Genetic background of lumbosacral transitional vertebrae in German shepherd dogs.

OBJECTIVES: Estimation of genetic parameters of lumbosacral transitional vertebrae based on data derived from radiographic screening of 27,597 German shepherd dogs. MATERIALS AND METHODS: Results of radiographic screening for lumbosacral transitional vertebrae classified according to a published scheme were collected. Obtained data were used for estimating variance components in single and multiple trait linear animal models to obtain heritabilities and additive genetic correlations for different types of lumbosacral transitional vertebrae. RESULTS: Estimations indicated a moderate heritability of lumbosacral transitional vertebrae of h2 = 0.27. Trait definitions reflecting the different types of lumbosacral transitional vertebrae revealed positive additive genetic correlations of rg  > 0.5 between those types usually categorised as pathologic. CLINICAL SIGNIFICANCE: Results of comprehensive genetic analyses enable the development of breeding measures against lumbosacral transitional vertebrae to reduce their prevalence and support management of potentially correlated diseases in German shepherd dogs.

[Innovative ultrasound-based diagnosis of renal tumors]. / Innovative Ultraschalldiagnostik bei Nierentumoren.

BACKGROUND: In Germany, renal tumours are detected earlier also due to advancing technology within ultrasound devices and its more widespread application. Ultrasound diagnosis is usually the first imaging procedure available to urologists. For all renal lesions larger than 1 cm in diameter, fat content can be revealed by quantitative measurements within CT/MRI diagnostic modalities to confirm the suspected diagnosis of angiomyolipoma, or in patients with potentially malignant renal lesions referral (with all the their imaging data) to the multidisciplinary tumour team. As a further step, biopsy may be indicated, especially in the case of inflammatory lesions or suspected lymphoma; otherwise patients with a solid tumour are treated within a tumour stage-appropriate urological therapy regime. RESULTS: Contrast-enhanced ultrasonography (CEUS) is currently unable to distinguish between benign and malignant renal tumours. Nevertheless, this noninvasive method is useful in everyday clinical practice: in excluding renal pseudolesions, in inflammatory lesions, for follow-up of traumatic pseudolesions, and for the differential diagnosis of atypical renal cyst diagnosis versus renal cancer. Contrast-enhanced sonography also reveals the microperfusion of kidney tumors, providing clues for distinguishing between clear cell and papillary types of renal cell carcinoma. The method is also utilised in CEUS-controlled biopsy procedures of renal lesions. CONCLUSIONS: Contrast-enhanced sonography augments CT/MRI imaging with real-time information on the perfusion of the kidney tumour and can be a therapy-relevant aid for the multidisciplinary cancer conference with the ultrasound examinations being presented as video clips for comment thereon.

Invited review: Genetics and claw health: Opportunities to enhance claw health by genetic selection.

Routine recording of claw health status at claw trimming of dairy cattle has been established in several countries, providing valuable data for genetic evaluation. In this review, we examine issues related to genetic evaluation of claw health; discuss data sources, trait definitions, and data validation procedures; and present a review of genetic parameters, possible indicator traits, and status of genetic and genomic evaluations for claw disorders. Different sources of data and traits can be used to describe claw health. Severe cases of claw disorders can be identified by veterinary diagnoses. Data from lameness and locomotion scoring, activity information from sensors, and feet and leg conformation traits are used as auxiliary traits. The most reliable and comprehensive information is data from regular hoof trimming. In genetic evaluation, claw disorders are usually defined as binary traits, based on whether or not the claw disorder was present (recorded) at least once during a defined time period. The traits can be specific disorders, composite traits, or overall claw health. Data validation and editing criteria are needed to ensure reliable data at the trimmer, herd, animal, and record levels. Different strategies have been chosen, reflecting differences in herd sizes, data structures, management practices, and recording systems among countries. Heritabilities of the most commonly analyzed claw disorders based on data from routine claw trimming were generally low, with ranges of linear model estimates from 0.01 to 0.14, and threshold model estimates from 0.06 to 0.39. Estimated genetic correlations among claw disorders varied from -0.40 to 0.98. The strongest genetic correlations were found among sole hemorrhage (SH), sole ulcer (SU), and white line disease (WL), and between digital/interdigital dermatitis (DD/ID) and heel horn erosion (HHE). Genetic correlations between DD/ID and HHE on the one hand and SH, SU, or WL on the other hand were, in most cases, low. Although some of the studies were based on relatively few records and the estimated genetic parameters had large standard errors, there was, with some exceptions, consistency among studies. Various studies evaluate the potential of various data soureces for use in breeding. The use of hoof trimming data is recommended for maximization of genetic gain, although auxiliary traits, such as locomotion score and some conformation traits, may be valuable for increasing the reliability of genetic evaluations. Routine genetic evaluation of direct claw health has been implemented in the Netherlands (2010); Denmark, Finland, and Sweden (joint Nordic evaluation; 2011); and Norway (2014), and other countries plan to implement evaluations in the near future.

