Differential expression of chemokine and matrix re-modelling genes is associated with contrasting schistosome-induced hepatopathology in murine models

The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we investigated the contribution of variations in host gene expression to the contrasting hepatic pathology observed between two inbred mouse strains following Schistosoma japonicum infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in S. japonicum-infected BALB/c and CBA mice. We show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with the significantly greater accumulation of neutrophils at granulomatous regions seen in histological sections of hepatic tissue. In contrast, up-regulated expression of the eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the more pronounced hepatic damage in these mice. Profibrotic genes showed similar levels of expression in both mouse strains, as did genes associated with Th1 and Th2 responses. However, imbalances in expression of matrix metalloproteinases (e.g. MMP12, MMP13) and tissue inhibitors of metalloproteinases (TIMP1) may contribute to the contrasting pathology observed in the two strains. Overall, these results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. This improved understanding of the immunopathogenesis in the murine model schistosomiasis provides the basis for a better appreciation of the complexities associated with chronic human schistosomiasis.

Secondary curve behavior in Lenke Type 1C adolescent idiopathic scoliosis after thoracoscopic selective anterior thoracic fusion

Study Design. Analysis of a case series of 24 Lenke 1C adolescent idiopathic scoliosis (AIS) patients receiving selective thoracoscopic anterior scoliosis correction. Objective. To report the behaviour of the compensatory lumbar curve in a group of Lenke IC AIS patients following thoracoscopic anterior scoliosis correction, and to compare the results of this study with previously published data. Summary of Background Data. Several prior studies have reported spontaneous lumbar curve correction for both anterior and posterior selective fusion in Lenke 1C/King-Moe II patients; however to our knowledge no previous studies have reported outcomes of thoracoscopic anterior correction for this curve type. Methods. All AIS patients with a curve classification of Lenke 1C and a minimum of 24 months follow-up were retrieved from a consecutive series of 190 AIS patients who underwent thoracoscopic anterior instrumented fusion. Cobb angles of the major curve, instrumented levels, compensatory lumbar curve, and T5-T12 kyphosis were recorded, as well as coronal spinal balance, T1 tilt angle and shoulder balance. All radiographic parameters were measured before surgery and at 2, 6, 12 and 24 months after surgery. Results. Twenty-four female patients with right thoracic curves had a mean thoracic Cobb angle of 53.0° before surgery, decreasing to 24.9° two years after surgery. The mean lumbar compensatory Cobb angle was 43.5° before surgery, spontaneously correcting to 25.4° two years after surgery, indicating balance between the thoracic and lumbar scoliotic curves. The lumbar correction achieved (41.8%) compares favourably to previous studies. Conclusions. Selective thoracoscopic anterior fusion allows spontaneous lumbar curve correction and achieves coronal balance of main thoracic and compensatory lumbar curves, good cosmesis and patient satisfaction. Correction and balance are maintained 24 months after surgery.

Identification of vitronectin as a novel insulin-like growth factor-II binding protein

We have previously reported the presence of a 70 kDa insulin-like growth factor (IGF)-II-specific binding protein in chicken serum using Western ligand blotting approaches. In order to ascertain the identity of this 70 kDa IGF-II binding species, the protein has been purified from chicken serum using a combination of ion-exchange and gel-permeation chromatography. Interestingly, amino acid sequencing of the purified protein revealed that it has the same N-terminal sequence as chicken vitronectin (VN). The protein has the ability to specifically bind IGF-II and not IGF-I as determined by ligand blotting, cross-linking and competitive binding assay approaches. In addition, the protein binds 125I-des(l-6)-IGF-II, suggesting that the interaction with IGF-II is different to those with other characterized IGF-binding proteins. Importantly, we have ascertained that both human and bovine VN also specifically bind IGF-II. These results are particularly relevant in the light of the recent report that the urokinase-type plasminogen activator receptor, a protein that also binds VN, has been shown to associate with the cation-independent mannose-6-phosphate/GF-II receptor and suggest a possible role for IGF-II in cell adhesion and invasion.

The effect of intraoperative force on scoliosis correction at the apex : a biomechanical investigation

Adolescent idiopathic scoliosis (AIS) is a complex 3D deformity of the spine, which may require surgical correction in severe cases. Computer models of the spine provide a potentially powerful tool to virtually ‘test’ various surgical scenarios prior to surgery. Using patient-specific computer models of seven AIS patients who had undergone a single rod anterior procedure, we have recently found that the majority of the deformity correction occurs at the apical joint or the joint immediately cephalic to the apex. In the current paper, we investigate the biomechanics of the apical joint for these patients using clinically measured intra-operative compressive forces applied during implant placement. The aim of this study is to determine a relationship between the compressive joint force applied intra-operatively and the achievable deformity correction at the apical joint.

