Aging is not equal across memory systems.

The present experiments compared the effects of aging on learning several hippocampus- and striatum-sensitive tasks in young (3-4 month) and old (24-28 month) male Fischer-344 rats. Across three sets of tasks, aging was accompanied not only by deficits on hippocampal tasks but also by maintained or even enhanced abilities on striatal tasks. On two novel object recognition tasks, rats showed impaired performance on a hippocampal object location task but enhanced performance on a striatal object replacement task. On a dual solution task, young rats predominately used hippocampal solutions and old rats used striatal solutions. In addition, on two maze tasks optimally solved using either hippocampus-sensitive place or striatum-sensitive response strategies, relative to young rats, old rats had impaired learning on the place version but equivalent learning on the response version. Because glucose treatments can reverse deficits in learning and memory across many tasks and contexts, levels of available glucose in the brain may have particular importance in cognitive aging observed across tasks and memory systems. During place learning, training-related rises in extracellular glucose levels were attenuated in the hippocampus of old rats compared to young rats. In contrast, glucose levels in the striatum increased comparably in young and old rats trained on either the place or response task. These extracellular brain glucose responses to training paralleled the impairment in hippocampus-sensitive learning and the sparing of striatum-sensitive learning seen as rats age, suggesting a link between age-related changes in learning and metabolic substrate availability in these brain regions.

The cross-sectional association between diabetes and orthostatic hypotension in community-dwelling older people.

AIMS: Orthostatic hypotension is a recognized complication of diabetes, but studies examining prevalence in diabetes are limited. The aim of this study was to ascertain the prevalence of orthostatic hypotension and the pattern of orthostatic BP response in a cohort of people with diabetes aged ≥ 50 years, embedded within the Irish Longitudinal Study of Ageing. METHODS: Orthostatic hypotension was defined as a drop in systolic blood pressure (SBP) ≥ 20 mmHg or drop in diastolic blood pressure (DBP) ≥ 10 mmHg at 30 s after standing. Diabetes was defined by self-report but cross-checked against HbA1c and medication records. Multilevel mixed effects linear regression models were used to compare orthostatic BP in people with and without diabetes. RESULTS: Some 3222 people were included, 7% (213 of 3222) of whom had diabetes. Prevalence of orthostatic hypotension in the group with diabetes was 22% (46 of 213) vs. 13% in those without diabetes; χ2 = 12.43; P < 0.001. Multilevel models demonstrated prolonged recovery of DBP in people with diabetes, with only 41% (87 of 213) returning to baseline by 60 s. Logistic regression models demonstrated that diabetes was associated with a significantly increased likelihood of orthostatic hypotension (odds ratio 1.84, 95% confidence interval 1.30-2.59; P = 0.001) and this remained robust after controlling for covariates. CONCLUSION: Over one-fifth of older people with diabetes had orthostatic hypotension. Recovery of DBP is related to dynamic changes in total peripheral resistance and impairment of this baroreflex-mediated response may explain the higher prevalence in diabetes. Given the prognostic implications when co-existing with diabetes, orthostatic hypotension may represent a potentially modifiable risk factor for adverse outcomes in late-life diabetes.

Clinical utility of portable electrophysiology to measure fatigue in treatment-naïve non-small cell lung cancer.