Invited review: Opportunities for genetic improvement of metabolic diseases.

Metabolic disorders are disturbances to one or more of the metabolic processes in dairy cattle. Dysfunction of any of these processes is associated with the manifestation of metabolic diseases or disorders. In this review, data recording, incidences, genetic parameters, predictors, and status of genetic evaluations were examined for (1) ketosis, (2) displaced abomasum, (3) milk fever, and (4) tetany, as these are the most prevalent metabolic diseases where published genetic parameters are available. The reported incidences of clinical cases of metabolic disorders are generally low (less than 10% of cows are recorded as having a metabolic disease per herd per year or parity/lactation). Heritability estimates are also low and are typically less than 5%. Genetic correlations between metabolic traits are mainly positive, indicating that selection to improve one of these diseases is likely to have a positive effect on the others. Furthermore, there may also be opportunities to select for general disease resistance in terms of metabolic stability. Although there is inconsistency in published genetic correlation estimates between milk yield and metabolic traits, selection for milk yield may be expected to lead to a deterioration in metabolic disorders. Under-recording and difficulty in diagnosing subclinical cases are among the reasons why interest is growing in using easily measurable predictors of metabolic diseases, either recorded on-farm by using sensors and milk tests or off-farm using data collected from routine milk recording. Some countries have already initiated genetic evaluations of metabolic disease traits and currently most of these use clinical observations of disease. However, there are opportunities to use clinical diseases in addition to predictor traits and genomic information to strengthen genetic evaluations for metabolic health in the future.

Maternal Lineage of Warmblood Mares Contributes to Variation of Gestation Length and Bias of Foal Sex Ratio.

Maternal lineage influences performance traits in horses. This is probably caused by differences in mitochondrial DNA (mtDNA) transferred to the offspring via the oocyte. In the present study, we investigated if reproductive traits with high variability-gestation length and fetal sex ratio-are influenced by maternal lineage. Data from 142 Warmblood mares from the Brandenburg State Stud at Neustadt (Dosse), Germany, were available for the study. Mares were grouped according to their maternal lineage. Influences on the reproduction parameters gestation length and sex ratio of offspring were analyzed by simple and multiple analyses of variance. A total of 786 cases were included. From the 142 mares, 119 were assigned to six maternal lineages with n≥10 mares per lineage, and 23 mares belonged to smaller maternal lineages. The mean number of live foals produced per mare was 4.6±3.6 (±SD). Live foal rate was 83.5%. Mean gestation length was 338.5±8.9 days (±SD) with a range of 313 to 370 days. Gestation length was affected by maternal lineage (p<0.001). Gestation length was also significantly influenced by the individual mare, age of the mare, year of breeding, month of breeding and sex of the foal (p<0.05). Of the 640 foals born alive at term, 48% were male and 52% female. Mare age group and maternal lineage significantly influenced the sex ratio of the foals (p<0.05). It is concluded that maternal lineage influences reproductive parameters with high variation such as gestation length and foal sex ratio in horses. In young primiparous and aged mares, the percentage of female offspring is higher than the expected 1:1 ratio.

Invited review: overview of new traits and phenotyping strategies in dairy cattle with a focus on functional traits.

