Influence of surgical intervention at the level of the dorsal spinous processes on the biomechanics of the equine thoracolumbar spine.

BACKGROUND: Surgical treatment options for horses with overriding dorsal spinous processes include interspinous ligament desmotomy and partial spinous process ostectomy. The impact of spinal surgery on the three-dimensional biomechanics of the equine thoracolumbar spine and the epaxial musculature is unclear. OBJECTIVES: To investigate the influence of interspinous ligament desmotomy and cranial wedge ostectomy on the biomechanics of the equine thoracolumbar spine and the paraspinal Musculi multifidi. STUDY DESIGN: Ex-vivo experiments. METHODS: Twelve equine thoracolumbar spine specimens were mounted in a custom-made mechanical test rig. Based on computed tomographic imaging, distances between dorsal spinous processes and the spinal range of motion (lateral bending, axial rotation, flexion, extension) were compared before and after desmotomy and cranial wedge ostectomy performed at two or five surgical sites. Anatomical dissection was subsequently conducted to document surgical trauma to the Musculi multifidi following desmotomy. RESULTS: The distance between spinous processes in neutral position did not increase significantly after desmotomy (median preoperative = 7.2 mm, interquartile range [IQR] = 3.6 mm; median postoperative = 7.4 mm, IQR = 3.7 mm; p = 0.09), but increased significantly after ostectomy (median preoperative = 8.8 mm, IQR = 4.2 mm; median postoperative = 13 mm, IQR = 6.1 mm; p < 0.001). Both surgical procedures significantly increased the rotational spinal range of motion (p = 0.001), particularly at the level T14/T15 (median preoperative = 6.4°, IQR = 3.2°; median postoperative = 8.2°, IQR = 3.5°; increase = 28.1%; p = 0.02). Musculi multifidi injury was evident at all desmotomy sites. MAIN LIMITATIONS: Ex-vivo study with limited sample size. CONCLUSIONS: Neither interspinous ligament desmotomy nor cranial wedge ostectomy resulted in an increased range of motion during flexion, extension or lateral bending but both procedures influenced the rotational component of the equine thoracolumbar spinal mobility.

Computed tomographic study analysing functional biomechanics in the thoracolumbar spine of horses with and without spinal pathology.

To better understand physiological and pathological movement patterns in the equine thoracolumbar spine, investigation of the biomechanics on a segmental level requires a constant moment. A constant moment along the spinal column means that the same torque acts on each vertebral segment, allowing the range of motion of different segments to be compared. The aims of this study were to investigate the range of motion of the equine thoracolumbar spine in horses with and without spinal pathology and to examine whether the pressure between the spinous processes depends on the direction of the applied moment. Thoracolumbar spine specimens (T8-L4) of 23 horses were mounted in a custom-made mechanical test rig to investigate spinal biomechanics during lateral bending, axial rotation, flexion and extension using computed tomographic imaging. Results were compared between horses with spondylosis, overriding spinous processes and specimens free of gross pathology. The interspinous space pressure was additionally determined using a foil sensor. The median lateral bending between T9 and L3 was 3.7°-4.1° (IQR 5.4°-8.0°). Maximum rotational movement with inconsistent coupled motion was observed at T9-T16 (p < 0.05). The dorsoventral range of motion was greatest in segments T9-T11 (p < 0.05). Spondylosis and overriding spinous processes restricted spinal mobility, depending on the severity of the condition. There was no significant difference in interspinous pressure during motion (p = 0.54). The biomechanical study confirmed that the range of motion of intervertebral joints depends on the anatomical position of the joint and the direction of the moment applied. Restricted mobility was evident in the presence of different grades of overriding spinous processes or spondylosis. A better understanding of equine spinal biomechanics in horses with spinal pathology facilitates individual rehabilitation.

Phase I study of the angiogenesis inhibitor BIBF 1120 in patients with advanced solid tumors.

