Cervical spondylodiscitis: change in clinical picture and operative management during the last two decades. A series of 50 patients and review of literature.

PURPOSE: The incidence of spondylodiscitis is increasing. This study evaluates the behavior of cervical spondylodiscitis over a period of two decades in a single institution and compares the findings with the literature. METHODS: Between 1994 and 1999, 20 consecutive patients (group A) suffering from cervical spondylodiscitis underwent surgical treatment in our institution. These were compared to another group consisting of 30 patients (group B) undergoing surgery for the same disease between 2004 and 2009 again in our institution. All patients in both series underwent surgical debridement and reconstruction followed by antibiotic therapy for 8-12 weeks. RESULTS: The mean age at presentation increased significantly from 59.7 to 64.5 years. Male predominance was noticed in both groups. Accompanying neurological deficit was almost the same (40-45 %), while septicaemia increased from 15 to 40 %. Radiologically, epidural abscess formation increased from 60 to 80 %. The disease was mostly monosegmental in group A (85 %); while in group B, the disease became significantly more aggressive affecting two and three segments in 43.3 % of the cases. There was an increased tendency toward anterior alone surgery in group B (56.7 %) in comparison to group A (35 %). Mean period of follow-up was 2.8 years. Healing of the inflammation was the rule. Mortality rate increased from 5 to 10 %. CONCLUSIONS: Cervical spondylodiscitis has increased and became more aggressive. While radical surgical debridement, stable reconstruction together with antibiotic therapy remained a reliable approach to achieve complete healing of the inflammation, anterior alone surgery became more applicable.

Surface-mediated priming during in vitro generation of monocyte-derived dendritic cells.

Ex vivo-generated human dendritic cells (DC) are most commonly generated from monocytes using standard cell culture dishes. To elucidate the effect of the plastic surface during the differentiation process, we compared a standard adhesive plastic dish with four different mainly non-adherent surfaces. Untouched monocytes were cultured for 3 days in the presence of IL-4 and GM-CSF. Time-lapse videos were recorded, and the phenotype of the cells was analysed by flow cytometry. The cytokine profiles were analysed using a 25-plex cytokine assay. The use of non-adherent surfaces led to a significant reduction in expression of CD14 and CD38, and a significant increase in expression of CD86 compared to standard culture dishes. Expression levels of DC-SIGN and PD-L2 were reduced significantly on cells cultured on non-adherent surfaces. The cytokine production was independent on the surface used. The surface-mediated priming should therefore be considered when aiming to induce specific immune responses. This is especially important with regard to DC-based immunotherapy, where an adjustment of the surface during the DC generation process might have highly beneficial effects.

2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis.

This first update of the ASAS/EULAR recommendations on the management of ankylosing spondylitis (AS) is based on the original paper, a systematic review of existing recommendations and the literature since 2005 and the discussion and agreement among 21 international experts, 2 patients and 2 physiotherapists in a meeting in February 2010. Each original bullet point was discussed in detail and reworded if necessary. Decisions on new recommendations were made - if necessary after voting. The strength of the recommendations (SOR) was scored on an 11-point numerical rating scale after the meeting by email. These recommendations apply to patients of all ages that fulfill the modified NY criteria for AS, independent of extra-articular manifestations, and they take into account all drug and non-drug interventions related to AS. Four overarching principles were introduced, implying that one bullet has been moved to this section. There are now 11 bullet points including 2 new ones, one related to extra-articular manifestations and one to changes in the disease course. With a mean score of 9.1 (range 8-10) the SOR was generally very good.

Comparison of a minimally invasive procedure versus standard microscopic discotomy: a prospective randomised controlled clinical trial.