For several decades, breeding goals in dairy cattle focussed on increased milk production. However, many functional traits have negative genetic correlations with milk yield, and reductions in genetic merit for health and fitness have been observed. Herd management has been challenged to compensate for these effects and to balance fertility, udder health and metabolic diseases against increased production to maximize profit without compromising welfare. Functional traits, such as direct information on cow health, have also become more important because of growing concern about animal well-being and consumer demands for healthy and natural products. There are major concerns about the impact of drugs used in veterinary medicine on the spread of antibiotic-resistant strains of bacteria that can negatively impact human health. Sustainability and efficiency are also increasingly important because of the growing competition for high-quality, plant-based sources of energy and protein. Disruptions to global environments because of climate change may encourage yet more emphasis on these traits. To be successful, it is vital that there be a balance between the effort required for data recording and subsequent benefits. The motivation of farmers and other stakeholders involved in documentation and recording is essential to ensure good data quality. To keep labour costs reasonable, existing data sources should be used as much as possible. Examples include the use of milk composition data to provide additional information about the metabolic status or energy balance of the animals. Recent advances in the use of mid-infrared spectroscopy to measure milk have shown considerable promise, and may provide cost-effective alternative phenotypes for difficult or expensive-to-measure traits, such as feed efficiency. There are other valuable data sources in countries that have compulsory documentation of veterinary treatments and drug use. Additional sources of data outside of the farm include, for example, slaughter houses (meat composition and quality) and veterinary labs (specific pathogens, viral loads). At the farm level, many data are available from automated and semi-automated milking and management systems. Electronic devices measuring physiological status or activity parameters can be used to predict events such as oestrus, and also behavioural traits. Challenges concerning the predictive biology of indicator traits or standardization need to be solved. To develop effective selection programmes for new traits, the development of large databases is necessary so that high-reliability breeding values can be estimated. For expensive-to-record traits, extensive phenotyping in combination with genotyping of females is a possibility.

Genomic selection: Status in different species and challenges for breeding.

Technical advances and development in the market for genomic tools have facilitated access to whole-genome data across species. Building-up on the acquired knowledge of the genome sequences, large-scale genotyping has been optimized for broad use, so genotype information can be routinely used to predict genetic merit. Genomic selection (GS) refers to the use of aggregates of estimated marker effects as predictors which allow improved individual differentiation at young age. Realizable benefits of GS are influenced by several factors and vary in quantity and quality between species. General characteristics and challenges of GS in implementation and routine application are described, followed by an overview over the current status of its use, prospects and challenges in important animal species. Genetic gain for a particular trait can be enhanced by shortening of the generation interval, increased selection accuracy and increased selection intensity, with species- and breed-specific relevance of the determinants. Reliable predictions based on genetic marker effects require assembly of a reference for linking of phenotype and genotype data to allow estimation and regular re-estimation. Experiences from dairy breeding have shown that international collaboration can set the course for fast and successful implementation of innovative selection tools, so genomics may significantly impact the structures of future breeding and breeding programmes. Traits of great and increasing importance, which were difficult to improve in the conventional systems, could be emphasized, if continuous availability of high-quality phenotype data can be assured. Equally elaborate strategies for genotyping and phenotyping will allow tailored approaches to balance efficient animal production, sustainability, animal health and welfare in future.

Correlations of unfavorable movement characteristics in warmblood foals and mares with routinely assessed conformation and performance traits.

New movement traits reflecting unfavorable movement characteristics were defined on the basis of detailed movement evaluations (DME) of warmblood foals and mares performed in connection with regular breeding events of the Oldenburg horse breeding societies in 2009 and 2010. DME information was available for 3374 foals and 2844 mares and used for correlation analyses with conformation information on 1987 mares from studbook inspections (SBI) in 2009 and performance information on 2758 mares from mare performance tests (MPT) in 2000 to 2008. Analyses of variance revealed few significant differences between scores for SBI and MPT traits in mares without and with indications of imbalance (IMB) in general or specific findings like irregular tail tone or posture (TTP). SBI scores for general impression and development were significantly lower and MPT scores for trot under rider tended to be higher in IMB-positive mares. Genetic parameters were estimated in linear animal models with residual maximum likelihood. Additive genetic correlations and Pearson correlation coefficients between univariately predicted breeding values indicated unfavorable genetic correlations of IMB and TTP with dressage-related conformation and performance traits. For SBI and MPT traits, we found similarities between the correlation patterns for DME traits in foals and mares. The results implied that breeding of dressage horses may benefit from revision of current movement evaluation and consideration of specific movement characteristics.

