Adult outcomes of attention deficit hyperactivity disorder and conduct disorder: are the risks independent or additive?

METHODS: Data were obtained from a longitudinal study sample of 754 adoptees and categorized based on review of the available adoption agency, medical, and psychiatric records of the biological parents. Categorical data were analyzed using chi2 or Fisher's exact tests, as appropriate. Logistic regression analyses were used to assess the relative contribution of variables. RESULTS: There was not a statistically significant difference in the frequency or type of self-reported adult disruptive behavior, arrests, jail stays, felony arrests, or frequency of conduct disorder (CD) when inattentiveness, impulsivity, and hyperactivity were analyzed individually. The contributions of attention deficit hyperactivity disorder (ADHD) were independent and no additional increased risk for future illegal behavior was conferred by the combination of the disorders. While the effect of CD on illegal behavior was correlated with substance abuse and dependence, ADHD continued to be a significant contributor after controlling for substance abuse and dependence. CONCLUSIONS: Data indicated that ADHD and CD are related but different disorders conferring risk for adult illegal behavior or arrest. In this sample, inattention was the most common domain impaired among those with ADHD, followed closely by hyperactivity, with impulsivity reported least often among those endorsing symptoms of ADHD.     

Expression of interleukin-15 in human skeletal muscle – effect of exercise and muscle fibre type composition

The cytokine interleukin-15 (IL-15) has been demonstrated to have anabolic effects in cell culture systems. We tested the hypothesis that IL-15 is predominantly expressed by type 2 skeletal muscle fibres, and that resistance exercise regulates IL-15 expression in muscle. Triceps brachii, vastus lateralis quadriceps and soleus muscle biopsies were obtained from normally physically active, healthy, young male volunteers ( n = 14), because these muscles are characterized by having different fibre-type compositions. In addition, healthy, normally physically active male subjects ( n = 8) not involved in any kind of resistance exercise underwent a heavy resistance exercise protocol that stimulated the vastus lateralis muscle and biopsies were obtained from this muscle pre-exercise as well as 6, 24 and 48 h post-exercise. IL-15 mRNA levels were twofold higher in the triceps (type 2 fibre dominance) compared with the soleus muscle (type 1 fibre dominance), but Western blotting and immunohistochemistry revealed that muscle IL-15 protein content did not differ between triceps brachii, quadriceps and soleus muscles. Following resistance exercise, IL-15 mRNA levels were up-regulated twofold at 24 h of recovery without any changes in muscle IL-15 protein content or plasma IL-15 at any of the investigated time points. In conclusion, IL-15 mRNA level is enhanced in skeletal muscles dominated by type 2 fibres and resistance exercise induces increased muscular IL-15 mRNA levels. IL-15 mRNA levels in skeletal muscle were not paralleled by similar changes in muscular IL-15 protein expression suggesting that muscle IL-15 may exist in a translationally inactive pool.     

Cloning,sequencing and analysis of the yeastS. uvarum ERG10 gene encoding acetoacetyl CoA thiolase

Summary TheERG10 gene specific toS. uvarum, a brewing yeast, has been cloned by complementation of anS. cerevisiae erg10 mutant.S. uvarum contains two differentERG10 genes. One of these is similar to theS. cerevisiae ERG10 gene; they are structurally different, but functionally homologous. The clonedERG10 gene has been located on chromosome XVI, and we have shown that it is allelic to the previously isolatedtsm0115 mutants. Northern blot and sequence analysis indicate that theERG10 gene is highly expressed, and biochemical and genetic evidence show that it encodes the cytoplasmic acetoacetyl CoA thiolase.     

