Altrenogest treatment reduces the stress response of three-year-old warmblood mares during their initial equestrian training.

Horse mares are frequently treated with the progestin altrenogest with the aim to suppress estrous behavior and its negative impact on equestrian performance. Progestogens, however, also have sedative effects in males, and females of different species. The aim of our study was therefore to investigate altrenogest-induced changes in the stress response of female horses during initial equestrian training. Three-yr-old Warmblood mares were randomly assigned to treatment with altrenogest (ALT; 0.044 mg/kg once daily; n = 6) or sunflower oil (CON; n = 5) for 12 wk during training. At predefined steps of the training program (free movement, lunging without and with side reins, lunging with saddle, mounting of a rider, free riding, riding by an unfamiliar rider) salivary cortisol concentration, and heart rate were determined from 60 min before to 120 min after training. The same procedures were performed during repeated gynecologic examinations and 2 novel object tests. Bodyweight and body condition scores (BCS) were assessed at 4-wk intervals. During all training units, salivary cortisol concentration and heart rate increased (P < 0.001), but the increase was smaller in group ALT mares (time x treatment P < 0.001). Gynecologic examinations and novel object tests induced a much smaller increase in cortisol and heart rate (P < 0.001) than equestrian training with no difference between groups ALT and CON. Initially, bodyweight, and BCS decreased during training. The subsequent increase was larger in group ALT vs CON (time x treatment P < 0.05). In conclusion, altrenogest reduced the stress response of 3-yr-old mares to equestrian training. The use of altrenogest during equestrian competitions should therefore be reconsidered.

Transient suppression of ovulatory ovarian function in pony mares after treatment with slow-release deslorelin implants.

Behavior during the estrous cycle of mares can affect their performance and therefore inhibition of cyclical ovarian activity is indicated. We hypothesized that implants containing the GnRH analog deslorelin downregulate GnRH receptors and inhibit ovulation in mares. The estrous cycles of Shetland mares were synchronized with 2 injections of a PGF2α analog. One day after the second injection (day 0), mares received 9.4 (group D1, n = 6) and 4.7 mg deslorelin (D2, n = 5) as slow-release implants or 1.25 mg short-acting deslorelin as a control (C, n = 5). Ultrasonography of the reproductive tract and ovaries and observation of estrous behavior and collection of blood samples for analysis of progesterone and LH concentrations were performed every second day until day 10 and thereafter at 5-d intervals. Stimulation tests with the GnRH-agonist buserelin were performed on days 10 and 45. Until day 50, there were less spontaneous ovulations in group D1 (P < 0.01) and estrous behavior was reduced in groups D1 and D2 compared with group C (P < 0.05). The time until first ovulation (D1 62.0 ± 8.6, D2 44.2 ± 14.1, C 22.2 ± 3.1 d, P < 0.05) and the number of days with estrous behavior (P < 0.05) differed among groups. On day 10 after treatment, a GnRH stimulation test revealed interactions between group and time (P < 0.001) in plasma LH concentration that were no longer detectable on day 45 after treatment. In conclusion, long-acting deslorelin implants result in a transient downregulation of pituitary GnRH receptors that is associated with inhibition of ovulation and estrous behavior in Shetland mares.

Doppler and Duplex Sonography for the Diagnosis of the Irreversible Cessation of Brain Function ("Brain Death"): Current Guidelines in Germany and Neighboring Countries.

Extra- and transcranial sonography of brain-supplying arteries is accepted worldwide in brain death protocols as a valid "ancillary" method of proving brain circulatory arrest. Color-coded duplex sonography and CT angiography have been newly incorporated in the fourth update of the German Medical Association's guidelines for the determination of the irreversible cessation of brain function ("brain death"), effective July 2015. The updated guidelines address in more detail the diagnostic procedures and the required qualifications of the examiners. The present article summarizes the guidelines and the recommendations regarding the application and documentation of ultrasound findings for the diagnosis of brain circulatory arrest in children and adults, as valid in Germany. The method, limitations, and procedure in the case of inconclusive findings are described. Age-related minimum values of mean arterial pressure for the diagnosis of cerebral circulatory arrest in children are presented. A concise overview of the respective regulations for the use of sonography for diagnosing brain death in other countries, especially in the countries neighboring Germany, is given.