Genetic analyses of new movement traits using detailed evaluations of warmblood foals and mares.

Detailed movement evaluations of warmblood foals and mares were performed in connection with regular breeding events of the Oldenburg horse breeding societies in 2009 and 2010. Unfavourable movement characteristics considered indicative for impaired balance were noted by a special judge (SJ) and the regular judges of the breeding events (RJ) and served as the basis for definition of new movement traits. Detailed movement information on 3374 foals and 2844 mares showed that more severe findings like irregular motion pattern in hind legs or irregularity in general motion pattern occurred only sporadically (prevalences of 1-2%). Irregular tail tone or posture was documented for 4% of the foals and 5% of the mares, resulting in prevalences of the comprehensive trait indications of imbalance (IMB) of 6.2% (foals) and 5.5% (mares). Binary coding was used for all traits, and genetic parameters were estimated bivariately in linear animal models with residual maximum likelihood. Comparative analyses between judges revealed that differences between trait definitions of SJ and RJ were larger in the mares than in the foals, but justified combined use of SJ and RJ information in both age groups. Heritability estimates for the movement traits ranged on the original scale from 0.02 to 0.26 in the foals and from 0.03 to 0.12 in the mares, with heritabilities for IMB on the underlying liability scale of 0.46 (foals) and 0.22 (mares). Comparative analyses between age groups indicated that common genetic factors may be responsible for findings of impaired balance in foals and mares. The results implied that horse breeding may benefit from using the early available information on the movement of foals obtained by detailed movement evaluations, although favourable combination of foal and mare data in future genetic evaluations may require refined recording of unfavourable movement characteristics in the adult horses.

A genome-wide association study for quantitative trait loci of show-jumping in Hanoverian warmblood horses.

Show-jumping is an economically important breeding goal in Hanoverian warmblood horses. The aim of this study was a genome-wide association study (GWAS) for quantitative trait loci (QTL) for show-jumping in Hanoverian warmblood horses, employing the Illumina equine SNP50 Beadchip. For our analyses, we genotyped 115 stallions of the National State stud of Lower Saxony. The show-jumping talent of a horse includes style and ability in free-jumping. To control spurious associations based on population stratification, two different mixed linear animal model (MLM) approaches were employed, besides linear models with fixed effects only and adaptive permutations for correcting multiple testing. Population stratification was explained best in the MLM considering Hanoverian, Thoroughbred, Trakehner and Holsteiner genes and the marker identity-by-state relationship matrix. We identified six QTL for show-jumping on horse chromosomes (ECA) 1, 8, 9 and 26 (-log(10) P-value >5) and further putative QTL with -log(10) P-values of 3-5 on ECA1, 3, 11, 17 and 21. Within six QTL regions, we identified human performance-related genes including PAPSS2 on ECA1, MYL2 on ECA8, TRHR on ECA9 and GABPA on ECA26 and within the putative QTL regions NRAP on ECA1, and TBX4 on ECA11. The results of our GWAS suggest that genes involved in muscle structure, development and metabolism are crucial for elite show-jumping performance. Further studies are required to validate these QTL in larger data sets and further horse populations.

Evaluation of parotid gland lesions with standard ultrasound, color duplex sonography, sonoelastography, and acoustic radiation force impulse imaging - a pilot study.

PURPOSE: To evaluate the impact of standard ultrasound (US), color duplex sonography (CDS), sonoelastography (SE), and acoustic radiation force impulse (ARFI) imaging in the differentiation of parotid gland lesions. MATERIALS AND METHODS: From September 2010 to February 2011, 33 parotid gland lesions of 32 patients were included in this study. Patients underwent high-resolution B-mode US (THI, 9 - 14 MHz), CDS, SE, and ARFI quantification. Then parotidectomy was performed and samples were analyzed by (immuno-) histology. Data was extracted via unpaired t-test and expressed in p-values. RESULTS: There were 12 Wathin's tumors (WT), 11 pleomorphic adenomas (PA), 3 other benign tumors, 3 ductal dilatations, 2 neuroendocrine carcinomas, 1 non-Hodgkin lymphoma, and 1 malignant melanoma metastasis. In B-mode US, acoustic enhancement showed statistical significance between PA and WT (p < 0.005), and CDS determined different vascularization patterns (p < 0.0005). While SE did not visualize any significant difference between PA and WT, ARFI quantification determined different mean values for both entities (p < 0.003). CONCLUSION: B-mode US, CDS, and ARFI quantification distinguish PA from WT. The predictive value of the modern techniques for the differentiation of benign and malignant parotid lesions has to be assessed in a larger series.

