The disengage deficit in hemispatial neglect is restricted to between-object shifts and is abolished by prism adaptation.

We sought to determine the effects of prism adaptation on peripherally cued visual attention shifting in patients with spatial neglect, using a task devised by Egly et al. (J Exp Psychol Gen 123:161-177, 1994) based on the classic Posner paradigm. This task allowed a comparison of "within-object" versus "between-object" attention shifts. A display was presented containing two parallel outline rectangles, and subjects were asked to make rapid responses to a target, which would appear at one end of one of the rectangles. The target location was pre-cued with 75% validity: on invalid trials attention was directed either to the other end of the same rectangle, or to the other rectangle. Healthy subjects and right-hemisphere patients without neglect showed a left-right symmetrical pattern, with a larger validity effect when required to shift attention between rectangles, thus indicating a greater difficulty of attention-shifting between than within the respective shapes. The neglect patients showed the typical leftward "disengage deficit" previously observed in neglect, but only for attention shifts between objects, indicating that the effect is object-based rather than purely spatial. A comparison of vertical and horizontal shift costs showed that this attention-shifting deficit for left-hemifield target stimuli was directional rather than hemifield-based: it was absent for vertical shifts of attention within the left hemifield. Finally, we found that prism adaptation abolished the disengage deficit. We found no effects of prism adaptation in the control subjects. We argue that prism adaptation has a powerful effect on one of the fundamental manifestations of the neglect syndrome.

Choosing between alternative wrist postures: action planning needs perception.

When normal subjects grasp with their right hand a rectangular object placed at different orientations in the horizontal plane, they change from a 'thumb left' (clockwise) to a 'thumb right' (anti-clockwise) grasp when the orientation exceeds about 110 degrees , with respect to the mid-sagittal plane. This suggests planning of the final grip orientation at, or before the start of the prehension movement. The current study assessed performance of two visual agnosic patients (SB and DF) on a grasping task requiring the planning of final grip posture. Five healthy subjects were also tested. Subjects were required to grasp a triangular-section block, which was presented at one of seven different orientations (80-140 degrees). The healthy subjects showed a consistent relation between object orientation and hand orientation just before contact. In addition, they consistently used a clockwise grasp when object orientation was less than 100 degrees , and an anti-clockwise grasp when it was more than 110 degrees, with a sharply defined switch-point being identifiable for each subject. For both visual agnosic patients, hand orientation was also reliably related to object orientation. However, the selection of grasp posture was markedly abnormal: they did not consistently switch between clockwise and anti-clockwise grasps within the normal orientation range, and the switch, when it did occur, was not at all sharply defined. These results suggest that the planning of hand orientation during a grasp depends on a perceptually based judgement of the awkwardness of alternative movements. This would presumably involve ventral stream processing, which is disrupted in the visual agnosic patients.

Contralateral visual search deficits following TMS.

Transcranial magnetic stimulation of posterior parietal vs. superior temporal sites cause differential effects on conventional conjunction vs. feature search tasks, respectively. We now report that when a decision has to be made on the target's left/right location, different lateralized deficits emerge in these two cases. With full-field arrays, we found a specific PPC search deficit for contralateral space. With smaller, structured arrays presented in left or right hemispace, we found a specific STG deficit for contralateral parts of the array.

Visuospatial neglect in near and far space: dissociation between line bisection and letter cancellation.

The differential performance on a line bisection and a cancellation task in near and far space was studied. A group of 10 patients with severe left-sided visuospatial neglect and a group of 10 right-brain damaged patients without neglect were examined. The stimuli were presented at a distance of 60 cm (near space) and 160 cm (far space), respectively, and corrected for visual angle. In the line bisection task, patients were asked to point to the estimated line centre with a pencil (near space) or a stick (far space). In the cancellation task, patients pointed to all target stimuli they could detect using either a pencil (near space) or a stick (far space). Most patients with left hemineglect showed a more prominent neglect in far space as compared to near space for the line bisection task, whereas no difference of performance between near and far space was found in the control patients. In contrast, no group showed a distance effect in the cancellation task. The observation that only line bisection is influenced by the distance of the stimulus suggests that line bisection and cancellation are processed differentially. It is proposed that line bisection requires an allocentric reference system focusing attention on objects, whereas cancellation tasks are based on an egocentric reference system responsible for visuospatial attention. Our results indicate that distance changes perception within the allocentric but not within the egocentric system.

