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PubMed2002

Structural and energetic processes related to P300: LORETA findings in depression and effects of antidepressant drugs.

Noninvasive electrophysiological neuroimaging applied to cognitive components of event-related potentials (ERPs) may differentiate between structural and energetic processes related to information processing. The structural level, revealed by the location of the local maxima of the current source density distribution, describes the time-dependent network of activated brain areas. The magnitude of the source strength, a measure of the energetic component, describes the allocation of processing resources. ERPs were recorded in an odd-ball paradigm and low-resolution brain electromagnetic tomography (LORETA) was applied for standard and target ERP components. In a group of 60 menopausal depressed patients of 45-60 years of age, reduced P300 source strength was observed bilaterally, temporally and medially prefrontally reaching to rostal parts of the anterior cingulate, compared with 29 age-matched controls. In a double-blind, placebo-controlled study, 2 mg of the antidepressant citalopram induced a significant increase of P300 source strength in the (left) prefrontal cortex and precuneus compared with placebo, reaching to the posterior cingulate. Similar increases were observed after 800 mg S-adenosyl-L-methionine (SAMe) administered intravenously in ten young healthy subjects aged 22-33, and they were even more pronounced in ten elderly healthy subjects aged 56-71. Thus, ERP-tomography identified changes in energetic sources in brain areas predominantly involved in depression and in antidepressant action.

Acoustic Stimulation↗
PubMed1997

Hospital based primary care clinics. Complementary to general practice.

OBJECTIVE: To describe the patients attending a hospital based primary care clinic (HBPCC) focusing on the main medical and non-medical reasons for their seeking health care at the clinic, and their expectations of, and satisfaction with the care. METHODS: The study was set in a HBPCC in the northern region of metropolitan Melbourne, Australia. Bilingual interviewers assisted consecutive new patients to complete a pre- and post-consultation questionnaire seeking information on the presenting complaint, patient-reported reason for encounter (RFE), doctor-recorded health problem, treatments received, and patient expectations of and satisfaction with care. RESULTS: The sample (n = 197) was young (mean age 33 years). A high proportion came from a low socioeconomic group (68%) and there was a higher than expected proportion of patients with a non-English speaking background (NESB) (53%). Three-quarters had a regular GP elsewhere. Important reasons for choosing this service were accessibility and familiarity: being part of a hospital: case of obtaining radiological examinations, and the quality of the doctors. The commonest health problem was trauma related (14-16%). The main body systems involved were locomotor, skin, digestive, respiratory, pregnancy related and non specific. Patients were mostly satisfied with their cares those with ill-defined problems were more likely to report that their expectation were not completely met. There were no significant demographic and ethnic variations in the outcome variables. CONCLUSION: HBPCCs can complement the GP's ongoing relationship with patients from NESB and lower socioeconomic groups to improve the continuity and coordination of healthcare. Experienced and culturally sensitive GPs, good communications, and an effective and comprehensive interpreter service are necessary to facilitate this care coordination. One strategy is a hospital based department of general practice linking academic GPs and a local divisional network of GPs, to provide this clinical service and undertake teaching and research in the areas highlighted by this study.

Adult↗
PubMed1988

Differing patterns of capillary distribution in fish and mammalian skeletal muscle.

The heterogeneity of capillary supply to muscles of different metabolic capacity and fibre size was assessed in slow and fast muscles from a fish and a mammal. The area surrounding each capillary delineated by equidistant boundaries from adjacent vessels, the capillary domain, was derived from morphometric analysis of histological sections. This 2-D integration of intercapillary distances may reveal heterogeneity of supply that is hidden by a global approach, especially when compared with the more usual 0- and 1-D indices of capillarisation. Mean radii of the equivalent Kroghian tissue cylinders (R) and heterogeneity of their lognormal distribution, represented by the logarithmic standard deviation (LogSD), were calculated. In eel slow muscle there was a 35-fold greater capillary density (CD) than fast muscle (698 vs 20 mm-2) although heterogeneity of capillary spacing was similar (LogSD congruent to 0.06). The difference in CD between slow and fast muscles of rat was less pronounced, but there was significantly lower heterogeneity in the aerobic tissue (LogSD = 0.08 vs 0.10) corresponding to a range in domain area of around 350-2300 microns 2 and 400-2900 microns 2, respectively. The overall capillary to fibre ratio (C:F) is inappropriate for sparse networks where many fibres lack direct capillary contact. The cumulative fraction of individual domains overlapping a muscle fibre (local capillary to fibre ratio, LCFR) plotted against fibre area showed the best correlation of any index in all tissue and was strongest in both fish muscles (r = 0.9), indicating a functionally homologous spatial distribution of capillaries with respect to muscle fibres in tissue of widely differing oxidative capacity. These data suggest that maximal oxygen supply to, or metabolite removal from, muscle fibres is not restricted to contiguous capillaries but also involves those remote from the fibre surface.

