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PubMed1997

Comparison of lipid vesicle fusion induced by the putative fusion peptide of fertilin (a protein active in sperm-egg fusion) and the NH2-terminal domain of the HIV2 gp41.

A peptide representing a putative fusion domain of fertilin, a sperm surface protein involved in sperm-egg fusion was synthesized. Its interaction with model membranes was characterized and compared with that of a synthetic peptide representing the fusion peptide of HIV-2rod gp41. The fertilin fusion peptide interaction with lipid vesicles is dependent upon the presence of negatively charged lipids in the membrane. Its fusogenic activity does not require PE and is not inhibited by addition of lysolecithin in the medium. These conditions are quite opposite to those obtained with the HIV2 peptide and suggest that the lipid mixing mediated by the two peptides corresponds to two different molecular mechanisms.

ADAM Proteins↗
PubMed1994

Mutations in the fusion peptide and heptad repeat regions of the Newcastle disease virus fusion protein block fusion.

Nonconservative mutations were introduced by site-specific mutagenesis into the fusion peptide and the adjacent heptad repeat region of the fusion protein of Newcastle disease virus in order to determine the role of both regions in the fusion activity of the protein. Mutations in both regions that allowed for proper folding and intracellular transport of the protein blocked the fusion activity of the protein when assayed in the presence of the hemagglutinin-neuraminidase protein.

Amino Acid Sequence↗
PubMed1996

A multifunctional vector system for heterologous expression of proteins in Escherichia coli. Expression of native and hexahistidyl fusion proteins, rapid purification of the fusion proteins, and removal of fusion peptide by Kex2 protease.

Vectors have been constructed for the general purpose of expressing foreign proteins in E. coli. These vectors allow the production in high yield of either native proteins or of fusion proteins which contain, at their amino terminus, the peptide Met Gly His6 Ser Gly Leu Phe Lys Arg/, where Leu Phe Lys Arg/ is the recognition site for Kex2 protease which cleaves at the site indicated by /. The His6 sequence is used as a ligand for the one-step affinity purification of the expressed proteins on columns containing Ni or Zn ions chelated to iminodiacetic acid-agarose. After affinity chromatography, the purification peptide is cleaved off with Kex2 protease from Saccharomyces cerevisiae. The vectors also allow site-directed mutagenesis and sequencing of the cloned gene to be expressed without any intermediate subcloning. For practical examples of over-expression, affinity purification, and removal of the purification peptide, we chose a high-molecular-weight protein, phospholipase C gamma 1 (PLC gamma 1, M(r) 148,000) and a low-molecular-weight protein, Hit-1 (M(r) 16,000). Both were obtained pure and in high yield. PLC gamma 1 was fully active; the function of Hit-1 is not known. A set of companion vectors for co-expression of additional proteins has also been developed. These allow expression of proteins which enhance the production or activity of the protein of primary interest and of proteins which exhibit trans-interactions.

Bacteriophage T7↗
PubMed2006

Biomechanical assessment of anterior lumbar interbody fusion with an anterior lumbosacral fixation screw-plate: comparison to stand-alone anterior lumbar interbody fusion and anterior lumbar interbody fusion with pedicle screws in an unstable human cadaver model.

STUDY DESIGN: Human lumbosacral cadaveric specimens were tested in an in vitro biomechanical flexibility experiment using physiologic loads in 5 sequential conditions. OBJECTIVE: To determine the biomechanical differences between anterior lumbar interbody fusion (ALIF) using cylindrical threaded cages alone or supplemented with an anterior screw-plate or posterior pedicle screws-rods. SUMMARY OF BACKGROUND DATA: Clinically and biomechanically, stand-alone ALIF performs modestly in immobilizing the unstable spine. Pedicle screws improve fixation stiffness significantly, but supplementary anterior instrumentation has not been studied. METHODS: There were 7 specimens tested: (1) intact, (2) after discectomy and facetectomy to induce moderate rotational and translational hypermobility, (3) with 2 parallel ALIF cages, (4) with cages plus a triangular anterior screw-plate, and (5) with cages plus pedicle screws-rods. Pure moments without preload induced flexion, extension, lateral bending, and axial rotation; linear shear forces induced anteroposterior translation. Angular and linear motions were measured stereophotogrammetrically, and range of motion (ROM) and stiffness were quantified. RESULTS: Compared to the destabilized spine, interbody cages alone reduced ROM by 77% during flexion, 53% during extension, 60% during lateral bending, 69% during axial rotation, and 71% during anteroposterior shear (P < 0.001, analysis of variance/Fisher least significant difference). Addition of an anterior plate or pedicle screws-rods, respectively, further reduced ROM by 8% or 13% during flexion (P = 0.21), 21% or 28% during extension (P = 0.15), 5% or 25% during lateral bending (P = 0.04), 11% or 18% during axial rotation (P = 0.13), and 18% or 18% during anteroposterior shear (P = 0.17). Compared to stand-alone ALIF, both the anterior screw-plate and pedicle screw-rod fixation reduced vertebral ROM to less than 1.2 degrees of rotation and less than 0.1 mm of translation. CONCLUSIONS: The anterior screw-plate and pedicle screws-rods both substantially reduced ROM and increased stiffness compared to stand-alone interbody cages. There was no significant difference in the amount by which the supplementary fixation devices limited flexion, extension, axial rotation, or anteroposterior shear; pedicle screws-rods better restricted lateral bending.

