The influence of Young's modulus of loaded implants on bone remodeling: an experimental and numerical study in the goat knee

The aim of this study was to examine the influence of the Young's modulus of the implant material on the bone remodeling in a loaded condition. A combined animal experimental and computational study was set up. The animal experimental group comprised of 16 Saanen goats, each receiving one titanium implant (Young's modulus 110 GPa) and one high-density polyethylene (HDPE) implant (Young's modulus 1 GPa) in the left femoral condyle. Both types of implants received a titanium coating of 100 nm thickness. The implants protruded in the knee joint space and were directly weight bearing. The first group of eight goats was sacrificed after 6 weeks of loading and the second group of eight goats after 6 months of loading. The 16 femoral condyles with the 32 implants were prepared for microfocus computed tomography (micro-CT) scanning and histological sectioning. Three-dimensional trabecular bone parameters were calculated on the micro-CT images for the zones neck, middle, and apex of the implant. The percent of bone contact with the implant was measured on longitudinal histological sections. An axisymmetric finite element (FE) model was created to compare peri-implant bone strains and relative motion between a titanium and a HDPE implant for the experimental loading condition, and to assess the influence of different bone-implant interface (contact) conditions. From the statistical analysis of the 3D bone parameters, the difference between the titanium and HDPE implants was not significantly different (p > 0.05) between the zones (neck, middle, and apex) for both groups of goats. The implants could be considered in their entirety. After 6 weeks of loading, the PE implant presented lower connectivity and smaller marrow spaces in the circular region of 0-500 microm. In the region 500-1500 microm more bone volume was present for the PE implant. After 6 months, the PE implants showed more bone volume and thicker trabeculae than the titanium implants for the entire length of the implant. This effect was already present in the smallest region of interest, 0-500 microm. After 6 months more fibrous encapsulation was found around titanium implants. FE results demonstrated a substantial influence of the interface conditions on peri-implant strains and relative motion. For interface conditions that were representative for the early postoperative situation (involving press-fit and friction), differences in peri-implant bone strain distributions between titanium and HDPE could be related to the experimentally observed differences in amounts of bone and fibrous encapsulation. In contrast, differences in relative motion did not seem to play a role. Both the experimental and computational results suggest that implant stiffness can affect the peri-implant tissue response, which may be related to differences in peri-implant strains.     

Reduced cooperativeness and reward-dependence in depression with above-normal plasma vasopressin concentration

The neuropeptide vasopressin is centrally involved in the regulation of social behaviour and response to stress. We previously found support for a subcategory of depression defined by above-normal plasma vasopressin (AVP) concentration. This subcategory is validated by a positive family history of depression and correlating plasma AVP and cortisol concentrations. The data support the validity of above-normal plasma AVP concentration as a genetically determined biological marker for a subcategory of depression. The aim of the present study was to test whether above-normal plasma AVP concentration in depression is related to personality characteristics reflecting a specific social behaviour style. The data of 78 patients from a previously investigated sample were reanalysed. Fifty-eight patients were available after 2 years, 15 of whom with initially above-normal plasma AVP. The dimensions of the Temperament and Character Inventory (TCI) were scored, with particular focus on the dimensions of Cooperativeness (CO) and Reward-dependence (RD). Normative subjects and other depressed subjects were used as controls. After full remission, patients with initially above-normal AVP had low CO compared with normal and patient controls. During depression, these patients had both low CO and low RD compared with normal controls and low RD compared with patient controls. Low CO is a presumably premorbid trait and reduced RD a state-dependent characteristic in depression with above-normal plasma AVP. The low CO further supports the validity of above-normal plasma AVP concentration as a genetically determined biological marker for a subcategory of depression.     

Neuroregenerative effects of lentiviral vector-mediated GDNF expression in reimplanted ventral roots

Traumatic avulsion of spinal nerve roots causes complete paralysis of the affected limb. Reimplantation of avulsed roots results in only limited functional recovery in humans, specifically of distal targets. Therefore, root avulsion causes serious and permanent disability. Here, we show in a rat model that lentiviral vector-mediated overexpression of glial cell line-derived neurotrophic factor (GDNF) in reimplanted nerve roots completely prevents motoneuron atrophy after ventral root avulsion and stimulates regeneration of axons into reimplanted roots. However, over the course of 16 weeks neuroma-like structures are formed in the reimplanted roots, and regenerating axons are trapped at sites with high levels of GDNF expression. A high local concentration of GDNF therefore impairs long distance regeneration. These observations show the feasibility of combining neurosurgical repair of avulsed roots with gene-therapeutic approaches. Our data also point to the importance of developing viral vectors that allow regulated expression of neurotrophic factors.     

Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury

Rubrospinal neurons (RSNs) undergo marked atrophy after cervical axotomy. This progressive atrophy may impair the regenerative capacity of RSNs in response to repair strategies that are targeted to promote rubrospinal tract regeneration. Here, we investigated whether we could achieve long-term rescue of RSNs from lesion-induced atrophy by adeno-associated viral (AAV) vector-mediated gene transfer of brain-derived neurotrophic factor (BDNF). We show for the first time that AAV vectors can be used for the persistent transduction of highly atrophic neurons in the red nucleus (RN) for up to 18 months after injury. Furthermore, BDNF gene transfer into the RN following spinal axotomy resulted in counteraction of atrophy in both the acute and chronic stage after injury. These novel findings demonstrate that a gene therapeutic approach can be used to reverse atrophy of lesioned CNS neurons for an extended period of time.     

A study of the effects of long-term use on individual sensitivity to temazepam and lorazepam in a clinical population

Aims The central effects of benzodiazepines may be attenuated after chronic use by changes in pharmacokinetics, pharmacodynamics or both. This attenuation may be influenced by the dosing pattern and the characteristics of the user population. The objectives of this study were to evaluate drug sensitivity in long-term users of temazepam and lorazepam in a clinical population. Methods The sensitivity to benzodiazepine effects in chronic users (1–20 years) of lorazepam (n=14) or temazepam (n=13) was evaluated in comparison with age and sex matched controls. Drug sensitivity was evaluated by plasma concentration in relation to saccadic eye movement parameters, postural stability and visual analogue scales. Results Pharmacokinetics of lorazepam and temazepam did not differ between patients and control subjects. Chronic users of lorazepam showed clear evidence of reduced sensitivity, indicated by lack of any pharmacodynamic difference between patients and controls at baseline, when drug concentrations were similar to the peak values attained in the control subjects after administration of 1–2.5 mg of lorazepam. In addition, there was a two- to four fold reduction in the slopes of concentration-effect plots for measures of saccadic eye movements and body sway (all; P≤0.01). By contrast, sensitivity in chronic users of temazepam was not different from controls. The difference between the temazepam and the lorazepam group appears to be associated with a more continuous drug exposure in the latter, due to the longer half-life and a more frequent intake of lorazepam. This pattern of use may be partly related to the more anxious personality traits that were observed in the chronic users of lorazepam. Conclusions Chronic users of lorazepam show evidence of tolerance to sedative effects in comparison with healthy controls. Tolerance does not occur in chronic users of temazepam. The difference may be related to pharmacological properties, in addition to different patterns of use, associated with psychological factors.     

MR-guided biopsy using a T2-weighted single-shot Zoom Imaging sequence (Local Look technique)

The purpose of this study was to demonstrate the utility of a T2-weighted single shot turbo spin-echo technique — the so-called “Local Look” (LoLo) and more recently renamed “Zoom Imaging” technique — for MR-guided percutaneous interventions. We performed 28 procedures on 22 patients using a 1.5-T system for MR guidance. All procedures were controlled with the LoLo technique, which acquires T2-weighted images in 600 msec. This is achieved by using a small field of view (250 × 125 mm) along with a maximum echo train length, the so-called “single shot method.” To prevent backfolding artifacts, the 90° and 180° pulses were oriented orthogonally to each other. Because signal is created only in the region in which the pulses overlap, no backfolding can occur from outside this area. Half of the biopsies were additionally monitored using a fast gradient-echo sequence, which was compared with the LoLo technique. All of the procedures were technically successful, and there were no procedural complications. The LoLo technique produced images that had good contrast between the lesion and the needle artifact, and the artifact size was smaller than that produced by the gradient-echo technique. Subjective judgment of the ability to accurately delineate the needle tip indicated that the LoLo technique was either superior to (73%) or equal to (27%) the gradient-echo sequence in all cases. The LoLo technique is an accurate and effective method for MR guidance of percutaneous procedures, because it shows good lesion contrast and small needle artifacts. The additional use of a gradient-echo sequence during the procedure planning stage is advisable in more difficult cases, particularly when adjacent blood vessels are a concern. Monitoring of the needle tip is best performed with the LoLo technique.