Advanced diffusion MRI provides evidence for altered axonal microstructure and gradual peritumoral infiltration in GBM in comparison to brain metastases.

PURPOSE: In contrast to peritumoral edema in metastases, GBM is histopathologically characterized by infiltrating tumor cells within the T2 signal alterations. We hypothesized that depending on the distance from the outline of the contrast-enhancing tumor we might reveal imaging evidence of gradual peritumoral infiltration in GBM and predominantly vasogenic edema around metastases. We thus investigated the gradual change of advanced diffusion metrics with the peritumoral zone in metastases and GBM. METHODS: In 30 patients with GBM and 28 with brain metastases, peritumoral T2 hyperintensity was segmented in 33% partitions based on the total volume beginning at the enhancing tumor margin and divided into inner, middle and outer zones. Diffusion Tensor Imaging (DTI)-derived fractional anisotropy and mean diffusivity as well as Diffusion Microstructure Imaging (DMI)-based parameters Dax-intra, Dax-extra, V­CSF and V-intra were employed to assess group-wise differences between inner and outer zones as well as within-group gradients between the inner and outer zones. RESULTS: In metastases, fractional anisotropy and Dax-extra were significantly reduced in the inner zone compared to the outer zone (FA p = 0.01; Dax-extra p = 0.03). In GBM, we noted a reduced Dax-extra and significantly lower intraaxonal volume fraction (Dax-extra p = 0.008, V­intra p = 0.006) accompanied by elevated axial intraaxonal diffusivity in the inner zone (p = 0.035). Between-group comparison of the outer to the inner zones revealed significantly higher gradients in metastases over GBM for FA (p = 0.04) as well as the axial diffusivity in the intra- (p = 0.02) and extraaxonal compartment (p < 0.001). CONCLUSION: Our findings provide evidence of gradual alterations within the peritumoral zone of brain tumors. These are compatible with predominant (vasogenic) edema formation in metastases, whereas our findings in GBM are in line with an axonal destructive component in the immediate peritumoral area and evidence of tumor cell infiltration with accentuation in the tumor's vicinity.

FLAIR vascular hyperintensities in acute ICA and MCA infarction: a marker for mismatch and stroke severity?.

BACKGROUND: Vascular hyperintensities of brain-supplying arteries on stroke FLAIR MRI are common and represent slow flow or stasis. FLAIR vascular hyperintensities (FVH) are discussed as an independent marker for cerebral hypoperfusion, but the impact on infarct size and clinical outcome in acute stroke patients is controversial. This study evaluates the association of FVH with infarct morphology, clinical stroke severity and infarct growth in patients with symptomatic internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion. METHODS: MR images of 84 patients [median age 73 years (IQR 65-80), 56.0% male, median NIHSS 7 (IQR 3-13)] with acute stroke due to symptomatic ICA or MCA occlusion or stenosis were reviewed. Vessel occlusions were identified by MRA time of flight and graded with the TIMI score. Diffusion and perfusion deficit volumes on admission and FLAIR lesion volumes on discharge were assessed. The presence and number of FVH were evaluated according to MCA-ASPECT areas, and associations with MR volumes, morphology of infarction, recanalization status, presence of white matter disease and hemorrhagical transformation as well as with stroke severity (NIHSS), stroke etiology and thrombolysis rate were analyzed. RESULTS: FVH were detectable in 75 (89.3%) patients. The median number of FVH was 4 (IQR 2-7). Patients with FVH >4 presented with more severe strokes due to NIHSS (p = 0.021), had larger initial DWI lesions (p = 0.008), perfusion deficits (p = 0.001) and mismatch volumes/ratios (p = 0.005). The final infarct volume was larger (p = 0.005), and hemorrhagic transformation was more frequent (p = 0.029) in these patients. CONCLUSIONS: The presence of FVH indicates larger ischemic areas in brain parenchyma predominantly caused by proximal anterior circulation vessel occlusion. A high count of FVH might be a further surrogate marker for initial ischemic mismatch and stroke severity.

Spinal diffusion tensor tractography for differentiation of intramedullary tumor-suspected lesions.

