An unbinding problem? The disintegration of visible,previously attended objects does not attract attention

In seven experiments, observers searched for a scrambled object among normal objects. The critical comparison was between repeated search in which the same set of stimuli remained present in fixed positions in the display for many (>100) trials and unrepeated conditions in which new stimuli were presented on each trial. In repeated search conditions, observers monitored an essentially stable display for the disruption of a clearly visible object. This is an extension of repeated search experiments in which subjects search a fixed set of items for different targets on each trial (Wolfe, Klempen, & Dahlen, 2000) and can be considered as a form of a "change blindness" task. The unrepeated search was very inefficient, showing that a scrambled object does not "pop-out" among intact objects (or vice versa). Interestingly, the repeated search condition was just as inefficient, as if participants had to search for the scrambled target even after extensive experience with the specific change in the specific scene. The results suggest that the attentional processes involved in searching for a target in a novel scene may be very similar to those used to confirm the presence of a target in a familiar scene.     

Evaluation of self-reported skin problems among workers exposed to toluene diisocyanate (TDI) at a foam manufacturing facility

Toluene diisocyanate, or TDI (CAS 584-84-9) is a well-known asthmagen and respiratory irritant. TDI is also known for its ability to irritate the skin and mucous membranes. To further investigate the dermal effects of TDI, NIOSH investigators conducted a cross-sectional study at a flexible foam manufacturing plant. A total of 114 workers participated in the study. Participants completed a medical questionnaire, provided blood for antibody testing to TDI and other allergens, and a subset of participants reporting skin symptoms underwent skin patch testing to a standard diisocyanate panel. Production line workers were more than twice as likely to report skin problems as those working in nonproduction areas (PRR = 2.66; 95% CI = 1.14-16.32; P = 0.02). Age, gender and duration of employment at the plant were comparable among participants working in production and nonproduction areas. Of the 100 participants who provided blood samples for antibody testing, specific IgG antibody to TDI was detected in two individuals, and none of the samples demonstrated specific IgE antibody to TDI. Of the 26 workers who underwent skin patch testing, none developed reactions to the diisocyanate allergens. These results suggest that the skin symptoms among study participants represent an irritant rather than an immunologic reaction to TDI, or to an unidentified allergen present in the foam.     

The blood-brain barrier and its role in immune privilege in the central nervous system

The blood-brain barrier (BBB) provides both anatomical and physiological protection for the central nervous system (CNS), strictly regulating the entry of many substances and blood borne cells into the nervous tissue. Increased understanding of how the unique microenvironment in the CNS influences the BBB is crucial for developing novel therapeutic approaches to CNS diseases. In this review, we discuss those characteristics of the BBB that play an important role in maintaining immune privilege in the CNS, as well as factors that regulate immune cell invasion through the BBB and thereby modulate immune responses in the nervous tissue. In general, immune cell invasion across the BBB is highly restricted and carefully regulated. A florid invasion of activated white blood cells can create a predominantly proinflammatory local environment in the CNS, leading to immune-mediated diseases of the nervous tissue. Recent developments in cellular and molecular biological methods have allowed closer analysis of BBB function, and led to an improved understanding of the active role of the BBB in immune-mediated diseases of the CNS.     

"Beware of coming too close to me"--development-oriented psychotherapy of a dangerous aggressive boy with early complex trauma experiences

Early maltreatment of children can lead to severe disorders in the regulation of behaviour and affect, alterations in awareness and distorted perception. In development-oriented psychotherapy, therapeutic interventions which are directed to regulating processes, decentration or mentalization, desomatization and symbolization of enacted messages play a central role. The results of early traumatization and of therapeutic interventions are portrayed, examining the multi-dimensional diagnosis and therapy of a dangerously aggressive 12-year-old boy as an example. From this, it becomes clear how, through new experiences with regulating others, he gradually surfaces from a world of annihilation and destruction and learns to survive and to live.     

