Showing papers by "Children's Memorial Hospital published in 2008"

Pediatric central nervous system germ cell tumors: a review.

Abstract: Central nervous system (CNS) germ cell tumors (GCTs) represent approximately 3% of primary pediatric brain tumors and encompass a wide pathologic spectrum. CNS GCTs are most commonly located in the pineal and suprasellar regions of the brain and can be divided into major groups including germinomas and nongerminomatous GCTs (NGGCTs), with teratomas often considered a separate category. The clinical presentation varies by location and size, and it frequently includes endocrine abnormalities, visual changes, and signs of increased intracranial pressure. Neuroimaging studies cannot differentiate GCTs from other tumors, and therefore, the diagnosis usually requires histologic confirmation. The rare exceptions are the cases where characteristic elevations of tumor markers, including alpha-fetoprotein and/or beta-human chorionic gonadotropin are documented in the serum and/or cerebrospinal fluid. In these cases, the imaging findings along with the tumor marker elevation may be diagnostic in themselves without the need for tissue confirmation. Treatment and prognosis differ greatly between groups. Germinomas have a superior prognosis than NGGCTs. Five-year overall survival rates >90% were reported initially with the use of craniospinal irradiation. More recently, the use of chemotherapy in addition to radiation therapy has afforded the ability to decrease the dose and volume of radiation therapy without affecting survival rates. NGGCTs are less radiosensitive than germinomas, but the use of adjuvant chemotherapy has improved survival rates in this group as well. The standard management for CNS GCTs remains controversial. Treatment regimens aimed to improve progression-free and overall survival times are ongoing.

Mutation in BAG3 Causes Severe Dominant Childhood Muscular Dystrophy

Abstract: Objective Myofibrillar myopathies (MFM) are morphologically distinct but genetically heterogeneous muscular dystrophies in which disintegration of Z disks and then of myofibrils is followed by ectopic accumulation of multiple proteins. Cardiomyopathy, neuropathy, and dominant inheritance are frequent associated features. Mutations in αB-crystallin, desmin, myotilin, Zasp, or filamin-C can cause MFM, and were detected in 32/85 patients of the Mayo MFM cohort. Bag3, another Z-disk associated protein, has antiapoptotic properties and its targeted deletion in mice causes fulminant myopathy with early lethality. We therefore searched for mutations in BAG3 in 53 unrelated MFM patients.

Molecular and clinical genetics of mitochondrial diseases due to POLG mutations

Abstract: Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial disease in children and adults. They are responsible for a heterogeneous group of at least 6 major phenotypes of neurodegenerative disease that include: 1) childhood Myocerebrohepatopathy Spectrum disorders (MCHS), 2) Alpers syndrome, 3) Ataxia Neuropathy Spectrum (ANS) disorders, 4) Myoclonus Epilepsy Myopathy Sensory Ataxia (MEMSA), 5) autosomal recessive Progressive External Ophthalmoplegia (arPEO), and 6) autosomal dominant Progressive External Ophthalmoplegia (adPEO). Due to the clinical heterogeneity, time-dependent evolution of symptoms, overlapping phenotypes, and inconsistencies in muscle pathology findings, definitive diagnosis relies on the molecular finding of deleterious mutations. We sequenced the exons and flanking intron region from approximately 350 patients displaying a phenotype consistent with POLG related mitochondrial disease and found informative mutations in 61 (17%). Two mutant alleles were identified in 31 unrelated index patients with autosomal recessive POLG-related disorders. Among them, 20 (67%) had Alpers syndrome, 4 (13%) had arPEO, and 3 (10%) had ANS. In addition, 30 patients carrying one altered POLG allele were found. A total of 25 novel alterations were identified, including 6 null mutations. We describe the predicted structural/functional and clinical importance of the previously unreported missense variants and discuss their likelihood of being pathogenic. In conclusion, sequence analysis allows the identification of mutations responsible for POLG-related disorders and, in most of the autosomal recessive cases where two mutant alleles are found in trans, finding deleterious mutations can provide an unequivocal diagnosis of the disease.

