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1.
Acta Orthop ; 94: 626-634, 2023 12 29.
Article in English | MEDLINE | ID: mdl-38157007

ABSTRACT

BACKGROUND AND PURPOSE: We conducted a systematic review and meta-analysis of RSA studies to investigate the early and long-term migration patterns of acetabular cups and the influence of implant factors on cup migration over time. METHODS: We performed a systematic search of PubMed, Embase, and Scopus databases to identify all RSA studies of cup migration following primary total hip replacement (THR). Proximal migration at 3 and 6 months, 1, 2, 5, and 10 years were considered for analysis. Implant factors investigated included fixation type, head size, bearing surface, uncemented coating design, and the decade of RSA introduction. RESULTS: 47 studies reported the proximal migration of 83 cohorts (2,328 cups). Besides 1 threaded cup design, no implant factor investigated was found to significantly influence proximal migration. The mean pooled 2-year proximal migration of cemented cups (0.14 mm, 95% confidence interval [CI] 0.08-0.20) was not significantly different from uncemented cups (0.12 mm, CI 0.04-0.19). The mean pooled proximal migration at 6 months was 0.11 mm (CI 0.06-0.16) and there was no significant increase between 6 months and 2 years (0.015 mm, CI 0.000-0.030). 27 of 75 cohorts (36%) reported mean proximal migration greater than 0.2 mm at 2 years, which has previously been identified as a predictor of implants at risk of long-term loosening. CONCLUSION: Our meta-analysis demonstrated that the majority of cup migration occurs within the first 6 months. With one exception, no implant factors influenced the 2-year proximal migration of acetabular cups. 36% of studies with 2-year migration were considered at risk of long-term loosening. Further investigation and comparison against long-term survivorship data would validate 6-month and/or 1-year proximal migration measurements as an earlier predictor of long-term loosening than the current 2-year threshold.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Humans , Hip Prosthesis/adverse effects , Follow-Up Studies , Arthroplasty, Replacement, Hip/adverse effects , Acetabulum/surgery , Reoperation , Prosthesis Failure , Prosthesis Design
3.
J Biomech ; 145: 111351, 2022 12.
Article in English | MEDLINE | ID: mdl-36334320

ABSTRACT

Accurate rupture risk assessment of ascending aortic aneurysms is important for reducing aneurysm-related mortality. More recently, computational models have been shown to better predict rupture risk than diameter-based measurements. However, it remains unclear whether finite element (FE) models of the ascending aorta can predict rupture location, and over what timeframe those predictions are reliable. The aim of this study was to evaluate FE models of the ascending aorta generated from computed tomography (CT) scans in predicting rupture location. Pre- and post-rupture CT scans were obtained of 12 patients who underwent emergency surgical repair for ascending aorta rupture with varying time intervals between scans (20 days - 6 years). A rigid iterative closest point (ICP) registration was used to overlay post-rupture aortic geometries with pre-rupture FE models and directly compare predicted regions of high equivalent strain with actual rupture. The FE model predicted the rupture location in the 5 patients with the shortest time intervals between the pre- and post-rupture scans (20 days - 2 years, 3 months). However, rupture location was not predicted in the 4/5 patients with greater than 3 years between scans. Achieving a physiological equivalent strain distribution in the FE model was highly dependent on the resolution of the pre-rupture scan and whether contrast agent was present. The results suggest there may be a time interval beyond which FE predictions of rupture location may not be reliable. The results in this study may help clinical validation of FE models of ascending aortic aneurysms predicting rupture risk.


Subject(s)
Aneurysm, Ascending Aorta , Humans , Finite Element Analysis , Tomography, X-Ray Computed
4.
Br J Neurosurg ; 35(5): 532-540, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34355992

ABSTRACT

OBJECT: The purpose of this review is to highlight the major factors limiting the progress of robotics development in the field of cranial neurosurgery. METHODS: A literature search was performed focused on published reports of any Neurosurgical technology developed for use in cranial neurosurgery. Technology was reviewed and assessed for strengths and weaknesses, use in patients and whether or not the project was active or closed. RESULTS: Published reports of 24 robots are discussed going back to 1985. In total, there were 9 robots used in patients (PUMA, Robot Hand, EXPERT, Neuromate, Evolution 1, ROSA, iSYS1, NeuroArm and NeuRobot) and only 2 active today (ROSA, NeuroArm). Of all clinically active systems, only three were used in more than 30 patients (ROSA, iSYS1 & NeuroArm). Projects were limited by cost, technology adoption, and clinical utility to actually improve workflow. The most common use of developed robots is for Stereotaxis. CONCLUSIONS: There is a clear void in the area of cranial neurosurgery regarding robotics technology despite success in other fields of surgery. Significant factors such as cost, technology limitations, market size and regulatory pathway all contribute to a steep gradient for success.


