University of Virginia Children's Hospital

OBJECTIVE: The goal was to create a functional status outcome measure for large outcome studies that is well defined, quantitative, rapid, reliable, minimally dependent on subjective assessments, and applicable to hospitalized pediatric patients across a wide range of ages and inpatient environments. METHODS: Functional Status Scale (FSS) domains of functioning included mental status, sensory functioning, communication, motor functioning, feeding, and respiratory status, categorized from normal (score = 1) to very severe dysfunction (score = 5). The Adaptive Behavior Assessment System II (ABAS II) established construct validity and calibration within domains. Seven institutions provided PICU patients within 24 hours before or after PICU discharge, high-risk non-PICU patients within 24 hours after admission, and technology-dependent children. Primary care nurses completed the ABAS II. Statistical analyses were performed. RESULTS: A total of 836 children, with a mean FSS score of 10.3 (SD: 4.4), were studied. Eighteen percent had the minimal possible FSS score of 6, 44% had FSS scores of >or=10, 14% had FSS scores of >or=15, and 6% had FSS scores of >or=20. Each FSS domain was associated with mean ABAS II scores (P < .0001). Cells in each domain were collapsed and reweighted, which improved correlations with ABAS II scores (P < .001 for improvements). Discrimination was very good for moderate and severe dysfunction (ABAS II categories) and improved with FSS weighting. Intraclass correlations of original and weighted total FSS scores were 0.95 and 0.94, respectively. CONCLUSIONS: The FSS met our objectives and is well suited for large outcome studies.

CONTEXT: Despite evidence that patients with acute lung injury (ALI) have pulmonary surfactant dysfunction, trials of several surfactant preparations to treat adults with ALI have not been successful. Preliminary studies in children with ALI have shown that instillation of a natural lung surfactant (calfactant) containing high levels of surfactant-specific protein B may be beneficial. OBJECTIVE: To determine if endotracheal instillation of calfactant in infants, children, and adolescents with ALI would shorten the course of respiratory failure. DESIGN, SETTING, AND PATIENTS: A multicenter, randomized, blinded trial of calfactant compared with placebo in 153 infants, children, and adolescents with respiratory failure from ALI conducted from July 2000 to July 2003. Twenty-one tertiary care pediatric intensive care units participated. Entry criteria included age 1 week to 21 years, enrollment within 48 hours of endotracheal intubation, radiological evidence of bilateral lung disease, and an oxygenation index higher than 7. Premature infants and children with preexisting lung, cardiac, or central nervous system disease were excluded. INTERVENTION: Treatment with intratracheal instillation of 2 doses of 80 mL/m2 calfactant or an equal volume of air placebo administered 12 hours apart. MAIN OUTCOME MEASURES: Ventilator-free days and mortality; secondary outcome measures were hospital course, adverse events, and failure of conventional mechanical ventilation. RESULTS: The calfactant group experienced an acute mean (SD) decrease in oxygenation index from 20 (12.9) to 13.9 (9.6) after 12 hours compared with the placebo group's decrease from 20.5 (14.7) to 15.1 (9.0) (P = .01). Mortality was significantly greater in the placebo group compared with the calfactant group (27/75 vs 15/77; odds ratio, 2.32; 95% confidence interval, 1.15-4.85), although ventilator-free days were not different. More patients in the placebo group did not respond to conventional mechanical ventilation. There were no differences in long-term complications. CONCLUSIONS: Calfactant acutely improved oxygenation and significantly decreased mortality in infants, children, and adolescents with ALI although no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was observed.