Aged↗
PubMed2002

Outcome of posterior lumbar interbody fusion versus posterolateral fusion for spondylolytic spondylolisthesis.

STUDY DESIGN: This retrospective study analyzed the outcome of 44 patients who had decompression, pedicle screw-rod fixation, and fusion for Grades 1 and 2 spondylolytic spondylolisthesis. OBJECTIVE: To evaluate the outcome of two methods for stabilization and fusion: posterolateral fusion and circumferential fusion involving posterior lumbar interbody fusion and posterolateral fusion for low grades of isthmic spondylolisthesis. SUMMARY OF BACKGROUND DATA: It has been suggested that stabilization with instrumented fusion is somewhat unpredictable due to lack of anterior support. Does circumferential fusion using posterior lumbar interbody fusion circumvent all the problems, and is it better than posterolateral fusion clinically? METHODS: A single surgeon treated 21 patients with instrumented posterolateral fusion and 23 patients with instrumented circumferential fusion, (i.e., posterior lumbar interbody fusion, and posterolateral fusion. These two groups were compared for clinical outcome, fusion rate, and correction of slippage. RESULTS: The minimum follow-up period for the patients was 2.1 years. The clinical satisfactory outcome on the Oswestry index was 81% for posterolateral fusion and 69% for posterior lumbar interbody fusion. The subjective outcome was 86% and 65%, respectively, for the two groups (P > 0.05). However, a consideration of subjective scores showed that three patients (14.3%) in posterolateral fusion group and eight patients (34.8%) in posterior lumbar interbody fusion group had an unsatisfactory outcome (P = 0.0135), which was very significant. There were two nonunions in the posterolateral fusion group and none in the posterior lumbar interbody fusion group (P > 0.05). The correction of slippage and the loss of correction at the last follow-up assessment was better in the posterior lumbar interbody fusion group, although this was not statistically significant (P > 0.05). Radicular symptoms and neurologic improvement were statistically similar between the two groups. CONCLUSIONS: Posterolateral fusion has a better clinical outcome in low grades of isthmic spondylolisthesis, although posterior lumbar interbody fusion is more predictable in maintaining correction and achieving union. Careful patient selection is needed for each operation, and adjacent level disc degeneration may influence the procedure offered to the patient.

Adult↗
PubMed1998

Posterolateral fusion for isthmic spondylolisthesis in adults: analysis of fusion rate and clinical results.

This is a retrospective study of 83 consecutive adult patients with isthmic spondylolisthesis who underwent identical decompressive surgery combined with posterolateral spine fusion. We sought to determine factors that affect the fusion rate and clinical outcomes for adult patients with isthmic spondylolisthesis. The outcome of operative treatment for isthmic spondylolisthesis in adults has been poorly documented, as opposed to the treatment of children and adolescents. From 1989 to 1994, 83 consecutive adult patients (age 19-66 years; average, 38 years) underwent surgical treatment consisting of the Gill procedure and posterolateral fusion for isthmic lumbosacral spondylolisthesis. Seventy-three patients (46 men and 27 women) were available for an average of 3.8 years' follow-up (1.0-7.4 years). Thirty-eight underwent one-level fusion, and 35 underwent two-level fusions. Pedicle screw instrumentation was performed in 69 patients. A postoperative questionnaire including the Roland index, clinical charts, and radiographs were reviewed by an independent observer to assess the postoperative course, clinical results, and fusion status. Twenty-five variables were evaluated to determine which affected the fusion and success rates. Primary radiologic fusion and clinical success rates were 78 and 71%, respectively. There was a strong positive correlation between radiologic fusion and clinical success. Overall, single-level fusions showed an 82% fusion rate, and two-level fusions, a 74% rate. For two-level fusions, a significantly higher fusion rate was achieved with a rigid pedicle screw-fixation system than a semirigid system (79 vs. 57%). For smokers, cessation from smoking postoperatively did not increase the fusion rate, and patients who continued to smoke after surgery showed a significantly higher rate of pseudarthrosis. Worker's compensation status did not affect clinical results significantly. Patients who continued to take nonsteroidal antiinflammatory drugs (NSAIDs) >3 months postoperatively showed significantly lower fusion and success rates (44 and 37%). Single-level lumbar fusion for isthmic spondylolisthesis was equally effective with either rigid or semirigid pedicle screw instrumentation. For multilevel spine fusion in isthmic spondylolisthesis, rigid pedicle screw-fixation systems resulted in a high fusion rate. A smoking history or NSAIDs use postoperatively had strong negative influences on the fusion and clinical success rates.