Subject(s)
Neurosurgery , Robotics , Humans , Imaging, Three-Dimensional , Neurosurgical Procedures
5.
World J Surg Oncol ; 19(1): 37, 2021 Feb 02.
Article in English | MEDLINE | ID: mdl-33530997

ABSTRACT

BACKGROUND: Denosumab (XgevaTM) is a fully human antibody to RANK-Ligand, an important signal mediator in the pathogenesis of giant cell tumour of bone (GCTB). The use of denosumab in the treatment of GCTB has changed the way in which these tumours are managed over the past years. CASE PRESENTATION: Described is the case of an acute fracture through a GCTB of the distal radius of a fit and well 32-year-old, non-smoking, female patient following a simple fall onto her outstretched, dominant hand. The aim was to enable joint sparing management for the patient, as opposed to an acute fusion procedure of the carpus. The patient underwent percutaneous k-wire fixation with application of plaster and immediate commencement with denosumab to halt the activity of the GCTB. Bone healing was rapid; plaster and k-wires were removed after 6 weeks. At 6 months denosumab, was ceased and an open curettage and grafting procedure of the tumour bed was undertaken (using MIIG X3, Wright Medical, aqueous calcium sulphate as graft material). CONCLUSIONS: The use of denosumab in the acute setting of pathological fracture through giant cell tumour of bone allowing joint salvage has not been previously described. The treatment was well tolerated and functional outcomes are excellent, with very promising 4-year follow-up. This novel approach may allow for more joint sparing strategies in the future for other patients in this difficult situation. Further cases will need to be gathered to establish this technique as a suitable treatment pathway.


Subject(s)
Bone Density Conservation Agents , Bone Neoplasms , Fractures, Spontaneous , Giant Cell Tumor of Bone , Adult , Bone Density Conservation Agents/therapeutic use , Bone Neoplasms/drug therapy , Denosumab/therapeutic use , Female , Fractures, Spontaneous/drug therapy , Fractures, Spontaneous/etiology , Giant Cell Tumor of Bone/drug therapy , Humans , Neoplasm Recurrence, Local , Prognosis
6.
J Orthop Surg Res ; 16(1): 127, 2021 Feb 10.
Article in English | MEDLINE | ID: mdl-33568171

ABSTRACT

BACKGROUND: With the fourth largest metropolitan population density, motor vehicle drivers in Adelaide, South Australia, record the most number of motor vehicle insurance claims in Australia. Previous studies have shown a rise in cycling-related emergency department presentations from 2005 to 2010. There is no specific data available specifically related to South Australia. Our institution is the largest level 1 trauma centre in South Australia and Northern Territory and has a local geographic pool of the central metropolitan region of Adelaide. The aims of this study were to establish the demographics of cycling-related presentations to our institution that involved the admission of a patient under the Orthopaedic and Trauma service. Secondary aims were to investigate whether there were any common variables among these presentations that could be modified to prevent or reduce the morbidity of cycling-related trauma. METHODS: A prospective study was performed at our institution from 1 March 2018 until 31 December 2019 of all inpatient admissions under the Orthopaedics and Trauma department, where the patient was injured as a cyclist. We collated patient-reported information about the accident and their cycling habits. RESULTS: One hundred and ten patients were included in the study. One hundred and thirty-one injuries were recorded, requiring 89 surgical procedures. Eighty were upper limb injuries (61%), 49 were lower limb (37%), and 2 injuries occurred in either the spine or ribs. The most common reason for the accident was excessive cyclist speed. CONCLUSIONS: The majority of cyclists admitted to our unit with orthopaedic injuries were male patients who assessed themselves as experienced riders, and yet still were involved in accidents that resulted predominantly from episodes of poor judgement. Speed is a common and avoidable factor involved in the presentation of orthopaedic-related trauma to the public system. Involvement of other vehicles was relatively uncommon, as was poor weather; upper limb injuries predominate in this group.


Subject(s)
Bicycling/injuries , Cost of Illness , Orthopedic Procedures/statistics & numerical data , Wounds and Injuries/epidemiology , Wounds and Injuries/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Australia/epidemiology , Female , Humans , Male , Middle Aged , Prospective Studies , Trauma Centers/statistics & numerical data , Trauma Severity Indices , Wounds and Injuries/prevention & control , Wounds and Injuries/surgery , Young Adult
7.
JBJS Rev ; 8(4): e0170, 2020 04.
Article in English | MEDLINE | ID: mdl-32304493

ABSTRACT

* Radiostereometric analysis (RSA) studies of acetabular component migration following revision total hip arthroplasty (THA) have a large variation in their methodology and reporting of results, and, therefore, they may not be directly comparable. Standardization of RSA reporting is recommended. * In our review of RSA studies, there was a trend for cemented acetabular components to have larger amounts of early proximal migration than uncemented acetabular components. Results regarding cemented and uncemented components should be reported separately. * Cohorts that addressed larger acetabular defects were associated with a larger amount of early migration. * Reporting the migration result at 1 and 2 years postoperatively may enable earlier identification of poorly performing implants.


