Toe walking in children with cerebral palsy: a possible functional role for the plantar flexors.

Equinus and toe walking are common locomotor disorders in children with cerebral palsy (CP) walking barefoot or with normal shoes. We hypothesized that, regardless of the type of footwear, the plantar flexors do not cause early equinus upon initial foot contact but decelerate ankle dorsiflexion during weight acceptance (WA). This latter action promoted by early flat-foot contact is hypothesized to be functional. Hence, we performed an instrumented gait analysis of 12 children with CP (Gross Motor Function Classification System class: I or II; mean age: 7.2 yr) and 11 age-matched typically developing children. The participants walked either barefoot, with unmodified footwear (4° positive-heel shoes), or with 10° negative-heel shoes (NHSs). In both groups, wearing NHSs was associated with greater ankle dorsiflexion upon initial foot contact, and greater tibialis anterior activity (but no difference in soleus activity) during the swing phase. However, the footwear condition did not influence the direction and amplitude of the first ankle movement during WA and the associated peak negative ankle power. Regardless of the footwear condition, the CP group displayed 1) early flattening of the foot and ample dorsiflexion (decelerated by the plantar flexors) during WA and 2) low tibialis anterior and soleus activities during the second half of the swing phase (contributing to passive equinus upon foot strike). In children with CP, the early action of plantar flexors (which typically decelerate the forward progression of the center of mass) may be a compensatory mechanism that contributes to the WA's role in controlling balance during gait.NEW & NOTEWORTHY Adaptation to walking in negative-heel shoes was similar in typically developing children and children with cerebral palsy: it featured ankle dorsiflexion upon initial contact, even though (in the latter group) the soleus was always spastic in a clinical examination. Hence, in children with cerebral palsy, the early deceleration of ankle dorsiflexion by the plantar flexors (promoted by early flattening of the foot, and regardless of the type of footwear) may have a functional role.

[Psychosocial aspects of coping with tinnitus and psoriasis patients. A comparative study of suicidal tendencies, anxiety and depression]. / Psychosoziale Aspekte der Krankheitsverarbeitung bei Tinnitus- und Psoriasis-Patienten. Eine Vergleichsstudie hinsichtlich Suizidalität, Angstlichkeit und Depressivität.

BACKGROUND: Treatment of tinnitus is primarily the task of ENT specialists, while treatment of the psychiatric diseases lies in the hand of psychotherapists. Different from mostly very apparent dermatological diseases, the severity level of tinnitus can often only be determined by psychological test batteries as well as a specific psychosomatic exploration. In this study patients with psoriasis were compared with tinnitus patients regarding quality of life, anxiety, depression and imminent suicidal tendencies, in order to realize the psychological impact and find appropriate instruments for treatment. METHODS: Between February and April 2005, 89 tinnitus patients, who underwent in-patient therapy in a neurootological and psychosomatic hospital, and 105 psoriasis patients, who had in-patient treatment from October 1999 until October 2004 in a specialized clinic, were examined with psychological tests, which included the Tinnitus questionnaire proposed by Goebel und Hiller, the Symptoms Check List of Derogatis SCL-90-R, the HADS and the suicide rating according to Pöldinger. RESULTS: Tinnitus in-patients suffered significantly more from suicidal tendencies, depression and anxiety in contrast to patients with psoriasis, who suffered more from problems associated with their outward appearance. CONCLUSION: The use of a specific psychological test diagnostic is very helpful in the hand of the ENT specialist, but the Tinnitus questionnaire of Goebel and Hiller enables an initial screening.

Brief Report: Self-Injurious Behaviors in Preschool Children with Autism Spectrum Disorder Compared to Other Developmental Delays and Disorders.