From Suspicion of Physical Child Abuse to Reporting: Primary Care Clinician Decision-Making

Abstract: OBJECTIVES. The goals were to determine how frequently primary care clinicians reported suspected physical child abuse, the levels of suspicion associated with reporting, and what factors influenced reporting to child protective services. METHODS. In this prospective observational study, 434 clinicians collected data on 15 003 child injury visits, including information about the injury, child, family, likelihood that the injury was caused by child abuse (5-point scale), and whether the injury was reported to child protective services. Data on 327 clinicians indicating some suspicion of child abuse for 1683 injuries were analyzed. RESULTS. Clinicians reported 95 (6%) of the 1683 patients to child protective services. Clinicians did not report 27% of injuries considered likely or very likely caused by child abuse and 76% of injuries considered possibly caused by child abuse. Reporting rates were increased if the clinician perceived the injury to be inconsistent with the history and if the patient was referred to the clinician for suspected child abuse. Patients who had an injury that was not a laceration, who had>1 family risk factor, who had a serious injury, who had a child risk factor other than an inconsistent injury, who were black, or who were unfamiliar to the clinician were more likely to be reported. Clinicians who had not reported all suspicious injuries during their career or who had lost families as patients because of previous reports were more likely to report suspicious injuries. CONCLUSIONS. Clinicians had some degree of suspicion that approximately 10% of the injuries they evaluated were caused by child abuse. Clinicians did not report all suspicious injuries to child protective services, even if the level of suspicion was high (likely or very likely caused by child abuse). Child, family, and injury characteristics and clinician previous experiences influenced decisions to report. Language: en

Clinicians' description of factors influencing their reporting of suspected child abuse: report of the Child Abuse Reporting Experience Study Research Group.

Abstract: OBJECTIVES. Primary care clinicians participating in the Child Abuse Reporting Experience Study did not report all suspected physical child abuse to child protective services. This evaluation of study data seeks (1) to identify factors clinicians weighed when deciding whether to report injuries they suspected might have been caused by child abuse; (2) to describe clinicians’ management strategies for children with injuries from suspected child abuse that were not reported; and (3) to describe how clinicians explained not reporting high-suspicion injuries. METHODS. From the 434 pediatric primary care clinicians who participated in the Child Abuse Reporting Experience Study and who indicated they had provided care for a child with an injury they perceived as suspicious, a subsample of 75 of 81 clinicians completed a telephone interview. Interviewees included 36 clinicians who suspected child abuse but did not report the injury to child protective services (12 with high suspicion and 24 with some suspicion) and 39 who reported the suspicious injury. Interviews were analyzed for major themes and subthemes, including decision-making regarding reporting of suspected physical child abuse to child protective services and alternative management strategies. RESULTS. Four major themes emerged regarding the clinicians’ reporting decisions, that is, familiarity with the family, reference to elements of the case history, use of available resources, and perception of expected outcomes of reporting to child protective services. When they did not report, clinicians planned alternative management strategies, including active or informal case follow-up management. When interviewed, some clinicians modified their original opinion that an injury was likely or very likely caused by abuse, to explain why they did not report to child protective services. CONCLUSIONS. Decisions about reporting to child protective services are guided by injury circumstances and history, knowledge of and experiences with the family, consultation with others, and previous experiences with child protective services.

Outcomes of 5-year survivors of pediatric liver transplantation: report on 461 children from a north american multicenter registry.