PURPOSE: BIBF 1120 is an oral, potent angiokinase inhibitor targeting receptors of the vascular endothelial growth factors, platelet-derived growth factors, and fibroblast growth factors. This phase I, accelerated titration study assessed the maximum tolerated dose, safety, pharmacokinetics, and pharmacodynamic effects of BIBF 1120. PATIENTS AND METHODS: Sixty-one patients with advanced cancers received BIBF 1120 in successive cohorts. Twenty-five received 50 to 450 mg once daily and 36 received 150 to 300 mg twice daily in 4-week treatment courses interspersed by 1 week of washout. Dynamic contrast-enhanced magnetic resonance imaging assessed antiangiogenic effect in 42 patients. RESULTS: Most frequent BIBF 1120-related adverse events were mostly mild to moderate (Common Toxicity Criteria grade 1-2) nausea (68.9%), vomiting (45.9%), and diarrhea (44.3%). The majority of dose-limiting adverse events of Common Toxicity Criteria grade 3 or 4 were reversible liver enzyme elevations. The maximum tolerated dose was 250 mg of BIBF 1120 for once and twice daily dosing. BIBF 1120 was absorbed moderately fast (t(max) = 1-3 hours at steady state), with no deviation from dose linearity and no decrease of exposure over time. The gMean terminal half-life was from 13 to 19 hours. One complete and two partial responses occurred in patients with renal cell cancer (n = 2) and colorectal cancer (n = 1). Dynamic contrast-enhanced magnetic resonance imaging showed a significant reduction in tumor blood flow in 55% of evaluable patients. CONCLUSIONS: BIBF 1120 dosed continuously displayed a favorable safety and pharmacokinetics profile, and first efficacy signals were observed. Twice daily dosing permitted increased drug exposure without additional toxicity. Two hundred milligrams BIBF 1120 twice daily is the recommended dose for phase II monotherapy studies.

Spectroscopic findings in attention-deficit/hyperactivity disorder: review and meta-analysis.

OBJECTIVES: The last decade has seen an increasing interest in the method of magnet resonance spectroscopy (MRS) since this is the only research tool that allows a non-invasive in vivo assessment of neurochemical aspects of ADHD without employing ionising radiation. In this paper we review published MRS results with respect to childhood, adolescence and adult ADHD. METHOD: We searched the Medline (Pub Med) database using the key words ADHD, attention-deficit/hyperactivity disorder, magnet resonance spectroscopy, MRS and spectroscopy. Citations of identified articles were also searched for relevant studies. Meta-analyses were performed for the measured metabolites and regions of assessment. RESULTS: Sixteen studies could be identified that used MRS to investigate the neurobiology of ADHD. Two regions could be identified as the focus of spectroscopic investigations--the frontal lobe including anterior cingulate cortex and parts of prefrontal cortex and the basal ganglia, mostly striatum, alongside the fronto-striato-thalamo-frontal circuits. As for metabolites, in the majority of studies the ratios to creatine and not absolute concentrations of metabolites were estimated. Choline compounds, N-acetyl-aspartate and glutamate/glutamine (to creatine ratios) could be identified as being altered in several studies in ADHD. The meta-analysis showed increased choline compounds in several researched regions. DISCUSSION: MRS is a promising tool for the non-invasive in vivo assessment of the cerebral neurochemistry in ADHD. More regions of interest (ROI) like amygdala, hippocampus, thalamus and cerebellum should be assessed in future studies. Further methodological improvements of MRS are desirable in order to assess the absolute metabolite concentration of several ROIs at the same time. Such developments will open novel perspectives in spectroscopic investigations of ADHD.

Amplitopicity of the human auditory cortex: an fMRI study.

Whereas specialized frequency-encoding patterns in the human auditory cortex are generally accepted, termed tonotopicity, a similar principle of intensity encoding--amplitopicity--is debated controversially. This functional magnetic resonance imaging study describes the relationship of the activation volume and the spatial distribution of activated clusters under different sound pressure levels (SPL) across the temporal plane including the transverse temporal gyrus (TTG). Nine healthy subjects with no hearing deficiencies were investigated using an echo-planar imaging technique at 1.5 T. A boxcar stimulation paradigm was applied with a 5-Hz pulsed sine tone of 1000 Hz frequency at three SPLs of 70, 82, and 90 dB. Linear cross-correlation analysis (correlation coefficient > 0.3 corresponding to P < 0.08) of the functional data set revealed bilateral BOLD response within the auditory cortex of the nine subjects with moderate increase of activation volume for higher sound pressure levels. With increasing sound pressure a two-dimensional drift of cortical activation was observed (a) from the ventral to the dorsal edge and (b) from lateral to medial parts of TTG. This latero-medial drift therefore mimics the well-accepted principle of tonotopy for frequency-encoding neurons. This study demonstrates the existence of an amplitopic pattern of intensity-encoding neuronal clusters that in part resembles the tonotopic distribution of frequency-encoding neurons. This finding has to be integrated into the understanding of the auditory organization for the interpretation of higher auditory functions such as sound perception or speech.