Shared and distinct neurophysiological components of the digits forward and backward tasks as revealed by functional neuroimaging

The digits forward (DF) and backward (DB) tasks are widely used neuropsychological measures believed to tap overlapping systems of phonological processing and working memory. Studies of focal brain lesions have partially elucidated the brain regions essential for these tasks; however relatively little information exists on the underlying functional neuroanatomy in the intact brain. We therefore examined the shared and separate neural systems of these tasks in two positron emission tomography (PET) experiments. In Experiment 1, eight healthy participants performed verbal DF, DB, and a sensorimotor control task during measurement of regional cerebral blood flow (rCBF). DF and DB each activated frontal, parietal, and cerebellar regions as well as prominently activating medial occipital cortex. To eliminate possible visuospatial confounds, Experiment 2 replicated the first experiment in six additional healthy participants who were blindfolded during the study. No differences in activation were found between the two experimental groups. Combined data from both experiments demonstrate that DF and DB rely upon a largely overlapping functional neural system associated with working memory, most notably right dorsolateral prefrontal cortex (DLPFC) and bilateral inferior parietal lobule (IPL) as well as the anterior cingulate, a region associated with attentional effort. The degree of activation increased linearly with increasing task difficulty in DF. DB additionally recruited bilateral DLPFC, left IPL, and Broca's area. Medial occipital cortex (including higher and lower visual processing areas) was robustly activated in both DF and DB and could not be attributed to visual processing per se, suggesting a possible visual imagery strategy for these aural-verbal tasks.     

Peer, family integration and other determinants of cannabis use among teenagers

Cannabis consumption is on the rise in the French-speaking Community of Belgium, especially among teenagers. The physical and mental harms related to that drug prompted us to search for factors associated with cannabis consumption. The aim of this paper is thus to identify a series of potential predictors of teenager's cannabis use and particularly the influence of peer and family integration. The data analyzed were taken from the 1998 data bank "Health Behavior in School-Aged Children", an international quantitative cross-national study, which takes place every four years. The variables investigated were peer and family integration and the habit of drug consumption (tobacco, alcohol or a narcotic other than cannabis) as potential determinants of the experimentation, current usage of cannabis (at least once a month) and regular usage (at least once a week). Apart from the socio-demographic variables, these predictors were investigated by univariate and multivariate analysis (logistic regression). The analyses covered 744 students in Catholic high schools. Results showed that 30.2% of students had tried to smoke cannabis and 50% of them continued to smoke it at least during the previous month. Age, number of income in the family, strong peer group integration [OR 7.7; CI 95% (3.5;17.3)] and drug-consumption habit [for example, tobacco use: OR 7.4; CI 95% (4.8;11.32)] were associated with cannabis experimentation. Age, gender, nationality, average family integration [OR 2.13; CI 95% (1.1;4.1)] and other drugs use as addiction to nicotine [OR 9.5; CI 95% (5.6;16.3)] determined the current consumption of the substance. Preventive action should aim at improving the teenager's integration into the family circle in order to prevent the trial and consumption of cannabis. In addition, prevention should include the consumption of (addictive) substances in general.     

T-cell proliferative responses following sepsis in neonatal rats

Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment of animals with COX-2 inhibitor also significantly prevented the sepsis-associated mortality in neonates. In conclusion, the present study demonstrated T-cell suppression during neonatal sepsis is accompanied by a decrease in IL-2 production. Such suppressions were ameliorated with COX-2 inhibitor suggesting a role for PGE2 in the suppressed T-cell-mediated immune function in neonatal sepsis.     

