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PubMed2006

Surgical treatment of chronic posterolateral rotatory instability of the knee using capsular procedures.

Chronic posterolateral rotatory instability of the knee was introduced as a diagnostic classification by Hughston and associates in the early 1970s and occurs as a result of dysfunctional healing of a strained arcuate complex, causing a patulous posterolateral capsuloligamentous complex to exist. This capsular redundancy allows varying degrees of recurvatum and adduction instability during single-limb stance. Eradication of the redundant pouch with a capsular shift-type reconstruction has been shown to eliminate the instability and hold up under long-term follow-up studies. Understanding the complex normal and injured anatomy of the posterolateral corner of the knee is essential for effective reconstruction of this instability.

Chronic Disease↗
PubMed2006

Ulnar coronoid process anatomy: possible implications for elbow instability.

Ulnar coronoid process fractures are relatively uncommon injuries usually occurring with elbow dislocations and contributing to elbow instability. Recent evidence suggests coronoid tip fractures have a role in the instability. We sought to quantify the capsular and brachialis attachments of the ulnar coronoid process to better understand why instability occurs. We prepared eight fresh-frozen cadaveric specimens to ascertain the specific attachment locations. After dissection, we isolated and resected the proximal ulna, including the coronoid process and its soft tissue attachments. We then embedded, sectioned, and stained the specimens. The average distance from the tip of the coronoid to the proximal capsule was 2.36 +/- 0.39 mm. The average distance from the tip of the coronoid to the proximal brachialis insertion was 10.13 +/- 1.6 mm. Most coronoid tip fractures included disruption of the anterior capsule, which potentially explains why instability can be associated with these fractures.

Cadaver↗
PubMedDate not supplied

Chronic recurrent anterior sternoclavicular joint instability: results of surgical management.

Chronic anterior sternoclavicular joint (SCJ) instability may cause pain and persistent functional limitation in active patients. Although SCJ reconstruction and medial clavicular resection have been advocated in these situations, the results of surgical treatment are not well characterized. The purpose of this investigation was to determine the functional outcome of surgical treatment in adolescent and young adult patients with chronic recurrent anterior SCJ instability. Fifteen patients with chronic recurrent anterior SCJ instability refractory to nonoperative therapy who underwent joint reconstruction or medial clavicular resection were evaluated for pain and function using the American Shoulder and Elbow Surgeons (ASES) Standard Shoulder Assessment Form and the Simple Shoulder Test (SST). At average follow-up of 55 months, the mean ASES score was 85 and the mean SST score was 10.9. Sixty percent of patients reported stable, pain-free joints, although 87% (n = 13) reported some limitations of athletic or recreational activity. There were no surgical complications, and no patient underwent subsequent revision procedures. Although subsequent activity modification is often required, surgical treatment of chronic anterior SCJ instability in adolescents and young adults can provide near-complete pain relief and return of shoulder and upper extremity function.

Adolescent↗
PubMed2004

Craniovertebral instability with spinal cord compression in a 17-month-old boy with Sly syndrome (mucopolysaccharidosis type VII): a surgical dilemma.

STUDY DESIGN: A case study with review of surgical technique in craniovertebral stabilization for young children with mucopolysaccharidosis. OBJECTIVES: To describe an interesting patient with a rare metabolic disorder and review surgical technique for craniovertebral instability in this rare patient population. SUMMARY OF BACKGROUND DATA: Craniovertebral instability has been reported in patients with mucopolysaccharidosis and poses a problem for spinal surgery because of the inherent metabolic disorder and age at presentation. We present the first case of craniovertebral instability and spinal cord compression occurring in Sly syndrome (mucopolysaccharidosis type VII) who is the youngest patient afflicted with this metabolic disorder to undergo craniovertebral stabilization. METHODS: A 17-month-old boy presented with inability to support his head, decreasing muscle strength in all extremities, distended abdomen, and shortness of breath. The patient was found to have a dilated cardiomyopathy, hepatosplenomegaly, abnormal hepatobiliary function, corneal clouding, and a questionable tracheal anomaly. Genetic testing provided a diagnosis of Sly syndrome, mucopolysaccharidosis type VII. Magnetic resonance imaging revealed focal stenosis with significant spinal cord compression at the craniovertebral junction. Neurologic examination revealed normal muscle volume with strength 3/5 in all extremities and significant weakness in the neck muscles with instability at the craniovertebral junction. RESULTS: On a concerted preoperative medical clearance by pediatric intensive care, pediatric neuroanesthesia, pediatric cardiology, pediatric gastroenterology, and pediatric neurosurgery, the patient underwent occipital to C3 decompression and fusion with autogenous rib grafts. The patient was placed in a prefitted halo-vest after surgery and was neurologically intact. CONCLUSIONS: This case demonstrates the heterogeneity of cervical spine deformities among the mucopolysaccharidosis syndromes and confirms the propensity for deposition of glycosaminoglycans at the craniovertebral junction. Further studies should investigate the etiology for this propensity of glycosaminoglycan deposition at the craniovertebral junction. We think that this case demonstrates that, with appropriate preoperative planning, these patients can undergo successful posterior cervical arthrodesis despite their age or metabolic defects.

