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PubMed2006

Stochastic modelling of colon cancer: is there a role for genomic instability?

Three stochastic models of genomic instability recently developed by Little and Wright (Math. Biosci., (2003) 183, 111-34), with two, three and five stages, and the two-stage genomic instability model of Nowak et al. (Proc. Natl Acad. Sci. USA, (2002) 99, 16226-16231) are compared with the four-stage model proposed by Luebeck and Moolgavkar (Proc. Natl Acad. Sci. USA, (2002) 99, 15095-15100) that does not assume such an instability mechanism. All models are fitted to US colon cancer incidence data. The best fitting models are the two-stage model of Nowak et al. and the two-stage model of Little and Wright, with the four-stage model of Luebeck and Moolgavkar not markedly inferior. The fits of the three-stage and five-stage models are somewhat worse (P<0.05), the five-stage model fitting particularly poorly (P<0.01). Both optimal genomic instability models predict cellular mutation rates that are at least 10 000 times higher after genomic destabilization, for both sexes. Therefore, the results of this paper are somewhat at variance with those of previous analyses of Little and Wright in suggesting that equivalently good fit may be obtained by models that do not assume a role for genomic destabilization in the induction of colon cancer as for those that do.

Colonic Neoplasms↗

PubMed2005

Mismatch repair system and aging: microsatellite instability in peripheral blood cells from differently aged participants.

Age-related alterations of DNA repair could be involved in the accumulation of genetic damage with age. Few data suggest a possible alteration with age of the mismatch repair system, evidenced by the acquisition of microsatellite instability. We aimed to point out a possible implication of this repair system in the accumulation of genetic damage with age. Peripheral blood cell DNA from 226 participants, 110 young (25-35 years), 58 old (85-97 years), and 58 centenarian was analyzed at five polymorphic microsatellite loci (CD4, p53, VWA31, TPOX, and FES/FPS) to point out age-related instabilities or modifications in allele frequencies. FES/FPS microsatellite was the most instable, showing both the appearance of trizygosis in DNA from old participants and differences in allele patterns among age groups, thus indicating an association between increased microsatellite instability and aging, one of the possible causes of which being an impairment of mismatch repair system capacity with age.

Adult↗

PubMed2004

Chromosomal instability.

PURPOSE OF REVIEW: This review discusses numerical and structural chromosomal instability in cancer cells and its possible etiologies, highlighting the recent literature. RECENT FINDINGS: Defects in chromosomal segregation, telomere stability, and the DNA damage response play significant roles in chromosomal instability in cancer. SUMMARY: The pace of discoveries into the biologic basis of chromosomal instability in cancer cells is quickening and the various causes, previously thought to be unrelated, are being found to be intertwined. Because chromosomal instability is likely to be a main mechanism behind tumor evasion of therapy, understanding the causes and their implications for diagnostic and prognostic evaluation and therapy is of tantamount importance.

Cell Transformation, Neoplastic↗

PubMed2001

Kinematic evaluation of atlantoaxial joint instability: an in vivo cineradiographic investigation.

Although range of motion has been considered the best parameter to quantify atlantoaxial instability, no other kinematic parameters have been determined for dynamic quantification. The objectives of this study were to investigate the kinematics of the normal and pathologic atlantoaxial joints by cineradiography and to determine the in-vivo kinematic parameters, if any, for the quantification of atlantoaxial instability. Sagittal plane motion of the atlantoaxial joints was analyzed by cineradiography in 12 healthy volunteers and 15 patients with atlantoaxial subluxation. In both flexion and extension, C1-C2 sagittal rotation and C1 translation in the sagittal plane were measured continuously to determine the time-displacement curves for both parameters. All patients with atlantoaxial subluxation and seven of the volunteers had the sigmoid pattern in their time-displacement curves in sagittal rotation. In these cases, atlantoaxial motion showed different points of the onset of rapid increase in motion in their sigmoid curves between flexion and extension. The discrepancy between these points was more significant in the patients than in the volunteers. In most of the patients who had atlantoaxial instability, subluxation occurred when the atlantoaxial joints were still in a more extended position and they were reduced when they were still in more flexed position. The discrepancy showed characteristics similar to those of the neutral zone observed during in vitro investigations, suggesting that it becomes a good indicator of in vivo atlantoaxial instability.