PURPOSE: Cancer-related fatigue (CRF) biology remains poorly understood. Responsible mechanisms may be central or peripheral and originate anywhere from the brain to muscle fiber. Objective measurement is complex and previously limited to specialized laboratories. Portable electroencephalography (EEG) and electromyography (EMG) may enhance objective measurement. This study evaluated the feasibility and acceptability of portable EMG-EEG in CRF assessment. METHODS: A prospective observational feasibility study compared ten outpatients with inoperable, treatment-naïve non-small cell lung cancer and CRF to ten healthy volunteers. All completed a sustained isometric hand-grip contraction at 30% maximal level until self-perceived exhaustion. 128-channel EEG and 2-channel EMG signals of forearm muscles were recorded. Device acceptability was evaluated by questionnaire. RESULTS: The task was evaluated in two stages; first and last 20 s. CRF cohort perceived exhaustion earlier than volunteers (mean 137 ± 76 s vs 208 ± 51 s). As fatigue progressed, EMG amplitude increased significantly (CRF p = 0.02; volunteers: p = 0.04) in both groups as did EMG beta band power (CRF p = 0.008; volunteers: p = 0.006). The increase was significantly less in CRF (amplitude p = 0.032; beta power: p = 0.014). EEG beta band power in the contralateral motor cortex increased significantly (CRF p = 0.03; volunteers: p = 0.019) in both cohorts but to greater extent (p = 0.024) in CRF. One hundred percent device acceptability was reported. CONCLUSIONS: A laboratory-based evaluation was successfully adapted to the outpatient setting during routine visits. High acceptability supports clinical utility. In CRF, a higher degree of cortical activation was required to drive a much lower level of muscle performance. This suggests impairment of both central and peripheral mechanisms in CRF.

Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC) is associated with worse outcomes relative to other breast cancer subtypes. Chemotherapy remains the standard-of-care systemic therapy for patients with localized or metastatic disease, with few biomarkers to guide benefit. METHODS: We will discuss recent advances in our understanding of two key biological processes in TNBC, homologous recombination (HR) DNA repair deficiency and host anti-tumor immunity, and their intersection. RESULTS: Recent advances in our understanding of homologous recombination (HR) deficiency, including FDA approval of PARP inhibitor olaparib for BRCA1 or BRCA2 mutation carriers, and host anti-tumor immunity in TNBC offer potential for new and biomarker-driven approaches to treat TNBC. Assays interrogating HR DNA repair capacity may guide treatment with agents inducing or targeting DNA damage repair. Tumor infiltrating lymphocytes (TILs) are associated with improved prognosis in TNBC and recent efforts to characterize infiltrating immune cell subsets and activate host anti-tumor immunity offer promise, yet challenges remain particularly in tumors lacking pre-existing immune infiltrates. Advances in these fields provide potential biomarkers to stratify patients with TNBC and guide therapy: induction of DNA damage in HR-deficient tumors and activation of existing or recruitment of host anti-tumor immune cells. Importantly, these advances provide an opportunity to guide use of existing therapies and development of novel therapies for TNBC. Efforts to combine therapies that exploit HR deficiency to enhance the activity of immune-directed therapies offer promise. CONCLUSIONS: HR deficiency remains an important biomarker target and potentially effective adjunct to enhance immunogenicity of 'immune cold' TNBCs.

T cell anergy and activation are associated with suboptimal humoral responses to measles revaccination in HIV-infected children on anti-retroviral therapy in Nairobi, Kenya.

HIV-infected children are less capable of mounting and maintaining protective humoral responses to vaccination against measles compared to HIV-uninfected children. This poses a public health challenge in countries with high HIV burdens. Administration of anti-retroviral therapy (ART) and revaccinating children against measles is one approach to increase measles immunity in HIV-infected children, yet it is not effective in all cases. Immune anergy and activation during HIV infection are factors that could influence responses to measles revaccination. We utilized a flow cytometry-based approach to examine whether T cell anergy and activation were associated with the maintenance of measles-specific immunoglobulin (Ig)G antibodies generated in response to measles revaccination in a cohort of HIV-infected children on ART in Nairobi, Kenya. Children who sustained measles-specific IgG for at least 1 year after revaccination displayed significantly lower programmed cell death 1 (PD-1) surface expression on CD8(+) T cells on a per-cell basis and exhibited less activated CD4(+) T cells compared to those unable to maintain detectable measles-specific antibodies. Children in both groups were similar in age and sex, CD4(+) T cell frequency, duration of ART treatment and HIV viral load at enrolment. These data suggest that aberrant T cell anergy and activation are associated with the impaired ability to sustain an antibody response to measles revaccination in HIV-infected children on ART.