Subject(s)
Acetabulum/diagnostic imaging , Arthroplasty, Replacement, Hip/adverse effects , Hip Prosthesis/adverse effects , Postoperative Complications/diagnostic imaging , Reoperation/adverse effects , Arthroplasty, Replacement, Hip/instrumentation , Humans , Radiostereometric Analysis
8.
J Orthop Res ; 38(7): 1497-1505, 2020 07.
Article in English | MEDLINE | ID: mdl-32039492

ABSTRACT

Radiostereometric analysis (RSA) is the most accurate method of measuring component migration using radiographs but is restricted to use in prospective studies. Ein-Bild-Roentgen-analyze (EBRA)-Cup can be used retrospectively, but its accuracy to measure component migration following revision is unknown. This study aimed to determine the accuracy of EBRA-Cup measurements of uncemented acetabular component migration after revision total hip replacement (THR). The secondary aim was to compare the number of cases identified using EBRA-Cup and RSA as having proximally migrated above and below 1 mm at 2 years postoperatively. EBRA-Cup measurements were performed on plain antero-posterior pelvic radiographs taken at the same time as RSA radiographs in a prospective cohort of 53 hips undergoing acetabular revision. At 2 years, the mean difference between the RSA and EBRA-Cup measurements for 17 components used to treat pelvic discontinuity was 0.90 mm, significantly greater than the mean difference of 0.28 mm for 36 components without discontinuity (P = .0001). The mean difference between the RSA and EBRA-Cup measurements at 2 years for hips that were reconstructed with an acetabular component alone, 0.28 mm, was significantly lower than hips that were reconstructed with an acetabular component in combination with an augment and/or cage, 0.74 mm (P = .0005). In conclusion, EBRA-Cup can accurately measure migration of uncemented acetabular components used at revision THR. The presence of pelvic discontinuity, and addition of augments and cages, significantly influenced the accuracy of EBRA-Cup measurements. EBRA-Cup and RSA had good agreement on classification of components that migrated proximally above or below 1 mm at 2 years, with 100% sensitivity, and 87% specificity.


Subject(s)
Acetabulum/surgery , Arthroplasty, Replacement, Hip/instrumentation , Hip Joint/diagnostic imaging , Hip Prosthesis , Prosthesis Failure , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Radiostereometric Analysis
9.
J Bone Joint Surg Am ; 100(22): 1926-1933, 2018 Nov 21.
Article in English | MEDLINE | ID: mdl-30480597

ABSTRACT

BACKGROUND: The acetabular components used in revision total hip arthroplasty (THA) to treat severe acetabular bone defects have high rates of re-revision at mid to long-term follow-up. Early translation of acetabular components used in revision THA is a good predictor of later loosening, and radiostereometric analysis (RSA) is the most sensitive method to measure migration. The objectives of the present study were to use RSA to compare the migration of the porous tantalum acetabular components used to treat severe bone defects with the previously established acceptable proximal translation threshold of ≤1 mm within 2 years, and to determine the effect on migration of the addition of inferior screws through the component into the ischium or pubis. METHODS: RSA was utilized to measure the migration of 55 porous tantalum components used to treat severe acetabular defects (28 Paprosky IIIA, 27 Paprosky IIIB; 21 hips with pelvic discontinuity) at a mean follow-up of 4 years (range, 2 to 12 years). RESULTS: Forty-eight of the 55 components migrated less than the threshold that predicts later loosening (>1 mm) and 50 had not been re-revised at the time of the latest follow-up. Seven components, none of which had inferior screw fixation, exceeded the translation threshold. Of these, 6 were implanted to treat pelvic discontinuity. Of those 6 components, 5 were re-revised for loosening related to patient symptoms. At 2 years, the absolute median proximal translation of components with inferior screw fixation was |0.3| mm (range, |0.1| to |0.9| mm), compared with |0.4| mm (range, |0.03| to |16.4| mm) for those without inferior screws (p = 0.04). CONCLUSIONS: As measured with use of RSA, the majority of porous tantalum acetabular components used in a revision THA to treat severe acetabular defects had acceptable early migration. This predicts good long-term survivorship of these components. The use of inferior screws further improved acetabular component fixation. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Acetabulum/surgery , Arthroplasty, Replacement, Hip , Bone Diseases/surgery , Foreign-Body Migration/diagnostic imaging , Hip Prosthesis , Prosthesis Design , Prosthesis Failure , Reoperation , Tantalum , Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Porosity , Prospective Studies , Radiostereometric Analysis , Severity of Illness Index
10.
Clin Cancer Res ; 23(14): 3575-3584, 2017 Jul 15.
Article in English | MEDLINE | ID: mdl-28193626

