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Biomedical subjects

S Breit

Publications and source records attributed to S Breit.

At least 19 recordsLinked to original sources

mdclust--exploratory microarray analysis by multidimensional clustering.

MOTIVATION: Unsupervised clustering of microarray data may detect potentially important, but not obvious characteristics of samples, for instance subgroups of diagnoses with distinct gene profiles or systematic errors in experimentation. RESULTS: Multidimensional clustering (mdclust) is a method, which identifies sets of sample clusters and associated genes. It applies iteratively two-means clustering and score-based gene selection. For any phenotype variable best matching sets of clusters can be selected. This provides a method to identify gene-phenotype associations, suited even for settings with a large number of phenotype variables. An optional model based discriminant step may reduce further the number of selected genes.

Cluster Analysis↗

Variation in the ossification process of the anconeal and medial coronoid processes of the canine ulna.

This morphological and radiographic study investigates the ossification process of the anconeal and medial coronoid processes of the ulna in a sample of 142 dogs ranging in age from neonatal to 44 weeks. The anconeal process was noted to develop by appositional ossification, formation of a separate ossification center, or a combination of both. Several developmental stages of the ossification center of the anconeal process as well as its anatomic position and radiographic appearance are described. Differences have been noted in the shape of this ossification center as well as the ossification process itself. The medial coronoid process develops exclusively by appositional ossification. Unlike ossification of the anconeal process, ossification of the medial coronoid process was completed earlier (p < 0.05) in smaller than in the larger dogs. In smaller dogs, both the medial coronoid and anconeal processes were found to be mature by the age of 16 weeks. In the larger dogs, ossification of the anconeal process was completed not before 14 weeks of age and ossification of the medial coronoid process was completed about 6 weeks later.

Animals↗

A morphometric investigation on breed-specific features affecting sagittal rotational and lateral bending mobility in the canine cervical spine (c3-c7).

Vertebral and inter-vertebral parameters obtained in large breeds (n = 74), small breeds (n = 35), and Dachshunds (n = 30) were compared to reveal potential differences in the range of motion of the cervical spine between these three groups of breeds. Body size normalized dimensions of vertebral and inter-vertebral parameters and correlations between these indicate large canine breeds to have a tendency towards higher range of motion in sagittal rotation and lateral bending compared with Dachshunds and small breeds. Higher mobility in large breeds is based on significantly (P < 0.05) lower vertebral endplate heights and widths, shorter vertebral bodies and longer inter-vertebral discs, wider but shorter cranial and caudal articular surfaces, larger differences in width between caudal and cranial joining facets (compared with Dachshunds from C3/4 to C6/7, compared with small breeds from C4/5 to C5/6), and larger differences in length between caudal and cranial joining facets. Large differences in width between caudal and cranial joining facets were associated with small distances between the most medial (C3/4 to C6/7) and lateral (C3/4 to C5/6) aspects of the articular surfaces as well as with small differences in length between caudal and cranial joining facets (C3/4 to C5/6). This suggests that from C3/4 to C5/6 a higher range of motion in lateral bending is coupled to a lower range of motion in sagittal rotation. The present findings contribute also to explain the higher incidence of degenerative lesions of the cervical spine in large dogs.

Animals↗

The subchondral split line patterns of the medial coronoid process in canine ulnae.

The subchondral split line patterns of the canine medial coronoid process (MCP) were compared with fragmentation line patterns of the MCP in case of elbow dysplasia. Split line patterns were determined in paired ulnae from the killed 26 large-breed dogs ranging in age between 0.8 and 15 years and in two ulnae affected by fragmentation of the MCP. The macerated ulnae were degreased with methylene chloride and decalcified in 5% nitric acid. The subchondral bony layer was pierced at right angles in regular intervals using a round needle that was dipped in black liquid acrylic colour. Three main types of split line patterns could be differentiated (i.e. a sagittal type, a transverse type and an intermediate type). In the sagittal type, split lines were aligned in parallel to the lateral border and at right angles to the rim of the tip and medial border of the MCP. In the transverse type, split lines were orientated in a transverse line to both collateral borders. The intermediate type was characterized as a transition type between sagittal and transverse type as the split lines were aligned obliquely to the longitudinal axis of the MCP. These three types corresponded well with the fissure and fragmentation line patterns of the MCP. The present findings strongly suggest an association between split line pattern and type of fragmentation of the MCP.

Animals↗

The gross and radiographic appearance of sacroiliac ankylosis capsularis ossea in the dog.

