Executive and compensatory memory retraining in traumatic brain injury

A controlled treatment outcome study was conducted comparing the efficacy of memory remediation treatment with no treatment on traumatic brain-injury patients. The memory remediation treatment consisted of both compensatory and executive training skills and was delivered 6 hours weekly over a 2 1/2-week period. Six subjects in the treatment group and 6 subjects in the control group were matched on WAIS-R FSIQ scores, pre-test memory scores and age. Pre-and post-test measures were obtained for both groups on a paragraph memory task. A significant difference was demonstrated between the treatment and control post-test memory scores. The experimental group significantly improved memory scores beyond that of the control group, suggesting that memory remediation is effective for head-injury patients with memory deficits. Discussion of findings and suggestions for further investigation are presented.     

Administration of Half-Dose Theophylline Together with Ketotifen to Asthmatic Children—A Double-Blind, Placebo-Controlled Study

Administration of theophylline to asthmatic children is frequently associated with an adverse influence on their behavior. The efficacy and behavioral effects of the administration of high-dose theophylline (T) and ketotifen (K) in various combinations were evaluated prospectively in a double-blind, placebo controlled study in 55 children with moderately severe perennial asthma. During a baseline period of 2 weeks, theophylline (serum level of 10-20 μg/ml) was administered to all the children. After this period the patients were randomly allocated into four comparable groups. The children were treated during a 12-week period with: T + K-Placebo (T group); T + K (T + K group); half-dose T + K (T/ 2 + K group); or placebo of both T and K (P group). During the 12-week treatment period, as compared to the baseline period, only the three groups of children who received active therapy (T + P, T + K, T/2 + K) showed a similar reduction in the number of days with asthmatic symptomatology, improvement of the total asthmatic symptoms score, and increased PEFR. The behavioral activity of the children (assessed by the Conner's rating scale) improved significantly only in the groups receiving placebo or T/2 + K. The results of this study suggest that a combination therapy of half the recommended therapeutic dose of theophylline with ketotifen can be clinically as effective as therapy with a full dose of theophylline, but with significantly less adverse behavioral effects.     

Monitoring the protective effects of minocycline treatment with radiolabeled annexin V in an experimental model of focal cerebral ischemia.

Minocycline is an antibiotic now recognized to have antiapoptotic and antiinflammatory properties. Because of these properties, minocycline may be of benefit in reducing neuronal apoptosis from ischemia and subsequent postischemic inflammation if administered soon after a stroke. We now explore the feasibility of using (99m)Tc-annexin V, an in vivo marker of apoptosis, with SPECT to monitor the antiapoptotic effects of minocycline therapy. METHODS: CB6/F1 adult male mice underwent unilateral distal middle cerebral artery occlusion (dMCA) occlusion and were imaged and sacrificed at 1, 3, 7, or 30 d after injury. Animals were given minocycline (or vehicle) 30 min and 12 h after dMCA occlusion and then given 22.5 mg/kg twice daily for up to 7 d. Before imaging, behavioral tests were performed to evaluate the neurologic function. After imaging, brains were collected for histology and assessed for the degree of apoptosis and microglial activation. RESULTS: (99m)Tc-Annexin V uptake in injured hemispheres was significantly decreased 2- to 3-fold by minocycline at all time points. Minocyline reduced infarct size as seen histologically and improved behavioral indices as late as 30 d. Infarct volume as seen histologically correlated with radiolabeled annexin V uptake seen by SPECT. In situ fluorescent microscopy demonstrated that annexin V bound primarily to neurons at 1 and 3 d, with a shift toward microglia by 7 and 30 d. CONCLUSION: We found that minocycline significantly reduces neuronal apoptosis and infarct size and improves neurologic outcome in mice after acute focal cortical ischemia.     