A Prospective randomised controlled study was done to determine statistical difference between the standard microsurgical discotomy (MC) and a minimally invasive microscopic procedure for disc prolapse surgery by comparing operation duration and clinical outcome. Additionally, the transferability of the results was determined by a bicentric design. The microscopic assisted percutaneous nucleotomy (MAPN) has been advocated as a minimally invasive tubular technique. Proponents have claimed that minimally invasive procedures reduce postoperative pain and accelerate the recovery. In addition, there exist only a limited number of well-designed comparison studies comparing standard microdiscotomy to a tubular minimally invasive technique that support this claim. Furthermore, there are no well-designed studies looking at the transferability of those results and possible learning curve phenomena. We studied 100 patients, who were planned for disc prolapse surgery at two centres [50 patients at the developing centre (index) and 50 patients at the less experienced (transfer) centre]. The randomisation was done separately for each centre, employing a block-randomisation procedure with respect to age and preoperative Oswestry score. Operation duration was chosen as a primary outcome parameter as there was a distinguished shortening observed in a preliminary study at the index centre enabling a sound case number estimation. The following data were compared between the two groups and the centres with a 12-month follow-up: surgical times (operation duration and approach duration), the clinical results, leg and back pain by visual analogue scale, the Oswestry disability index, length of hospital stay, return to work time, and complications. The operation duration was statistically identical for MC (57.8 +/- 20.2 min) at the index centre and for MAPN (50.3 +/- 18.3 min) and MC (54.7 +/- 18.1 min) at the transfer centre. The operation duration was only significantly shorter for the MAPN technique at the index centre with 33.3 min (SD 12.1 min). There was a huge clinical improvement for all patients regardless of centre or method revealed by a repeated measures ANOVA for all follow-up visits Separate post hoc ANOVAs for each centre revealed that there was a significant time-method (MAPN vs. MC) interaction at the index centre (F = 3.75, P = 0.006), whereas this crucial interaction was not present at the transfer centre (F = 0.5, P = 0.7). These results suggest a slightly faster clinical recovery for the MAPN patients only at the index centre. This was due to a greater reduction in VAS score for back pain at discharge, 8-week and 6-month follow up (P < 0.002). The Oswestry-disability scores reached a significant improvement compared to the initial values extending over the complete follow-up at both centres for both methods without revealing any differences for the two methods in either centre. There was no difference regarding complications. The results demonstrate that a shorter operation duration and concomitant quicker recovery is comprehensible at an experienced minimally invasively operating centre. These advantages could not be found at the transfer centre within 25 minimally invasive procedures. In conclusion both procedures show equal mid term clinical results and the same complication rate even if the suggested advantages for the minimally invasive procedure could not be confirmed for the transfer centre within the framework of this study.

Local topological analysis of densitometer-generated scan images of the proximal femur for differentiation between patients with hip fracture and age-matched controls.

SUMMARY: We evaluate densitometer-generated scan images of the proximal femur with respect to topological properties of bone mineral distribution patterns in selected regions of interest. In a population of 100 post-menopausal women, the method has a highly discriminative potential with a performance superior to standard densitometry. Results vary with anatomical location within the proximal femur. INTRODUCTION: The objectives of the study were to evaluate densitometer-generated scan images of the proximal femur with respect to topological properties of bone mineral distribution patterns in selected regions of interest, to test the ability for differentiation between post-menopausal women hip fracture and controls, and to compare results with standard bone densitometry. MATERIALS AND METHODS: We used dual-energy X-ray absorptiometry (DXA) to measure the femoral bone mineral density (BMD) of 100 post-menopausal women (73.4 +/- 12.2), 50 of whom had a recent hip fracture. Local bone mineral distribution in the scanner-generated images was analyzed in the standard DXA-regions of interest (ROIs; femoral neck, the shaft, the trochanteric area; and the total hip) using an optimized, local topological parameter MF2D. Performance of topological analysis and BMD was tested by receiver-operator characteristic and discriminant analysis. RESULTS: Area under the curve (AUC) for correct differentiation between patients with and without fractures by BMD in the different ROIs ranged from 0.64 to 0.71; AUC of regional density-pattern analysis varied between 0.79 and 0.84. Using multivariate statistical models, between 71% and 84% of patients were correctly identified as fracture/non-fracture cases by regional topological analysis, whereas BMD reached levels from 58% to 68%. CONCLUSION: Our analysis indicates that identification of patients with hip fracture by regional evaluation of density patterns varies with anatomical location within the proximal femur. In our study population, performance of the novel parameter was superior to densitometry.