This study was carried out to determine the incidence and to describe the radiographic appearance of ankylosis capsularis ossea at the canine sacroiliac joint, as well as to determine factors, which might cause radiographic misinterpretation of this finding. Bone specimens of 646 pelves of pure-bred dogs were assessed for morphological evidence of ankylosis capsularis ossea. The lesion was most commonly present at the cranioventral aspects of the sacroiliac joint. More than 50% of adult dogs had signs of being at least mildly affected. Among these, large and giant breeds were most commonly involved. Unlike moderate and severe degrees of this disease, smaller osteophytes had not been visualised on radiographs. For radiographic diagnosis, angled views of the sacrum are recommended. In central views of the sacrum, the presence of increased sacral concavity consistent with increased ilial convexity of the caudal aspect of the sacroiliac contact area might simulate the presence of ankylosis capsularis ossea. The clinical importance of the present findings is discussed in context with human literature.

Animals↗

Differentiation between lumbosacral transitional vertebrae, pseudolumbarisation, and lumbosacral osteophyte formation in ventrodorsal radiographs of the canine pelvis.

Ventrodorsal radiographs of the pelvis (n=150) of Rottweilers, Golden Retrievers, and German Shepherd dogs and macerated spines (n=800) from a variety of breeds were assessed for morphological evidence of lumbosacral transitional vertebrae as well as for factors that might lead to radiographic misinterpretation of this condition. Those alterations closely resembling the radiographic appearance of transitional vertebrae were identified to be: (1) calcification of the dorsal and ventral sacroiliac ligaments (=pseudolumbarisation), which might be interpreted as a costal process at S1 (or the corresponding vertebra in cases of numerical vertebral variations); and (2) osteophyte formation at the lumbosacral junction simulating separation of the cranial articular processes from the assembly of the sacral wing as seen in transitional vertebrae.

Animals↗

Morphometric investigations of breed-specific features in feline skulls and considerations on their functional implications.

A total of 17 parameters (nine lengths, four heights, four widths) was used to characterize the shape of the skull in a sample of 69 pure bred cats. Results of the discriminant analysis confirmed three phenotypically different skull formations, i.e. the round-shaped, the triangular and the cuneiform. Further statistical analyses revealed that the appearance of the skull was especially variable in the case of a round shape and that the lengths had been especially affected by these characteristics. The round shape of the brachycephalic skull was attributed to a reduction in length of the face and braincase as well. In many cases, this condition was associated with disproportional increase in height and width of the braincase and an increase in convexity of the calvaria. The decrease in length of the face was more pronounced at the dorsal surface of the nose than at the palate. Therefore, the inclination of the bony nasal aperture became flatter and the inclination of the maxilloturbinate became steeper. As a result, the ventral nasal meatus changed its direction twice. This condition might predispose to dyspnoea by restricting the air passageways within the nasal cavity. Round-shaped skulls were also associated with a decrease in facial width. Morphological variants that were frequently seen in round-shaped skulls include almost rectangular inclination of the nasal bone and more distant extension of the foramen magnum between the occipital condyles.

Animals↗

The course of the nasolacrimal duct in brachycephalic cats.

Casts of the nasolacrimal duct system were obtained from 50 euthanised cats including brachy-, meso- and dolichocephalic breeds. The course of the nasolacrimal duct, which was assessed radiographically and gross-anatomically, was strongly related to the shape of the skull. In meso- and dolichocephalic cats the nasolacrimal duct formed a dorsally opened arch with the descending part being directed rostroventrally. The main part of the duct passed the nasal cavity in a rather horizontal course parallel to the hard palate and was located ventrally to the lacrimal foramen. However, foreshortening of the face was associated with a right-angled or even acute-angled alignment of the duct. In higher degrees of brachycephaly the main part of the duct ascended beyond the level of the lacrimal foramen and passed the nasal cavity dorsal to the level of the lacrimal foramen. This specific course of the nasolacrimal duct in brachycephalic cats was consistent with a steeper alignment and attachment of the maxilloturbinate. Accessory orifices of the nasolacrimal duct opening into the nasal cavity had never been observed. The present results strongly suggest that the specific course of the nasolacrimal duct in brachycephalic cats might hinder the drainage of the lacrimal fluid irrespective of the diameter of the lumen of the nasolacrimal duct system.

Animals↗

Bioinformatics for medical diagnostics: assessment of microarray data in the context of clinical databases.

MOTIVATION: To identify genes suitable for medical diagnostics microarray data is assessed in the context of clinical databases, which store complex information about the patient phenotype. The wealth of data and lacking standards make it difficult to analyse this kind of data. RESULTS: We present a workflow for exploratory analysis of microarray data together with clinical data consisting of four steps: definition of clinically meaningful research questions in a masterfile, generation of analysis files, selection and characterization of differentially expressed genes, and estimation of classification accuracy. We applied this workflow to large data sets from the field of cardiology and oncology (n~500 patients). Systematic data management of microarray data and clinical data helps to make results more transparent and comparable.

Cardiology↗

Relevance of image fusion for target point determination in functional neurosurgery.

