Influenza immunization in immunosuppressed children

Optimal influenza immunization of individuals with malignancy and other immunodeficient states requires and understanding of responses to currently recommended regimens. Children with acute lymphocytic leukemia and other malignancies between three and 17 years of age were immunized with bivalent influenza vaccine containing A/New Jersey/76 and A/Victoria/75. Folowing a two-dose immunization schedule, only 37% (25468) on cancer chemotherapy seroconverted to a hemagglutination inhibition titer greater than or equal to 20 for A/NJ/76; the seroconversion rate in those not on chemotherapy was 92% (68/74, P less than 0.001). The immune response to the A/Vic/75 antigen was also related to a history of recent chemotherapy. There was no correlation between the immune response and the peripheral white blood cell count except at counts less than or equal to 1,000. The optimum time to immunize children with malignancies is when they have been off chemotherapy for one month and have peripheral white blood counts greater than 1,000.     

Toxicologic evaluation of modified gum acacia: mutagenicity, acute and subchronic toxicity.

Modified gum acacia, produced from acacia gum by a process analogous to the production of modified food starch, was tested for mutagenicity in the microbial reverse mutation assay. The assay employed a wide range of dose levels, both with and without metabolic activation. Test results gave no indication that modified gum acacia possessed any mutagenic potential. The acute oral toxicity of modified gum acacia was determined in two studies employing Sprague-Dawley rats, and the LD50 values were found to be >2000 mg/kg. The primary dermal irritation potential of modified gum acacia was evaluated in rabbits by the Draize method. Test results indicated that modified gum acacia was slightly irritating by the Environmental Protection Agency (EPA) classification but not a primary irritant by Consumer Product Safety Commission (CPSC) guidelines. The subchronic toxicity of modified gum acacia was examined in Sprague-Dawley rats fed diets containing 0%, 1%, 2.5%, and 5% modified gum acacia for 13 weeks. No dose-related effects on survival, growth, hematology, blood chemistry, organ weights, or pathologic lesions were observed. Results of these studies indicate that modified gum acacia does not possess mutagenic potential and that animals are not adversely affected by acute or subchronic exposure to modified gum acacia.     

Animal models of age-related dementia: neurobehavioral dysfunctions in autoimmune mice

The development of strategies for treatment of Alzheimer's disease and other age-associated dementias is an important goal of research in the neurosciences. It is suggested that advances in understanding of the etiology of those disorders would provide the most obvious avenues to development of preventative treatments. Research findings from both clinical investigations and studies of animal models are presented which suggest a neuroimmunologic component in age-associated dementia. Clinical studies suggest an association between dementia and brain-reactive autoantibodies in subsets of patients with Alzheimer's disease. Studies of mice suggest that: 1) when compared with normal genotypes, mutant mice with accelerated autoimmunity show learning and memory impairments at earlier chronological ages; 2) the learning and memory deficits of autoimmune and normal mice are qualitatively similar; 3) the behavioral deficits of normal aged and autoimmune mice are sensitive to similar pharmacologic interventions. Overall, these findings suggest that intervention strategies targeting the immune system might be useful in the treatment or prevention of aging-associated dementia. Autoimmune mice would be useful as models for the development and testing of such immune-based interventions.     

Rapid induction of Pavlovian approach to an ethanol-paired visual cue in mice

Rationale Although many studies have shown Pavlovian conditioned approach to cues paired with natural reinforcers, it has been quite difficult to induce such behavior with drug reinforcers. Objectives This experiment tested a novel Pavlovian procedure for inducing approach to a conditioned stimulus (CS) paired with ethanol. Methods Mice (NZB/B1NJ, DBA/2J) received intraperitoneal injections of ethanol (2 g/kg) immediately before 10-min exposure to a rectangular chamber that contained a distinctive visual cue (star) at one end (Paired group, CS+ trials). On alternate days, saline injection preceded apparatus exposure with no distinctive cues (CS− trials). Unpaired control mice received ethanol in the home cage 60–75 min after each CS+ trial. Results NZB/B1NJ Paired group mice spent increasing amounts of time (>85% of the session) in proximity to the star, whereas Unpaired group mice did not. DBA/2J Paired group mice spent slightly more time on the star side than Unpaired group mice but did not show an acquisition curve. Postconditioning tests showed a strong preference for the star side in Paired groups from both strains after saline injection. However, only NZB/B1NJ mice showed a preference after ethanol. Conclusions This study provides the first unambiguous demonstration of Pavlovian conditioned approach to an ethanol-paired visual stimulus in the absence of any contingency between the animal’s behavior and drug exposure. This effect, which is remarkable both in terms of its magnitude and the rapidity with which it was produced (within 2–3 trials), may be related to the cue-associated craving that accompanies alcohol and drug addiction.