ABSTRACT

Purpose: Standard therapy for newly diagnosed glioblastoma (GBM) is surgical resection, followed by concurrent radiotherapy and temozolomide chemotherapy. In this phase II clinical trial, the addition of an autologous heat-shock protein vaccine to standard therapy was evaluated. Tumor-induced immunosuppression, mediated by expression of PD-L1 on tumor and circulating immune cells, may impact the efficacy of vaccination. Expression of PD-L1 on peripheral myeloid cells was evaluated for the first time as a predictor of survival.Experimental Design: In this single arm, phase II study, adult patients with GBM underwent surgical resection followed by standard radiation and chemotherapy. Autologous vaccine (Prophage) was generated from resected tumors and delivered in weekly vaccinations after completion of radiotherapy. The primary endpoint was overall survival.Results: Forty-six patients received the vaccine with a median overall survival of 23.8 months [95% confidence interval (CI), 19.8-30.2]. Median overall survival for patients with high PD-L1 expression on myeloid cells was 18.0 months (95% CI, 10.0-23.3) as compared with 44.7 months (95% CI, incalculable) for patients with low PD-L1 expression (hazard ratio 3.3; 95% CI, 1.4-8.6; P = 0.007). A multivariate proportional hazards model revealed MGMT methylation, Karnofsky performance status, and PD-L1 expression as the primary independent predictors of survival.Conclusions: Vaccination with autologous tumor-derived heat shock proteins may improve survival for GBM patients when combined with standard therapy and warrants further study. Systemic immunosuppression mediated by peripheral myeloid expression of PD-L1 is a recently identified factor that may significantly impact vaccine efficacy. Clin Cancer Res; 23(14); 3575-84. ©2017 AACR.


Subject(s)
B7-H1 Antigen/immunology , Glioblastoma/drug therapy , Programmed Cell Death 1 Receptor/immunology , Vaccines, Subunit/administration & dosage , Adult , Aged , DNA Methylation/immunology , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Glioblastoma/immunology , Glioblastoma/pathology , Heat-Shock Proteins/immunology , Heat-Shock Proteins/therapeutic use , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Peptides/immunology , Peptides/therapeutic use , Prognosis , Vaccines, Subunit/immunology
11.
J Med Case Rep ; 9: 275, 2015 Nov 27.
Article in English | MEDLINE | ID: mdl-26614305

ABSTRACT

INTRODUCTION: We report the progression of an intraoperative L5-S1 lumbar disc herniation that occurred during a routine microdiscectomy and transforaminal lumbar interbody fusion, which, to the best of our knowledge, has never been previously reported in the literature. The objective of this report is to bring to light the possibility of a lumbar disc herniating intraoperatively, and to demonstrate that accompanying neurologic involvement can be detected and subsequently addressed with the aid of neurophysiologic monitoring. CASE PRESENTATION: A 36-year-old African American woman, who had previously undergone minimally invasive microdiscectomy for a right L5-S1 herniated nucleus pulposus with full recovery, presented with a large reherniation of the L5-S1 disc on the right side. During her operation, while a tap was followed into the L5 left pedicle, there was a sudden profound spasm of our patient's legs and back that lasted for the duration of 15 seconds, culminating in the loss of all somatosensory evoked potentials in our patient's lower extremities. Exploration of this previous microlaminotomy site revealed a massive disc extrusion protruding through the microlaminotomy. Immediate removal of this extruded disc material restored all somatosensory evoked potentials and our patient awoke with no neurologic deficits. CONCLUSIONS: An intraoperative disc herniation in the lumbar spine, though very rare, can occur and can result in neurologic compromise as evidenced by the loss of somatosensory evoked potentials. By identifying the event, it can be remedied by evaluating the disc visually, removing extruded fragments and decompressing nerve roots with recovery of somatosensory evoked potentials and normal neurologic function postoperatively. If neurophysiological monitoring shows there is a sudden loss of response, then consideration should be given to the possibility of an acute intraoperative herniation.


Subject(s)
Diskectomy/adverse effects , Intervertebral Disc Displacement/surgery , Lumbar Vertebrae/surgery , Spinal Fusion/methods , Adult , Electromyography , Female , Humans , Lumbosacral Region , Magnetic Resonance Imaging , Neurosurgical Procedures
12.
Clin Orthop Relat Res ; 473(12): 3811-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26194560