BACKGROUND AND PURPOSE: Primary MRI diagnosis of spinal intramedullary tumor-suspected lesions can be challenging and often requires spinal biopsy or resection with a substantial risk of neurological deficits. We evaluated whether Diffusion Tensor Imaging (DTI) tractography can facilitate the differential diagnosis. MATERIALS AND METHODS: Twenty-five consecutive patients with an intramedullary tumor-suspected lesion considered for spinal surgery were studied with a Diffusion-weighted multi-shot read out segmented EPI sequence (RESOLVE). White matter tracts ("streamlines") were calculated using the FACT algorithm and visually co-registered to a T2-weighted 3D sequence. The fused images were assessed concerning spinal streamline appearance as normal, displaced or terminated. Definite diagnosis was verified by histological analysis or further clinical work-up. RESULTS: All patients with normal appearing streamlines (n=6) showed an acute inflammatory demyelinating pathology in the further clinical work-up. In 10 patients streamline displacing lesions were found from which 5 patients underwent a surgical treatment with histologically confirmed low-grade tumors like ependymomas and pilocytic astrocytomas. In nine patients streamlines were terminated, from which 6 patients received a histology proven diagnoses with a more heterogenous spectrum (3 cases of high grade tumor, 1 case of low grade tumor with intralesional hemorrhage and 2 cases with gliosis but no tumor cells). CONCLUSION: Using multi-shot DTI spinal tractography acute inflammatory lesions can be differentiated from other tumorous intramedullary lesions. The entity diagnosis of spinal tumors seems to be more challenging, primarily due to the variety of factors like invasivity, expansion or intralesional hemorrhage.

The 'Toolbox' of strategies for managing Haemonchus contortus in goats: What's in and what's out.

A dynamic and innovative approach to managing the blood-consuming nematode Haemonchus contortus in goats is critical to crack dependence on veterinary anthelmintics. H. contortus management strategies have been the subject of intense research for decades, and must be selected to create a tailored, individualized program for goat farms. Through the selection and combination of strategies from the Toolbox, an effective management program for H. contortus can be designed according to the unique conditions of each particular farm. This Toolbox investigates strategies including vaccines, bioactive forages, pasture/grazing management, behavioural management, natural immunity, FAMACHA, Refugia and strategic drenching, mineral/vitamin supplementation, copper Oxide Wire Particles (COWPs), breeding and selection/selecting resistant and resilient individuals, biological control and anthelmintic drugs. Barbervax(®), the ground-breaking Haemonchus vaccine developed and currently commercially available on a pilot scale for sheep, is prime for trialling in goats and would be an invaluable inclusion to this Toolbox. The specialised behaviours of goats, specifically their preferences to browse a variety of plants and accompanying physiological adaptations to the consumption of secondary compounds contained in browse, have long been unappreciated and thus overlooked as a valuable, sustainable strategy for Haemonchus management. These strategies are discussed in this review as to their value for inclusion into the 'Toolbox' currently, and the future implications of ongoing research for goat producers. Combining and manipulating strategies such as browsing behaviour, pasture management, bioactive forages and identifying and treating individual animals for haemonchosis, in addition to continuous evaluation of strategy effectiveness, is conducted using a model farm scenario. Selecting strategies from the Toolbox, with regard to their current availability, feasibility, economical cost and potential ease of implementation depending on the systems of production and their complementary nature, is the future of managing H. contortus in farmed goats internationally and maintaining the remaining efficacy of veterinary anthelmintics.

Variation in immune responsiveness of sheep to the antigens of intestinal nematodes and blowfly larvae.

The total and IgG1 antibody responses to the intestinal nematode parasites Haemonchus contortus and Trichostrongylus colubriformis were measured in the serum of 160 lambs, 4 months of age. These antibodies had developed as the result of natural exposure to the parasites on pasture. Three sires were examined and strong sire effects on half-sib progeny were found. Plotting of ELISA antibody results in two dimensions revealed clustering of responses within sire groups. Bimodal antibody distributions were also observed within sire groups and the whole population for T. colubriformis. A bimodal distribution of antibodies to H. contortus was found for one sire group but not for the whole population. The injection of blowfly larvae (Lucilia cuprina) extract into 42/160 lambs at a later age (12 months) was followed by increased antibodies to L. cuprina and an apparent increase in antibodies to T. colubriformis. A bimodal distribution for antibodies to L. cuprina was found in one sire group and in the whole population. These bimodal distributions of antibodies to L. cuprina did not coincide with the distribution of antibodies to T. colubriformis or H. contortus, measured on the same serum samples. It was concluded that high and low responder sire groups could be differentiated in lamb populations for all three parasites. These effects persisted during lamb maturation and appeared to be genetic effects. Finally, cross-reacting antibodies between L. cuprina and T. colubriformis appear to be stimulated by injection of L. cuprina antigens.

[Nausea and vomiting in the postoperative phase. Expert- and evidence-based recommendations for prophylaxis and therapy]. / Ubelkeit und Erbrechen in der postoperativen Phase. Experten- und evidenzbasierte Empfehlungen zu Prophylaxe und Therapie.