Occurrence of Polyphenols, Organic Acids, and Sugars among Diverse Elderberry Genotypes Grown in Three Missouri (USA) Locations.

Elderberry (Sambucus spp.) is an emerging horticultural crop used in a variety of foods, wines, and dietary supplements. A better understanding of the elderberry juice complex including its putative health-promoting compounds in relation to genetic and environmental parameters is needed. A multi-location planting of nine elderberry genotypes was established in 2008 at three geographically-diverse sites in Missouri, USA. Fruits were harvested from replicated plots 2009-2011, frozen, and later prepared for laboratory analysis. Polyphenols, organic acids, and sugars were quantified by HPLC and the results evaluated for response to genotype, site, and year. The American genotypes 'Ocoee' and 'Ozark' were consistently higher in chlorogenic acids compared to other genotypes, whereas 'Ocoee' was significantly higher in rutin than 'Ozark'. The European 'Marge' was significantly higher in isoquercitrin and other flavonoids compared to most North American genotypes. Significant differences in polyphenols were also detected among sites and production years. Malic, citric, and tartaric acids varied significantly among genotypes, sites, and years, whereas succinic, shikimic, and fumaric acids generally did not. Levels of lactic, acetic, and propionic acids were negligible in most samples. The American genotype 'Ocoee' was higher in citric and tartaric acids, while lower in malic acid. The sugars glucose and fructose also responded significantly to genotype, site, and year. 'Ocoee', 'Ozark', and 'Marge' perform very well in Missouri horticulturally and appear to have additional potential as cultivars based on their unique juice characteristics.

Horticultural Performance of Eight American Elderberry Genotypes at Three Missouri Locations.

American elderberry (Sambucus nigra subsp. canadensis) is being increasingly cultivated in North America for its edible and medicinal fruit and flowers, yet remains largely undeveloped as a horticultural crop. Productive genotypes with desirable horticultural attributes, including disease and insect resistance, precocity, uniform fruit ripening, and large berry size are needed in order to advance the commercial production of elderberries. A four-year study of eight elderberry genotypes was established in 2008 at three diverse Missouri (USA) locations. Phenology, plant morphology, pest susceptibility, productivity, and fruit characteristics data were collected over three growing seasons, 2009-2011. Significant differences for most phenological, horticultural, and fruit juice characteristics were observed among the three sites, three years, and eight genotypes. The genotype 'Ozark' was the earliest to break bud, produced fruit with high levels of soluble solids, and out-yielded most other genotypes at the three sites over the three-year study. None of the new genotypes produced berries as large as or larger than the standard 'York' which is known for its large fruit. Some of the genotypes tested, especially 'Ozark' show promise as potential cultivars and as breeding stock for further development of elderberry as a commercially-viable horticultural crop.

'Marge': a European Elderberry for North American Producers.

Elderberries are being increasingly produced and consumed in North America for their edible and medicinal flowers and fruits. The American elderberry (Sambucus nigra subsp. canadensis) is native to, and most often cultivated in North America. The European elderberry (S. nigra subsp. nigra) has been developed into an economically-important horticultural crop in Europe, but most European cultivars do not perform well in the midwestern USA. The genotype S. nigra subsp. nigra 'Marge' is an open-pollinated seedling of S. nigra subsp. nigra 'Haschberg', which is one of the most popular elderberry cultivars grown in Europe. In a four-year study (one establishment year followed by 3 production years; 2008-2011) at three Missouri (USA) locations, 'Marge' significantly out-performed and out-yielded eight American elderberry genotypes within the same replicated field plots. Across 3 production years at all three sites, 'Marge' achieved budbreak later, flowered earlier, suffered less Eriophyid mite damage, was taller, produced larger berries, and yielded significantly greater amounts of fruit compared with all eight American elderberry genotypes in the study. At one site, 'Marge' produced three times the yield (1.89 kg/plant) compared with the next highest-producing American elderberry genotype (0.65 kg/plant). It is an exceptionally robust and drought-resistant elderberry. The phenotypic attributes of 'Marge' are similar to that of European elderberry except that it performs exceptionally well in the midwestern USA. DNA marker results, along with phenological and morphological characteristics, indicate that 'Marge' is a European elderberry (S. nigra subsp. nigra). As with most European genotypes, 'Marge' does not fruit on first-year wood, and will therefore require a different pruning regimen compared with American elderberry for success in North American production. We do not yet know how 'Marge' will perform outside the midwestern USA, but it is so productive, unique, and mite resistant, that it merits introduction as a cultivar.