Adult↗

PubMed1996

Shoulder instability in athletes. The Asian perspective.

Recently, there has been an upsurge of interest among the orthopaedic sports medicine community in Asia on this subject of athletic shoulder instability. This is particularly prominent in countries such as Japan, Korea, Taiwan, and Hong Kong, where sports requiring throwing and overhead use of the upper limb are popular. In this review, the classification of the condition is analyzed with a specific account of the rotator interval injury. A systematic plan of clinical assessment is presented highlighting the specific regional considerations in clinical practice and cost-effectiveness of the health care systems in Asia. The management of athletic shoulder instability depends on patient attitude and cultural background. In Asia, the popular choice of Bankart repair with capsular shift procedure is presented with special reference to the unique experience of multidirectional and habitual posterior instability. Arthroscopic surgery is becoming popular in Asia, and the indications and limitations of the technique in the management of shoulder instability are discussed.

Arthroscopy↗

PubMed1997

Anterior release test. A new test for occult shoulder instability.

Occult shoulder instability is recognized as a significant contributor to shoulder dysfunction in throwing athletes. Diagnosis of occult instability by physical examination remains challenging. The anterior release test is a test for physical examination of the shoulder. It was developed to facilitate detection of occult anterior instability. One hundred shoulders were examined preoperatively by the same examiner. Based on surgical findings, the shoulders were classified as anterior instability or other. The results of examination were compared with the operative findings. Sensitivity was calculated as 91.9%, specificity 88.9%, positive predictive value 87.1%, negative predictive value 93.0%, and accuracy 90.2%. The anterior release test is a reliable and reproducible test for the detection of the unstable shoulder.

Adolescent↗

PubMed2001

Arthroscopic treatment of instability attributable to capsular injury or laxity.

Among the many causes of shoulder instability are traumatic capsular injury associated with the Bankart lesion and capsular laxity as seen in multidirectional instability. Previously, open surgical procedures were the most commonly accepted surgical treatment of these disorders. However, because of the foresight of surgeons such as Richard Caspari, arthroscopy rapidly is becoming the surgical treatment of choice. Current studies have shown a 97% satisfactory outcome of arthroscopic Bankart repair. Similarly, the arthroscopic treatment of multidirectional instability has produced a 93% satisfactory outcome. These results parallel the gold standard open surgical techniques of the past and subsequently have led to a change in the treatment of shoulder instability.

Arthroscopy↗

PubMed2002

Glenoid shape in atraumatic posterior instability of the shoulder.

Glenoid shape is related closely to shoulder stability and its abnormality is thought to affect the humeral head position in shoulders with atraumatic instability. However, it is unclear how the glenoid shape in shoulders with atraumatic instability is different from the glenoid shape in normal shoulders. The current authors investigated glenoid shape of 45 healthy individuals (20 males and 25 females; average age, 22 years) and 20 patients with atraumatic posterior instability with multidirectional laxity (six males and 14 females; average age, 19 years) using three-dimensional magnetic resonance imaging. The tilting angles of the glenoid bone were measured in five consecutive planes perpendicular to the long axis of the glenoid and cross sections were divided into three types (concave, flat, convex). In healthy individuals, the average tilting angles from the bottom to the top of the glenoid bone were 3.0 degrees +/- 3.6 degrees, 1.0 degrees +/- 3.2 degrees, -1.0 degrees +/- 2.0 degrees, -2.3 degrees +/- 3.9 degrees, and -6.9 degrees +/- 3.7 degrees anteriorly, and tilting angles of patients were -6.1 degrees +/- 4.0 degrees, -4.0 degrees +/- 3.6 degrees, -4.8 degrees +/- 3.2 degrees, -5.5 degrees +/- 2.7 degrees, and -7.5 degrees +/- 3.1 degrees. The type of cross section also was different on the bottom plane where the concave shape accounted for 78% of healthy individuals whereas it accounted for 0% of patients. The loss of tilting angles and concavity of the inferior glenoid would correlate with the direction of the head translation in posterior instability.

Adolescent↗

PubMed2003

Recurrent anterior hip instability after a simple hip dislocation: a case report.

