We like to move it - patients with schizophrenia spectrum disorders are impaired in estimating their physical fitness levels and benefit from individualized exercise.

BACKGROUND: People with schizophrenia spectrum disorders (SSD) engage less in physical activity than healthy individuals. The impact of subjectively assessed physical fitness levels on motivation for sports engagement and its relation to objective fitness parameters in SSD is unclear. METHODS: 25 patients with SSD (P-SSD) and 24 healthy controls (H-CON) participated in a randomized controlled study. Individual anaerobic thresholds (AT) were determined by an incremental exercise test and on separate days, aerobic exercise (cycling at 80% of workload at AT) and non-exercise control (sitting on an ergometer without cycling) sessions were performed. Demographic, clinical and objective physical fitness data (i.e., weekly physical activity, workload at AT, heart rate) were collected. Subjective physical fitness parameters were assessed before and after exercise and control sessions. RESULTS: Weekly physical activity in P-SSD was lower than in H-CON (p < 0.05) attributed to reduced engagement in sport activities (p < 0.001). Workload and percentage of predicted maximal heart rate at AT were also reduced in P-SSD compared to H-CON (both p < 0.05). Although objective and subjective physical fitness parameters were related in H-CON (p < 0.01), this relationship was absent in P-SSD. However, during exercise sessions subjective physical fitness ratings increased to a stronger extent in P-SSD than H-CON (p < 0.05). CONCLUSION: The missing relationship between subjective and objective physical fitness parameters in people with SSD may represent a barrier for stronger engagement in physical activity. Accordingly, supervised exercise interventions with individually adjusted workload intensity may support realistic subjective fitness estimations and enhance motivation for sports activity in individuals with SSD.

[Video-based head impulse test. Importance for routine diagnostics of patients with vertigo]. / Videobasierter Kopfimpulstest. Bedeutung für die Routinediagnostik von Schwindelerkrankungen.

Dizziness is one of the most common complaints in Germany which leads to medical consultation. Diagnosis is based on patient history, clinical examination and laboratory tests. In order to find or exclude a vestibular lesion, methods such as caloric irrigation, rotational chair tests or vestibular-evoked myogenic potentials were previously applied. Recently, a new diagnostic tool has been made available for application in daily practice: the video head impulse test (vHIT). Due to the easy and fast application for the examiner, good tolerance by the patient and high sensitivity for vestibular lesions, the vHIT has the potential to improve the diagnosis and therapy of patients suffering from vertigo in widespread medical care in Germany. This article reports on experiences with this new method after examination of over 1,500 patients in the academic vertigo centre in Lübeck. The principles and application of the vHIT in daily clinical routine are described and the many advantages but also some pitfalls are highlighted. As a consequence of a wider clinical use it is expected that the vHIT will lead to an increased detection of vestibular dysfunctions not only in clinically suspected vestibular diseases but also in other common neurological diseases (e.g. polyneuropathy or cerebellar ataxia). This may change the prevalence of different vestibular diseases, broaden knowledge about other common diseases with gait imbalance as the leading symptom and provide a quantitative measure that can be used to longitudinally assess the effects of therapeutic interventions.

Autosomal dominant Parkinson's disease in a large German pedigree.

OBJECTIVE: While several genes have been identified to cause Parkinson's disease (PD), monogenic forms explain only a small proportion of cases. We report clinical and genetic results in a large family with late-onset autosomal dominant PD. METHODS: Thirty-eight family members of a five-generation Northern German PD family underwent a detailed neurologic examination, and transcranial sonography was performed in fifteen of them. Comprehensive mutation analysis of known PD-causing genes and a genome-wide linkage analysis were performed. RESULTS: Late-onset definite PD was found in five subjects with a mean age at onset of 63 years. Another six individuals presented either with probable/possible PD or with subtle parkinsonian signs. Six members with a mean age of 79 years had an essential tremor phenotype. Mode of PD inheritance was compatible with autosomal dominant transmission. One of three examined patients with definite PD demonstrated an increased area of substantia nigra hyperechogenicity upon transcranial sonography. Comprehensive linkage and mutational analysis excluded mutations in known PD-causing genes. Genome-wide linkage analysis suggested a putative disease gene in an 11.3-Mb region on chromosome 7p15-21.1 with a multipoint LOD score of 2.0. CONCLUSIONS: The findings in this family further demonstrate genetic heterogeneity in familial autosomal dominant late-onset PD.