Abstract: OBJECTIVES.Although liver transplantation has been the standard of care therapy for life-threatening liver diseases for 20 years, data on the long-term impact of liver transplantation in children have been primarily limited to single-center experiences. The objective of this study was to characterize and evaluate the clinical course of children who have survived 5 years after pediatric liver transplantation in multiple centers across North America. PATIENTS AND METHODS.Patients enrolled in the Studies of Pediatric Liver Transplantation database registry who had undergone liver transplantation at 1 of 45 pediatric centers between 1996 and 2001 and survived 5 years from liver transplantation were identified and their clinical courses retrospectively reviewed. RESULTS.The first graft survival for 461 five-year survivors was 88%, with 55 (12%) and 10 (2%) children undergoing a second and third liver transplantation. At the 5-year anniversary clinic visit, liver function was preserved in the majority with daily use of immunosuppression therapy, including a calcineurin inhibitor and oral prednisone, reported by 97% and 25% of children, respectively. The probability of an episode of acute cellular rejection occurring within 5 years after liver transplantation was 60%. Chronic rejection occurred in 5% patients. Posttransplant lymphoproliferative disease was diagnosed in 6% children. Calculated glomerular filtration rate was 90 mL/minute per 1.73 m 2 in 13% of 5-year survivors. Age- and genderadjusted BMI 95th percentile was noted in 12%, with height below the 10th percentile in 29%. CONCLUSIONS.Children who are 5-year survivors of liver transplantation have good graft function, but chronic medical conditions and posttransplantation complications affect extrahepatic organs. A comprehensive approach to the management of these patients’ multiple unique needs requires the expertise and commitment of health care providers both beyond and within transplant centers to further optimize long-term outcomes for pediatric liver transplant recipients. Pediatrics 2008;122:e1128‐e1135

Role of Brain Inflammation in Epileptogenesis

Abstract: Inflammation is known to participate in the mediation of a growing number of acute and chronic neurological disorders. Even so, the involvement of inflammation in the pathogenesis of epilepsy and seizure-induced brain damage has only recently been appreciated. Inflammatory processes, including activation of microglia and astrocytes and production of proinflammatory cytokines and related molecules, have been described in human epilepsy patients as well as in experimental models of epilepsy. For many decades, a functional role for brain inflammation has been implied by the effective use of anti-inflammatory treatments, such as steroids, in treating intractable pediatric epilepsy of diverse causes. Conversely, common pediatric infectious or autoimmune diseases are often accompanied by seizures during the course of illness. In addition, genetic susceptibility to inflammation correlated with an increased risk of epilepsy. Mounting evidence thus supports the hypothesis that inflammation may contribute to epileptogenesis and cause neuronal injury in epilepsy. We provide an overview of the current knowledge that implicates brain inflammation as a common predisposing factor in epilepsy, particularly childhood epilepsy.

Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the "Head Start" I and II protocols.

Abstract: Purpose To determine the survival of infants and young children with non-metastatic medulloblastoma using intensive myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue (AuHCR). Methods Twenty-one children less than 3 years old at diagnosis with non-metastatic medulloblastoma were enrolled on two identical serial studies, “Head Start” I and “Head Start” II. After surgery, patients received five cycles of induction chemotherapy consisting of vincristine, cisplatin, cyclophosphamide and etoposide. Following induction, all patients underwent myeloablative chemotherapy using carboplatin, thiotepa and etoposide with AuHCR. Irradiation was used only at relapse. Results The 5-year event-free (EFS) and overall survival (OS) rates (±SE) for all patients, patients with gross total resection, and patients with residual tumor were 52 ± 11% and 70 ± 10%, 64 ± 13% and 79 ± 11%, and 29 ± 17% and 57 ± 19%, respectively. The 5-year EFS and OS ( ± SE) for patients with desmoplastic and classical medulloblastoma were 67 ± 16% and 78 ± 14%, and 42 ± 14 and 67 ± 14%, respectively. There were four treatment related deaths. The majority of survivors (71%) avoided irradiation completely. Mean intellectual functioning and quality of life (QoL) for children surviving without irradiation was within average range for a majority of survivors tested. Conclusion This strategy of brief intensive chemotherapy for young children with non-metastatic medulloblastoma eliminated the need for craniospinal irradiation 52% of the patients, and may preserve QoL and intellectual functioning. The excellent survival rates are somewhat dampened by high toxic mortality. Pediatr Blood Cancer 2008;50:1169–1175. © 2008 Wiley-Liss, Inc.