Malformations of cortical development containing dysplastic neuronal and glial elements, including hemimegalencephaly and focal cortical dysplasia, are common causes of intractable paediatric epilepsy. In this study we performed multiplex targeted sequencing of 10 genes in the PI3K/AKT pathway on brain tissue from 33 children who underwent surgical resection of dysplastic cortex for the treatment of intractable epilepsy. Sequencing results were correlated with clinical, imaging, pathological and immunohistological phenotypes. We identified mosaic activating mutations in PIK3CA and AKT3 in this cohort, including cancer-associated hotspot PIK3CA mutations in dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia type IIa. In addition, a germline PTEN mutation was identified in a male with hemimegalencephaly but no peripheral manifestations of the PTEN hamartoma tumour syndrome. A spectrum of clinical, imaging and pathological abnormalities was found in this cohort. While patients with more severe brain imaging abnormalities and systemic manifestations were more likely to have detected mutations, routine histopathological studies did not predict mutation status. In addition, elevated levels of phosphorylated S6 ribosomal protein were identified in both neurons and astrocytes of all hemimegalencephaly and focal cortical dysplasia type II specimens, regardless of the presence or absence of detected PI3K/AKT pathway mutations. In contrast, expression patterns of the T308 and S473 phosphorylated forms of AKT and in vitro AKT kinase activities discriminated between mutation-positive dysplasia cortex, mutation-negative dysplasia cortex, and non-dysplasia epilepsy cortex. Our findings identify PI3K/AKT pathway mutations as an important cause of epileptogenic brain malformations and establish megalencephaly, hemimegalencephaly, and focal cortical dysplasia as part of a single pathogenic spectrum.

OBJECTIVE: After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. PATIENTS AND METHODS: Relevant manuscripts published in the English language were searched in Medline by using search terms "opioid," "opiate," "sedation," "analgesia," "child," "infant-newborn," "tolerance," "dependency," "withdrawal," "analgesic," "receptor," and "individual opioid drugs." Clinical and preclinical studies were reviewed for data synthesis. RESULTS: Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. CONCLUSIONS: Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal.

A complication of severe brain injury is a syndrome of intermittent agitation, diaphoresis, hyperthermia, hypertension, tachycardia, tachypnea, and extensor posturing. To capture the main features of this syndrome, derived through literature review and our own case series, we propose the term paroxysmal autonomic instability with dystonia. We reviewed reports of autonomic dysregulation after brain injury and extracted essential features. From the clinical features, consistent themes emerge regarding signs and symptoms, differential diagnosis, and pharmacological therapies. We used these findings to make recommendations regarding diagnosis and treatment. Paroxysmal autonomic instability with dystonia appears to be a distinctive syndrome after brain injury that can mimic other life-threatening conditions. Early recognition may lead to fewer diagnostic tests and a rational approach to management. Prospective trials of specific drugs are needed to determine optimal efficacy.

BACKGROUND: Although breastfeeding is touted as providing many health benefits to infants, some aspects of this relationship remain poorly understood. METHODS: The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective longitudinal study that follows children from birth through childhood, and collects data on illness events, breastfeeding duration, and time to introduction of formula or foods at 3 month intervals up until 4 years of age and at 6 months intervals thereafter. Exclusive and non-exclusive breastfeeding is examined in relation to the 3-month odds of a respiratory or gastrointestinal infection for 6861 children between the ages of 3-18 months, and 5666 children up to the age of 4 years. Analysis was performed using logistic regression models with generalized estimating equation methodology. All models were adjusted for potential confounding variables. RESULTS: At 3-6 months of age, breastfeeding was found to be inversely associated with the odds of respiratory infections with fever (OR = 0.82, 95% CI = 0.70-0.95), otitis media (OR = 0.76, 95% CI = 0.62-0.94), and infective gastroenteritis (OR = 0.55, 95% CI = 0.46-0.70), although the inverse association with respiratory illnesses was observed only for girls during the winter months. Between 6 and 18 months of age, breastfeeding within any 3 month period continued to be inversely associated with the odds of ear infection and infective gastroenteritis, and additionally with the odds of conjunctivitis, and laryngitis and tracheitis, over the same 3 month period within this age range. However, breastfeeding in this group was associated with increased reports of common cold. Duration of exclusive breastfeeding was inversely associated with the odds of otitis media up to 48 months of age (OR = 0.97, 95% CI = 0.95-0.99) after breastfeeding had stopped. CONCLUSIONS: This study demonstrates that breastfeeding can be protective against multiple respiratory and gastrointestinal acute illnesses in some children up to at least 6 months of age, with duration of exclusive breastfeeding being somewhat protective of otitis media even after breastfeeding has stopped. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00279318 . Date of registration: January 17, 2006 (proactively registered). First Posted: January 19, 2006.