[Summary and comments on the WSES guidelines on open abdomen in trauma and non-trauma patients]. / Zusammenfassung und Kommentar zur WSES-Leitlinie Abdomen apertum bei Trauma- und Nichttraumapatienten.

The first edition of the World Society of Emergency Surgeons (WSES) guidelines on the indications and treatment of open abdomen in trauma as well as in non-trauma patients was published at the end of 2018. Publications from 1980 to 2017 were included in the evaluation. Based on the GRADE system each publication was checked for its evidence and evaluated in a Delphi process. In this article the aspects of the guidelines are presented and commented on.

Vergence deficits in patients with cerebellar lesions.

The cerebellum is part of the cortico-ponto-cerebellar circuit for conjugate eye movements. Recent animal data suggest an additional role of the cerebellum for the control of binocular alignment and disconjugate, i.e. vergence eye movements. The latter is separated into two different components: fast vergence (to step targets) and slow vergence (to ramp and sinusoidal targets). The aim of this study was to investigate whether circumscribed cerebellar lesions affect these dynamic vergence eye movements. Disconjugate fast and slow vergence, conjugate smooth pursuit and saccades were binocularly recorded by a scleral search coil system in 20 patients with acute cerebellar lesions (all ischemic strokes except for one) and 20 age-matched healthy controls. Patients showed impairment of slow vergence while fast vergence was unaffected. Slow vergence gain to sinusoidal targets was significantly reduced, both in convergence and divergence direction. Divergence but not convergence velocity to ramp targets was reduced. Conjugate smooth pursuit eye movements to sinusoidal and to step-ramp targets were impaired. Patients had saccadic hypometria. All defects were particularly expressed in patients with vermis lesions. In contrast to recent animal data fast vergence was not impaired in any of our patient subgroups. We conclude that (i) the human cerebellum, in particular the vermis, is involved in the processing of dynamic vergence eye movements and (ii) cerebellar lesions elicit dissociable effects on fast and slow vergence.

fMRI evidence for sensorimotor transformations in human cortex during smooth pursuit eye movements.

Smooth pursuit eye movements (SP) are driven by moving objects. The pursuit system processes the visual input signals and transforms this information into an oculomotor output signal. Despite the object's movement on the retina and the eyes' movement in the head, we are able to locate the object in space implying coordinate transformations from retinal to head and space coordinates. To test for the visual and oculomotor components of SP and the possible transformation sites, we investigated three experimental conditions: (I) fixation of a stationary target with a second target moving across the retina (visual), (II) pursuit of the moving target with the second target moving in phase (oculomotor), (III) pursuit of the moving target with the second target remaining stationary (visuo-oculomotor). Precise eye movement data were simultaneously measured with the fMRI data. Visual components of activation during SP were located in the motion-sensitive, temporo-parieto-occipital region MT+ and the right posterior parietal cortex (PPC). Motor components comprised more widespread activation in these regions and additional activations in the frontal and supplementary eye fields (FEF, SEF), the cingulate gyrus and precuneus. The combined visuo-oculomotor stimulus revealed additional activation in the putamen. Possible transformation sites were found in MT+ and PPC. The MT+ activation evoked by the motion of a single visual dot was very localized, while the activation of the same single dot motion driving the eye was rather extended across MT+. The eye movement information appeared to be dispersed across the visual map of MT+. This could be interpreted as a transfer of the one-dimensional eye movement information into the two-dimensional visual map. Potentially, the dispersed information could be used to remap MT+ to space coordinates rather than retinal coordinates and to provide the basis for a motor output control. A similar interpretation holds for our results in the PPC region.

Distributed representations of the "preparatory set" in the frontal oculomotor system: a TMS study.