BACKGROUND: For the treatment of medically refractory movement disorders such as Parkinson's disease, essential tremor and primary dystonia, deep brain stimulation (DBS) has become one of the main treatment options. The targets for implantation of the stimulation electrodes are various nuclei within the basal ganglia or the thalamic and subthalamic area. Accurate target localisation is of major importance for outcome and patient safety. The goal of this study was to evaluate the role of image fusion in the determination of target co-ordinates. METHOD: We conducted a retrospective study on 10 patients in whom 17 DBS electrodes had been implanted. Coordinates of the anterior and posterior commissures and of the DBS targets were compared on pre- and postoperative computerised tomography (CT) and fused CT/magnetic resonance scans. The targets as defined on the images were further compared with the targets derived intra-operatively with microelectrode recordings (MER) and macrostimulation. FINDINGS: The achievable mean target accuracy was of the order of the diameter of the DBS electrode and of the accuracy of the image fusion algorithm, i.e. about 1 mm. However, the maximal differences were between 1.8 mm and 3.2 mm. INTERPRETATION: Image fusion is a helpful tool for accurate determination of target point co-ordinates in DBS. In combination with intraoperative, electrophysiological recordings and stimulation which are still considered to be the most reliable localisation methods, image fusion may help to discern the anatomical and functional three-dimensionality of the target nuclei. Image fusion may reduce the number of trajectories needed for intraoperative electrophysiological determination of the optimal electrode localisation and thus lower the risk of complications.

Aged↗

Osteological features in pure-bred dogs predisposing to thoracic or lumbar spinal cord compression.

Consistent with those vertebral sites most commonly clinically affected by spinal cord compression, body size normalised midsagittal diameters of the caudal vertebral foramen limits T10-T12 were significantly (P<0.05) lower in Dachshunds relative to other breeds. Minimal midsagittal diameters in Yorkshire Terriers and Maltese were noted at T11cd/12cr. However, these diameters were always larger (P<0.05) in small breeds compared to those in Dachshunds and large breeds suggesting that the small breeds investigated are at lower risk of developing clinical signs if a compressive disease occurs at that site. In large breeds, minimal values were present at L1cd/L2cr and in agreement with clinical findings correlate with those spinal sites most susceptible to spinal cord compression in nonchondrodystrophic large breeds. Caudal displacement of the lumbosacral enlargement of the spinal cord relative to the position previously noted in large breeds was confirmed for the Dachshunds and 50% of small breeds. However, caudal displacement was also noticed in the German Shepherd dogs.

Aging↗

Osteological and morphometric observations on intervertebral joints in the canine pre-diaphragmatic thoracic spine (Th1-Th9).

The incidence of facet aplasia was investigated in three groups of pure-bred dogs. We examined large breeds (Rough Collies, Doberman Pinschers, Rottweilers, Bernese Mountain Dogs, German Shepherd Dogs), chondrodystrophic breeds (Dachshunds, Pekinese dogs), and small breeds (Yorkshire Terriers, Maltese dogs). Uni- or bilateral aplasia of zygapophyseal (facet) joints was exclusively found in juvenile and adult small dogs, in which the incidence of aplasia ranged from between 26% (Th1) and 63% (Th8). There was no evidence that aplasia of zygapophyseal joints increases the risk of developing intervertebral disc disease or deformative spondylosis in small breeds. By applying the findings of previous empirical studies on intervertebral disc geometry and its biomechanical behaviour on the present morphometric results, there was an indication that the intervertebral disc may well compensate for the functional loss of aplastic zygapophyseal joints in small dogs. Biomechanical factors and their potential role as inducing agents of facet aplasia in the pre-diaphragmatic thoracic spine are also discussed.

Aging↗

Shape and orientation of articular facets of cervical vertebrae (C3-C7) in dogs denoting axial rotational ability: an osteological study.

Macerated cervical vertebrae of 139 adult and 39 juvenile dogs were assessed for morphological evidence of axial rotation, which is denoted by the shape and orientation of the articular facets. The potential effect of the presence of caudal costal foveae at C7 on facet geometry was also investigated. Four variations of caudal facet shape were evident, namely, plane, concave, convex and sigmoid. The earliest onset of change in shape from plane to curved was noticed in juvenile dogs who were older than 8 weeks. The incidence of curved facets denoting axial rotation ability was observed to increase on descending down the cervical spine. Concave caudal facets were more frequently present in males and in large dogs (P < 0.001), compared to Dachshunds and small breeds. The degree of concavity was not related to age but was associated with the transverse distance between the most medial aspects of the caudal and corresponding cranial facets (P < 0.05). In large breeds, the presence of concave caudal facets at C7 was inversely related to the presence of caudal costal foveae (P < 0.01). The effect of axial rotation is discussed in context with clinical literature suggesting that axial rotation might attribute to the development of the wobbler syndrome.

