How to prevent overlooking cervical spine injuries: pitfalls in spinal diagnostics.

Many patients with a cervical spine injury do not show clinical signs of the injury. Therefore, cervical spine trauma may not be recognized, especially in unconscious and multiply injured patients. Due to proximity to the spinal cord, neurological deficits inclusive of complete tetraplegia are possible. Since cervical spine injuries are typically associated with injuries at other spinal levels, accurate knowledge of the trauma mechanism is essential. Even mild clinical symptoms need to be carefully evaluated in a standardized fashion with clinical and radiological examinations including plane X-rays and possibly CT scans.

Heterologous priming-boosting with DNA and modified vaccinia virus Ankara expressing tryparedoxin peroxidase promotes long-term memory against Leishmania major in susceptible BALB/c Mice.

Leishmaniasis affects 12 million people, but there are no vaccines in routine clinical use. Th1 polarizing vaccines that elicit long-term protection are required to prevent disease in susceptible populations. We recently showed that heterologous priming-boosting with tryparedoxin peroxidase (TRYP) DNA followed by TRYP-modified vaccinia virus Ankara (TRYP MVA) protected susceptible BALB/c mice from Leishmania major. Here we compared treatment with TRYP DNA with treatment with TRYP DNA/TRYP MVA. We found that equivalent levels of protection during the postvaccination effector phase correlated with equivalent levels of serum immunoglobulin G2a and gamma interferon (IFN-gamma) in draining lymph nodes. In contrast, challenge infection during the memory phase revealed that there was enhanced clinical efficacy with TRYP DNA/TRYP MVA. This correlated with higher levels of effector phase splenic IFN-gamma, sustained prechallenge levels of memory phase IFN-gamma, and a more polarized post-L. major challenge Th1 response compared to the Th2/T(reg) response. Thus, TRYP DNA/TRYP MVA, but not TRYP DNA alone, provides long-term protection against murine leishmaniasis.

Anterior vertebral body replacement with a titanium implant of adjustable height: a prospective clinical study.

In the operative treatment of spinal injuries, the reconstruction of the anterior column of the thoracolumbar spine is still controversial. We conducted a prospective clinical study to investigate the clinical and radiological outcome of 50 patients treated with a vertebral body replacement of adjustable height (Synex). Fifty consecutive patients were evaluated during in-patient treatment and at 12 and 20 months post-operatively in clinical notes and radiographs. 38/50 patients were operated for traumatic fractures. Out of 50 patients 45 attended the follow-up clinic 1 year post-operatively and 39 of these patients were examined after 20 months. Twenty-five patients returned to pre-injury activities within 1 year. This number increased to 29/39 patients at 20 months. Seventy-three percent of the patients returned to their job. After 1 year 25/45 patients complained of little or no back pain and 6 months later six patients were limited in their back function. At 1 year only three patients complained of surgical site pain which was improved at their final follow-up at 20 months. Individual satisfaction was determined using a score on a visual analog scale containing 19 questions on back pain, and functional limitation of the spine that has to be filled in by the patients at three different points of time. The score decreased from 87/100 pre-operatively to 65/100 at 1 year follow-up (P<0.001). The average permanent correction of the injured vertebra was 16.8 degrees (88%) including 2.3 degrees (12%) loss of correction at 12 months after operation. Bony integration was obtained in 83%. Early and intermediate outcome with the Synex vertebral replacement device for reconstruction of the anterior column appears promising. The loss of correction or reduction was only minimal. On the basis of our results we recommend the Synex implant as an alternative for the fixation and stabilisation of thoracolumbar fractures. However, long-term results and a clinically random control study are still required.

Lordoplasty: report on early results with a new technique for the treatment of vertebral compression fractures to restore the lordosis.