We compared the prevalence of self-injurious behaviors (SIB) in preschoolers aged 30-68 months with autism spectrum disorder (ASD) (n = 691) versus other developmental delays and disorders (DD) (n = 977) accounting for sociodemographic, cognitive, and medical factors. SIB prevalence was higher in ASD versus all DD [adjusted odds-ratio (aOR) 2.13 (95% confidence interval (95% CI) 1.53, 2.97)]. In subgroup analyses, SIB prevalence was higher in ASD versus DD without ASD symptoms [aOR 4.42 (95% CI 2.66, 7.33)], but was similar between ASD and DD with ASD symptoms [aOR 1.09 (95% CI 0.68, 1.77)]. We confirmed higher prevalence of SIB in ASD versus DD, independent of confounders. In children with DD, SIB prevalence increased with more ASD symptoms. These findings are informative to clinicians, researchers, and policymakers.

Gait post-stroke: Pathophysiology and rehabilitation strategies.

We reviewed neural control and biomechanical description of gait in both non-disabled and post-stroke subjects. In addition, we reviewed most of the gait rehabilitation strategies currently in use or in development and observed their principles in relation to recent pathophysiology of post-stroke gait. In both non-disabled and post-stroke subjects, motor control is organized on a task-oriented basis using a common set of a few muscle modules to simultaneously achieve body support, balance control, and forward progression during gait. Hemiparesis following stroke is due to disruption of descending neural pathways, usually with no direct lesion of the brainstem and cerebellar structures involved in motor automatic processes. Post-stroke, improvements of motor activities including standing and locomotion are variable but are typically characterized by a common postural behaviour which involves the unaffected side more for body support and balance control, likely in response to initial muscle weakness of the affected side. Various rehabilitation strategies are regularly used or in development, targeting muscle activity, postural and gait tasks, using more or less high-technology equipment. Reduced walking speed often improves with time and with various rehabilitation strategies, but asymmetric postural behaviour during standing and walking is often reinforced, maintained, or only transitorily decreased. This asymmetric compensatory postural behaviour appears to be robust, driven by support and balance tasks maintaining the predominant use of the unaffected side over the initially impaired affected side. Based on these elements, stroke rehabilitation including affected muscle strengthening and often stretching would first need to correct the postural asymmetric pattern by exploiting postural automatic processes in various particular motor tasks secondarily beneficial to gait.

Influence of H-HOPE intervention for premature infants on growth, feeding progression and length of stay during initial hospitalization.

OBJECTIVE: To examine whether premature infants receiving the maternally administered H-HOPE (Hospital to Home Transition-Optimizing Premature Infant's Environment) intervention had more rapid weight gain and growth, improved feeding progression and reduced length of hospital stay, compared with controls. STUDY DESIGN: Premature infants born at 29-34 weeks gestational age and their mothers with at least two social-environmental risk factors were randomly assigned to H-HOPE intervention (n=88) or an attention control (n=94) groups. H-HOPE consists of a 15-min multisensory intervention (Auditory, Tactile, Visual and Vestibular stimuli) performed twice daily prior to feeding plus maternal participatory guidance on preterm infant behavioral cues. RESULT: H-HOPE group infants gained weight more rapidly over time than infants in the control group and grew in length more rapidly than control infants, especially during the latter part of the hospital stay. CONCLUSION: For healthy preterm infants, the H-HOPE intervention appears to improve weight gain and length over time from birth to hospital discharge.

UVB activates ERK1/2 and p38 signaling pathways via reactive oxygen species in cultured keratinocytes.