Fibroblast growth factor-2 but not Mel-CAM and/or beta3 integrin promotes progression of melanocytes to melanoma

A variety of melanoma-associated antigens have been identified that mediate adhesion, growth, proteolysis, and modulation of immune response. However, the mechanisms by which human normal melanocytes become malignant are not clearly understood. Among the most consistent observations is the up-regulation of fibroblast growth factor-2 (FGF-2) and of the adhesion molecules beta3 integrin and Mel-CAM during melanoma progression. To evaluate the potential role of FGF-2, beta3 integrin and Mel-CAM in melanoma development we overexpressed FGF-2, beta3 integrin and Mel-CAM in normal human melanocytes using replication-deficient adenoviruses as a gene delivery vehicle. Fibroblast growth factor-2 overexpressing melanocytes in monolayer culture displayed cytological atypia. Furthermore, in human skin reconstructs where the physiological milieu is recreated in vitro, FGF-2-overexpressing melanocytes exhibited marked proliferation, upwards migration, cluster formation and type IV collagen expression within the epidermal compartment, simulating early radial growth phase melanoma. In contrast, overexpression of beta3 integrin and/or Mel-CAM in melanocytes did not affect their biological behaviour in human skin reconstructs. The described results of the current and previous studies emphasise the key role of FGF-2 in melanoma development and progression, underscoring the promise of FGF-2 as a target for therapy.     

Decremental Pulmonary Venous Pulse Propagation: Impact for Catheter Ablation in Focal Atrial Fibrillation

Background: Electrical isolation of pulmonary veins (PV's) is crucial to achieve success in catheter ablation for trigger elimination in focal atrial fibrillation (AF). To guide ostial PV radiofrequency (RF) delivery, it is necessary to identify the electrical breakthrough (EBT) between PV and left atrium. For this purpose, coronary sinus (CS) fixed rate pacing is commonly used. This study evaluated, whether CS extrastimulus pacing is superior in identifying the EBT area as compared to fixed rate pacing. Methods: In 9 patients (51 ± 10 years) undergoing a left sided electrophysiological study for AF ablation, 25 PV's (10 right and 15 left-sided PV's) were mapped using a 4 French fixed-wire catheter with eight 6 mm coiled Platinum electrodes in a distal looped configuration (Revelation Helix, Cardima Inc.). For mapping and ablation the electrode loop was positioned in the PV ostium rectangular to the longitudinal PV axis. EBT area was identified as those electrodes indicating the earliest PV signals during CS pacing. We measured number of EBT electrodes and time between EBT and the latest activated bipoles at the electrode loop during fixed rate and extrastimulus pacing. The reduction of two or more EBT electrodes was defined as a significant benefit in EBT identification. Results: In 22 of 25 PV's mapped PV potentials could be observed. Performing fixed rate pacing the EBT area was identified in a mean of 4.2 ± 1 electrodes, whereas using extrastimulus pacing, EBT area could be significantly reduced to 2.3 ± 0.8 electrodes. The time between EBT and latest electrode activated increased from 14 ± 7 ms to 22 ± 10 ms indicating an intrapulmonary conduction delay during extrastimulus pacing. In 13 of 22 PV's mapped (59%), extrastimulus pacing was beneficial in the identification of the EBT, as the primary target for RF delivery. Conclusions: CS extrastimulus pacing induces intra-PV decremental conduction properties allowing one to identify a more localised and smaller EBT area as the primary target for RF delivery. Performing PV ablation to treat focal AF, extrastimulus maneouvers allow to unmask the true EBT and thus may help to limit intrapulmonary RF delivery.     

Clinical heterogeneity of childhood diabetes in Baranya county

INTRODUCTION: Immune mediated type 1 diabetes is the most frequent form of childhood diabetes while type 2 and other forms are more rare in childhood in the Caucasian population. Differentiation of various diabetes subtypes has importance in the choice of treatment and prognosis. AIMS: The aim of the study was to describe clinical heterogeneity of childhood diabetes and to evaluate possibilities of phenotypical classification. METHODS: Two hundred twenty eight children (128 girls and 100 boys) with diabetes diagnosed at the Department of Pediatrics, University of Pécs, in the period of 1978-2000 were examined. Glycated hemoglobin levels, insulin requirement, body weight at diagnosis and association of type 1 diabetes with other disorders were analysed. RESULTS: Thirty one patients (13.6%) had permanently low (< 8%) glycated hemoglobin levels. Low glycated hemoglobin level associated with low insulin requirement (< 0.5 U/kg/day) was observed in three patients (1.4%) with 4 years of disease duration and in 2 patients (0.9%) during the whole disease course. These patients can be classified as non-classical type 1 diabetes cases. Obesity associated with less than 0.5 U/kg/day insulin requirement observed at least for two years from diagnosis was found in 2 cases (0.9%). These cases may be diagnosed as having childhood type 2 diabetes. The authors identified two diabetes patients with Down syndrome while MODY and transient neonatal diabetes were observed in one cases each. Diabetes associated conditions diagnosed in single cases each were as follows: thymus tumor, Duchenne muscular dystrophy, autoimmune polyglandular syndrome type 2, and T-cell lymphoma. CONCLUSIONS: Childhood diabetes cases can be classified into several subgroups on clinical grounds, insulin requirement, and glycemic control. The data suggest that the prevalence of type 2 and non-classical type 1 diabetes is probably only a few percent among children with diabetes in Hungary. Due to phenotypic overlap between different forms of diabetes, measurement of beta-cell specific autoantibodies and C peptide levels can be recommended for etiologic classification.     