Cement augmentation using PMMA cement is known as an efficient treatment for osteoporotic vertebral compression fractures with a rapid release of pain in most patients and prevention of an ongoing kyphotic deformity of the vertebrae treated. However, after a vertebroplasty there is no chance to restore vertebral height. Using the technique of kyphoplasty a certain restoration of vertebral body height can be achieved. But there is a limitation of recovery due to loss of correction when deflating the kyphoplastic ballon and before injecting the cement. In addition, the instruments used are quite expensive. Lordoplasty is another technique to restore kyphosis by indirect fracture reduction as it is used with an internal fixateur. The fractured and the adjacent vertebrae are instrumented with bone cannulas bipediculary and the adjacent vertebrae are augmentated with cement. After curing of the cement the fractured vertebra is reduced by applying a lordotic moment via the cannulas. While maintaining the pretension the fractured vertebra is reinforced. We performed a prospective trial of 26 patients with a lordoplastic procedure. There was a pain relief of about 87% and a significant decrease in VAS value from 7.3 to 1.9. Due to lordoplasty there was a significant and permanent correction in vertebral and segmental kyphotic angle about 15.2 degrees and 10.0 degrees , respectively and also a significant restoration in anterior and mid vertebral height. Lordoplasty is a minimal invasive technique to restore vertebral body height. An immediate relief of pain is achieved in most patients. The procedure is safe and cost effective.

From genome to vaccines for leishmaniasis: screening 100 novel vaccine candidates against murine Leishmania major infection.

The genomic sequence of Leishmania major provides a rich source of vaccine candidates. One hundred randomly selected amastigote-expressed genes were screened as DNA vaccines, and efficacy determined following high-dose L. major footpad challenge in BALB/c mice. Fourteen protective novel vaccine candidates were identified; seven vaccines exacerbated disease. There were no differences in the number of predicted MHC H-2d class I or II epitopes mapping to protective versus exacerbatory antigens. A proportion of both protective (7/14; 50%) and exacerbatory (4/7; 57%) proteins showed short (8- to 18-mer) 100% amino acid sequence identities to human, mouse or gut flora proteins. A high proportion of these (4/7 protective; 3/4 exacerbatory) showed full or partial overlap with RANKPEP-predicted H-2d classes I and II epitopes. Our data suggest, therefore, that there may be little difference between antigens/epitopes that drive regulatory versus effector CD4 T cell populations. The best novel protective antigen was an amastin-like gene that maps to a 17-gene tandem array on Leishmania chromosome 8 and is closely related to 37 other amastin-like genes. Two ribosomal proteins, a V-ATPase subunit, and a dynein light chain orthologue were the only other protective genes with putative functions.

[Vertebral body replacement with Synex in combined posteroanterior surgery for treatment of thoracolumbar injuries]. / Der Wirbelkörperersatz mit Synex bei kombinierter dorsoventraler Behandlung thorakolumbaler Verletzungen.

OBJECTIVE: Reduction and stabilization of unstable spinal injuries with reconstruction of the anterior column resulting in a permanent restitution of the physiologic spinal alignment, stability and load-bearing capacity. INDICATIONS: Unstable injuries and lesions of the spine from T4 to L5 resulting in a reduced load-bearing capacity of the anterior spinal column caused by vertebral fractures and injury of the intervertebral disks, posttraumatic kyphotic deformities, pathologic fractures, tumors. Relative indications: younger patients with monosegmental injuries; patients with severe osteoporosis. CONTRAINDICATIONS: Concomitant serious thoracic injuries or preexisting cardiopulmonary disease precluding anterior intervention. SURGICAL TECHNIQUE: Combined posteroanterior treatment with (1) posterior reduction and stabilization with an internal fixator and interlaminar fusion with autogenous bone grafts; (2) thoracoscopic anterior approach with reconstruction of the anterior column with a distractible titanium implant for vertebral body replacement (Synex), interbody fusion with autogenous bone grafts and/or beta-tricalciumphosphate. RESULTS: 50 consecutive patients (29 men, 21 women) with an average age of 43 years (20-77 years) were treated with Synex. The most frequent indication was acute injury (n = 36). A bisegmental reconstruction was performed in 30 patients, a monosegmental in 20. Mean follow-up 19.5 months (14-31 months) in 41 patients. 18/33 patients returned to their previous occupation, and 32/41 resumed their recreational activities. At follow-up, 32/41 were free of symptoms or complained of only occasional pain, eight reported marked pain and one severe pain. A VAS spine score (0-100 points, visual analog scale, 19 items) was used for assessment; the preoperative score amounted to 83.1 +/- 20.2 (21-100), the postoperative score to 63.8 +/- 19.5 (25-99). The mean decrease in VAS spine score was 19.3 +/- 22.3. The average degree of correction measured radiologically for patients with fresh injuries or posttraumatic malalignment was 18.6 degrees +/- 10 degrees and the loss of correction 2.1 degrees +/- 2.9 degrees . No implant-related complications were observed.