Improvement of complex regional pain syndrome after plasmapheresis.

Complex regional pain syndrome is a severe complication following trauma that is associated with vasomotor, sudomotor and sensory disturbances in an affected limb or region of the body. The exact physiopathology is not fully understood yet. Recently, autoantibody findings suggested an immune-mediated physiopathology of the disease. We here describe two otherwise treatment-resistant patients with complex regional pain syndrome and high-titre beta2 adrenergic receptor autoantibodies, who did respond to plasmapheresis. Both patients showed strong improvement of pain and autonomic symptoms measured by impairment level sum score.

Shunt volume dynamics in stroke patients with patent foramen ovale.

A variation in right atrial and pulmonary arterial pressure might result in a shunt dynamic across a patent foramen ovale (PFO). In the present study we tested if peak exercise facilitates a restoration of right to left shunt (RLS) in stroke patients who demonstrated a functional PFO closure (no evidence of RLS across an initially demonstrated PFO). In stroke patients with PFO demonstrating a functional closure, the RLS was reassessed on peak exercise using contrast-enhanced transcranial Doppler sonography. The exercise procedure consisted of a cardiopulmonary exercise test with supplementary stress echocardiography for assessment of pulmonary circulation. Four stroke patients with initially PFO curtain pattern and a subsequent functional PFO closure (no evidence for RLS) underwent the procedure. In all four patients a RLS could be resurrected during peak physical exercise after a Valsalva strain. While in two patients peak exercise led to an RLS in a countable range of microembolic signals, in two patients a curtain pattern was obtained. One patient showed evidence for reoccurrence of RLS on peak exercise without a Valsalva strain. The patients with curtain pattern had a better peak exercise performance. Although the systolic pulmonary arterial pressure increased during exercise in all patients, there was no direct correlation with the detected RLS. After a functional PFO closure peak exercise combined with a Valsalva strain facilitates the reoccurrence of RLS in stroke patients.

7 Tesla MRI demonstrates vascular pathology in Balo's concentric sclerosis.

Baló's concentric sclerosis (BCS) is an inflammatory demyelinating disease related to multiple sclerosis; its underlying pathology remains unclear. At 7 T MRI in a 19-year-old female BCS patient, microhaemorrhages and ectatic veins were found in T2 hyperintense regions, features which have not been previously reported in conjunction with BCS, and these findings may support the view that vascular pathology plays a role in BCS. MRS data suggest that neuron loss and lipid turnover still took place months after a remission. Plasma exchange was effective in treating a relapse with severe motor deficits, and the off-label use of natalizumab was successful in maintaining remission in this patient.

Structural brain abnormalities in patients with Parkinson disease: a comparative voxel-based analysis using T1-weighted MR imaging and magnetization transfer imaging.

BACKGROUND AND PURPOSE: In PD, tissue damage occurs in specific cortical and subcortical regions. Conventional MR images have only limited capacity to depict these structural changes. The purpose of the current study was to investigate whether voxel-based MT imaging could indicate structural abnormalities beyond atrophy measurable with T1-weighted MR imaging. MATERIALS AND METHODS: Thirty-six patients with PD without dementia (9 in H&Y stage 1, thirteen in H&Y 2, eleven in H&Y 3, three in H&Y 4) and 23 age-matched control subjects were studied with T1-weighted MR imaging and MT imaging. Voxel-based analyses of T1-weighted MR imaging was performed to investigate brain atrophy, while MT imaging was used to study abnormalities within existing tissue. Modulated GM and WM probability maps, sensitive to volume, and nonmodulated maps, indicative of tissue density, were obtained from T1-weighted MR imaging. Effects seen on MTR images, but absent on density maps, were attributed to damage of existing tissue. RESULTS: Contrary to T1-weighted MR imaging, MT imaging was sensitive to the progression of brain pathology of the neocortex and paraventricular WM. MTR images and T1-based volume images, but not density images, showed a progression of disease in the olfactory cortex, indicating the occurrence of atrophy as well as damage to existing tissue in this region. MTR images revealed bilateral damage to the SN, while T1-weighted MR imaging only showed left-sided abnormalities. CONCLUSIONS: The findings suggest that voxel-based MT imaging permits a whole-brain unbiased investigation of CNS structural integrity in PD and may be a valuable tool for identifying structural damage occurring without or before measurable atrophy.

