Changes in attentional resources during the acquisition of laparoscopic surgical skills.

BACKGROUND: Increasing familiarity and practice might free up mental resources during laparoscopic surgical skills training. The aim of the study was to track changes in mental resource allocation during acquisition of laparoscopic surgical skills. METHODS: Medical students with no previous experience in laparoscopic surgery took part in a 5-week laparoscopic training curriculum. At the beginning and end of the training period, one of the training tasks was combined with a secondary auditory detection task that required pressing a foot switch for defined target tones, creating a dual-task situation. During execution of the two concurrent tasks, continuous electroencephalographic measurements were made, with special attention to the P300 component, an index of mental resources. Accuracy and reaction times of the secondary task were determined. RESULTS: All 14 participants successfully completed the training curriculum. Target times for successful completion of individual tasks decreased significantly during training sessions (P <0.001 for all tasks). Comparing results before and after training showed a significant decrease in event-related brain potential amplitude at the parietal electrode cluster (P300 component, W = 67, P = 0.026), but there were no differences in accuracy (percentage correct responses: W = 48, P = 0.518) or reaction times (W = 42, P = 0.850) in the auditory detection task. CONCLUSION: The P300 decrease in the secondary task over training demonstrated a shift of mental resources to the primary task: the surgical exercise. This indicates that, with more practice, mental resources are freed up for additional tasks.

Striatal dysfunction in X-linked dystonia-parkinsonism is associated with disease progression.

BACKGROUND AND PURPOSE: X-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative adult-onset movement disorder associated with striatal atrophy. As the dopaminergic system has not yet been systemically studied in this basal ganglia model disease, it is unclear whether nigrostriatal dysfunction contributes to parkinsonism in XDP. METHODS: Pre- and post-synaptic dopaminergic function was assessed in XDP. A total of 10 123 jod-benzamide (IBZM) single-photon emission computed tomography (SPECT) images were obtained for nine patients aged 42.3 ± 9.5 years (SD; range 30-52) and one asymptomatic mutation carrier (38 years), and four ioflupane (FP-CIT) SPECT images were obtained for four patients, aged 41.5 ± 11.6 years (range 30-52 years). Structural magnetic resonance imaging was also performed for all mutation carriers and 10 matched healthy controls. RESULTS: All patients were men who suffered from severe, disabling segmental or generalized dystonia and had varying degrees of parkinsonism. IBZM SPECT images were pathological in 8/9 symptomatic patients with distinct reduced post-synaptic tracer uptake in the caudate nucleus and putamen, and unremarkable in the asymptomatic mutation carrier. Longer disease duration was correlated with lower IBZM binding ratios. All subjects exhibited slightly reduced FP-CIT uptake values compared to controls for each analyzed region (-37% to -41%) which may be linked to basal ganglia volume loss. Visual inspection revealed physiological FP-CIT uptake in 1/4 patients. CONCLUSIONS: This nuclear imaging study provides evidence that the functional decline of post-synaptic dopaminergic neurotransmission is related to disease duration and ongoing neurodegeneration. Given the severe striatal cell loss which could be verified with post-synaptic nuclear imaging, both parkinsonism and dystonia in XDP are probably mainly due to striatal dysfunction.

Mild Thyrotoxicosis Leads to Brain Perfusion Changes: An Arterial Spin Labelling Study.

Hypo- and hyperthyroidism have effects on brain structure and function, as well as cognitive processes, including memory. However, little is known about the influence of thyroid hormones on brain perfusion and the relationship of such perfusion changes with cognition. The present study aimed to demonstrate the effect of short-term experimental hyperthyroidism on brain perfusion in healthy volunteers and to assess whether perfusion changes, if present, are related to cognitive performance. It is known that an interaction exists between brain perfusion and cerebral oxygen consumption rate and it is considered that neural activation increases cerebral regional perfusion rate in brain areas associated with memory. Measuring cerebral blood flow may therefore represent a proxy for neural activity. Therefore, arterial spin labelling (ASL) measurements were conducted and later analysed to evaluate brain perfusion in 29 healthy men before and after ingesting thyroid hormones for 8 weeks. Psychological tests concerning memory were performed at the same time-points and the results were correlated with the imaging results. In the hyperthyroid condition, perfusion was increased in the posterior cerebellum in regions connected with cerebral networks associated with cognitive control and the visual cortex compared to the euthyroid condition. In addition, these perfusion changes were positively correlated with changes of performance in the German version of the Auditory Verbal Learning Task [AVLT, Verbaler Lern-und-Merkfähigkeits-Test (VLMT)]. Cerebellar perfusion and function therefore appears to be modulated by thyroid hormones, likely because the cerebellum hosts a high number of thyroid hormone receptors.