There are no consensus guidelines for the management of postoperative nausea and vomiting (PONV) in German speaking countries. This meeting was intended to develop such guidelines on which individual health care facilities can derive their specific standard operating procedures (SOPs). Anesthesiologists reviewed published literature on key topics which were subsequently discussed during two meetings. It was emphasized that recommendations were based on the best available evidence. The clinical relevance of individual risk factors should be viewed with caution since even well proven risk factors, such as the history of PONV, do not allow the identification of patients at risk for PONV with a satisfactory sensitivity or specificity. A more useful approach is the use of simplified risk scores which consider the presence of several risk factors simultaneously. Most individual antiemetic interventions for the prevention of PONV have comparable efficacy with a relative risk reduction of about 30%. This appears to be true for total intravenous anesthesia (TIVA) as well as for dexamethasone and other antiemetics; assuming a sufficiently high, adequate and equipotent dosage which should be weight-adjusted in children. As the relative risk reduction is context independent and similar between the interventions, the absolute risk reduction of prophylactic interventions is mainly dependent on the patient's individual baseline risk. Prophylaxis is thus rarely warranted in patients at low risk, generally needed in patients with a moderate risk and should include a multimodal approach in patients at high risk for PONV. Therapeutic interventions of PONV should be administered promptly using an antiemetic which has not been used before. The group suggests algorithms where prophylactic interventions are mainly dependent on the patient's risk for PONV. These algorithms should provide evidence-based guidelines allowing the development of SOPs/policies which take local circumstances into account.

[The applicability of a detection method independent of a laboratory for progesterone in the blood plasma of mares (Hygia progesterone test)]. / Untersuchungen zur Anwendbarkeit eines laborunabhängigen Progesteron-Nachweisverfahrens im Blutplasma von Stuten (Hygia Progesteron-Test).

A rapid progesterone assay for cow's milk was checked as to whether it was applicable to mares' blood plasma. The "Hygia Progesterone-Test" is an on-farm test which serves for qualitative analysis. It is generally unusable for mares' plasma but sufficiently precise only in cases of larger or smaller progesterone levels. In cases of moderate amounts of progesterone the test is imprecise. The test can be carried out quickly and easily, but the preparation of blood samples takes more time than preparation of milk samples. The test can be recommended for usage in veterinary practice only, but not for animal owners.

[Double ovulation in mares. Clinical, hormone analytical and sonographic studies]. / Zur Doppelovulation bei Stuten. Klinische, hormonanalytische und sonographische Untersuchungen.

108 mares with a total of 135 oestrous cycles were examined. 30% of the mares showed development of double follicles, found by palpation and ultrasonography. Eight cases of double ovulation, four of them synchronous and four asynchronous, were examined closely. These cases of double ovulation showed different growth and different development of the follicular wall. This occurred at the same time in cases of synchronous double ovulation whereas it differed in case of asynchronous double ovulation. The later ovulating follicle was still growing while the first one had already burst. With both forms of double ovulation an equal concentration of progesterone was detected in peripheral blood. On the day of ovulation the rate of progesterone was low (1 ng/ml blood plasma) and it first started rising from the day +1 on. Double follicles matured slower than single follicles. Mares with synchronous double ovulation showed the typical oestrus behavior. This behavior was less distinct after the first ovulation in mares with asynchronous double ovulation. All four mares with asynchronous and two mares with synchronous double ovulation became pregnant. Twins did not occur. A possible relationship between double ovulation and twin pregnancy is discussed.

[Ovarian structure and function in the mare from the clinical viewpoint with special regard to ultrasonography]. / Ovaraufbau und Funktion bei der Stute aus klinischer Sicht unter besonderer Berücksichtigung der Ultrasonographie.

Ultrasonography is a good means of monitoring follicular development in the mare and allows objective observation and measurement of follicular growth as well as identification of corpora lutea and hematoma in the ovary. The significance of ultrasonography in this field lies in the specific anatomical structure of the mare's ovary and the different phenomena preceding and accompanying ovulation, which are described in this paper. The last part deals with the handling and use of ultrasonography.

The immunogenetics of resistance to Trichostrongylus colubriformis and Haemonchus contortus parasites in sheep.