Effects of a flexibility and relaxation programme, walking, and nordic walking on Parkinson's disease.

Symptoms of Parkinson's disease (PD) progress despite optimized medical treatment. The present study investigated the effects of a flexibility and relaxation programme, walking, and Nordic walking (NW) on walking speed, stride length, stride length variability, Parkinson-specific disability (UPDRS), and health-related quality of life (PDQ 39). 90 PD patients were randomly allocated to the 3 treatment groups. Patients participated in a 6-month study with 3 exercise sessions per week, each lasting 70 min. Assessment after completion of the training showed that pain was reduced in all groups, and balance and health-related quality of life were improved. Furthermore, walking, and Nordic walking improved stride length, gait variability, maximal walking speed, exercise capacity at submaximal level, and PD disease-specific disability on the UPDRS in addition. Nordic walking was superior to the flexibility and relaxation programme and walking in improving postural stability, stride length, gait pattern and gait variability. No significant injuries occurred during the training. All patients of the Nordic walking group continued Nordic walking after completing the study.

[Cognitive deterioration after cardiosurgery]. / Kognitive Störungen nach kardiochirurgischen Eingriffen.

Over 100,000 heart surgeries are performed in Germany annually. Although severe neurological complications like ischaemic strokes have meanwhile become rare occurrences, subtle neuropsychological changes are still frequently recognized after major heart surgeries. The hitherto unsolved problem of postoperative cognitive decline (POCD) is portrayed in this article. Multifactorial aetiologies including microembolism and preoperative risk factors are supposed to play a significant role in POCD. A variety of neuroprotective strategies such as intraoperative microemboli filtration have been suggested to minimize cerebral risks. The utility of neuroprotective methods has recently been verified in randomized studies.

Frequency of Fabry disease in patients with small-fibre neuropathy of unknown aetiology: a pilot study.

BACKGROUND: Early occurrence of small-fibre neuropathy (SFN) is a common feature of Fabry disease (FD) - an X-linked storage disorder caused by reduced activity of the α-galactosidase A (α-GAL). Although SFN may result from different disorders, the cause is often unclear. Therefore, we investigated the frequency of FD in patients with SFN of unknown aetiology. METHODS: Patients with idiopathic SFN, established by sensory quantitative testing and/or skin biopsy, were examined for mutations in the α-GAL gene. Where mutations in the α-GAL gene were identified, levels of globotriaosylceramide (Gb(3)) were measured in urine and blood and the α-GAL activity was evaluated. When new mutations were detected, a diagnostic work-up was performed as well as a Gb(3) accumulation in the skin, lyso-Gb(3) in blood and Gb(3)_24 in urine were proved. RESULTS: Twenty-four of 29 eligible patients were enrolled in the study. Mutations in the α-GAL gene were observed in five patients. A typical mutation for FD (c.424T>C, [C142R]) was detected in one patient. In four patients, a complex intronic haplotype within the α-GAL gene (IVS0-10C>T [rs2071225], IVS4-16A>G [rs2071397], IVS6-22C>T [rs2071228]) was identified. The relevance of this haplotype in the pathogenesis of FD remains unclear until now. However, these patients showed increased concentrations of Gb(3) and/or lyso-Gb(3), while no further manifestations for FD could be proved. CONCLUSIONS: Fabry disease should be considered in patients with SFN of unknown aetiology, and screening for FD should be included in the diagnostic guidelines for SFN. The significance of the intronic haplotype regarding SFN needs further evaluation.

