"Bucking" for a diagnosis.

Foreign body ingestions are all too common in children. The adverse effects of many of these ingestions are well known. We present an interesting case report of "Buckyballs" and the implications of ingesting or placing in other orifices these strong rare-earth magnets. We illustrate that these toys can be of possible disastrous consequences. Although these products were removed from the marketplace, there is still the possibility of negative consequences. Our aim was to inform the physician population of their persistence and negative effects.

Untethering an unusual cause of kidney injury in a teenager with Down syndrome.

Acute kidney injury (AKI) is characterized by the acute nature and the inability of kidneys to maintain fluid homeostasis as well as adequate electrolyte and acid-base balance, resulting in an accumulation of nitrogenous waste and elevation of serum blood urea nitrogen and creatinine values. Acute kidney injury may be a single isolated event, yet oftentimes, it results from an acute chronic kidney disease. It is critical to seek out the etiology of AKI and to promptly manage the underlying chronic kidney disease to prevent comorbidities and mortality that may ensue. We described a case of a 16-year-old adolescent girl with Down syndrome who presented with AKI and electrolyte aberrance.Abdominal and renal ultrasounds demonstrated a significantly dilated bladder as well as frank hydronephrosis and hydroureter bilaterally. Foley catheter was successful in relieving the obstruction and improving her renal function. However, a magnetic resonance imaging was pursued in light of her chronic constipation and back pain, and it revealed a structural defect (tethered cord) that underlies a chronic process that was highly likely contributory to her AKI. She was managed accordingly with a guarded result and required long-term and close monitoring.

Acute neurological deterioration in ovarioleukodystrophy related to EIF2B mutations: pregnancy with oocyte donation is a potentially precipitating factor.

Mutations in the eukaryotic translation initiation factor 2B (eIF2B) represent a heterogenous group of autosomal recessive leucodystrophy characterized by a diffuse CSF-like aspect of the white matter at MRI designed as vanishing white matter (VWM) and episodes of acute deterioration after stresses. The mild juvenile and adult forms are often associated with primary ovarian failure, a syndrome referred to as ovarioleukodystrophy (OLD). We reported case of a woman with OLD who successfully underwent in vitro fertilization with donated oocytes and embryo transfer. Pregnancy was complicated by a non-convulsive epileptic status leading to the identification of compound heterozygous EIF2B5 mutation (p.Arg113His and p.Arg299His). The patient gave birth to a healthy child by Caesarean section. In conclusion, we report for the first time that in vitro fertilization and embryo transfer can lead to a successful procreation in patients with OLD related to EIF2B mutations. However this procedure must be considered with cautiousness, because of its potential neurological risks.

From quantum to classical modeling of radiation reaction: A focus on stochasticity effects.

Radiation reaction in the interaction of ultrarelativistic electrons with a strong external electromagnetic field is investigated using a kinetic approach in the nonlinear moderately quantum regime. Three complementary descriptions are discussed considering arbitrary geometries of interaction: a deterministic one relying on the quantum-corrected radiation reaction force in the Landau and Lifschitz (LL) form, a linear Boltzmann equation for the electron distribution function, and a Fokker-Planck (FP) expansion in the limit where the emitted photon energies are small with respect to that of the emitting electrons. The latter description is equivalent to a stochastic differential equation where the effect of the radiation reaction appears in the form of the deterministic term corresponding to the quantum-corrected LL friction force, and by a diffusion term accounting for the stochastic nature of photon emission. By studying the evolution of the energy moments of the electron distribution function with the three models, we are able to show that all three descriptions provide similar predictions on the temporal evolution of the average energy of an electron population in various physical situations of interest, even for large values of the quantum parameter χ. The FP and full linear Boltzmann descriptions also allow us to correctly describe the evolution of the energy variance (second-order moment) of the distribution function, while higher-order moments are in general correctly captured with the full linear Boltzmann description only. A general criterion for the limit of validity of each description is proposed, as well as a numerical scheme for the inclusion of the FP description in particle-in-cell codes. This work, not limited to the configuration of a monoenergetic electron beam colliding with a laser pulse, allows further insight into the relative importance of various effects of radiation reaction and in particular of the discrete and stochastic nature of high-energy photon emission and its back-reaction in the deformation of the particle distribution function.

[CACH/VWM syndrome and leucodystrophies related to EIF2B mutations]. / Le syndrome CACH/VWM et les leucodystrophies liées à des mutations EIF2B.