Using Radon transform of standard radiographs of the hip to differentiate between post-menopausal women with and without fracture of the proximal femur.

UNLABELLED: Texture features based on the Radon transform were extracted from clinical radiographs of the hip in post-menopausal women. The novel algorithm allowed us to identify patients with fracture of the proximal femur and may provide an alternative to measuring bone mineral density in predicting the fracture-risk in osteoporosis, especially where densitometry is regionally unavailable. INTRODUCTION: The aim of this study is to introduce an algorithm for differentiation between patients with and without fracture of the hip using parameters based on the Radon transform (RT) and applied to standard radiographs of the proximal femur and to compare the results with bone mineral density (BMD). METHODS: The study comprised 50 post-menopausal women (78.6 +/- 11.5 years of age), including 25 patients with hip fracture and 25 age-matched controls. We obtained lumbar and femoral BMD and standard femoral radiographs. In the radiographs we analysed trabecular patterns of the hip in a region-of-interest of 57 x 29 mm using the RT. From the histogram-representation of the RT, we extracted several characteristic parameters. By ROC and discriminant-analysis, we assessed the statistical power of both methods. RESULTS: For correct differentiation between fracture and non-fracture cases by femoral BMD, area-under-the-curve (AUC) was 0.78; AUC for the RT-based parameters ranged from 0.73 to 0.8. By combination of densitometric and textural information in a multivariate model the fracture status of 84% of subjects was predicted correctly, identification of fracture cases rose to 88%. CONCLUSION: Identification of fracture patients by RT applied to femoral radiographs was feasible and seemed to have a discriminative potential comparable to that of standard densitometry. In the future, the new method may provide an alternative to DXA or in conjunction with conventional densitometry may enhance the detection of patients with elevated risk of hip fracture.

Expression of cathepsin K and matrix metalloproteinase 1 indicate persistent osteodestructive activity in long-standing ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is a common, largely genetically determined, rheumatic disease that is characterised by spinal inflammation and new bone formation. However, the exact pathogenesis and pathology are still not clear. OBJECTIVE: To analyse tissue obtained at spinal surgery by immunohistochemistry and compare the specimen of patients with AS to those with degenerative disc disease (DDD). METHODS: Bony and soft tissue specimens of 30 patients with AS and 20 with DDD were obtained during spinal osteotomy from different anatomic regions including articular and spinous processes, interspinous ligaments and intervertebral disks. Immunohistolochemistry was performed with established markers for cathepsin K, matrix metalloproteinase (MMP)1, MMP3 and receptor activator for nuclear factor kappaB (RANK) ligand. RESULTS: Cathepsin K and MMP1-positive cells were only observed in AS specimens. Cathepsin K-positive multinucleated cells were detected at articular processes adjacent to fibrous tissues. MMP1 was expressed in smaller mononuclear cells attached to bone. Invasion of bone by MMP1 cells was seen at entheseal sites. In the intervertebral disks, most mononuclear cells were cathepsin K-positive. Isolated cells expressing these matrix-degrading enzymes found in DDD never showed signs of invasion. No differences were found for MMP3 between AS and DDD. Clear expression of RANK ligand was only detected in one patient with AS. CONCLUSIONS: Cathepsin K is strongly expressed in different regions of the spine in AS. Cathepsin K was mainly expressed by mononuclear cells, fibroblast-like cells and cells attached to bone and at sites of bone remodelling, suggestive of high osteoclastic activity. This supports the role of persistent inflammation in the pathogenesis of AS. How these changes relate to osteoproliferation remains to be determined.

Automated classification of normal and pathologic pulmonary tissue by topological texture features extracted from multi-detector CT in 3D.

