Praziquantel in clonorchiasis and opisthorchiasis

A single stool examination revealed pathogenic intestinal parasites in 462 (58%) of 796 vietnamese and cambodian refugees. 56 (7.0%) were infected with Clonorchis sinensis and/or Opisthorchis viverrini. These patients received Praziquantel in a dosage of 20 mg/kg bwt. p.day on 3 consecutive days. Parasitological controls were completed after 12 months. No further excretion of eggs could be detected in 88% of the patients. Concurrent infections with other trematodes and cestodes were also cured. Nematode infections remained uninfluenced. No change of haematological and biochemical parameters could be observed during therapy. Diarrhea and epigastric pain were common side effects, which are probably not effects of the drug itself. They rather seem to be due to the release of parasitic antigens. This is also indicated by a further increase of circulating Ig E after therapy

Komplizierte Malaria tropica

Bei elf von 43 nichtimmunen Patienten mit Malaria tropica traten eine oder mehrere Organkomplikationen auf: zerebrale Malaria, akute respiratorische Insuffizienz, akutes Nierenversagen, Sekundärinfektion, Autoimmunhämolyse, spontane Milzruptur und akute Pankreatitis. Die Parasitämie betrug 0,1 bis 60 %. Initiale antiparasitäre Therapie mit Chinin parenteral führte in neun Fällen zu rascher Rückbildung der Parasitämie. Zusätzlich wurde ein zweites schizontozides Mittel entsprechend der Resistenzlage gegeben. Die supportive Therapie umfaßte intensivmedizinische Überwachung mit Bilanzierung von Elektrolyt- und Wasserhaushalt sowie gegebenenfalls eine frühzeitige Hämodialyse und (oder) endotracheale Intubation mit PEEP-Beatmung. In einem Fall mit exzessiver Parasitämie wurde eine Austauschtransfusion durchgeführt. Heparin wurde nur bei nachgewiesener disseminierter intravasaler Gerinnung gegeben, Corticosteroide nur bei persistierender Autoimmunhämolyse. Alle Patienten überlebten ohne zurückbleibende Defekte. Die retrospektive Analyse zeigt, daß neben einer raschen spezifischen Therapie die supportive Behandlung der einzelnen Organkomplikationen für Verlauf und Prognose der komplizierten Malaria tropica mitentscheidend ist

Visual saliency and semantic incongruency influence eye movements when inspecting pictures

Models of low-level saliency predict that when we first look at a photograph our first few eye movements should be made towards visually conspicuous objects. Two experiments investigated this prediction by recording eye fixations while viewers inspected pictures of room interiors that contained objects with known saliency characteristics. Highly salient objects did attract fixations earlier than less conspicuous objects, but only in a task requiring general encoding of the whole picture. When participants were required to detect the presence of a small target, then the visual saliency of nontarget objects did not influence fixations. These results support modifications of the model that take the cognitive override of saliency into account by allowing task demands to reduce the saliency weights of task-irrelevant objects. The pictures sometimes contained incongruent objects that were taken from other rooms. These objects were used to test the hypothesis that previous reports of the early fixation of congruent objects have not been consistent because the effect depends upon the visual conspicuity of the incongruent object. There was an effect of incongruency in both experiments, with earlier fixation of objects that violated the gist of the scene, but the effect was only apparent for inconspicuous objects, which argues against the hypothesis

Salience-based selection: attentional capture by distractors less salient than the target

Current accounts of attentional capture predict the most salient stimulus to be invariably selected first. However, existing salience and visual search models assume noise in the map computation or selection process. Consequently, they predict the first selection to be stochastically dependent on salience, implying that attention could even be captured first by the second most salient (instead of the most salient) stimulus in the field. Yet, capture by less salient distractors has not been reported and salience-based selection accounts claim that the distractor has to be more salient in order to capture attention. We tested this prediction using an empirical and modeling approach of the visual search distractor paradigm. For the empirical part, we manipulated salience of target and distractor parametrically and measured reaction time interference when a distractor was present compared to absent. Reaction time interference was strongly correlated with distractor salience relative to the target. Moreover, even distractors less salient than the target captured attention, as measured by reaction time interference and oculomotor capture. In the modeling part, we simulated first selection in the distractor paradigm using behavioral measures of salience and considering the time course of selection including noise. We were able to replicate the result pattern we obtained in the empirical part. We conclude that each salience value follows a specific selection time distribution and attentional capture occurs when the selection time distributions of target and distractor overlap. Hence, selection is stochastic in nature and attentional capture occurs with a certain probability depending on relative salience