IL-10 from regulatory T cells determines vaccine efficacy in murine Leishmania major infection.

Leishmaniasis affects 12 million people, but there are no vaccines. Immunological correlates of vaccine efficacy are unclear. Polarized Th1 vs Th2 responses in Leishmania major-infected mice suggested that a shift in balance from IL-4 to IFN-gamma was the key to vaccine success. Recently, a role for IL-10 and regulatory T cells in parasite persistence was demonstrated, prompting re-evaluation of vaccine-induced immunity. We compared DNA/modified vaccinia virus Ankara heterologous prime-boost with Leishmania homolog of the receptor for activated C kinase (LACK) or tryparedoxin peroxidase (TRYP). Both induced low IL-4 and high IFN-gamma prechallenge. Strikingly, high prechallenge CD4 T cell-derived IL-10 predicted vaccine failure using LACK, whereas low IL-10 predicted protection with TRYP. The ratio of IFN-gamma:IL-10 was thus a clear prechallenge indicator of vaccine success. Challenge infection caused further polarization to high IL-10/low IFN-gamma with LACK and low IL-10/high IFN-gamma with TRYP. Ex vivo quantitative RT-PCR and in vitro depletion and suppression experiments demonstrated that Ag-driven CD4+ CD25+ T regulatory 1-like cells were the primary source of IL-10 in LACK-vaccinated mice. Anti-IL-10R treatment in vivo demonstrated that IL-10 was functional in determining vaccine failure, rendering LACK protective in the presence of high IFN-gamma/low IL-5 responses.

DNA-Salmonella enterica serovar Typhimurium primer-booster vaccination biases towards T helper 1 responses and enhances protection against Leishmania major infection in mice.

Successful resolution of infections by intracellular pathogens requires gamma interferon (IFN-gamma). DNA vaccines promote T helper 1 (Th1) responses by triggering interleukin-12 (IL-12) release by dendritic cells (DC) through Toll-like receptor 9 (TLR9). In humans TLR9 is restricted to plasmacytoid DC. Here we show that DNA-Salmonella enterica serovar Typhimurium primer-booster vaccination, which provides alternative ligands to bind TLR4 on myeloid DC, strongly biases towards Th1 responses compared to vaccination with DNA alone. This results in higher immunoglobulin G2a (IgG2a) responses compared to IgG1 responses, higher IFN-gamma responses compared to IL-10 CD4(+)-T-cell responses, and enhanced protection against Leishmania major infection in susceptible BALB/c mice.

Prospective multicenter study with a new implant for thoracolumbar vertebral body replacement.