Suppression of acute proinflammatory cytokine and chemokine upregulation by post-injury administration of a novel small molecule improves long-term neurologic outcome in a mouse model of traumatic brain injury

Abstract: Traumatic brain injury (TBI) with its associated morbidity is a major area of unmet medical need that lacks effective therapies. TBI initiates a neuroinflammatory cascade characterized by activation of astrocytes and microglia, and increased production of immune mediators including proinflammatory cytokines and chemokines. This inflammatory response contributes both to the acute pathologic processes following TBI including cerebral edema, in addition to longer-term neuronal damage and cognitive impairment. However, activated glia also play a neuroprotective and reparative role in recovery from injury. Thus, potential therapeutic strategies targeting the neuroinflammatory cascade must use careful dosing considerations, such as amount of drug and timing of administration post injury, in order not to interfere with the reparative contribution of activated glia. We tested the hypothesis that attenuation of the acute increase in proinflammatory cytokines and chemokines following TBI would decrease neurologic injury and improve functional neurologic outcome. We used the small molecule experimental therapeutic, Minozac (Mzc), to suppress TBI-induced up-regulation of glial activation and proinflammatory cytokines back towards basal levels. Mzc was administered in a clinically relevant time window post-injury in a murine closed-skull, cortical impact model of TBI. Mzc effects on the acute increase in brain cytokine and chemokine levels were measured as well as the effect on neuronal injury and neurobehavioral function. Administration of Mzc (5 mg/kg) at 3 h and 9 h post-TBI attenuates the acute increase in proinflammatory cytokine and chemokine levels, reduces astrocyte activation, and the longer term neurologic injury, and neurobehavioral deficits measured by Y maze performance over a 28-day recovery period. Mzc-treated animals also have no significant increase in brain water content (edema), a major cause of the neurologic morbidity associated with TBI. These results support the hypothesis that proinflammatory cytokines contribute to a glial activation cycle that produces neuronal dysfunction or injury following TBI. The improvement in long-term functional neurologic outcome following suppression of cytokine upregulation in a clinically relevant therapeutic window indicates that selective targeting of neuroinflammation may lead to novel therapies for the major neurologic morbidities resulting from head injury, and indicates the potential of Mzc as a future therapeutic for TBI.

Effect of antibiotic pretreatment on cerebrospinal fluid profiles of children with bacterial meningitis.

Abstract: OBJECTIVE. The goal of this study was to evaluate the effect of antibiotic administration before lumbar puncture on cerebrospinal fluid profiles in children with bacterial meningitis. METHODS. We reviewed the medical records of all children (1 month to 18 years of age) with bacterial meningitis who presented to 20 pediatric emergency departments between 2001 and 2004. Bacterial meningitis was defined by positive cerebrospinal fluid culture results for a bacterial pathogen or cerebrospinal fluid pleocytosis with positive blood culture and/or cerebrospinal fluid latex agglutination results. Probable bacterial meningitis was defined as positive cerebrospinal fluid Gram stain results with negative results of bacterial cultures of blood and cerebrospinal fluid. Antibiotic pretreatment was defined as any antibiotic administered within 72 hours before the lumbar puncture. RESULTS. We identified 231 patients with bacterial meningitis and another 14 with probable bacterial meningitis. Of those 245 patients, 85 (35%) had received antibiotic pretreatment. After adjustment for patient age, duration and severity of illness at presentation, and bacterial pathogen, longer duration of antibiotic pretreatment was not significantly associated with cerebrospinal fluid white blood cell count, cerebrospinal fluid absolute neutrophil count. However, antibiotic pretreatment was significantly associated with higher cerebrospinal fluid glucose and lower cerebrospinal fluid protein levels. Although these effects became apparent earlier, patients with ≥12 hours of pretreatment, compared with patients who either were not pretreated or were pretreated for CONCLUSIONS. In patients with bacterial meningitis, antibiotic pretreatment is associated with higher cerebrospinal fluid glucose levels and lower cerebrospinal fluid protein levels, although pretreatment does not modify cerebrospinal fluid white blood cell count or absolute neutrophil count results.

Modeling the Cardiac Tissue Electrode Interface Using Fractional Calculus

Abstract: The tissue electrode interface is common to all forms of biopotential recording (e.g., ECG, EMG, EEG) and functional electrical stimulation (e.g., pacemaker, cochlear implant, deep brain stimulation). Conventional lumped element circuit models of electrodes can be extended by generalization of the order of differentiation through modification of the defining current-voltage relationships. Such fractional order models provide an improved description of observed bioelectrode behaviour, but recent experimental studies of cardiac tissue suggest that additional mathematical tools may be needed to describe this complex system.