Selection for conformation and conformational homogeneity of litters in the German shepherd dog.

Breeding standards of most dog breeds specify tolerable ranges of certain conformation traits. In the German shepherd dog (GSD), current means for withers height (WH) and BW are close to the upper breed limits. Therefore, strategies to avoid a further increase in size and to maximize the proportion of dogs fitting the breeding standard with respect to WH and BW should be compared. Body measurements were available for 14,416 male and 21,612 female GSD from 26,155 litters. Withers height and body mass index (BMI; i.e., BW/WH(2)) were considered direct selection traits. Using information on 17,154 GSD from litters with at least 2 dogs with conformation data, we defined within-litter variances of WH (vWH) and BMI (vBMI) as traits to select for the conformational homogeneity of litters. Officially recorded scores for canine hip dysplasia (CHD) of all dogs were used to monitor possible side effects of conformation selection on CHD. Genetic parameters were estimated multivariately in linear animal models by using Gibbs sampling. Heritabilities ranged between 0.19 and 0.34 for all traits, and additive genetic correlations between WH and vWH were -0.11 and those between BMI and vBMI were 0.11. The expected selection response was studied using the relative breeding values (RBV) of parents, assuming exclusion of sires, dams, or both with RBV larger than 120 and comparing means of WH, BMI, and CHD scores between offspring of all and selected parents. Concurrent selection for small WH and vWH was found to reduce the mean WH in males and females most efficiently while having little effect on CHD distributions. Multiple-trait selection for WH, vWH, BMI, and vBMI was hindered by the negative genetic correlations between the traits, and it tended to interfere with improvement of CHD status. Use of the RBV for WH and vWH for conformation selection is therefore recommended to maximize breeding success with regard to conformation and conformational homogeneity in the GSD.

Evaluation of ACE, SP17, and FSHB as candidates for stallion fertility in Hanoverian warmblood horses.

The research of fertility in humans and other mammals has strongly advanced in the recent years. The examination of molecular mechanisms influencing horse fertility is relatively recent. We chose the angiotensin converting enzyme (ACE), the sperm autoantigenic protein 17 (SP17) and the follicle stimulating hormone (FSHB) as candidates for determining stallion fertility and to analyze associations of intragenic single nucleotide polymorphisms (SNPs), flanking microsatellites and candidate-gene linked haplotypes with the pregnancy rate per oestrus (PRO) in 179 Hanoverian stallions. Fertility traits analyzed were the least square means of PRO for stallions (LSMs) and the paternal and embryonic component of breeding values for PRO (BVs). We detected nine SNPs and two flanking microsatellites in ACE, eight SNPs and two flanking microsatellites in SP17 and four SNPs and one flanking microsatellite in FSHB. Three SP17-associated SNPs and the two flanking microsatellites showed significant association with the embryonic component of BVs and one SP17-associated microsatellite was also significantly associated with the paternal component of BVs. Two ACE-associated SNPs were significantly associated with the embryonic component of BVs. Significantly associated haplotypes were shown for all three candidate genes and the tested fertility parameters. The final regression analysis model indicated that haplotypes of all three candidate genes significantly contributed to the paternal and embryonic fertility components of PRO. This is the first report of associations of ACE, SP17 and FSHB with fertility traits of stallions.

Genetic analyses of elbow and hip dysplasia in the German shepherd dog.