Age Factors↗

On biomechanical properties of the sacroiliac joint in purebred dogs.

Relative to the Yorkshire Terriers and Maltese dogs the mean expected sacroiliac joint load was calculated to be 1.4-1.6 times higher in other small breeds and 1.7-2.7 times higher in large breeds. The statistically significantly different (p < 0.01, p < 0.001) and mechanically less efficient inclination angles of the wings of the sacrum in adult large breeds (especially German Shepherd Dogs) suggest even higher forces acting on their sacroiliac ligaments. Unlike the case in small breeds, the sacral auricular surface was concave in large dogs to improve interlocking between sacrum and ilium and to reduce craniocaudal translation. An additional ossification center forming the ventral aspect of the transverse process of the second sacral vertebra was present in large breeds, occasionally in midsized and small, but never in toy breeds. This and the relationship between age and inclination angles of the wings of the sacrum in juvenile specimens indicate an affection of the three-dimensional modeling of the wings of the sacrum by formative stimuli such as body weight and locomotion.

Aging↗

Breed specific osteological features of the canine lumbosacral junction.

Inefficient facet geometry suggests the lumbosacral junction to be mechanically imperfect in a large number of dogs (especially German Shepherd Dogs) resulting in a significantly higher prevalence of osteophyte formation and increase in the longitudinal extension of the articular surface covering the caudal articular process of the seventh lumbar vertebra. Such osteological features give evidence for lumbosacral craniocaudal translation, were predominantly noticed in combination with axial rotation and are taken to be anatomic risk factors that can predispose to the development of lumbosacral stenosis. The statistically significant relationship between age and the magnitude of the caudal facet inclination angles of the seventh lumbar vertebra in juvenile specimens indicate an affection of the three-dimensional modeling of the immature caudal articular processes by formative stimuli such as body weight and locomotion. However, results additionally indicate an association between the magnitude of these inclination angles and vertebral body dimensions also suggesting a congenital influence on facet geometry.

Aging↗

Changing serine-485 to alanine in the opossum parathyroid hormone (PTH)/PTH-related peptide receptor enhances PTH stimulation of phospholipase C in a stably transfected human kidney cell line: a useful model for PTH-analog screening?

Using site-directed mutagenesis, we have introduced a serine-485-to-alanine mutation in the opossum parathyroid hormone (PTH) receptor. This amino acid is considered to be phosphorylated by protein kinase A upon ligand binding. Both wild-type (WT) and mutant receptor were stably expressed in 293-EBNA HEK cells. The mutant receptor showed comparable binding characteristics and only a slight increase in cAMP production compared with WT. However, the PTH dose-dependent increase in inositol phosphate production was 24-fold for the mutant receptor vs. 6-fold for the WT receptor. This mutant might prove useful in the sensitive detection of phospholipase C activation through various ligands, as the PTH receptor becomes a target of therapeutic intervention in osteoporosis.

Alanine↗

Unilateral lesion of the nigrostriatal pathway induces an increase of neuronal activity of the pedunculopontine nucleus, which is reversed by the lesion of the subthalamic nucleus in the rat.

The role of the pedunculopontine nucleus (PPN) in the pathophysiology of Parkinson's disease is still unclear. Using microrecordings, we investigated the changes occurring in PPN neurons after lesions of the substantia nigra compacta (SNc) and the role of the subthalamic nucleus (STN) in these changes. In normal rats the firing rate of PPN neurons was 10.6 +/- 1.4 spikes/s, the majority of neurons (91%) having a regular firing pattern, 6% irregular and 3% in bursts. In rats with 6-hydroxydopamine lesions of the SNc, the firing rate increased significantly to 18.3 +/- 3.0 spikes/s compared with normal rats. In addition, the firing pattern changed significantly: 70% of the neurons discharged regularly, 27% irregularly and 3% in bursts. In rats with ibotenic acid lesions of the STN, the firing rate decreased significantly to 7.2 +/- 0.9 spikes/s and the firing pattern changed significantly: 50% of the neurons discharged regularly, 43% irregularly and 7% in bursts. The rats with combined SNc and STN lesions showed no change in the firing rate (8.5 +/- 1.0 spikes/s) compared to normal rats. The firing pattern changed significantly: 69% of the cells discharged regularly, 26% irregularly and 5% in bursts. These findings demonstrate that PPN neurons are overactive and more irregular in the 6-hydroxydopamine-lesioned rats, suggesting the implication of this nucleus in the pathophysiology of parkinsonism. Moreover, the fact that STN lesions induced a reduction in the firing rate of the PPN in normal rats and a normalization of the firing rate in rats with 6-hydroxydopamine lesions suggests that this nucleus is under major control of the STN.

Action Potentials↗