We have previously shown that hydrogen peroxide is an important mediator of ultraviolet B induced phosphorylation of the epidermal growth factor receptor in human keratinocytes. Here we demonstrate that physiologic doses of ultraviolet B and hydrogen peroxide stimulate activation of two related but distinct mitogen-activated protein kinase pathways: extracellular regulated kinase 1 and 2 (ERK1/2), as well as p38, the mammalian homolog of HOG1 in yeast which is a major kinase for a recently identified stress-induced signaling pathway. The time-dependent activation of ERK1/2 and p38 are distinct, and ultraviolet B-induced ERK1/2 activation is downregulated more rapidly than p38. Using dihydrorhodamine or Amplex as specific fluorescent dye probes, we show that ultraviolet B-induced peroxides can be inhibited by ascorbic acid. Ascorbic acid strongly blocks ERK1/2 and p38 activation by ultraviolet B and hydrogen peroxide whereas pyrrolidine dithiocarbamate and butyl hydroxyanisole are less effective. Pyrrolidine dithiocarbamate was unable to inhibit ultraviolet B-induced p38 activation. Cell death was increased after ultraviolet B when ERK1/2 activation was attenuated by the specific inhibitor PD098059. The distinct time courses and extents of activation and inhibition of ERK1/2 and p38 indicate that these pathways are separate and regulated independently in keratinocytes. Specific types of reactive oxygen species induced by ultraviolet B as well as selective activation or inhibition of specific phosphatases may mediate these responses in keratinocytes. These findings demonstrate that reactive oxygen species are important multifunctional mediators of ultraviolet B-induced ERK1/2 and p38 signaling transduction pathways and suggest that ERK1/2 may play an important part in protecting keratinocytes from cell death following oxidative stress.

H2O2 is an important mediator of UVB-induced EGF-receptor phosphorylation in cultured keratinocytes.

Exposure of human keratinocytes to physiologic doses of ultraviolet B (UVB) radiation induces phosphorylation of the epidermal growth factor receptor (EGFR). We demonstrate that H2O2 generated by UVB mediates EGFR phosphorylation. Using dihydrorhodamine 123 as a specific fluorescent dye probe, we show that UVB irradiation (50-800 J per m2) of keratinocytes leads within minutes to concentration-dependent intracellular production of H2O2. A corresponding concentration-dependent increase in the release of extracellular H2O2 was measured by using Amplex, a derivative of dihydrophenoxazine. The levels of intracellular H2O2 that are induced by UVB irradiation and that stimulate EGFR phosphorylation correlate strongly with the response induced by exogenously added H2O2. UVB or H2O2 demonstrated concentration- and time-dependent stimulation of EGFR phosphorylation that was initially observed within 1-5 min and exhibited a proportionate delay for UVB-induced production of H2O2. EGFR phosphorylation induced by UVB or H2O2 declined significantly toward baseline levels by 4 h and could be restimulated after H2O2 but not after UVB exposure. Phosphorylation of EGFR was inhibited by the structurally unrelated antioxidants butylated hydroxyanisole, N-acetyl-L-cysteine, and pyrrolidine dithiocarbamate, or by the H2O2-degrading enzyme catalase. These data indicate that generation of H2O2 by UVB radiation of human keratinocytes participates in the rapid, ligand-independent phosphorylation of EGFR and implicate H2O2 as a biologic mediator in EGFR activation and regulation of the downstream signaling cascade. UVB-induced H2O2 has the potential to initiate or modulate early EGFR-mediated signaling events that could play an important role in the cellular response to oxidative stress.

H2O2 is required for UVB-induced EGF receptor and downstream signaling pathway activation.

Ultraviolet radiation (UVR)-induced receptor phosphorylation is increasingly recognized as a widely occurring phenomenon. However, the mechanisms, mediators, and sequence of events involved in this process remain ill-defined. We have recently shown that exposure of human keratinocytes to physiologic doses of ultraviolet B radiation (UVB) activates epidermal growth factor receptor (EGFR)/extracellular-regulated kinase 1 and 2 (ERK1/2), and p38 signaling pathways via reactive oxygen species. Here we demonstrate that UVB exposure increased intra- and extracellular H2O2 production rapidly in a time-dependent manner. An EGFR-specific monoclonal antibody abrogated EGFR autophosphorylation and markedly decreased the phosphorylation of ERK1/2 whereas p38 activation was unaffected. Overexpression of catalase strongly inhibited UVB-induced EGFR/ERK1/2 pathway activation. These findings establish the sequence of events after UVB irradiation: (i) H2O2 generation, (ii) EGFR phosphorylation, and (iii) ERK activation. Our results identify UVB-induced H2O2 as a second messenger that is required for EGFR and dependent downstream signaling pathways activation.

Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates.