A computer model to simulate scoliosis surgery

Use of patient-specific computer models as a pre-operative planning tool permits predictions of the likely deformity correction and allows a more detailed investigation of the biomechanical influence of different surgical procedures on the scoliotic spinal anatomy. In this paper, patient-specific computer models are used of adolescent idiopathic scoliosis patients who underwent a single rod anterior procedure at the Mater Children’s Hospital in Brisbane, to predict deformity correction and to investigate the change in biomechanics of the scoliotic spine due to surgical compressive forces applied during implant placement.

Is the iPhone a useful clinical tool to monitor spinal deformity patients?

The progression of spinal deformity is traditionally monitored on hard copy radiographs using the Cobb method with a protractor and pencil. The rotation of the spine and ribcage (rib hump) in scoliosis is measured with a hand-held inclinometer/Scoliometer. The iPhone and other smart phones, can accurately sense inclination, and can therefore be used to measure Cobb angles and rib hump angulation. The purpose of this study was to quantify the performance of the iPhone compared to the standard protractor (Cobb angles) and the Scoliometer (rib hump).

Intrapleural analgesia following endoscopic scoliosis correction

Endoscopic (thoracoscopic) scoliosis correction plays an important part in the surgical options available for treating adolescent idiopathic scoliosis. However, there is a paucity of literature examining optimum methods of analgesia following this type of surgery. Intra-pleural analgesia has been successfully used following cardiothoracic procedures [1-3]. The role of intra-pleural analgesia after keyhole anterior selective thoracic scoliosis correction is examined and described.

Polycaprolactone-based scaffold plus recombinant human bone morphogenetic protein (rhBMP-2) in an ovine model of anterior spinal fusion

Synthetic scaffolds combined with growth factors have the potential to replace allograft or autograft as a graft material for spinal interbody fusion. Such tissue engineering approaches may be useful in Adolescent Idiopathic Scoliosis (AIS) surgery, however there are no studies to date examining the use of such biodegradable implants in combination with biologics in a thoracic spine model. This in vivo study examines the use of biodegradable polycaprolactone (PCL) based scaffolds with rhBMP-2 as a bone graft substitute in a sheep thoracic fusion model, where an anterior approach is used to simulate minimally invasive surgical deformity correction in the setting of AIS.

CT and X-Ray analysis of sagittal curve changes following thoracoscopic anterior scoliosis surgery

Normal thoracic kyphosis Cobb angle for T5-T12 is most commonly reported as a range of 20-40º [1]. Patients with adolescent idiopathic scoliosis (AIS) exhibit a reduced thoracic kyphosis or hypokyphosis [2] accompanying the coronal and rotary distortion components. As a result, surgical restoration of the thoracic kyphosis while maintaining lumbar lordosis and overall sagittal balance is a critical aspect of achieving good clinical outcomes in AIS patients. Previous studies report an increase in thoracic kyphosis after anterior surgical approaches [3] and a flattening of sagittal contours following posterior approaches [4]. Difficulties with measuring sagittal parameters on radiographs are avoided with reformatted sagittal CT reconstructions due to the superior endplate clarity afforded by this imaging modality and are the subject of analysis in this study.

Modelling the flow of cane constituents in the milling process

A model has been developed to track the flow of cane constituents through the milling process. While previous models have tracked the flow of fibre, brix and water through the process, this model tracks the soluble and insoluble solid cane components using modelling theory and experiment data, assisting in further understanding the flow of constituents into mixed juice and final bagasse. The work provided an opportunity to understand the factors which affect the distribution of the cane constituents in juice and bagasse. Application of the model should lead to improvements in the overall performance of the milling train.