Nucleus Accumbens Deep Brain Stimulation for Alcohol Addiction - Safety and Clinical Long-term Results of a Pilot Trial.

We report on the long-term clinical outcome (up to 8 years) of 5 patients who received deep brain stimulation (DBS) of the nucleus accumbens to treat their long-lasting and treatment-resistant alcohol addiction. All patients reported a complete absence of craving for alcohol; 2 patients remained abstinent for many years and 3 patients showed a marked reduction of alcohol consumption. No severe or long-standing side effects occurred. Therefore, DBS could be a promising, novel treatment option for severe alcohol addiction, but larger clinical trials are needed to further investigate the efficacy of DBS in addiction.

Septic shock in children in an urban area in Western Germany--outcome, risk factors for mortality and infection epidemiology.

BACKGROUND: Only sparse data exist about children with septic shock in Europe. The present study aimed to evaluate demographics, treatment, outcome and risk factors for mortality in Western Germany. PATIENTS: Children with septic shock aged 2 months to 17 years. METHODS: In a multi-center retrospective study of 20 children's hospitals data were obtained and analyzed by chart review. Risk factors for mortality were identified and assessed by multivariate regression analysis. RESULTS: Overall mortality in 83 cases with septic shock was 25% (21 patients). Significant risk factors were high PRISM III score, low pH, low arterial systolic blood pressure, presence of disseminated intravascular coagulation and extent of multi-organ failure, but not lactate (p=0.05) and base excess (p=0.065). Mortality in hospitals which treated 10 or more patients (category 1) was 17% and increased to 22% in hospitals which treated 3-6 patients (category 2). In hospitals with only 1 or 2 patients (category 3) mortality rate was 61% (p<0.01 when compared to category 1 or 2). A stepwise increase was also seen in the severely sick patients according to PRISM III (>19): category 1: 23%, category 2: 40%, category 3: 62.5% (p<0.05 for comparison of category 1 and 3). Multivariate analysis of significant risk factors revealed low number of treated patients as the only individual risk factor for mortality. CONCLUSION: Mortality from pediatric septic shock in an urban area in Western Germany is high. Disease severity and treatment in a department with few cases were associated with increased mortality.

Performance monitoring and behavioral adaptation during task switching: an fMRI study.

Despite significant advances, the neural correlates and neurochemical mechanisms involved in performance monitoring and behavioral adaptation are still a matter for debate. Here, we used a modified Eriksen-Flanker task in a magnetic resonance imaging (MRI) study that required the participants to derive the correct stimulus-response association based on a feedback given after each flanker stimulus. Participants had to continuously monitor and adapt their performance as the stimulus-response association switched after a jittered time interval without notice. After every switch an increase of reaction times was observed. At the neural level, the feedback indicating the need to switch was associated with activation of the precuneus, the cingulate cortex, the insula and a brainstem region tentatively identified as the locus coeruleus. This brainstem system appears to interact with this cortical network and seems to be essential for performance monitoring and behavioral adaptation. In contrast, the cerebellum crus and prefrontal areas are activated during error feedback processing. Furthermore we found activations of the hippocampus and parahippocampal gyrus bilaterally after a correct feedback in learnable stimulus-response associations. These results highlight the contribution of brainstem nuclei to performance adaptation.

Audiovisual perception of natural speech is impaired in adult dyslexics: an ERP study.

