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Phenotypic and dynamical transitions in model genetic networks. II. Application to the evolution of segmentation mechanisms.

Knowledge of the genetic control of segmentation in Drosophila has made insect segmentation a paradigmatic case in the study of the evolution of developmental mechanisms. In Drosophila, the patterns of expression of segmentation genes are established simultaneously in all segments by a complex set of interactions between transcriptional factors that diffuse in a syncytium occupying the whole embryo. Such mechanisms cannot act in short germ-band insects where segments appear sequentially from a cellularized posterior proliferative zone. Here, we compare mechanisms of segmentation in different organisms and discuss how the transition between the different types of segmentation can be explained by small and progressive changes in the underlying gene networks. The recent discovery of a temporal oscillation in expression during somitogenesis of vertebrate homologs of the pair-rule gene hairy enhances the plausibility of an earlier proposal that the evolutionary origin of both the short- and long germ-band modes of segmentation was an oscillatory genetic network (Newman 1993). An implication of this scenario is that the self-organizing, pattern-forming system embodied in an oscillatory network operating in the context of a syncytium (i.e., a reaction-diffusion system)-which is hypothesized to have originated the simultaneous mode of segmentation-must have been replaced by the genetic hierarchy seen in modern-day Drosophila over the course of evolution. As demonstrated by the simulations in the accompanying article, the tendency for "emergent" genetic networks, associated with self-organizing processes, to be replaced through natural selection with hierarchical networks is discussed in relation to the evolution of segmentation.

Animals↗

PubMed2005

A segment of cold shock protein directs the folding of a combinatorial protein.

It has been suggested that protein domains evolved by the non-homologous recombination of building blocks of subdomain size. In earlier work we attempted to recapitulate domain evolution in vitro. We took a polypeptide segment comprising three beta-strands in the monomeric, five-stranded beta-barrel cold shock protein (CspA) of Escherichia coli as a building block. This segment corresponds to a complete exon in homologous eukaryotic proteins and includes residues that nucleate folding in CspA. We recombined this segment at random with fragments of natural proteins and succeeded in generating a range of folded chimaeric proteins. We now present the crystal structure of one such combinatorial protein, 1b11, a 103-residue polypeptide that includes segments from CspA and the S1 domain of the 30S ribosomal subunit of E. coli. The structure reveals a segment-swapped, six-stranded beta-barrel of unique architecture that assembles to a tetramer. Surprisingly, the CspA segment retains its structural identity in 1b11, recapitulating its original fold and deforming the structure of the S1 segment as necessary to complete a barrel. Our work provides structural evidence that (i) random shuffling of nonhomologous polypeptide segments can lead to folded proteins and unique architectures, (ii) many structural features of the segments are retained, and (iii) some segments can act as templates around which the rest of the protein folds.

Amino Acid Sequence↗

PubMed2000

Mechanisms that direct ordered assembly of T cell receptor beta locus V, D, and J gene segments.

T cell receptor (TCR) beta variable region genes are assembled in progenitor T cells from germ-line Vbeta, Dbeta, and Jbeta segments via an ordered two-step process in which Dbeta to Jbeta rearrangements occur on both alleles before appendage of a Vbeta to a preexisting DJbeta complex. Direct joining of Vbeta segments to nonrearranged Dbeta or Jbeta segments, while compatible with known restrictions on the V(D)J recombination mechanism, are infrequent within the endogenous TCRbeta locus. We have analyzed mechanisms that mediate ordered Vbeta, Dbeta, and Jbeta assembly via an approach in which TCRbeta minilocus recombination substrates were introduced into embryonic stem cells and then analyzed for rearrangement in normal thymocytes by recombinase-activating gene 2-deficient blastocyst complementation. These analyses demonstrated that Vbeta segments are preferentially targeted for rearrangement to Dbeta as opposed to Jbeta segments. In addition, we further demonstrated that Vbeta segments can be appended to nonrearranged endogenous Dbeta segments in which we have eliminated the ability of Dbeta segments to join to Jbeta segments. Our findings are discussed in the context of the mechanisms that regulate the ordered assembly and utilization of V, D, and J segments.

