Even though there are hundreds of reports in the published literature supporting the hypothesis that G protein-coupled receptors (GPCR) form and function as dimers this remains a highly controversial ...area of research and mechanisms governing homodimer formation are poorly understood. Crystal structures revealing homodimers have been reported for many different GPCR. For adrenergic receptors, a potential dimer interface involving transmembrane domain 1 (TMD1) and helix 8 (H8) was identified in crystal structures of the beta1-adrenergic (β1-AR) and β2-AR. The purpose of this study was to investigate a potential role for TMD1 and H8 in dimerization and plasma membrane expression of functional β2-AR. Charged residues at the base of TMD1 and in the distal portion of H8 were replaced, singly and in combination, with non-polar residues or residues of opposite charge. Wild type and mutant β2-AR, tagged with YFP and expressed in HEK293 cells, were evaluated for plasma membrane expression and function. Homodimer formation was evaluated using bioluminescence resonance energy transfer, bimolecular fluorescence complementation, and fluorescence correlation spectroscopy. Amino acid substitutions at the base of TMD1 and in the distal portion of H8 disrupted homodimer formation and caused receptors to be retained in the endoplasmic reticulum. Mutations in the proximal region of H8 did not disrupt dimerization but did interfere with plasma membrane expression. This study provides biophysical evidence linking a potential TMD1/H8 interface with ER export and the expression of functional β2-AR on the plasma membrane. This article is part of a Special Issue entitled: Interactions between membrane receptors in cellular membranes edited by Kalina Hristova.
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•Mutations that disrupt β2-Adrenergic Receptor (β2-AR) homodimerization•Homodimer formation was evaluated using BRET, BiFC and FCS.•Transmembrane domain 1 (TMD1) and helix 8 (H8) regulate trafficking & homodimers.•A TMD1/H8 interface is linked with ER export and expression of functional β2-AR.
Background The treatment of AOSpine A3 and A4 fractures is controversial with no consensus regarding their management in the absence of neurologic deficits. While conservative management with spinal ...orthosis is a reasonable treatment option, it is believed to run the risk of progressive segmental kyphosis. Methodology A retrospective chart review was conducted of all patients undergoing treatment for thoracolumbar burst fractures from T11 to L2. Patients treated with conservative management with lumbar orthosis were included. Upright radiographs at the time of presentation and the one-year follow-up were compared. Results In total, 112 patients were evaluated as being treated with thoracolumbar orthosis. Of these, 61 patients presented with A3 fractures compared with 51 who presented with A4 fractures. Of these, two patients in each group failed conservative management and required surgical intervention. At the one-year follow-up, A3 fractures demonstrated an average change in Cobb angle of 4.1 degrees compared with 6.1 degrees in A4 fractures (p = 0.021). In addition, A4 fractures demonstrated a significantly worse kyphotic angle and Gardner angle at the one-year follow-up (p = 0.05 and p = 0.026, respectively). Conclusions A3 and A4 fractures can be safely treated with orthosis with overall low rates for failure; however, A4 fractures result in significantly worse segmental kyphosis at the one-year follow-up.
INTRODUCTION:
The role of fusion as an adjunct to decompression in patients with stenosis associated with spondylolisthesis remains an area of controversy. We recently reported significant variation ...in treatment recommendations regarding fusion from an expert panel using data from the SLIP II study. We found that this variability was due to both surgeon specific and patient specific variables
METHODS:
A pilot study using de-identified data from the SLIP II study was performed. Expert panel recommendations were examined and patients whose recommendations reflected a consensus for decompression alone or decompression and fusion were identified. A consensus was defined as >80% agreement among panelists. Five patients were identified where there was >80% consensus for decompression alone and ten patients were identified where there was >80% consensus for decompression and fusion. Each of these 15 cases was then carefully examined to determine which characteristics (from the clinical vignette, imaging, and other patient collected data) most consistently differed between the two cohorts.
