Corrigendum to: 'Molecular basis of carbohydrate-deficient glycoprotein syndromes type I with normal phosphomannomutase activity'.
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Journal Article↗
Biomedical subjects
M Aebi
Publications and source records attributed to M Aebi.
Minimally invasive bone harvesting tools.
The most readily available source for autologous bone graft used in spinal fusion (the gold standard) is the iliac crest. However, the open surgical approach for harvesting corticocancellous iliac bone is associated with a marked increase in morbidity. This study suggests two alternatives to the traditional open harvesting procedure. For anterior interbody fusion procedures using a cage, the autologous bone is harvested regionally from a neighboring vertebral body. Alternatively, using minimally invasive techniques, a custom bone graft harvester with a flexible tube and cutting tip allows harvesting of autologous bone from a single entry point at the iliac crest. The effect on the mechanical strength of a lumbar vertebra of removing a cylindrical regional bone graft was studied in a cadaveric model. The bone defect was filled using three different filler materials: a porous tri-calcium phosphate plug, a porous tantalum plug, and a self-setting calcium phosphate cement. After plug removal, the vertebral body's strength in flexion/compression loading was reduced significantly, but could be restored to at least intact values with any of the three filler materials. The minimally invasive bone graft harvester was tested in three cadaveric pelves. With the cutting tip being guided within the cortical boundaries of the pelvis, cancellous bone volumes of 10-20 cc could be harvested from each iliac bone. Regional bone graft harvest in anterior spine surgery is suggested to be anatomically safe and biomechanically acceptable. Any of the three filler materials can restore the vertebral body's mechanical strength, but the filler's long-term resorption/remodeling or osteointegration behavior is unknown. The minimally invasive bone graft harvester is a novel tool, which performed satisfactorily under laboratory conditions, but clinical results are still missing.
Bone Transplantation↗
Synframe: a preliminary report.
Both endoscopic lumbar spinal surgery and the non-standardized and unstable retractor systems for the lumbar spine presently on the market have disadvantages and limitations in relation to the minimally invasive surgical concept, which have been gradually recognized in the last few years. In an attempt to resolve some of these issues, we have developed a highly versatile retractor system, which allows access to and surgery at the lumbar, thoracic and even cervical spine. This retractor system - Synframe - is based on a ring concept allowing 360 degrees access to a surgical opening in anterior as well as posterior surgery. The ring is concentrically laid over the surgical opening for the approach and is used as a carrier for retractor arms, which are instrumented with either different sizes or types of blades and/or different sizes of Hohmann hooks. In posterior surgery, nerve root retractors can also be installed. This ring also functions as a carrier for fiberoptic illumination devices and different sizes of endoscopes, used to transmit the surgical procedure out of the depth of the surgical exposure for both teaching purposes and for the surgical team when it has no longer direct visual access to the procedure. The ring is stable, being fixed onto the operating table, allowing precise minimally open approaches and surgical procedures under direct vision with optimal illumination. This ring system also opens perspectives for an integrated minimally open surgical concept, where the ring may be used as a reference platform in computer-navigated surgery.
Equipment Design↗
Hybrid computer-guided and minimally open surgery: anterior lumbar interbody fusion and translaminar screw fixation.
Less invasiveness is the way forward for spinal surgery. Minimal disruption of tissue, preservation of muscle function, and restoration of normal spinal alignment are still the goals of most surgical procedures. An anterior lumbar fusion technique using a less invasive procedure with the addition of translaminar screws is described. The autograft is harvested from the vertebral body, thus avoiding the morbidity associated with an iliac crest bone graft. The operative steps for the procedure are described.
Bone Screws↗
Cages: designs and concepts.
Many new interbody fusion cages have been recently developed, but clinical studies analyzing fusion outcome are still scarce. Radiological methods to assess fusion are not standardized and are often unreliable. Cages have been stated to provide good segmental distraction, provide axial load support and reduce segmental mobility, but there have been reports of failed fusions because of implant failure. This paper presents a critical opinion on current cage designs, stressing their clinical and biomechanical implications. Threaded cage designs compromise endplate integrity, and when placed in pairs have inherent limitations for distraction. Non-threaded cage designs usually preserve endplate integrity, but geometry may be inadequate to provide a good surface match to the endplate. The concept of an open frame type cage is believed to have biological advantages, because large graft volumes inside the cage can be in direct contact with host bone. Cadaveric tests suggest that open frame constructs have compressive strength similar to that of full surface contact cages. Restoration of segmental height, sagittal balance and increased neuroforaminal clearance are all functions of disc space distraction. The effect of cage instrumentation on axial load distribution, however, is not well understood. Biomechanical experiments strongly suggest supplementing cage instrumentation with posterior fixation, to achieve a marked increase in initial segmental stability. In the absence of gross segmental instability, micromotion at the host graft interface may still exist. As a result, fusion will never occur, instead a pseudoarthrosis will develop. For monitoring fusion, the use of non-metallic cages has distinct advantages, because no metal artifacts will disturb radiological assessment.