Phase I Clinical Trial of Cilengitide in Children With Refractory Brain Tumors: Pediatric Brain Tumor Consortium Study PBTC-012

Abstract: Purpose A phase I trial of the antiangiogenesis agent cilengitide (EMD 121974), an alpha v beta 3,5 integrin antagonist, was performed to estimate the maximum-tolerated dose (MTD) and describe dose-limiting toxicities (DLTs) and the incidence and severity of other toxicities when administered to children with refractory brain tumors. Patients and Methods Thirty-one assessable patients received intravenous cilengitide over 1 hour twice a week for up to 52 weeks at dosages from 120 to 2,400 mg/m 2 . Serial blood and urine samples for clinical

Ser1369Ala Variant in Sulfonylurea Receptor Gene ABCC8 Is Associated With Antidiabetic Efficacy of Gliclazide in Chinese Type 2 Diabetic Patients

Abstract: OBJECTIVE—The purpose of this study was to investigate whether genetic variants could influence the antidiabetic efficacy of gliclazide in type 2 diabetic patients. RESEARCH DESIGN AND METHODS—A total of 1,268 type 2 diabetic patients whose diabetes was diagnosed within the past 5 years and who had no recent hypoglycemic treatment were enrolled from 23 hospitals in China. All of the patients were treated with gliclazide for 8 weeks. Fasting and oral glucose tolerance test 2-h plasma glucose, fasting insulin, and A1C were measured at baseline and after 8 weeks of treatment. We used two independent cohorts to test the associations of 25 single nuclear polymorphisms in 11 candidate genes with the antidiabetic efficacy of gliclazide. A general linear regression model was used to test the association with adjustment for important covariates. RESULTS—After 8 weeks of gliclazide therapy, mean fasting plasma glucose (FPG) was reduced from 11.1 mmol/l at baseline to 7.7 mmol/l. In cohort 1, we genotyped all 25 SNPs (n = 661) and found that Ser1369Ala of the ABCC8 gene and rs5210 of the KCNJ11 gene were significantly associated with decreases in FPG (P = 0.002). We further genotyped Ser1369Ala in cohort 2 (n = 607) and confirmed the association identified in cohort 1. In the pooled analysis, compared with subjects with the Ser/Ser genotype, subjects with the Ala/Ala genotype had a 7.7% greater decrease in FPG (P < 0.001), an 11.9% greater decrease in 2-h plasma glucose (P = 0.003), and a 3.5% greater decrease in A1C (P = 0.06) after 8 weeks of treatment with gliclazide. CONCLUSIONS—In two independent cohorts of Chinese type 2 diabetic patients, we found consistent evidence that the Ser1369Ala variant in the ABCC8 gene can influence the antidiabetic efficacy of gliclazide.

Treatment of Wilms tumor relapsing after initial treatment with vincristine, actinomycin D, and doxorubicin. A report from the National Wilms Tumor Study Group.

Abstract: Objective We evaluated the use of alternating cycles of cyclophosphamide/etoposide and carboplatin/etoposide in children entered on National Wilms Tumor Study (NWTS)-5 who were diagnosed between August 1, 1995 and May 31, 2002 and who relapsed after chemotherapy with vincristine, actinomycin D, and doxorubicin (VAD) and radiation therapy (DD-4A). Patients and methods One hundred three patients who relapsed or had progressive disease after initial VAD chemotherapy and radiation therapy were registered on stratum C of the NWTS-5 Relapse protocol. Twelve patients were not evaluable: five due to insufficient data, six due to major protocol violations, and one for refusal of therapy. Among the 91 remaining patients, 14 with stage V Wilms tumor (WT), 1 with contralateral relapse, and 16 who did not achieve a complete response (CR) to the initial three-drug chemotherapy were not included in this analysis. Relapse treatment included alternating courses of the drug pairs cyclophosphamide/etoposide and carboplatin/etoposide, surgery, and radiation therapy. Results The outcomes of 60 patients were analyzed. The lung was the only site of relapse for 33 patients; other sites of relapse included the operative bed, the abdomen, and liver. Four-year event-free survival (EFS) and overall survival (OS) were 42.3 and 48.0% respectively for all patients and were 48.9 and 52.8% for those who relapsed in the lungs only. Thrombocytopenia was the most frequent toxicity. Conclusion These results demonstrate that approximately one-half of children with unilateral WT who relapse after initial treatment with VAD and radiation therapy can be successfully retreated.