Dixyrazine for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy.

BACKGROUND: The study assessed the efficacy and safety of dixyrazine, an alternative neuroleptic drug to droperidol, in the prophylaxis of postoperative nausea and vomiting (PONV). METHODS: A total of 197 patients scheduled for laparoscopic cholecystectomy under general anesthesia were randomized to receive either dixyrazine 10 mg or placebo double-blinded at the end of surgery. Scores pertaining to PONV episodes, analgetic supply, rescue medication, adverse events and patient satisfaction were collected over the first 2 h in the PACU and the next 22 h in the ward. RESULTS: The incidence of PONV over the entire 24-h period was reduced from 32% in the placebo group to 13% in the dixyrazine group (P< or =0.004). The incidence of nausea in the first 2 h was reduced from 15% in the placebo group to 4% in the dixyrazine group (P< or =0.02) and from 12% to 5% in the next 22 h. The incidence of emetic episodes was not different between the two groups. Postoperative shivering was significantly less prevalent in the dixyrazine than in the placebo group (2% vs. 13%; P< or =0008), and opioid analgesics were required significantly less often (61% vs. 75%; P< or =0.01). No significant adverse effects were observed. Patient satisfaction was similar in both groups. CONCLUSION: Prophylactic dixyrazine is an effective, safe, and cheap antiemetic drug for laparoscopic cholecystectomy without involving any significant adverse events.

Avoidance of obstacles in the absence of visual awareness.

The spatial character of our reaching movements is extremely sensitive to potential obstacles in the workspace. We recently found that this sensitivity was retained by most patients with left visual neglect when reaching between two objects, despite the fact that they tended to ignore the leftward object when asked to bisect the space between them. This raises the possibility that obstacle avoidance does not require a conscious awareness of the obstacle avoided. We have now tested this hypothesis in a patient with visual extinction following right temporoparietal damage. Extinction is an attentional disorder in which patients fail to report stimuli on the side of space opposite a brain lesion under conditions of bilateral stimulation. Our patient avoided obstacles during reaching, to exactly the same degree, regardless of whether he was able to report their presence. This implicit processing of object location, which may depend on spared superior parietal-lobe pathways, demonstrates that conscious awareness is not necessary for normal obstacle avoidance.

Validation of an ESI-MS/MS screening method for acylcarnitine profiling in urine specimens of neonates, children, adolescents and adults.

BACKGROUND: Acylcarnitine (AC) profiling in dried blood spots by means of electrospray ionisation tandem mass spectrometry (ESI-MS/MS) has proven to be a useful method in neonatal screening, able to detect inborn errors of fatty acid oxidation, amino acid, organic acid and carnitine metabolism. Furthermore, this method is becoming increasingly applied in selective screening and in prenatal and postmortal diagnostics of inborn metabolic disorders, where urine is commonly used as specimen of interest. We therefore developed and validated a butylation method of acylcarnitine profiling in urine by ESI-MS/MS without previous chromatographic separation. METHODS: Random urine specimens were used for investigation of the analytical imprecision of the method. Recovery, precision and linearity were determined using methanolic standard solutions of free carnitine, octanoylcarnitine and palmitoylcarnitine at various concentrations. RESULTS: The mean coefficients of variation of within-run and run-to-run analysis of these analytes were found between 10% and 20% and demonstrated that the method fulfills the analytical requirements within the relevant ranges of concentration. Creatinine-related and age-related reference values of free carnitine and the ACs (C2-C18) were established. The definite discrimination was possible between patients with fatty acid oxidation disorders, organic acidurias, and healthy controls. The AC profiles from patients with various specific disorders were diagnostically helpful during acute deterioration and even during conditions of well-compensated metabolic state. CONCLUSION: The method used in this study is suitable both for selective screening and for confirmation of diagnosis with the advantage of high-throughput quantitative measurement.