Equipment Design↗
Multi-allelic origin of congenital disorder of glycosylation (CDG)-Ic.
Congenital disorders of glycosylation (CDG), formerly known as carbohydrate-deficient glycoprotein syndrome, represent a family of genetic diseases with variable clinical presentations. Common to all types of CDG characterized to date is a defective Asn-linked glycosylation caused by enzymatic defects of N-glycan synthesis. Previously, we have identified a mutation in the ALG6 alpha1,3 glucosyltransferase gene as the cause of CDG-Ic in four related patients. Here, we present the identification of seven additional cases of CDG-Ic among a group of 35 untyped CDG patients. Analysis of lipid-linked oligosaccharides in fibroblasts confirmed the accumulation of dolichyl pyrophosphate-Man9GlcNAc2 in the CDG-Ic patients. The genomic organization of the human ALG6 gene was determined, revealing 14 exons spread over 55 kb. By polymerase chain reaction amplification and sequencing of ALG6 exons, three mutations, in addition to the previously described A333 V substitution, were detected in CDG-Ic patients. The detrimental effect of these mutations on ALG6 activity was confirmed by complementation of alg6 yeast mutants. Haplotype analysis of CDG-Ic patients revealed a founder effect for the ALG6 allele bearing the A333 V mutation. Although more than 80% of CDG are type Ia, CDG-Ic may be the second most common form of the disease.
Alleles↗
Immaterial rights in medical research.
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Marketing of Health Services↗
Biomechanical stability of five stand-alone anterior lumbar interbody fusion constructs.
Anterior lumbar interbody fusion (ALIF) cages are expected to reduce segmental mobility. Current ALIF cages have different designs, suggesting differences in initial stability. The objective of this study was to compare the effect of different stand-alone ALIF cage constructs and cage-related features on initial segmental stability. Human multisegmental specimens were tested intact and with an instrumented L3/4 disc level. Five different ALIF cages (I/F, BAK, TIS, SynCage, and ScrewCage) were tested non-destructively in axial rotation, flexion/extension and lateral bending. A cage 'pull-out' concluded testing. Changes in neutral zone (NZ) and range of motion (ROM) were analyzed. Cage-related measurements normalized to vertebral dimensions were used to predict NZ and ROM. No cage construct managed to reduce NZ. The BAK and TIS cages had the largest NZ increase in flexion/extension and lateral bending, respectively. Cages did reduce ROM in all loading directions. The TIS cage was the least effective in reducing the ROM in lateral bending. Cages with sharp teeth had higher 'pull-out' forces. Antero-posterior and mediolateral cage dimensions, cage height and wedge angle were found to influence initial stability. The performance of stand-alone ALIF cage constructs generally increased the NZ in any loading direction, suggesting potential directions of initial segmental instability that may lead to permanent deformity. Differences between cages in flexion/extension and lateral bending NZ are attributed to the severity of geometrical cage-endplate surface mismatch. Stand-alone cage constructs reduced ROM effectively, but the residual ROM present indicates the presence of micromotion at the cage-endplate interface.
Adult↗
Decompensation following scoliosis surgery: treatment by decreasing the correction of the main thoracic curve or "letting the spine go".