A new leukoencephalopathy, the CACH syndrome (Childhood Ataxia with Central nervous system Hypomyelination) or VWM (Vanishing White Matter) was identified on clinical and MRI criteria. Classically, this disease is characterized by (1) an onset between 2 and 5 years of age, with a cerebello-spastic syndrome exacerbated by episodes of fever or head trauma leading to death after 5 to 10 years of disease evolution, (2) a diffuse involvement of the white matter on cerebral MRI with a CSF-like signal intensity (cavitation), (3) a recessive autosomal mode of inheritance, (4) neuropathologic findings consistent with a cavitating orthochromatic leukodystrophy with increased number of oligodendrocytes with sometimes "foamy" aspect. A total of 148 cases have been reported so far. This disease is linked to mutations in the five EIF2B genes encoding the five subunits of the eukaryotic initiation factor 2B (eIF2B), involved in the protein synthesis and its regulation under cellular stresses. Clinical symptoms are variable, from fatale infantile forms (Cree leukoencephalopathy) and congenital forms associated with extra-neurological affections, to juvenile and adult forms (ovarioleukodystrophy) characterized by cognitive and behaviour dysfunctions and by a slow progression of the disease, leading to the term of eIF2B-related leukoencephalopathies. Prevalence of these remains unknown. Diagnosis lays on the detection of EIF2B mutations, affecting predominantly the EIF2B5 gene. A decrease in the intrinsic activity of the eIF2B factor (the guanine exchange activity, GEF) in lymphoblasts from patients seems to have a diagnostic value. The patho-physiology of the disease would involve a deficiency in astrocytes maturation leading to an increased susceptibility of the white matter to cellular stress. No specific treatment exists except the "prevention" of cellular stress. Corticosteroids sometimes proved to be useful in acute phases. Prognosis seems to correlate with the age of onset, the earliest forms being more severe.

Parental and Pediatricians' Perception of Need for Subspecialty Training in Pediatric Emergency Medicine for Delivering Emergency Care to Pediatric Patients.

The quality of pediatric emergency care may depend on the competence of the emergency department physicians. It is important to know whether parents and general pediatricians associate the quality of pediatric emergency care with the pediatric emergency medicine (PEM) training of the emergency department physicians. We designed the study to determine parental and pediatricians' opinion and expectation in regard to this question. Most of the surveyed parents' and pediatricians' recognize the importance of PEM training and believed that physicians trained in PEM can provide better emergency care for children. However, 53.8% of parents, especially Spanish speaking and with Medicaid/no insurance coverage, believe that the emergency care provided for their children by general pediatricians and PEM physicians is equivalent. The results of our study could be utilized by accredited PEM planners in the creation of strategies to ensure the quality of emergency care for children population.

A new large CFTR rearrangement illustrates the importance of searching for complex alleles.

The p.Val754Met variant, described in 1996 in a CF patient, has been considered a CF mutation. However, biochemical aspects, results of functional studies and, finally, the identification of a complex deletion removing exons 3 to 10 and 14b to 16 in cis of p.Val754Met in a CF patient, argue against a strong deleterious effect. An inventory through the French CF network of patients carrying p.Val754Met led to the registration of seven patients (CF: n=4; idiopathic chronic pancreatitis: n=3) and six healthy individuals, all heterozygous for the variation. Extensive CFTR gene analysis was carried out, including the search for large rearrangements and other possible mutations. The complex deletion, whose breakpoints are described here, was found only in the four CF patients, in association with the same haplotype. This data, added to the fact that the p.[Phe508del]+[Val754Met] genotype was found in a healthy individual, bring further arguments against the association of p.Val754Met with CF. We thus suggest looking for a possible complex allele whenever p.Val754Met is detected and considering it neutral regarding genetic counseling when found in isolation.

Sensitivity and specificity of decreased CSF asialotransferrin for eIF2B-related disorder.