Neck muscle vibration induces lasting recovery in spatial neglect.

OBJECTIVES: To evaluate whether neck muscle vibration is an effective technique for neglect rehabilitation, with lasting beneficial effects. METHODS: The effects of differential treatment of visual exploration training alone or in combination with neck muscle vibration were evaluated in a crossover study of two matched groups of 10 patients suffering from left sided neglect. Each group received a sequence of 15 consecutive sessions of exploration training and combined treatment. The effects of treatment were assessed with respect to different aspects of the neglect disorder such as impaired perception of the egocentric midline, exploration deficits in visual and tactile modes, and visual size distortion. The transfer of treatment effects to activities of daily living was examined by a reading test and a questionnaire of neglect related everyday problems. All variables were measured six times: three baseline measurements, two post-treatment measurements, and one follow up after two months. RESULTS: The results showed superior effects of combination treatment. A specific and lasting reduction in the symptoms of neglect was achieved in the visual mode, which transferred to the tactile mode with a concomitant improvement in activities of daily living. The improvement was evident two months after the completion of treatment. In contrast, isolated exploration training resulted in only minor therapeutic benefits in visual exploration without any significant transfer effects to other tasks. CONCLUSIONS: Neck muscle vibration is a decisive factor in the rehabilitation of spatial neglect and induces lasting recovery when given as a supplement to conventional exploration training.

Activation of spinach pullulanase by reduction results in a decrease in the number of isomeric forms.

Spinach starch debranching enzyme, a limit dextrinase or pullulanase (EC 3.2.1.41), is a monomeric protein of 100 kDa that produces up to seven coexisting and mutually interconvertible isomers of different specific activity, a phenomenon that has been termed microheterogeneity and for which a structural explanation has not yet been presented. The enzyme can be activated by reduction, in particular by thiol reagents, and inactivated by oxidation and the concomitant change of the patterns of its isomeric forms could be quantified by chromatofocusing. The hypothesis was examined that reduction of the enzyme's thiol groups shifts the isomer pattern towards the forms with a higher specific activity while oxidation favours the less active forms. Using TCEP as reductant only the form with the highest specific activity was obtained. This form was almost inaccessible for proteolysis by trypsin while the oxidized and GSH-activated enzyme yielded four peptides when treated with trypsin. Their sequence indicated cleavage predominantly of loops connecting the beta-strands and alpha-helices of the (beta/alpha)(8)-barrel which forms the catalytic site of the pullulanase. Formation of various disulphide bridges between the loops connecting the barrel structures -- predominantly on one side -- may be the reason for the microheterogeneity of the spinach pullulanase. In vivo, the enzyme maintains its activated state due to the high concentration of GSH in the chloroplast. However, the chloroplast's pH shifts from day (pH 8) to night (pH 7) and thus could also alter the activity of the protein in accordance with the required function in starch metabolism.

Time-dependent inhibition of glioblastoma cell proliferation by dexamethasone.

Because of the outstanding importance of the glucocorticoid Dexamethasone (DEX) as supportive therapy in the management of brain tumours, the direct effect of DEX on tumour cell proliferation is of particular interest. Previous in vitro studies led to contradictory results. To characterise more precisely the influence of DEX, we investigated the glioblastoma multiforme (GM) cell lines A172, T98G and 86HG39. Cells were treated with DEX concentrations ranging from 5 x 10(-9) to 5 x 10(-5) M from 24 to 240h under different treatment conditions. Influence of DEX on glioma cell viability was assessed daily for 5 days by MTT-assay: (I) with continuous DEX incubation (acute treatment), (II) in a recultivation period without DEX after 5 days of DEX pre-incubation (pre-treatment), (III) with continuous DEX incubation after 5 days of DEX pre-incubation (combination treatment). DEX acute treatment led to strongly decreased proliferation of A172 cells, whereas T98G and 86HG39 cells remained uninfluenced. In opposite, a time-delayed inhibition of cell proliferation was observed in all three cell lines after DEX pre-treatment. Combination treatment induced a significant increase of the inhibitory effect in A172 and T98G cells. These data show a variable, partial time-dependent inhibitory effect of DEX on the proliferation of GM cells and may open new treatment strategies for malignant brain tumours.