A 35-year-old woman sustained a simple anterior hip dislocation after a fall. Initial treatment involved a closed reduction under sedation with brace immobilization. Nine months after the initial dislocation, she began having recurrent anterior hip instability (four events) requiring closed reduction under anesthesia. Secondary to the recurrent dislocations, she had a derotational subtrochanteric femoral osteotomy at an outside hospital for the anterior instability. After this procedure she sustained five additional anterior dislocations requiring closed reduction under anesthesia. After nine anterior dislocations, she had periacetabular osteotomy retroverting her acetabulum with repair of the anterior hip capsule which has successfully solved the recurrent instability. To the author's knowledge this is the first reported case of recurrent anterior hip instability treated successfully with a periacetabular osteotomy.

Acetabulum↗

PubMed2005

Flexion instability without dislocation after posterior stabilized total knees.

UNLABELLED: Flexion instability after cruciate-retaining total knee arthroplasty has been well documented. We identified an analogous patient group with symptomatic flexion instability without dislocation after primary posterior stabilized total knee arthroplasty. We sought to determine the typical symptoms and exam findings that lead to the diagnosis, to assess the reliability of revision total knee arthroplasty as a treatment, and to assess the technical difficulties encountered during revision total knee arthroplasty. Between 1995 and 2001, 10 patients had revision of a well-fixed posterior stabilized total knee arthroplasty for isolated symptomatic flexion instability. The typical constellation of symptoms and physical findings included a sense of instability without giving way, recurrent knee effusions, multiple areas of soft tissue tenderness about the knee, and substantial anterior tibial translation at 90 degrees of flexion. The revision operation focused on balancing the flexion and extension gaps while taking care to fill the enlarged flexion gap. Revision total knee arthroplasty was reliable in alleviating pain (mean Knee Society Pain scores improved from 68 points preoperatively to 89 points postoperatively), improving stability (nine of 10 patients had < 5 mm anterior tibial translation postoperatively) and improving patient satisfaction (nine of 10 patients were satisfied). We had no particular technical difficulties with the revision total knee arthroplasty procedures and had reliably achieved well-balanced flexion and extension gaps. LEVEL OF EVIDENCE: Therapeutic study, Level IV-1 (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Aged↗

PubMed1986

Lumbar spine osteolysis: an entity caused by spinal instability.

Presented is a new entity in the spectrum of complications following spinal decompression. It occurs in patients with spinal instability after decompression. Thereafter, instability accelerates, leading to a rapid clinical and radiologic deterioration. The presenting symptoms are back pain and lower extremity weakness, resembling spinal stenosis. Erythrocyte sedimentation rate and temperature remain normal. Radiologically, a distinct form of progressing osteolysis is present. This entity may present a difficult diagnostic problem and is usually diagnosed erroneously as a destructive osteomyelitis. Craig needle biopsy results are normal. Treatment consists of stabilization rather than antibiotic therapy and debridement. It is apparent that patients with spinal instability are to be considered "at risk" as further decompression may accelerate the instability, resulting in progressive osteolysis.

Aged↗

PubMed1987

Lumbar instability: a dynamic approach by traction-compression radiography.

Translatory segmental instability was provoked by successive axial traction and compression of the lumbar spine in 117 patients with a known spondyl- or retro-olisthetic displacement. Lateral spot radiography showed an anteroposterior translatory movement of 5 mm or more in 24 of 45 patients with lytic spondylolisthesis of L5, in all of 7 patients with degenerative spondylolisthesis of L4, and in 37 of 65 patients with a retro-olisthetic displacement of L3, L4, or L5. In cases of spondyl- and retro-olisthetic instability the upper vertebra moved posteriorly during traction and anteriorly during compression. Severity of low-back pain (LBP) symptoms did not show any correlation with the degree of the maximal displacement but correlated significantly with the amount of instability both in the case of spondyl- and retro-olisthesis. Traction-compression radiography proved a simple and practical method to diagnose and measure translatory segmental instability even when conventional flexion-extension load failed to provoke any abnormal movement (eg, in the case of spondylolisthesis).

Adolescent↗

PubMed1989

Follow-up study of atlanto-axial instability in Down's syndrome without separate odontoid process.

