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Current Pediatric Reviews
ISSN: 1573-3963
Current Pediatric Reviews
Volume 2, Number 1, February 2006
Contents
Editorial Pp. 1
Proinflammatory Cytokines and Chemokines in Neonatal
Brain Damage Pp. 3-15
Marietta Xanthou
[Abstract]
Electroencephalographic Profiles of Children with
Symptoms of Attention Deficit Hyperactivity Disorder: A Review
of the Literature Pp. 17-32
Jennifer K. Penberthy, M. Layne Kalbfleisch, Mark Quigg, Tim
Loboschefski, Daniel Cox, Carolyn Runyon and Boris Kovatchev
[Abstract]
Non-Synostotic Plagiocephaly and Brachycephaly: An
Overview Pp. 33-39
B. Lynne Hutchison, Edwin A. Mitchell and John M.D. Thompson
[Abstract]
Pharmacological Treatment of Hypoxic-Ischemic Reperfusion
Injury of the Newborn Brain in the Clinical Setting: What
are the Possibilities in the Near Future? Pp. 41-48
Helen Torrance, Manon Benders and Frank van
Bel
[Abstract]
Cycle Helmets for Children- Education or Enforcement?
Pp. 49-52
Nicholas P. Mann and Angela Lee
[Abstract]
Nosocomial Infections In Paediatrics:
Simple Preventive Measures, Great Results
Pp. 53-61
Javier N. Guevara, Dora E. Calderón, María G.
Aramburú de la Guardia and Xavier Sáez-Llorens
[Abstract]
Chronic Granulomatous Disease in Childhood Pp.
63-75
Cecilia Barese and W. Scott Goebel
[Abstract]
Knemometry for Assessment of Growth Suppressive Effects
of Exogenous Glucocorticoids Pp. 77-83
Anders J. Schou
[Abstract]
Endocrine Abnormalities Induced by Antiepileptic Drugs
Pp. 85-92
Alberto Verrotti, Mariapaola Ciampani, Mariapina
Pomilio, Giuseppe Latini and Francesco Chiarelli
[Abstract]
Idiopathic Hypercalciuria in Children Pp.
93-98
Nicolaidou Polyxeni and Anna Papadopoulou
[Abstract]
Abstracts
[Back to top]
Editorial
Neonatal brain injury is common, essential to appropriate
treatment and prevention is a thorough understanding of the
pathogenesis. Two articles in this issue of the journal focus
on this important topic. Dr. Xanthou analyses the mechanism
through which proinflammatory cytokines and chemokines may
lead to neuro-degeneration and brain damage. The vunerability
of preterm infants to white matter damage, due to immature
oligodendrocytes and deficient endogenous protective mechanisms,
is described. Therapeutic possibilities of modifying or blocking
the activity of proinflammatory cyokines and chemokines in
preventing brain damage are discussed. Dr. Torrance and colleagues
describe mechanisms of hypoxic ischaemic reperfusion injury
and promising pharmacological neuro-protective strategies.
In addition, they discuss beneficial effects of early intervention
of combination therapy with moderate hypothermia.
Dr. Penberthy and colleagues discuss a possible advance in
the diagnosis of attention deficit/hyperactivity deficit.
Although, neither traditional nor quantitative EEG has revealed
persuasive or consistent patterns of EEG abnormalities, they
highlight that an advanced quantitative EEG analysis has yielded
promising results in small preliminary studies.
The impact of preventative measures is reviewed in several
articles. Drs. Mann and Lee emphasise that in the UK approximately
28 children die per year from cycle injuries, usually directly
attributable to head injuries. They note that helmets reduced
the risk of severe brain injury by 74% and also result in
reduction in upper and mid facial injuries. This is without
a reduction in cycling activity. The case for introduction
of legislation in more countries to maximise helmet wearing
by young cyclists is emphasised. Nosocomial infections are
a major cause of mortality and morbidity particularly amongst
vulnerable patients. There are many preventative strategies
including health care personnel education and isolation. Dr.
Saez-Llorens reminds us that hand washing is the single most
effective measure to prevent nosocomial infection. Supine
sleeping position has been associated with a reduction in
sudden infant death syndrome, but is associated with an increase
in referrals for positional or non-synostotic plagiocephaly
(NSP). The review highlights that NSP is common and most mild
to moderate cases revert to normal by the age of two years.
Infants at increased risk are described, including those who
are less active, which may explain why developmental delay
is sometimes associated with NSP.