The present study used event-related brain potentials (ERPs) to investigate audiovisual integration processes in the perception of natural speech in a group of German adult developmental dyslexic readers. Twelve dyslexic and twelve non-dyslexic adults viewed short videos of a male German speaker. Disyllabic German nouns served as stimulus material. The auditory and the visual stimulus streams were segregated to create four conditions: in the congruent condition, the spoken word and the auditory word were identical. In the incongruent condition, the auditory and the visual word (i.e., the lip movements of the utterance) were different. Furthermore, on half of the trials, white noise (45 dB SPL) was superimposed on the auditory trace. Subjects had to say aloud the word they understood after they viewed the video. Behavioral data. Dyslexic readers committed more errors compared to normal readers in the noise conditions, and this effect was particularly present for congruent trials. ERPs showed a distinct N170 component at temporo-parietal electrodes that was smaller in amplitude for dyslexic readers. Both, normal and dyslexic readers, showed a clear effect of noise at centro-parietal electrodes between 300 and 600 ms. An analysis of error trials reflecting audiovisual integration (verbal responses in the incongruent noise condition that are a mix of the visual and the auditory word) revealed more positive ERPs for dyslexic readers at temporo-parietal electrodes 200-500 ms poststimulus. For normal readers, no such effect was present. These findings are discussed as reflecting increased effort in dyslexics under circumstances of distorted acoustic input. The superimposition of noise leads dyslexics to rely more on the integration of auditory and visual input (lip reading). Furthermore, the smaller N170-amplitudes indicate deficits in the processing of moving faces in dyslexic adults.

Marked retroperitoneal lymphadenopathy in hairy cell leukemia: a case report.

Hairy cell leukemia (HCL) is uncommonly associated with lymphadenopathy, while retroperitoneal lymphadenopathy is extremely uncommon. We report on a patient with a 12-year history of HCL who developed painless jaundice and ascites, accompanied by positional discomfort with persistent nausea. Computed tomography examination revealed 2 large retroperitoneal masses, which at autopsy consisted of HCL with focally intermixed pancreatic and peripancreatic tissue. Lymphadenopathy was not identified above the diaphragm or below the aortic bifurcation. No vasculitis or an unusual HCL histology was identified. As previous reports, our findings suggest that HCL with massive lymphadenopathy has a specific site predilection, but it is not necessarily accompanied by vasculitis or an unusual histology.

The significance of job-anxiety in a working population.

BACKGROUND: Job-anxiety, as distinguished from trait-anxiety, is associated with long-term sickness absence. The prevalence of job-anxiety within a working population is not known. Identifying individuals who would benefit from intervention might be useful. AIMS: To investigate job-anxiety in employees not undergoing treatment for mental health illness, firstly by assessing the level of job-anxiety and work-related avoidance tendencies in a working sample, and secondly by testing whether job-anxiety is distinguishable from trait-anxiety. METHODS: Cross-sectional survey of a convenience sample obtained through personal contact distribution. Employees from different professional settings completed an anonymous questionnaire and provided information on their employment status. The State-Trait-Anxiety Inventory (STAI-T) was used to measure trait-anxiety and the Job-Anxiety-Scale (JAS) was used to assess job (state) anxiety. RESULTS: There was a 69% response rate (240 responses); 188 responses were available for analysis of whom 62% were women. There were no employees with high trait-anxiety. Ten employees (5%) reported increased job-anxiety and of these nine employees reported high 'tendencies of avoidance and workplace absence'. Avoidance was most often accompanied by the comorbid job-anxieties 'job-related social anxiety', 'fear of changes at work' and 'fears of existence', 'anticipatory' and 'conditioned' job-anxiety and 'panic symptoms'. CONCLUSIONS: In this sample, self-reported job-anxiety appeared as a specific type of anxiety as opposed to trait-anxiety. In the workplace job-anxiety can present as job-avoidance and sickness absence and should be distinguished from trait-anxiety. In practice, employers and occupational health practitioners should be aware of those employees prone to sickness absence.

Human hypothalamus shows differential responses to basic motivational stimuli--an invasive electrophysiology study.