Clinical and roentgenologic studies were performed in 69 children with Down's syndrome, without the separate odontoid process, that could be followed for more than 5 years. At the follow-up examination, the atlanto-odontoid process interval (AOI) in flexion, neutral, and extension of the cervical vertebrae significantly decreased when compared with the one at the initial examination. This was particularly obvious up to 5 years of age. Although 14 of 69 cases (20.3%) had atlanto-axial instability at the initial examination, this decreased to four cases (5.8%) at the follow-up examination. However, there were two cases of atlanto-axial instability who were over 10 years of age. There was no significant difference in the minimum sagittal diameter (MSD) at the atlantal level between each position at both the initial and follow-up examinations. Moreover, there was a tendency for the MSD of the cases of positive instability at the follow-up examination to be smaller than those of the cases of negative instability. The degree of ligament laxity improved with increasing age and there was statistically the negative correlation. Although there was a tendency for the AOI to decrease with improvement of the degree of ligament laxity, the correlation could not be confirmed.

Aging↗

PubMed1991

Os odontoideum with posterior atlantoaxial instability.

Nine patients who had os odontoideum with posterior atlantoaxial instability are reviewed. Three parameters were measured on the lateral radiographs: the distance from the os odontoideum to the spinous process of the axis in extension (Dext), the distance from the os odontoideum to the posterior arch of the atlas (Datl), and the degree of instability (Inst). Patients were classified into four groups: Group I, local symptoms (N = 3); Group II, transient myelopathy (N = 0); Group III, progressive myelopathy (N = 6); and Group IV, cerebral symptoms (N = 0). The development of cervical myelopathy was not related to degree of instability but to distance from the os to the spinous process of the axis (Dext). Dext was more than 16 mm in Group I and less than or equal to 16 mm in Group III. Five of six patients in Group III underwent myelography. Based on myelographic findings, Group III was further subdivided into two groups, Group IIIA (N = 2) and Group IIIB (N = 3), according to the following characteristics: In Group IIIA, the distance from the os to the posterior arch of the atlas was more than 13 mm, and the spinal cord was impinged between the os odontoideum and the lamina of the axis in extension and reduced in flexion. In Group IIIB, Datl was less than or equal to 13 mm, and the spinal cord was compressed at the level of the atlas during flexion and extension. Stenotic Datl of 13 mm or less specifically defined severe cervical myelopathy. Surgical treatment for cervical myelopathy in os odontoideum with posterior instability is suggested as follows: in the absence of canal stenosis of the atlas (Group IIIA), atlantoaxial fusion in a reduced position is indicated; when associated with canal stenosis of the atlas (Group IIIB), laminectomy of the atlas followed by occiput-to-C2 arthrodesis is indispensable.

Adolescent↗

PubMed1996

Cervical interbody xenograft with plate fixation: evaluation of fusion after 7 years of use in post-traumatic discoligamentous instability.

STUDY DESIGN: This retrospective study analyzed clinical and radiologic follow-up evaluations of cervical arthrodesis where interbody xenograft combined with internal fixation was used for management of post-traumatic discoligamentous instability. OBJECTIVES: To report results of use of xenograft to avoid the various disadvantages linked to the use of autologous or allogenous bone graft. SUMMARY OF BACKGROUND DATA: Ligamentous instability of the cervical spine is unlikely to heal in a high proportion of cases, and surgical arthrodesis is usually indicated. Anterior arthrodesis has proved to be a safe procedure, but many problems are associated with the use of autograft or allograft. Given the great number of xenograft procedures, there are relatively few reports in the literature. METHODS: A retrospective study analyzed a consecutive series of 52 patients presenting with post-traumatic discoligamentous instability of the cervical spine in which cervical interbody xenografts with plate fixations were done. Follow-up clinical evaluation for neck pain and radiologic evaluation for arthrodesis stability and xenograft fusion at various points in time were done. RESULTS: The long-term results in 41 patients were satisfactory: no infectious complications, extrusion, fracture, loss of height, or resorption of the graft. Seventy-five percent fusion was seen before 9 months after surgery, and 100% fusion was seen 3-18 months after surgery (average, 7.4 months). CONCLUSIONS: Interbody xenograft combined with a rigid plate fixation avoids the problems linked to autologous or allogenous bone graft and gives a safe and solid interbody fusion when arthrodesis is required in ligamentous instability of the cervical spine.

Adolescent↗

PubMed1997

Instantaneous center of rotation and instability of the cervical spine. A clinical study.