Immunomodulatory therapy for pediatric inflammatory bowel disease: changing patterns of use, 1990-2000

OBJECTIVE: To identify changes over the past decade in physicians' attitudes regarding the use of immunomodulatory agents for the treatment of children with inflammatory bowel disease (IBD), we surveyed the membership of the North American Society for Pediatric Gastroenterology and Nutrition and compared the responses to those from an identical survey performed in 1990. METHODS: Surveys were mailed to 718 physicians in January, 2000. All surveys returned by mid-February were analyzed, and results compared to those obtained in the 1990 survey. RESULTS: Thirty-nine percent (278/718) of surveys were returned, compared to 27% (105/385) in 1990. Overall, 93% of the current survey's respondents agreed with the statement "immunomodulatory agents are effective in the treatment of children and adolescents with IBD." Compared to 1990, significant increases (p < 0.0001) were noted in the percentage of respondents who prescribe immunomodulatory agents to children with all forms of IBD. Indications for immunomodulation that showed significant increases (p < 0.001) since 1990 included treatment of perianal and non-perianal fistulae; growth failure; use as initial, primary therapy; and use as prophylaxis against postoperative recurrence. 6-Mercaptopurine and azathioprine continue to be the agents prescribed by the greatest percentage of respondents. More physicians are willing to use immunomodulatory agents in children younger than 5 yr, and duration of use is longer than in 1990. Currently, physicians seem to favor the use of immunomodulatory agents over colectomy for children with either intractable ulcerative or Crohn's colitis. Most respondents remain concerned about potential bone marrow and immune suppression, but concerns regarding malignancy, teratogenicity, and infertility have lessened. CONCLUSION: These survey findings document that pediatric gastroenterologists have widely accepted the use of immunomodulators in the treatment of children and adolescents with IBD.     

Polymers derived from the amino acid L-tyrosine: polycarbonates,polyarylates and copolymers with poly(ethylene glycol)

The natural amino acid L-tyrosine is a major nutrient having a phenolic hydroxyl group. This feature makes it possible to use derivatives of tyrosine dipeptide as a motif to generate diphenolic monomers, which are important building blocks for the design of biodegradable polymers. Particularly useful monomers are desaminotyrosyl-tyrosine alkyl esters (abbreviated as DTR, where R stands for the specific alkyl ester used). Using this approach, a wide variety of polymers have been synthesized. Here, tyrosine-derived polycarbonates, polyarylates, and polyethers are reviewed with special emphasis on recent developments relating to cellular and in vivo responses, sterilization techniques, surface characterization, drug delivery, and processing and fabrication techniques. The commercial development of tyrosine-derived polycarbonates is most advanced, with one polymer, poly(DTE carbonate) (E=ethyl), being under review by the USA Federal Drug Administration.     

Apoptotic susceptibility of cancer cells selected for camptothecin resistance: gene expression profiling,functional analysis,and molecular interaction mapping

To study the molecular mechanisms by which drug resistance develops, we compared DU145 humanprostate cancer cells with a subline selected for resistance to camptothecin.Differences in gene expression level were assessed by hybridizing the two cell types against each other using quadruplicate "Oncochip" cDNA microarrays that included 1648 cancer-related genes. Expression levels differing by a factor of >1.5 were detected for 181 of the genes. These differences were judged statistically reliable on the basis of a stratum-adjusted Kruskal-Wallis test, after taking into account a dye-dependent variable. The 181 expression-altered genes included a larger than expected number of the "apoptosis-related" genes (P = 0.04). To assess whether this observation reflected a generalized resistance of RCO.1 to apoptosis, we exposed the cells to a range of stresses (cisplatin, staurosporine, UV, ionizing radiation, and serum starvation) and found greatly reduced apoptotic responses for RC0.1 (relative to DU145) using flow cytometric Annexin V and terminal deoxynucleotidyl transferase-mediated nick end labeling assays. We next examined the apoptosis-related genes in the context of a molecular interaction map and found expression differences in the direction "expected" on the basis of the apoptosis-resistance of RC0.1 for BAD, caspase-6, and genes that signal via the Akt pathway. Exposure of the cells to wortmannin, an inhibitor of the Akt effector phosphatidylinositol 3-kinase, provided functional support for involvement of the Akt pathway. However, closer examination of the molecular interaction map revealed a paradox: many of the expression differences observed for apoptosis-related genes were in the direction "contrary" to that expected given the resistance of RC0.1. The map indicated that most of these unexpected expression differences were associated with genes involved in the nuclear factor kappa B and transforming growth factor beta pathways. Overall, the patterns that emerged suggested a two-step model for the selection process that led to resistance in RC0.1 cells. The first hypothesized step would involve a decrease in apoptotic susceptibility through changes in the apoptosis-control machinery associated with the Bcl-2 and caspase gene families, and also in antiapoptotic pathways operating through Akt/PKB. The second step would involve changes in multifunctional upstream genes (including some genes in the nuclear factor kappa B and transforming growth factor beta pathways) that can facilitate apoptosis but that would also tend to contribute to cell proliferation in the presence of drug. Thus, we propose that a downstream blockade of apoptosis was "permissive" for the selection of upstream pathway changes that would otherwise have induced apoptosis. This model is analogous to one suggested previously for the relationship between oncogene function and apoptosis in carcinogenesis.     