The hypothalamus supports basic motivational behaviours such as mating and feeding. Recording directly from the posterior inferior hypothalamus in a male patient receiving a deep brain stimulation (DBS) electrode for the alleviation of cluster headache, we tested the hypothalamic response to different classes of motivational stimuli (sexually relevant: pictures of dressed and undressed women; pictures of food) and pictures of common objects as control. Averaged local field potentials (LFP) to sexually relevant stimuli were characterized by a biphasic significantly enhanced response (relative to objects; bootstrapping statistics) with a first phase starting at around 200 ms and a second phase peaking at around 600 ms. Sexually relevant stimuli also showed a greatly enhanced positivity relative to other stimulus classes in surface event-related potentials in a group of 11 male control participants. It is suggested that the hypothalamus is involved in the recruitment of attentional resources by sexually relevant stimuli reflected in this surface positivity. In a second session, the response to food stimuli relative to objects was tested in two states: after fasting for 14 h, LFPs to food and object stimuli showed significant differences in between 300 and 850 ms, which disappeared after a full high-calorie meal, thus replicating classic studies in monkeys [Rolls et al., Brain Res (1976) 111:53-66]. The current data are the first to demonstrate hypothalamic responses to the sight of motivational stimuli in man and thus shows that recording from DBS electrodes might provide important information about the cognitive functions of subcortical structures.

Contribution of PET imaging to the initial staging and prognosis of patients with Hodgkin's disease.

BACKGROUND: Positron emission tomographic (PET) scanning utilizing [18F]fluorodeoxyglucose (FDG) is a new method of tumor imaging based on the increased glucose metabolic activity of malignant tumors. In Hodgkin's disease (HD), PET has proven value for the evaluation of residual masses following treatment and for the early diagnosis of relapse. In the initial staging of HD, PET frequently shows a higher stage than conventional methods (upstaging by PET). In the present study, we evaluated the frequency of stage changes by PET in a multicenter setting and determined its prognostic relevance. PATIENTS AND METHODS: A total of 73 patients with newly diagnosed HD were staged with both conventional methods and whole-body PET scanning. All histological types and stages were represented. The median time of follow-up after the initial diagnosis was 25 months (range 1 month to 5 years). The response to treatment was determined by standard clinical and diagnostic criteria. For the purpose of this analysis, data from a PET center associated with a university medical center and a PET center associated with a group oncology practice were combined. RESULTS: A total of 21 patients (28.8%) were upstaged by PET compared with conventional methods. In two cases (2.7%), a lower stage was suggested by PET scanning. With one possible exception, the upstaging had no obvious clinical or biological correlate. Among 12 patients in stage I (A + B) by conventional methods, seven were upstaged by PET (58.3%), four to stage II, one to stage III and two to stage IV. Among 42 patients in stage II, eight were upstaged by PET (19.0%), six to stage III and two to stage IV. Among 12 patients in stage III, six (50%) were upstaged to stage IV by PET. If only early-stage patients and major changes are considered (stages IA-IIB to III or IV), among 49, 10 were upstaged to III or IV, whereas in 39 staging was unchanged following PET. In the former group, three relapsed or were refractory compared with none in the latter group (P<0.006). In advanced stage patients (IIIA or IIIB) a trend toward treatment failure was apparent in patients who were upstaged by PET. CONCLUSIONS: PET scanning is an interesting new modality for the accurate staging of patients with HD and frequently shows a higher stage than conventional methods. PET should be performed at initial diagnosis and should be included in prospective studies of patients with HD. Upstaging by PET may represent a risk factor for a more advanced stage or a biologically more aggressive tumor. Patients with early-stage disease as identified by conventional methods have a significant risk of treatment failure if a more advanced stage is indicated by PET. At present, major stage changes suggested by PET imaging should be confirmed by an independent diagnostic method.

Constraints for emotion specificity in fear and anger: the context counts.

We investigated psychophysiological responses to fear and anger inductions during real-life and imagination. Female participants (N = 158) were assigned to a fear-treatment, fear-control, anger-treatment, or anger-control group. Context (real-life, imagination) was varied in two sessions of fixed order. Eleven self-report and 29 somatovisceral variables were registered. Results showed that (a) except during anger imagination, control groups were emotionless; (b) in control groups, contexts prompted diverging somatovisceral responses, but similar emotion self-reports; except during fear imagination, the emotion inductions (c) were successful and (d) produced specific emotion reports; (e) during real-life, somatovisceral fear and anger responses exhibited a marked cardiovascular defense reflex; (f) in addition, real-life fear showed an adrenaline-like specific response pattern, whereas real-life anger showed specific forehead temperature and EMG extensor increases, accompanied by an elevated DBP during imagination. A Component Model of Somatovisceral Response Organization is proposed.