Effects of racist provocation and social support on cardiovascular reactivity in african american women

It has been speculated that exposure to the chronic stress of racism contributes to the high rates of hypertension among African Americans. Social support may buffer the effects of stress on cardiovascular (CV) health by attenuating stress-induced CV responses that have been linked to hypertension. In this study we investigated the effects of racism and social support on CV reactivity in African American women. Participants showed greater increases in CV and emotional responses while responding and listening to racist provocation. Augmented blood pressure (BP) persisted through recovery following racial stress. Participants receiving no support showed the greatest increases in anger during racist provocation. No significant effects were seen for support on CV reactivity. These results provide some of the first evidence that interactive confrontation with racism elicits significant increases in CV reactivity and emotional distress. Furthermore, individuals receiving less support may be at greater risk for the potentially health-damaging effects of racial stress. These findings may have significant implications for the health of African Americans.     

Histidinuria: A renal and intestinal histidine transport deficiency found in two mentally retarded children

Two siblings presenting slight mental retardation showed an abnormal elimination of histidine, their blood levels for the same amino acid being normal. The percentage of tubular resorption of histidine was calculated in both boys, and the values were 40.1 per cent (case 1) and 52.8 per cent (case 2). All other amino acids essayed were normal. After an oral overload test with histidine, a low intestinal absorption was found in the two boys, the values of this test in the parents being intermediate between those of the children and of the three normal controls and corresponding to heterozygosity. In view of the studies carried out on the two boys, it is possible to conclude that they are suffering from an impairment in their histidine membrane transport system which affects the kidney and intestines. Since they are siblings a genetically determined trait may be suspected.     

Modeling for Lesch-Nyhan disease by gene targeting in human embryonic stem cells

Human embryonic stem (ES) cells are pluripotent cells derived from blastocyst-stage embryos. It has been suggested that these cells should play a major role in transplantation medicine and be able to advance our knowledge in human embryology. We propose that these cells should also play a vital role in the creation of models of human disorders. This aspect would be most valuable where animal models failed to faithfully recapitulate the human phenotype. Lesch-Nyhan disease is caused by a mutation in the HPRT1 gene that triggers an overproduction of uric acid, causing gout-like symptoms and urinary stones, in addition to neurological disorders. Due to biochemical differences between humans and rodents, a mouse lacking the HPRT expression will fail to accumulate uric acid. In this research we demonstrate a model for Lesch-Nyhan disease by mutating the HPRT1 gene in human ES cells using homologous recombination. We have verified the mutation in the HPRT1 allele at the DNA and RNA levels. By using selection media, we show that HPRT1 activity is abolished in the mutant cells, and the HPRT1-cells show a higher rate of uric acid accumulation than the wild-type cells. Therefore, these cells recapitulate to some extent the characteristics of Lesch-Nyhan syndrome and can help researchers further investigate this genetic disease and analyze drugs that will prevent the onset of its symptoms. We therefore suggest that human diseases may be modeled using human ES cells.     

Development and characterisation of neutralising monoclonal antibody to the SARS-coronavirus

There is a global need to elucidate protective antigens expressed by the SARS-coronavirus (SARS-CoV). Monoclonal antibody reagents that recognise specific antigens on SARS-CoV are needed urgently. In this report, the development and immunochemical characterisation of a panel of murine monoclonal antibodies (mAbs) against the SARS-CoV is presented, based upon their specificity, binding requirements, and biological activity. Initial screening by ELISA, using highly purified virus as the coating antigen, resulted in the selection of 103 mAbs to the SARS virus. Subsequent screening steps reduced this panel to seventeen IgG mAbs. A single mAb, F26G15, is specific for the nucleoprotein as seen in Western immunoblot while five other mAbs react with the Spike protein. Two of these Spike-specific mAbs demonstrate the ability to neutralise SARS-CoV in vitro while another four Western immunoblot-negative mAbs also neutralise the virus. The utility of these mAbs for diagnostic development is demonstrated. Antibody from convalescent SARS patients, but not normal human serum, is also shown to specifically compete off binding of mAbs to whole SARS-CoV. These studies highlight the importance of using standardised assays and reagents. These mAbs will be useful for the development of diagnostic tests, studies of SARS-CoV pathogenesis and vaccine development.