Animals↗
PubMed2005

Modeling water and carbon fluxes above summer maize field in North China Plain with back-propagation neural networks.

In this work, datasets of water and carbon fluxes measured with eddy covariance technique above a summer maize field in the North China Plain were simulated with artificial neural networks (ANNs) to explore the fluxes responses to local environmental variables. The results showed that photosynthetically active radiation (PAR), vapor pressure deficit (VPD), air temperature (T) and leaf area index (LAI) were primary factors regulating both water vapor and carbon dioxide fluxes. Three-layer back-propagation neural networks (BP) could be applied to model fluxes exchange between cropland surface and atmosphere without using detailed physiological information or specific parameters of the plant.

Agriculture↗
PubMed1993

A neural network model for texture discrimination.

A model of texture discrimination in visual cortex was built using a feedforward network with lateral interactions among relatively realistic spiking neural elements. The elements have various membrane currents, equilibrium potentials and time constants, with action potentials and synapses. The model is derived from the modified programs of MacGregor (1987). Gabor-like filters are applied to overlapping regions in the original image; the neural network with lateral excitatory and inhibitory interactions then compares and adjusts the Gabor amplitudes in order to produce the actual texture discrimination. Finally, a combination layer selects and groups various representations in the output of the network to form the final transformed image material. We show that both texture segmentation and detection of texture boundaries can be represented in the firing activity of such a network for a wide variety of synthetic to natural images. Performance details depend most strongly on the global balance of strengths of the excitatory and inhibitory lateral interconnections. The spatial distribution of lateral connective strengths has relatively little effect. Detailed temporal firing activities of single elements in the lateral connected network were examined under various stimulus conditions. Results show (as in area 17 of cortex) that a single element's response to image features local to its receptive field can be altered by changes in the global context.

Cybernetics↗
PubMed1996

The kindling-activated neuronal network: recruitment of somatostatin-synthesizing neurons.

The present study demonstrates the anatomical extent of the kindling-activated neuronal network in general, and specifically the recruitment of extrahippocampal somatostatin (SST)-synthesizing neurons into this network. It has been known that SST neurons of the hippocampal formation are activated during episodes of seizure, however, it was not known if this activation was a local event or extended to other areas in the brain. We were therefore interested in determining if and which SST neurons outside the hippocampal formation might be recruited into this seizure-activated neuronal network. Using the kindling model of seizure elicitation, expression of the Fos protein in activated, depolarized neurons was utilized to identify seizure-activated neurons. Subsequently, the mRNA for SST was identified through in situ hybridization in the same tissue section, allowing the identification of seizure-activated, SST-synthesizing neurons. The results show that: (a) the majority of SST-synthesizing neurons in the forebrain and diencephalon became activated during the kindling development; (b) their recruitment into the kindling-activated neuronal network occurred progressively; and, (c) these SST-synthesizing neurons represented a component of the kindling-activated neuronal network throughout the development of kindling-induced seizures.

Animals↗
PubMed2001

Controlled release of clot-dissolving tissue-type plasminogen activator from a poly(L-glutamic acid) semi-interpenetrating polymer network hydrogel.

With the aim of developing an effective therapeutic modality for treatment of thrombosis, a tissue-type plasminogen activator (t-PA)-loaded porous poly(L-glutamic acid) (PLGA) semi-interpenetrating polymer network (semi-IPN) hydrogel was developed as a possible local drug delivery system. Porous structure of hydrogel was essential in this system to yield a large surface area so that t-PA release could be facilitated. This semi-IPN hydrogel was prepared using the method of free-radical polymerization and crosslinking of polyethylene glycol (PEG)-methacrylate through the PLGA network. Sodium bicarbonate (NaHCO(3)) was added to function as a foaming agent under acidic conditions, rendering the semi-IPN hydrogel to be porous. While the added NaHCO(3) provided gas foam in the reaction mixture, the pH in the hydrogel increased to about 7 to 8, which stimulated the polymerization. The porous structure that was presented at both the surface and sublayer was stabilized during hydrogel formation and freeze-drying. The hydrogel thus prepared possessed a porous structure of 10-20 microm in diameter, as determined by scanning electron microscopy. Results showed that the above hydrogel preparation process did not significantly alter the specific activity of the entrapped t-PA with regard to plasminogen activation and fibrin clot lysis ability. The t-PA release from this semi-IPN hydrogel was examined by measuring the plasmin activity using the chromogenic substrate S-2251. Findings in this paper demonstrated that the porous structure of the hydrogel facilitated t-PA release when compared to the dense structure. Aside from the porous structure, other factors including the content of the crosslinker, PLGA and t-PA could all be varied to regulate t-PA release from the hydrogel. These results suggest that a porous PLGA semi-IPN hydrogel could potentially be a useful local delivery system to release active t-PA primarily at the site of a thrombus.