Adherence to antiretroviral treatment among pregnant and postpartum HIV-infected women

Abstract: Among women with HIV infection, pregnancy is a time when maintenance of maternal health and reduction of vertical HIV transmission are primary concerns. Few studies have examined adherence to Antiretroviral Treatment (ART) during pregnancy and in the postpartum period when the demands of childcare may significantly interfere with women's self-care behaviors. This study examined ART use and adherence in HIV-infected pregnant and postpartum women participating in the Women and Infants Transmission Study (WITS-IV) in the US. Adherence was assessed through a self-report interview during the third trimester of pregnancy and six-month postpartum. Data were also collected on demographics, biomedical markers and health related symptoms. During the third trimester visit, 77% (309/399) of women completed the self-report adherence measure; 61% (188/309) reported complete adherence. Factors associated with non-adherence included advanced HIV disease status, higher HIV-RNA viral load, more health-related symptoms and alcohol and tobacco use. At six-month postpartum, 55% (220/399) completed the measure; 44% (97/220) of these women reported complete adherence. Factors associated with non-adherence during the postpartum period were ethnicity, more health-related symptoms and WITS clinical site. Results of multivariate analyses using Generalized Estimated Equation analyses across the two visits revealed that more health-related symptoms, higher HIV-RNA viral load, increased alcohol use and clinical site were independently associated with ART non-adherence. These analyses indicate that medication adherence is more likely during pregnancy than postpartum in HIV-infected women, perhaps provoked by motivation to reduce vertical transmission and/or intensive antepartum surveillance. Further investigation is warranted to clarify factors implicated in women's decision-making process regarding ART medication adherence.

Prematurity, chorioamnionitis, and the development of recurrent wheezing: a prospective birth cohort study.

Abstract: Background Prematurity ( Objective To investigate the relationship of prematurity and chorioamnionitis with the development of early childhood recurrent wheezing. Methods The Boston Birth Cohort (n = 1096) were followed prospectively from birth to a mean age of 2.2 ± 2 years. Perinatal and postnatal clinical data and placental pathology were collected. The primary outcome was recurrent wheezing (≥2 physician documented episodes). Secondary outcomes included physician-diagnosed asthma, food allergy, and eczema. Preterm children were grouped by gestational age into moderately (33-36.9 weeks) and very preterm ( Results Prematurity was associated with recurrent wheezing (odds ratio [OR], 1.7; 95% CI, 1.2-2.6). However, when subjects were grouped by degree of prematurity with or without chorioamnionitis, the highest risk of wheezing (OR, 4.0; 95% CI, 2.0-8.0) and physician-diagnosed asthma (OR, 4.4; 95% CI, 2.2-8.7) was present in the very preterm children with chorioamnionitis. The effect on both wheezing (OR, 5.4; 95% CI, 2.4-12.0) and asthma (OR, 5.2; 95% CI, 2.3-11.9) was greater in African Americans. Neither prematurity nor chorioamnionitis was associated with food allergy or eczema. Conclusion We found a strong joint effect of prematurity and chorioamnionitis on early childhood wheezing. This effect was stronger in African American subjects.

Neutrophil gelatinase-associated lipocalin as a biomarker of disease activity in pediatric lupus nephritis