To provide a novel, robust algorithm for classification of lung tissue depicted by multi-detector computed tomography (MDCT) based on the topology of CT-attenuation values and to compare discriminative results with densitometric methods. Two hundred seventy-five cubic volumes of interest (VOI, edge length 40 pixels) were obtained from MDCT chest CT (isotropic voxel size, edge length 0.6 mm) of 21 subjects with and without pathology (emphysema, fibrosis). All VOIs were visually consensus-classified by two radiologists. Texture features based on the Minkowski functionals (MF) as well as on the CT attenuation values are determined. Classification results of both approaches were assessed by receiver-operator characteristic and discriminant analysis. By densitometric (topological) parameters, normal and abnormal VOIs were distinguished with an area under the curve ranging from 0.78 to 0.85 (0.87 to 0.96). Correlation between both groups of parameters was non-significant (p > or = 0.36). By combined information of densitometric and topological quantities, the radiologists' ratings were reproduced for 92% of VOIs, ranging from 85.7% (fibrosis) to 98% (normal VOIs). Our method performs well for identification of VOIs containing abnormal lung-tissue. Combined information of densitometry and topology increases the number of correctly classified VOIs further. When extended to CT data depicting whole lungs, topological analysis may allow to enhance density-based analysis and improve monitoring texture changes with progression of pulmonary disease.

Differentiation between post-menopausal women with and without hip fractures: enhanced evaluation of clinical DXA by topological analysis of the mineral distribution in the scan images.

UNLABELLED: We introduce an algorithm to evaluate hip DXA scans using quantitative image analysis procedures based on the Minkowski functionals (MF) for differentiation between post-menopausal women with and without hip fracture. In a population of 30 post-menopausal women, the new parameter has a highly discriminative potential with a performance superior to standard densitometry providing complementary information compared to BMD. INTRODUCTION: We introduce a novel algorithm to evaluate DXA scans of the hip using quantitative image analysis based on the Minkowski functionals (MF) to identify post-menopausal women with hip-fracture and to compare the results with densitometry. METHODS: BMD of 30 women (73.9 +/- 10.3 years), 15 of whom had a recent hip fracture, is obtained by DXA using the "total hip" ROI. The topology of mineral distribution in the scan images is evaluated using the MF-based parameter MF2D. ROC analysis is employed to assess the discriminative potential (fracture/non-fracture). RESULTS: The area-under-the-curve (AUC) for identification of patients with/without fractures by BMD is .72(p = 0.04), AUC for MF2D is .85(p = 0.001). No statistically significant correlation exists between MF2D and BMD. By discriminant analysis we can show that by combination of MF2D and BMD the outcome increases significantly: using BMD or MF2D alone, 63% and 70% of cases are classified correctly versus 77% of cases in the multivariate model. CONCLUSION: The topology-based parameter has a high predictive potential with respect to identification of patients with high risk of hip fracture, performance is superior to densitometry. The new method provides information complementary to BMD. Best classification results are obtained when BMD and MF2D are combined in a multivariate model.

Acute ascending motoric paraplegia following intrathecal chemotherapy for treatment of acute lymphoblastic leukemia in children: case reports and review of the literature.

Severe side effects of chemotherapy in pediatric patients with acute lymphoblastic leukemia are rare, but well-known. We present two pediatric patients who developed ascending motoric paraplegia (AMP) following intrathecal chemotherapy. Both patients suffered from progressive weakness of their lower extremities, neurogenic bladder dysfunction, autonomous neural dysregulation and minor sensory deficits. Despite an initially similar clinical picture, progression and outcome were fairly different. There is convincing evidence that AMP is caused by spinal cord toxicity of intrathecally applied toxic agents such as cytarabin and/or methotrexate leading to spinal demyelinisation as demonstrated by elevated myelin basic protein in cerebrospinal fluid.

The 3D-based scaling index algorithm: a new structure measure to analyze trabecular bone architecture in high-resolution MR images in vivo.