Animals↗

PubMed2004

Plant regeneration from encapsulated nodal segments of Dalbergia sissoo Roxb., a timber-yielding leguminous tree species.

One of the alternative methods adopted in recent years is to use biotechnological approaches for improving the tree species. The synthetic seeds offer several advantages, e.g., easy handling, storability, reduced size of propagules, and transportability. Germplasm can be effectively stored in the form of synthetic seeds. A protocol has been developed for plant regeneration from encapsulated nodal segments of Dalbergia sissoo Roxb. Nodal segments collected from basal sprouts of mature trees were encapsulated in calcium alginate beads. Inability of nodal segments entrapped in calcium alginate beads to form root was a major problem. To avoid this problem, an appropriate root induction treatment was given to nodal segments for 10 days, prior to encapsulation to allow formation of root primordia. For synthetic seeds production and subsequent conversion into plantlet, nodal segments with root primordia were encapsulated using sodium alginate and calcium chloride as gelling matrix. The best gel complexation was achieved using 3% sodium alginate and 75 mmol/L CaCl2 2H2O. Maximum percentage response (85%) for conversion of encapsulated nodal segments into plantlets was achieved on 1/2-MS medium without plant growth regulators, after 25 days of culture. The frequency of conversion of encapsulated nodal segments into plantlets affected by the concentration of sodium alginate, and the presence or absence of 1/2-MS nutrients in calcium alginate beads. Plantlets with well developed roots and shoots were transferred to pots containing autoclaved mixture of peat moss and soil (1:1). Plants were also established in pots. The conversion of encapsulated nodal segments into plantlets also occurred when calcium alginate beads having entrapped nodal segments were directly sown in autoclaved peat moss moistened with 1/2-MS0 medium. Out of 60 encapsulated nodal segments, in each experiments, stored at 4 degrees C for 30 days, 44 plants developed under in vitro conditions, and 27 on peat moss moistened with 1/2-MS0.

Agriculture↗

PubMed1999

The relationships between spinal sagittal configuration, joint mobility, general low back mobility and segmental mobility in female homecare personnel.

The aim of this study was to investigate joint mobility, segmental and general spinal mobility and their interrelationship in 607 women working as homecare personnel. Joint mobility (mainly peripheral) was estimated using the "Beighton" score. Spinal posture and mobility were measured by Debrunner's kyphometer. Passive segmental mobility and pain provocation were estimated manually. Reliability tests between two physiotherapists of segmental mobility and pain provocation (n = 150 subjects) were performed. Positive correlations were found between joint mobility, sagittal thoraco-lumbar mobility and segmental mobility. Hyperlordosis (>39 degrees) was associated with greater lumbar mobility. The reliability of manual segmental mobility and segmental pain provocation was good, especially in the lowest back segments (kappa approximately 0.7). Joint mobility, general mobility and segmental spinal mobility intercorrelated. Segmental mobility manually estimated showed intertester reliability. The good positive correlation between sagittal lumbar mobility and manually tested segmental mobility indicates criterion validity for the latter.

Adult↗

PubMed1982

Organization, structure, and assembly of immunoglobulin heavy chain diversity DNA segments.

We have identified, cloned, and sequenced eight different DNA segments encoding the diversity (D) regions of mouse immunoglobulin heavy-chain genes. Like the two D segments previously characterized (16, 17), all eight D segments are flanked by characteristic heptamers and nonamers separated by 12-bp spacers. These 10 D segments, and several more D segments identified but not yet sequenced, can be classified into three families based on the extent of sequence homology. The SP2 family consists of nine highly homologous D segments that are all 17-bp long and clustered in a chromosomal region of approximately 60 kb. The FL16 family consists of up to four D segments, two of which were mapped in the 5' end region of the SP2-D cluster. The two FL16D segments are 23 and 17 bp long. The third, the Q52 family, is a single-member family of the 10-bp-long DQ52, located 700 bp 5' to the JH cluster. We argue that the D-region sequences of the majority of heavy chain genes arise from these germline D segments by various somatic mechanisms, including joining of multiple D segments. We present a specific model of D-D joining that does not violate the 12/23-bp spacer rule.