Menstrual migraine: treatment options.

More than half of women with migraine note an association of headache attacks and their menstrual cycles. Headaches associated with menses are often more severe and disabling than headaches that occur other times of the month. First-line therapies include acute agents used for migraine in general; however, for many women, these therapies provide incomplete relief. In these situations, treatment options include short-term perimenstrual prevention employing nonsteroidal anti-inflammatory medications, triptans, or hormone-containing preparations. Should these options not suffice, or if menstrual cycles are irregular, continuous prevention using hormonal therapies or standard anti-migraine prophylaxis should be considered.

PDBe: Protein Data Bank in Europe.

The Protein Data Bank in Europe (PDBe; pdbe.org) is a partner in the Worldwide PDB organization (wwPDB; wwpdb.org) and as such actively involved in managing the single global archive of biomacromolecular structure data, the PDB. In addition, PDBe develops tools, services and resources to make structure-related data more accessible to the biomedical community. Here we describe recently developed, extended or improved services, including an animated structure-presentation widget (PDBportfolio), a widget to graphically display the coverage of any UniProt sequence in the PDB (UniPDB), chemistry- and taxonomy-based PDB-archive browsers (PDBeXplore), and a tool for interactive visualization of NMR structures, corresponding experimental data as well as validation and analysis results (Vivaldi).

Improving access to health information for older migrants by using grounded theory and social network analysis to understand their information behaviour and digital technology use.

Migrant well-being can be strongly influenced by the migration experience and subsequent degree of mainstream language acquisition. There is little research on how older Culturally And Linguistically Diverse (CALD) migrants who have 'aged in place' find health information, and the role which digital technology plays in this. Although the research for this paper was not focused on cancer, we draw out implications for providing cancer-related information to this group. We interviewed 54 participants (14 men and 40 women) aged 63-94 years, who were born in Italy or Greece, and who migrated to Australia mostly as young adults after World War II. Constructivist grounded theory and social network analysis were used for data analysis. Participants identified doctors, adult children, local television, spouse, local newspaper and radio as the most important information sources. They did not generally use computers, the Internet or mobile phones to access information. Literacy in their birth language, and the degree of proficiency in understanding and using English, influenced the range of information sources accessed and the means used. The ways in which older CALD migrants seek and access information has important implications for how professionals and policymakers deliver relevant information to them about cancer prevention, screening, support and treatment, particularly as information and resources are moved online as part of e-health.

Biodegradation of Polychlorinated Dibenzo--Dioxins by Strain NSYSU.

The dioxin-degrading bacterium strain NSYSU (NSYSU strain) has been isolated from dioxin-contaminated soil by selective enrichment techniques. In the present study, the NSYSU strain was investigated for its capability to biodegrade polychlorinated dibenzo--dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) under aerobic and anaerobic conditions. High-resolution gas chromatography-mass spectrometry and a chemically activated luciferase gene expression bioassay were performed to determine the presence of dioxin compounds. The results indicate that the NSYSU strain could degrade PCDDs and PCDFs under anaerobic conditions in liquid cultures. The main intermediates of the dechlorination process were identified. The results of the bioreactor test indicate that the NSYSU strain could also degrade PCDDs and PCDFs effectively in soil slurries under aerobic conditions. Results from the bioreactor experiment show that approximately 98 and 97% of octachlorodibenzofuran and OCDD were degraded, respectively. The dioxin concentrations in soil slurry decreased from 5823 to 1198 pg toxic equivalency g, resulting in total dioxin removal of 79%. These first findings suggest that the NSYSU strain has the potential to be an effective tool for the bioremediation of soils contaminated with highly recalcitrant organic compounds.

'I could never do that before': effectiveness of a tailored Internet support intervention to increase the social participation of youth with disabilities.