INTRODUCTION: The purpose of this study was to obtain different structure measures as the three-dimensional (3D)-based scaling index method (SIM) and standard two-dimensional (2D) bone histomorphometric parameters from high-resolution (HR) magnetic resonance (MR) images of the distal radius and to compare these parameters with bone mineral density (BMD) in their diagnostic performance to differentiate postmenopausal patients with and without vertebral fractures. METHODS: Axial HR-MR images of the distal radius were obtained at 1.5 T in 40 postmenopausal women (17 with osteoporotic spine fractures and 23 controls). Trabecular microarchitecture analysis was performed using the new structure measure mP(alpha), derived from the SIM, as well as standard morphological 2D parameters. BMD of the spine was obtained using quantitative computed tomography (QCT). Receiver operating characteristic (ROC) analyses were used to determine diagnostic performance in differentiating both groups. Results were validated by bootstrapping techniques. RESULTS: Significant differences between both patient groups were obtained using mP(alpha), 2D parameters, and spine BMD (p<0.05). In comparison with the 2D texture parameters [area under the curve (AUC) up to 0.67], diagnostic performance was significantly higher for mP(alpha)(AUC=0.85; p<0.05). There was a trend for a higher AUC value for mP(alpha) compared with BMD of the spine (AUC=0.71; p=0.81). CONCLUSION: mP(alpha) yielded a robust measure of trabecular bone microarchitecture for HR-MR images of the radius, which significantly improved the diagnostic performance in differentiating postmenopausal women with and without osteoporotic spine fractures compared with standard 2D bone histomorphometric parameters. This 3D characterization of trabecular microarchitecture may provide a new approach to better assess the strength of human cancellous bone using HR-MR image data.

Mini-open approach combined with percutaneous transarticular screw fixation for C1-C2 fusion.

This paper describes a limited exposure for posterior C1-C2 arthrodesis aided by percutaneous transarticular fixation. The purpose of this study was to report the fusion rate using the aforementioned method. Fifty-seven patients (54 females and three males) with C1-C2 instability due to rheumatoid disease constituted the material of this study. The exposure was restricted to C0-C3 levels. The drilling and insertion of the screws was done through two mini stab wounds. A special sleeve and screwdriver were developed to facilitate this step. An autogenous iliac bone graft was fixed between the decorticated posterior arch of the atlas and the lamina of the axis vertebra. The mean of the atlantodental interval decreased from 8.5 mm (SD 2.3 mm) to 2.6 mm (SD 0.6 mm) at the immediate postoperative periods and reached 2.7 mm (SD 0.7 mm) after a mean follow-up of 30.4 months (SD 5.6 months). Malposition of the screws was observed in two patients and warranted a second operation in one. Fusion was evident in 98% of the cases. Percutaneous insertion of the screws in posterior C1-C2 transarticular fixation reduces the size of the exposure and the surgical trauma to the cervical segments below the fixation.

A less invasive approach technique for operative treatment of lumbar canal stenosis. Technique and preliminary results.

UNLABELLED: The aim of this prospective study is to evaluate the efficacy of a less invasive approach for the operative treatment of lumbar canal stenosis. Using transmuscular dilatation this technique minimises surgical trauma. Through a working channel with a 11 mm outer diameter and under operative microscope guidance, decompression of the neural elements can be achieved. MATERIAL AND METHODS: From November 1998 to December 2001 38 consecutive patients with a mean age of 73.2 years were operated upon using this technique. The study included 56 lumbar segments. The mean follow up was 32 (18-55) months. The Visual Analogue Scale (VAS) for back and leg pain together with the Oxford Claudication Score (OCS) were used to assess the functional results. RESULTS: The average operating time for one level decompression was 74 minutes and the average blood loss was 32 ml/patient. Two patients (5.2 %) required revision by open surgery. The OCS improved from 29.4 preoperatively to 16.9 postoperatively (p < 0.001). VAS for back pain and leg pain also showed a significant improvement (p < 0.001). CONCLUSIONS: This less invasive approach is effective in decompressing lumbar canal stenosis. It has the advantage of early mobilisation and a short hospital stay, especially in elderly patients (mean age here: 73.2 years).

Long-term noninvasive ventilation in children and adolescents with neuromuscular disorders.