Blood Coagulation↗
PubMed1997

Physician-hastened death. Advisory guidelines for the San Francisco Bay area from the Bay Area Network of Ethics Committees.

Recent high court opinions and pending Supreme Court rulings on the legality of physician-hastened death necessitate a pragmatic response from the medical profession. Adopting a "harm reduction" perspective on this contentious topic, the Bay Area Network of Ethics Committees developed practice guidelines for responding to a patient request for hastened death. The guidelines will be offered to the local medical community for use by individuals and health care institutions if the practice of physician-hastened death becomes legal. A multidisciplinary consensus process was used in developing the guidelines, which address clinical, ethical, and procedural concerns.

Ethics Consultation↗
PubMed2003

Spatiotemporal characterization of paced cardiac activation with body surface potential mapping and self-organizing maps.

In this study self-organizing maps (SOM) were utilized for spatiotemporal analysis and classification of body surface potential mapping (BSPM) data. Altogether 86 cardiac depolarization (QRS) sequences paced by a catheter in 18 patients were included. Spatial BSPM distributions at every 5 ms over the QRS complex were first presented to an untrained SOM. The learning process of the SOM units organized the maps in such a way that similar BSPMs are represented in particular areas of the SOM network. Thereafter, time trajectories and distance maps were created on the trained SOM from sequential maps in a selected paced QRS. The trajectories and distance maps can be applied as such for the localization of abnormal ventricular activation, as well as quantitative input for statistical classification. The results indicate that the method has potential for locating endocardial sites of abnormal ventricular activation, despite the patient material being too limited to provide a reliable statistical evaluation of the source localization accuracy.

Algorithms↗
PubMed1978

Cerebral venous angioma: computerized tomography and angiographic diagnosis.

Four cases of cerebral venous angioma were studied by both CT and angiography. All cases showed similar angiographic findings: a normal arterial phase and a local network of small veins that converged centrally into a single large draining vein. However, CT showed nodular areas of high density in three cases, and a curvilinear enhanced lesion representing the draining vein in the other. CT findings are nonspecific but very useful for detecting the lesion and demonstrating the associated hematoma. Angiographic findings are not so obvious as in AVM, but are necessary for the final diagnosis of the venous angioma.

Adult↗
PubMed2006

Approaches to patient health information exchange and their impact on emergency medicine.

Regional health information organizations and electronic health information exchange may have an important impact on the practice of emergency medicine in the United States. Regional health information organizations are local or regional information-sharing networks that enable electronic data interchange among stakeholders in a given geographic area. These stakeholders may include hospitals, skilled nursing facilities, clinics, private physicians' offices, pharmacies, laboratories, radiology facilities, health departments, payers, and possibly the patients themselves. Regional health information organizations are being formed across the country to improve the safety and efficiency of clinical care; improve public health efforts, biosurveillance, and disaster management response; and potentially create large databases of deidentified aggregate data for research. Because of the unique need for rapid access to information and the acuity of the clinical environment, few areas of the health care delivery system stand to change and benefit more from health information exchange than our nation's emergency departments. This article will explain the motivation for the development of regional health information organizations, identify some of the important issues in their formation, and discuss how their development might affect the practice of emergency medicine.

Confidentiality↗
PubMed2006

Dual time scales for categorical decision making in auditory cortex.

Category formation allows us to group perceptual objects into meaningful classes and is fundamental to cognition. Categories can be derived from similarity relationships of object features by using prototypes or multiple exemplars, or from abstract relationships of features and rules . A variety of brain areas have been implicated in categorization processes, but mechanistic insights on the single-cell and local-network level are still rare and limited to the matching of individual objects to categories . For directional categorization of tone steps, as in melody recognition , abstract relationships between sequential events (higher or lower in frequency) have to be formed. To explore the neuronal mechanisms of this categorical identification of step direction, we trained monkeys for more than two years on a contour-discrimination task with multiple tone sequences. In the auditory cortex of these highly trained monkeys, we identified two interrelated types of neuronal firing: Increased phasic responses to tones categorically represented the reward-predicting downward frequency steps and not upward steps; subsequently, slow modulations of tonic firing predicted the behavioral decisions of the monkeys, including errors. Our results on neuronal mechanisms of categorical stimulus identification and of decision making attribute a cognitive role to auditory cortex, in addition to its role in signal processing.