Cytomegalovirus retinitis in advanced HIV-infected patients treated with protease inhibitors: incidence and outcome over 2 years

We prospectively studied the incidence of cytomegalovirus (CMV) retinitis in 93 patients treated with highly active antiretroviral therapy (HAART) containing a protease inhibitor (PI), during a median follow-up period of 24 months. The median initial CD4+ count was 22 cells/microl (range, 1-311 cells/microl), and the median plasma HIV viral load was 5.1 log10 copies/ml (range, 2.4-6.4 log10 copies/ml). The fundus was examined monthly in patients with a history of CMV retinitis or an initial CD4+ count <50 cells/microl and every 3 months in the other patients. Of patients with previously controlled CMV retinitis, 1 of 7 relapsed. In addition, 6 of 59 patients with a CD4+ count <50 cells/microl and no history of CMV retinitis before starting PI therapy developed CMV retinitis. Of them, 3 had at least one relapse during follow-up. CD4+ counts were <40 cells/microl at the time of primary or recurrent CMV retinitis, except in two cases (147 cells/microl and 203 cells/microl). In conclusion, the incidence of CMV retinitis was 0.091 per patient-year among study subjects with advanced HIV infection who were receiving HAART (95% confidence interval [CI], 0.037-0.145). The time to progression of CMV retinitis (mean, 215 days; 95% CI, 113-317 days) was longer than reported before widespread use of PIs.     

Effect of d-amphetamine repeated administration on rat antioxidant defences

The purpose of this study was to evaluate rat tissue antioxidant status after repeated administration of d-amphetamine. Three groups of four rats each were used: control, d-amphetamine sulphate dosed (s.c., 20 mg/kg per day), and pair-fed. After 14 days of d-amphetamine daily administration, superoxide dismutase (CuZnSOD and MnSOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GRed), glutathione-S-transferase (GST), glutathione (GSH), cysteine and thiobarbituric acid reactive substances (TBARS) were measured in liver, kidney, and heart. Various serum and urine parameters were also analysed. d-Amphetamine treatment induced an increase of liver GSH, as well as a decrease of cysteine and MnSOD levels in this organ. A small increase in serum transaminases was also observed in comparison to the pair-fed group. Hepatic levels of TBARS, GPx, GRed and CuZnSOD were found to be similar among the three groups of rats. d-Amphetamine treatment induced an increase of kidney GST, GRed and catalase levels, and an elevation of N-acetyl-β-d-glucosaminidase efflux to the urine, accompanied by a decrease in urinary creatinine, compared to the pair-fed group. In d-amphetamine treated animals, heart cysteine levels were significantly depleted when compared to the pair-fed group, but all three groups of rats were found to have similar heart antioxidant enzyme levels. These results indicate that repeated administration of d-amphetamine caused a certain degree of stress in liver and kidney, which was followed by adaptations of antioxidant defences. The mechanisms involved in d-amphetamine-induced toxicity may explain the different adaptations observed for the studied organs. Received: 19 October 1998 / Accepted: 11 January 1999     

Research strategies for safety evaluation of nanomaterials, part V: role of dissolution in biological fate and effects of nanoscale particles.

Dissolution, translocation, and disposition have been shown to play a key role in the fate and effects of inhaled particles and fibers. Concepts that have been applied in the micron size range may be usefully applied to the nanoscale range, but new challenges are presented based on the small size and possible change in the dissolution:translocation relationship. The size of the component molecule itself may be on the nanoscale. Solute concentration, surface area, surface morphology, surface energy, dissolution layer properties, adsorbing species, and aggregation are relevant parameters in considering dissolution at the nanoscale. With regard to the etiopathology caused by these types of particulates, the metrics of dose (particle number, surface area, mass or shape) is not yet well defined. Analytical procedures for assessing dissolution and translocation include chemical assay and particle characterization. Leaching of substituents from particle surfaces may also be important. Compartmentalization within the respiratory tract may add another dimension of complexity. Dissolution may be a critical step for some nanoscale materials in determining fate in the environment and within the body. This review, combining aspects of particle toxicology, material science, and analytical chemistry, is intended to provide a useful basis for developing relevant dissolution assay(s) for nanoscale particles.