Adult↗
PubMedDate not supplied

Bilateral implantation of low-profile interbody fusion cages: subsidence, lordosis, and fusion analysis.

BACKGROUND CONTEXT: The use of interbody fusion cages as a treatment for degenerative disc disease has become widespread. Low-profile cages have been developed to allow a closer fit when implanting bilateral cages in patients with smaller vertebral bodies. Some surgeons feel the open design also allows better bone contact and visualization. This is particularly true when two low-profile cages are used adjacent to one another. Because of the open design of low-profile interbody fusion cages, there has been concern regarding such issues as subsidence, lordosis and fusion rates. PURPOSE: This retrospective review of paired bilateral reduced profile interbody fusion cages was completed to assess changes in subsidence, lordosis and fusion. As a secondary goal, patient outcomes were measured to determine overall health since surgery and the patient's satisfaction with the spine surgery, in an attempt to assess the effect of the outcome variables cited supra. STUDY DESIGN: This was a retrospective evaluation of patients who underwent anterior lumbar interbody fusion with low-profile interbody fusion cages. PATIENT SAMPLE: Seventy-one consecutive patients who underwent bilateral implantation of low-profile interbody fusion cages were evaluated. OUTCOME MEASURES: A patient self-evaluation, which included a Short Form (SF)-36 and questions regarding patient satisfaction were administered to patients who were at least 1 year postoperative. Subsidence and lordosis measurements were completed. Fusion was assessed by the operating surgeon. METHODS: Low-profile interbody fusion cages (BAK/Proximity, Centerpulse Spine-Tech, Inc., Minneapolis, MN) were implanted bilaterally in at least one level from L3-L4 to L5-S1. Most patients had degenerative disc disease with leg and back pain that was not responsive to conservative treatment and demonstrated segmental instability or collapse. A small percentage of patients had either a degenerative spondylolisthesis (7.0%) or an isthmic spondylolisthesis (4.2%). Autograft harvested from the iliac crest was used in all cases. Demographic, surgical and follow-up data were retrospectively collected from patient charts. A clinical outcome questionnaire that included an SF-36 as well as questions regarding patient satisfaction was either mailed to each patient who was at least 1 year postsurgery or given to patients to complete at their 1-year visit. Patients were routinely followed radiographically before surgery, immediately after surgery and at 3, 6, 12 and 24 months after surgery. Fusion was assessed by the operating surgeon using lateral radiographs often in conjunction with a thin-slice computed tomography (CT) scan. Criteria for a successful fusion were lack of motion, anterior bridging bone and lack of lucencies on flexion/extension X-rays and/or contiguous bone through the cage using a thin-cut sagittal CT scan. Lateral X-rays on each patient were also measured for subsidence and lordosis changes. RESULTS: A total of 71 patients (45 men, 26 women) with a mean age of 43.4 years (range, 25 to 74) were evaluated. Thirty-six percent of the patients were smokers, and 96% were worker's compensation patients. Thirty-two percent of the patients had previous lumbar surgery. A total of 100 operative levels were evaluated. There were 45 one-level, 23 two-level and three three-level cases. Forty-nine percent were level L5-S1, 43% were L4-L5 and 8% were L3-L4. The mean duration of symptoms was 31.5 months. Mean surgical time, mean blood loss and mean hospital stay were 139 minutes, 186 cc and 3.34 days, respectively. There were no intraoperative or postoperative complications attributable to the construct and no cases of cage migration or collapse. Patients who were at least 1-year postsurgery and had follow-up X-rays or had undergone a CT scan at this time point were evaluated for fusion status. Sixty-three patients were assessed for fusion. Fifty-four (86%) of these patients were determined to have a solid fusion. Mean time to fusion was 10 months. Fusion was assessed as solid only if all operative levels were fully fused. Mean subsidence of the anterior region was 1.97 mm, whereas the mean subsidence of the posterior region was 0.82 mm. Lordosis was unchanged at all surgical levels with mean lordosis in L3-L4 decreasing only slightly from 13 degrees before surgery to 12 degrees after surgery. L4-L5 and L5-S1 showed only slight increases in lordosis changing from 17 to 18 degrees at L4-L5 and from 17 to 19 degrees at L5-S1. These changes were not statistically significant. The clinical outcome questionnaires had a return rate of 68%. Of the 48 patients who completed the questionnaire, 75% responded that they were happy with the surgical results and would definitely recommend the surgery to a friend. Sixty-seven percent agreed that surgery met their expectations or that surgery improved their condition enough that they would go through it again for the same outcome. The results of the SF-36 portion of the survey revealed that the physical and mental composite scores were within normal range of the US population that has experienced back pain or sciatica. CONCLUSION: Bilateral implantation of low-profile cages in this patient population led to satisfactory outcomes. Subsidence and changes in lordosis were minimal. Fusion rates were good, especially for one-level cases. Patient satisfaction was relatively high, considering the population consisted of 96% worker's compensation cases. With proper surgical technique, bilateral low-profile cages can be used effectively to treat patients with degenerative disc disease.

