Effects of methylphenidate and behavior modification on the social and academic behavior of children with disruptive behavior disorders: the moderating role of callous/unemotional traits.

This study examined whether response to behavior modification with and without methylphenidate differed for children with attention-deficit/hyperactivity disorder (ADHD) and conduct problems (CP) depending on the presence of callous/unemotional (CU) traits. Participants were 37 children ages 7 to 12, including 19 with ADHD/CP-only and 18 with ADHD/CP-CU, referred to a university-based summer treatment program. Results showed that ADHD/CP-CU children had worse behavior in the behavior-therapy-only (BT-only) condition, especially on measures of CP, noncompliance, and rule violations, but these differences largely disappeared when medication was added to BT. Children with ADHD/CP-CU were also less likely to be normalized by treatment than were children with ADHD/CP-only. These findings, though tentative, suggest that children with ADHD/CP-CU may not show a sufficient positive response to BT alone and that the combination of medication and BT may be especially important for them.     

5'-Nucleotidase activity increases in aging rat brain.

The enzyme 5'-nucleotidase is present in glial and neuronal membranes, and catalyzes the formation of adenosine, which in turn can act as a neuromodulator or neurotransmitter. The present study found marked increases in histochemically demonstrated 5'-nucleotidase activity in most regions of rat brain from young adulthood (3-4 months) to middle age (12-18 months), with smaller or no changes between middle and old age (24-32 months). The aging adult cerebellum showed alterations in the histochemical pattern, with declines in the molecular layer and increases in the Purkinje layer. Both myelin and synaptic plasma membrane fractions from forebrain showed increases in enzyme activity. Assays of various other body tissues suggested that the increases are fairly specific to brain, and thus apparently do not represent a ubiquitous cellular mechanism of aging. Changes in brain 5'-nucleotidase activity during aging probably reflect the increasing number and size of glial cells, and perhaps also affect synaptic transmission through regulation of adenosine.     

[I]Vasoactive intestinal peptide binding in rodent suprachiasmatic nucleus: Developmental and circadian studies

The suprachiasmatic nucleus (SCN) of rat and hamster have been studied extensively and shown to play critical roles in circadian rhythmicity. [¹²⁵I]Vasoactive intestinal peptide (VIP) binding levels are high in the rat SCN, suggesting that VIP receptors may be an important component of SCN function. In contrast to previously demonstrated diurnal variations in VIP immunoreactivity and VIP mRNA, the present study found [¹²⁵I]VIP binding to be stable across the light-dark cycle in both rat and hamster SCN. High [¹²⁵I]VIP labeling appeared to be coextensive with the rat SCN but extended somewhat beyond the cytoarchitectonic boundaries of the hamster SCN. Binding density in hamster SCN was slightly higher than in rat. In the developing rat SCN, [¹²⁵I]VIP binding levels distinguished the SCN on embryonic day 18, and appeared to increase to postnatal day 10 before declining to adult levels. The early presence of [¹²⁵I]VIP binding suggests possible involvement of VIP receptors in fetal entrainment of circadian rhythms.     

In vitro activity of ceftriaxone and other cephalosporins against 602 clinical isolates of staphylococci from geographically diverse medical centers

The in vitro activity of ceftriaxone and six additional antimicrobial agents (ceftizoxime, cefoperazone, cefuroxime, fleroxacin, ciprofloxacin, and trimethoprim/sulfamethoxazole) was assessed or 602 recent clinical isolates of staphylococci from six geographically distinct medical centers in North America. All seven antimicrobial agents were active (90–100% of strains susceptible) against oxacillin-susceptible (OS) strains of Staphylococcus aureus (OSSA) and coagulase-negative staphylococci (OSCNS) but had limited activity against oxacillin resistant (OR) staphylococci. Our assessment of the in vitro antistaphylococcal activity of ceftriaxone against contemporary isolates of Staphylococcus aureus and coagulase-negative staphylococci indicates that the activity versus OS staphylococci has not changed over the past decade despite widespread use of the drug. It appears that these agents will continue to be useful for empiric therapy in those centers in which OR strains are uncommon.Corresponding author.     

