Evaluating an adapted reverse categorisation task to assess cognitive flexibility in young children with Down syndrome.

BACKGROUND: Accurate measurement of cognitive skills is necessary to advance both developmental and intervention science for individuals with Down syndrome (DS). This study evaluated the feasibility, developmental sensitivity and preliminary reliability of a reverse categorisation measure designed to assess cognitive flexibility in young children with DS. METHODS: Seventy-two children with DS ages 2.5-8 years completed an adapted version of a reverse categorisation task. Twenty-eight of the participants were assessed again 2 weeks later for retest reliability. RESULTS: This adapted measure demonstrated adequate feasibility and developmental sensitivity, and preliminary evidence for test-retest reliability when administered to children with DS in this age range. CONCLUSIONS: This adapted reverse categorisation measure may be useful for future developmental and treatment studies that target early foundations of cognitive flexibility in young children with DS. Additional recommendations for use of this measure are discussed.

Energy transfer analysis of Fos-Jun dimerization and DNA binding.

The protooncogenes fos and jun encode proteins that bind to DNA as dimeric complexes and regulate gene expression. Protein dimerization is mediated by a leucine zipper and results in juxtaposition of regions of each protein rich in basic amino acids that comprise a bimolecular DNA binding domain. We have developed an approach based on resonance energy transfer for the quantitative analysis of dimerization and DNA binding by Fos and Jun in solution. Fos-(118-211) and Jun-(225-334) polypeptides were labeled with either 5-iodoacetamidofluorescein or rhodamine X iodoacetamide on unique cysteine residues located in their DNA binding domains. Formation of heterodimeric complexes between the labeled proteins allowed resonance energy transfer between the donor fluorescein and the acceptor rhodamine fluorophores. DNA binding induced a conformational transition that increased the efficiency of resonance energy transfer. This increase was consistent with a 3-A reduction in the distance between the fluorophores. Using this assay, we determined the affinity of the Fos-Jun interaction and examined the kinetics of dimerization and DNA binding as well as the rate of subunit exchange. Dimerization and DNA binding by Fos and Jun were rapid, with half-times of < 10 s. In the absence of DNA, Fos and Jun subunits exchanged rapidly, with a half-time of < 10 s. In contrast, in the presence of DNA, the complex was extremely stable. Thus, leucine zipper-containing transcription factors may exchange subunits readily when free in solution, but not when bound to DNA.

A gel electrophoresis system for resolving over 500 nucleotides with a single sample loading.

A procedure for the resolution of over 500 nucleotides in a single loading on a sequencing gel is described. The method uses exponential wedge spacers to achieve compression of the band spacing in the lower portion of the gel. The method is simple and reliable and reduces the cost of electrophoresis and autoradiography supplies by at least a factor of two.

Masseter muscle spasm in children: implications of continuing the triggering anesthetic.

This retrospective study was undertaken to examine the management and outcome of children who developed isolated masseter muscle spasm (MMS) after the administration of intravenous succinylcholine during anesthetic induction. The inhalation anesthetics used for induction were continued in all of these cases. The medical records of 68 patients (male/female ratio, 1.7:1), identified from approximately 42,000 anesthetics given during the period 1980-1989, were reviewed. Fifty-seven children (2.3-12 yr old) were diagnosed as having isolated MMS, i.e., MMS without spasm of other muscles; 11 experienced generalized rigidity in combination with MMS. Anesthetic and postoperative management of these two groups differed. The overall incidence of MMS was 0.3% of inhalation anesthetics during which succinylcholine was given. Intraoperative arrhythmias occurred in 33% of the patients who developed isolated MMS and more frequently in older children. Most children experienced some degree of hypercarbia and/or metabolic acidosis, but the significance of these abnormalities in the spontaneously ventilating, fasting child is unknown. Serum creatine kinase levels when measured 18-24 h postoperatively were elevated in all but one child (n = 45). There was no long-term morbidity and no mortality. We conclude that failure of the masseter muscles to relax after succinylcholine is not uncommon in children. Based on our experience, and accepting that MMS may be part of the clinical spectrum of malignant hyperthermia, we believe that anesthesia can be continued safely in cases of isolated MMS when careful monitoring accompanies diagnostic evaluation. This differs from the current practice of discontinuing the anesthetic or switching to a nontriggering anesthetic technique.

1-Desamino-8-D-arginine vasopressin (desmopressin) decreases operative blood loss in patients having Harrington rod spinal fusion surgery. A randomized, double-blinded, controlled trial.

To evaluate the effect of 1-desamino-8-D-arginine vasopressin (desmopressin) on blood loss in surgery, we conducted a randomized, double-blind trial of the drug in 35 patients with normal hemostatic function who were having spinal fusion with Harrington rod instrumentation. Seventeen patients were designated to receive 10 micrograms/m2 of desmopressin, and 18, to receive a placebo. Preoperative testing showed that desmopressin increased factor VIII coagulant activity, von Willebrand antigen concentrations, glass bead platelet retention, and prothrombin consumption and decreased the partial thromboplastin and bleeding times (p less than or equal to 0.0003). During surgery, desmopressin reduced blood loss by 32.5% (547 mL; 95% confidence interval [CI], 19 to 1075; p = 0.015) and reduced the need for concentrated erythrocyte transfusions by 25.6% (0.86 units; 95% CI, 0.08 to 1.65; p = 0.022). After surgery, desmopressin reduced the duration of treatment with analgesic agents by 13.1% (34.0 hours; 95% CI, -5.2 to 72.7; p = 0.105), presumably by decreasing bleeding in the surgical wound. When adjusted for the origin of the scoliosis by two-way analysis of variance, this effect was even more evident (p = 0.014). Multiple regression analysis showed that the best three predictors of blood loss in surgery and transfusion requirements were the bleeding time, glass bead platelet retention, and the use of desmopressin.