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Carpal instability.

This review addresses the pathoanatomical basics as well as the clinical and radiological presentation of instability patterns of the wrist. Carpal instability mostly follows an injury; however, other diseases, like CPPD arthropathy, can be associated. Instability occurs either if the carpus is unable to sustain physiologic loads ("dyskinetics") or suffers from abnormal motion of its bones during movement ("dyskinematics"). In the classification of carpal instability, dissociative subcategories (located within proximal carpal row) are differentiated from non-dissociative subcategories (present between the carpal rows) and combined patterns. It is essential to note that the unstable wrist initially does not cause relevant signs in standard radiograms, therefore being "occult" for the radiologic assessment. This paper emphasizes the high utility of kinematographic studies, contrast-enhanced magnetic resonance imaging (MRI) and MR arthrography for detecting these predynamic and dynamic instability stages. Later in the natural history of carpal instability, static malalignment of the wrist and osteoarthritis will develop, both being associated with significant morbidity and disability. To prevent individual and socio-economic implications, the hand surgeon or orthopedist, as well as the radiologist, is challenged for early and precise diagnosis.

Biomechanical Phenomena↗

MR imaging in sports-related glenohumeral instability.

Sports-related shoulder pain and injuries represent a common problem. In this context, glenohumeral instability is currently believed to play a central role either as a recognized or as an unrecognized condition. Shoulder instabilities can roughly be divided into traumatic, atraumatic, and microtraumatic glenohumeral instabilities. In athletes, atraumatic and microtraumatic instabilities can lead to secondary impingement syndromes and chronic damage to intraarticular structures. Magnetic resonance (MR) arthrography is superior to conventional MR imaging in the diagnosis of labro-ligamentous injuries, intrinsic impingement, and SLAP (superior labral anteroposterior) lesions, and thus represents the most informative imaging modality in the overall assessment of glenohumeral instability. This article reviews the imaging criteria for the detection and classification of instability-related injuries in athletes with special emphasis on the influence of MR findings on therapeutic decisions.

Athletic Injuries↗

Genomic instability in hepatocellular carcinoma revealed by using the random amplified polymorphic DNA method.

PURPOSE: To investigate the genomic instability and their association with clinicopathological characteristics in hepatocellular carcinoma (HCC). METHODS: DNA isolated from tumors and corresponding non-cancerous liver tissues of 56 patients with HCC was amplified with ten random 10-mer arbitrary primers by the random amplified polymorphic DNA (RAPD) method. RESULTS: All the cases of HCC were demonstrated to have genomic instability by at least one primer. The incidence of genomic instability ranged from 20 to 70% in each case, and 17.9-50% in each primer. Serum AFP concentration, HBV infection, tumor size, histological grade, tumor capsule invasion, as well as intrahepatic metastasis were associated with the genomic instability on certain primers. CONCLUSIONS: Genomic instability is a frequent event in HCC. The RAPD is an effective method for the identification and analysis of genomic instability in HCC, and it may provide new information for further evaluating the molecular mechanism of hepatocarcinogenesis.

Adult↗

Accuracy of the clinical examination to predict radiographic instability of the lumbar spine.

Forty-nine patients with low-back pain referred for flexion-extension radiographs due to suspicion of lumbar instability were studied to examine the relationship between the clinical presentation and the presence of radiographic instability of the lumbar spine. Patients had a mean age of 39.2 (+/-11.3) years, with a mean Oswestry score of 20.4% (+/-13.3). The median duration of symptoms was 78 days. All patients underwent both a radiographic and clinical examination. The reliability of the radiographic variables was high, while the reliability of clinical variables ranged from moderate to good. Twenty-eight patients (57%) had radiographic instability based on published norms. Clinical variables related to the presence of radiographic instability were age, lumbar flexion range of motion, total extension range of motion, the Beighton scale for general ligamentous laxity, and segmental intervertebral motion testing. The presence of at least 53 degrees of lumbar flexion or a lack of hypomobility with intervertebral motion testing resulted in a positive likelihood ratio of 4.3 (95% CI: 1.8, 10.6), for predicting radiographic instability. The results of this study indicate that various factors from the clinical examination are useful for predicting radiographic instability. If the findings of this study can be replicated, these clinical factors could be used to inform treatment decision-making without a sole reliance on radiographic assessment.