Health Status↗
PubMed1997

Adding posterior lumbar interbody fusion to pedicle screw fixation and posterolateral fusion after decompression in spondylolytic spondylolisthesis.

STUDY DESIGN: This is a retrospective study analyzing 76 patients treated by decompression, pedicle screw instrumentation, and fusion for spondylolytic spondyiolisthesis with symptomatic spinal stenosis. OBJECTIVES: To verify the advantages of adding posterior lumbar interbody fusion to the usual posterolateral fusion with pedicle screw instrumentation. SUMMARY OF BACKGROUND DATA: Stabilization after decompression of spondylolytic spondylolisthesis is difficult because of a lack of fusional bone bases, gap between the transverse process bases, and incompetent anterior disc support. Posterior lumbar interbody fusion offers anterior support, reduction, and a broad fusion base. METHODS: Forty patients were treated with posterolateral fusion, and 36 were treated with additional posterior lumbar interbody fusion. They were compared for union, reduction of the deformity, and clinical results. RESULTS: The patients were followed up for more than 2 years. Nonunion was observed in three patients who underwent posterolateral fusion (7.5%), and no cases of nonunion was found in patients who underwent posterior lumbar interbody fusion. Reduction of slippage was 28.3% in those who underwent posterolateral fusion and 41.6% in those who had posterior lumbar interbody fusion (P = 0.05). In the posterolateral fusion group, eight patients (20%) had recurrence of deformity, with loss of reduction more than 50%. Hardware failures occurred in two patients who had posterolateral fusion. There was no major neurologic complications in both groups. Both groups had satisfactory results in more than 90% of patients, with marked improvement of claudication. However, subjective improvement of back pain by Kirkaldy-Willis criteria revealed differences in the excellent results. An excellent result was reported by 45% in the posterolateral fusion group and by 75% in posterior lumbar interbody fusion group. CONCLUSIONS: The addition of posterior lumbar interbody fusion to posterolateral fusion after a complete decompression and pedicle screw fixation is a recommended procedure for the treatment of spondylolytic spondylolishesis with spinal stenosis.

Adult↗
PubMed1991

Complementation between avirulent Newcastle disease virus and a fusion protein gene expressed from a retrovirus vector: requirements for membrane fusion.

The cDNA derived from the fusion gene of the virulent AV strain of Newcastle disease virus (NDV) was expressed in chicken embryo cells by using a retrovirus vector. The fusion protein expressed in this system was transported to the cell surface and was efficiently cleaved into the disulfide-linked F1-F2 form found in infectious virions. The cells expressing the fusion gene grew normally and could be passaged many times. Monolayers of these cells would plaque, in the absence of trypsin, avirulent NDV strains (strains which encode a fusion protein which is not cleaved in tissue culture). Fusion protein-expressing cells would not fuse if mixed with uninfected cells or uninfected cells expressing the hemagglutinin-neuraminidase (HN) protein. However, the fusion protein-expressing cells, if infected with avirulent strains of NDV, would fuse with uninfected cells, suggesting that fusion requires both the fusion protein and another viral protein expressed in the same cell. Fusion was also seen after transfection of the HN protein gene into fusion protein-expressing cells. Thus, the expressed fusion protein gene is capable of complementing the virus infection, providing an active cleaved fusion protein required for the spread of infection. However, the fusion protein does not mediate cell fusion unless the cell also expresses the HN protein. Fusion protein-expressing cells would not plaque influenza virus in the absence of trypsin, nor would influenza virus-infected fusion protein-expressing cells fuse with uninfected cells. Thus, the influenza virus HA protein will not substitute for the NDV HN protein in cell-to-cell fusion.

Animals↗
PubMedDate not supplied

Poly(ethylene glycol) (PEG)-mediated fusion between pure lipid bilayers: a mechanism in common with viral fusion and secretory vesicle release?