Amino Acid Sequence↗

PubMed2003

Genetic algorithm based deliverable segments optimization for static intensity-modulated radiotherapy.

The static delivery technique (also called step-and-shoot technique) has been widely used in intensity-modulated radiotherapy (IMRT) because of the simple delivery and easy quality assurance. Conventional static IMRT consists of two steps: first to calculate the intensity-modulated beam profiles using an inverse planning algorithm, and then to translate these profiles into a series of uniform segments using a leaf-sequencing tool. In order to simplify the procedure and shorten the treatment time of the static mode, an efficient technique, called genetic algorithm based deliverable segments optimization (GADSO), is developed in our work, which combines these two steps into one. Taking the pre-defined beams and the total number of segments per treatment as input, the number of segments for each beam, the segment shapes and weights are determined automatically. A group of interim modulated beam profiles quickly calculated using a conjugate gradient (CG) method are used to determine the segment number for each beam and to initialize segment shapes. A modified genetic algorithm based on a two-dimensional binary coding scheme is used to optimize the segment shapes, and a CG method is used to optimize the segment weights. The physical characters of a multileaf collimator, such as the leaves interdigitation limitation and leaves maximum over-travel distance, are incorporated into the optimization. The algorithm is applied to some examples and the results demonstrate that GADSO is able to produce highly conformal dose distributions using 20-30 deliverable segments per treatment within a clinically acceptable computation time.

Adult↗

PubMed1995

Utility of Tc-99m GSA SPECT imaging in estimation of functional volume of liver segments in health and liver diseases.

The authors examined whether there was a difference in liver function among hepatic segments in liver cirrhosis cases, and in cases of hepatocellular carcinoma (HCC) associated with liver cirrhosis. If the average counts in the lateral segment of the left lobe were set at 1, the average counts in the right upper and lower segment of the liver were 0.75 approximately 1.02 (0.89 +/- 0.09, mean +/- SD) in normal cases, 0.38 approximately 2.24 (1.01 +/- 0.39) in liver cirrhosis cases, and 0.61 approximately 2.85 (1.15 +/- 0.58) in HCC cases. There is a significant difference between normal cases and liver cirrhosis cases or HCC cases (P < 0.001). Also, in HCC cases, if the average counts in the cancer-bearing segment of the liver were set at 1, the average counts in the noncancerous segment of the liver were 0.55 approximately 2.85 (1.23 +/- 0.58), and many average counts in the cancer-bearing segment were equal to, or lower than those in the noncancerous segment. It has been found that there were significant differences in function among hepatic segments in liver cirrhosis cases, and in HCC cases. Furthermore, the liver function in the cancer-bearing segment tended to be worse due to the existence of carcinoma compared with that in the noncancerous segment.

Adult↗

PubMed1997

Methods to enhance in vivo urothelial growth on seromuscular colonic segments in the dog.