Adult↗

The influence of vertebral instability on peridural circulation and concomitant peridural fibrosis formation.

An animal model of vertebral instability was used to analyze the effect of chronic lumbar instability on the peridural vasculature and fibrosis formation. Fifty mature male domestic rabbits were divided into five equal groups. The vertebral instability was performed by excision of supra and interspinous ligaments between L2-L3 and L3-L4, excision of transverse and spinous processes and making bilateral laminectomies and facetectomies in groups I, II, III and IV. In group V only para vertebral muscle dissection was performed without vertebral instability. The simulation of the long term effects of overuse model on unstable spines (chronic instability) were performed with the use of Electrical Neuromuscular Stimulator to simulate cyclic flexion-extension movement in groups I, II. The rabbits in group I and III were sacrified for the histological evaluation at postoperative fifth day. The rabbits in groups I II, IV and V were sacrified at postoperative 21st day. There was no peridural venous endothelial injury or stasis but there was an increased amount of polymorph nuclear leukocytes in both group I (unstable-overuse) and group III (unstable-no overuse) after sacrification at postoperative fifth day. Peridural fibrosis and also vascular changes with different grades were seen in group II, VI and V after sacrification at postoperative 21st day. The grade of the venous changes and the mean amount of peridural scar formation were prominently higher in group II (unstable-overuse) than in group IV (unstable-no overuse) and V (control group). There was no difference between group IV and V for peridural scar formation and vascular changes. In conclusion, the instability of the lumbar spine with overuse could be a cause of peridural venous circulatory impairment, resulting in fibrosis formation.

Animals↗

Arthroscopic versus open repair for traumatic anterior shoulder instability: a meta-analysis.

PURPOSE: The purpose of this study was to critically evaluate the literature to determine whether open or arthroscopic surgical repair for traumatic recurrent anterior shoulder instability results in a better outcome. TYPE OF STUDY: Meta-analysis. METHODS: The search involved clinical studies in all languages in the MEDLINE database from 1966 to October 31, 2003. The following key words were used: (1) anterior shoulder instability, (2) Bankart lesion, (3) traumatic recurrent anterior shoulder instability, and (4) arthroscopic and open Bankart repair. All abstracts were reviewed and articles were included if there was a direct clinical comparison between arthroscopic and open repair for traumatic recurrent anterior shoulder instability. These articles were manually cross-referenced for additional abstracts. The final group of articles was independently critically appraised and the following outcomes were extracted: recurrent instability, return to activity, reoperation rate, and cause of recurrence. RESULTS: The search terms resulted in 677, 183, 68, and 51 hits respectively. From these, 18 articles were determined to be eligible for full review including 2 foreign-language articles. Cross-referencing identified 2 unpublished studies. Eleven studies were included in the final analysis: 1 randomized trial, 2 pseudo-experimental designs, 4 prospective cohorts, 3 retrospective studies, and 1 case control study. Pooled Mantel-Haenszel odds ratio for recurrent instability and return to activity were 2.04 ( P = .003; 95% confidence interval, 1.27, 3.29) and 2.85 ( P = .004; 95% confidence interval, 1.40, 5.78), respectively, in favor of the open repair. CONCLUSIONS: Based on this meta-analysis, open repair has a more favorable outcome with respect to recurrence and return to activity. LEVEL OF EVIDENCE: Level III, Systematic Review of Level III (and II/I) Studies.

Anterior Cruciate Ligament↗

Arthroscopic anterior stabilization and posterior capsular plication for anterior glenohumeral instability: a report of 71 cases.