RESULTS:
With regard to demographic factors, the fusion cohort was younger (60 years vs 67.2 years, p = 0.077), and had a lower health state based on EQ-5D scores (0.50 vs 0.68, p = 0.04). There was no difference in the ODI between the cohorts (37.2 vs 37, p = 0.49).With regard to imaging characteristics, we found that greater degree of spondylolisthesis (24% vs 12%, p < 0.001), greater facet angle from horizontal (54 vs 48 degrees p = 0.12), and movement on dynamic images all predicted a recommendation for fusion.
CONCLUSION:
In examining the subset of patients with consensus from the expert panel regarding the utility of fusion, it is apparent that younger age, lower EQ-5D, sagittally-oriented facets, mobile spondylolisthesis, and degree of anterolisthesis were all associated with recommendation for fusion. This information provides significant evidence that particular patient characteristics drive senior surgeon decision making regarding the utility of fusion as an adjunct to decompression in this patient population. This has important policy implications and may help to explain disparate results from contemporary clinical trials.
Thoracolumbar burst fractures include a spectrum of treatment options ranging from conservative management to multilevel fusion with or without corpectomy. Given the variability of treatment options, ...consideration of radiographic outcomes with different treatment modalities should be a critical consideration in management.
A retrospective review was conducted evaluating all patients presenting with spine fractures over a 7-year period. Inclusion criteria were limited to adults with acute, traumatic burst fractures of the thoracolumbar joint levels T11-L2. Patients were categorized by nonoperative management, short-segment fusion, multilevel fusion without anterior column reconstruction, and corpectomy. Radiographic information collected included kyphotic angle (KA), Cobb angle (CA), and Gardner angle (GA).
In total, 117 patients (70.5%) were successfully treated nonoperatively, 4 (2.4%) underwent short-segment fusion, 28 (16.9%) underwent multilevel fusion, and 12 (7.2%) underwent corpectomy. All nonoperative patients demonstrated significantly worse kyphosis at 1-year follow-up as measured by KA, CA, and GA (
< 0.001). Patients undergoing corpectomy had the largest improvement in kyphosis with an average improvement of 14.1° on KA, 8.1° on CA, and 11.0° on GA (
< 0.001,
= 0.098
and
= 0.004, respectively). In comparison, patients undergoing multilevel fusion showed an average improvement of 2.6°, 2.7°, and 3.3° of correction on GA, CA, and KA, respectively (
> 0.05).
Nonoperative and short-segment fusion burst fracture patients demonstrated significantly worse kyphosis at 1-year follow-up. Patients undergoing corpectomy demonstrated a superior improvement in kyphotic correction compared with those undergoing multilevel fusion and short-segment fusion.
Even though there are hundreds of reports in the published literature supporting the hypothesis that G protein-coupled receptors (GPCR) form and function as dimers this remains a highly controversial ...area of research and mechanisms governing homodimer formation are poorly understood. Crystal structures revealing homodimers have been reported for many different GPCR. For adrenergic receptors, a potential dimer interface involving transmembrane domain 1 (TMD1) and helix 8 (H8) was identified in crystal structures of the beta
-adrenergic (β
-AR) and β
-AR. The purpose of this study was to investigate a potential role for TMD1 and H8 in dimerization and plasma membrane expression of functional β
-AR. Charged residues at the base of TMD1 and in the distal portion of H8 were replaced, singly and in combination, with non-polar residues or residues of opposite charge. Wild type and mutant β
-AR, tagged with YFP and expressed in HEK293 cells, were evaluated for plasma membrane expression and function. Homodimer formation was evaluated using bioluminescence resonance energy transfer, bimolecular fluorescence complementation, and fluorescence correlation spectroscopy. Amino acid substitutions at the base of TMD1 and in the distal portion of H8 disrupted homodimer formation and caused receptors to be retained in the endoplasmic reticulum. Mutations in the proximal region of H8 did not disrupt dimerization but did interfere with plasma membrane expression. This study provides biophysical evidence linking a potential TMD1/H8 interface with ER export and the expression of functional β
-AR on the plasma membrane. This article is part of a Special Issue entitled: Interactions between membrane receptors in cellular membranes edited by Kalina Hristova.
The presence of symptomatic lumbar facet cysts has been associated with segmental instability. Given this association, decompression versus decompression with fusion is a frequently debated topic. ...Multiple grading scales have been devised to identify patients at high risk for development of cyst recurrence; however, there exists no external evaluation of these scales.