Many drugs given to children have side-effects. Dr. Schou
reviews the role of knemometry in the assessment of growth
suppressive effects of glucocorticoid treatment and describes
the effects of exogenous glucocorticoids on different components
of the lower leg. Epilepsy is a common problem in childhood.
Although many efficacious drugs are available, Dr. Verrotti
and colleagues remind us that endocrinological side-effects
can occur.
Two comprehensive reviews of the presentation, investigation
and management of clinical conditions are also included. Drs.
Polyxeni and Papadopoulou discuss idiopathic hypercalciuria,
the most common cause of urolithiasis in children. They highlight
that although this complex metabolic disease is considered
to be of genetic origin, no specific gene or polymorphisms
have been identified. Drs. Barese and Goebel review chronic
granulomatous disease (CGD) in childhood. They discuss that
current efforts to develop curative therapies include allogeneic
bone marrow transplantation for CGD patients with HLA identical
sibling donors and transplantation of autologous gene corrected
hematopoietic stem cells for patients who lack suitable marrow
donors.
Prof. Anne Greenough
Dept. of Child Health
King’s College Hospital
Denmark Hill
London, SE5 9RS
UK
E-mail: anne.greenough@kcl.ac.uk
[Back to top]
Proinflammatory Cytokines and Chemokines in Neonatal
Brain Damage
Marietta Xanthou
During perinatal asphyxia the inflammatory response to tissue
injury and the production of cytokines occur after the excitotoxic
cascade, at the reperfusion state, as hypoxia upregulates
numerous proinflammatory genes of cytokines and chemokines.
During perinatal infections CD14 and TLRs expressed on various
cells bind to pathogen derived molecules and induce the synthesis
of proinflammatory cytokines and chemokines. When the infection
is located in uterus these inflammatory mediators enter the
fetal circulation by crossing the placenta. Subsequently they
cross the blood-brain barrier and cause local inflammation
in the fetal brain. In experimental studies as well as in
clinical, epidemiologic and neuropathologic studies concerning
the newborn infant, an association between perinatal asphyxia
and/or infection, cytokines, chemokines and brain damage has
been found. In this review we analyse the mechanisms through
which proinflammatory cytokines and chemokines may lead to
neurodegeneration and brain damage. Particular emphasis is
given to the white matter damage of the brain of preterm infants.
Preterm infants are more vulnerable to brain damage because
of their immature vascular ependymal factors, immature oligodendrocytes
and deficient endogenous protective mechanisms. The methods
used to modify or block the activity of proinflammatory cytokines
and chemokines in order to prevent brain damage are being
discussed.
[Back to top]
Electroencephalographic Profiles of Children with
Symptoms of Attention Deficit Hyperactivity Disorder: A Review
of the Literature
Jennifer K. Penberthy, M. Layne Kalbfleisch, Mark Quigg, Tim
Loboschefski, Daniel Cox, Carolyn Runyon and Boris Kovatchev
This article will review the use of electroencephalographic
(EEG) data in children with Attention Deficit/Hyperactivity
Disorder (ADHD) or symptoms indicative of ADHD, both in research
directed at determining the pathophysiology of ADHD, as well
as research attempting to use the EEG as a diagnostic tool.
In addition, we briefly review concepts important in quantitative
analysis of EEG data. Overall, although some studies show
enhancement of certain frequency bands relative to others
within groups of ADHD children compared to normal controls,
to date neither traditional nor quantitative EEG has revealed
pervasive or consistent patterns of EEG abnormalities with
sufficient specificity or sensitivity to separate children
with ADHD from normal subjects. An exciting and promising
recent development in this area of research involves advanced
quantitative EEG analysis that has revealed an index shown,
in small preliminary studies, to clearly and reliably differentiate
ADHD from non-ADHD males. The use of EEG as a diagnostic tool
for ADHD warrants further study, including additional large
studies to help determine and clarify the specificity and
sensitivity of the multiple EEG measures in differentiating
ADHD and its subtypes from non-ADHD and other medical and
psychiatric disorders.
[Back to top]
Non-Synostotic Plagiocephaly and Brachycephaly: An
Overview
B. Lynne Hutchison, Edwin A. Mitchell and John M.D. Thompson
Although the supine sleep position in infants has greatly
reduced SIDS incidence, it has been associated with an increase
in referrals of positional, or non-synostotic, plagiocephaly
(NSP). Deformation of the soft infant skull may occur in response
to the exertion of gravity on the cranium lying on a firm
surface, particularly in the presence of a favoured head position.
NSP is characterised by patent cranial sutures and unilateral
or central occipital flattening, often with associated compensational
changes in other parts of the cranium. Differentiation between
lambdoid synostosis and NSP can largely be made using clinical
examination.