BACKGROUND: Youth use the Internet for a variety of purposes including social networking. Youth with disabilities are limited in their social networks and friendships with peers. The aim was to investigate the effectiveness of tailored one-on-one support strategies designed to facilitate social participation of youth with disabilities through the use of the Internet for social networking. METHODS: Eighteen youth aged 10-18 years with cerebral palsy, physical disability or acquired brain injury received support, training and assistive technology at their home to learn to use the Internet for building social networks. The Canadian Occupational Performance Measure (COPM) and Goal Attainment Scale (GAS) were used to evaluate objective changes in performance and satisfaction. Interviews with the youth identified subjective changes they experienced through participation in the programme and to determine whether and how the intervention influenced their social participation. RESULTS: Youth showed an increase in performance and satisfaction with performance on identified goals concerning social networking on the COPM; Paired T-test showed that these differences were statistically significant at P < 0.001. GAS T-scores demonstrated successful outcomes (>50) for 78% of the youth. Interviews showed that youth were positive about the benefits of hands-on training at home leading to increased use of the Internet for social networking. CONCLUSIONS: The Internet could be a viable method to facilitate social participation for youth with disabilities. Youth identified the benefits of one-to-one support at home and training of the family compared with typical group training at school. Despite its success with this group of youth, the time and effort intensive nature of this approach may limit the viability of such programmes. Further longitudinal research should investigate whether Internet use is sustained post intervention, and to identify the factors that best support ongoing successful and safe use.

SELDI-TOF derived serum biomarkers failed to differentiate between patients with beryllium sensitisation and patients with chronic beryllium disease.

BACKGROUND: People exposed to beryllium may develop beryllium sensitisation (BeS) and, in some cases, progress to chronic beryllium disease (CBD). OBJECTIVES: The objective of this study was to test the ability of proteomic technology to identify patterns of serum protein biomarkers that allow differentiation between BeS and CBD and thus remove the need for invasive bronchoscopic procedures. METHODS: Initially, SELDI-TOF methodology and analysis was performed on serum samples from 30 CBD and 31 BeS patients. RESULTS: This 'starter set' yielded two distinct biomarker pattern sets with eight candidate proteins. The first set differentiated between BeS and CBD with 83.3% sensitivity and 82.3% specificity, with 10-fold cross-validation of 75% and 79%, respectively. The second set of biomarkers yielded higher sensitivity (90.0%) and higher specificity (90.3%), with 10-fold cross-validation of 71.7% and 82.3%, respectively. Due to its greater sensitivity and specificity, the second set of biomarkers was used as the framework for differentiating between CBD and BeS in a second set of serum samples from 450 patients with BeS and CBD. When this larger set of samples was subjected to the biomarker framework in a blinded fashion, it yielded a sensitivity of 43.53% and a specificity of 38.93%. CONCLUSIONS: Due to these low sensitivity and specificity values, we have concluded that, currently, the unique set of SELDI-TOF derived biomarkers does not possess the qualities that would allow it to differentiate between a CBD patient and a BeS patient using serum protein biomarkers. Future refinements in sample collection or proteomic technology may be needed to improve biomarker discovery.

Extracellular levels of glucose in the hippocampus and striatum during maze training for food or water reward in male rats.

Glucose potently enhances cognitive functions whether given systemically or directly to the brain. The present experiments examined changes in brain extracellular glucose levels while rats were trained to solve hippocampus-sensitive place or striatum-sensitive response learning tasks for food or water reward. Because there were no task-related differences in glucose responses, the glucose results were pooled across tasks to form combined trained groups. During the first 1-3 min of training for food reward, glucose levels in extracellular fluid (ECF) declined significantly in the hippocampus and striatum; the declines were not seen in untrained, rewarded rats. When trained for water reward, similar decreases were observed in both brain areas, but these findings were less consistent than those seen with food rewards. After the initial declines in ECF glucose levels, glucose increased in most groups, approaching asymptotic levels ∼15-30 min into training. Compared to untrained food controls, training with food reward resulted in significant glucose increases in the hippocampus but not striatum; striatal glucose levels exhibited large increases to food intake in both trained and untrained groups. In rats trained to find water, glucose levels increased significantly above the values seen in untrained rats in both hippocampus and striatum. The decreases in glucose early in training might reflect an increase in brain glucose consumption, perhaps triggering increased brain uptake of glucose from blood, as evident in the increases in glucose later in training. The increased brain uptake of glucose may provide additional neuronal metabolic substrate for metabolism or provide astrocytic substrate for production of glycogen and lactate.