Halofantrin zur Behandlung der importierten Malaria bei nicht-immunen Reisenden

Im Rahmen einer prospektiven Multizenterstudie wurden die Wirksamkeit (Kriterien: Heilungsrate, Zeit bis zur Entfieberung oder Parasitenfreiheit) und Verträglichkeit (Kriterien: klinische Nebenwirkungen, veränderte Laborparameter) von Halofantrin bei 96 nicht-immunen Malaria-Patienten (71 Männer, 25 Frauen, mittleres Alter 34,3 [21-62] Jahre) untersucht, die aus Hochresistenzgebieten nach Deutschland oder in die Schweiz zurückgekehrt waren. 63 Patienten wurden mit einer Eintagestherapie behandelt (dreimal 500 mg Halofantrin); die folgenden 33 Patienten erhielten einen zusätzlichen Therapiezyklus nach einer Woche. In der zweiten Gruppe war die Therapie in allen Fällen wirksam, während bei der Eintagestherapie fünf von 41 Patienten (12,2 %) mit Malaria tropica einen Rückfall erlitten. Die Zeit bis zur Entfieberung betrug 45 Stunden, die Zeit bis zur Parasitenfreiheit 66 Stunden. Bei fünf Behandelten kam es unter der Therapie zu leichten Transaminasenanstiegen, die jedoch spontan innerhalb weniger Tage zurückgingen und am ehesten infektionsbedingt waren. - Bei guter Verträglichkeit ist Halofantrin für die Therapie und Stand-by-Therapie von multiresistenten Plasmodien-Infektionen geeignet. Die Behandlung muß nach 7 Tagen wiederholt werden.The efficacy (criteria: cure rate, time to resolution of fever or absence of parasites) and safety (criteria: clinical side effects, altered laboratory parameters) of halofantrin were investigated in a multi-centre study of 96 non-immune patients (71 men, 25 women, mean age 34.3 [21-62] years) with malaria imported from regions of high resistance into Germany or Switzerland. The initial 63 patients received one-day treatment (three doses of 500 mg halofantrin), while the last 33 patients received an additional course of treatment one week later. Treatment was curative in all patients in the second group, but relapses occurred in five of the 41 patients (12.2 %) with falciparum malaria who received one-day therapy. Fever resolved after a mean of 45 hours and parasites were absent after a mean of 66 hours. There were small increases in transaminase values (most probably because of the infection) in five patients, but all became normal again within a few days. - Halofantrin is a safe drug and is suitable for both therapy and stand-by therapy of resistant Plasmodium infections. Treatment should be repeated after 7 days

Liposome-Coupled Antigens Are Internalized by Antigen-Presenting Cells via Pinocytosis and Cross-Presented to CD8+ T Cells

We have previously demonstrated that antigens chemically coupled to the surface of liposomes consisting of unsaturated fatty acids were cross-presented by antigen-presenting cells (APCs) to CD8+ T cells, and that this process resulted in the induction of antigen-specific cytotoxic T lymphocytes. In the present study, the mechanism by which the liposome-coupled antigens were cross-presented to CD8+ T cells by APCs was investigated. Confocal laser scanning microscopic analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-based liposomes received processing at both MHC class I and class II compartments, while most of the antigens coupled to the surface of saturated-fatty-acid-based liposomes received processing at the class II compartment. In addition, flow cytometric analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-liposomes were taken up by APCs even in a 4°C environment; this was not true of saturated-fatty-acid-liposomes. When two kinds of inhibitors, dimethylamiloride (DMA) and cytochalasin B, which inhibit pinocytosis and phagocytosis by APCs, respectively, were added to the culture of APCs prior to the antigen pulse, DMA but not cytochalasin B significantly reduced uptake of liposome-coupled antigens. Further analysis of intracellular trafficking of liposomal antigens using confocal laser scanning microscopy revealed that a portion of liposome-coupled antigens taken up by APCs were delivered to the lysosome compartment. In agreement with the reduction of antigen uptake by APCs, antigen presentation by APCs was significantly inhibited by DMA, and resulted in the reduction of IFN-γ production by antigen-specific CD8+ T cells. These results suggest that antigens coupled to the surface of liposomes consisting of unsaturated fatty acids might be pinocytosed by APCs, loaded onto the class I MHC processing pathway, and presented to CD8+ T cells. Thus, these liposome-coupled antigens are expected to be applicable for the development of vaccines that induce cellular immunity