The condition is common and most mild to moderate cases of
NSP revert to the normal range by the age of two years. At
increased risk are males, firstborns, non-singletons, premature
infants, less active infants, those exposed to intrauterine
crowding or a difficult delivery, supine sleepers and infants
with neck rotation abnormalities. It is unclear at present
whether developmental delays that are sometimes associated
with NSP are causal or resultant of plagiocephaly.
Treatment involves keeping pressure off the flattened part
of the skull and treating neck rotation abnormalities. Prevention
revolves around early awareness of the head shape and varying
the head-lying position from birth.
[Back to top]
Pharmacological Treatment of Hypoxic-Ischemic Reperfusion
Injury of the Newborn Brain in the Clinical Setting: What
are the Possibilities in the Near Future?
Helen Torrance, Manon Benders and Frank van
Bel
Despite ongoing research and new insights into the pathophysiological
pathways of neonatal hypoxic-ischemic reperfusion brain injury,
effective treatment is not yet available. This review briefly
covers the mechanisms of hypoxic-ischemic reperfusion injury
and focuses on promising pharmacological neuroprotective strategies
which may become available for clinical use in the near future.
Furthermore, the beneficial effects of early intervention
and combination therapy with moderate hypothermia are discussed.
[Back to top]
Cycle Helmets for Children- Education or Enforcement?
Nicholas P. Mann and Angela Lee
Cycling is a healthy activity for children, but accidents
do occur and can result in death or disability. In the UK,
around 28 children per year die from cycle injuries and most
of these are directly attributable to head injury, and figures
for permanent brain injury are around 1,000 children a year.
What are the potential benefits of legislation on helmet usage
and reduction in injury?
Early studies from 1996 showed that helmets reduced the risk
of severe brain injury by 74%. Subsequent studies in other
countries have confirmed these initial findings, and a meta-analysis
using 16 studies by Attewell in 2001 showed clear benefits
of helmets in reducing injury including when there has been
a motor vehicle impac; a situation that is more likely to
lead to serious injury than a fall from a bike. Furthermore,
upper and mid facial injuries are reduced by helmet usage
and Thompson et al. have demonstrated a protective
effect of 65%.
Legislation for compulsory wearing of cycle helmets has been
introduced in many countries including over one-third of States
in USA, with significant reductions in head injury rates and
deaths. Initial concerns about a reduction of cycling activity
have not been confirmed. There is a good case for continued
introduction of legislation to maximise helmet wearing by
young cyclists.
[Back to top]
Nosocomial Infections In Paediatrics: Simple Preventive
Measures, Great Results
Javier N. Guevara, Dora E. Calderón, María G.
Aramburú de la Guardia and Xavier Sáez-Llorens
A nosocomial infection (NI) is an infection contracted in
a hospital or other health-care facility. An essential requirement
for the diagnosis of NI is the lack of evidence of infection
(subclinical or within the incubation period) on admission
to the hospital. The onset of a NI usually begins 48-72 hours
after hospitalization or can be longer in infections with
long or variable incubation period such as hepatitis or varicella.
Owing to the number and constant variability of factors that
contribute to the development and persistence of NIs within
the hospital environment, these conditions represent an important
public health issue. NIs add to the length of hospital stay,
contribute to the economic burden for the family and the institution
and are responsible for the increased mortality associated
with hospitalization. Accordingly, hospital-acquired infections
are a true challenge for both the treating clinician as well
as health authorities and administrators of tertiary medical
institutions. The introduction of new technologies, especially
in PICU and NICU, health-care equipment and immune status
characteristics are some factors related with the development
of nosocomial infections. Indeed, the study of factors associated
with these hospital-acquired infections is crucial for their
prevention in our patients. Hand washing is the single most
effective measure to prevent the development of NIs with great
results. Cleaning of surfaces and recommendations for inanimate
objects, health-care personnel education in aseptic technique
practices and isolation measures are a part of goals to prevent
the spread of nosocomial infections.
[Back to top]
Chronic Granulomatous Disease in Childhood
Cecilia Barese and W. Scott Goebel
Chronic granulomatous disease (CGD) is a genetic immunodeficiency
that commonly presents in infancy and early childhood. Currently,
life expectancy is beyond the fourth decade of life if the
disease is promptly diagnosed and treated. CGD is characterized
by increased susceptibility to recurrent and often life-threatening
infections caused by bacteria and fungi. The hallmark of the
disease is the formation of inflammatory granulomas, which
can cause obstruction of the hollow viscera. Therapeutic management
of CGD patients relies on the early and aggressive treatment
of acute infections, as well as lifelong antibiotic and antifungal
prophylaxis. Interferon gamma has a role in the prevention
and management of intractable infections. Current efforts
for the development of curative therapies focus on allogeneic
bone marrow transplantation for CGD patients with HLA-identical
sibling donors, and transplantation of autologous gene-corrected
hematopoietic stem cells for patients who lack suitable marrow
donors. Significant recent achievements in these fields provide
a realistic hope for a lifelong cure of CGD.