Coronal decompensation following correction of adolescent idiopathic scoliosis (AIS) has been reported to be due to the Cotrel-Dubousset rod derotation maneuver, or to a hypercorrection of the main thoracic curve. The treatment of such decompensation consists classically in observation, bracing, or extension of the instrumentation in the lumbar spine for a King 2 curve, or in the upper thoracic spine for a King 5 curve. As the postoperative decompensation is related to a hypercorrection of the main thoracic curve (relative to the compensatory curve), we hypothesized that if we were to "let the spine go" to some of its initial deformity, the balance of the patient would be improved. The purpose of the study was therefore to report on two cases where a postoperative imbalance following scoliosis surgery was successfully treated by decreasing the correction of the main thoracic curve. Two patients with AIS were found to have significant imbalance after scoliosis surgery. Both patients had been treated for a right thoracic curve (82 degrees and 85 degrees respectively) with an anterior release and posterior instrumentation. The revision surgery consisted for both patients in removing all the hooks between the end vertebrae of the main thoracic curve. This was done before the 3rd postoperative month for both patients. After revision surgery, the balance of both patients improved dramatically within a few weeks. The shoulders became almost level, and the trunk shift improved concomitantly. The Cobb angle increased by 8 degrees and 10 degrees, and the apical vertebra shifted to the right by 15 and 10 mm for the respective patients. These results were stable at 1-year follow-up. In the event of a persisting imbalance, we recommend, in selected cases, letting the spine go by removing all the implants located between the end vertebrae of the main thoracic curve. This adjustment or fine-tuning of the instrumentation should be done before the fusion takes place, and is best achieved with an instrumentation in which the hooks can be easily removed from the rod.
Adolescent↗
Posterolateral and anterior interbody spinal fusion models in the sheep.
Posterolateral and anterior interbody spinal arthrodesis is a frequent procedure, but high nonunion rates are reported and harvesting autologous bone graft from the iliac crest significantly increases morbidity. Bone graft substitutes are an alternative, but to date clinical results are not conclusive. Bone substitutes can be organic or inorganic, biologic or synthetic. They can have osteoconductive properties, inductive properties or both. Animal experiments are essential to investigating bone substitutes using biomechanical and histologic methods not available in clinical studies. Few authors reported on instrumented anterior fusion models, but none used the sheep model. In the current study posterolateral and anterior interbody fusion models in sheep are described. Both models used instrumented fusions, applying porous mineral scaffolds, alone or mixed with bone. The surgical techniques are described step-by-step and potential difficulties are highlighted. Preliminary results are reported for the posterolateral fusion model using coralline graft substitutes. The coral granules mixed with locally harvested bone had fusion outcomes similar to pure autologous bone. The graft substitute showed marked resorption between 12 and 20 weeks. All fusions had bone cortex and good trabecular connectivity. Histologic evaluation suggests after 20 weeks nearly the entire surface of the substitute is covered with new bone. Porous mineral bone substitutes mixed with locally harvested autologous bone are thought to be a valid alternative for posterolateral fusions.
Animals↗
Deficiency of dolichol-phosphate-mannose synthase-1 causes congenital disorder of glycosylation type Ie.
Congenital disorders of glycosylation (CDG), formerly known as carbohydrate-deficient glycoprotein syndromes, lead to diseases with variable clinical pictures. We report the delineation of a novel type of CDG identified in 2 children presenting with severe developmental delay, seizures, and dysmorphic features. We detected hypoglycosylation on serum transferrin and cerebrospinal fluid beta-trace protein. Lipid-linked oligosaccharides in the endoplasmic reticulum of patient fibroblasts showed an accumulation of the dolichyl pyrophosphate Man(5)GlcNAc(2) structure, compatible with the reduced dolichol-phosphate-mannose synthase (DolP-Man synthase) activity detected in these patients. Accordingly, 2 mutant alleles of the DolP-Man synthase DPM1 gene, 1 with a 274C>G transversion, the other with a 628delC deletion, were detected in both siblings. Complementation analysis using DPM1-null murine Thy1-deficient cells confirmed the detrimental effect of both mutations on the enzymatic activity. Furthermore, mannose supplementation failed to improve the glycosylation status of DPM1-deficient fibroblast cells, thus precluding a possible therapeutic application of mannose in the patients. Because DPM1 deficiency, like other subtypes of CDG-I, impairs the assembly of N-glycans, this novel glycosylation defect was named CDG-Ie.
Amino Acid Sequence↗
Molecular basis of carbohydrate-deficient glycoprotein syndromes type I with normal phosphomannomutase activity.