Abstract: We hypothesized that neutrophil gelatinase- associated lipocalin (NGAL) is an early predictive bio- marker of disease activity in lupus nephritis. NGAL in serial plasma (PNGAL) and urine (UNGAL) samples was measured by enzyme-linked immunosorbent assay (ELISA) in 85 participants with pediatric systemic lupus erythema- tosus (pSLE), healthy children (n=50), and children with juvenile idiopathic arthritis (JIA) (n=30). Disease activity was measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Plasma and urinary NGAL were significantly increased in subjects with pSLE compared with those with JIA or with healthy controls (all p<0.03), and unrelated to subjects' age, weight, or height. Plasma and urinary NGAL were stable in pSLE subjects with unchanged disease activity. The pSLE subjects with worsening global or renal disease activity had a mean ± standard error (SE) increase of UNGAL (in ng/ml) of 11.5± 6.4 or 36.6±12.1 (p<0.01), corresponding to a 156% or 380% increase, respectively. PNGAL increased with wors- ening disease but to a much lesser degree than UNGAL (global disease activity (mean ± SE): 7.3±6.2 or 21%; renal disease activity: 20.2±6.0 or 51%; both p=not significant). In conclusion, NGAL in urine but not in plasma represents a novel biomarker for renal disease activity in pSLE.

Intensive chemotherapy followed by consolidative myeloablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) in young children with newly diagnosed supratentorial primitive neuroectodermal tumors (sPNETs): report of the Head Start I and II experience.

Abstract: Background Children with newly diagnosed supratentorial primitive neuroectodermal tumors (sPNET) have poor outcomes compared to medulloblastoma patients, despite similar treatments. In an effort to improve overall survival (OS) and event-free survival (EFS) and to decrease radiation exposure, the Head Start (HS) protocols treated children with newly diagnosed sPNET utilizing intensified induction chemotherapy (ICHT) followed by consolidation with myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR). Procedures Between 1991 and 2002, 43 children with sPNET were prospectively treated on two serial studies (HS I and II). After maximal safe surgical resection, patients on HS I and patients with localized disease on HS II were treated with five cycles of ICHT (vincristine, cisplatin, cyclophosphamide, and etoposide). Patients on HS II with disseminated disease received high-dose methotrexate during ICHT. If the disease remained stable or in response, patients received a single cycle of high-dose myeloablative chemotherapy followed by AuHCR. Results Five-year EFS and OS were 39% (95%CI: 24%, 53%) and 49 (95%CI: 33%, 62%), respectively. Non-pineal sPNET patients faired significantly better than those patients with pineal sPNETs. Metastasis at diagnosis, age, and extent of resection were not significant prognostic factors. Sixty percent of survivors (12 of 20) are alive without exposure to radiation therapy. Conclusions ICHT followed by AuHCR in young patients with newly diagnosed sPNET appears to not only provide an improved EFS and OS for patients who typically have a poor prognosis, but also it successfully permitted deferral and elimination of radiation therapy in a significant proportion of patients. Pediatr Blood Cancer 2008;50:312–318. © 2007 Wiley-Liss, Inc.

The organizational impact of a new graduate pediatric nurse mentoring program.

Abstract: Successful mentoring programs for new graduate nurses are designed to provide professional supports to ease the transition of these newcomers from student to practicing nurse. In the financially constrained health care environment, a resource-intensive program can be sustained only by leaders who see quantitative evidence of organizational impact over time. A descriptive study was undertaken at a pediatric academic medical center to compare the job satisfaction and retention rates of two cohorts of new graduate nurses: one before and one after the implementation of a Pediatric RN Internship Program. In this study overall job satisfaction was significantly higher in the post-internship group as compared to the pre-internship group. Improved job satisfaction was also reflected in a lower turnover rate (12% vs. 20% in the pre-internship group) that was sustained during the 2-year post-intervention study period. By lowering turnover rates, organizations avoid costs associated with recruitment, orientation, and temporary labor coverage for vacant RN positions.

Pendred syndrome and iodide transport in the thyroid

Abstract: Pendred syndrome is an autosomal recessive disorder characterized by sensorineural hearing impairment, presence of goiter, and a partial defect in iodide organification, which may be associated with insufficient thyroid hormone synthesis. Goiter development and development of hypothyroidism are variable and depend on nutritional iodide intake. Pendred syndrome is caused by biallelic mutations in the SLC26A4 gene, which encodes pendrin, a transporter of chloride, bicarbonate and iodide. This review discusses the controversies surrounding the potential role of pendrin in mediating apical iodide efflux into the lumen of thyroid follicles, and discusses its functional role in the kidney and the inner ear.