BACKGROUND: Preterm neonates are exposed to multiple painful procedures after birth and exhibit acute physiological responses to pain. Occurrence of early intraventricular hemorrhage within 24 to 72 hours after birth suggests a role of pain and stress in the multifactorial causation of severe intraventricular hemorrhage and periventricular leukomalacia. We proposed that such neurologic outcomes in preterm neonates who require ventilatory support may be reduced by morphine analgesia or midazolam sedation compared with a placebo. OBJECTIVES: To define the incidence of clinical outcomes in the target study population, to estimate the effect size and adverse effects associated with analgesia and sedation, and to calculate the sample size for a definitive test of this hypothesis. METHODS: Sixty-seven preterm neonates were randomized in a pilot clinical trial from 9 centers. Neonates of 24 to 32 weeks gestation were eligible if they had been intubated and required ventilatory support for less than 8 hours and if they were enrolled within 72 hours after birth. Exclusion criteria included major congenital anomalies, severe intrapartum asphyxia, and participation in other research studies. Severity of illness was assessed by the Clinical Risk Index for Babies, and neonates were randomized to receive continuous infusions of morphine sulfate, midazolam hydrochloride, or 10% dextrose (placebo). Masked study medications were continued as long as clinically necessary, then weaned and stopped according to predefined criteria. Levels of sedation (COMFORT scores) and responses to pain (Premature Infant Pain Profile scores) were measured before, during, and 12 hours after discontinuation of drug infusion. Cranial ultrasound examinations were performed as part of routine practice, and poor neurologic outcomes were defined as neonatal death, severe intraventricular hemorrhage (grade III or IV), or periventricular leukomalacia. RESULTS: No significant differences occurred in the demographic, clinical, and socioeconomic variables related to mothers and neonates in the 3 groups or in the severity of illness at birth as measured by Clinical Risk Index for Babies scores. Two neonates in the placebo group and 1 neonate in the midazolam group died; no deaths occurred in the morphine group. Poor neurologic outcomes occurred in 24% of neonates in the placebo group, 32% in the midazolam group, and 4% in the morphine group (likelihood ratio chi2 = 7.04, P = .03). Secondary clinical outcomes and neurobehavioral outcomes at 36 weeks' postconceptional age were similar in the 3 groups. Responses elicited by endotracheal tube suction (Premature Infant Pain Profile scores) were significantly reduced during the morphine (P<.001) and midazolam (P = .002) infusions compared with the placebo group. CONCLUSIONS: This pilot trial suggests that preemptive analgesia given by continuous low-dose morphine infusion may reduce the incidence of poor neurologic outcomes in preterm neonates who require ventilatory support. Limitations in the sample size of this pilot study suggest that these results should be confirmed in a large multicenter randomized trial.

Premorbid prevalence of ADHD and development of secondary ADHD after closed head injury.

OBJECTIVE: To determine premorbid prevalence of attention-deficit hyperactivity disorder (ADHD) in children with moderate and severe closed head injury (CHI), to determine incidence of ADHD 1 year after injury, and to characterize children who develop ADHD by demographic, neuropsychiatric, and outcome variables. METHOD: Ninety-nine children who had severe and moderate CHI were followed up for 1 year. Premorbid and 1-year postinjury psychiatric status were ascertained by parent and child structured interviews and questionnaires measuring affective lability, aggression, apathy, and social judgment. RESULTS: Premorbid prevalence of ADHD was 0.20, significantly higher than in a reference population (0.045). Fifteen of the remaining 80 children (0.19) developed full ADHD criteria (except for age of onset) by the end of the first year. Children who developed secondary ADHD (S-ADHD) had significantly greater premorbid psychosocial adversity, posttraumatic affective lability and aggression, posttraumatic psychiatric comorbidity, and overall disability than children who did not develop S-ADHD. CONCLUSIONS: There is an excess prevalence of premorbid ADHD among children who present with moderate and severe CHI. Children with high psychosocial adversity are more likely to develop S-ADHD after CHI. S-ADHD has criteria in common with personality change due to CHI, a deficit in behavioral inhibition being the major overlapping feature.

UVB-induced epidermal growth factor receptor phosphorylation is critical for downstream signaling and keratinocyte survival.