PURPOSE: The pathophysiology, evaluation, description and clinical implications of renal damage associated with vesicoureteral reflux remain controversial. We summarized the current understanding of this important aspect of clinical vesicoureteral reflux. MATERIALS AND METHODS: We performed a detailed review of the literature on clinical, pathological and experimental data related to congenital vesicoureteral reflux and bladder dynamics. We also reviewed the clinical context and imaging evaluation with underlying experimental data related to post-infectious reflux nephropathy. RESULTS: Congenital reflux nephropathy is a pattern of impaired renal function and development with renal dysplasia as the most severe but not the only form. Mechanisms of developmental disruption are potentially related to vesicoureteral reflux dynamics during gestation and associated bladder dynamics, which may continue into postnatal life. Acquired renal injury associated with infection is related to particular bacterial and host factors that determine infection virulence, host inflammatory response and tissue recovery. As best seen on dimercapto-succinic acid scan, acute changes may resolve but may also persist as permanent renal scarring. Specific risk factors for acute pyelonephritis and renal scarring in patients with vesicoureteral reflux include higher reflux grade, dysfunctional voiding/elimination, recurrent pyelonephritic episodes and delayed initiation of antibiotic therapy. Low pressure sterile reflux is not a cause of reflux nephropathy. CONCLUSIONS: Renal damage associated with vesicoureteral reflux may be congenital or acquired and the respective pathophysiological mechanisms are likely different. Congenital damage is often dysplasia, which may be a result of disordered renal development secondary to significant alterations in bladder dynamics. These processes may continue into the newborn period while kidney maturation continues. Recognizing the clinical potential for ongoing effects on renal function and the role of bladder development are important for clinical care. Post-pyelonephritic acquired damage is the result of a complex interaction of host and bacterial factors that leads to acute alterations in renal function, and may lead to permanent renal scarring. Strategies for timely intervention as well as prevention are essential to limit the risk of permanent renal injury, which may predispose to hypertension and renal insufficiency in some patients.