PURPOSE: Results after arthroscopic treatment of anterior glenohumeral instability continue to improve as advancements are made in instrumentation and techniques. We present 71 cases of anterior glenohumeral instability treated with arthroscopic anterior stabilization and posterior capsular plication. TYPE OF STUDY: Case series. METHODS: Arthroscopic anterior reconstruction and posterior inferior "pinch-tuck" capsular plication was performed in 71 shoulders (67 patients) with anterior glenohumeral instability. The average follow-up was 33.3 months (range, 20 to 24 months). Outcomes were assessed by completion of the Simple Shoulder Test (SST), Western Ontario Shoulder Instability (WOSI) Index, a Rowe score, and a subjective self-assessment shoulder instability form. RESULTS: Postoperative dislocation occurred in 5 patients (7%). The average SST score was 11.2 (12 maximum) and the average WOSI Index was 85.6% (range, 30.6% to 100%). The average Rowe score was 85. Ninety-seven percent of patients reported they were able to return to their normal activity level, and 90% of patients reported that they were able to return to their previous level of athletics; 100% of patients reported that they were doing better than before surgery and were satisfied with their result; 100% of patients reported that they would undergo the procedure again. CONCLUSIONS: Arthroscopic anterior stabilization using suture anchors, combined with posterior capsular suture plication, is a reliable treatment option for anterior glenohumeral instability. LEVEL OF EVIDENCE: Level IV.

Adolescent↗

X-ray-induced telomeric instability in Atm-deficient mouse cells.

The gene responsible for ataxia telangiectasia (AT) encodes ATM protein, which plays a major role in the network of a signal transduction initiated by double strand DNA breaks. To determine how radiation-induced genomic instability is modulated by the dysfunction of ATM protein, we examined radiation-induced delayed chromosomal instability in individual cell lines established from wild-type Atm(+/+), heterozygote Atm(+/-), and knock-out Atm(-/-) mouse embryos. The results indicate that Atm(-/-) mouse cells are highly susceptible to the delayed induction of telomeric instability and end-to-end chromosome fusions by radiation in addition to the elevated spontaneous telomeric instability detected by telomere fluorescence in situ hybridization (FISH). The telomeric instability was characterized by abnormal telomere FISH signals, including loss of the signals and the extra-chromosomal signals that were associated and/or not associated with chromosome ends, suggesting that Atm deficiency makes telomeres vulnerable to breakage. Thus, the present study shows that Atm protein plays an essential role in maintaining telomere integrity and prevents chromosomes from end-to-end fusions, indicating that telomeres are a target for the induction of genomic instability by radiation.

Animals↗

A survey of the surgical management of acute and chronic scapholunate instability.

PURPOSE: Scapholunate instability is a challenging problem and controversy persists among hand surgeons with respect to treatment choice. The purpose of this study was to evaluate the pattern of practice among specialized hand surgeons in the management of both acute and chronic scapholunate instability. METHODS: A mailed survey study was sent to the 1,628 members of the American and Canadian Societies for Surgery of the Hand. Hand surgeons were asked to complete a comprehensive management questionnaire that examined a surgeon's treatment algorithm in the clinical case of acute and chronic scapholunate instability. The algorithm included the choices of further investigation, timing of surgery, surgical approach, surgical procedure, fixation, and predicted outcome. RESULTS: Of the 468 hand surgeons who responded to the survey the vast majority elected to perform surgery when confronted with a case of scapholunate instability. Early surgical intervention within 6 weeks of injury using an open dorsal approach was favored in both acute and chronic cases. The preferred surgical procedure in the acute case was scapholunate repair combined with a capsulodesis followed by scapholunate ligament repair alone. Favored management of the chronic case included Blatt capsulodesis alone, capsulodesis combined with a scapholunate ligament repair, or scaphotrapezium-trapezoid arthrodesis. A majority of surgeons used K-wire fixation, especially of the scapholunate and scaphocapitate in both acute and chronic cases. CONCLUSIONS: This survey confirms a consensus for the early soft tissue surgical management of acute scapholunate instability using a scapholunate ligament repair with or without a capsulodesis. The management of chronic scapholunate instability is highly variable among respondents and the choice of either a soft tissue or bony procedure may depend to a large extent on intraoperative findings.

