems and reveal optimal experimental conditions that must be employed for the accurate measurements of ferrous ions, whether free in solution, or after reduction of protein-bound ferric ions.

Absence of urinary opioid peptides in children with autism.

OBJECTIVE: It has been claimed for a number of years that the urine of children with autism contains exogenously derived opioid peptides. This finding is said to reflect a disturbance in the integrity of the gut epithelium, act as a diagnostic marker for autism and predict treatment response to a diet excluding gluten and casein. The aim of the present study was to determine whether exogenous or endogenous peptides were present in the urine of children with autism or of control children. DESIGN: Case-control study SETTING: Cases were recruited from two tertiary referral centres specialising in autistic spectrum disorders, while controls were recruited from mainstream primary and secondary schools in the same geographical area. PARTICIPANTS: 65 boys with autism, mean age 7.4 years (range 5-11) and 158 control boys, mean age 7.8 years (range 4.2-11). INVESTIGATIONS: Urine samples were examined by high pressure liquid chromatography (HPLC) and matrix assisted laser desorbtion ionisation-time of flight mass spectrometry (MALDI-TOF MS) for the presence of a number of putative opioid peptides. OUTCOMES: There were no significant differences between the HPLC urinary profiles of the children affected by autism and the typically developing controls. In those cases where HPLC showed peaks in the locations at which opioid peptides might be expected to be found, MALDI-TOF established that these peaks did not, in fact, represent opioid peptides. CONCLUSIONS: Given the lack of evidence for any opioid peptiduria in children with autism, opioid peptides can neither serve as a biomedical marker for autism nor be employed to predict or monitor response to a casein- and gluten-free diet.

Developing critical mass and growing our own academics.

Academic paediatrics is an exciting and rewarding career path but is not immune to the problems of recruitment and retention currently affecting most branches of medicine. The Modernising Medical Careers initiative, with its explicit academic training path, offers an unparalleled opportunity to develop novel schemes that promote recruitment and retention. Coordinated action is required to define, publicise and support the new academic training programmes and to attract the best trainees into them.

Medical investigation of children with autistic spectrum disorders.

Few well-constructed studies have systematically evaluated medical investigation protocols for children with autistic spectrum disorders. This is in large part due to the heterogeneous nature of the population and changing diagnostic frameworks. This review outlines the studies that have directed investigation strategies to date, and discusses how these might be applied in the clinical situation. The importance of listing the conditions that may be present on the basis of the specific clinical presentation, and using a thorough history and examination to generate a pre-test probability of the target disorders is emphasized if tests are to be useful in directing therapy or broader management approaches.

Medical, surgical, and health outcomes of gastrostomy feeding.

A prospective controlled study with repeated measures before and after surgery examined the medical, surgical, and health outcomes of gastrostomy for children with disabilities at a tertiary paediatric referral centre in the North Thames area, UK. Anthropometric measures included weight, mid-upper-arm and head circumference. Five-day prospective food diaries were completed and data on physical health and surgical outcomes recorded. Seventy-six children participated and underwent gastrostomy (44 males, 32 females; median age 3 y 4 mo, range 4 mo-17 y 5 mo), and 35/76 required an anti-reflux procedure. Categories of disability were: cerebral palsy (32/76), syndrome of chromosomal or other genetic origin (25/76), slowly progressive degenerative disease (11/76), and unconfirmed diagnosis (8/76). Most children had gross motor difficulties (99%) and were non-ambulant (83%). Oromotor problems were identified in 78% of children, 69% aspirated, and 65% were fed nasogastrically before surgery. The mean weight before surgery was -2.84 standard deviation score (SDS; SD 2.21, range -9.8 to 3.4). Two-thirds of children achieved catch-up growth postoperatively: weight-for-age (mean difference 0.51 SDS, 95% CI 0.23-0.79, p=0.001) and mid-upper arm circumference (mean difference 1.12 cm, 95% confidence interval 0.50-1.75, p=0.001). Health gains included a reduction in drooling, secretions, vomiting, and constipation. Major surgical complications were found in 13/74 children. The study provides evidence that catch-up growth and health gains are possible following gastrostomy.

Behaviour problems in adult women with Rett syndrome.

BACKGROUND: Despite considerable interest in the genetic, physical and neurological aspects of Rett syndrome (RS), there have been few studies of associated behavioural and emotional features. Furthermore, few case studies or surveys have included adult women with RS. The main aim of the present study was to compare behaviour problems in a sample of women with RS against data from normative samples. METHODS: The primary carers of 50 women with RS completed the community version of the Aberrant Behavior Checklist. RESULTS: Women with RS were rated as having lower levels of irritability, hyperactivity and inappropriate speech behaviours than normative samples of adults with intellectual disability. CONCLUSIONS: A number of factors may affect the presentation of behaviour problems in women with RS (e.g. cognitive impairments or physical disabilities). Therefore, more research is needed in order to generate information about the behavioural phenotype of RS. The implications of the present data for future research are also discussed.

Guidelines for reporting clinical features in cases with MECP2 mutations.

An international group recommends that papers relating phenotypes to genotypes involving mutations in the X chromosome gene MECP2 should provide a minimum data set reporting the range of disturbances frequently encountered in Rett Syndrome. A simple scoring system is suggested which will facilitate comparison among the various clinical profiles. Features are described which should prompt screening for MECP2 mutations.

Growth and nutrition in Rett syndrome.

PURPOSE/METHOD: In this paper we review the existing literature on factors that contribute to growth failure in Rett syndrome (RS) with particular emphasis on the extent and nature of the feeding difficulties that arise. Data on growth and feeding related problems, collected over four years in a specialized clinic for females with Rett syndrome are presented and management protocols developed in the clinic discussed. RESULTS/CONCLUSION: Feeding related problems and growth failure occur commonly in Rett syndrome yet our understanding of the mechanisms causing growth failure are poorly understood. Both nutritional and non-nutritional factors are thought to contribute and it has not been possible to develop efficacious intervention strategies. Consequently, clinical management of growth failure in Rett syndrome is not evidence based.