SUMMARY The Gross Motor Function Measure (GMFM) and computerized gait analysis are commonly used to assess patients with cerebral palsy (CP). The authors investigated correlations between the GMFM and gait parameters in 32 children aged 3 to 18 (mean 8.9) years with spastic CP. Of the gait parameters, cadence and normalized velocity correlated most strongly with the GMFM score, and hip and knee excursion and percentage single support also correlated directly with the GMFM. In a stepwise multiple regression, cadence alone was a significant predictor of GMFM score. Time and distance parameters, hip and knee excursion in the sagittal plane and GMFM values all moved consistently further from pediatric norms as functional severity increased. The study confirms that gait is representative of general motor status in CP and that the GMFM and gait analysis are complementary measures in the functional assessment of these children. RÉSUMÉ Relations entre l'analyse de la démarche et le trouble moteur global dans l'IMC Une évaluation du trouble moteur global (GMFM) et une analyse de la demarche par ordinateur a été pratiquée systématiquement pour caractériser des IMC (CP). Lés auteurs ont recherche les corrélations entre le GMFM et les paramètres de la démarche chez 32 enfants âgés de 3 à 18 ans (moyenne 8,9) préscntant une IMC spastique. Parmi les paramétres de la démarche, les corrélations les plus élevées avec le GMFM concernaient la cadence et la vitesse normalisée: l'excursion de la hanche ct du genouet le pourcentage de support unipodal présentaient également une corrélation directe avec le GMFM. Dans une analyse de variance à régression multiple, la cadence à elle seule était prédictive du score GMFM. Les paramétres de distance et de temps, l'excursion de la hanche et du genou dans un plan sagittal et les valeurs GMFM s'éloignaient des normes pédiatriques avec la gravité fonctionnelle. Cette étude confirme que la démarche est un reflet de l'état moteur global dans l'IMC et que le GMFM et l'analyse de la démarche sont des mesures complémentaires dans l'évaluation fonctionnelle des enfants examinés. ZUSAMMENFASSUNG Beziehung zwischen Ganganalyse und grobmotorischer Funktion bei Cerebralparese Der Gross Motor Function Measure (GMFM) und die Komputerganganalyse werden in der Regel zur Beurteilung von Patienten mit Cerebralparese (CP) herangezogen. Die Autoren untersuchten die Zusammenhänge zwischen dem GMFM und Gangparametern bei 32 Kindern mit spastischer CP im Alter 3 und 18 (im Mittel 8,9) Jahren. Von den Gangparametern korrelierten Kadenz und geregelte Geschwindigkeit am stärksten mit dem GMFM Score und auch der Hüft‐ und Knieexcursion und der Anteil des single support korrelierten direkt mit dem GMFM. Nach einer schrittweisen multiplen Regressionsanalyse blieb nur noch die Kadenz als signifikanter Parameter für den GMFM. Zeit und Entfernungsparametcr, Hüft‐ und Knieexcursion in einer sagittalen Ebene und GMFM Werte entfernten sich mit zunehmendcr Funktionsverschlcchterung von den pädiatrischen Normalwerten. Die Studie bestütigt, daś der Gang fur den allgemeinen motorischen Status bei Cerebralparese repräsentativ ist und daß der GMFM und die Ganganalyse komplementäre Methoden für die funktionellc Beurteilung dieser Kinder sind. RESUMEN Relatión del análisis de la marcha con la fitneión nwtora grosera en la parálisis cerebral La Medición de la Función Motora Grosera (MFMG) y el análisis computarizado de la marcha se usan corrientemente para cvaluar los pacicntes con parálisis cerebral (PC). Los auiores investigaron las correlaciones cntre la MFMG y los parámetros de la marcha en 32 niños de 3 a 18 años (promedio 8,9) con PC espástica. De los parámetros de la marcha, la cadencia y la velocidad normalizadas sc correlacionaban muy fuertementc con el puntagc de MFMG; el recorrido de la cadera y la rodilla y el porcentage de soporte simple apoyan también la correlación directa con el puntage MFMG. En una regresión múltiple del paso, la cadencia sola era un predictor significativo del puntage MFMG. Los parámetros de tiempo y distancia, la excursión de cadera y rodilla en un piano sagital y los valores de MFMG todos son factores añadidos a las normas pediátricas con mayor valor al aumcntar la gravedad funcional. El estudio confirma que la marcha es representativa del estado motor general en la PC y que el análisis MFMG y de la marcha constituyen medicioncs complementarias en la evaluación funcional de estos niños.

The mechanisms responsible for the elevated levels of circulating GH observed in diabetes mellitus (DM) remain incompletely defined. To assess the episodic fluctuations in serum GH as a reflection of hypothalamic-pituitary activity, we accumulated GH concentration-time series in a total of 48 adult men and women with and without insulin-dependent DM by obtaining serum samples at 10-min intervals over 24 h. Significant pulses of GH release were subsequently identified and characterized by an objective, statistically based pulse detection algorithm (Cluster) and fixed circadian (24-h) periodicities of secretory activity, resolved using Fourier expansion time-series analysis. Compared to those in age-matched controls, integrated 24-h concentrations of GH were 2- to 3.5-fold higher in diabetic men (P = 0.002) and women (P = 0.0005). Both men and women with DM had over 50% more GH pulses per 24 h than their non-DM counterparts. In addition, maximal GH pulse amplitude was markedly elevated in the men and women with DM (P = 0.0019 and 0.0189, respectively). That the increase in maximal pulse amplitude was accounted for by greater baseline levels was documented by a higher interpulse valley mean GH concentration in the diabetics compared to the controls (P = 0.0437 and 0.0056, men and women, respectively) and the absence of any difference in incremental pulse amplitude for either sex (P greater than 0.05). DM men had larger GH pulse areas (P = 0.039) than control men, apparently accounted for by greater pulse width (P = 0.0037). Pulse areas in DM and non-DM women were indistinguishable. Time-series analysis revealed that the 24-h (circadian) rhythms of serum GH concentrations exhibited significantly increased amplitudes in the diabetic group as a whole (compared to the controls, P = 0.011). However, the times of maximal GH concentrations (acrophases) were not significantly different. As a group, serum insulin-like growth factor-I was lower in DM vs. non-DM individuals (P = 0.0014), although when separated by sex this difference did not reach statistical significance in women (P = 0.317). The present data confirm the higher circulating levels of GH previously reported to occur in individuals with poorly controlled DM. The altered frequency of GH pulses together with enhanced interpulse GH concentrations and an amplified circadian GH rhythm are compatible with hypothalamic dysfunction associated with dysregulation of somatostatin and/or GHRH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