CC chemokine receptor 5 gene polymorphisms in beryllium disease.

CC chemokine receptor 5 (CCR5) is expressed on type-1 T-helper cells, which are involved in the pathogenesis of the granulomatous lung disease chronic beryllium disease (CBD). CCR5 gene (CCR5) polymorphisms are associated with sarcoidosis severity. The present study explores associations between CCR5 polymorphisms and CBD and its disease progression. Eight CCR5 polymorphisms were genotyped in CBD (n = 88), beryllium sensitisation (BeS; n = 86) and beryllium-exposed nondiseased controls (n = 173) using PCR with sequence-specific primers. Pulmonary function and bronchoalveolar lavage data were examined for associations with genotypes. There were no significant differences in genotype and allele frequency between CBD, BeS individuals and controls. In CBD, associations were found with decline in forced expiratory volume in 1 s and forced vital capacity and the CCR5 -3458 thymidine (T)T genotype (p<0.0001), and an increase in alveolar-arterial oxygen tension difference at rest (p = 0.003) and at maximum exercise (p = 0.01) and the -5663 adenine allele. Increased bronchoalveolar lavage lymphocyte numbers were associated with CCR5 -2459 guanine/-2135T (p = 0.01) only in the combined CBD and BeS group. This is the first study showing that CCR5 polymorphisms are associated with worsening pulmonary function over time in CBD, suggesting that CCR5 is important in the progression of pulmonary function in CBD. Further studies would be useful to clarify the mechanism whereby CCR5 polymorphisms affect progression of CBD.

A novel adaptor-related protein complex.

Coat proteins are required for the budding of the transport vesicles that mediate membrane traffic pathways, but for many pathways such proteins pathways, but for many pathways such proteins have not yet been identified. We have raised antibodies against p47, a homologue of the medium chains of the adaptor complexes of clathrin-coated vesicles (Pevsner, J., W. Volknandt, B.R. Wong, and R.H. Scheller. 1994. Gene (Amst.). 146:279-283), to determine whether this protein might be a component of a new type of coat. p47 coimmunoprecipitates with three other proteins: two unknown proteins of 160 and 25 kD, and beta-NAP, a homologue of the beta/beta'-adaptins, indicating that it is a subunit of an adaptor-like heterotetrameric complex. However, p47 is not enriched in preparations of clathrin-coated vesicles. Recruitment of the p47-containing complex onto cell membranes is stimulated by GTP gamma S and blocked by brefeldin A, indicating that, like other coat proteins, its membrane association is regulated by an ARF. The newly recruited complex is localized to non-clathrin-coated buds and vesicles associated with the TGN. Endogenous complex in primary cultures of neuronal cells is also localized to the TGN, and in addition, some complex is associated with the plasma membrane. These results indicate that the complex is a component of a novel type of coat that facilitates the budding of vesicles from the TGN, possibly for transporting newly synthesized proteins to the plasma membrane.

9 -Tetrahydrocannabinol and ethyl alcohol: evidence for cross-tolerance in the rat.

Rats trained in a one-way avoidance situlation were made tolerant to the depressant effects of Delta(9)-tetrahydrocannabinol. Ethyl alcohol (3.2 grams per kilogram, intraperitoneally) did not greatly affect rats that were tolerant to delta(9)tetrahydrocannabinol but depressed the behavior of nontolerant rats. Rats made tolerant to ethyl alcohol were less affected by Delta(9)-tetrahydrocannabinol.