[Back to top]
Knemometry for Assessment of Growth Suppressive Effects
of Exogenous Glucocorticoids
Anders J. Schou
Exogenous glucocorticoids are commonly used in the treatment
of various conditions including asthma, rhinitis, and a range
of renal, gastrointestinal and malignant diseases in children.
Glucocorticoid treatment has numerous systemic side effects
beside the beneficial effects. An important and well described
side effect is growth suppression. Knemometry, i.e. measurement
of the lower leg length, is a well established method for
assessment of short term growth. The present article reviews
the role of knemometry in the assessment of growth suppressive
effects of glucocorticoid treatment, and the present data
on lower leg growth during glucocorticoid treatment are summarized.
Our knowledge on the effects of exogenous glucocorticoids
in the different components (bones, cartilage, cutis and subcutis,
etc.) of the lower leg is reviewed, and integrated with recent
studies assessing such effects by new methods.
[Back to top]
Endocrine Abnormalities Induced by Antiepileptic Drugs
Alberto Verrotti, Mariapaola Ciampani, Mariapina
Pomilio, Giuseppe Latini and Francesco Chiarelli
Epilepsy is a neurological disorder commonly seen in pediatric
age. A large number of anti epileptic Drugs are now available
for the treatment of this disease; although many of these
drugs have good efficacy in the treatment of both partial
and generalized epilepsies, their use can be associated with
various endocrinological side effects. During treatment are
commonly observed changes in serum levels of many hormones,
such as insulin, luteinizing hormone, follicle stimulating
hormone, corticotrophin and the main sexual hormones. Therefore,
in epileptic patients treated with antiepileptic, it is common
to observe a number of clinical problems like abnormalities
in pubertal development, weight gain, gonad dysfunction, hypothyroidism,
etc.
Both seizures and drugs could compromise hormonal balance
in epileptic patients, but it is not yet clear to distinguish
their effects.
The aim of this review is to focus on the main endocrinological
abnormalities induced by antiepileptic drugs, in order to
achieve a critical analysis of the recent researches on this
topic and to offer practical advice for a better care of epileptic
children.
[Back to top]
Idiopathic Hypercalciuria in Children
Nicolaidou Polyxeni and Anna Papadopoulou
Idiopathic Hypercalciuria (IH), a heterogenous disorder,
is the most common cause of urolithiasis in children. IH patients
present frequently with gross or microscopic hematuria, abdominal
pain and a variety of urinary tract complaints (frequency-dysuria
syndrome, enuresis, recurrent tract infection), with-noncalculus
manifestation more prevalent than stone disease. Recently,
osteopenia has been found in a high percentage of IH children
even at the time of diagnosis. IH is characterized by urinary
calcium excretion greater than 4mg/kg/day with normocalcemia
in the absence of any other causes of hypercalciuria such
as vitamin D intoxication, primary hyperparathyroidism, hyperthyroidism,
immobilization, endogenous or exogenous glucocorticoid excess,
distal renal tubular acidosis and furesemide medication. This
complex metabolic disease is considered to be of genetic origin,
as in some cases, it seems to be inherited in an autosomal
dominant pattern. A variety of genes participating in the
mechanisms of Ca homeostasis, have attracted the interest
of researchers in order to elucidate the pathogenetic mechanism
of the disease and thus determining the appropriate treatment
for any distinct patient. However, no specific gene or polymorphisms
are yet identified. Furthermore, studies on the pathophysiology
of IH distinguish two prominent types of IH: the absorptive,
characterized by increased intestinal Ca absorption, and the
renal, characterized by decreased tubular Ca reabsorption.
The distinction between renal and absorptive type could direct
towards the better therapeutic protocol. Generally, the main
goal of treatment applied on hypercalciuric children should
be to alleviate and finally eliminate the symptoms of the
disease, to prevent renal stone formation or recurrence and
to permit the acquisition of the optimal bone mass. Initial
management of those patients consists primarily of high fluid
intake and dietary salt restriction. If the symptoms persist,
thiazide diuretics prescription is ideal, especially for IH
patients of renal type.
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