OBJECTIVE: Prospective study of the efficacy of calf lung surfactant extract in pediatric respiratory failure. DESIGN: Multi-institutional, prospective, randomized, controlled, unblinded trial. SETTING: Eight pediatric intensive care units (ICU) of tertiary medical centers. PATIENTS: Forty-two children with acute hypoxemic respiratory failure characterized by diffuse, bilateral pulmonary infiltrates, need for ventilatory support, and an oxygenation index of >7. INTERVENTION: Instillation of intratracheal surfactant (80 mL/m2). MEASUREMENTS AND MAIN RESULTS: Ventilator parameters, arterial blood gases, and derived oxygenation and ventilation indices were recorded before and at intervals after surfactant administration. Complications and outcome measures, including mortality, duration of mechanical ventilation, and length of pediatric ICU and hospital stay, were also examined. Patients who received surfactant demonstrated rapid improvement in oxygenation and, on average, were extubated 4.2 days (32%) sooner and spent 5 fewer days (30%) in pediatric intensive care than control patients. There was no difference in mortality or overall hospital stay. Surfactant administration was associated with no serious adverse effects. CONCLUSIONS: Administration of calf lung surfactant extract, calfactant, appears to be safe and is associated with rapid improvement in oxygenation, earlier extubation, and decreased requirement for intensive care in children with acute hypoxemic respiratory failure. Further study is needed, however, before widespread use in pediatric respiratory failure can be recommended.

OBJECTIVE: To prospectively assess the presence of posttraumatic stress disorder (PTSD) in children hospitalized following acute physical injury. The focus was identification of the incidence of PTSD, PTSD symptoms, and exploration of factors associated with development of PTSD symptoms and disorder. METHOD: Forty children ages 8-17 were interviewed approximately 1 month following a serious injury and assessed for PTSD, pretrauma behavior problems, levels of peritraumatic fear, and posttraumatic thought suppression. RESULTS: Twenty-two and a half percent of participants met DSM-IV diagnostic criteria for PTSD; 47.5% met criteria for at least two of the three PTSD symptom clusters. Greater thought suppression was associated with increased symptoms of PTSD, as were the child's peritraumatic fear response and pretrauma internalizing behaviors. CONCLUSIONS: Results suggest that many children who have been hospitalized for physical trauma may be experiencing clinically significant PTSD symptomatology and may benefit from psychological as well as medical intervention.