PURPOSE: We demonstrated survival and expansion in vivo of urothelial free autografts on demucosalized seromuscular segments. MATERIALS AND METHODS: Four methods of in vivo urothelial expansion were investigated on demucosalized colonic segments in the canine model. Group 1 underwent colonic mucosal removal by manual stripping, group 2 underwent removal of colonic mucosa and submucosa, and group 3 underwent manual stripping of the colonic mucosa followed by treatment with protamine sulfate and urea. In the 3 groups urothelial autografts were then placed on the seromuscular segment and tubularized over a balloon splint. In group 4 the colonic mucosa was removed but the grafts were not tubularized. Instead the colonic segment was sutured to the parietal peritoneum. RESULTS: Group 4 grafts had no epithelial growth and shrinkage of the bowel segment. Group 1 grafts had minimal growth with no expansion and colonic mucosal regrowth. Group 2 grafts demonstrated growth and expansion, although these colonic segments had a significant inflammatory response and fibrosis. Group 3 grafts had the best growth and expansion with the least inflammatory response, and 1 colonic segment was almost completely covered with urothelium. CONCLUSIONS: We demonstrated in vivo expansion of urothelial autografts grown on seromuscular colonic segments. Preservation of the submucosa is essential to prevent fibrosis of the seromuscular colonic segment and a balloon stent is crucial to prevent graft contraction. Treatment of the demucosalized segment with protamine sulfate and urea results in better urothelial expansion and less colonic mucosal regrowth.

Animals↗

PubMed1999

Multiple-segment osteotomy in maxillofacial surgery.

Multiple-segment osteotomy is defined as an osteotomy that divides the tooth-bearing arch of the maxilla or mandible into three or more segments. Combining large-segment orthognathic surgery and unitooth or small-segment surgery is an effective approach for dealing with a wide range of dentofacial deformities with occlusal problems. The indications for a multiple-segment osteotomy included dentofacial deformities and malocclusions requiring stable correction within a short overall treatment period. From 1991 to 1997, a total of 85 patients had multiple-segment osteotomy orthognathic procedures performed at Chang Gung Memorial Hospital. The indications for surgery were maxillary protrusion/deformity (31 patients), mandibular prognathism (51 patients), and noncleft maxillary retrusion (three patients). The types of osteotomies performed were Le Fort I, anterior segmental osteotomies of the maxilla or the mandible, palatal split, posterior segment, and unitooth or double-tooth segments. Follow-up ranged from 6 months to 7 years; stability was seen in movements, with only three complications (one partial gingival loss and two inferior mental paresthesias). No osteotomized segments were lost. The average overall treatment time was approximately 15 months, including 3 to 6 months of preoperative and 9 to 12 months of postoperative orthodontic treatment. This is at least 6 months shorter than traditional orthognathic surgery. Experience with 85 consecutive patients has shown that the results are good and the procedure is safe, with minimal complications.

Adolescent↗

PubMed1985

A biomechanical analysis of spinal instrumentation systems in thoracolumbar fractures. Comparison of traditional Harrington distraction instrumentation with segmental spinal instrumentation.

A total of 61 biomechanical tests were performed on 25 cadaveric spinal segments to investigate the comparative strengths of three instrumentation systems: 1) conventional Harrington distraction instrumentation (HRI), 2) segmentally wired Harrington distraction rods, and 3) Luque segmental spinal instrumentation (SSI). In type I testing in which axial preload was applied to normal specimens, and then progressive rotation until ultimate failure followed, five of six Harrington systems failed at the bone-metal interface. In contrast, all six Luque SSI vertebral segments disrupted in a location removed from the bone-metal interface. In Type-II testing (six specimens) in which axial loading of experimentally produced unstable burst fractures was applied, the most stable fixation in resisting compressive loads was segmentally wired Harrington distraction rods (P less than 0.001). In Type-III testing (six specimens), there was axial preloading, then progressive rotation applied to translational fracture-dislocations and this showed that the ability to resist torsion was lowest with plain HRI, slightly improved by segmentally wired HRI, and the stiffest system was Luque SSI (P less than 0.05). The three methods of testing cadaveric segments provided a relevant laboratory model for investigation of spinal instrumentation systems in thoracolumbar fracture stabilization. The results compare favorably with other biomechanical studies, information derived from in vitro and ex vivo animal models and clinical experience with failures of fixation. The biomechanical advantages of segmentally wired Harrington distraction instrumentation in resisting axial loads seem to justify this method of fixation in unstable burst fractures. Similarly, the use of Luque segmental spinal instrumentation with L-rods coupled together is the best method of achieving rotational stability in translational injuries (fracture-dislocations). However, the above biomechanical considerations should be balanced against the increased operative time, more exacting technical expertise required, and possible risk of iatrogenic neurologic sequelae in implementing segmental fixation in unstable thoracolumbar fracture management.

