3,4-Dichioropropionanilide-Induced Atrophy of the Thymus: Mechanisms of Toxicity and Recovery

The herbicide 3,4-dichioropropionanilide (propanil) has severalwell-documented neurotoxic and immunotoxic effects on mice.We report here a detailed characterization of the effects ofpropanil exposure on the thymus. We found that at doses of 100–200mg/kg, propanil induces significant thymic atrophy between 2and 7 days postexposure. This atrophy is characterized by adecrease in thymus/body ratio and a decrease in cellularity.Flow cytometric analyses of thymuses from propanil- and vehicle-treatedmice indicate that the CD4⁺ CD8⁺ population of immature cells,is most significantly decreased in propanil-exposed mice. Weperformed cell cycle analysis of thymocyte populations usingtwo-color surface staining and the DNA binding dye 7-aminoactinomycinD to determine whether thymic atrophy was associated with changesin the percentages of cells in the S, G₂ and M phases of thecell cycle. We found a high percentage of proliferating CD4⁺CD8⁺thymocytes 4 days after exposure. Thus, recovery of the thymusoccurs following increases in thymocyte proliferation, mostnotably the immature CD4⁺ CD8⁺ thymocytes. We tested the hypothesisthat glucocorticoids play a role in the observed atrophy byexamining thymuses in adrenalectomized, propanil-treated mice.No atrophy was observed in those animals. These results suggestthat propanil has an immunotoxic effect on the thymus that appearsto be mediated, in part, by endogenous glucocorticoids.     

Results of clinical surveillance during the Japanese first palivizumab season in 2002–2003

BACKGROUND: In Japan, palivizumab was approved in 2002 for prophylaxis of severe respiratory syncytial virus disease in high-risk infants. In order to evaluate the efficacy and safety of this drug, a questionnaire survey was conducted. METHODS: A questionnaire was sent to member institutions of the Japan Neonatologist Association. The subjects were premature infants who were considered possible candidates for treatment with palivizumab. RESULTS: A total of 6302 case reports, including those of 2806 infants receiving palivizumab (group P) and 3496 infants not receiving palivizumab (group NP), respectively, were retrieved. Background characteristics revealed significant lower gestational age (GA) and birthweight for group P (P < 0.0001). Sex ratio did not differ significantly, while use of oxygen and mechanical ventilation in the neonatal intensive care unit, and presence of chronic lung disease were significantly higher for infants in group P (P < 0.0001). When comparison of hospitalization rate for respiratory symptoms was performed with stratification by eligibility criteria, in the group of infants born at 29-35 weeks GA the hospitalization rate was 4.0% and 5.7% in groups P and NP, respectively (P < 0.05). Multivariate analysis also showed that prophylaxis with palivizumab was the only variable that significantly decreased rate of hospitalization (odds ratio 0.630, P= 0.0053). The incidence of adverse events associated with the administration of palivizumab was low. CONCLUSION: In this non-randomized questionnaire survey, multivariate analysis showed that palivizumab significantly decreased the rate of hospitalization due to respiratory symptoms for infants born prematurely at 29-35 weeks GA. These data confirmed the efficacy and safety of palivizumab.     

Donepezil‐induced sleep spindle in a patient with dementia with Lewy bodies: a case report

Here, we report a case of rapid eye movement sleep behavioural disorder in an elderly patient with dementia with Lewy bodies. Pretreatment polysomnography revealed atonia during rapid eye movement sleep, absence of sleep spindles and loss of slow‐wave sleep. Administration of donepezil, an acetylcholinesterase inhibitor, markedly improved delusional symptoms and cognitive function. Pretreatment polysomnography performed after donepezil administration revealed a considerable number of sleep spindles. The effects of cholinergic modulation induced by donepezil seemed to cause remarkable improvement in mental status, incorporating associated with sleep spindles generated by the thalamocortical circuit involved in this patient.