Neuroendocrine differentiation is a relevant prognostic factor in stage III-IV colorectal cancer.

OBJECTIVE: To determine the prognostic relevance of neuroendocrine differentiation in colorectal cancer. METHODS: The survival of 116 patients with colorectal cancer of stages III (n = 59) and IV (n = 57) was correlated with the extent of neuroendocrine differentiation. Chromogranin A and synaptophysin were used as neuroendocrine markers. Based on the degree of immunoreactivity for these markers, tumours were classified as 0 (no expression of neuroendocrine markers), 1 (< 2% cells staining positive for neuroendocrine markers) and 2 (> 2% cells staining positive for neuroendocrine markers). Patients were followed up for more than 5 years or until death. RESULTS: Seven of 59 (11.8%) stage III cancers and 13/57 (22.8%) stage IV cancers belonged to group 2. The 96 patients of groups 0 and 1 lived for 48.9 months, whereas the 20 patients of group 2 survived for only 18.6 months (Kaplan-Meier survival curves, P < 0.001). The difference was most striking in stage III disease with 79.4 months' survival for combined groups 0 and 1, and 38.9 months' survival for group 2 (P < 0.01). Using the multivariate Cox regression model, the presence of more than 2% of cells with neuroendocrine differentiation was found to be an independent prognostic parameter for stage III and IV disease. No correlation was observed between neuroendocrine differentiation and tumour location, grade, depth of invasion or stage. CONCLUSION: Neuroendocrine differentiation is often seen in colorectal cancer. It is an independent prognostic factor in stage III-IV colorectal cancer.

Different effects of valproic acid on proliferation and migration of malignant glioma cells in vitro.

Valproic acid (VPA) has been considered as a possible treatment agent for malignant gliomas. In order to characterise the possibilities of VPA, we investigated the effects on cell migration and proliferation. Human cell lines T98G, A172, 85HG66 and 86HG39 were treated with VPA or left untreated, afterwards Boyden chamber assay was used for measuring vertical migration. In a second assay cells were stimulated to create spheroids and spheroid migration was measured. Proliferation was assessed using a cell counter. VPA decreased proliferation of 86HG39 > A172 > 85HG66 cells, whereas T98G remained uninfluenced. The influence of VPA on migration was different; whereas VPA dose-dependently stimulated migration of 86HG39 cells, migration of T98G and 85HG66 decreased, whereas A172 cells remained uninfluenced. Only 86HG39 and A172 cells created spheroids. In both cell lines Boyden-chamber-findings were confirmed by analysing the influence of VPA on spheroid migration. These non-uniform data demonstrate that the benefit of VPA in glioma treatment is not clear and needs further investigation.

Visual background motion reduces size distortion in spatial neglect.

Patients with visual neglect show deficits in horizontal size perception in their neglected hemispace, as previously reported. The present study examined whether this size distortion can be modulated by visual background motion to the left or right while the patient performs a visual size judgment task. Six neglect patients and six normal subjects were investigated with a psychophysical size judgment task. All neglect patients showed a significant perceptual underestimation of horizontal bars in their left hemispace expressed as an overestimation of horizontal object size in the baseline (no motion) condition. Slow visual motion of background stimuli towards the right, ipsilesional side aggravated the deficit slightly, but not significantly, whereas leftward background motion completely normalized the size distortion (in four cases) or even led to an overcompensation (in two cases). This facilitatory effect was specific as it was obvious for the constant errors in the size judgments, but not in their accuracy as reflected by unchanged difference thresholds. These results suggest that coherent background motion restores temporarily the disturbed perception and representation of horizontal object size in spatial neglect.