A retrospective review of 54 patients undergoing initial treatment for lumbar synovial cysts at a single institution over the past 12 years was conducted. Surgical treatment consisted of decompression with cystectomy without fusion. Patients were assessed and classified according to the NeuroSpine Surgery Research Group (NSURG) and Rosenstock Classification systems. Five neurosurgeons reviewed the preoperative magnetic resonance images, and results were classified. Interrater reliability was assessed using both Gwet’s AC1 coefficient and Krippendorff’s alpha. A 1-way analysis of variance was used to evaluate predictive ability of both classification systems.
In total, of the 54 patients who underwent decompression, 7 had cyst recurrence. Overall cyst recurrence was most common in NSURG grade 2 cysts (3/12, 25%) followed by grade 1 cysts (4/27, 14.8%). Of the NSURG grade 3 and 4 patients, none had cyst recurrence. In the Rosenstock grades the most common recurrence was in grade 3 cysts (1/4, 25%) followed by grade 1 cysts (5/26, 19.2%). Interrater reliability demonstrated good reproducibility on Gwet’s AC1 and Krippendorff’s alpha on both grading scales. Neither score was predictive of cyst recurrence (P > 0.05).
The Rosenstock and NeuroSpine scores demonstrate good overall interrater reliability but are inconsistent in their ability to predict recurrence of lumbar facet cysts.
It can sometimes be challenging to find a suitable clip to treat an unusual aneurysm, or when the surrounding anatomy is unusual, especially in resource-limited environments. We describe a method to ...modify aneurysm clips based on the method originated by Sugita et al in 1985. Herein clip modification (Clip-Mod) is used to treat anatomically difficult anterior communicating artery aneurysms.
The Department of Neurological Surgery database was reviewed to find aneurysm patients treated using modified aneurysm clips. Clip-Mod was performed during surgery by shortening the tines of titanium aneurysm clips by abrasion applied from the side of a standard 3-mm surgical diamond drill bit under constant irrigation. Note that the thickness of the tines and the clip spring were not modified or contacted by the drill.
Four cases used modified aneurysm clips, from 648 total clip-treated aneurysms (0.6%) by 2 surgeons over a 14-year period. Three patients presented with subarachnoid hemorrhages that were determined to be due to anterior communicating artery aneurysms. One patient presented with an incidental unruptured anterior communicating artery aneurysm. All 4 patients were treated with 3-mm titanium clips shortened intraoperatively to 1- to 2-mm lengths, to achieve aneurysm obliteration without stenosing parent or perforating vessels.
All 4 patients have done well clinically with no reoccurrences after 2–6 years' follow-up, which included angiographic evaluation. The use of this “Clip-Mod” technique thus appears useful for anterior communicating artery aneurysms. Clip-Mod could also be considered for treating other aneurysms when the “perfect” length clip is not available.
White blood cell count, sedimentation rate and c reactive protein were within normal limits. A final diagnosis of Rosai-Dorfman disease was made. 3 Discussion RDD typically presents as a benign, ...self-limiting disorder of painless, bilateral, cervical lymphadenopathy, associated with fever, weight loss, and elevated erythrocyte sedimentation rate (ESR) 2. Radiation, either via whole brain radiation and/or stereotactic radiosurgery, has resulted in clinical improvement in patients with both intracranial and spinal lesions 1,2.
Abstract
We present the case of a venous malformation (VM) masquerading as a schwannoma. VMs are thin-walled vascular dilations of various sizes that typically present as soft, compressible, blue ...masses that are associated with pain or dysesthesia. VMs are commonly found in the head and neck as well as the distal extremities. Notably, slow-flow VMs are hypointense on T1-weighted imaging, hyperintense on T2-weighted imaging, and enhance markedly with contrast. However, VMs tend to be poorly circumscribed and fraught with venous lakes and phleboliths. Conservative therapy and sclerotherapy are the primary treatment options. In this case report, we present a VM presenting near the neurovascular bundle of the upper extremity axilla. Our case is unique in that the patient presented with symptoms and imaging qualities characteristic for a peripheral nerve schwannoma.
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