We have recently shown that UVB radiation activates epidermal growth factor receptor (EGFR)/extracellular regulated kinase 1 and 2 (ERK1/2) and p38 signaling pathways in keratinocytes. However, the functional relevance of these processes for downstream signaling and cell survival remains to be determined. The specific EGFR inhibitor PD153035 markedly decreased UVB-induced phosphorylation of EGFR, ERK1/2 and shc, whereas p38 activation was unaffected. PD153035 pretreatment followed by UVB reduced clonogenic potential and enhanced peroxide production, apoptosis and cell death. Our data suggest that ligand-independent phosphorylation of EGFR and likely dependent downstream signaling pathways regulate cellular defense mechanisms important for cell survival following oxidative stress.

Perinatal factors influencing the outcome of 501- to 1000-gm newborns.

This article is a review of the various factors relating to fetal and neonatal mortality in infants of a particular birth weight. Factors influencing survival positively also are considered, including various presentations and some specific maternal factors.

Methodological considerations when assessing restricted and repetitive behaviors and aggression.

Methodological issues impacting the relationship between aggression and restricted, repetitive, and stereotyped behaviors and interests (RRSBI) were examined in 2648 children and adolescents with autism spectrum disorders (ASD) using a multi-method, multi-informant analysis model to assess the effects of informant, assessment method, and aggression phenotype. Overall, a significant, but small relationship was found between RRSBI and aggression (p < .05). There was significant heterogeneity of estimates with large effect sizes observed when utilizing teacher report and a broad phenotype of aggression. Variance in estimates was attributed to differences in informant and assessment method with two times greater effect attributed to informant. Results suggest strategies to optimize future investigations of the relationship between RRSBI and aggression. Findings also provide the opportunity for the development of targeted interventions for aggression in youth with ASD.

Fracture of the femur at cesarean section: case report and review of literature.

In this article, we report a case of a newborn who was delivered by cesarean section for breech presentation and who sustained a fracture of the femur. Nine-month follow-up revealed good healing of the fracture. We also present a short review and discussion of only six other similarly reported cases. We suggest that although cesarean section decreases the trauma-related morbidity in breech presentation, it does not reduce it to zero.

Thrombocytopenia in the high-risk infant.

One-hundred twenty-nine high-risk infants with thrombocytopenia and 238 control infants without thrombocytopenia were evaluated. Mothers of thrombocytopenic babies had similar history to those of nonthrombocytopenic babies, although fewer chronic narcotic abusers were found among mothers of thrombocytopenic babies. Thrombocytopenia was more common in babies less than 37 weeks' gestation and in sick babies compared to healthy babies. Sixty percent of infants had no recognizable cause of thrombocytopenia. Features associated with thrombocytopenia included umbilical line placement, respiratory assistance, hyperbilirubinemia, phototherapy, prematurity, respiratory distress syndrome, low Apgar score, sepsis, meconium aspiration, and necrotizing entercolitis. Thrombocytopenic babies had Apgar score, sepsis, meconium aspiration, and necrotizing entercolitis. Thrombocytopenic babies had more complications, more hemorrhage, and greater mortality than nonthrombocytopenic babies. Platelet size was increased in two babies with immune thrombocytopenia and in none of the others. This study shows that neonatal thrombocytopenia is often associated with high-risk factors and with increased hemorrhage, morbidity, and mortality. This relationship suggests an important prognostic value to platelet size was increased in two babies with immune thrombocytopenia and in none of the others. This study shows that neonatal thrombocytopenia is often associated with high-risk factors and with increased hemorrhage, morbidity, and mortality. This relationship suggests an important prognostic value to platelet counts, although the extent to which the thrombocytopenia contributed directly to morbidity and mortality is not clear.

Effect of nimodipine on systemic, renal, and cerebral haemodynamics after a mild hypoxic-ischaemic insult in newborn piglets.