Adolescent↗

PubMed2000

Successful short-segment instrumentation and fusion for thoracolumbar spine fractures: a consecutive 41/2-year series.

STUDY DESIGN: A retrospective review of all the surgically managed spinal fractures at the University of Missouri Medical Center during the 41/2-year period from January 1989 to July 1993 was performed. Of the 51 surgically managed patients, 46 were instrumented by short-segment technique (attachment of one level above the fracture to one level below the fracture). The other 5 patients in this consecutive series had multiple trauma. These patients were included in the review because this was a consecutive series. However, they were grouped separately because they were instrumented by long-segment technique because of their multiple organ system injuries. OBJECTIVES: The choice of the anterior or posterior approach for short-segment instrumentation was based on the Load-Sharing Classification published in a 1994 issue of Spine. The purpose of this review was to demonstrate that grading comminution by use of the Load-Sharing Classification for approach selection and the choice of patients with isolated fractures who are cooperative with spinal bracing for 4 months provide the keys to successful short-segment treatment of isolated spinal fractures. SUMMARY OF BACKGROUND DATA: The current literature implies that the use of pedicle screws for short-segment instrumentation of spinal fracture is dangerous and inappropriate because of the high screw fracture rate. METHODS: Charts, operative notes, preoperative and postoperative radiographs, computed tomography scans, and follow-up records of all patients were reviewed carefully from the time of surgery until final follow-up assessment. The Load-Sharing Classification had been used prospectively for all patients before their surgery to determine the approach for short-segment instrumentation. Denis' Pain Scale and Work Scales were obtained during follow-up evaluation for all patients. RESULTS: All patients were observed over 40 months except for 1 patient who died of unrelated causes after 35 months. The mean follow-up period was 66 months (51/2 years). No patient was lost to follow-up evaluation. Prospective application of the Load-Sharing Classification to the patients' injury and restriction of the short-segment approach to cooperative patients with isolated spinal fractures (excluding multisystem trauma patients) allowed 45 of 46 patients instrumented by the short-segment technique to proceed to successful healing in virtual anatomic alignment. CONCLUSIONS: The Load-Sharing Classification is a straightforward way to describe the amount of bony comminution in a spinal fracture. When applied to patients with isolated spine fractures who are cooperative with 3 to 4 months of spinal bracing, it can help the surgeon select short-segment pedicle-screw-based fixation using the posterior approach for less comminuted injuries and the anterior approach for those more comminuted. The choice of which fracture-dislocations should be strut grafted anteriorly and which need only posterior short-segment pedicle-screw-based instrumentation also can be made using the Load-Sharing Classification.

Adolescent↗

PubMed1999

Clinical characteristics of ST-segment elevation in lead V6 in patients with Q-wave acute inferior wall myocardial infarction.

BACKGROUND: Precordial ST-segment depression in acute inferior infarction is well recognized, but few studies have evaluated ST-segment elevation in lateral precordial leads. The present study examined the clinical significance of ST-segment elevation in lead V6 in patients with acute Q-wave inferior myocardial infarction. METHODS: We studied the initial electrocardiography of 125 consecutive patients with acute Q-wave inferior myocardial infarction admitted to hospital within 12 h of the onset of chest pain. They were classified into two groups: group 1 = 34 patients with ST-segment elevation in lead V6; group 2 = 91 patients with no ST-segment elevation in lead V6. RESULTS: Among the seven clinical variables examined, the number of left ventricular asynergic segments (P < 0.001) and pulmonary capillary wedge pressure (P = 0.001) were related to ST-segment elevation in lead V6. The incidences of major arrhythmias (50% compared with 31%, P = 0.04), pericardial effusion (32% compared with 9%, P = 0.003), and pericardial rub (15% compared with 2%, P = 0.02) during the patients' stay in hospital were greater in group 1 than in group 2. Among the patients in group 1, the right coronary artery was the culprit artery in 22 of 24 patients (92%) with ST segment depression in lead I, whereas the circumflex artery was the culprit artery in nine of 10 patients (90%) with isoelectric or ST-segment elevation in lead I. CONCLUSION: The presence of ST-segment elevation in lead V6 in patients with acute Q-wave inferior myocardial infarction was associated with larger infarct size, and greater incidences of major arrhythmias and pericardial involvement during the patient's stay in hospital.