Atlanto-Occipital Joint↗
PubMed2006

Surgical treatment of chronic posteromedial instability using capsular procedures.

Patients with posteromedial corner injuries of the knee present a significant problem to the clinician. Often the symptoms of anteromedial rotatory instability may be overlooked due to concurrent anterior cruciate ligament and/or posterior cruciate ligament injuries. When addressing concurrent ligamentous injuries to the knee, the clinician may fail to isolate anteromedial rotatory instability on physical examination and imaging studies may not specifically identify damage to posteromedial corner structures. This unrecognized and untreated damage results in residual functional laxity and can potentially lead to chronic and progressive instability of the knee. This paper contains descriptions of 2 surgical techniques that address posteromedial instability. Both techniques require an understanding of posteromedial corner knee anatomy, careful preoperative planning, and extensive postoperative rehabilitation.

Chronic Disease↗
PubMed2005

A novel logistic model based on clinicopathological features predicts microsatellite instability in colorectal carcinomas.

High-frequency microsatellite instability has been reported to be associated with good prognosis in colorectal adenocarcinoma. However, methods to assess microsatellite instability (MIN) are based on genetic assays and are not ideally suited to most histopathology laboratories. The aim of the present study was to develop a model for prediction of MIN status in colorectal cancer based on phenotypic characteristics. Clinicopathological features of a cohort of 204 patients with primary colon cancer were retrospectively reviewed following predetermined criteria. Genetic assessment of MIN status was performed on DNA extracted from sections of formalin-fixed, paraffin-embedded specimens by testing a panel of 11 microsatellite markers. Logistic regression analysis generated a mathematical tool capable of identifying colorectal tumors displaying MIN status with a sensitivity of 77.8% and a specificity of 96.8%. Features associated with instability included the proximal location of the lesions, occurrence of solid and/or mucinous differentiation, absence of cribriform structures, presence of peritumoral Crohn-like reaction, expansive growth pattern, high Ki67 proliferative index, and p53-negative phenotype. This approach predicts microsatellite instability in colorectal carcinoma with an overall assigned accuracy of 95.1% and a negative predictive value of 97.8%. Implementation of this tool to routine histopathological studies could improve the management of patients with colorectal cancer, especially those presenting with stage II and III of the disease. It will also assist in identifying a subset of patients likely to benefit from adjuvant chemotherapy.

Aged↗
PubMed1995

Natural history and treatment of instability of the hip in proximal femoral focal deficiency.

We studied 67 patients with 78 affected femurs to determine the natural history of proximal femoral focal deficiency (PFFD) with respect to hip instability and to establish guidelines for management. Using the classification systems of Aitken and Fixsen and Lloyd-Roberts as applied to a radiograph taken at age 12-15 months, we could accurately predict development of hip instability, defined as formation of a pseudoarthrosis or complete failure of hip development. The pseudoarthrosis occurred either at the cervical or subtrochanteric level of the femur. Cervical instability was difficult to treat operatively, but subtrochanteric instability fused spontaneously in 30% of cases and responded well to operative treatment when necessary. For unilateral failure of hip joint formation, various surgical procedures were used to assist prosthetic fitting, but bilateral cases were treated nonoperatively.

Adolescent↗
PubMed2005

Chromosomal instability and human cancer.

Genetic instability is a defining feature of human cancer. The main type of genetic instability, chromosomal instability (CIN), enhances the rate of gross chromosomal changes during cell division. CIN is brought about by mutations of CIN genes, i.e. genes that are involved in maintaining the genomic integrity of the cell. A major question in cancer genetics is whether genetic instability is a cause and hence a driving force of tumorigenesis. A mathematical framework for studying the somatic evolution of cancer sheds light onto the causal relations between CIN and human cancer.

Chromosomal Instability↗
PubMed2005

Telomere-related genome instability in cancer.

Genome instability is a hallmark of most human cancers. Although a mutator phenotype is not required for tumorigenesis, it can foster mutations that promote tumor progression. Indeed, several inherited cancer-prone syndromes are due to mutations in DNA repair pathways. However, sporadic tumors are usually proficient in DNA repair, making it unlikely that unrepaired lesions are a major source of genome instability in sporadic cancers. A decade ago, I argued in another CSHL Press publication that a "collapse in telomere function can explain a significant portion of the genetic instability in tumors" (de Lange 1995). Since that time, the structure of mammalian telomeres has been analyzed, the consequences of telomere dysfunction have been determined, a mouse model for cancer-relevant aspects of telomere biology has been developed, and the nature and magnitude of cancer genome rearrangements have been revealed. In light of these developments, this is an opportune time to revisit the conjecture that telomere dysfunction contributes to genome instability in human cancer.