Acute Disease↗

The clinical implications of scaphotrapezium-trapezoidal arthritis with associated carpal instability.

PURPOSE: Common causes of dorsal intercalated segment instability (DISI) include scapholunate dissociations and scaphoid fracture nonunions. Although less common than these, scaphotrapezium-trapezoidal (STT) osteoarthritis (OA) may also be associated with the development of a DISI deformity. The clinical implications of this form of carpal instability in cases of STT arthritis are still unknown. To study the radiographic progression and incidence of this entity, we reviewed our patients and report on 24 wrists with DISI in the presence of STT arthritis. METHODS: A retrospective chart and radiographic review was performed on all patients seen between 1994 and 2004, with the diagnosis of STT arthritis to identify a subgroup of patients with DISI deformity on the presenting radiographs. Patients' clinical and surgical courses were noted. Postoperative radiographic changes were recorded, as were clinical outcomes. RESULTS: Sixteen patients with 24 wrists having STT arthritis and DISI deformity on presenting radiographs were identified. The median STT arthritis grade was 3.0 based on a modified Eaton and Glickel grading system. The median radiolunate angle was -21 degrees of dorsal tilt. All patients had normal scapholunate angles. Abnormal scaphoid extension was seen in 19 of 24 wrists as measured by the radioscaphoid angle. Concomitant carpometacarpal arthritis was seen in 67% (n = 16) of the wrists, and midcarpal arthritis was identified in 50% (n = 8) of patients. Fifteen wrists required surgery for the symptoms and were followed up for a mean of 29 months after surgery. In the surgical group the radiolunate angles increased by mean of 6 degrees after surgery. Four of the 15 wrists required revisional surgery for persistent pain. CONCLUSIONS: Patients with STT arthritis may present with carpal instability that is not related to radiographic scapholunate instability. This instability is characterized by a normal scapholunate angle with an extension stance of the scaphoid and lunate. Midcarpal arthritis may be present. Surgical intervention for patients with STT arthritis and DISI deformity may lead to radiographic progression of midcarpal instability.

Adult↗

Overexpression of hepatitis C virus NS5A protein induces chromosome instability via mitotic cell cycle dysregulation.

Hepatocellular carcinoma (HCC) is a common primary cancer associated with high incidences of genetic variations including chromosome instability. Moreover, it has been demonstrated that hepatitis C virus (HCV) is one of the major causes of HCC. However, no previous work has assessed whether HCV proteins are associated with the induction of chromosome instability. Here, we found that liver cell lines constitutively expressing full-length or truncated versions of the HCV genome show a high incidence of chromosome instability. In particular, the overexpression of HCV NS5A protein in cultured liver cells was found to promote chromosome instability and aneuploidy. Further experiments showed that NS5A-induced chromosome instability is associated with aberrant mitotic regulations, such as, an unscheduled delay in mitotic exit and other mitotic impairments (e.g. multi-polar spindles). Thus, our results indicate that HCV NS5A protein may be directly involved in the induction of chromosome instability via mitotic cell cycle dysregulation, and provide novel insights into the molecular mechanisms of HCV-associated hepatocarcinogenesis.

Carcinoma, Hepatocellular↗

A new clinical outcome measure of glenohumeral joint instability: the MISS questionnaire.

