Ruxolitinib in Aicardi-Goutières syndrome

Metabolic Brain Disease - Aicardi-Goutières Syndrome (AGS) is a monogenic leukodystrophy with pediatric onset, clinically characterized by a variable degree of neurologic impairment. It...     

The Role of Ultrasound in Penetrating Trauma

A dramatic reduction of penetrating trauma is not to be expected in the near future, especially in some regions of the world. In order to identify the body structures damaged after stab or firearm wounds, complementary diagnostic studies play an essential role in assessing the severity of the case. The inclusion of ultrasound among the diagnostic tests for assessing abdominal injuries after blunt trauma because of its confident, repetitive, non-invasive, communicable, and low-cost means to obtain the relevant information is derived from rapidly widespread use of the method for other injury mechanisms, such as penetrating trauma. The excellent results in sensitivity and specificity obtained by ultrasound in the search of free fluid among patients with blunt trauma have pushed emergency physicians to try a similar implementation in the penetrating trauma setting. Ultrasonography enables experienced examiners to obtain diagnostic details from the injured patient. Regarding free fluid, it is possible to determine its presence and composition through the peritoneal aspiration after a sonoguided puncture. On the other hand, ultrasound is able to detect morphologic changes in solid organs after penetrating trauma. In order to reach these possibilities which are offered by the ultrasound technology, a planifying training and education program must be developed.     

Farm workers'occupational allergy to Tetranychus urticae: clinical and immunologic aspects

A group of 46 farm workers (32 men), affected by a recurrent "occupational disease of undetermined origin", underwent an immunologic investigation with a Tetranychus urticae (TU) whole-body extract (TU-WBE) prepared in our laboratory. The patients suffered from seasonal attacks of rhinitis, during the summer and autumn periods, when working in open fields (30 subjects) or in greenhouse flower cultivation (16 subjects). In most patients, rhinitis was associated with bronchial asthma (16 subjects), urticaria (14 subjects), or both (three subjects). Allergic alveolitis or other common allergic diseases had been excluded, and a diagnosis of "occupational disease of undetermined origin" had been made before by other medical centers. Ten healthy farm workers and 10 atopic townsmen were chosen as control groups. An in vivo and in vitro diagnostic trial by skin prick testing (SPT) and serum specific IgE dosage with TU-WBE were done in all subjects. Thirty-six patients (78%) were found to be positive to both SPT and the IgE enzyme allergosorbent test (EAST), with a good correlation between IgE serum levels and cutaneous wheal size. Control groups did not show any reaction. The IgE-EAST homologous inhibition test was positive. The IgE-EAST cross-inhibition test excluded cross-reactivity between TU and Dermatophagoides pteronyssinus. The TU-exposure test was positive for the 36 patients with TU-WBE-specific IgE. Three patients who were negative for TU-WBE-specific IgE reacted to the TU-exposure test; in these patients, the scratch-chamber test (Finn chamber) with eggs and droppings from TU was positive. We suggest the possibility of a TU allergy also in those subjects in whom clinical symptoms can be attributed to other common allergens.
Astarita C, Franzese A, Scala G, Sproviero S, Raucci G. Farm workers'occupational allergy to Tetranychus urticae : clinical and immunologic aspects.     

Residual association at C9orf72 suggests an alternative amyotrophic lateral sclerosis-causing hexanucleotide repeat

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons. Single-nucleotide polymorphism rs3849942 is associated with ALS, tagging a hexanucleotide repeat mutation in the C9orf72 gene. It is possible that there is more than 1 disease-causing genetic variation at this locus, in which case association might remain after removal of cases carrying the mutation. DNA from patients with ALS was therefore tested for the mutation. Genome-wide association testing was performed first using all samples, and then restricting the analysis to samples not carrying the mutation. rs3849942 and rs903603 were strongly associated with ALS when all samples were included (rs3849942, p = [3 × 2] × 10⁻⁶, rank 7/442,057; rs903603, p = [7 × 6] × 10⁻⁸, rank 2/442,057). Removal of the mutation-carrying cases resulted in loss of association for rs3849942 (p = [2 × 6] × 10⁻³, rank 1225/442,068), but had little effect on rs903603 (p = [1 × 9] × 10⁻⁵, rank 8/442,068). Those with a risk allele of rs903603 had an excess of apparent homozygosity for wild type repeat alleles, consistent with polymerase chain reaction failure of 1 allele because of massive repeat expansion. These results indicate residual association at the C9orf72 locus suggesting a second disease-causing repeat mutation.     

Development of an Objective Scoring System for Measurement of Resident Performance on the Human Patient Simulator

Background: The decrease in the percentage of patients having cesarean delivery during general anesthesia has led some educators to advocate the increased use of simulation-based training for this anesthetic. The authors developed a scoring system to measure resident performance of this anesthetic on the human patient simulator and subjected the system to tests of validity and reliability.

Methods: A modified Delphi technique was used to achieve a consensus among several experts regarding a standardized scoring system for evaluating resident performance of general anesthesia for emergency cesarean delivery on the human patient simulator. Eight third-year and eight first-year anesthesiology residents performed the scenario and were videotaped and scored by four attending obstetric anesthesiologists.

Results: Third-year residents scored an average of 150.5 points, whereas first-year residents scored an average of 128 points (P = 0.004). The scoring instrument demonstrated high interrater reliability with an intraclass correlation coefficient of 0.97 (95% confidence interval, 0.94-0.99) compared with the average score.     

A novel NF1 gene mutation in an Italian family with neurofibromatosis type 1

Purpose

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder with an estimated incidence of one in 3,500 births. Clinically, NF1 is characterized by café-au-lait (CAL) spots, neurofibromas, freckling of the axillary or inguinal region, Lisch nodules, optic nerve glioma, and bone dysplasias. NF1 is caused by inactivating mutations of the 17q11.2-located NF1 gene. We present a clinical and molecular study of an Italian family with NF1.

Methods

The proband, a 10-year-old boy, showed large CAL spots and freckling on the axillary region and plexiform neurofibromas on the right side only. His father (47?years old) showed, in addition to the similar signs, numerous neurofibromas of various sizes on his thorax, abdomen, back, and shoulder. Two additional family members (a brother and a sister of the proband) presented only small CAL spots. The coding exons of NF1 gene were analyzed for mutations by denaturing high-performance liquid chromatography and sequencing in all family members.

Results

The mutational analysis of the NF1 gene revealed a novel frameshift insertion mutation in exon 4c (c.654 ins A) in all affected family members. This novel mutation creates a shift on the reading frame starting at codon 218 and leads to the introduction of a premature stop at codon 227.

Conclusions

The segregation of the mutation with the affected phenotype and its absence in the 200 normal chromosomes suggest that it is responsible for the NF1 phenotype.     

Clonal analysis of F1 hybrid helper T cells. I-A subregion-encoded hybrid determinants restrict the activity of keyhole limpet hemocyanin- specific helper T cells

Clonal expansion of isolated precursors to helper T cells was induced in limiting dilution cultures of keyhole limpet hemocyanin (KLH)-primed F1 hybrid lymph node cells. Progeny of each isolated precursor was tested for helper activity by transfer to independent cultures with hapten-primed B cells of either parental or F1 hybrid origin. The major histocompatibility complex (MHC) restriction specificity of each F1 hybrid helper T clone was determined. To assess the contribution of I-A and I-E subregion-encoded genes to the expression of these restriction elements, helper T cell cultures derived from F1 hybrids between strains with recombinant H-2 haplotypes were analyzed. Parental and unique F1 hybrid MHC determinants that are encoded entirely within the I-A subregion were found to restrict the activity of KLH-specific helper T cells.