Effects of half the tidal volume during cardiopulmonary resuscitation on acid-base balance and haemodynamics in pigs.

The effects of half the tidal volume during cardiopulmonary resuscitation (CPR) on haemodynamics, acid-base balance, and oxygenation were studied in anaesthetized pigs. The animals were ventilated with a mean tidal volume of 12.5 +/- 0.5 ml/kg at a rate of 14/minute resulting in a mean arterial pCO2 of 40 +/- 3 mmHg. They were randomly assigned to two groups: in one group ventilation was performed with half the pre-arrest tidal volume (50% group; n = 9), in the other group ventilation remained unchanged during CPR (100% group; n = 10). After 8 minutes of CPR attempts were made to restore spontaneous circulation with epinephrine and countershocks. There were no differences in advanced life support requirements, haemodynamic parameters, and resuscitability between the two groups. During CPR up to 5 minutes after restoration of spontaneous circulation (ROSC) dead space ventilation was significantly higher in the 50% group compared with the 100% group (p < 0.05). During CPR (at 3 and 7 minutes) arterial pO2 values were significantly lower (218 +/- 136 and 221 +/- 120 mmHg vs. 381 +/- 130 and 352 +/- 147 mmHg; FiO2 1.0) and hyperventilation was less pronounced (34.4 +/- 7.3 and 31.3 +/- 7.7 mmHg vs. 26.2 +/- 5.6 and 26.9 +/- 6.3 mmHg) in the 50% group. Our results suggest that half the tidal volume during CPR is likely to establish a more physiological acid-base balance and has no adverse effects on haemodynamics in intubated pigs ventilated with pure oxygen.

Protein heterogeneity of spinach pullulanase results from the coexistence of interconvertible isomeric forms of the monomeric enzyme.

Purified pullulanase (starch-debranching enzyme, R-enzyme, EC 3.2.1. 41) from spinach (Spinacia oleracea L.) chloroplasts separated into at least seven individual enzymically active proteins (isomers, numbered 1-7) on isoelectric focusing or column chromatofocusing. At their isoelectric points (between pH 4.7 and 5.2) these forms were rather stable. At slightly alkaline pH, each converted into the whole set of isomers. PAGE of the purified enzyme under denaturing or non-denaturing conditions resulted in one protein band. When substrate (amylopectin or pullulan) was included in the gel, the native enzyme as well as any of the individual isomers separated into two (sometimes three) bands ('substrate-induced forms', numbered I-III) with different specific activities, dissociation constants of the enzyme-substrate complexes and activation energies. Each substrate-induced form produced the whole set of seven isomers on isoelectric focusing. The specific activity of the total enzyme reflected the relative proportions of the substrate-induced forms. To some extent the relative proportions, as determined by crossed immunoelectrophoresis, could be shifted in favour of the more or the less active forms by reduction with dithiothreitol, and gentle oxidation respectively. Activation by dithiothreitol did not alter the mode of action of the enzyme but only increased the velocity of substrate degradation and extended its activity into the pH range of the chloroplast. As a consequence of isomer interconversion, microheterogeneity could serve to regulate pullulanase activity in a biochemical manner that shares some features with allosteric regulation.

Head and trunk orientation modulate visual neglect.

Five patients with left visual neglect after right hemisphere lesions were examined with a line bisection and a reading task under five different conditions: head and trunk straight ahead, head or trunk oriented 20 degrees to the left and head or trunk oriented 20 degrees to the right. Fixation was always straight ahead. Five patients with right hemisphere lesions but without neglect and five normal subjects served as controls. In all neglect patients, turning the head or trunk to the left reduced line bisection and reading errors significantly as compared with the other three conditions and with the control groups. The modulation of neglect behaviour by trunk as well as head position supports the hypothesis of a disturbed egocentric coordinate system leading to neglect.

[Hemi-neglect versus hemianopia. Differential diagnosis]. / Hemineglekt versus Hemianopsie. Hinweise zur Differentialdiagnose.