The aim of the current study was to investigate the long-term impact of nocturnal noninvasive (positive-pressure) ventilation (NIV) on sleep, sleep-disordered breathing (SDB) and respiratory function in children and adolescents with progressive neuromuscular disorders (NMD). Thirty patients (12.3 +/- 4.1 yrs) with various inherited NMD were treated with NIV for ventilatory insufficiency (n=14) or symptomatic SDB (n=16). Patients were prospectively followed with sleep studies, spirometry and peak inspiratory muscle pressure. Ten patients were studied before and after 3 nights withdrawal from NIV. NIV normalised nocturnal gas exchange in all patients and diurnal gas exchange in patients with ventilatory insufficiency. The effects persisted over 25.3 +/- 12.7 months. Nocturnal transcutaneous partial pressure of carbon dioxide improved from (baseline versus latest control) 7.1 +/- 1.3 to 5.5 +/- 0.6 kPa (53.7 +/- 9.9 to 41.6 +/- 4.8 mmHg), diurnal carbon dioxide arterial tension from 6.3 +/- 1.6 to 5.4 +/- 0.5 kPa (47.5 +/- 11.9 to 40.6 +/- 3.6 mmHg). NIV improved respiratory disturbance index, arousals from sleep, nocturnal heart rate and sleep architecture. Vital capacity decreased in five adolescents with Duchenne muscular dystrophy -183 +/- 111 mL x yr(-1) but remained stable in 25 children with other conditions (8 +/- 78 mL x yr(-1)). Three nights withdrawal of NIV in 10 previously stable patients resulted in prompt deterioration of SDB and gas exchange back to baseline but could be instantly normalised by resumption of NIV. Noninvasive (positive-pressure) ventilation has favourable long-term impact on nocturnal and diurnal gas exchange and sleep and in patients with non-Duchenne neuromuscular disorders on vital capacity as well. It is indicated in children and adolescents with symptomatic sleep-disordered breathing or ventilatory insufficiency due to neuromuscular disorders.

Local 3D scaling properties for the analysis of trabecular bone extracted from high-resolution magnetic resonance imaging of human trabecular bone: comparison with bone mineral density in the prediction of biomechanical strength in vitro.

RATIONALE AND OBJECTIVES: A novel, nonlinear morphologic measure [DeltaP(alpha)] based on local 3D scaling properties was applied to high-resolution magnetic resonance images (HR-MRI) of human trabecular bone to predict biomechanical strength in vitro. METHODS: We extracted DeltaP(alpha) and traditional morphologic parameters (apparent trabecular volume fraction, apparent trabecular separation) from HR-MR images of 32 femoral and 13 spinal bone specimens. Furthermore, bone mineral density (BMD) and maximum compressive strength (MCS) were determined. The morphologic measures were compared with BMD in predicting the biomechanical strength. RESULTS: In the vertebral (femoral) specimens, R2 for MCS versus DeltaP(alpha) was 0.87 (0.61) (P < 0.001). Correlation between BMD and MCS was 0.53 (P = 0.05) (0.79 [P < 0.001]) for the vertebral (femoral) specimens. For the femoral specimens, prediction of MCS could be improved further by combining BMD and morphologic parameters by multiple regression (R2 = 0.88). CONCLUSIONS: Morphologic measures extracted from HR-MRI considering local 3D-scaling properties can be used to predict biomechanical properties of bone in vitro. They are superior to 2-dimensional standard linear morphometric measures and, depending on the anatomic location, more reliably predict bone strength as measured by MCS than does BMD.

A new minimally invasive posterior approach for the treatment of cervical radiculopathy and myelopathy: surgical technique and preliminary results.

Degenerative cervical disorders predominantly lead to anterior spinal cord compression (by bony spurs at the posterior margin of the vertebral body or by degenerated disc), which may be central and/or foraminal. In a smaller percentage of cases, there is encroachment of the canal mainly from posterior by bulging yellow ligaments or bony appositions, resulting in compression syndromes of roots or spinal cord. The aim of this work is to present a minimally invasive posterior approach avoiding detachment of muscles for the treatment of cervical radiculopathy and myelopathy. Thirteen patients suffering from cervical radiculopathy (four patients) or myelopathy (nine patients) were operated according to this technique. In principle, the technique secures access to the diseased spinal segment via a percutaneously placed working channel (11 mm outer diameter and 9 mm inner diameter). The cervical paraspinal muscles are not deflected, but just spread between their fibres by special dilators. All further steps are performed through this channel under control of three-dimensional vision through the operating microscope. The mean follow-up period was 17 months (one patient died 9 months postoperatively), and patients were evaluated using a modified version of the Oswestry Index, called the Neck Disability Index (NDI), and the visual analogue scale (VAS) for neck and arm pain. The mean NDI (P<0.0001) improved from 13.2 (preoperatively) to 4.8 (postoperatively). The VAS for arm pain (P<0.001) and for neck pain (P<0.001) also showed marked postoperative improvement. Complete recovery of the preoperative neurological deficit was found in four patients, while the remaining eight patients showed improvement of the neurological symptoms during the follow-up period. There were no intra-operative or postoperative complications and no re-operation. The preliminary experience with this technique, and the good clinical outcome, seem to promise that this minimally invasive technique is a valid alternative to the conventional open exposure for treatment of lateral disc prolapses, foraminal bony stenosis and central posterior ligamentous stenosis of the cervical spine.