Acoustic Stimulation↗
PubMed2002

Complex hallucinations following occipital lobe damage.

Visual hallucinations may accompany many neurological and psychiatric disorders. A common localization principle is that lesions to the early sensory cortices lead to elementary hallucinations, whereas complex perceptual experiences are related to the pathology of higher-level cortical regions. We report the case of a patient who experienced complex, non-stereotyped, multimodal (visual and somatosensory) hallucinations following an acute ischaemic vascular lesion in the right medial occipital lobe. This illustrates that the phenomenology of hallucinations not necessarily reflects the exact localization of cerebral pathology. Instead, the damaged area may serve as a focus of an abnormally activated neuronal network.

Aged↗
PubMed1993

Low-grade fibromyxoid sarcoma. A report of 12 cases.

Twelve cases of low-grade fibromyxoid sarcoma are presented. The patients' ages ranged from 6 to 51 years; all but three were between 26 and 46 years of age. The tumor was located in the thigh or inguinal area in four patients, in the shoulder area in three patients, and in the axilla-chest wall area, the perineum, the small bowel mesentery, the neck, and the buttock in one patient each. Tumor size (maximum dimension) varied from 3.5 to 15 cm in the nine cases in which it was known (median, 9.5 cm). Histologically, the neoplasms demonstrated contrasting fibrous and myxoid areas, a swirling, whorled growth pattern (at least in part), and bland, deceptively benign-appearing fibroblastic spindle cells; cellularity was low to moderate, mitotic figures were uncommon, and nuclear pleomorphism was usually absent or slight. Focal histologic findings in a minority of the cases included increased perivascular cellularity, moderate nuclear pleomorphism (more often in recurrent tumors), and, in myxoid areas, a rich capillary vascular network (vascularity was usually not prominent). On follow-up, nine patients experienced local recurrence (from one to numerous times); recurrence was subsequently controlled in five cases but not in the remaining four. Distant metastasis occurred in seven cases, chiefly to the lungs, but two of these patients were rendered tumor-free (to latest follow-up) by excision of metastases. At latest follow-up, four patients had died of tumor at 8, 9, 31, and 31 1/2 years, respectively, three were alive with recurrent or metastatic tumor at 6 1/2, 12 1/2, and 50 years, respectively, and five were alive and tumor-free at 5 1/2, 10 1/2, 12, 22 1/2, and 44 years, respectively. One tumor, in the patient who died at 31 years, demonstrated "dedifferentiation" at 30 years. Low-grade fibromyxoid sarcoma is a distinctive, indolent soft-tissue sarcoma.

Adolescent↗
PubMed2004

The CD2v protein of African swine fever virus interacts with the actin-binding adaptor protein SH3P7.

The predicted extracellular domain of the CD2v protein of African swine fever virus (ASFV) shares significant similarity to that of the CD2 protein in T cells but has a unique cytoplasmic domain of unknown function. Here we have shown that CD2v is expressed as a glycoprotein of approximately 105 kDa in ASFV-infected cells. In the absence of an extracellular ligand, the majority of CD2v appears to localize to perinuclear membrane compartments. Furthermore, we have shown using the yeast two-hybrid system and by direct binding studies that the cytoplasmic tail of CD2v binds to the cytoplasmic adaptor protein SH3P7 (mAbp1, HIP55), which has been reported to be involved in diverse cellular functions such as vesicle transport and signal transduction. A cDNA clone encoding a variant form of SH3P7 could also be identified and was found to be expressed in a wide range of porcine tissues. Deletion mutagenesis identified proline-rich repeats of sequence PPPKPC in the ASFV CD2v protein to be necessary and sufficient for binding to the SH3 domain of SH3P7. In ASFV-infected cells, CD2v and SH3P7 co-localized in areas surrounding the perinuclear virus factories. These areas also stained with an antibody that recognizes a Golgi network protein, indicating that they contained membranes derived from the Golgi network. Our data provide a first molecular basis for the understanding of the immunomodulatory functions of CD2v in ASFV-infected animals.

Actins↗
PubMed1998

Limbic gamma rhythms. I. Phase-locked oscillations in hippocampal CA1 and subiculum.