Membrane fusion is fundamental to the life of eukaryotic cells. Cellular trafficking and compartmentalization, import of food stuffs and export of waste, inter-cellular communication, sexual reproduction, and cell division are all dependent on this basic process. Yet, little is known about the molecular mechanism(s) by which fusion occurs. It is known that fusing membranes must somehow be docked and brought into close contact. Specific proteins, many of which have been identified within the past decade, accomplish this. An electrical connection or 'fusion pore' is established between compartments surrounded by the fusing membranes. Three primary views of the mechanism of pore formation during secretory and viral fusion have been proposed within the past decade. In one view, a protein ring forms an initial transient connection that expands slowly by recruiting lipid so as to form a lipidic junction. In another view, the initial fusion pore consists of a protein-lipid complex that transforms slowly until the fusion proteins dissociate from the complex to form an irreversible lipidic pore. In a third view, the initial pore is a transient lipid pore that fluctuates between open and closed states before either expanding irreversibly or closing. Recent work has helped define the mechanism by which poly(ethylene glycol) (PEG) mediates fusion of highly curved model membranes composed only of synthetic phospholipids. PEG is a highly hydrated polymer that can bring vesicle membranes to near molecular contact by making water between them thermodynamically unfavourable. Disrupted packing in the contacting monolayers of these vesicle membranes is necessary to induce fusion. The time course and sequence of molecular events of the ensuing fusion process have also been defined. This sequence of events involves the formation of an initial, transient intermediate in which outer leaflet lipids have mixed and small transient pores join fusing compartments ('stalk'). The transient intermediate transforms in 1-3 min to a fusion-committed, second intermediate ('septum') that then 'pops' to form the fusion pore. Inner leaflet mixing, which is shown to be distinct from outer leaflet mixing, accompanies contents mixing that marks formation of the fusion pore. Both the sequence of events and the activation energies of these events correspond well to those observed in viral membrane fusion and secretory granule fusion. These results strongly support the contention that both viral and secretory fusion events occur by lipid molecule rearrangements that can be studied and defined through the use of PEG-mediated vesicle fusion as a model system. A possible mechanism by which fusion proteins might mediate this lipidic process is described.

Animals↗
PubMedDate not supplied

Does rigid instrumentation increase the fusion rate in one-level anterior cervical discectomy and fusion?

BACKGROUND CONTEXT: Although plate fixation enhances the fusion rate in multilevel anterior cervical discectomy and fusion (ACDF), debate exists regarding the efficacy of nonplating to rigid plate fixation in one-level ACDF. PURPOSE: To determine the efficacy of nonplating to rigid plate fixation in regards to fusion rate and clinical outcome in patients undergoing one-level ACDF with autograft. STUDY DESIGN: A review of 69 consecutive patients who underwent one-level ACDF with autograft and with or without rigid anterior cervical plate fixation. PATIENT SAMPLE: Sixty-nine patients who underwent one-level ACDF (mean age, 45 years) were evaluated for radiographic evidence of fusion (mean, 14 months) and for clinical outcome. All patients received tricortical iliac crest autografts. Disc space distraction was 2 mm, the grafts were inserted with the cortical surface positioned anteriorly, and each graft was countersunk 2 mm from the anterior vertebral border. Thirty-eight patients underwent nonplated ACDF and 31 patients underwent plated ACDF. Eighteen Orion (Sofamor-Danek, Memphis, TN), eight Atlantis (Sofamor-Danek) and five PEAK polyaxial (Depuy-Acromed, Rayham, MA) anterior cervical plating systems were used. Rigid plate fixation was used in all patients with instrumentation. Postoperatively, hard collars were worn 6 to 8 weeks in nonplated patients and soft collars were worn for 3 to 4 weeks in plated patients. Twenty-four patients were smokers (54.2% nonplating; 45.8% plating) and work-related injuries entailed 23 patients (47.8% nonplating; 52.2% plating). OUTCOME MEASURES: Fusion was assessed based on last follow-up of lateral neutral, flexion and extension radiographs. Radiographs were evaluated blindly to assess fusion and instrumentation integrity between nonplated and plated patients. Clinical outcomes were assessed with the Cervical Spine Outcomes Questionnaire and also assessed on last follow-up as excellent, good, fair or poor based on Odom's criteria. METHODS: Fusion rate and postoperative clinical outcome were assessed in 69 patients who underwent one-level ACDF with autograft and with or without rigid anterior plate fixation. Additional risk factors were also analyzed. Statistical significance was established at p<.05. RESULTS: Sixty-six patients (95.7%) achieved a solid fusion (100% nonplated; 90.3% plated). Nonunions occurred in three patients (1 smoker; 2 nonsmokers) with Orion instrumentation. Slight screw penetration into the involved and uninvolved interbody spaces occurred in one patient who was a nonsmoker and did not achieve fusion. One superficial cervical wound infection was noted in a nonplated patient. No other intraoperative or postoperative complications were noted. No statistically significant difference was noted between nonplating to rigid plating upon fusion rate (p>.05). All nonunions occurred at the C5-C6 level. Mean estimated intraoperative blood loss was significantly greater in plated patients (p=.043). Revision surgery involved 9.7% of the plated patients, whereas none of the nonplated patients required reoperation. Postoperative clinical outcome was assessed in all patients (mean, 21 months). Excellent results were noted in 18.8%, good results in 72.5% and fair results in 8.7% of the patients. Nonunion patients reported satisfactory clinical outcome. No statistical significance was noted between clinical outcome of fused and nonfused patients, the presence of a work-related injury and the use of plating (p>.05). Demographics and history of smoking were not factors influencing fusion or clinical outcome in this series (p>.05). The effect on fusion by various plate types could not be discerned from this study. CONCLUSION: A 100% and 90.3% fusion rate was obtained for one-level nonplated and plated ACDF procedures with autograft, respectively. The effects of smoking or level of fusion could not be discerned from these one-level cases. Excellent and good clinical outcome results were obtained for 91.3%. Nonplating or rigid plate fixation for ACDF in properly selected patients to treat radiculopathy with or without myelopathy has a high fusion rate and yields a satisfactory clinical outcome. Although controversy exists as to the efficacy of rigid plate fixation in one-level ACDF, solid bone fusion can be adequately obtained without plate fixation and instrumentation-related complications can be avoided. In line with the literature, plate fixation should be reserved for patients unwilling or unable to wear a hard orthosis postoperatively for an extended period of time or for those patients who seek a quicker return to normal activities. Proper patient selection, meticulous operative technique and postoperative care is essential to promote optimal graft-host incorporation.