Stress and strain in the contractile and cytoskeletal filaments of airway smooth muscle.

Stress and strain are omnipresent in the lung due to constant lung volume fluctuation associated with respiration, and they modulate the phenotype and function of all cells residing in the airways including the airway smooth muscle (ASM) cell. There is ample evidence that the ASM cell is very sensitive to its physical environment, and can alter its structure and/or function accordingly, resulting in either desired or undesired consequences. The forces that are either conferred to the ASM cell due to external stretching or generated inside the cell must be borne and transmitted inside the cytoskeleton (CSK). Thus, maintaining appropriate levels of stress and strain within the CSK is essential for maintaining normal function. Despite the importance, the mechanisms regulating/dysregulating ASM cytoskeletal filaments in response to stress and strain remained poorly understood until only recently. For example, it is now understood that ASM length and force are dynamically regulated, and both can adapt over a wide range of length, rendering ASM one of the most malleable living tissues. The malleability reflects the CSK's dynamic mechanical properties and plasticity, both of which strongly interact with the loading on the CSK, and all together ultimately determines airway narrowing in pathology. Here we review the latest advances in our understanding of stress and strain in ASM cells, including the organization of contractile and cytoskeletal filaments, range and adaptation of functional length, structural and functional changes of the cell in response to mechanical perturbation, ASM tone as a mediator of strain-induced responses, and the novel glassy dynamic behaviors of the CSK in relation to asthma pathophysiology.

USE OF NATIVE PLANTS FOR REMEDIATION OF TRICHLOROETHYLENE: II. CONIFEROUS TREES.

The phytoremediation of trichloroethylene (TCE) from contaminated groundwater has been extensively studied using the hybrid poplar tree (Populus spp.). Several metabolites of TCE have been identified in the tissue of poplar including trichloroethanol (TCEOH) and dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA). In addition to the use of hybrid poplar for the phytoremediation of TCE, it is important to screen native tree species that could be successful candidates for field use. This study involves a greenhouse-based comparison of four different native southeastern conifers to a hybrid poplar species for their potential to phytoremediate TCE through the analysis of various plant tissues for TCE and major TCE metabolites, as well as several growth parameters that are desirable for phytoremediation. Longleaf pine (Pinus palustris), Leyland cypress (X Cupressocyparis leylandii), two varieties of Loblolly pine (Pinus taeda), and hybrid poplar species H11-11 (Populus trichocarpa x deltoides) were examined for the concentration of TCE and its metabolites in their tissue following treatment with either a low (50 mg L-1) or high dose of TCE (150 mg L-1) for 2 mo. The amount of water taken up, change in height of the tree, TCE transpiration, and total fresh weight of various tissue types were also measured. All trees contained detectable levels of TCE in their root and stem tissue. TCEOH was found only in the tissue of longleaf pine, suggesting that TCE metabolism was occurring in this tree. TCAA was only detected in the leaves of hybrid poplar and piedmont loblolly pine. Conifers took up less water over the 2-mo treatment period than hybrid poplar and grew at a slower rate. However, phytoremediation field sites may benefit from the evergreen's ability to transpire water throughout the winter months.

USE OF NATIVE PLANTS FOR REMEDIATION OF TRICHLOROETHYLENE: I. DECIDUOUS TREES.

