Cognitive and behavioral outcome following mild traumatic head injury in children.

OBJECTIVES: To investigate outcome in children with mild traumatic head injury (THI) at 1 week and 3 months postinjury and to identify factors associated with persisting problems. DESIGN: Postconcussional symptomatology, behavior ratings, and neuropsychological test performance were examined at 1 week and 3 months postinjury. SETTING: Participants were recruited from successive presentations to emergency departments of two major hospitals. PARTICIPANTS: 130 Children with mild THI were compared with 96 children having other minor injuries as controls. RESULTS: Children with mild THI experienced headaches, dizziness, and fatigue but exhibited no cognitive impairments, relative to controls, at 1 week postinjury. By 3 months, symptoms had resolved. However, 17% of children showed significant ongoing problems. They were more likely to have a history of previous head injury, learning difficulties, neurological or psychiatric problems, or family stressors. CONCLUSIONS: Persisting problems following mild head injury in children are more common in those with previous head injury, preexisting learning difficulties, or neurological, psychiatric, or family problems. These "at-risk" children should be identified in the emergency department and monitored.     

Regulation of striatal dopamine release through 5-HT1 and 5-HT2 receptors

Dopamine (DA) release in the striatum is regulated by 5-hydroxytryptamine (5-HT, serotonin) through putative heteroreceptors. However, the effect of 5-HT is controversial. The present study investigated the effects of different 5-HT receptor ligands on DA release in the rat striatum by using in vivo microdialysis in conscious and freely moving rats. Perfusion with 5-carboxamidotryptamine, anpirtoline, pindobind-5-HT1A, and isamoltane demonstrated the involvement of 5-HT1A and 5-HT1B receptors in facilitating DA release. In contrast, 5-HT2 receptors mediated inhibition of DA efflux, as shown by experiments with DOI [R-(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] and ketanserin. A 5-HT3 agonist (1-(m-chlorophenyl)-biguanide hydrochloride) did not have any effect. None of the agonists used affected DA uptake into striatal synaptosomes. Unilateral 6-hydroxydopamine lesioning of the nigrostriatal DA pathway led to a selective decrease in 5-HT2 receptors. It is concluded that there are 5-HT2 heteroreceptors at the dopaminergic terminals that mediate inhibition of DA release. Further investigation is required to clarify the localization of the 5-HT1 receptors in the striatum.     

Adjusting for measurement error to assess health effects of variability in biomarkers. Multicenter AIDS Cohort Study.

Longitudinal studies of health effects often relate individuals' biomarker levels to disease progression. Repeated measurements also provide an opportunity to assess within-individual biomarker variability, and it is reasonable to postulate that this measure might provide additional information about a particular outcome variable. Given the existing precedent for application of adjustment methods to account for measurement error in subject-specific average levels of a covariate, this concept motivates the application of such methods to incorporate variability as well. In this paper, we investigate the nature of the relationship between the decline of CD4 cell count induced by infection with human immunodeficiency virus, and CD4 level and variability prior to infection. We first describe the distribution of repeated CD4 measurements prior to infection using a model that accounts both for random average levels and random subject-specific variance components. Based on this model, we define true unobservable random variables that correspond to prior level and stability. We perform a linear regression analysis, using these latent variables as covariates, by means of a full maximum likelihood approach. We compare the resulting parameter estimates with those based on regressions employing sample-based estimates of pre-infection levels and variances, and empirical Bayes estimates of these quantities. Although the final inferences are similar to those based on the unadjusted analysis, we find that the magnitude of association with prior level decreases, while that with prior stability increases. Stratified analyses indicate that smoking status affects the relationship between prior CD4 level and initial CD4 decline. We point out advantages associated with the maximum likelihood approach in this particular application.     

Isolated pedunculated congenital corneal dermoid

PURPOSE: To investigate a case of isolated pedunculated congenital corneal dermoid. METHODS: Case report. RESULTS: In a 14-day-old infant, the pedunculated portion of the dermoid was removed and confirmed by histopathologic examination. No surgical complication or recurrence was encountered, and the patient is waiting for a rotational autokeratoplasty. CONCLUSIONS: Prompt treatment of such an unusual tumor is important to allow for visual rehabilitation and development.     

Discovery of novel non-peptide CCR1 receptor antagonists

Ligands for the CCR1 receptor (MIP-1alpha and RANTES) have been implicated in a number of chronic inflammatory diseases, most notably multiple sclerosis and rheumatoid arthritis. Because these ligands share a common receptor, CCR1, we sought to discover antagonists for this receptor as an approach to treating these disorders. A novel series of 4-hydroxypiperidines has been discovered by high throughput screening (HTS) which potently inhibits the binding of MIP-1alpha and RANTES to the recombinant human CCR1 chemokine receptor. The structure-activity relationships of various segments of this template are described as the initial HTS lead 1 was optimized synthetically to the highly potent receptor antagonist 6s. This compound has been shown to have at least 200-fold selectivity for inhibition of CCR1 over other human 7-TM receptors, including other chemokine receptors. In addition, data obtained from in vitro functional assays demonstrate the functional antagonism of compound 6s and structurally related analogues against the CCR1 receptor in a concentration dependent manner. The discovery and optimization of potent and selective CCR1 receptor antagonists represented by compound 6s potentially represent a novel approach to the treatment of chronic inflammatory diseases.     

Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy.

The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor-derived cell line.     

Random primed polymerase chain reaction differentiates Codonopsis pilosula from different localities

DNA fingerprints distinctive among the samples from different localities in China were successfully reproduced for the Chinese herb Dangshen, the roots of CODONOPSIS PILOSULA, (Campanulaceae). Similarity index (S.I.) analysis revealed that C. PILOSULA samples from the same province generated similar DNA fingerprints, while samples of different provinces displayed different DNA fingerprints. This method may be a general and valuable tool for locality authentication of other Chinese herbal medicinal materials.