ABSTRACT

BACKGROUND: The incidence of acetabular fractures in osteoporotic patients is increasing. Immediate total hip arthroplasty (THA) has potential advantages, but achieving acetabular component stability is challenging and, at early followup, reported revision rates for loosening are high. QUESTIONS/PURPOSES: This study measured acetabular component stability and the initial surface contact achieved between the acetabular component and unfractured region of the pelvis after THA using an oversized acetabular component and cup-cage reconstruction. METHODS: Between November 2011 and November 2013, we treated 40 acute acetabular fractures in patients older than 70 years of age. Of these, 12 (30%) underwent immediate THA using an oversized acetabular component with screws inserted only into the ilium and a cup-cage construct. Postoperatively all patients were mobilized without weightbearing restrictions. Indications for immediate THA after acetabular fractures were displaced articular comminution deemed unreducible. Eleven of the 12 were prospectively studied to evaluate the initial stability of the reconstructions using radiostereometric analysis. One of the patients died of a pulmonary embolism after surgery, and the remaining 10 (median age, 81 years; range, 72-86 years) were studied. Of these, five were analyzed at 1 year and five were analyzed at 2 years. Acetabular component migration was defined as acceptable if less than the limits for primary THA that predict later loosening (1.76 mm of proximal migration and 2.53° of sagittal rotation). The contact surface between the acetabular component and ilium in direct continuity with the sacroiliac joint, and the ischium and pubis in direct continuity with the symphysis pubis, was measured on postoperative CT scans. RESULTS: At 1 year the median proximal migration was 0.83 mm (range, 0.09-5.13 mm) and sagittal rotation was 1.3° (range, 0.1°-7.4°). Three of the 10 components had migration above the suggested limits for primary THA at 1 year postoperatively. The contact surface achieved at surgery between the acetabular component and pelvis ranged from 11 to 17 cm(2) (15%-27% of each component). CONCLUSIONS: The majority of acetabular components in this cohort were stable despite the small contact surface achieved between the component and pelvic bone. Three of 10 migrated in excess of the limits that predict later loosening in primary THA but it remains to be seen whether these limits apply to this selected group of frail osteoporotic patients. We continue to use this technique routinely to treat patients with the same indications, but since the analysis of these data we have added screw fixation of the acetabular component to the ischial tuberosity and the superior pubic ramus. LEVEL OF EVIDENCE: Level IV, therapeutic study.


Subject(s)
Acetabulum/surgery , Arthroplasty, Replacement, Hip/instrumentation , Hip Fractures/surgery , Hip Prosthesis , Joint Instability/prevention & control , Osteoporotic Fractures/surgery , Prosthesis Failure , Acetabulum/diagnostic imaging , Acetabulum/injuries , Acetabulum/physiopathology , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip/adverse effects , Biomechanical Phenomena , Bone Density , Female , Hip Fractures/diagnostic imaging , Hip Fractures/physiopathology , Humans , Joint Instability/diagnostic imaging , Joint Instability/etiology , Joint Instability/physiopathology , Male , Osteoporotic Fractures/diagnostic imaging , Osteoporotic Fractures/physiopathology , Prospective Studies , Prosthesis Design , Radiography , Risk Factors , Time Factors , Treatment Outcome
13.
J Neurosurg ; 112(3): 658-65, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19698048

ABSTRACT

OBJECT: Treatment of cerebral aneurysms by endovascular deployment of liquid embolic agents has been proposed as an alternative strategy to conventional coiling, and new materials are being developed for embolization. In this study, the authors used a single-injection, biocompatible, biodegradable and pH-responsive acrylated chitosan (aCHN) with conjugated vascular endothelial growth factor (rhVEGF) in a rat aneurysm model. METHODS: The efficacy of the aCHN formulation with rhVEGF was tested using a common carotid artery occlusion model in rats, and the extent of embolization was evaluated using quantitative, qualitative, and histopathological techniques after 14 days of implantation. RESULTS: The mean occlusion was significantly greater for the rhVEGF/aCHN-treated group (96.8 +/- 3.0%) than for the group receiving aCHN (74.7 +/- 5.6%) (p < 0.01). Through qualitative evaluation, intimal and medial proliferation were significantly greater with rhVEGF/aCHN than with aCHN and controls (p < 0.001). Degradation of the aCHN filler was monitored in concert with the production of extracellular matrix components. Macrophages migrated in and proliferated inside the occluded carotid artery lumens were identified by histological and immunostainings. Results showed resorption of chitosan with concurrent development of collagen and elastin into the vessel lumen, suggesting clot maturation into fibrosis. CONCLUSIONS: Chitosan with a bioactive agent such as rhVEGF showed excellent results in occluding aneurysms in a rat model.


Subject(s)
Carotid Artery Diseases/therapy , Carotid Artery, Common , Embolization, Therapeutic/methods , Intracranial Aneurysm/therapy , Animals , Biocompatible Materials/therapeutic use , Brain/pathology , Brain/physiopathology , Carotid Artery Diseases/pathology , Carotid Artery Diseases/physiopathology , Carotid Artery, Common/pathology , Carotid Artery, Common/physiopathology , Chitosan/therapeutic use , Collagen/metabolism , Disease Models, Animal , Elastin/metabolism , Extracellular Matrix/metabolism , Fibrosis/pathology , Fibrosis/physiopathology , Hydrogen-Ion Concentration , Intracranial Aneurysm/pathology , Intracranial Aneurysm/physiopathology , Macrophages/pathology , Macrophages/physiology , Mitogens/therapeutic use , Rats , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/therapeutic use
14.
J Neurosurg ; 110(5): 1015-20, 2009 May.
Article in English | MEDLINE | ID: mdl-19119878