MHC class II and CD40 play opposing roles in dendritic cell survival.

In contrast to very immature dendritic cells (DC), mature DC are largely resistant to death by CD95 (CD95/APO-1) ligation. Investigation of other potential death-inducing ligands showed that mature DC were instead highly susceptible to apoptosis induced by cross-linking of MHC class II. Thus, increasing DC maturity correlates with increased resistance to CD95 killing, but an increased susceptibility to class II-mediated killing. Anti-I-A/I-E monoclonal antibodies (mAb) induced rapid (<2 h) apoptotic cell death in mature epidermal, spleen and bone marrow-derived DC, as determined by annexin/propidium iodide staining, morphological changes, decreased diploidy and loss in mitochondrial membrane potential. Although full class II-mediated killing required DC cytoskeletal motion, divalent cations and phosphatase activity, neither caspase activation, respiration, RNA or protein synthesis, NO production, nor CD95:CD95L interactions were required. Strikingly, DC pretreated by CD40 mAb cross-linking, but not by lipopolysaccharide or TNF-alpha, were completely resistant to class II-mediated killing. CD40-mediated protection was reduced in the presence of the SB202190 inhibitor of the mitogen-activated protein kinase p38 pathway, but appeared to be independent of p42/44 extracellular signal-related kinase or NF-KB activation. Our findings show that in addition to its role as an activator of antigen-presenting cell function, CD40 provides an important counter-signal against class II-induced apoptosis. Thus, these data point to an important role of the T cell in regulating DC survival.

Involvement of the cavernous sinus by malignant (extracranial) tumour: palliation in six cases without surgery.

Involvement of the cavernous sinus region due to haematogenous spread or by local extension of a malignant head and neck tumour does not occur frequently. Six patients were treated by external beam radiation with (n=3) or without neoadjuvant chemotherapy between December 1989 and February 1996. Manifestations of the condition mainly consisted of fifth and sixth cranial nerve deficits (n=4). Complete resolution of cranial nerve deficits after therapy occurred in two of the four patients with only three individuals having been evaluable. Three of the six patients survived for more than 3 years. Thus, palliation can be achieved by chemoradiation or radiotherapy alone, and long term survival is not precluded.

Multiple myeloma metastatic to the thigh: successful treatment with radiation therapy.

A 64-year-old man with metastatic multiple myeloma in the thigh was treated with radiation therapy. After a total dose of 30 Gy/10 fractions, significant resolution of the tumor in the thigh was observed. This case confirms the accepted dictum that multiple myeloma is a radioresponsive neoplastic disorder.

Foamy virus capsids require the cognate envelope protein for particle export.

Unlike other subclasses of the Retroviridae the Spumavirinae, its prototype member being the so-called human foamy virus (HFV), require the expression of the envelope (Env) glycoprotein for viral particle egress. Both the murine leukemia virus (MuLV) Env and the vesicular stomatitis virus G protein, which efficiently pseudotype other retrovirus capsids, were not able to support export of HFV particles. Analysis of deletion and point mutants of the HFV Env protein revealed that the HFV Env cytoplasmic domain (CyD) is dispensable for HFV particle envelopment, release, and infectivity, whereas deletion of the membrane-spanning-domain (MSD) led to an accumulation of naked capsids in the cytoplasm. Neither alternative membrane association of HFV Env deletion mutants lacking the MSD and CyD via phosphoglycolipid anchor nor domain swapping mutants, with the MSD or CyD of MuLV Env and VSV-G exchanged against the corresponding HFV domains, could restore particle envelopment and the release defect of pseudotypes. However, replacement of the HFV MSD with that of MuLV led to budding of HFV capsids at the intracellular membranes. These virions were of apparently wild-type morphology but were not naturally released into the supernatant and they were noninfectious.

Myasthenia gravis: a review with emphasis on the potential role of thymectomy.

Review of our results with thymectomy for myasthenia gravis supports the role of early surgery for this debilitating and often lethal disease. The data presented here confirm the fact that thymectomy has rare complications and low operative mortality. Approximately 80 percent of patients with myasthenia gravis can expect clinical improvement with surgery, which also offers a chance for complete remission.