Experimental Evidence of Cerebral Injury from Profound Hypothermia During Cardiopulmonary Bypass

Choreoathetosis, seizures, and impaired mental development continue to occur in children undergoing cardiopulmonary bypass (CPB) and profound hypothermia with or without circulatory arrest. Although there is some evidence that the hypothermia itself may be causing these neurologic problems, skepticism remains because of lack of evidence from experimental studies simulating the clinical setting. In this experimental study, we examined the effect of profound and moderate hypothermia on the brain while maintaining normal flow rates during CPB. Ten adult mongrel dogs equally divided into two groups were anesthetized and subjected to CPB and varying levels of hypothermia (group 1, ≤15°C; group 2, ≤32°C). Both groups were kept at the desired temperature for 1 hour prior to rewarming and discontinuation of CPB. The dogs were euthanized 4–6 weeks later and neuropathologic studies were performed. The mean CPB flow rates during cooling and at the desired rectal temperature were comparable in both groups: group 1, 108 ± 10 ml/kg/min versus 106 ± 7 ml/kg/min in group 2 (p= NS) and 95 ± 12 ml/kg/min in group 1 versus 101 ± 5 ml/kg/min in group 2 (p= NS). Because of the difference in temperature between the two groups, the mean cooling time (onset of CPB to desired rectal temperature) was longer in group 1 (70 ± 14 minutes) than in group 2 (28 ± 11 minutes, p= 0.007). Hence, the total mean CPB time was also longer in group 1 (198 ± 25 minutes) than in group 2 (143 ± 13 minutes, p= 0.002). The lowest mean blood and rectal temperature achieved in group 1 were 11 ± .9°C and 12 ± 1°C versus 29 ± .4°C (p < 0.001) and 30 ± .6°C (p= 0.001), respectively, in group 2 (p= 0.001). Neuronal loss and degeneration was noted in all dogs in group 1 ranging from 2 to 8 cells per 1000 cells counted compared to none in group 2 (p= 0.05). These lesions occurred in both the basal ganglia and the cortex, although they were more marked in the caudate when compared to the cortex and cerebellum. Both in the cortex and in the caudate, neuronal loss was more marked around the capillaries. We conclude that the use of profound hypothermia of ≤15°C and maintenance of normal flow rates during cooling at this temperature for 1 hour produces neuronal loss and degeneration in the brain. These lesions being more marked around capillaries points to the vulnerability of the neurons, probably because of their high lipid content to injury from the cold perfusate.     

Disentangling the Overlap between Tourette's Disorder and ADHD

Objective : To identify similarities and differences in neuropsychiatric correlates in children with Tourette's syndrome (TS) and those with ADHD. Method : The sample consisted of children with Tourette's syndrome with ADHD( N = 79), children with Tourette's syndrome without ADHD ( N = 18), children with ADHD ( N = 563), psychiatrically referred children ( N = 212), and healthy controls ( N = 140). Results: Disorders specifically associated with Tourette's syndrome were obsessive compulsive disorder (OCD) and simple phobias. Rates of other disorders, including other disruptive behavioral, mood, and anxiety disorders, neuropsychologic correlates, and social and school functioning were indistinguishable in children with Tourette's and ADHD. However, children with Tourette's syndrome plus ADHD had more additional comorbid disorders overall and lower psychosocial function than children with ADHD. Conclusions: These findings confirm previously noted associations between Tourette's syndrome and OCD but suggest that disruptive behavioral, mood, and anxiety disorders as well as cognitive dysfunctions may be accounted for by comorbidity with ADHD. However, Tourette's syndrome plus ADHD appears to be a more severe condition than ADHD alone.     

Intracranial leiomyosarcoma: A neuro-oncological consequence of acquired immunodeficiency syndrome

We describe a case of glioblastoma treated with chemoradiotherapy that spread to the dura mater with direct invasion of the skull base, protrusion into the homolateral nasal fossa, and penetrated of the frontal sinus, the orbital wall and the ethmoidal sinuses. Only eight cases of glioblastoma showing this development have been described in the literature; one of these, however, had a sarcomatous component which was absent in our case.     

Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer's Disease Cooperative Study

CONTEXT: Several reports from small clinical trials have suggested that estrogen replacement therapy may be useful for the treatment of Alzheimer disease (AD) in women. OBJECTIVE: To determine whether estrogen replacement therapy affects global, cognitive, or functional decline in women with mild to moderate AD. DESIGN: The Alzheimer's Disease Cooperative Study, a randomized, double-blind, placebo-controlled clinical trial conducted between October 1995 and January 1999. SETTING: Thirty-two study sites in the United States. PARTICIPANTS: A total of 120 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 28 who had had a hysterectomy. INTERVENTIONS: Participants were randomized to estrogen, 0.625 mg/d (n = 42), or 1.25 mg/d (n = 39), or to identically appearing placebo (n = 39). One subject withdrew after randomization but before receiving medication; 97 subjects completed the trial. MAIN OUTCOME MEASURES: The primary outcome measure was change on the Clinical Global Impression of Change (CGIC) 7-point scale, analyzed by intent to treat; secondary outcome measures included other global measures as well as measures of mood, specific cognitive domains (memory, attention, and language), motor function, and activities of daily living; compared by the combined estrogen groups vs the placebo group at 2, 6, 12, and 15 months of follow-up. RESULTS: The CGIC score for estrogen vs placebo was 5.1 vs 5.0 (P = .43); 80% of participants taking estrogen vs 74% of participants taking placebo worsened (P = .48). Secondary outcome measures also showed no significant differences, with the exception of the Clinical Dementia Rating Scale, which suggested worsening among patients taking estrogen (mean posttreatment change in score for estrogen, 0.5 vs 0.2 for placebo; P = .01). CONCLUSIONS: Estrogen replacement therapy for 1 year did not slow disease progression nor did it improve global, cognitive, or functional outcomes in women with mild to moderate AD. The study does not support the role of estrogen for the treatment of this disease. The potential role of estrogen in the prevention of AD, however, requires further research.     

The Economic Value of Childhood Varicella Vaccination in France and Germany

OBJECTIVE: To determine the economic impact of childhood varicella vaccination in France and Germany. METHODS: A common methodology based on the use of a varicella transmission model was used for the two countries. Cost data (2002 per thousand) were derived from two previous studies. The analysis focused on a routine vaccination program for which three different coverage rates (CRs) were considered (90%, 70%, and 45%). Catch-up strategies were also analyzed. A societal perspective including both direct and indirect costs and a third-party payer perspective were considered (Social Security in France and Sickness Funds in Germany). RESULTS: A routine vaccination program has a clear positive impact on varicella-related morbidity in both countries. With a 90% CR, the number of varicella-related deaths was reduced by 87% in Germany and by 84% in France. In addition, with a CR of 90%, routine varicella vaccination induces savings in both countries from both societal (Germany 61%, France 60%) and third-party payer perspectives (Germany 51%, France 6.7%). For lower CRs, routine vaccination remains cost saving from a third-party payer perspective in Germany but not in France, where it is nevertheless cost-effective (cost per life-year gained of 6521 per thousand in the base case with a 45% CR). CONCLUSION: Considering the impact of vaccination on varicella morbidity and costs, a routine varicella vaccination program appears to be cost saving in Germany and France from both a societal and a third-party payer perspective. For France, routine varicella vaccination remains cost-effective in worst cases when a third-party payer perspective is adopted. Catch-up programs provide additional savings.