Adult↗
PubMed2000

Anterior lumbar fusion improves discogenic pain at levels of prior posterolateral fusion.

STUDY DESIGN: A descriptive case review. OBJECTIVES: To assess the outcomes of anterior lumbar interbody fusion for painful discs within a solid posterolateral spinal fusion. SUMMARY OF BACKGROUND DATA: Some patients continue to have pain after posterolateral spinal fusion despite apparently solid arthrodesis. One potential etiology is pain that arises from a disc within the fused levels. METHOD: Retrospective review of 176 patients with anterior interbody fusion, which located 20 who had anterior interbody fusion levels of prior posterolateral spinal fusion. All had low back pain, solid posterolateral spinal fusion, and painful disc(s) at the posterolateral spinal fusion level(s) but not elsewhere. Pain was measured by the Numerical Rating Scale, function by Oswestry Disability Questionnaire, and patient satisfaction by the North American Spine Society Outcome Questionnaire. RESULTS: Follow-up data were available for 18 patients (90%). Mean follow-up was 58 months (25 to 102). There were 10 men and 8 women. Mean age was 45 years (26 to 72). Diagnoses were degenerative discs, herniated nucleus pulposus, spondylolisthesis, and spinal stenosis. Eight patients had injuries after the previous posterolateral spinal fusion that precipitated new symptoms. Two patients had one level fusion, 14 had two levels, and 1 each had three and four levels. Four patients had one prior surgery, 5 had two, and 9 had three or more. All patients had solid anterior interbody fusion by radiograph. Mean Numerical Rating Scale improved from 7.9 before surgery to 4.7 after (P< 0.001). Mean Oswestry Disability Questionnaire improved from 56.3 before surgery to 47.9 after (P = 0.04). Of 15 patients unable to work before anterior interbody fusion, 5 returned to work. Sixteen patients (89%) were satisfied with their results. CONCLUSION: Low back pain that continues or recurs after apparently solid posterolateral spinal fusion may be caused by painful disc(s) at motion segment(s) within the fusion. A solid posterolateral spinal fusion may not protect the residual disc(s) from injury. Anterior interbody fusion can provide significant improvements in pain and function and a high degree of patient satisfaction in this clinical setting.

Disability Evaluation↗
PubMed2000

Direct current electrical stimulation increases the fusion rate of spinal fusion cages.

STUDY DESIGN: A randomized experimental evaluation of direct current stimulation in a validated animal model with an experimental control group, using blinded radiographic, biomechanical, histologic, and statistical measures. OBJECTIVES: To evaluate the efficacy of the adjunctive use of direct current stimulation on the fusion rate and speed of healing of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. SUMMARY OF BACKGROUND DATA: Titanium lumbar interbody spinal fusion cages have been reported to be 90% effective for single-level lumbar interbody fusion. However, fusion rates are reported to be between 70% and 80% in patients with multilevel fusions or with risk factors such as obesity, tobacco use, or metabolic disorders. The authors hypothesized that direct current stimulation would increase the fusion rate of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. METHODS: Twenty-two sheep underwent lumbar discectomy and fusion at L4-L5 with an 11- x 20-mm Bagby and Kuslich (BAK) cage packed with autograft. Seven sheep received a BAK cage and no current. Seven sheep had a cage and a 40-microA current applied with a direct current stimulator. Eight sheep had a BAK cage and a 100-microA current applied. All sheep were killed 4 months after surgery. The efficacy of electrical stimulation in promoting interbody fusion was assessed by performing radiographic, biomechanical, and histologic analyses in a blinded fashion. RESULTS: The histologic fusion rate increased as the direct current dose increased from 0 microA to 40 microA to 100 microA (P < 0.009). Histologically, all animals in the 100-microA group had fusions in both the right and left sides of the cage. Direct current stimulation had a significant effect on increasing the stiffness of the treated motion segment in right lateral bending (P < 0.120), left lateral bending (P < 0.017), right axial rotation (P < 0.004), left axial rotation (P < 0.073), extension (P < 0.078), and flexion (P < 0.029) over nonstimulated levels. CONCLUSION: Direct current stimulation increased the histologic and biomechanical fusion rate and the speed of healing of lumbar interbody spinal fusion cages in an ovine model at 4 months.

Animals↗
PubMed2002

A biomechanical comparison of posterolateral fusion and posterior fusion in the lumbar spine.