Three possible immunogenetic markers for resistance to intestinal parasites in sheep have been studied. Allotypes of the major histocompatibility complex (MHC) of the sheep have been investigated as markers, using serological typing or gene probes, for associations between allotypes and resistance to parasites in selected high responder and low responder lines of sheep. Only the serologically-determined class I ovine leucocyte antigen (OLA) types SY 1a and SY 1b have been found to be consistently associated with increased resistance to Trichostrongylus colubriformis, but this association has not extended to the immunologically distinct Haemonchus contortus parasite. Gene probes of the sheep DRB, DQB and DQA MHC class II loci have detected animals with increased susceptibility to T. colubriformis. Eosinophilia was investigated as a marker and found to be associated with increased resistance to parasites in lines of Australian Merinos and New Zealand Romneys selected for resistance on the basis of low faecal egg count. Blood eosinophilia was distinct from eosinophil infiltration of the gut which was poorly associated with resistance. The mechanism of parasite resistance appeared to involve the release of vasoactive amines and leukotrienes into intestinal mucus, since the selected high responder sheep to T. colubriformis and H. contortus had significantly increased amounts of these agents in their gut mucus, compared with selected low responder or random-bred sheep. Antibodies to T. colubriformis and H. contortus have also been used as markers to select high responder sire groups of lambs in contact with the parasites, for the first time, at weaning. This assay had the advantage of detecting distinct antigens for the two parasites, which would allow resistance to the species of parasite to be selected in the lambs. Vaccines have been developed against H. contortus using 'novel' gut antigens from the parasite, but variable responsiveness of the host sheep seemed to result in varying degrees of protection which were stimulated by these vaccines.

The eosinophil leucocyte, a phenotypic marker of resistance to nematode parasites, is associated with calm behaviour in sheep.

The hypothesis that behaviour in sheep is influenced by resistance to infections with Trichostrongylus colubriformis and Haemonchus contortus was explored. Sheep were assessed phenotypically as resistant and susceptible in four ways and thereafter, the effect of resistance on several behavioural traits was measured in an arena test. The behavioural parameters recorded for each sheep were: approach/avoidance distance; travel; number of moves; and spread. Four phenotypic groups of sheep were set up each with two subgroups: ovine lymphocyte antigen (OLA) type (subgroups SY1a type vs other types); blood eosinophil leucocyte counts (high vs low); T. colubriformis and H. contortus serum antibodies (high vs low titres) and faecal egg count (FEC) (high vs low). Only the behavioural comparison between sheep with high versus low eosinophil leucocyte count showed consistent differences that were statistically significant, although other comparisons favoured associations between OLA type SY1a, low FEC and reduced approach/avoidance distance and/or locomotor behaviour. The eosinophil leucocyte association was established on two non-overlapping test populations of sheep, with mean eosinophil leucocyte counts of 3.19 x 10(5)/mL blood for high and 0.83 x 10(5)/mL blood for low subgroups; results were reproduced on five separate occasions over 6 weeks to detect differences as approach/avoidance distance (P < 0.01), travel (P < 0.01), number of moves (P < 0.01), and spread (P < 0.05). High eosinophilia correlated with low FEC for the infected sheep, which identified sheep that were resistant to parasites. We concluded, therefore, that the resistant sheep were more at ease with the environment of the test than were the sheep with low eosinophil leucocyte counts. The strong association between high eosinophil leucocyte counts and behaviour is consistent with other reports which suggest that retention of normal levels of circulating eosinophil leucocytes is associated with resistance to stress.

The PCR typing of MHC-DRB genes in the sheep using primers for an intronic microsatellite: application to nematode parasite resistance.

The strong association between polymorphisms in an intronic microsatellite and the coding sequences for (BoLA)-DRB3 genes, previously described for demonstrating alleles of class II major histocompatibility complex (MHC) in the cow, was examined in sheep to see if similar polymorphisms could be demonstrated in the DRB region of the MHC. The bovine primes LA53 and LA54, previously used to amplify the bovine DRB3 microsatellites, were used with DNA from Australian sheep, eight DRB alleles were identified by length polymorphisms of polymerase chain reaction (PCR) products amplified from the DRB microsatellite region. Incomplete amplification of both alleles was sometimes found for sheep DNA samples using bovine primers, so a modified primer (LA53b) was used, and found to amplify the microsatellite next to intron 2 of the MHC more reliably than the LA53 primer. Two additional primers (LA31 and LA32), used in amplification of the exon 2 region of bovine DRB3, were used in the sheep, and the PCR products were analysed by single-stranded conformation polymorphism (SSCP). These primers successfully amplified the variable region of the ovine DRB region coded by exon 2, and the SSCP technique demonstrated polymorphisms with sheep DNA. Family studies demonstrated the segregation of alleles, by amplification both of intronic microsatellites and of the exon 2 variable region. Close correspondence was found between the two regions for several alleles, suggesting that the intronic microsatellites were closely linked to DRB-variable region alleles. Three families of Merino sheep with different antibody responses to intestinal nematode parasites were examined. The sire group with the highest antibody levels possessed two microsatellite alleles of closely similar length (alleles 3 and 4) inherited from the sire and present in high frequency in the lambs. In contrast, the other two sires did not possess these two alleles and the alleles were in low frequency in their progeny. Further studies are required in unrelated sheep to confirm whether these two alleles are associated with resistance to nematode parasites.