CT and radiographic analysis of sagittal profile changes after thoracoscopic anterior scoliosis surgery

Background. Previous studies report an increase in thoracic kyphosis after anterior approaches and a flattening of sagittal contours following posterior approaches. Difficulties with measuring sagittal parameters on radiographs are avoided with reformatted sagittal CT reconstructions due to the superior endplate clarity afforded by this imaging modality. Methods. A prospective study of 30 Lenke 1 adolescent idiopathic scoliosis (AIS) patients receiving selective thoracoscopic anterior spinal fusion (TASF) was performed. Participants had ethically approved low dose CT scans at minimum 24 months after surgery in addition to their standard care following surgery. The change in sagittal contours on supine CT was compared to standing radiographic measurements of the same patients and with previous studies. Inter-observer variability was assessed as well as whether hypokyphotic and normokyphotic patient groups responded differently to the thoracoscopic anterior approach. Results. Mean T5-12 kyphosis Cobb angle increased by 11.8 degrees and lumbar lordosis increased by 5.9 degrees on standing radiographs two years after surgery. By comparison, CT measurements of kyphosis and lordosis increased by 12.3 degrees and 7.0 degrees respectively. 95% confidence intervals for inter-observer variability of sagittal contour measurements on supine CT ranged between 5-8 degrees. TASF had a slightly greater corrective effect on patients who were hypokyphotic before surgery compared with those who were normokyphotic. Conclusions. Restoration of sagittal profile is an important goal of scoliosis surgery, but reliable measurement with radiographs suffers from poor endplate clarity. TASF significantly improves thoracic kyphosis and lumbar lordosis while preserving proximal and distal junctional alignment in thoracic AIS patients. Supine CT allows greater endplate clarity for sagittal Cobb measurements and linear relationships were found between supine CT and standing radiographic measurements. In this study, improvements in sagittal kyphosis and lordosis following surgery were in agreement with prior anterior surgery studies, and add to the current evidence suggesting that anterior correction is more capable than posterior approaches of addressing the sagittal component of both the instrumented and adjacent non instrumented segments following surgical correction of progressive Lenke 1 idiopathic scoliosis.

Reversal of acute coagulopathy during hypotensive resuscitation using small-volume 7.5% NaCl adenocaine and Mg2+ in the rat model of severe hemorrhagic shock

OBJECTIVE: : Acute traumatic coagulopathy occurs early in hemorrhagic trauma and is a major contributor to mortality and morbidity. Our aim was to examine the effect of small-volume 7.5% NaCl adenocaine (adenosine and lidocaine, adenocaine) and Mg on hypotensive resuscitation and coagulopathy in the rat model of severe hemorrhagic shock. DESIGN: : Prospective randomized laboratory investigation. SUBJECTS: : A total of 68 male Sprague Dawley Rats. INTERVENTION: : Post-hemorrhagic shock treatment for acute traumatic coagulopathy. MEASUREMENTS AND METHODS: : Nonheparinized male Sprague-Dawley rats (300-450 g, n = 68) were randomly assigned to either: 1) untreated; 2) 7.5% NaCl; 3) 7.5% NaCl adenocaine; 4) 7.5% NaCl Mg; or 5) 7.5% NaCl adenocaine/Mg. Hemorrhagic shock was induced by phlebotomy to mean arterial pressure of 35-40 mm Hg for 20 mins (~40% blood loss), and animals were left in shock for 60 mins. Bolus (0.3 mL) was injected into the femoral vein and hemodynamics monitored. Blood was collected in Na citrate (3.2%) tubes, centrifuged, and the plasma snap frozen in liquid N2 and stored at -80°C. Coagulation was assessed using activated partial thromboplastin times and prothrombin times. RESULTS: : Small-volume 7.5% NaCl adenocaine and 7.5% NaCl adenocaine/Mg were the only two groups that gradually increased mean arterial pressure 1.6-fold from 38-39 mm Hg to 52 and 64 mm Hg, respectively, at 60 mins (p < .05). Baseline plasma activated partial thromboplastin time was 17 ± 0.5 secs and increased to 63 ± 21 secs after bleeding time, and 217 ± 32 secs after 60-min shock. At 60-min resuscitation, activated partial thromboplastin time values for untreated, 7.5% NaCl, 7.5% NaCl/Mg, and 7.5% NaCl adenocaine rats were 269 ± 31 secs, 262 ± 38 secs, 150 ± 43 secs, and 244 ± 38 secs, respectively. In contrast, activated partial thromboplastin time for 7.5% NaCl adenocaine/Mg was 24 ± 2 secs (p < .05). Baseline prothrombin time was 28 ± 0.8 secs (n = 8) and followed a similar pattern of correction. CONCLUSIONS: : Plasma activated partial thromboplastin time and prothrombin time increased over 10-fold during the bleed and shock periods prior to resuscitation, and a small-volume (~1 mL/kg) IV bolus of 7.5% NaCl AL/Mg was the only treatment group that raised mean arterial pressure into the permissive range and returned activated partial thromboplastin time and prothrombin time clotting times to baseline at 60 mins.