Aneuploidy↗
PubMed2004

Chromosomal and microsatellite instability in sporadic gastric cancer.

BACKGROUND: Gastric cancer can progress through two pathways of genomic instability: chromosomal (CIN) and microsatellite instability (MSI). It is hypothesized that these two pathways are not always independent and that some tumors show overlap between these two mechanisms. METHODS: A total of 98 sporadic gastric cancers were classified based on their MSI status, using microsatellite assay with BAT26. Evidence for CIN was investigated by identifying loss of heterozygosity (LOH) events on chromosome arms, 5q, 10p, 17p, 17q, and 18q, which are regions harboring tumor suppressor genes that are significant in gastric cancer development. RESULTS: Twelve tumors (12%) showed high-frequency MSI (MSI-H). Overall, 43 of the tumors (44%) had at least one LOH event, with most frequent chromosomal losses observed on 10p and 18q (30%, respectively), followed by 5q (21%), 17p (14%), and 17q (12%). Interestingly, overlap was observed between CIN and MSI pathways. Of 43 cancers with LOH events, four (9%) were also MSI-H. It was also found that 48% of cancers without MSI-H had no LOH events identified, comprising a subgroup of tumors that were not representative of either of these two pathways of genomic instability. CONCLUSION: These results suggest that molecular mechanisms of genomic instability are not necessarily independent and may not be fully defined by either the MSI or CIN pathways in sporadic gastric cancers.

Adult↗
PubMed1998

Subtalar instability of the foot. A review and results after surgical treatment.

Most subtalar ligamentous injuries occur in combination with ankle ligament injuries, but the exact aetiology and the true incidence remain unknown. The aim of this study was to review the problem, propose a definition and to analyze the results of an anatomic reconstructive surgical technique in the treatment of subtalar instability. Twenty-two patients suffering from chronic subtalar instability of the foot were operated with anatomical reconstruction. The cervical, the lateral talo-calcaneal and the calcaneo-fibular ligaments were imbricated and reinforced with the lateral root of the inferior extensor retinaculum. After a minimum of 2 years follow-up the functional results were excellent or good in 18 of 22 (82%) patients and fair or poor in 4 of 22 (18%). All of the patients with unsatisfactory results suffered from residual ankle pain, two of whom also had residual instability. No reoperations have been performed. Surgical complications were seen in three patients, all minor nerve injuries of the lateral branch of the superficial peroneal nerve. These complications had no bearing on the functional results, however. This procedure was found to be feasible in patients with chronic subtalar instability.

Adult↗
PubMed1999

Long-term functional outcome after surgery of chronic ankle instability. A 5-year follow-up study of the modified Evans procedure.

Chronic ankle instability is a rather common consequence of poorly healed rupture of the lateral ligaments of the ankle. In some rare cases, instability symptoms can be caused by general laxity of the joints, but since these cases are normally bilateral, they can easily be distinguished from posttraumatic instability. This report presents the long-term (average follow-up 4.6 years) functional outcome after a modified Evans tenodesis of 48 patients. The follow-up examination consisted of a questionnaire evaluating the subjective assessment of the ankle, and clinical examination measuring ankle stability, range of motion and swelling, and atrophy of the calf muscles. Additionally, the functional recovery of the ankle was assessed by a standardized performance test protocol. According to the subjective assessment, 25 subjects (52%) considered the ankle fully recovered, or at least much better than before surgery. In the performance test, however, only 17 subjects (35%) achieved an excellent or good score. In the performance test protocol, two functional tests, walking down a staircase and balancing on a square beam, best demonstrated the impaired function of the injured ankle. The modified Evans procedure could restore the stability of the ankle to the preinjury level, although the ankle range of motion was significantly impaired, and swelling of the ankle and atrophy of the calf muscles were frequent findings at the follow-up. In conclusion, surgical treatment of chronic ankle instability by the Evans procedure restores the mechanical stability of the joint, but too frequently the function of the ankle does not return to the pre-injury level.

Adolescent↗
PubMed1986

Hip joint instability in breech pregnancy.

222 consecutive fetuses found by ultrasound to be in breech presentation in the 33rd gestational week were followed with repeated examinations in weeks 35 and 38. Ninety-one of these fetuses persisted in breech presentation until delivery, while cephalic version occurred in 131. The frequency of hip joint instability was 21% in the breech delivered group and 1.5% in the vertex delivered group. The position of the fetal legs was established at each ultrasound examination. The intrauterine fetal attitude was classified as extended when the fetuses had extended knees and maximally flexed hips at all ultrasound examinations. This occurred in 30 breech delivered fetuses, 47% of which developed hip joint instability. Only 8% of the breech born infants with flexed legs in utero developed hip joint instability. It is concluded that instability of the hip joint is a consequence of the intrauterine attitude, rather than of the breech delivery per se.