Surgical options in the treatment of the spinal disorders in ankylosing spondylitis.

Serious complications or unsatisfactory results in the past often have made patients as well as doctors hesitant to decide for surgery in ankylosing spondylitis. Though the techniques of correction for fixed flexion deformity still are demanding, decisive progress has been made toward less complications, less operative trauma and better quality of life after surgery. The present work represents a short review of the evolution of surgical techniques in treatment of spinal disorders encountered in ankylosing spondylitis. Emphasis is given to the benefits of improved instrumentation systems, intraoperative navigation, spinal cord monitoring and endoscopic surgery done in the prone position in completing the circumferential osteotomy of the thoracolumbar and lumbar spine in a safe and successful way. Fifty patients with deformities in the lumbar and thoracolumbar spine and 34 with deformities in the cervical spine were treated by instrumented corrective osteotomies. Excellent correction of the disturbed sagittal profile with restoration of a horizontal axis of vision was achieved in all of them. Neurological deterioration occurred in seven patients and was completely reversible in five of them.

Novel inhibitors of DNA gyrase: 3D structure based biased needle screening, hit validation by biophysical methods, and 3D guided optimization. A promising alternative to random screening.

Random screening provided no suitable lead structures in a search for novel inhibitors of the bacterial enzyme DNA gyrase. Therefore, an alternative approach had to be developed. Relying on the detailed 3D structural information of the targeted ATP binding site, our approach combines as key techniques (1) an in silico screening for potential low molecular weight inhibitors, (2) a biased high throughput DNA gyrase screen, (3) validation of the screening hits by biophysical methods, and (4) a 3D guided optimization process. When the in silico screening was performed, the initial data set containing 350 000 compounds could be reduced to 3000 molecules. Testing these 3000 selected compounds in the DNA gyrase assay provided 150 hits clustered in 14 classes. Seven classes could be validated as true, novel DNA gyrase inhibitors that act by binding to the ATP binding site located on subunit B: phenols, 2-amino-triazines, 4-amino-pyrimidines, 2-amino-pyrimidines, pyrrolopyrimidines, indazoles, and 2-hydroxymethyl-indoles. The 3D guided optimization provided highly potent DNA gyrase inhibitors, e. g., the 3,4-disubstituted indazole 23 being a 10 times more potent DNA gyrase inhibitor than novobiocin (3).

Immunofluorescent localization of type-V collagen as a fibrillar component of the interstitial connective tissue of human oral mucosa, artery and liver.

Polyclonal antibodies against native human type-V collagen were produced in rabbits and goats. Following purification, crossreaction of the antibodies with highly immunogenic peptides of basement membranes or the interstitial matrix was excluded on the basis of sensitive radioimmunoassays. These antibodies, when applied to cryostat sections of human oral mucosa, liver and arterial walls, never stained basement membranes as did antibodies against type-IV collagen or laminin. On the contrary, we observed delicate arborizing fibers in the interstitial compartment with extensions contacting structures such as subepidermal basement membranes. Arterioles contained a unilamellar sheath of longitudinally oriented fibers limited to the intimal layer. Larger arteries exhibited a multilamellar fibrous fluorescence over the whole intima, whereas the media showed a much weaker staining. The data identified type-V collagen as an interstitial fibrillar collagen rather than a basement membrane collagen, with a tissue pattern completely different from that of collagens types I, III, VI or fibronectin. A reinterpretation of the role of type-V collagen in connective tissue function is warranted.