Assessment of renal artery stenosis by phase-contrast magnetic resonance angiography

Three-dimensional (3D) phase-contrast magnetic resonance angiography (MRA) and velocity-encoded cine magnetic resonance (VEC-MR) imaging were performed in 23 subjects to assess the severity of renal artery stenosis. MRA was used for detection of stenosis, demonstrating a sensitivity of 100% and a specificity of 80%; the severity of stenosis was overestimated in 33%. VEC-MR was used to quantify the renal flow oattern and was successful in 11 subjects. Mean blood flow of normal renal arteries (420 +- 107 ml/min) was significantly higher (P < 0.01) than mean blood flow of stenotic arteries (131 +- 46ml/min). The flow profile displayed both systolic and diastolic peaks in 75% of the normal arteries, while the flow in stenotic arteries showed only a single systolic peak in all cases. The systolic peak in stenotic arteries occurred significantly later (32 +- 3% of the period of one cardiac cycle) than in normal subjects (21 +- 7%) (P < 0.05). Phase-contrast MR is likely to gain considerable importance in the noninvasive aetection and quantification of renal artery stenosis. Correspondence to: C. S. Richter     

Effect of intravenous ketanserin on the human action potential duration at fixed heart rate

Summary In this study any changes in action potential duration or Q-T interval due to acute doses of ketanserin were monitored. The effect of a bolus dose (10 or 20 mg) followed by an infusion (10 or 20 mg over 20 minutes) of ketanserin on the Q-T interval and action potential duration was studied in six patients undergoing routine cardiac catheterization. Action potential duration was measured with a silver-silver chloride electrode catheter while heart rate was kept constant by atrial pacing and reflex effects avoided by -adrenergic blockade. There were some prolongations of the action potential duration but they were not in excess of 40 msec and did not reach statistical significance (control 263±46.0 msec; bolus 269±52.1 msec; infusion 262±53.6 msec; nor were there any significant changes in Q-T interval. Thus acute intravenous doses of ketanserin, in the absence of hypokalaemia or other Q-T interval-prolonging drugs, have no consistent effect on Q-T interval or action potential duration; prolongation of the action potential, when it occurs, is small.     

Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron-exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are "private" and are distributed throughout the gene, except for exons 5 and 12-14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype-phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease.     

Fusion and Matrix Protein Gene Sequence Analysis of Paramyxoviruses of Type 1(PMV-1) Isolated from Pigeons in Slovenia

Paramyxoviruses of type 1 (PMV-l) isolated from pigeons were genetically analyzed. A part of the fusion and the matrix protein genes were amplified and sequenced, Typical amino acid sequences associated with virulence were determined at the fusion protein cleavage site in all PMV-1 isolates. All Slovene pigeon PMV-1 strains share high amino acid sequence similarity with other pigeon strains. In the phylogenetic tree, they are clustered together with pigeon PMV-1 isolates with moderate pathogenicity. Phylogenetic analysis obtained from the fusion and the matrix protein gene alignments showed the same branching order. Viruses circulating among pigeons were found to form quite unique lineage of virulent NDV strains.     

Effect of chronic vincristine treatment on mechanical withdrawal response and pre-pulse inhibition in the rat

Chemotherapeutic agents are associated with a number of serious side-effects. In addition to the development of peripheral neuropathy, patients often complain of additional symptoms related to attentional mechanisms. Although a great deal of interest is directed towards understanding the mechanisms underlying the development of peripheral neuropathy, there is a paucity of research that has examined the extent of impairment of attention in animals receiving chemotherapeutic agents. Therefore, the purpose of this experiment was to examine attentional mechanisms using the method of pre-pulse inhibition in animals that were chronically treated with vincristine. Although vincristine treated animals developed signs of peripheral neuropathy, there was no associated alteration of pre-pulse inhibition relative to vehicle treated animals. These results highlight the importance of continuing to develop methodology to model symptom burden in patients receiving chemotherapy.