Pain frequency and its association with participation, function, and health-related quality of life were evaluated in a sample of 198 children (58% male; mean age 10 years 7 months, SD 3 years 11 months; range 5 to 18 years) with moderate to severe cerebral palsy (CP). Gross Motor Functional Classification System (GMFCS) levels were III to V (23% level III, 23% level IV, 31% level V without a gastrostomy tube, and 23% were level V with a gastrostomy tube). Assessment was carried out using the parent-report Child Health Questionnaire (CHQ) and questions assessing health, medical utilization, and medication use. Pain frequency ranged from 'none' to 'every day'. Eleven percent of parents reported pain almost every day (z score=-0.38, p<0.001). Pain was related to severity of motor impairment and the presence of a gastrostomy; parents of the most severely affected children reported the highest pain frequency (p=0.05). Pain was correlated with school days missed (p=0.03) and days in bed (p=0.01). Children taking gastrointestinal medications were reported to have greater pain frequency (p<0.001). The Parental Impact--Emotional subscale of the CHQ was correlated with reported pain (r=0.38, p<0.001). Pain was frequent in children with moderate or severe CP. Pain was more prevalent with more severe impairment and was associated with educational and social consequences.

PURPOSE To improve the outcomes of patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), the proteasome inhibitor bortezomib was examined in the Children's Oncology Group phase III clinical trial AALL1231, which also attempted to reduce the use of prophylactic cranial radiation (CRT) in newly diagnosed T-ALL. PATIENTS AND METHODS Children and young adults with T-ALL/T-LL were randomly assigned to a modified augmented Berlin-Frankfurt-Münster chemotherapy regimen with/without bortezomib during induction and delayed intensification. Multiple modifications were made to the augmented Berlin-Frankfurt-Münster backbone used in the predecessor trial, AALL0434, including using dexamethasone instead of prednisone and adding two extra doses of pegaspargase in an attempt to eliminate CRT in most patients. RESULTS AALL1231 accrued 824 eligible and evaluable patients from 2014 to 2017. The 4-year event-free survival (EFS) and overall survival (OS) for arm A (no bortezomib) versus arm B (bortezomib) were 80.1% ± 2.3% versus 83.8% ± 2.1% (EFS, P = .131) and 85.7% ± 2.0% versus 88.3% ± 1.8% (OS, P = .085). Patients with T-LL had improved EFS and OS with bortezomib: 4-year EFS (76.5% ± 5.1% v 86.4% ± 4.0%; P = .041); and 4-year OS (78.3% ± 4.9% v 89.5% ± 3.6%; P = .009). No excess toxicity was seen with bortezomib. In AALL0434, 90.8% of patients with T-ALL received CRT. In AALL1231, 9.5% of patients were scheduled to receive CRT. Evaluation of comparable AALL0434 patients who received CRT and AALL1231 patients who did not receive CRT demonstrated no statistical differences in EFS ( P = .412) and OS ( P = .600). CONCLUSION Patients with T-LL had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. Systemic therapy intensification allowed elimination of CRT in more than 90% of patients with T-ALL without excess relapse.

OBJECTIVE: Hospital care for children with viral lower respiratory illness (VLRI) is highly variable, and its relationship to severity and impact on outcome is unclear. Using the Pediatric Comprehensive Severity Index, we analyzed the correlation of institutional practice variation with severity and resource utilization in 10 children's medical centers. METHODS: Demographics, clinical information, laboratory results, interventions, and outcomes were extracted from the charts of consecutive infants with VLRI from 10 children's medical centers. Pediatric Component of the Comprehensive Severity Index scoring was performed at admission and at maximum during hospitalization. The correlation of patient variables, interventions, and resource utilization at the patient level was compared with their correlation at the aggregate institutional level. RESULTS: Of 601 patients, 1 died, 6 were discharged to home health care, 4 were discharged to rehabilitative care, and 2 were discharged to chronic nursing care. Individual patient admission severity score correlated positively with patient hospital costs (r = 0.48), but institutional average patient severity was negatively correlated with average institutional costs (r = -0.26). Maximal severity score correlated well with costs (r = 0.66) and length of stay (LOS; r = 0.64) at the patient level but poorly at the institutional level (r = 0.07 costs; r = 0.40 LOS). The institutional intensity of therapy was negatively correlated with admission severity (r = -0.03) but strongly correlated with costs (r = 0.84) and LOS (r = 0.83). CONCLUSIONS: Institutional differences in care practices for children with VLRI were not explained by differences in patient severity and did not affect the children's recovery but correlated significantly with hospital costs and LOS.