Effects of educational attainment and occupational status on cognitive and functional decline in persons with Alzheimer-type dementia

Researchers have suggested that educational attainment and occupational status--indicators of cognitive and/or neurologic "reserve"--can help persons compensate for clinical manifestations of Alzheimer's disease (AD), such as the rates of cognitive and functional decline. The effects of educational attainment on rates of decline could be "direct" independent of occupational status), "indirect" (working through occupational status), or both. We used multilevel analysis for repeated measures to study the effects of educational attainment and occupational status on rates of decline in cognition (Mini-Mental State Examination, MMSE) and function (Cleveland Scale for Activities of Daily Living). Subjects included persons with "probable" or "possible" AD, drawn from our Alzheimer's Disease Research Center registry (N = 482 in the analysis of cognitive decline, and N = 450 in the analysis of functional decline). When controlling for year of birth, gender, ethnicity, and duration of illness, we found that there was an inverse relationship between number of years of education and rate of decline in MMSE, but effects of occupational status were not significant. This implies a "direct" effect of education on decline in MMSE, but no "indirect" effect through occupational status. Neither educational attainment nor occupational status affected rate of decline in functional ability. We conclude that education slows the rate of cognitive decline in persons with AD, but not through its impact on occupational status. Thus, the protective effects of reserve may be established early in life, before people enter the workforce.     

Inhibition of neointimal formation after stent placement with adenovirus-mediated gene transfer of I kappa B alpha in the hypercholesterolemic rabbit model: initial results

PURPOSE: To evaluate the feasibility and efficacy of the local application of a replication-defective adenovirus construct for the expression of the antiinflammatory protein I kappa B alpha, inhibitor of nuclear factor kappa B (NF-kappa B), to reduce neointimal formation after stent placement. MATERIALS AND METHODS: Nitinol stents were implanted in the iliac arteries of hypercholesterolemic rabbits, followed by balloon dilation (30 seconds at 6 atm). Local adenovirus-mediated transfer of I kappa B alpha (3 mL of 10(9) plaque-forming units per milliliter at 6 atm) was performed and compared with three control groups: stent alone, stent plus local delivery of phosphate-buffered saline (PBS) (3 mL at 6 atm), and stent plus local delivery of control adenovirus coding for green fluorescent protein (GFP) (3 mL of 10(9) plaque-forming units per milliliter at 6 atm). A multichannel balloon was used for local drug delivery and balloon dilation. Animals were sacrificed 1 or 4 weeks after treatment. Effective transfection was demonstrated with immunofluorescence staining. Angiographic patency and luminal diameter were evaluated at quantitative angiography. Luminal and neointimal areas were measured on surface-stained ground sections with methylmethacrylate embedding and the cutting-grinding technique. RESULTS: All vessels with stents were patent at angiography. Neointimal area was negligible in all groups 1 week after stent placement (range, 0.42-0.52 mm(2); P =.44; analysis of variance). Neointimal formation was demonstrated in all groups 4 weeks after implantation but was significantly reduced with I kappa B alpha treatment compared with treatment with stent alone (by 22%, from 2.80 mm(2) +/- 0.20 to 2.28 mm(2) +/- 0.14, P =.05), stent plus PBS (by 43%, from 3.26 mm(2) +/- 0.25 to 2.28 mm(2) +/- 0.14, P =.005), and stent plus GFP (by 53%, from 2.32 mm(2) +/- 0.19 to 1.51 mm(2) +/- 0.08, P <.005). CONCLUSION: Local adenovirus-mediated I kappa B alpha gene transfer has the potential to reduce intimal hyperplasia after stent placement.