Gamma oscillations (approximately 40 Hz) were induced in transverse hippocampal slices by tetanic stimulation of CA1 and/or subiculum. Tetanic stimulation of each site elicited population gamma oscillations in the surrounding tissue <400 micro(m) away. Stimulation of CA1 alone could evoke activity at both CA1 and subiculum. Subicular stimulation, however, did not transmit to CA1. When the rostral end of CA1 was stimulated, gamma oscillations transmitted across <1.5 mm of silent CA1 before reappearing in the subiculum. Tetanic stimulation of CA1 increased [K+]o to 8.2 +/- 1.5 mM (mean +/- SE). The location of the peak increase corresponded to the site of local gamma generation. Silent areas of CA1 experienced smaller [K+]o increases, to 4.9 +/- 0.7 mM. The subiculum, which generated gamma, remained at the baseline 3.0 mM. Although fluctuations in [K+]o may have an impact on the generation of gamma rhythms, they are not necessary for them. Gamma oscillations had similar frequencies in CA1 and subiculum (40.4 +/- 2.9 and 43.9 +/- 3.1 Hz, respectively). When present in both, the oscillations typically were phase locked with the subiculum lagging by 5.4 +/- 1.8 ms. When both CA1 and subiculum were stimulated the lag decreased by 28%. These delays approximate those expected for the conduction velocity of axons between the two regions, here estimated at 0.52 +/- 0.07 m/s. Transmission of gamma oscillations from CA1 to subiculum was blocked by the focal addition of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor antagonist, 6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-dione, to the subiculum. Oscillations induced in CA1 by local tetanic stimulation were blocked by focal application of the gamma-aminobutyric acid-A (GABAA) receptor antagonist, bicuculline, to CA1. Focal application of bicuculline to the subiculum blocked gamma due to subicular stimulation but not that due to CA1 stimulation. Bath-applied bicuculline disrupted subicular gamma evoked by subicular stimulation and led to a transient period of epileptiform responses before completely blocking responses. The further addition of the GABAB receptor antagonist, CGP 55845A, reversed this block, restoring the epileptic discharges evoked by tetanic stimulation. This suggests that the subiculum differs from hippocampal CA3 and neocortex, in having a powerful GABAB receptor-dependent mechanism to prevent epileptic discharges. The subiculum generates gamma rhythms both in response to local stimulation and to gamma rhythms evoked in CA1. Subicular gamma differs from that in CA1 in the presence of population spike doublets rather than singlets on many cycles. In both areas, generation of gamma by local stimulation depends on GABAA receptors, suggesting that the subiculum shares the interneuronal network mechanism we proposed for CA1.

Animals↗
PubMed1987

Increased prolactin binding and morphological changes in the wound epithelium of regenerating limbs of Notophthalmus viridescens.

Distribution of prolactin has been examined in regenerating forelimbs from the newt Notophthalmus viridescens. Specific prolactin binding was demonstrated in homogenates of unamputated tissue, and of regenerating limbs at from 3 to 21 days postamputation. Labeled prolactin that was injected intraperitoneally into animals with one regenerating limb accumulated in the most distal portion of the regenerate at 7 and 14 days postamputation. Light-microscopic autoradiography demonstrated that labeled prolactin was localized most heavily in the apical, outer layer of the wound epithelium. Scanning electron microscopy demonstrated that, in addition to changes in prolactin affinity following amputation, morphological changes occurred in the apical wound epithelium as well. Cell surfaces of the stump epidermis were characterized by periodic dispersion of papillae among a network of interconnecting structures 1-2 microns across. By contrast, the surfaces of cells from the area in which labeled prolactin was found to localize most intensely were characterized by lack of papillae and, depending on the stage of regeneration, a pattern of microvilli and microplicae. These morphological alterations appear to reflect functional and biochemical differences between stump epidermis and wound epithelium.

Animals↗
PubMed2004

Combinatorial codes in ventral temporal lobe for object recognition: Haxby (2001) revisited: is there a "face" area?

Haxby et al. [Science 293 (2001) 2425] recently argued that category-related responses in the ventral temporal (VT) lobe during visual object identification were overlapping and distributed in topography. This observation contrasts with prevailing views that object codes are focal and localized to specific areas such as the fusiform and parahippocampal gyri. We provide a critical test of Haxby's hypothesis using a neural network (NN) classifier that can detect more general topographic representations and achieves 83% correct generalization performance on patterns of voxel responses in out-of-sample tests. Using voxel-wise sensitivity analysis we show that substantially the same VT lobe voxels contribute to the classification of all object categories, suggesting the code is combinatorial. Moreover, we found no evidence for local single category representations. The neural network representations of the voxel codes were sensitive to both category and superordinate level features that were only available implicitly in the object categories.

Adult↗