Cortical Surround Interactions and Perceptual Salience via Natural Scene Statistics

Spatial context in images induces perceptual phenomena associated with salience and modulates the responses of neurons in primary visual cortex (V1). However, the computational and ecological principles underlying contextual effects are incompletely understood. We introduce a model of natural images that includes grouping and segmentation of neighboring features based on their joint statistics, and we interpret the firing rates of V1 neurons as performing optimal recognition in this model. We show that this leads to a substantial generalization of divisive normalization, a computation that is ubiquitous in many neural areas and systems. A main novelty in our model is that the influence of the context on a target stimulus is determined by their degree of statistical dependence. We optimized the parameters of the model on natural image patches, and then simulated neural and perceptual responses on stimuli used in classical experiments. The model reproduces some rich and complex response patterns observed in V1, such as the contrast dependence, orientation tuning and spatial asymmetry of surround suppression, while also allowing for surround facilitation under conditions of weak stimulation. It also mimics the perceptual salience produced by simple displays, and leads to readily testable predictions. Our results provide a principled account of orientation-based contextual modulation in early vision and its sensitivity to the homogeneity and spatial arrangement of inputs, and lends statistical support to the theory that V1 computes visual salience

The Time Course of Segmentation and Cue-Selectivity in the Human Visual Cortex

Texture discontinuities are a fundamental cue by which the visual system segments objects from their background. The neural mechanisms supporting texture-based segmentation are therefore critical to visual perception and cognition. In the present experiment we employ an EEG source-imaging approach in order to study the time course of texture-based segmentation in the human brain. Visual Evoked Potentials were recorded to four types of stimuli in which periodic temporal modulation of a central 3° figure region could either support figure-ground segmentation, or have identical local texture modulations but not produce changes in global image segmentation. The image discontinuities were defined either by orientation or phase differences across image regions. Evoked responses to these four stimuli were analyzed both at the scalp and on the cortical surface in retinotopic and functional regions-of-interest (ROIs) defined separately using fMRI on a subject-by-subject basis. Texture segmentation (tsVEP: segmenting versus non-segmenting) and cue-specific (csVEP: orientation versus phase) responses exhibited distinctive patterns of activity. Alternations between uniform and segmented images produced highly asymmetric responses that were larger after transitions from the uniform to the segmented state. Texture modulations that signaled the appearance of a figure evoked a pattern of increased activity starting at ∼143 ms that was larger in V1 and LOC ROIs, relative to identical modulations that didn't signal figure-ground segmentation. This segmentation-related activity occurred after an initial response phase that did not depend on the global segmentation structure of the image. The two cue types evoked similar tsVEPs up to 230 ms when they differed in the V4 and LOC ROIs. The evolution of the response proceeded largely in the feed-forward direction, with only weak evidence for feedback-related activity

Spatial and Temporal Dynamics of Attentional Guidance during Inefficient Visual Search

Spotting a prey or a predator is crucial in the natural environment and relies on the ability to extract quickly pertinent visual information. The experimental counterpart of this behavior is visual search (VS) where subjects have to identify a target amongst several distractors. In difficult VS tasks, it has been found that the reaction time (RT) is influenced by salience factors, such as the target-distractor similarity, and this finding is usually regarded as evidence for a guidance of attention by preattentive mechanisms. However, the use of RT measurements, a parameter which depends on multiple factors, allows only very indirect inferences about the underlying attentional mechanisms. The purpose of the present study was to determine the influence of salience factors on attentional guidance during VS, by measuring directly attentional allocation. We studied attention allocation by using a dual covert VS task in subjects who had 1) to detect a target amongst different items and 2) to report letters briefly flashed inside those items at different delays. As predicted, we showed that parallel processes guide attention towards the most relevant item by virtue of both goal-directed and stimulus-driven factors, and we demonstrated that this attentional selection is a prerequisite for target detection. In addition, we show that when the target is characterized by two features (conjunction VS), the goal-directed effects of both features are initially combined into a unique salience value, but at a later stage, grouping phenomena interact with the salience computation, and lead to the selection of a whole group of items. These results, in line with Guided Search Theory, show that efficient and rapid preattentive processes guide attention towards the most salient item, allowing to reduce the number of attentional shifts needed to find the target