Adult↗

PubMed2004

Interruption of the bilateral segmental arteries at several levels: influence on vertebral blood flow.

STUDY DESIGN: The effect of ligation of the bilateral segmental arteries at the levels of T11, T12, and T13 on blood flow of the T12 vertebra was studied in a dog model. OBJECTIVES: To determine the reduction of the vertebral blood flow resulting from interruption of bilateral segmental arteries at one to three vertebral levels. SUMMARY OF BACKGROUND DATA: Intraoperative hemorrhage can be sometimes massive in patients with hypervascular spinal tumors, especially in radical resection such as total en bloc spondylectomy. The recent development of new embolization techniques ensures more aggressive, more extensive, and safer preoperative embolization for spinal tumors. METHODS: The blood flow of the T12 vertebra of 12 female dogs was measured after ligation of the bilateral segmental arteries at one to three levels, including the T12. Spinal cord evoked potentials were recorded in this procedure. Spinal angiography using a silicon compound was performed on another 10 dogs after clipping and section of the bilateral segmental arteries. RESULTS: The blood flow of the T12 vertebra decreased to 70.13 +/- 6.37% of the control value after ligation of the bilateral segmental arteries of T12, to 46.48 +/- 8.97% after ligation of the bilateral segmental arteries of T12 and either T11 or T13, to 24.11 +/- 8.31% after ligation of T11, T12, and T13, respectively. The angiogram after ligation and section of T12 and the two levels including T12 showed thick and clear contrast medium in the cut distal ends of the T12 segmental arteries. After interruption at three levels (T11, T12, and T13), however, the cut distal ends of the T12 segmental arteries were seen thin and faint on the angiogram. No significant changes occurred in spinal cord evoked potentials after ligation of the segmental arteries at three levels in all six dogs. CONCLUSION: Interruption of the bilateral segmental arteries at three levels, one target vertebra and the two adjacent vertebrae, reduced the blood flow of the target vertebra to one fourth of the control value in the lower thoracic spine in dogs. This result suggests that preoperative embolization at three levels, the levels of the tumor vertebra and the adjacent vertebrae above and below it, may reduce intraoperative hemorrhage effectively during total en bloc spondylectomy for hypervascular spinal tumors.

Angiography↗

PubMed2004

Adjacent segment disease after lumbar or lumbosacral fusion: review of the literature.