When do seizures usually improve with the ketogenic diet

Abstract: Summary Purpose: Parents often expect immediate seizure improvement after starting the ketogenic diet (KD) for their children The purpose of this study was to determine the typical time to seizure reduction as well as the time after which it was unlikely to be helpful in those children started on the KD Methods: Records of all children started on the KD at Johns Hopkins Hospital, Baltimore (n = 83) and Children's Memorial Hospital, Chicago (n = 35) from November 2003 to December 2006 were examined to determine the first day in which seizures were reportedly improved Results: Of the 118 children started on the KD, 99 (84%) had documented seizure reduction The overall median time to first improvement was 5 days (range: 1–65 days) Seventy-five percent of children improved within 14 days In those children who were fasted at KD onset, the time to improvement was quicker (median 5 vs 14 days, p < 001) with a higher percentage improving within 5 days (60% vs 31%, p = 001) No difference was identified between fasting and nonfasting in regards to long-term outcomes, however Discussion: The KD works quickly when effective, typically within the first 1–2 weeks Starting the KD after a fasting period may lead to a more rapid, but equivalent long-term seizure reduction, confirming prior reports If the KD has not led to seizure reduction after 2 months, it can probably be discontinued

Effect of mouse allergen and rodent environmental intervention on asthma in inner-city children

Abstract: Background Mouse allergens are prevalent in inner-city households, and increasing levels of exposure are associated with sensitization in children with asthma. Objectives To examine mouse allergen sensitization and exposure in inner-city children, mouse allergen as an independent risk factor for asthma morbidity, and the efficacy of a rodent environmental intervention. Methods We conducted a subanalysis of children with asthma aged 5 to 11 years enrolled in the Inner-City Asthma Study. After randomization, 150 participants received a home rodent-specific environmental intervention. Asthma morbidity measures were obtained bimonthly. Bedroom dust was collected and analyzed for Mus m 1 at baseline and every 6 months for 2 years. Results Twenty-two percent of children tested positive to mouse. Most bedrooms (80%) had detectable mouse allergen. Sensitization occurred at low levels of exposure. Sensitization and exposure were associated with increased asthma morbidity, including hospitalizations. Mouse allergen levels on the bedroom floor decreased 27.3% (95% confidence interval, −46.1% to −1.9%) in intervention homes. Mouse allergen reduction was associated with less missed school, sleep disruption, and caretaker burden but not symptoms or medical utilization. Conclusions Mouse allergen is prevalent in inner-city homes. Sensitization seems to occur at low levels of exposure. Mouse allergen is an independent risk factor for asthma morbidity. The described environmental intervention reduced mouse allergen levels and asthma-related sleep and activity disturbance.

The improvement of care for paediatric and congenital cardiac disease across the World: a challenge for the World Society for Pediatric and Congenital Heart Surgery.

Abstract: The diagnosis and treatment for paediatric and congenital cardiac disease has undergone remarkable progress over the last 60 years. Unfortunately, this progress has been largely limited to the developed world. Yet every year approximately 90% of the more than 1,000,000 children who are born with congenital cardiac disease across the world receive either suboptimal care or are totally denied care.While in the developed world the focus has changed from an effort to decrease post-operative mortality to now improving quality of life and decreasing morbidity, which is the focus of this Supplement, the rest of the world still needs to develop basic access to congenital cardiac care. The World Society for Pediatric and Congenital Heart Surgery [http://www.wspchs.org/] was established in 2006. The Vision of the World Society is that every child born anywhere in the world with a congenital heart defect should have access to appropriate medical and surgical care. The Mission of the World Society is to promote the highest quality comprehensive care to all patients with pediatric and/or congenital heart disease, from the fetus to the adult, regardless of the patient's economic means, with emphasis on excellence in education, research and community service.We present in this article an overview of the epidemiology of congenital cardiac disease, the current and future challenges to improve care in the developed and developing world, the impact of the globalization of cardiac surgery, and the role that the World Society should play. The World Society for Pediatric and Congenital Heart Surgery is in a unique position to influence and truly improve the global care of children and adults with congenital cardiac disease throughout the world [http://www.wspchs.org/].