ABSTRACT

OBJECT: One mechanism that contributes to cerebral vasospasm is the impairment of potassium channels in vascular smooth muscles. Adenosine triphosphate-sensitive potassium channel openers (PCOs) appear to be particularly effective for dilating cerebral arteries in experimental models of subarachnoid hemorrhage (SAH). A mode of safe administration that provides timed release of PCO drugs is still a subject of investigation. The authors tested the efficacy of locally delivered intrathecal cromakalim, a PCO, incorporated into a controlled-release system to prevent cerebral vasospasm in a rat model of SAH. METHODS: Cromakalim was coupled to a viscous carrier, hyaluronan, 15% by weight. In vitro release kinetics studies showed a steady release of cromakalim over days. Fifty adult male Sprague-Dawley rats weighing 350-400 g each were divided into 10 groups and treated with various doses of cromakalim or cromakalim/hyaluronan in a rat double SAH model. Treatment was started 30 minutes after the second SAH induction. Animals were killed 3 days after treatment, and the basilar arteries were processed for morphometric measurements and histological analysis. RESULTS: Controlled release of cromakalim from the cromakalim/hyaluronan implant at a dose of 0.055 mg/kg significantly increased lumen patency in a dose-dependent manner up to 94 +/- 8% (mean +/- standard error of the mean) of the basilar arteries of the sham group compared with the empty polymer group (p = 0.006). Results in the empty polymer group were not different from those in the SAH-only group, with a lumen patency of 65 +/- 12%. Lumen patencies of the cromakalim-only groups did not differ in statistical significance at low (64 +/- 9%) or high (66 +/- 7%) doses compared to the SAH-only group. CONCLUSIONS: Treatment of SAH with a controlled-release cromakalim/hyaluronan implant prevented experimental cerebral vasospasm in this rat double hemorrhage model; this inhibition was dose-dependent. The authors' results confirm that sustained delivery of cromakalim perivascularly to cerebral vessels could be an effective therapeutic strategy in the treatment of cerebral vasospasm after SAH.


Subject(s)
Absorbable Implants , Cromakalim/administration & dosage , Drug Delivery Systems , Potassium Channels/drug effects , Subarachnoid Hemorrhage/complications , Vasodilator Agents/administration & dosage , Vasospasm, Intracranial/prevention & control , Animals , Hyaluronic Acid , Male , Rats , Rats, Sprague-Dawley
15.
Neurol Res ; 31(5): 528-33, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19055874

ABSTRACT

OBJECTIVE: The adult brain is capable of neurogenesis after cerebral ischemia. We investigated the presence of new neural precursors after transient middle cerebral artery ischemia adult rats. METHODS: Transient middle cerebral artery ischemia was induced in adult Wistar rats (n=13) using the monofilament method. In the experimental group (n=8), animals were harvested at days 3, 7, 10, 17 and 21 after ischemia. Five animals served as controls. Sagittal sections through the ischemic cortex were double-stained for neural (nestin and beta-tubulin, nestin and PCNA), glial (nestin and GFAP) and oligodendroglial (nestin and O4, CNP and PCNA) precursors. Double-stained cells were also counted under high-power view and tabulated over time. RESULTS: In the subventricular zone (SVZ), there was positive double-staining starting at day 3 showing proliferating astrocytic precursors (nestin + GFAP, 5-20% of cells), neuronal stem cells (nestin + PCNA, 95% of cells) and neuronal precursors (nestin + beta-tubulin, 50% of cells). Within the penumbra, a more robust response showed more astrocytic precursors (50-80% of cells), premature and differentiated oligodendrocytes, neuronal stem cells (85% of cells) and neuronal precursors (15% of cells). In the area of the stroke, there was an intermediate response consisting of more astrocytic precursors (10-20% of cells), premature oligodendrocytes (45-100% of cells), neuronal stem cells (95% of cells) and neuronal precursors (25% of cells). Results were confirmed with cell counting analysis. DISCUSSION: Our results show that not only do neural precursors proliferate in the SVZ, there is definite and real response in the penumbra and ischemic cortex, suggesting the ability of repair in the central nervous system.