Phytoremediation of trichloroethylene (TCE) can be accomplished using fast-growing, deep-rooting trees. The most commonly used tree for phytoremediation of TCE has been the hybrid poplar. This study looks at native southeastern trees of the United States as alternatives to the use of hybrid poplar. The use of native trees for phytoremediation allows for simultaneous restoration of contaminated sites. A 2-mo, greenhouse-based study was conducted to determine if sycamore (Plantanus L.), eastern cottonwood (Populus deltoides), sweetgum (Liquidambar styraciflua L.), and willow (Salix sachalinensis) trees possess the ability to degrade TCE by assessing TCE metabolite formation in the plant tissue. In addition to the metabolic capabilities of each tree species, growth parameters were measured including change in height, water usage, total fresh weight of each tissue type, and calculated total leaf surface area. Willow trees had the greatest increase in height among all trees tested; however, at higher concentrations TCE inhibits growth. Sycamore trees had the highest overall leaf surface area and total biomass, which correlated with sycamore trees also having the highest average water usage over the course of the experiment. Carbon tubes used to sample transpiration gases from sycamore, sweetgum, and cottonwood trees did not contain detectable levels of TCE. Tenex sample collection tubes used to sample willow trees during TCE exposure showed average TCE concentrations of up to 0.354 ng TCE cm-2 leaf tissue. All exposed trees contained TCE in the root, stem, and leaf tissues. The concentration of TCE remaining in tissues at the conclusion of the experiment varied, with the highest levels found in the roots and the lowest levels found in the leaves. Metabolites were also observed in different tissue types of all trees tested. The highest concentrations of trichloroacetic acid were observed in the leaves of the sycamore trees and cottonwood trees. Based on the growth parameters tested and the ability to metabolize TCE, sycamore and native cottonwood species are the best candidates for phytoremediation from this study.

Spatial Accuracy of a Clinically Established Noninvasive Electrocardiographic Imaging System for the Detection of Focal Activation in an Intact Porcine Model.

BACKGROUND: Noninvasive electrocardiographic imaging (ECGi) is used clinically to map arrhythmias before ablation. Despite its clinical use, validation data regarding the accuracy of the system for the identification of arrhythmia foci is limited. METHODS: Nine pigs underwent closed-chest placement of endocardial fiducial markers, computed tomography, and pacing in all cardiac chambers with ECGi acquisition. Pacing location was reconstructed from biplane fluoroscopy and registered to the computed tomography using the fiducials. A blinded investigator predicted the pacing location from the ECGi data, and the distance to the true pacing catheter tip location was calculated. RESULTS: A total of 109 endocardial and 9 epicardial locations were paced in 9 pigs. ECGi predicted the correct chamber of origin in 85% of atrial and 92% of ventricular sites. Lateral locations were predicted in the correct chamber more often than septal locations (97% versus 79%, P=0.01). Absolute distances in space between the true and predicted pacing locations were 20.7 (13.8-25.6) mm (median and [first-third] quartile). Distances were not significantly different across cardiac chambers. CONCLUSIONS: The ECGi system is able to correctly identify the chamber of origin for focal activation in the vast majority of cases. Determination of the true site of origin is possible with sufficient accuracy with consideration of these error estimates.

Increased levels of nerve growth factor in the airways of patients with sarcoidosis.

OBJECTIVES: Nerve growth factor (NGF) is a potent neuronal growth factor with inflammatory properties that recently has been proposed to be of importance in airway pathology. A role for NGF in the inflammatory granulomatous lung disease sarcoidosis is not well elucidated. The aims of this study were to investigate the secreted levels of NGF in bronchoalveolar lavage fluid (BALF) from sarcoidosis patients compared with patients with resolved disease, patients with another granulomatous disease--chronic beryllium disease (CBD)--and healthy subjects and also to investigate the relationship between NGF levels and markers of inflammation. METHODS AND RESULTS: NGF levels in BALF from 56 patients with active sarcoidosis (22 with Löfgren's syndrome), nine subjects with resolved sarcoidosis, six patients with CBD, and 31 healthy subjects were compared. A 10-fold elevation of NGF levels was found in patients with active sarcoidosis compared with subjects with clinically resolved sarcoidosis, patients with CBD and healthy subjects. In sarcoidosis patients, positive correlations between concentrations of NGF and lymphocytes, eosinophils and interferon-gamma, interleukin (IL)-4, IL-10, IL-12 were found. CONCLUSIONS: We demonstrate that secreted levels of NGF are markedly enhanced in the airways in active pulmonary sarcoidosis. Furthermore, a relationship between NGF and pulmonary inflammation in sarcoidosis is supported.