Neglect and hemianopia represent frequent disorders in brain damaged patients. Differential diagnosis of both disorders may be difficult since both may present in diagnostic tests and daily life as a failure to perceive or react to stimuli in the contralesional hemispace or hemifield. The present paper summarizes several useful techniques in order to achieve a correct distinction. After a short review of the clinical phenomenology of hemianopia and -neglect the following topics are described: (1) subjective complaints and awareness of deficits (2) aetiology and lesion localisation, (3) uni-versus multimodal deficits; (4) extinction, (5) drawing from memory; (6) visual-spatial disorders; (7) line bisection, (8) effectiveness of attentional "cueing" strategies; (9) specific perimetric techniques; (10) visual evoked potentials and eye movement registration. The differences between hemianopia and -neglect are contrasted for all these topics. Taken all these possible features together the association and/or dissociation of hemineglect and postchiasmatic scotomata can efficiently be diagnosed. The results are summarized in a table at the end of the paper.

Moderate induced hypotension provides satisfactory operating conditions in maxillofacial surgery.

Patients scheduled for maxillofacial surgery were randomly assigned to receive isoflurane (n = 22) or nitroglycerin (n = 18) in order to induce hypotension. Surgeons, blinded for the actual level of blood pressure and the technique used for inducing hypotension, were asked to rate operating conditions on a scale from 1 to 5. Systolic arterial pressure (SAP) and mean arterial pressure (MAP) were reduced by 26% for both groups. Although blood pressure levels showed little variation throughout the induced hypotension period, scores of 2 to 5 were given significantly more often at incision and at 30 min compared to the following measuring points (P < 0.01). In total, the surgical field was rated significantly more often with a score of 1 and 2 than with a score of 3 to 5 (P < 0.01). A relation between score and SAP and/or MAP could not be found. There was also no relation between scores and the technique used for hypotension. Our data suggest that, with the exception of the first half hour of surgery, on average a SAP of 89 mmHg and a MAP of 65 mmHg were sufficient to produce satisfactory operating conditions.

Nimodipine after circulatory arrest: effects on oxygen delivery and consumption.

PURPOSE: Evaluation of the effects of nimodipine administration during and after cardiopulmonary resuscitation (CPR) on oxygen delivery and consumption was the aim of this study. METHODS: A randomized double-blind study in 32 anesthetized domestic pigs was performed. After 5 minutes of ventricular fibrillation (VF) and 5 minutes of external CPR, epinephrine (50 micrograms/kg) and either nimodipine or placebo (10 micrograms/kg bolus, 1 microgram/kg/min continuously throughout 4 hours of observation) were administered. One minute later (equal to 11 minutes VF), the first countershock was given. If this failed to restore spontaneous circulation, epinephrine and countershocks were repeated for a maximum of 30 minutes. RESULTS: Eleven of 12 nimodipine- and 7 of 14 placebo-treated pigs could be resuscitated successfully and survived the observation period (P < .05). Hemodynamic responses to nimodipine were characterized by significant decreases in systemic vascular resistance and mean arterial pressure from 10 minutes after restoration of spontaneous circulation onwards with consequent significant increases in cardiac output. Median systemic oxygen delivery indices (DO2I) in nimodipine-treated pigs were significantly higher at all measuring points when compared with placebo-treated animals. Median systemic oxygen consumption indices (VO2I) did not differ significantly between groups. Median oxygen extraction ratios in nimodipine-treated pigs were in the same range as prearrest and were lower when compared with placebo-treated pigs (at 30 minutes P < .05 and at 120 minutes P < .01). DO2I and VO2I were poorly correlated in all pigs treated with nimodipine and in 3 of 7 animals treated with placebo, suggesting supply independency in these animals. This difference between groups was significant (P < .05). CONCLUSIONS: Our findings suggest that in nimodipine-treated animals, a lower oxygen deficit or a better redistribution of regional blood flow occurred after circulatory arrest and resuscitation.