Behavioural and emotional features in Rett syndrome.

PURPOSE/METHOD: There is increasing agreement that many genetic disorders have characteristic behavioural phenotypes; that is genetic anomalies have specific effects on behaviour. In this paper the existing literature is reviewed with an aim to identify behavioural and emotional features that are candidates for Rett syndrome (RS) specific behaviours. RESULT/CONCLUSION: A number of behavioural and emotional features have been reported to be common in individuals with RS. These behaviours may constitute an RS-specific profile of behaviour or behavioural phenotype. Alternatively, these behaviours may simply reflect the multiple disabilities found in individuals with severe or profound cognitive impairment. The diagnostic criteria for Rett syndrome include a number of the behavioural features, such as hand stereotypies and breathing difficulties, although other behavioural features are not included.

A model for the assessment and management of children with multiple disabilities.

Children with multiple disabilities present complex management problems, both for their families and for the professionals involved in their care. For any one child, the list of functional and medical problems that need to be addressed is frequently reflected in an even longer list of involved professionals, leading to conflicting advice and problems in co-ordination of care. A hierarchical model for assessment and management is proposed, which highlights the interdependency of apparently different areas of functioning. The model aims to assist both parents and professionals in determining priorities, to improve interdisciplinary working, and to underpin staff training. Illustrative case studies indicate the importance of resolving issues in areas such as visual functioning, positioning and nutrition before integrated functions such as communication skills can be addressed successfully.

Service evaluation and development: experience of a paediatric disability team.

Classical audit frameworks encourage the use of audit cycles, with performance being evaluated against predefined quality targets and modified accordingly. This approach has obvious validity in clinical settings where treatments have very clear endpoints and outcome measures can be prioritized with ease. The situation becomes more complex in disability service settings, where the impact of clinical intervention is often qualitative rather than quantitative, and where management strategies are dependent on working in partnership with families, purchasers and other professional colleagues. There is thus a danger of neglecting aspects of service delivery which are of major importance to one sector of this extensive network. To ensure that service goals and standards comprehensively reflect the specific concerns of all parties, it is proposed that measures of service quality should be defined within the context of a dynamic multi-user framework. Development of such a framework is dependent on collating information on specific needs from parents, referrers, purchasers and other involved professionals, and determining areas of overlap, as well as areas of potential conflict. Audit techniques for key issues can then be devised, alongside a timetable to revisit these issues at appropriate intervals. Application of this approach is illustrated by reference to our own paediatric disability service.

Surgical treatment of severe autistic regression in childhood epilepsy.

We report 2 children with partial epilepsy who manifested social and language regression and partial recovery after surgical treatment. One child had seizures since the first 2 weeks of life, caused by a right temporal dysembryoplastic neuroepithelial tumor and regression in the latter part of the first year; seizures were relieved and some functions were recovered after temporal lobe resection at 12 months of age. The second child developed epilepsy at 3 years 3 months, and between 5 years 9 months and 6 years 1 month he became aphasic (Landau-Kleffner syndrome) and lost social functioning, manifesting a very severe behavior disorder. He exhibited a significant improvement in communication, social functioning, and behavior after left multiple subpial transections. Both children manifested evidence of subclinical seizure activity in both temporal lobes. Their clinical picture was one of combined language and autistic regression, and the autistic features demonstrated a clear response to surgical treatment. We suggest that in pediatric epilepsy surgical programs, autistic regression should prompt urgent investigation if drug treatment is not effective.

Developmental setback in severe visual impairment.

Developmental setback in children initially thought to be of normal cognitive potential is a serious complication of severe visual impairment; the prevalence, diagnostic specificity, clinical presentation, and factors that contribute to its genesis require systematic investigation. The findings are reported of a retrospective case review over a 15 year period of children attending the developmental vision clinic at the Wolfson Centre of the Institute of Child Health. One hundred and two children met the inclusion criteria of a period of normal development confirmed at initial assessment when aged less than 16 months, absence of additional disabilities, and follow up to at least 2.5 years of age. Developmental setback in their second or third year occurred in 10 (31%) of 32 children who were totally blind throughout (minimal perception of light or less), one (4%) of 25 who, though blind at first assessment, showed visual improvement, and none of 49 children with better vision throughout (awareness for near, large objects). This represents a significantly greater risk for totally blind children than for the other groups. The course and characteristics of the affected children varied, but all had visual diagnoses involving the nervous elements of the visual system, and 60% had major social adversity factors. The role of primary maldevelopment of the central nervous system, the degree of visual impairment, the developmental and emotional climate, and the stage of attentional and behavioural development in the causation of adverse developmental outcome are discussed.

Evaluation and audit in a paediatric disability service.

Parental and professional responses to questionnaires evaluating a paediatric disability service are reported and the viability of auditing structural, process, and outcome aspects of clinical practice are discussed. Expectations of waiting time to first appointment (met for only 52% of consumers) illustrate structural issues. Process issues are reflected in consumer reactions to outreach work (for example, 94% of parents and 84% of professionals found this supportive). Outcome measures such as consumer satisfaction with the service (76% of consumers reported being 'very satisfied' and 20% 'fairly satisfied') suggest that service aims are being met. Good concurrence of service aims with consumer needs is indicated by parental reasons for referral (for example, 75% for diagnostic help, 73% for a better understanding of the disorder, 88% for practical help), referrers' reasons (for example, 55% for a second diagnostic opinion, 45% due to lack of local expertise), and reports from most other professionals involved with the case that a similar service was not provided locally.