Late postoperative complications occurred after posterior fusion and posterolateral fusion as a result of biomechanical alterations. The stress change between the two fusion procedures has not been well reported. To differentiate the biomechanical alteration that occurs with posterior fusion and posterolateral fusion of the lumbar spine, the load sharing of the vertebrae, disc, facet joint, bone graft, and the range of motion were computed in a finite element model. Five finite element models, including the intact lumber spine, posterior fusion, posterior fusion with implant, posterolateral fusion, and posterolateral fusion with implant, were created for stress analysis. The finite element model estimated that the differences between these two fusion procedures were within 7% in stress of the adjacent disc, 3% in force of the facet joint above the fusion mass, and 5% in the range of motion. However, the stress of the pedicle in posterolateral fusion without an implant was at most two times greater than that in the intact lumbar spine under lateral bending. The stress of pars interarticularis in posterior fusion without an implant was also at most two times greater than that in the intact lumbar spine under lateral bending. After the implant was added, the discrepancy between the two fusion procedures decreased but still remained a relatively large difference. Therefore, the largest changes of posterior fusion and posterolateral fusion were in the pars interarticularis and pedicle, respectively.

Adult↗
PubMed2004

Structural and functional properties of an unusual internal fusion peptide in a nonenveloped virus membrane fusion protein.

The avian and Nelson Bay reoviruses are two of only a limited number of nonenveloped viruses capable of inducing cell-cell membrane fusion. These viruses encode the smallest known membrane fusion proteins (p10). We now show that a region of moderate hydrophobicity we call the hydrophobic patch (HP), present in the small N-terminal ectodomain of p10, shares the following characteristics with the fusion peptides of enveloped virus fusion proteins: (i) an abundance of glycine and alanine residues, (ii) a potential amphipathic secondary structure, (iii) membrane-seeking characteristics that correspond to the degree of hydrophobicity, and (iv) the ability to induce lipid mixing in a liposome fusion assay. The p10 HP is therefore predicted to provide a function in the mechanism of membrane fusion similar to those of the fusion peptides of enveloped virus fusion peptides, namely, association with and destabilization of opposing lipid bilayers. Mutational and biophysical analysis suggested that the internal fusion peptide of p10 lacks alpha-helical content and exists as a disulfide-stabilized loop structure. Similar kinked structures have been reported in the fusion peptides of several enveloped virus fusion proteins. The preservation of a predicted loop structure in the fusion peptide of this unusual nonenveloped virus membrane fusion protein supports an imperative role for a kinked fusion peptide motif in biological membrane fusion.

Amino Acid Sequence↗
PubMed2005

Is autograft the gold standard in achieving radiographic fusion in one-level anterior cervical discectomy and fusion with rigid anterior plate fixation?

STUDY DESIGN: A review of 66 consecutive patients at a single institution who underwent one-level anterior cervical discectomy and fusion (ACDF) with rigid anterior plate fixation with allograft or autograft. OBJECTIVES: To address the efficacy of allograft to autograft with primary respect to fusion rate and secondary attention to risk factors and clinical outcome in patients undergoing one-level ACDF with rigid anterior plate fixation. SUMMARY OF BACKGROUND DATA: Although autograft is considered the gold standard in achieving optimal fusion, when compared with allograft in noninstrumented one-level ACDF and in plated and nonplated multilevel ACDF, the efficacy of allograft to autograft in one-level ACDF with rigid anterior plate fixation is not thoroughly understood. METHODS: Sixty-six consecutive patients (mean age, 45 years) at a single institution who underwent one-level ACDF with rigid anterior plate fixation with allograft (n = 35) or autograft (n = 31) were reviewed for radiographic fusion (mean, 12 months), risk factors, and clinical outcome (mean, 17 months). Smokers entailed 33.3% of the patients, and 45.5% of all patients presented with a work-related injury. An independent blinded observer reviewed at last follow-up lateral neutral and flexion/extension plain radiographs for radiographic fusion and instrumentation integrity. Clinical outcome was assessed on last follow-up and rated according to the Odom criteria. The threshold for statistical significance was established at P < 0.05. RESULTS: Solid fusion was achieved in 63 patients (95.5%). Fusion was noted in 100% of the allograft patients, whereas 90.3% of the autograft cases achieved fusion. No statistically significant difference was noted between allograft to autograft with regard to fusion rate (P > 0.05). Three patients developed nonunions (1 smoker; 2 nonsmokers) and entailed Orion instrumentation. In the one patient who was a nonsmoker with a nonunion, slight screw penetration into the involved and uninvolved interbody spaces was noted. No other intraoperative, postoperative, or radiographic complication was noted. All of the nonunions occurred early in the series. Postoperatively, excellent results were reported in 19.7%, good results in 71.2%, and fair results in 9.1% of the patients. Satisfactory clinical outcome was noted in all nonunion patients. A nonstatistically significant difference was noted with regard to clinical outcome of fused and nonfused patients, demographics, and the presence of a work-related injury (P > 0.05). The impact of smoking was not a factor influencing fusion or clinical outcome in this series (P > 0.05). A statistically significant difference was noted in plate-type on fusion rate (P < 0.05). CONCLUSION: A 100% and 90.3% radiographic fusion rate was obtained for allograft and autograft in one-level ACDF procedures with rigid anterior plate fixation, respectively. Although autograft achieved a higher incidence of nonunion than allograft, this may be attributed to the use of autograft early in the experience of plate application and fixation in this series. The effects of smoking were not found to be a significant factor influencing fusion in these plated patients. In 90.9% of the patients, excellent and good clinical outcome results were reported. The use of allograft in one-level ACDF with rigid plate fixation yields similar and high fusion rates as autograft. The use of allograft bone eliminates complications and pitfalls associated with autologous donor site harvesting. However, the use of autograft is a viable alternative to avoid the risk of infection, disease transmission, and histocompatibility differences associated with allograft. The use of allograft or autograft bone in properly selected patients for one-level ACDF with rigid anterior plate fixation can result in high fusion rates with excellent and good clinical outcomes.