Couples therapy at end of life

This study reports on a preliminary uncontrolled study of a treatment for couples in which one partner is diagnosed with a terminal illness. In this study nine couples, in which one partner was diagnosed with a terminal illness and had less than 18 months to live, were offered eight sessions of couples therapy. Follow-up data were available for six couples. Two patients died during treatment and a third patient moved out of the area prior to completing the follow-up assessment. Significant decreases were seen in the patients' distress about dying and the frequency of partners' worry about their partner dying. Improvements were also seen in relationship quality. While the size of the study precludes generalizing these findings to a larger population, this study supports further exploration of couples therapy as a potentially useful adjunct to end of life care.     

Emergency health surveillance after severe flooding in Louisiana, 1995

INTRODUCTION: In disaster situations, timely surveillance systems that provide illness, injury, and mortality information to public health officials and hospitals are essential for planning and evaluating interventions. OBJECTIVES: To describe flood surveillance methodology, the impact of the event on hospitals, and the number of daily patient visits due to selected illnesses and injuries before, during, and after severe flooding in southeastern Louisiana in May 1995. METHODS: Survey of disaster-area hospitals regarding flood impact. Emergency department surveillance of injuries and illnesses for the week before, the two days during, and the week after the flood. RESULTS: There occurred an increase in the number of persons who drowned or were injured that presented to the moderately affected hospitals during the storm, but there was no increase in visits for gastroenteritis to any group of hospitals. Services were disrupted in more than half of hospitals. The severely affected hospitals had the least variation in the average number of daily visits. None of the drownings were reported by those hospitals that reported severe service disruption. CONCLUSIONS: Data should be collected from all hospitals in or near disaster areas, even if they were not directly affected by the disaster. Public education about the danger of drowning during flash flooding must be improved. The Louisiana experience emphasizes the need for a disaster-preparedness plan for rapid surveillance of illnesses and injuries.     

Interindividual differences in functional interactions among prefrontal, parietal and parahippocampal regions during working memory

To clarify the neural systems deployed by individual subjects during working memory (WM), we collected functional neuroimaging data from healthy subjects, and constructed a model of 2-back WM using structural equation modeling (SEM). A group model was constructed, and models for each subject were validated against it. The group model consisted principally of regions in the prefrontal and parietal cortex, with considerable interindividual variance in the single-subject models. To explore this variance, subjects were split into two groups based on performance. Performance level and self-reported strategy scores were used in a correlation analysis against path weights between nodes of individual models. High performers utilized a left hemisphere sub-network involving inferior parietal lobule and Broca's area, whereas lower performers utilized a right hemisphere sub-network with interactions between inferior parietal lobule and dorsolateral prefrontal cortex. Further, we observed an interaction between the parahippocampal formation and the inferior parietal lobule that was related to the different strategies used by the individuals to perform the task. Strategy and performance level appear to be intricately related in this task, with neural systems supporting verbal processing producing better performance than those associated with spatial processing. These results demonstrate that individual behavioral characteristics are reflected in specific neurofunctional patterns at the system level and that these can be captured by analytical techniques such as SEM.