BACKGROUND: There are several therapeutic strategies for restoring the anterior column of the vertebral body after trauma, tumor and infection. We present a multicenter study with a new distractable titanium implant for vertebral body replacement. METHODS: Prospective documentation was collected of the first 126 patients treated with Synex during the 1st year of the clinical course. There was an evaluation of surgical indication, classification, localisation of the lesion, operative details, complications, and clinical course. RESULTS: A total of 70 men and 56 women (average age 46.9 years) underwent surgery for vertebral fracture, correction of posttraumatic kyphosis, infection, vertebral tumor and metastasis, and other diseases such as ankylosing spondylitis. Synex was used in open and minimally invasive surgery. In almost every case, an additional anteriorly or posteriorly stabilizing implant was used. Anterior fusion was performed with cement in tumors and autologous bone in fractures. Mono- and multisegmental lesions in the thoracic and lumbar spine were treated. CONCLUSIONS: The Synex implant is very easy to manage and is suitable for many indications such as vertebral fracture, correction of posttraumatic kyphosis, infection, vertebral tumor/metastasis, and other diseases. The vertebral body replacement can be used for defects of different sizes with the option of in situ distraction. No cases of implant failure, dislocation, or other implant-related complication have been observed. As a consequence of this prospective series, an additional implant size has been added, and the distraction device (spreading forceps) has been modified for more powerful spreading.

[Effect of short-distance spondylodesis of the thoracolumbar transition on neighboring facet joints. A biomechanical study]. / Einfluss einer kurzstreckigen Spondylodese des thorakolumbalen Ubergangs auf die angrenzenden Wirbelgelenke. Eine biomechanische Studie.

This study was performed to investigate the range of motion and the forces on the facet joints that are neighboured to spondylodesis on thoracolumbar spine. We used a special spine testing device for a continuous application of pure moments in each direction. For measuring the ranges of motion we used a magnetic tracking device for measuring forces on facet joints we chose a direct measuring system of quartz crystal and prepared for investigation of the spine. The biomechanical testing was done on 18 human spinal specimen. We investigated the range of motion and the forces on facet joints in T11/12 and L2/3 segment with a maximal loading of 8 Nm in each direction (flexion, extension, lateral bending and rotation). This was done before and after double level dorsal instrumentation T12-L2 with an internal fixateur. Statistical analysis was performed using the paired t-test and the Wilcoxon test (p < 0.05). After double level instrumentation there were significant larger ranges of motion in flexion and extension and significant larger forces on facet joints in left lateral bending in the T11/12 segment. No significant differences were found in the L2/3 segment. Our findings could be an indication for changing in joints loading. This could be an explanation for early degenerative changes in spinal segments adjacent to spondylodesis. The results confirm the demand of short segment instrumentation and early remove of implants to keep influence as low as possible.

From genomes to vaccines: Leishmania as a model.

The 35 Mb genome of Leishmania should be sequenced by late 2002. It contains approximately 8500 genes that will probably translate into more than 10 000 proteins. In the laboratory we have been piloting strategies to try to harness the power of the genome-proteome for rapid screening of new vaccine candidate. To this end, microarray analysis of 1094 unique genes identified using an EST analysis of 2091 cDNA clones from spliced leader libraries prepared from different developmental stages of Leishmania has been employed. The plan was to identify amastigote-expressed genes that could be used in high-throughput DNA-vaccine screens to identify potential new vaccine candidates. Despite the lack of transcriptional regulation that polycistronic transcription in Leishmania dictates, the data provide evidence for a high level of post-transcriptional regulation of RNA abundance during the developmental cycle of promastigotes in culture and in lesion-derived amastigotes of Leishmania major. This has provided 147 candidates from the 1094 unique genes that are specifically upregulated in amastigotes and are being used in vaccine studies. Using DNA vaccination, it was demonstrated that pooling strategies can work to identify protective vaccines, but it was found that some potentially protective antigens are masked by other disease-exacerbatory antigens in the pool. A total of 100 new vaccine candidates are currently being tested separately and in pools to extend this analysis, and to facilitate retrospective bioinformatic analysis to develop predictive algorithms for sequences that constitute potentially protective antigens. We are also working with other members of the Leishmania Genome Network to determine whether RNA expression determined by microarray analyses parallels expression at the protein level. We believe we are making good progress in developing strategies that will allow rapid translation of the sequence of Leishmania into potential interventions for disease control in humans.