BACKGROUND: The generation of saccades is influenced by the level of "preparatory set activity" in cortical oculomotor areas. This preparatory activity can be examined using the gap-paradigm in which a temporal gap is introduced between the disappearance of a central fixation target and the appearance of an eccentric target. METHODS: Ten healthy subjects made horizontal pro- or antisaccades in response to lateralized cues after a gap period of 200 ms. Single-pulse transcranial magnetic stimulation (TMS) was applied to the dorsolateral prefrontal cortex (DLPFC), frontal eye field (FEF), or supplementary eye field (SEF) of the right hemisphere 100 or 200 ms after the disappearance of the fixation point. Saccade latencies were measured to probe the disruptive effect of TMS on saccade preparation. In six individuals, we gave realistic sham TMS during the gap period to mimic auditory and somatosensory stimulation without stimulating the cortex. RESULTS: TMS to DLPFC, FEF, or SEF increased the latencies of contraversive pro- and antisaccades. This TMS-induced delay of saccade initiation was particularly evident in conditions with a relatively high level of preparatory set activity: The increase in saccade latency was more pronounced at the end of the gap period and when participants prepared for prosaccades rather than antisaccades. Although the "lesion effect" of TMS was stronger with prefrontal TMS, TMS to FEF or SEF also interfered with the initiation of saccades. The delay in saccade onset induced by real TMS was not caused by non-specific effects because sham stimulation shortened the latencies of contra- and ipsiversive anti-saccades, presumably due to intersensory facilitation. CONCLUSION: Our results are compatible with the view that the "preparatory set" for contraversive saccades is represented in a distributed cortical network, including the contralateral DLPFC, FEF and SEF.

Transcranial sonography findings in a large family with homozygous and heterozygous PINK1 mutations.

OBJECTIVE: To investigate substantia nigra (SN) echogenicity in members of a family with homozygous and heterozygous PTEN induced kinase (PINK1) mutations with or without signs of Parkinson's disease (PD). METHODS: Transcranial sonography (TCS) was used to investigate 20 members of a family with PINK1 mutations, including four homozygous and 11 heterozygous mutation carriers and five individuals with no mutation. For comparison, a healthy control group of 18 subjects without a positive family history of PD (control group) and a healthy control group of 15 subjects with a positive family history of sporadic PD (relative group) were investigated. For statistical analysis, the larger area of the two SNs echogenicity (aSNmax) of each individual was selected. RESULTS: A significantly increased aSNmax was found for all subgroups compared with the control group. The group of homozygous carriers of a PINK1 mutation had a significantly increased aSNmax compared with all of the other subgroups, except the group of heterozygous mutation carriers. CONCLUSIONS: These findings in carriers of a PINK1 mutation are comparable with those in carriers of Parkin mutations and non-genetic PD. The increased aSNmax in family members without a mutation suggests an additional contributing factor independent of the PINK1 mutation that may also play a role in relatives of patients with sporadic PD.

Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.

Eye movement deviations, particularly deficits of initial sensorimotor processing and sustained pursuit maintenance, and antisaccade inhibition errors, are established intermediate phenotypes for psychotic disorders. We here studied eye movement measures of 849 participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study (schizophrenia N=230, schizoaffective disorder N=155, psychotic bipolar disorder N=206 and healthy controls N=258) as quantitative phenotypes in relation to genetic data, while controlling for genetically derived ancestry measures, age and sex. A mixed-modeling genome-wide association studies approach was used including ~4.4 million genotypes (PsychChip and 1000 Genomes imputation). Across participants, sensorimotor processing at pursuit initiation was significantly associated with a single nucleotide polymorphism in IPO8 (12p11.21, P=8 × 10-11), whereas suggestive associations with sustained pursuit maintenance were identified with SNPs in SH3GL2 (9p22.2, P=3 × 10-8). In participants of predominantly African ancestry, sensorimotor processing was also significantly associated with SNPs in PCDH12 (5q31.3, P=1.6 × 10-10), and suggestive associations were observed with NRSN1 (6p22.3, P=5.4 × 10-8) and LMO7 (13q22.2, P=7.3x10-8), whereas antisaccade error rate was significantly associated with a non-coding region at chromosome 7 (P=6.5 × 10-9). Exploratory pathway analyses revealed associations with nervous system development and function for 40 top genes with sensorimotor processing and pursuit maintenance (P=4.9 × 10-2-9.8 × 10-4). Our findings suggest novel patterns of genetic variation relevant for brain systems subserving eye movement control known to be impaired in psychotic disorders. They include genes involved in nuclear trafficking and gene silencing (IPO8), fast axonal guidance and synaptic specificity (PCDH12), transduction of nerve signals (NRSN1), retinal degeneration (LMO7), synaptic glutamate release (SH3GL2), and broader nervous system development and function.

Dissociable cerebellar activity during spatial navigation and visual memory in bilateral vestibular failure.