Results from radiographic screening for canine hip dysplasia (CHD) and elbow dysplasia (CED) of 48 367 German shepherd dogs born in 2001-07 were used for the population genetic analyses. Available information included CHD scores for 47 730 dogs, CED scores for 28 011 dogs and detailed veterinary diagnoses of primary ED lesions for a subsample of 18 899 dogs. Quasi-continuous traits were CHD, CED and cases of CED without radiographically visible primary lesion (CED-ARTH). Binary coding was used for fragmented medial coronoid process of the ulna (FCP), borderline findings and mild to severe signs of dysplasia in hip and elbow joints. Genetic parameters were estimated in univariate threshold and multivariate linear and mixed linear-threshold models using Gibbs sampling. Correlations between univariately predicted breeding values (BV) indicated genetic differences between borderline and affected disease status for both CHD (r(BV) = 0.5) and CED (r(BV) = 0.3). Multivariate genetic analyses with separate consideration of borderline findings revealed moderate heritabilities of 0.2-0.3 for the quasi-continuous traits with positive additive genetic correlation of 0.3 between CHD and both CED and CED-ARTH. For FCP, heritability of 0.6 and additive genetic correlations of +0.1 to CHD and -0.1 to CED-ARTH were estimated. Results supported the relevant genetic determination of CHD and CED, argued for both diseases against interpretation of borderline findings as healthy and implied genetic heterogeneity of CED. Accordingly, future breeding strategies to reduce the prevalences of CHD and CED in the German shepherd dog should be most efficient when based on BV from multivariate genetic evaluation for CHD, CED-ARTH and FCP with use of the whole scale of categories for classification of CHD and CED.

ARFI-based tissue elasticity quantification and kidney graft dysfunction: first clinical experiences.

BACKGROUND AND PURPOSE: Beyond the medical history, the clinical exam and lab findings, non-invasive ultrasound parameters such as kidney size and Doppler values (e.g. the resistive index) are important tools assisting clinical decision making in the monitoring of renal allografts. The gold standard for the diagnosis of renal allograft dysfunction remains the renal biopsy; while an invasive procedure, the justifiable necessity for this derives from its definitive nature a requirement beyond the synopses of all non-invasive tools. "Acoustic Radiation Force Impulse Imaging"(ARFI)-quantification is a novel ultrasound-based technology measuring tissue elasticity properties. So far experience related to this new method has not been reported in renal transplant follow-up. The purpose of this study was to evaluate changes in ARFI-measurements between clinically stable renal allografts and biopsy-proven transplant dysfunction. METHODS: We employed "Virtual Touch™ tissue quantification" (Siemens Acuson, S2000) for the quantitative measurement of tissue stiffness in the cortex of transplant kidneys. We performed initial baseline and later disease-evaluative ultrasound examinations in 8 renal transplant patients in a prospective study design. Patients were first examined during stable allograft function with a routine post-transplant renal ultrasound protocol. A second follow-up examination was carried out on subsequent presentation with transplant dysfunction prior to allograft biopsy and histological evaluation. All patiens were examined using ARFI-quantification (15 measurements/kidney). Resistive indices (RI) were calculated using pulsed-wave Doppler ultrasound, and transplant kidney size was measured on B-mode ultrasound images. All biopsies were evaluated histologically by a reference nephropathologist unaware of the results of the ultrasound studies. Histopathological diagnoses were based on biopsy results, taking clinical and laboratory findings into account. Finally we calculated the relative changes in ARFI-quantification, resistive indices and the absolute change of kidney size on a percentage basis at these defined assessment times and compared the results with the final pathologic diagnosis. RESULTS: Histological results enumerated five cases of acute T-cell-mediated rejection, one case of calcineurin inhibitor toxicity and two cases of acute tubular necrosis. Calcineurin inhibitor toxicity and acute tubular necrosis were subsumed as "other pathologies". Mean ARFI-values showed an average increase of more than 15% percent in transplants with histologically proven acute rejection whereas no increase was seen in transplants with other pathologies. Mean RI-values showed no increase either in the diagnostic group of acute rejection, nor in the group with other pathologies. Kidney size showed a mean absolute increase of 0.5 centimetres in allografts with acute rejection, whereas a mean decrease of 0.17 centimetres was seen in the group with other pathologies. CONCLUSION: As shown before in other studies, RI values and kidney size are of doubtful utility in the evaluation of kidney allograft dysfunction. ARFI-based elasticity measurement shows promise as a complementary non-invasive parameter in follow-on diagnosis of renal allograft rejection.