Carbohydrate deficient glycoprotein syndromes (CDGS) are inherited disorders in glycosylation. Isoelectric focusing of serum transferrin is used as a biochemical indicator of CDGS; however, this technique cannot diagnose the molecular defect. Even though phosphomannomutase (PMM) deficiency accounts for the great majority of known CDGS cases (CDGS type Ia), newly discovered cases have significantly different clinical presentations than the PMM-deficient patients. These differences arise from other defects affecting the biosynthesis of N-linked oligosaccharides in the endoplasmic reticulum and in the Golgi compartment. The most notable is the loss of phosphomannose isomerase (PMI) (CDGS type Ib). It causes severe hypoglycemia, protein-losing enteropathy, vomiting, diarrhea, and congenital hepatic fibrosis. In contrast to PMM-deficiency, there is no developmental delay nor neuropathy. Most symptoms in the PMI-deficient patients can be successfully treated with dietary mannose supplements. Another defect is the lack of glucosylation of the lipid-linked oligosaccharide precursor. The clinical features of this form of CDGS are milder, but similar to, PMM-deficient patients. Yeast genetic and biochemical techniques were critical in unraveling these disorders since many of the defective genes were known in yeast and corresponding mutants were available for complementation. Yeast strains carrying mutations in the homologous genes are likely to provide conclusive identification of the primary defects in novel CDGS types that affect the synthesis and transfer of precursor oligosaccharides.
Carbohydrate Sequence↗
A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-Ic.
Carbohydrate-deficient glycoprotein syndrome (CDGS) represents a class of genetic diseases characterized by abnormal N-linked glycosylation. CDGS patients show a large number of glycoprotein abnormalities resulting in dysmorphy, encephalopathy, and other organ disorders. The majority of CDGSs described to date are related to an impaired biosynthesis of dolichyl pyrophosphate-linked Glc3Man9GlcNAc2 in the endoplasmic reticulum. Recently, we identified in four related patients a novel type of CDGS characterized by an accumulation of dolichyl pyrophosphate-linked Man9GlcNAc2. Elaborating on the analogy of this finding with the phenotype of alg5 and alg6 Saccharomyces cerevisiae strains, we have cloned and analyzed the human orthologs to the ALG5 dolichyl phosphate glucosyltransferase and ALG6 dolichyl pyrophosphate Man9GlcNAc2 alpha1,3-glucosyltransferase in four novel CDGS patients. Although ALG5 was not altered in the patients, a C-->T transition was detected in ALG6 cDNA of all four CDGS patients. The mutation cosegregated with the disease in a Mendelian recessive manner. Expression of the human ALG5 and ALG6 cDNA could partially complement the respective S. cerevisiae alg5 and alg6 deficiency. By contrast, the mutant ALG6 cDNA of CDGS patients failed to revert the hypoglycosylation observed in alg6 yeasts, thereby proving a functional relationship between the alanine to valine substitution introduced by the C-->T transition and the CDGS phenotype. The mutation in the ALG6 alpha1,3-glucosyltransferase gene defines an additional type of CDGS, which we propose to refer to as CDGS type-Ic.
Amino Acid Sequence↗
The dolichol pathway of N-linked glycosylation.
The oligosaccharide substrate for the N-linked protein glycosylation is assembled at the membrane of the endoplasmic reticulum. Dolichyl pyrophosphate serves as a carrier in this biosynthetic pathway. In this review, we discuss the function of the lipid carrier dolichol in oligosaccharide assembly and give an overview of the biosynthesis of the different sugar donors required for the building of the oligosaccharide. Yeast genetic techniques have made it possible to identify many different loci encoding specific glycosyltransferases required for the precise and ordered assembly of the dolichyl pyrophosphate-linked oligosaccharide. Based on the knowledge obtained from studying this pathway in yeast, we compare it to the process of N-linked protein glycosylation in archaea. We suggest that N-linked glycosylation in eukaryotes and in archaea share a common evolutionary origin.
Amino Acid Sequence↗
Immunohistochemical analysis of type-X-collagen expression in osteoarthritis of the hip joint.