Because many Ca2+ channel blocking agents are known to cause adverse systemic effects, in this study we tested the haemodynamic side effects of nimodipine with and without a mild hypoxic-ischaemic (HI) insult in a newborn piglet model. Fifteen min after completing a brief period of asphyxia we gave i.v. nimodipine as 5 micrograms kg-1 bolus followed by 0.1 microgram kg-1 min-1 continuous infusion for 105 min in six piglets, while the same treatment was repeated in five animals without preceding HI insult. At third group of six served as sham operated controls. In the HI insult group by 105 min of nimodipine infusion the mean BP dropped by 30% and the cardiac output dropped by 23% of respective baseline. In this group, the renal blood flow dropped between 65% and 77% of baseline and regional cerebral blood flow dropped between 28% and 55% of respective baseline by 45 min and 105 min of nimodipine fashion. In the group with no prior HI insult, 105 min of nimodipine infusion caused no significant changes in these variables. Despite nimodipine infusion, HI insult caused a significant increase in the mean brain water content compared to the two control groups: 89 +/- 3.2% compared to 82.7 +/- 0.5% in the nimodipine control group, and 83.7 +/- 1.7% in the sham group (P < 0.0001). We conclude that while nimodipine therapy without prior asphyxial insult does not cause significant adverse haemodynamic effects, its infusion after even a mild HI insult could cause reduction in renal blood flow and moderate reduction in regional cerebral blood flow, BP, and cardiac output, suggesting a differential effect. A 15 min lag between HI insult and nimodipine therapy may be too long to prevent cerebral oedema.

Depth of lesion model in children and adolescents with moderate to severe traumatic brain injury: use of SPGR MRI to predict severity and outcome.

OBJECTIVES: The utility of a depth of lesion classification using an SPGR MRI sequence in children with moderate to severe traumatic brain injury (TBI) was examined. Clinical and depth of lesion classification measures of TBI severity were used to predict neurological and functional outcome after TBI. METHODS: One hundred and six children, aged 4 to 19, with moderate to severe TBI admitted to a rehabilitation unit had an SPGR MRI sequence obtained 3 months afterTBI. Acquired images were analyzed for location, number, and size of lesions. The Glasgow coma scale (GCS) was the clinical indicator of severity. The deepest lesion present was used for depth of lesion classification. Speed of injury was inferred from the type of injury. The disability rating scale at the time of discharge from the rehabilitation unit (DRS1) and at 1 year follow up (DRS2) were functional outcome measures. RESULTS: The depth of lesion classification was significantly correlated with GCS severity, number of lesions, and both functional measures, DRS1 and DRS2. This result was more robust for time 1, probably due to the greater number of psychosocial factors impacting on functioning at time 2. Lesion volume was not correlated with the depth of lesion model. In multivariate models, depth of lesion was most predictive of DRS1, whereas GCS was most predictive of DRS2. CONCLUSIONS: A depth of lesion classification of TBI severity may have clinical utility in predicting functional outcome in children and adolescents with moderate to severe TBI.

Significance of genetic testing for paternal uniparental disomy of chromosome 6 in neonatal diabetes mellitus.

Two patients who presented at birth with neonatal diabetes mellitus (NDM) are described: one with paternal uniparental disomy for chromosome 6 and one with normal, biparental inheritance. The first child presented with low birth weight, macroglossia, hypertelorism, and club foot in addition to NDM. In this patient hyperglycemia was transient, and insulin treatment was discontinued at 4 months of age. The second child also presented with low birth weight but was normal in appearance, and insulin dependence continues after 5 years. Genetic analysis with polymorphic DNA markers for chromosome 6 indicated the presence of paternal uniparental disomy (UPD) in the first case and normal, biparental inheritance in the second case. Paternal UPD 6 has been reported in 8 previous cases of which 6 showed NDM. Three cases with paternal UPD 6 also included additional anomalies, such as macroglossia, not usually associated with NDM. Therefore the simultaneous finding of NDM and macroglossia should be a strong indicator for genetic testing. The genetic finding of paternal UPD 6 allows prediction of a transient, rather than permanent, form of diabetes mellitus and no increased recurrence risk of transient NDM in subsequent pregnancies.