ARFI-based tissue elasticity quantification in comparison to histology for the diagnosis of renal transplant fibrosis.

BACKGROUND AND PURPOSE: Until recently clinical diagnosis of chronic renal allograft dysfunction could only be established invasively by renal biopsy. Given the risks of that procedure, a non-invasive, diagnostic test would be very advantageous. Novel ultrasound-based elasticity tools, using "Acoustic Radiation Force Impulse (ARFI)" technology are now available. Previously this technique has been utilised to quantify liver fibrosis. First results of these studies are promising. The purpose of our study was to investigate correlation between stiffness values obtained by ARFI-quantification and histological fibrosis score in renal transplants. METHODS: We employed "Virtual Touch™ tissue quantification" (Siemens Acuson, S2000) to quantitatively measure tissue stiffness in the cortex of transplant kidneys. Eighteen patients were included in this prospective study, recording close temporal ARFI-quantification and fibrosis measurements. All patients undergoing renal transplant biopsy were examined with ARFI-quantification (15 measurements per transplant kidney). Resistive indices were also calculated from pulsed-wave Doppler ultrasound. Transplant biopsies were histologically evaluated by a reference nephropathologist and graded according to the percentage of fibrosis and to the BANFF-score. Due to the non-normal distribution of the data the Spearman-correlation-coefficient (rho) was used to assess the bivariate relationship of ARFI and fibrosis in the transplant kidney. RESULTS: There was a significant positive moderate correlation between mean ARFI-values and the grade of fibrosis (rho = +0.465; p = 0.026). This correlation was also valid for the mean ARFI-values and the BANFF-category (rho = +0.468; p = 0.025). There was no significant correlation between the mean ARFI-values and the resistive indices in the transplant kidney (rho = +0.034; p = 0.904). Nevertheless, a positive correlation between the mean RI-values of the kidney and the grade of fibrosis was established (rho = +0.563; p = 0.015). CONCLUSION: The mean values of ARFI measurements and the resistive indices are potentially independent explanation variables for evaluating the grade of fibrosis in transplant kidneys.

Simulation study on the effects of excluding offspring information for genetic evaluation versus using genomic markers for selection in dog breeding.

Different modes of selection in dogs were studied with a special focus on the availability of disease information. Canine hip dysplasia (CHD) in the German shepherd dog was used as an example. The study was performed using a simulation model, comparing cases when selection was based on phenotype, true or predicted breeding value, or genomic breeding value. The parameters in the simulation model were drawn from the real population data. The data on all parents and 40% of their progeny were assumed to be available for the genetic evaluation carried out by Gibbs sampling. With respect to the use of disease records on progeny, three scenarios were considered: random exclusion of disease data (no restrictions, N), general exclusion of disease data (G) and exclusion of disease data for popular sires (P). One round of selection was considered, and the response was expressed as change of mean CHD score, proportion of dogs scored as normal, proportion of dogs scored as clearly affected and true mean breeding value in progeny of popular sires in comparison with all sires. When no restrictions on data were applied, selection on breeding value was three times more efficient than when some systematic exclusion was practised. Higher selection response than in the exclusion cases was achieved by selecting on the basis of genomic breeding value and CHD score. Genomic selection would therefore be the method of choice in the future.

Evaluation of malignant liver tumors: biphasic MS-CT versus quantitative contrast harmonic imaging ultrasound.