Subject(s)
Brain Ischemia/physiopathology , Infarction, Middle Cerebral Artery/physiopathology , Neurogenesis/physiology , Adult Stem Cells/metabolism , Animals , Astrocytes/metabolism , Brain Ischemia/etiology , Brain Ischemia/metabolism , Immunohistochemistry , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/metabolism , Male , Neurons/metabolism , Oligodendroglia/metabolism , Rats , Rats, Wistar , Time Factors
16.
Neurosurgery ; 63(6): 1011-9; discussion 1019-21, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19057314

ABSTRACT

OBJECTIVE: The pharmacological treatment of cerebral vasospasm (CVS) now includes the experimental use of controlled-release biocompatible compounds that deliver a desired drug locally into the subarachnoid space. A controlled-release system consists of an active material that is incorporated into a carrier, usually in the form of a pellet or a gel. With such systems, the desired agent is delivered slowly and continuously, for long periods of time, directly to the desired site. This technology makes it possible to achieve high local concentrations of therapeutic agents while minimizing systemic toxicity and circumventing the need to cross the blood-brain barrier. This review describes controlled-release systems developed to date for local drug delivery in the treatment of CVS in both animal models and humans. METHODS: A MEDLINE PubMed database search was performed for articles published from 1975 to 2007 with the following search topics: "controlled-release system/polymer," "controlled-release implants," "cerebral vasospasm," "subarachnoid hemorrhage," "subarachnoid space," and "intracranial drug delivery." RESULTS: Over the past several decades, several controlled-release systems (lactic/ glycolic acid pellets, ethylene vinyl acetate copolymer, liposomes, silicone elastomers) have been developed to deliver various pharmacological agents (papaverine, nicardipine, ibuprofen, nitric oxide donor, calcitonin gene-related peptide, fasudil, recombinant tissue plasminogen activator) intracranially to treat subarachnoid hemorrhage in animal models (rats, rabbits, dogs, and primates). Animal studies have shown promising results, and the few human studies that have been published using controlled-release systems with papaverine or nicardipine report similarly encouraging outcomes. CONCLUSION: Controlled-release systems have evolved over the past few years and have been shown experimentally to be an effective strategy for the local delivery of drugs to treat CVS.


Subject(s)
Biocompatible Materials/administration & dosage , Delayed-Action Preparations/administration & dosage , Vasodilator Agents/administration & dosage , Vasospasm, Intracranial/drug therapy , Vasospasm, Intracranial/epidemiology , Humans , Treatment Outcome
17.
Surg Neurol ; 63(3): 229-34; discussion 234-5, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15734507

ABSTRACT

BACKGROUND: The Fisher grade (FG) is widely used to predict cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). We revisited the grading scale to determine its validity in the era of modern management. METHODS: We retrospectively reviewed the records of 134 patients with SAH. The amount and distribution of subarachnoid blood on admission computed tomography (CT) scan was quantified according to the FG and compared with development of symptomatic vasospasm. RESULTS: We reviewed 134 patients (median age, 54) who presented with aneurysmal SAH. Six (5%) were FG 1, 34 (25%) were FG 2, 25 (19%) were FG 3, and 69 (51%) were FG 4. Symptomatic vasospasm developed in no (0%) FG 1, 8 (24%) FG 2, 7 (28 %) FG 3, and 13 (19%) FG 4 patients (28 of 134 total patients; 21%). Development of symptomatic vasospasm was not associated with admission FG, Hunt and Hess grade, age, sex, or location of blood on presenting CT scan. Elevated transcranial Doppler blood flow velocity was associated with blood in the basal cisterns (P = .0047), lateral ventricles (P = .026), or blood in any ventricle (P = .04). Postoperative angiograms were obtained in 57 patients; moderate to severe vasospasm was observed in 5 (15%) FG 2, 6 (24%) FG 3, and 14 (20%) FG 4 patients. Twenty patients (71%) with symptomatic vasospasm had moderate or severe angiographic vasospasm. Angiographic vasospasm was associated with intraventricular blood (P = .054) but not with FG. CONCLUSIONS: Symptomatic vasospasm occurred in 21% of cases. The FG correlated with symptomatic vasospasm in only half the patients. A new predictive CT grading scale for vasospasm may be necessary.


Subject(s)
Severity of Illness Index , Subarachnoid Hemorrhage/diagnostic imaging , Tomography, X-Ray Computed/standards , Vasospasm, Intracranial/diagnostic imaging , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Cerebral Angiography , Cerebral Arteries/diagnostic imaging , Cerebral Arteries/physiopathology , Cerebrovascular Circulation/physiology , Disease Progression , Female , Humans , Intracranial Aneurysm/complications , Intracranial Aneurysm/surgery , Male , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , Sex Factors , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/surgery , Subarachnoid Space/diagnostic imaging , Subarachnoid Space/surgery , Ultrasonography, Doppler, Transcranial/standards , Vasospasm, Intracranial/etiology
18.
J Neurosurg ; 101(4): 594-9, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15481712