OBJECTIVE: This is a study estimating diagnostic accuracy of CSF asialotransferrin to transferrin ratio measurement in eIF2B related disorders by using clinical evaluation and EIF2B mutation analysis as the reference standard. eIF2B-related disorder is a relatively common leukodystrophy with broad phenotypic variation that is caused by mutations in any of the five EIF2B genes. There is a need for a simple and clinically valid screening tool for physicians evaluating patients with an unclassified leukodystrophy. METHODS: CSF two-dimensional gel (2DG) electrophoresis analyses to measure asialotransferrin to transferrin ratios were performed in 60 subjects including 6 patients with documented EIF2B gene mutations, patients with other types of leukodystrophy, and patients with no leukodystrophy. RESULTS: All six patients with mutation proven eIF2B-related disease showed low to nearly undetectable amounts of asialotransferrin in their CSF when compared to 54 unaffected controls by CSF 2DG analyses in this study. eIF2B-like patients, with clinically similar presentations but no mutations in EIF2B1-5, were distinguished from patients with mutations in EIF2B1-5 by this biomarker. Patients with mutations in EIF2B1-5 had asialotransferrin/transferrin ratio levels significantly different from the group as a whole (p < 0.001). Using 8% asialotransferrin/transferrin ratio as a cutoff, this biomarker has a 100% sensitivity (95% CI = 52-100%) and 94% specificity (95% CI = 84-99%). CONCLUSION: Decreased asialotransferrin/transferrin ratio in the CSF of patients with eIF2B-related disorder is highly sensitive and specific. This rapid (<48 hours) and inexpensive diagnostic tool for eIF2B-related disorders has the potential to identify patients with likely eIF2B-related disorder for mutation analysis.

Histologic phenotype-genotype correlation of corneal dystrophies associated with eight distinct mutations in the TGFBI gene.

PURPOSE: To establish a phenotype-genotype correlation of various autosomal-dominant corneal dystrophies among French subjects. DESIGN: Retrospective molecular genetic study and clinicopathologic correlation. PARTICIPANTS: Forty-four subjects from 26 unrelated French families were included in this study, and 60 corneal buttons could be examined at the histologic and ultrastructural levels. METHODS: Light microscopy and transmission electron microscopy were performed on corneal specimens obtained during keratoplasty. Blood samples were collected for DNA analysis. MAIN OUTCOME MEASURES: After genomic DNA extraction from peripheral blood leukocytes of each family member, exons of the TGFBI gene were amplified by polymerase chain reaction (PCR), and the PCR products were directly sequenced on both strands. RESULTS: Four different mutations were found to be responsible for dystrophy of granular type (R555W, R124L, R124H, and R124L+delT125-delE126), three other different mutations produced a lattice type (R124C, H626R, and A546T), and the last mutation identified was associated with the honeycomb-shaped dystrophy (R555Q). Each subtype of dystrophy showed, histologically and ultrastructurally, specific characteristics that are easily recognizable. However, besides these stereotyped forms, differential histologic diagnosis of atypical forms remains difficult, and these forms could be misdiagnosed. CONCLUSIONS: The characteristic biomicroscopic appearance and histopathologic features of each "classic" dystrophy present a significant degree of specificity and generally provide an accurate diagnosis. However, atypical forms in which clinical and histologic data alone could be misleading, are unequivocally diagnosed after DNA analysis.

Organization and sequence of human cardiac myosin binding protein C gene (MYBPC3) and identification of mutations predicted to produce truncated proteins in familial hypertrophic cardiomyopathy.

Cardiac myosin binding protein C (MyBP-C) is a sarcomeric protein belonging to the intracellular immunoglobulin superfamily. Its function is uncertain, but for a decade evidence has existed for both structural and regulatory roles. The gene encoding cardiac MyBP-C (MYBPC3) in humans is located on chromosome 11p11.2, and mutations have been identified in this gene in unrelated families with familial hypertrophic cardiomyopathy (FHC). Detailed characterization of the MYBPC3 gene is essential for studies on gene regulation, analysis of the role of MyBP-C in cardiac contraction through the use of recombinant DNA technology, and mutational analyses of FHC. The organization of human MYBPC3 and screening for mutations in a panel of French families with FHC were established using polymerase chain reaction, single-strand conformation polymorphism, and sequencing. The MYBPC3 gene comprises > 21,000 base pairs and contains 35 exons. Two exons are unusually small in size, 3 bp each. We found six new mutations associated with FHC in seven unrelated French families. Four of these mutations are predicted to produce truncated cardiac MyBP-C polypeptides. The two others should each produce two aberrant proteins, one truncated and one mutated. The present study provides the first organization and sequence for an MyBP-C gene. The mutations reported here and previously in MYBPC3 result in aberrant transcripts that are predicted to encode significantly truncated cardiac MyBP-C polypeptides. This spectrum of mutations differs from the ones previously observed in other disease genes causing FHC. Our data strengthen the functional importance of MyBP-C in the regulation of cardiac work and provide the basis for further studies.