STUDY DESIGN: Review of the literature. OBJECTIVES: Review the definition, etiology, incidence, and risk factors associated with as well as potential treatment options. SUMMARY OF BACKGROUND DATA: The development of pathology at the mobile segment next to a lumbar or lumbosacral spinal fusion has been termed adjacent segment disease. Initially reported to occur rarely, it is now considered a potential late complication of spinal fusion that can necessitate further surgical intervention and adversely affect outcomes. METHODS: MEDLINE literature search. RESULTS: The most common abnormal finding at the adjacent segment is disc degeneration. Biomechanical changes consisting of increased intradiscal pressure, increased facet loading, and increased mobility occur after fusion and have been implicated in causing adjacent segment disease. Progressive spinal degeneration with age is also thought to be a major contributor. From a radiographic standpoint, reported incidence during average postoperative follow-up observation ranging from 36 to 369 months varies substantially from 5.2 to 100%. Incidence of symptomatic adjacent segment disease is lower, however, ranging from 5.2 to 18.5% during 44.8 to 164 months of follow-up observation. The rate of symptomatic adjacent segment disease is higher in patients with transpedicular instrumentation (12.2-18.5%) compared with patients fused with other forms of instrumentation or with no instrumentation (5.2-5.6%). Potential risk factors include instrumentation, fusion length, sagittal malalignment, facet injury, age, and pre-existing degenerative changes. CONCLUSION: Biomechanical alterations likely play a primary role in causing adjacent segment disease. Radiographically apparent, asymptomatic adjacent segment disease is common but does not correlate with functional outcomes. Potentially modifiable risk factors for the development of adjacent segment disease include fusion without instrumentation, protecting the facet joint of the adjacent segment during placement of pedicle screws,fusion length, and sagittal balance. Surgical management, when indicated, consists of decompression of neural elements and extension of fusion. Outcomes after surgery, however, are modest.

Adult↗

PubMed2004

Relation between laminectomy and development of adjacent segment instability after lumbar fusion with pedicle fixation.

STUDY DESIGN: A retrospective study of 101 patients who had undergone posterolateral lumbar fusion, to analyze the association between adjacent instability and the extent of laminectomy. OBJECTIVES: To investigate the hypothesis that the integrity of the posterior complex (spinous process/supraspinous ligament/spinous process) between the fused segments and the neighboring motion segments significantly influences lumbar spine stability. SUMMARY OF BACKGROUND DATA: Spinal fusion with pedicle fixation accelerates the degeneration of adjacent motion segments. The lowest cranial motion segment is the most common level for the development of adjacent instability. Laminectomy, including removal of the spinous process, supraspinous ligament, interspinous ligament, lamina and ligamentum flavum, jeopardizes the integrity of the posterior complex of the spine. METHODS: This study enrolled 101 patients, followed up for at least 6 years, who had been treated with posterolateral lumbar fusion with pedicle fixation because of lumbar spondylolisthesis. The diagnosis of adjacent instability depended on the dynamic lateral views of the lumbosacral spine during each follow-up. The integrity of the posterior complex was based on the extent of laminectomy and the fusion level. RESULTS: At the cranial adjacent motion segment, 2 of 31 (6.5%) patients with preserved posterior complex integrity between the fused segment and motion segment developed adjacent instability, compared with 17 of 70 (24.3%) without preserved posterior complex integrity. At the caudal adjacent motion segment, none of 13 patients (0%) with preserved integrity developed adjacent instability, compared with 3 of 54 (5.6%) without preserved integrity. CONCLUSIONS: Damaging the integrity of the posterior complex between the fused segments and the neighboring motion segments may jeopardize lumbar spine stability. Sacrificing either the supraspinous ligament or the tendon insertion points on the spinous processes leads to an accelerated development of adjacent instability.

Adult↗

PubMed2006

Mechanical stiffness of segmental versus nonsegmental pedicle screw constructs: the effect of cross-links.