OBJECTIVE: Spatial orientation and navigation depends on information from the vestibular system. Previous work suggested impaired spatial navigation in patients with bilateral vestibular failure (BVF). The aim of this study was to investigate event-related brain activity by functional magnetic resonance imaging (fMRI) during spatial navigation and visual memory tasks in BVF patients. METHODS: Twenty-three BVF patients and healthy age- and gender matched control subjects performed learning sessions of spatial navigation by watching short films taking them through various streets from a driver's perspective along a route to the Cathedral of Cologne using virtual reality videos (adopted and modified from Google Earth). In the scanner, participants were asked to respond to questions testing for visual memory or spatial navigation while they viewed short video clips. From a similar but not identical perspective depicted video frames of routes were displayed which they had previously seen or which were completely novel to them. RESULTS: Compared with controls, posterior cerebellar activity in BVF patients was higher during spatial navigation than during visual memory tasks, in the absence of performance differences. This cerebellar activity correlated with disease duration. CONCLUSIONS: Cerebellar activity during spatial navigation in BVF patients may reflect increased non-vestibular efforts to counteract the development of spatial navigation deficits in BVF. Conceivably, cerebellar activity indicates a change in navigational strategy of BVF patients, i.e. from a more allocentric, landmark or place-based strategy (hippocampus) to a more sequence-based strategy. This interpretation would be in accord with recent evidence for a cerebellar role in sequence-based navigation.

Perilymph fistula associated with pulse-synchronous eye oscillations.

Three-dimensional eye movements (scleral search coil system) were recorded in a patient with a surgically acquired perilymph fistula of the left horizontal semicircular canal. Spontaneous horizontal pendular nystagmus was found to be related to the heart rate and may be caused by pressure transfer of blood pulses to the labyrinth. In addition, a contralesional horizontal jerk nystagmus was elicited by Valsalva maneuver, indicating that Ewald's first law may not only be valid for excitation but also for inhibition.

Visual search in patients with left visual hemineglect.

In patients with hemi-spatial neglect eye movement patterns during visual search reflect not only inattention for the contralesional hemi-field, but interacting deficits of multiple visuo-spatial and cognitive functions, even in the ipsilesional hemi-field. Evidence for these deficits is presented from the literature and from saccadic scan-path analysis during feature and conjunction search in 10 healthy subjects and in 10 patients with manifest or recovered left visual neglect due to right-hemispheric stroke. Deficits include (1) a rightward shift of spatial representation, (2) deficient spatial working memory and failure of systematic search strategies, leading to multiple re-fixations, more after frontal lesions, and (3) a reduced spotlight of attention and a deficient pop-out effect of color, more after temporo-parietal lesions.

Soluble intercellular adhesion molecule-1 in patients with lung cancer and benign lung diseases.

Intercellular adhesion molecule-1 (ICAM-1) expression correlates with tumour progression in patients with malignant melanoma or renal cell carcinoma. To assess the value of soluble ICAM-1 (sICAM-1) for lung cancer patients, sICAM-1 was determined by means of an enzyme-linked immunosorbent assay. Sera from 147 patients with lung cancer, from 75 patients with benign lung diseases and from 108 healthy adults were investigated for sICAM-1 expression. Significant differences in sICAM-1 levels were detected in lung cancer patients (387 +/- 176 ng/ml) and patients with benign lung diseases (365 +/- 110 ng/ml) compared to the group of healthy adults (310 +/- 90 ng/ml). There was no difference in sICAM-1 level among the subtypes of lung cancer. Advanced tumour stages and patients with progressive disease tended to be associated with higher sICAM-1 levels, the site of metastasis being relevant for the level attained. Patients with liver metastasis had the highest sICAM-1 levels (547 +/- 295 ng/ml) compared to patients with cerebral metastasis (317.8 +/- 92.2 ng/ml). An increase of sICAM-1 expression during the progression of the disease coincided with a poorer survival prognosis for the patients compared to patients with stable or falling sICAM-1 levels.

Challenges to Native American health care.

Native American health care programs face complex and unprecedented challenges resulting from the increased assumption of clinical operations by tribal authorities, shortfalls in Federal funding, modifications in state and Federal health and welfare programs, and intensifying involvement with managed care organizations. These challenges are further complicated by service populations that are increasing at a faster rate than the growth in funding. The authors conducted onsite surveys of 39 Native American health programs in 10 states in order to assess the organizational and management problems they faced. The trend toward transfer of health programs from the Indian Health Service to tribal operation seems likely to continue and accelerate. The survey results indicate that in order for programs to be effective in the long run, they will need to be guided by skilled managers able to adapt to these powerful changes in the health care environment.