ABSTRACT

OBJECT: Nimodipine has been shown to improve neurological outcome after subarachnoid hemorrhage (SAH); the mechanism of this improvement, however, is uncertain. In addition, adverse systemic effects such as hypotension have been described. The authors investigated the effect of nimodipine on brain tissue PO2. METHODS: Patients in whom Hunt and Hess Grade IV or V SAH had occurred who underwent aneurysm occlusion and had stable blood pressure were prospectively evaluated using continuous brain tissue PO2 monitoring. Nimodipine (60 mg) was delivered through a nasogastric or Dobhoff tube every 4 hours. Data were obtained from 11 patients and measurements of brain tissue PO2, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were recorded every 15 minutes. Nimodipine resulted in a significant reduction in brain tissue PO2 in seven (64%) of 11 patients. The baseline PO2 before nimodipine administration was 38.4+/-10.9 mm Hg. The baseline MABP and CPP were 90+/-20 and 84+/-19 mm Hg, respectively. The greatest reduction in brain tissue PO2 occurred 15 minutes after administration, when the mean pressure was 26.9+/-7.7 mm Hg (p < 0.05). The PO2 remained suppressed at 30 minutes (27.5+/-7.7 mm Hg [p < 0.05]) and at 60 minutes (29.7+/-11.1 mm Hg [p < 0.05]) after nimodipine administration but returned to baseline levels 2 hours later. In the seven patients in whom brain tissue PO2 decreased, other physiological variables such as arterial saturation, end-tidal CO2, heart rate, MABP, ICP, and CPP did not demonstrate any association with the nimodipine-induced reduction in PO2. In four patients PO2 remained stable and none of these patients had a significant increase in brain tissue PO2. CONCLUSIONS: Although nimodipine use is associated with improved outcome following SAH, in some patients it can temporarily reduce brain tissue PO2.


Subject(s)
Calcium Channel Blockers/pharmacology , Intracranial Aneurysm/complications , Intracranial Aneurysm/surgery , Nimodipine/pharmacology , Oxygen/analysis , Subarachnoid Hemorrhage/drug therapy , Aged , Brain/blood supply , Calcium Channel Blockers/administration & dosage , Female , Humans , Intracranial Pressure , Male , Middle Aged , Nimodipine/administration & dosage , Subarachnoid Hemorrhage/complications
19.
J Neuroimaging ; 14(2): 133-8, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15095558

ABSTRACT

Continuous arterial spin labeling perfusion magnetic resonance imaging (CASL-pMRI) uses magnetically labeled arterial blood water as a tracer to obtain quantifiable measurements of cerebral blood flow (CBF) (mL/100 g-1/min-1). CASL-pMRI was used to assess CBF changes in major vascular distributions in patients (n = 10) prior to and 3 months after carotid endarterectomy (CEA). No significant change in the global baseline CBF before and after CEA was observed in the group as a whole (P = .81). In patients with reduced CBF prior to CEA (< 50 ml/100 g/min), a significant increase in global CBF following CEA was observed. An inverse relationship existed between percent change in CBF after CEA versus baseline CBF within the anterior circulation (r = -.78, P < .05) but not in the posterior distribution (r = .25, P = .63). CASL-pMRI may provide a convenient, inexpensive, noninvasive method for identifying CEA patients at risk for hyperperfusion following carotid revascularization.


Subject(s)
Brain Ischemia/diagnosis , Brain/blood supply , Carotid Stenosis/diagnosis , Endarterectomy, Carotid , Image Enhancement/methods , Image Processing, Computer-Assisted/methods , Magnetic Resonance Angiography/methods , Postoperative Complications/diagnosis , Reperfusion Injury/diagnosis , Aged , Aged, 80 and over , Blood Flow Velocity/physiology , Brain Ischemia/surgery , Carotid Stenosis/physiopathology , Carotid Stenosis/surgery , Cerebral Infarction/diagnosis , Cerebral Infarction/physiopathology , Cerebral Infarction/surgery , Female , Follow-Up Studies , Humans , Ischemic Attack, Transient/diagnosis , Ischemic Attack, Transient/physiopathology , Ischemic Attack, Transient/surgery , Male , Middle Aged , Neurologic Examination , Postoperative Complications/physiopathology , Regional Blood Flow/physiology , Reperfusion Injury/physiopathology , Sensitivity and Specificity , Treatment Outcome
20.
Neurosurgery ; 54(1): 150-5; discussion 155-6, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14683552

ABSTRACT

Recent studies documenting the phenomenon of de novo neurogenesis within the adult brain have propelled this area of research to the forefront of neuroscience investigations and stroke pathogenesis and treatment. Traditional theories have suggested that the central nervous system is incapable of neural regeneration; hence the emergence of the field of stem cell biology as a discipline devoted to uncovering novel forms of neural repair. However, several recent experimental observations have shown that the adult brain is capable of ongoing neurogenesis in discrete regions of the uninjured brain and additional forms of endogenous neural regeneration in the presence of an inciting event (induction neurogenesis). Induction neurogenesis has the potential for providing new insights into the cause and treatment of acute stroke syndromes.


Subject(s)
Nerve Regeneration/physiology , Neurons/physiology , Stem Cell Transplantation , Stem Cells/physiology , Stroke/physiopathology , Stroke/therapy , Acute Disease , Animals , Humans
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