Conflicting data have been reported on the spatial distribution of type X-collagen expression in osteoarthritis, and no concise data exist on a possible correlation between type X-collagen expression and clinical and radiological alterations. Well defined clinical and radiological data were compared with histopathological and immunohistochemical findings to investigate the expression of type-X collagen in osteoarthritis of the hip joint. Femoral heads were obtained in toto from 11 patients undergoing routine hip arthroplasty for femoral neck fractures (n = 3) or osteoarthritis (n = 8) and from 13 patients (age: 12 days to 69 years) without any evidence of hip-joint pathology. Whole coronal sections from the femoral head were decalcified for routine histology and immunohistochemical analysis with use of type-specific monoclonal antibodies to type-X collagen. Our results demonstrate that type-X collagen is consistently found in osteoarthritic cartilage and is absent from normal adult cartilage (including the region of calcified cartilage). Except for the occurrence of type-X collagen in the middle zone of articular cartilage in advanced stages of osteoarthritis, there is no specific change in the staining pattern or intensity for the collagen during osteoarthritis, particularly when the staining is related to clinical and radiological parameters. Hardly more than 20% of the extracellular matrix stained for type-X collagen; therefore, we suggest that, in most cases, this type of collagen may not play a direct biomechanical role in the weakening of osteoarthritic cartilage but rather may contribute indirectly to a disturbance of the disc biomechanics by altering matrix-molecule interaction. However, expression of type-X collagen may indicate a change in chondrocyte phenotype that consistently coincides with the formation of chondrocyte clusters, one of the first alterations in osteoarthritis visible on histologic examination.
Adolescent↗
Unusual presentation of spinal cord compression related to misplaced pedicle screws in thoracic scoliosis.
Utilization of thoracic pedicle screws is controversial, especially in the treatment of scoliosis. We present a case of a 15-year-old girl seen 6 months after her initial surgery for scoliosis done elsewhere. She complained of persistent epigastric pain, tremor of the right foot at rest, and abnormal feelings in her legs. Clinical examination revealed mild weakness in the right lower extremity, a loss of thermoalgic discrimination, and a forward imbalance. A CT scan revealed at T8 and T10 that the right pedicle screws were misplaced by 4 mm in the spinal canal. At the time of the revision surgery the somatosensory evoked potentials (SSEP) returned to normal after screw removal. The clinical symptoms resolved 1 month after the revision. The authors conclude that after pedicle instrumentation at the thoracic level a spinal cord compression should be looked for in case of subtle neurologic findings such as persistent abdominal pain, mild lower extremity weakness, tremor at rest, thermoalgic discrimination loss, or unexplained imbalance.
Abdominal Pain↗
The 'MW' sacropelvic construct: an enhanced fixation of the lumbosacral junction in neuromuscular pelvic obliquity.
Fixation to the lumbosacral spine to correct pelvic obliquity in neuromuscular scoliosis has always remained a surgical challenge. The strongest fixation of the lumbosacral junction has been achieved with either a Galveston technique with rods or screws or with iliosacral screws. We have devised a new fixation system, in which iliosacral screws are combined with iliac screws. This is made possible by using the AO Universal Spine System with side opening hooks above and below the iliosacral screws and iliac screws below it. The whole sacropelvis is thus encompassed by a maximum width (MW) fixation, which gives an 'M' appearance on the pelvic radiographs and a 'W' appearance in the axial plane. We report on our surgical technique and the early results where such a technique was used. We feel that this new means of fixation (by combining the strongest fixation systems) is extremely solid and should be included in the wide armamentarium of sacropelvic fixation.
Adult↗
Adolescent idiopathic thoracic scoliosis: apical correction with specialized pedicle hooks.
Forty-one patients with thoracic adolescent idiopathic scoliosis (AIS) treated with only a posterior spine fusion using specialized pedicle hooks (SPH) (hooks augmented with 3.2-mm screws) at the apex of the curve were reviewed in order to assess the effectiveness of this correction method. Inclusion in the study group required a minimum of 2 years' follow-up and the same strategy of correction where the apical vertebrae (3 or 4 vertebrae on the concave side) were instrumented with SPH. The mean preoperative Cobb angle was corrected from 55 degrees (42 degrees -80 degrees) to 18 degrees (67%) postoperatively and to 23 degrees (58%) at the last follow-up (28-50 months) for a flexibility index of 46%. Apical vertebral translation was corrected to 70% at the last follow-up. Thoracic kyphosis remained unchanged, from 23 degrees to 26 degrees, and the lumbar lordosis went from -53 degrees to -59 degrees. The lumbar curve was corrected from 38 degrees to 18 degrees. Coronal balance improved from 10 to 1 mm; shoulder balance was improved from 15 to 5 mm. The rib hump was improved from an average of 30 mm preoperatively to 15 mm postoperatively, but only to 25 mm at the last follow-up (17% of correction). One case of a spastic bladder was observed postoperatively, which resolved completely after 8 months. Three patients had to have their instrumentation removed because of pain. There was no complication related to the use of the SPH. The authors conclude that apical correction with SPH allows effective scoliosis correction without spinal distraction and does not require supra- or infralaminar hook in the spinal canal.
Adolescent↗