STUDY DESIGN: This study was designed to investigate flexion and extension of the cervical spine in patients with "instability" of the cervical spine. OBJECTIVES: To establish a new method of calculating the instantaneous center of rotation (ICR) of the skull relative to the thorax and to compare the differences in the ICR between normal volunteers and patients. SUMMARY OF BACKGROUND DATA: "Instability" of the cervical spine commonly is investigated using functional radiographs, which is an unreliable method. Although the ICR was suggested as an objective parameter in measuring spinal "instability," the ICR of the skull relative to the thorax has not been studied before. METHOD: Three groups of subjects (27 normal volunteers, 28 patients with chronic cervical spondylosis, and 17 patients undergoing fusion for cervical disc degeneration) were measured with a CA-6000 system (OSI, CA). The ICR then were calculated and compared at various angles of flexion and extension. RESULTS: The horizontal component of the ICR in the preoperative group was found to have shifted anteriorly from 5 degrees to 25 degrees of flexion (P < 0.05) and at 5 degrees of extension (P < 0.05), compared with that of the healthy subjects. There also was a significant difference in the vertical component of the ICR at 15 degrees of flexion (P < 0.05). However, there were no significant differences in the horizontal and the vertical components of the ICR between the normal and nonoperative groups. CONCLUSION: The ICR in patients with "instability" of the cervical spine was found to have shifted anteriorly; the method described in this study might be useful for identifying patients who suffer from this condition.

Aged↗

PubMed1997

A dynamic approach to spinal instability. Part II: Hesitation and giving-way during interspinal motion.

STUDY DESIGN: Human lumbar functional spinal units (FSUs) were moved throughout their range of motion in sagittal and lateral bending, while the dynamics of this movement were computed in vitro. Functional spinal units were tested intact and after subsequent discectomy and unilateral facetectomy. OBJECTIVE: To determine whether the patterns of small jerks observed during intersegmental motion are sensitive to spinal instability. SUMMARY OF BACKGROUND DATA: Small jerks have been observed as hesitation during increasing velocity and as giving way during decreasing velocity in the experiments described in Part I of this study. METHODS: Human lumbar functional spinal units were moved from extension to flexion, flexion to extension, left to right, and right to left, by a pure moment. Range of motion and velocity and acceleration patterns of the main and coupled motions were evaluated in six degrees of freedom by position changes of attached infrared light-emitting diodes recorded by cameras. Functional spinal units were tested in three surgical conditions (intact, discectomy, and unilateral facetectomy) under two preload conditions (no preload and 400-N preload). Discontinuous accelerations and decelerations (jerks) were computed in these motions and their location in relation to the main angular motion determined. RESULTS: Jerks were observed in almost all motions, in the intact functional spinal units and after surgery. The parameters describing the magnitude of the jerk decreased with increasing component instability. In the sagittal plane, there was a surgical condition by motion direction interaction (P < 0.014) regarding the location of the jerk. Independent from the motion direction, the jerk occurred around the neutral position (in relation to the primary angular motion) in the intact functional spinal units, whereas it shifted from the neutral position toward the beginning of the motion with increasing component instability. CONCLUSION: The results suggest that a small jerk is a normal component of fast intersegmental motion. The jerk has a certain magnitude and location in an intact functional spinal unit, whereas both of the parameters describing the jerk are sensitive to component instability.

Acceleration↗

PubMed1998

Atlantoaxial instability complicating radiation therapy for recurrent nasopharyngeal carcinoma. A case report.

STUDY DESIGN: A case report of a patient in whom atlantoaxial instability developed secondary to repeat radiation therapy for recurrent nasopharyngeal carcinoma. OBJECTIVES: To illustrate a dramatic and previously unreported complication of local radiation to the posterior nasopharynx. SUMMARY OF BACKGROUND DATA: Nasopharyngeal carcinoma is an unusual tumor that usually is managed with local, external-beam radiation. It is not thought to involve the cervical spine directly, although local invasion of the skull base is common. METHODS: A review of the medical records and radiographs of the only patient known to develop this complication of radiation used to manage nasopharyngeal carcinoma. RESULTS: Atlantoaxial instability developed in a patient as a result of repeat radiation for a locally recurrent tumor. The instability was associated with intrusion of the anterior arch of C1 into the posterior nasopharynx and was managed successfully with a posterior stabilization using transarticular screws and supplemental wiring. CONCLUSIONS: Patients who have undergone local irradiation for nasopharyngeal carcinoma may be at risk for developing atlantoaxial instability.

Adult↗