PURPOSE: It was the aim of our study to establish the extent to which contrast enhancement with SonoVue(R) in combination with quantitative evaluation of contrast-medium dynamics facilitates the detection of malignant hepatic tumors. MATERIALS AND METHODS: One hundred patients with histologically confirmed malignant or benign hepatic tumors (maximum size 5 cm) were analyzed. We used a high-end ultrasound machine (Logic 9, GE Healthcare, Milwaukee, WI, USA), with a multifrequency curved array transducer (2.5 - 4 MHz), Contrast-enhanced ultrasound (bolus injection 2.4 mL SonoVue(R)) was carried out with the intermittent breath-holding technique. Native vascularization was analyzed with power Doppler sonography. The contrast-enhanced dynamic ultrasound investigation was carried out with contrast harmonic imaging in the true detection mode during the arterial, portal venous and late phases. The mechanical index was set at 0.15. Perfusion analysis was performed by post-processing of the raw data (time intensity curve [TIC] analysis). Biphasic 16- or 64-slice multislice computed tomography served as reference method in nearly all cases. RESULTS: One hundred patients with 59 malignant (43 colon, 5 breast, 2 endocrine metastases, 7 hepatocellular carcinomas and 2 kidney cancers) and 41 benign (12 circumscribed fatty changes, 2 abscesses, 7 focal nodular hyperplasias, 5 complicated cysts and 15 hemangiomas) tumors were included. The CT classification was true positive in 71 of 92 patients, false negative in 8 cases, and in 13 cases no final diagnosis was possible; sensitivity was 96.7 % and specificity was 71.4 % for CT. The quantitative contrast harmonic imaging ultrasound classification was true positive in 98 of 100 patients and false negative in 2 cases; the sensitivity was 98.6 % and the specificity was 96.6 %. The Fisher test showed a significant difference at p < 0.05. No investigator-dependency was noted. CONCLUSION: In our study contrast-enhanced ultrasound was more accurate than multislice computed tomography in the prediction of malignancy and benignity of liver tumors.

[Ultrasound diagnostics of renal blood vessels and transplant kidney]. / Ultraschalldiagnostik der Nierengefässe und der Transplantatniere.

Ultrasound is usually the first imaging technique used in clinical practice for the visualization of renal blood vessels, especially when there is suspicion of renal artery stenosis. Apart from B-mode ultrasound, colour Doppler ultrasound, pulsed-wave Doppler are used as well as contrast-enhanced ultrasound, which is being used more and more as a routine technique. Ultrasound is important in nephrology for the detection of renal artery stenosis and the resistance indices from pulse-wave Doppler are also helpful in acute renal failure. Nevertheless resistance indices should be used carefully and always by being aware of the pitfalls of this parameter.Another field of application for ultrasound is imaging of renal blood vessel damage as a result of trauma or iatrogenic damage caused during a biopsy. In this setting contrast-enhanced ultrasound appears to be a suitable and highly sensitive tool for the detection of active bleeding and for visualizing the extent and dynamics of expansion of a hematoma.Ultrasonography is frequently used in the field of kidney transplants for the diagnostics of drainage obstructions, perfusion disturbances, transplant arterial stenoses and lymphoceles. Furthermore, ultrasound is exceptionally well suited for follow-up observation after diagnostic or therapeutic measures (e.g. biopsy and placement or removal of DJ catheters).

Evaluation of SPATA1-associated markers for stallion fertility.

Stallion fertility is an economically important trait because the use of artificial insemination is increasing in the horse industry and superior sires are used more intensely. Molecular genetic markers may be useful as early indicators for a stallion's fertility and genetic improvement programmes. The testis-specific SPATA1 protein is involved in shaping the sperm head during spermatogenesis. Thus, the spermatogenesis associated 1 (SPATA1) gene was chosen as candidate for stallion fertility, and we analysed intragenic single nucleotide polymorphisms (SNPs) as genetic markers for the least square means (LSM) of the pregnancy rate per oestrus of stallions and breeding values (BV) for the paternal and embryonic component of the pregnancy rate per oestrus. We sequenced the cDNA of SPATA1 to verify the annotated mRNA sequence. One SPATA1-associated intronic SNP (BIEC2-968854) showed a significant association with the embryonic component of BVs of stallions for the pregnancy rate per oestrus. The embryonic component of BVs was positively associated with homozygous C/C stallions. Both the additive and dominance effects were significant with values of -5.8% (P = 0.01) and -6.4% (P = 0.02) for the embryonic component of BVs. For the same SNP, a suggestive association was found for the LSM of the pregnancy rate per oestrus of stallions. Heterozygous stallions had higher pregnancy rates per oestrus than homozygous stallions. The dominance effect was 4.1% with a nominal P-value of 0.02. The SNP BIEC2-968854 can change an SP1 binding site and thus we assume that gene regulation may be influenced through this intronic mutation. This is the first report on SPATA1 being associated with the pregnancy rate per oestrus for stallions.