Anti-SOX1 antibodies in patients with paraneoplastic and non-paraneoplastic neuropathy.

Anti-SOX1 antibodies have been described to be positive in patients with paraneoplastic Lambert-Eaton myasthenic syndrome and, in a lower amount, in patients with anti-Hu positive paraneoplastic neurological syndromes, and with SCLC alone, respectively. We found 5/32 patients with paraneoplastic neuropathy and, surprisingly, 4/22 patients with neuropathy of unknown origin positive for anti-SOX1 antibodies, whereas no patient with inflammatory neuropathy and no healthy controls showed any reactivity (p=0.007). All patients with neuropathy of unknown origin where followed up for four years without diagnosis of a tumour so far. Anti-SOX1 antibodies are associated with paraneoplastic neuropathies and may define another group of non-paraneoplastic, immune-mediated neuropathies.

Modeling variance structure of body shape traits of Lipizzan horses.

Heterogeneity of variance of growth traits over age is a common issue in estimating genetic parameters and is addressed in this study by selecting appropriate variance structure models for additive genetic and environmental variances. Modeling and partitioning those variances connected with analyzing small data sets were demonstrated on Lipizzan horses. The following traits were analyzed: withers height, chest girth, and cannon bone circumference. The measurements were taken at birth, and at approximately 6, 12, 24, and 36 mo of age of 660 Lipizzan horses born in Croatia between 1948 and 2000. The corresponding pedigree file consisted of 1,458 horses. Sex, age of dam, and stud-year-season interaction were considered fixed effects; additive genetic and permanent environment effects were defined as random. Linear adjustments of age at measuring were done within measuring groups. Maternal effects were included only for measurements taken at birth and at 6 mo. Additive genetic variance structures were modeled by using uniform structures or structures based on polynomial random regression. Environmental variance structures were modeled by using one of the following models: unstructured, exponential, Gaussian, or combinations of identity or diagonal with structures based on polynomial random regression. The parameters were estimated by using REML. Comparison and fits of the models were assessed by using Akaike and Bayesian information criteria, and by checking graphically the adequacy of the shape of the overall (phenotypic) and component (additive genetic and environmental) variance functions. The best overall fit was obtained from models with unstructured error variance. Compared with the model with uniform additive genetic variance, models with structures based on random regression only slightly improved overall fit. Exponential and Gaussian models were generally not suitable because they do not accommodate adequately heterogeneity of variance. Using the unstructured error variance model, the heritability estimates ranged from 0.17 to 0.33 for withers height, 0.07 to 0.27 for chest girth, and 0.14 to 0.30 for cannon bone circumference. This study demonstrated the necessity of accounting for heterogeneity of variances and covariances for body shape traits in Lipizzan horses, and possible difficulties in estimating variance and covariance components when applying more complicated structure models on a small data set. The choice of models depends not only on overall fit but also on the fit of genetic and environmental components.

A simultaneous EEG and transcranial Doppler technique to investigate the neurovascular coupling in the human visual cortex.

Due to lacking energy stores, high energy consumption and dependency on a strict aerobic glycolysis, the brain is very dependent on an adequate blood supply of active neurons. Adequate regulation of the functionally induced local cerebral blood flow is assured by neurovascular coupling. Our understanding of its role in different disease processes has improved considerably in the last few years. Consequently, a diagnostic tool is needed which allows an easy and cost-effective investigation of the coupling in clinical conditions. A combined EEG and Doppler technique might be suitable in this regard. This review gives a short overview of the neurophysiological background and the techniques, before validation studies and first clinical applications are addressed.

Severity of coronary artery disease but not degree of coronary stenosis is correlated to cerebrovascular reactivity.