Many standard shoulder outcome measures do not adequately cover the range of problems and issues specifically encountered in glenohumeral joint instability and have been shown not to be sensitive enough to detect clinical change with intervention adequately. The purpose of this report is to present a prospective evaluation of a new self-administered patient questionnaire specifically designed to assess glenohumeral joint instability. The evaluation involved test-retest reliability and comparison with the Shoulder Rating Questionnaire (SRQ). Sixty-four patients with confirmed glenohumeral joint instability were assessed with both the Melbourne Instability Shoulder Scale (MISS) and SRQ 12 preoperatively and at 6 months after shoulder reconstructive surgery. Twenty-two patients were recruited into a reliability study of the MISS questionnaire. The test-retest reliability of the MISS was found to be 0.98 (interclass correlation coefficient, mixed-model analysis of variance, absolute agreement). Assessment of agreement between the MISS and SRQ questionnaires indicated very poor pretest agreement (0.33) and moderate agreement at 6 months (0.66). The differences between the MISS and SRQ were statistically significant both before surgery (paired t = 13.2, degrees of freedom [ df ] = 63, P < .001) and at 6 months' follow-up (paired t = 7.9, df = 63, P = .001). Change in the questionnaire scores measured from surgery to 6 months' follow-up was significantly greater in the MISS (mean, 30; SD, 19.1; median, 30.8) than in the SRQ (mean, 16.6; SD, 12.8; median, 14.3) (Wilcoxon test: z = -5.8, P = .0001). The results of this study show that the MISS questionnaire is a reliable outcome questionnaire and has a greater range to detect changes in shoulder instability than more global outcome questionnaires such as the SRQ. The higher scores encountered on the SRQ may mean that it underestimates the severity of a patient's instability problem.

Adult↗

A longitudinal study of patients with multidirectional instability of the shoulder with seven- to ten-year follow-up.

The purpose of our study was to evaluate the long-term outcomes of patients with multidirectional instability of the shoulder initially treated with rehabilitation exercises. Sixty-four patients were treated for atraumatic multidirectional instability of the shoulder between 1987 and 1990. Preliminary evaluation was performed 2 years after initiation of treatment, and final evaluation of the patients was performed at a mean of 8 years after initiation of treatment. At the preliminary evaluation, 5 patients were lost to follow-up. Of the remaining 59 patients, 20 had undergone surgical treatment for stabilization of their shoulder. Of the 39 nonsurgically treated patients, 19 continued to have significant pain, and 18 continued to have significant instability of their shoulder. Of the 59 patients, 28 subjectively rated their shoulder condition as better or much better after conservative treatment. At the final evaluation, 2 more patients were lost to follow-up, and 1 additional patient had had surgical treatment. Thus, of the 57 patients available for final follow-up, 36 had received nonsurgical care, and 21 had undergone surgical treatment. Of the 36 nonsurgically treated patients, 23 rated their shoulders as good or excellent with regard to pain, and 17 were good or excellent with regard to instability. By the modified Rowe grading scale, 5 of 36 patients had excellent results, and 12 had good results. The remaining 19 patients were rated as having poor results. Only 8 patients reported that their shoulders were free of all pain and instability. Overall, of the entire group of 57 patients evaluated between 7 and 10 years after initiation of care, 17 had a satisfactory outcome from nonsurgical management based on stability and Rowe scores, 23 had good or excellent results with regard to pain, and 20 subjectively rated their shoulders as good or excellent. This review revealed a relatively poor response to nonsurgical treatment of multidirectional instability in this population of young, athletic patients.

Adolescent↗

Delayed activation of DNA damage checkpoint and radiation-induced genomic instability.

Ionizing radiation induces genomic instability, transmitted over many generations through the progeny of surviving cells. It is manifested as the expression of delayed effects such as delayed cell death, delayed chromosomal instability and delayed mutagenesis. Induced genomic instability exerts its delayed effects for prolonged periods of time, suggesting the presence of a mechanism by which the initial DNA damage in the surviving cells is memorized. Our recent studies have shown that transmitted memory causes delayed DNA breakage, which in turn activates DNA damage checkpoint, and is involved in delayed manifestation of genomic instability. Although the mechanism(s) involved in DNA damage memory remain to be determined, we suggest that ionizing radiation-induced mega-base deletion destabilizes chromatin structure, which can be transmitted many generations through the progeny, and is involved in initiation and perpetuation of genomic instability. The possible involvement of delayed activation of a DNA damage checkpoint in the delayed induction of genomic instability in bystander cells is also discussed.

Animals↗

Chromosome analysis in childhood cancer survivors and their offspring--no evidence for radiotherapy-induced persistent genomic instability.