Adult↗
PubMed2005

The fusion rate of calcium sulfate with local autograft bone compared with autologous iliac bone graft for instrumented short-segment spinal fusion.

STUDY DESIGN: A prospective study. OBJECTIVES: To compare the efficacy of calcium sulfate pellets plus laminectomy bone chips with a fresh autologous iliac bone graft for short-segment lumbar fusion. SUMMARY OF BACKGROUND DATA: Bone graft substitute material can be used to expand an existing quantity of available laminectomy bone chips. METHODS: Seventy-four patients underwent surgery for instrumented one- or two-segment fusion with decompression. Autologous iliac crest bone graft was placed in one posterolateral gutter, while on the other side, an equal quantity of autogenous laminectomy bone supplemented with calcium sulfate was placed. Radiographic assessment included radiographs alone; this was performed every 3 months (3 months to 12 months), then annually. The status of fusion and the relative size of the fusion bone mass on either side of the vertebra were compared. RESULTS: Using iliac crest bone graft (control side) versus autograft laminectomy bone with calcium sulfate (test side), there was no significant difference between the fusion rate and sizes of the fusion bone mass (P > 0.05). Follow-up periods ranged from 30 months to 34 months, averaging 32.5 months. For the 39 patients who received single-segment fusion, 34 patients (87.2%) exhibited bone fusion on the test side, and 35 patients (89.7%) had evidence of fusion on the control side. For the 35 patients who received two-segment fusion, 29 patients (82.9%) exhibited bone fusion on the test side and 30 patients (85.7%) demonstrated complete fusion on the control side. CONCLUSIONS: The fusion rate and fusion size between the two groups are similar. Calcium sulfate pellets may play a role as a bone graft extender in short-segment spinal fusion.

Adult↗
PubMed1991

Fusion of Sendai virus with human HL-60 and CEM cells: different kinetics of fusion for two isolates.

The kinetics of fusion of Sendai virus (Z strain) with the human promyelocytic leukemia cell line HL-60, and the human T lymphocytic leukemia cell line CEM was investigated. Fusion was monitored by fluorescence dequenching of octadecylrhodamine (R-18) incorporated in the viral membrane. For one virus isolate (Z/G), the overall rate of fusion (at 37 degrees C) increased as the pH was lowered, reaching a maximum at about pH 5, the lowest pH tested. For another isolate (Z/SF) the rate and extent of fusion were lower at pH 5 than at neutral pH. Lowering the pH from neutral to 5 after several minutes of incubation of either isolate with HL-60 cells resulted in an enhanced rate of fluorescence dequenching. Nevertheless, experiments utilizing NH4Cl indicated that fusion of the virus with cells was not enhanced by the mildly acidic pH of the endosome lumen. Analysis of the kinetics of fusion by means of a mass action model resulted in good simulation and predictions for the time-course of fusion. For the isolate which showed maximal fusogenic activity at pH 5, the rate constant of fusion (approx. 0.1 s-1) at neutral pH was in the range found previously for virus-liposome fusion, whereas the rate constant of adhesion was close to the upper limit for diffusion-controlled processes (1.4.10(10) M-1 s-1). However, for the other isolate (Z/SF) the rate constant of fusion at neutral pH was very small (less than 0.01 s-1), whereas the rate constant of adhesion was larger (greater than or equal to 2.10(10) M-1 s-1). Lowering the temperature decreased the fusion rate. Experiments involving competition with excess unlabeled virions indicated that not all binding sites for Sendai virus on HL-60 cells are fusion sites. The virus fusion activity towards HL-60 cells at neutral pH was not altered significantly by pre-incubation of the virus at pH 5 or 9, in contrast to earlier observations with liposomes and erythrocyte ghosts, or results based on erythrocyte hemolysis or cell-cell fusion.

Ammonium Chloride↗