BACKGROUND: A decade difference in peak incidences of coronary and cerebral ischemia assumes a protection of the brain vasculature. Therefore, we hypothesize that early indicators of cerebrovascular disease such as parameters of the neurovascular coupling show a higher correlation to coronary artery disease than morphologic parameters. METHODS: Stenotic degree (%) of coronary arteries (RCA, LCA, LAD, RCX) was determined together with the Gensini score by angiography in 96 patients (80 men; 62 +/- 10 years), which were grouped according to disease severity (sclerosis, 1-vessel disease (VD), 2-VD, 3-VD). Presence of internal carotid artery stenosis and left ventricular ejection fraction (LVEF) were established with duplex sonography. Resting and visually evoked hemodynamic responses were measured with transcranial Doppler ultrasound in both posterior cerebral arteries and expressed in terms of control system parameters. These were gain, natural frequency, attenuation, and rate time. Group differences and correlations between stenosis and parameters of vasoreactivity were tested. RESULTS: Groups differed in stenotic degree of coronary arteries, Gensini score, LVEF, carotid artery stenosis, resting flow velocity, and evoked responses (gain, p < 0.005; attenuation, p < 0.05). Stenosis of each coronary artery and LVEF were correlated to carotid artery stenosis but no association was found to cerebrovascular parameters. Only severity of coronary artery disease and the Gensini score were associated with disturbed cerebrovascular reactivity. Carotid artery stenosis was associated with decreased cerebrovascular parameters (attenuation, p < 0.05; rate time, p < 0.01). CONCLUSIONS: Although atherosclerosis is a systemic disease our data support concepts of a heterogeneous distribution of the disease indicating protection of brain vessels.

Elevated B-cell activating factor BAFF, but not APRIL, correlates with CSF cerebellar autoantibodies in pediatric opsoclonus-myoclonus syndrome.

Childhood opsoclonus-myoclonus syndrome (OMS) occurs idiopathic or, in association with a neuroblastoma, as a paraneoplastic syndrome. Since autoantibodies were identified in some patients, an autoimmune pathogenesis has been suspected. While the newly discovered B-cell activating factors BAFF and APRIL are involved in systemic autoimmune diseases, their association with neuroimmunological diseases is hardly understood. We here investigated the BAFF and APRIL levels in serum and cerebrospinal fluid (CSF) of OMS patients and their correlation with surface-binding autoantibodies. BAFF and APRIL were both determined by ELISA, and autoantibodies to cerebellar granular neurons (CGN) have been investigated by flow cytometry in 17 OMS patients, 16 neuroblastoma (NB) patients, 13 controls and 11 children with inflammatory neurological diseases (IND). BAFF, but no APRIL, was elevated in the CSF of OMS children and IND children. However, in contrast to IND patients, OMS patients did not have a blood-brain-barrier disturbance, indicating that BAFF was produced intrathecally in OMS patients, but not in IND patients. CSF BAFF levels showed a correlation with CSF CGN autoantibodies (r(2)=0.58, p<0.05). These data indicate that an activated B-cell system in the cerebrospinal fluid is involved in the pathogenesis of OMS, and BAFF may be a candidate parameter for the activation of B-cell immune system.

Autoregulative function in the brain in an endotoxic rat shock model.

OBJECTIVE AND DESIGN: Autoregulative function in the brain gets relevant in hypodynamic conditions of a sepsis syndrome. We investigated the temporal pattern and dose dependent effects of LPS-induced shock on autoregulative function in rats. MATERIAL AND SUBJECTS: Chloralose-anesthetized and mechanically ventilated male CD-rats (n = 30). TREATMENT: Animals were subjected to vehicle, 1 or 5 mg/kg b.w. lipopolysaccharide (LPS) from E. coli given intravenously. METHODS: Autoregulative function was tested repeatedly with a carotid compression technique assessing the transient hyperemic response ratio (THRR) in the cortex with laser Doppler flowmetry up to 270 min. THRR data from exsanguination experiments served as controls. RESULTS: Despite lower blood pressure levels in the high dose group (control: 114 +/- 7 mmHg; 1 mg/kg LPS group: 82 +/- 16 mmHg; 5 mg/kg LPS group: 62 +/- 16 mmHg; p < 0.05) progressive cerebral hyperemia occurred similarly in both groups. Compared to exsanguinations experiments autoregulative compensation for lower blood pressure levels was lacking in the high LPS dose group at the end of experiments. CONCLUSIONS: Cerebral autoregulation was affected by LPS-induced shock supporting the notion of vasoregulative failure in endotoxic shock.