Suggestions that the induction of genomic instability could play a role in radiation-induced carcinogenesis and heritable disease prompted the investigation of chromosome instability in relation to radiotherapy for childhood cancer. Chromosome analysis of peripheral blood lymphocytes at their first in vitro division was undertaken on 25 adult survivors of childhood cancer treated with radiation, 26 partners who acted as the non-irradiated control group and 43 offspring. A statistically significant increase in the frequency of dicentrics in the cancer survivor group compared with the partner control group was attributed to the residual effect of past radiation therapy. However, chromatid aberrations plus chromosome gaps, the aberrations most associated with persistent instability, were not increased. Therefore, there was no evidence that irradiation of the bone marrow had resulted in instability being transmitted to descendant cells. Frequencies of all aberration categories were significantly lower in the offspring group, compared to the partner group, apart from dicentrics for which the decrease did not reach statistical significance. The lower frequencies in the offspring provide no indication of transmissible instability being passed through the germline to the somatic cells of the offspring. Thus, in this study, genomic instability was not associated with radiotherapy in those who had received such treatment, nor was it found to be a transgenerational radiation effect.

Adult↗

Genomic instability in the progression of sporadic nasopharyngeal carcinoma.

OBJECTIVE: Genomic instability reflecting the susceptibility of the genome to acquire multiple genetic alterations plays a major role in tumorigenesis and tumor progression. We evaluated the prognostic significance of the extent of genomic instability in nasopharyngeal carcinoma. STUDY DESIGN AND SETTING: Genomic instability was assessed by inter-simple sequence repeats polymerase chain reaction (inter-SSR PCR) in 38 patients with nasopharyngeal carcinoma. Characterization and verification of band alterations shared in different tumors were carried out by sequencing and nest PCR. RESULTS: 31 (81.6%) of 38 patients showed genomic alterations, and genomic instability index ranged from 0 to 16.2%. A gain-based genomic damage shared in 6 tumors was identified on chromosome 6q27, a new mutator phenotype in nasopharyngeal carcinoma. Significantly more genomic alteration was found in patients without 5-year survival than that with 5-year survival (P<0.05), suggesting that higher genomic instability predicts a poor prognosis in nasopharyngeal carcinoma. CONCLUSIONS AND SIGNIFICANCE: Our data suggests that genomic instability can be an early event marker in carcinogenesis of nasopharyngeal carcinoma. Also, aggravation of genomic alterations is a poor prognosis for cancer recovery.

Carcinoma↗

Mechanisms leading to chromosomal instability.

Chromosomal instability is a common feature of cancer cells. Several cellular mechanisms lead to numerical and structural chromosomal instability in cancer cells, including defects in chromosomal segregation, cellular checkpoints that guard against reproduction of abnormal cells, telomere stability, and the DNA damage response. Human papillomavirus interferes with these processes, causing chromosomal instability and tumor formation in some of the epithelial cells which it infects. The rate of discoveries about the mechanisms leading to chromosomal instability in cancer cells is increasing rapidly. Although these mechanisms were thought to be unrelated, they are intimately intertwined, connecting the complex network of cellular pathways. Since chromosomal instability is undoubtedly a major cause of tumor evasion of therapy, understanding the mechanisms leading to chromosomal instability has major translational significance.

Cell Transformation, Neoplastic↗

Chronic elbow instability.

Chronic elbow instability without fractures in adults can be broken down into three types: (1) valgus instability, (2) posterolateral rotator instability, and (3) isolated radial head instability. By far the most common is valgus instability, which usually occurs in throwing athletes as a result of repetitive microtrauma to the anterior band of the medial collateral ligament. Surgical treatment is aimed at reconstruction of the anterior band of the medial collateral ligament. Posterolateral rotatory instability is much less common and is diagnosed by the lateral pivot-shift test of the elbow. It is usually the result of an undiagnosed acute injury to the lateral ulnar collateral ligament. Surgical treatment is aimed at its reconstruction. Isolated radial head subluxation in adults is extremely rare. The essential lesion is a disruption of the annular ligament. Surgical treatment is either radial head resection or reconstruction of the annular ligament.

Chronic Disease↗