SUMMARY The purpose of this cross‐sectional study was to determine correlates of linear growth in children with cerebral palsy (CP). 171 children with CP were measured and their charts reviewed, z scores were calculated for weight (Wz) and height (Hz). Hz correlated positively with Wz and head circumference, and negatively with age, the presence of spastic quadriplegia, non‐ambulation and seizures. The correlation between Hz and age was stronger when non‐ambulatory children were analysed separately. Multiple linear regression resulted in only Wz and age contributing significantly to the variance in stature as measured by Hz. These results provide preliminary evidence that nutritional status is a major correlate of growth in CP. The finding that linear growth worsens with age independent of nutrition suggests that other factors also influence growth in CP. RÉSUMÉ Corrélations cliniques de la croissance en laille chez l'enfant IMC Le but de cette étude transversale était d'établir des corrélations de croissance linéaire chez les enfants IMC. Des mesures fürent effectuees chez 171 IMC et les résultats fürent analysés. Des scores z fürent calculés pour le poids (Wz) et la taille (Hz). Hz était corrélée positivement avec Wz et le tour de tête, et négativement avec l'âge, la présence d'une quadriplégic spastique, l'absence de marchc et la comitialité. La corrélation entrc Hz et l'âge se montra plus élevée lorsquc les enfants ne marchant pas fürent étudiés séparément. La régression linéaire multiple montra que seuls Wz et l'âge contribuaient significativement à la variance de la taille mesurée. Ces résultats favorisent l'idée que l'état nutritionnel est un facteur majeur de croissance chez l'IMC. Le fait que la croissance linéaire s'altère avec l'âge indépendamment de l'alimentation suggère que d'autres facteurs influencent également la croissance chez l'IMC. ZUSAMMENFASSUNG Klinische Parameter des linearen Wachstums bei Kindern mil Cerebralparese Es war das Ziel dieser Querschnittsstudie, die Parameter des linearen Wachstums bei Kindern mil Cerebralparese (CP) zu untersuchen. 171 Kinder mit Cerebralparese wurden untersucht und ihre Meßkarten ausgewcrtet. Es wurden z Scores für Gewicht (Wz) und Größe (Hz) bestimmt. Hz korrelierte positiv mit Wz und Kopfumfang und negativ mit Alter, spastischer Tetraplegie, Gehunfähigkeit und Anfällen. Die Korrelation zwischen Hz und Alter war stärker, wenn die nicht gehfähigen Kinder getrennt analysiert wurden. Multiple lineare Regressionsberechnungen ergaben, daß nur Wz und Alter signifikant zur Veränderung der Statur, gemessen durch Hz, beitrugen. Diese Ergebnisse sind ein vorläufiger Beweis dafür, daß der Emahrungsstatus ein wichtiger Wachstumsfaktor bei CP ist. Der Befund, daß das lineare Wachstum unabhängig von der‐ Ernährung mit dem Alter schlechter wird, bedeuiet, daß noch andere Faktoren das Wachstum bei Patienten mit CP beeinflussen. RESUMEN Correlatión clínica del crecimiento lineal en niños con parálisis cerebral El propósito de este estudio transverso fue el determinar la c'orrelación del crecimiento lineal en niños con parálisis cerebral (PC). 171 niños con PC fueron tallados y sus gráficos revisados. Se calcularon z puntajes para el peso (Pz) y estatura (Ez). Ez se correlacionaba positivamente con Pz y con el perímetro craneal y negativamente con la edad, la presencia de una cuatriplejia espástica, la no ambulatión y las convulsiones. La correlatión entre Ez y la edad era mayor si se analizaban separadamente los niños que no andaban. Una regresión lineal múltiple sólo se dio en Pz y edad lo que contribuía significativamente a la varianza de la estatura medida en forma de Ez. Estos resultados proporcionan una evidencia preliminar de que el estado nutritivo es un importante correlativo del crecimiento en la PC. El hallazgo de que el crecimiento lineal empeora con la edad con independencia de la nutrición, sugiere que hay otros factors que influencian también el crecimiento en la PC.