STUDY DESIGN: A biomechanical study in porcine spines of the construct stiffness effects of segmental pedicle screws. Stiffness effects of supplementation of nonsegmental screw constructs with cross-links was also evaluated. OBJECTIVE: To assess the biomechanical differences between constructs using segmental versus nonsegmental pedicle screw-based instrumentation as well as the effect of cross-links. SUMMARY OF BACKGROUND DATA: An in vitro biomechanical comparison of segmental versus nonsegmental pedicle screw constructs with and without cross-links using porcine lumbar vertebrae was performed. Mechanical trade-offs of reducing the number of pedicle screws in a given construct and substituting a cross-link for a pair of screws are not well understood. METHODS: Three, 4, and 5-vertebral segments from 18 porcine spines were instrumented with segmental and nonsegmental pedicle screw constructs, and with nonsegmental screws augmented with cross-links. Unconstrained biomechanical testing in flexion, extension, and axial rotation with 6 degree-of-freedom motion tracking was performed. Statistical comparisons of stiffness data were conducted using 2-tailed paired t tests. RESULTS: There was a statistically significant increase in stiffness between models with segmental pedicle screws compared to nonsegmental pedicle screws in 6 of the 9 mechanical tests. The remaining 3 tests approached but did not reach statistical significance (P = 0.087, 0.062, and 0.078). When cross-links were added to the nonsegmental models, differences in stiffness compared to segmental pedicle screws were largely eliminated, decreasing well below statistical significance in 8 of 9 tests. The highest difference in nonsegmental models with cross-links and segmental pedicle screw models was observed for the 5-vertebrae fusion models, for which axial rotation testing maintained statistically significant differences (P = 0.006), and flexion testing approached significance (P = 0.062). CONCLUSIONS: Segmental pedicle screw constructs increased mechanical stiffness compared to nonsegmental constructs in our fusion models. Placement of a single cross-link with nonsegmental screws eliminated statistical differences for 3 and 4-vertebral level constructs, and may be a satisfactory alternative in this clinical setting. Caution in applying these results inlonger constructs is recommended, given persistent increased stiffness found for the segmental 5-vertebral level models.

Animals↗

PubMed2005

Aerosol transfer of bladder urothelial and smooth muscle cells onto demucosalized colonic segments for porcine bladder augmentation in vivo: a 6-week experimental study.

PURPOSE: In a pilot study we developed a cell transfer technology for populating demucosalized colonic segments with bladder urothelium. This process was achieved through aerosol transfer of a single cell suspension consisting of bladder urothelial cells, smooth muscle cells and fibrin glue onto demucosalized colonic segments. We further evaluate this new concept in a controlled study. MATERIALS AND METHODS: The study was performed on 20 piglets (20 kg). In all animals 50% of the bladder with excised, and a 10 cm segment of the sigmoid was isolated. Animals were then equally divided into 5 groups of 1) colocystoplasty only, 2) demucosalized colocystoplasty, 3) demucosalized colocystoplasty plus covering of the demucosalized sigmoid with fibrin glue only, 4) aerosol application of fibrin glue with single cell suspension of urothelial cells only to the demucosalized colon, and 5) aerosol application of fibrin glue with urothelial and smooth muscle cells to the demucosalized colon. The 4 corners of the augmented segments were marked with 5-zero polypropylene sutures. Animals were sacrificed 6 weeks later and the surface area of the augmented segment was measured. Segments were submitted to histological and immunohistochemical analysis. RESULTS: The surface area of the augmented segments showed an increase in group 1 animals, stabilization in groups 4 and 5, and marked reduction in groups 2 and 3. On hematoxylin and eosin, and Masson trichrome staining all group 1 animals showed normal colonic epithelium of the augment. All animals in groups 2 and 3 showed excessive scarring with urothelial coverage only at the augment periphery, while the central augment area showed no epithelium. Segments from groups 4 and 5 showed confluent epithelial covering with no fibrosis. There was no evidence of colonic epithelial re-growth in any animal in groups 2 to 5. Cytokeratin 7 and uroplakin III staining demonstrated complete coverage of the augmented segment with urothelium only in groups 4 and 5. CONCLUSIONS: The addition of aerosolized cells of urological origin is a viable augmentation approach that appears to achieve the much sought after inhibition of intrinsic fibrosis and contraction of colonic segments when incorporated into the urinary tract without this cellular component. Moreover, this technique appears to provide a histologically normal, confluent urothelium, which sets the stage for prevention of the well-documented biochemical aberrations inherent in augments containing gastrointestinal epithelium. While successful in this model regardless of the incorporation of urological smooth muscle cells, chronic studies are now warranted to validate the short-term results as well as determine whether the urological mesenchymal population (smooth muscle) will be required to sustain the uroepithelial phenotype in the long term.

Aerosols↗