[Lymph scintigraphy and pre- and intraoperative gamma probe measurements for localization of sentinel lymph nodes (SLN) in breast cancer]. / Lymphszintigraphie sowie prä- und intraoperative Sondenmessung zur Darstellung des Sentinel Lymph Node (SLN) beim Mammakarzinom.

UNLABELLED: Aim of this study was to prove the clinical value of nuclear medicine procedures to detect the sentinel lymph node (SLN) for SLN biopsy. METHODS: In 132 patients with breast cancer we performed lymph scintigraphy of the breast as well as both pre- and intraoperative gamma probe measurements correlating the results with the findings of histopathology. RESULTS: SLN were detectable in 62 of 110 patients according to a sensitivity of 56% when scanning was performed only at 1-2 h p.i. while the sensitivity increased to 86% (19 of 22 pts.) if sequential images were acquired up to 2 h p.i. One or more SLN were identified by a hand-held gamma probe transcutaneously prior to surgery in 96% (113 of 118 pts.) of the patients who showed up with no clinically suspected lymph node metastases. Intraoperatively, in additionally 2 patients the SLN could be found resulting in a sensitivity of 97% (115 of 118 pts.). In only 3 patients with clinically no tumor spread to axillary lymph nodes no SLN could be identified by the probe. Skip lesions, i.e. lymph node metastases in patients with tumor-free SLN, occurred in 2 cases: due to SLN biopsy in these patients lymph node staging was false negative compared to conventional staging by means of axillary lymph node dissection. CONCLUSION: The results demonstrate a high preoperative detection rate of SLN in patients with breast cancer using lymph scintigraphy and gamma probe measurements. Thus, nuclear medicine is capable of providing the basic requirements for SLN biopsy in the daily routine.

Survey of the taxonomic and tissue distribution of microsomal binding sites for the non-host selective fungal phytotoxin, fusicoccin.

The recent identification of the fusicoccin-binding protein (FCBP) in plasma membranes from monocotyledonous and dicotyledonous angiosperms has opened the basis for an elucidation of the toxin's mechanism(s) of action and indicated a widespread occurrence of the FCBP in plants. Results of a detailed taxonomic survey of fusicoccin-binding sites are reported. Binding sites were not found in prokaryotes, animal tissues, fungi and algae including the most direct extant ancestors of the land plants (Coleochaete). From the Psilotales (Psilophytatae) to the monocotyledonous angiosperms, all taxa analyzed possessed high-affinity microsomal fusicoccin-binding sites. A heterogeneous picture emerged for the Bryophyta. Anthoceros crispulus (Anthocerotae), the only hornwort available to study, lacked fusicoccin binding. Within the Hepaticae as well as the Musci, species lacking and species exhibiting toxin binding were found. The binding site thus seems to have emerged very early in the evolution of the land plants. The tissue distribution of fusicoccin-binding sites was studied in Vicia faba L. shoots. All tissues analyzed showed fusicoccin binding, although not to the same extent. On a per-cell basis, guard cells were found to contain, compared to mesophyll cells, a nine-fold higher number of binding sites. Based on cell surface area, the site density is by a factor of 32 higher in guard cells than in mesophyll cells. Tissue specific expression of the binding sites is suggested by these findings.

Effect of 4-aminopyridine on gravity dependence and neural integrator function in patients with idiopathic downbeat nystagmus.

Downbeat nystagmus (DBN) is a frequent sign in patients with cerebellar degeneration. It consists of an upward drift of the eye that does not depend on vertical head position (spontaneous drift, SD), a gravity-dependent component (GD), and a gaze-evoked drift reflecting gaze-holding impairment (deficient neural integrator function). The potassium-channel blocker 4-aminopyridine (4-AP) is reported to reduce DBN in patients with cerebellar atrophy but with little or no effect in patients with idiopathic DBN. We prospectively studied the effect of 4-AP on all three components in a large (n = 24) group of the clinically frequent idiopathic DBN. DBN was reduced by 22-31% when the head was off the head erect position. In contrast, there was no effect on vertical gaze-evoked drift. This indicates the therapeutic efficacy of 4-AP not only in patients with cerebellar atrophy but also in idiopathic DBN patients. This beneficial effect, which might be missed when gravity-dependent head positions are not tested, was not related to an improvement of gaze-holding deficit. We suggest it may be related to the restored inhibition of the overacting otolith-ocular reflex.