Investigated the relation between maternal resolution/nonresolution of a child's diagnosis of chronic medical condition to self-reported measures of parenting stress, marital quality, and social support. Mothers were administered the Reaction to Diagnosis Interview, and classified as Resolved/Unresolved with respect to the child's diagnosis. Mothers also completed the Parenting Stress Index, Dyadic Adjustment Scale (DAS), Support Functions Scale, and Family Support Scale. Fathers completed the DAS. Maternal resolution vs. nonresolution of diagnosis was related to parenting stress, husband marital satisfaction, and level and helpfulness of social support. Resolution of diagnosis was not related to need for support. Specific subclassifications of Resolved and Unresolved also were differentially related to level and helpfulness of social support. Findings suggest that resolution/nonresolution of diagnosis has implications not only for individual functioning and child-parent interactions, as found in previous research, but also for other intimate familial relationships and social ecology.

The study was designed to determine the strategies used by diplegic subjects to change walking speed. Two groups, limited community ambulators and community ambulators, were compared with controls to determine if ability to increase speed would decrease as a function of motor impairment. Compared with matched controls, diplegic subjects were slower and relied more on cadence to increase speed. The ability to change velocity and stride length was significantly less in the diplegic groups than in controls and accounted for the wider difference in their fast walking velocity. Velocity and stride length decreased, whereas stance time increased as a function of motor involvement. In the limited community ambulators, pelvic excursion was increased, whereas hip and knee excursion was reduced. By assessing fast speed, differences between controls and diplegic groups became more apparent.

Objective: ), a type of ketogenic diet (KD), in subjects with relapsing MS while exploring potential benefits of KDs in MS. Methods: was objectively monitored by daily urine ketone testing. Fatigue and depression scores and fasting adipokines were obtained at baseline and on diet. Brain MRI was obtained at baseline and 6 months. Intention to treat was used for primary data analysis, and a per-protocol approach was used for secondary analysis. Results: < 0.0001) on diet. Conclusions: improves fatigue and depression while also promoting weight loss and reducing serologic proinflammatory adipokines. Classification of evidence: The study is rated Class IV because of the absence of a non-KD control group.

Summary The study was designed to determine the strategies used by diplegic subjects to change walking speed. Two groups, limited community ambulators and community ambulators, were compared with controls to determine if ability to increase speed would decrease as a function of motor impairment. Compared with matched controls, diplegic subjects were slower and relied more on cadence to increase speed. The ability to change velocity and stride length was significantly less in the diplegic groups than in controls and accounted for the wider difference in their fast walking velocity. Velocity and stride length decreased, whereas stance time increased as a function of motor involvement. In the limited community ambulators, pelvic excursion was increased, whereas hip and knee excursion was reduced. By assessing fast speed, differences between controls and diplegic groups became more apparent.

AggR is a transcriptional regulator of enteroaggregative Escherichia coli (EAEC) and has been proposed as the defining factor for typical EAEC strains. Expression of multiple putative virulence factors, including the aggregative adherence fimbriae (AAF), dispersin, the dispersin translocator Aat, and the Aai type VI secretion system, have been found to be regulated by AggR. Here, we confirm the existence of at least 44 AggR-regulated genes using DNA microarray and real-time quantitative reverse transcription-PCR (qRT-PCR); these genes include chromosomal and plasmid-borne loci and 19 previously unsuspected genes. Two previously uncharacterized virulence plasmid-encoded open reading frames (ORFs) (designated ORF3 and ORF4) exhibit significant identity with isoprenoid biosynthesis genes of Bacteria and Archaea. The predicted ORF4 product is closely related to isopentenyl isomerase (IDI) enzymes, whereas the predicted product of the adjacent ORF3 exhibits an aspartate-rich region that is common among trans-isoprenyl phosphate synthases. We show that mutations in these ORFs confer changes in bacterial surface properties. AggR coordinately controls expression of a large number of EAEC genes.