Breech Presentation↗
PubMed2003

End resection initiates genomic instability in the absence of telomerase.

Telomere dysfunction causes genomic instability. However, the mechanism that initiates this instability when telomeres become short is unclear. We measured the mutation rate and loss of heterozygosity along a chromosome arm in diploid yeast that lacked telomerase to distinguish between mechanisms for the initiation of instability. Sequence loss was localized near chromosome ends in the absence of telomerase but not after breakage of a dicentric chromosome. In the absence of telomerase, the increase in mutation rate is dependent on the exonuclease Exo1p. Thus, exonucleolytic end resection, rather than chromosome fusion and breakage, is the primary mechanism that initiates genomic instability when telomeres become short.

Base Sequence↗
PubMed2004

Genomic instability and enhanced radiosensitivity in Hsp70.1- and Hsp70.3-deficient mice.

Heat shock proteins (HSPs) are highly conserved among all organisms from prokaryotes to eukaryotes. In mice, the HSP genes Hsp70.1 and Hsp70.3 are induced by both endogenous and exogenous stressors, such as heat and toxicants. In order to determine whether such proteins specifically influence genomic instability, mice deficient for Hsp70.1 and Hsp70.3 (Hsp70.1/3(-/-) mice) were generated by gene targeting. Mouse embryonic fibroblasts (MEFs) prepared from Hsp70.1/3(-/-) mice did not synthesize Hsp70.1 or Hsp70.3 after heat-induced stress. While the Hsp70.1/3(-/-) mutant mice were fertile, their cells displayed genomic instability that was enhanced by heat treatment. Cells from Hsp70.1/3(-/-) mice also display a higher frequency of chromosome end-to-end associations than do control Hsp70.1/3(+/+) cells. To determine whether observed genomic instability was related to defective chromosome repair, Hsp70.1/3(-/-) and Hsp70.1/3(+/+) fibroblasts were treated with ionizing radiation (IR) alone or heat and IR. Exposure to IR led to more residual chromosome aberrations, radioresistant DNA synthesis (a hallmark of genomic instability), increased cell killing, and enhanced IR-induced oncogenic transformation in Hsp70.1/3(-/-) cells. Heat treatment prior to IR exposure enhanced cell killing, S-phase-specific chromosome damage, and the frequency of transformants in Hsp70.1/3(-/-) cells in comparison to Hsp70.1/3(+/+) cells. Both in vivo and in vitro studies demonstrate for the first time that Hsp70.1 and Hsp70.3 have an essential role in maintaining genomic stability under stress conditions.

Animals↗
PubMed1995

A stiff collar can restrict atlantoaxial instability in rheumatoid cervical spine in selected cases.

OBJECTIVE: To study the efficiency of a stiff collar in restricting the instability of anterior atlantoaxial subluxation (AAS). METHODS: Twenty two successive patients with an unstable AAS were studied. Lateral view radiographs were taken of the cervical spine in flexion, extension, and neutral positions without a collar, and in full flexion with a custom made stiff collar. RESULTS: The collar restricted more than 30% of the maximal instability of the AAS in 50% of the patients. These patients had significantly shorter atlantoaxial distance in the neutral position than those in whom the collar was not able to restrict the instability. CONCLUSION: A stiff collar can restrict the atlantoaxial instability in selected rheumatic patients with an unstable AAS. Lateral view radiographs of the cervical spine in a neutral position can be used to identify the patients whom the collar will benefit.

Adult↗
PubMed2003

Evaluation of shoulder internal rotator muscle strength in baseball players with physical signs of glenohumeral joint instability.

OBJECTIVES: To identify whether subjects with glenohumeral translational instability present with a strength deficit in their internal rotator musculature, and therefore to determine if general strengthening exercises are warranted for the management of this condition. METHODS: Eighteen male baseball players were allocated to two groups on the basis of expert clinical evaluation of the presence (n=8) or absence (n=10) of shoulder translational instability. A strain gauge was used to calculate the force generated during maximal isometric internal rotation contractions in neutral shoulder rotation and 30 degrees of internal rotation. RESULTS: The Mann-Whitney test identified no significant difference in force production during the maximum contractions in neutral rotation between the two subject groups. In the position of 30 degrees shoulder internal rotation, subjects with glenohumeral translational instability produced significantly greater force than the control group (p<0.05). CONCLUSIONS: High load strength testing cannot be used as a diagnostic tool to identify people with glenohumeral instability. Similarly, heavy resistance strengthening exercises for the internal rotator musculature are not warranted during rehabilitation.

Adolescent↗
PubMed2005

Low level microsatellite instability may be associated with reduced cancer specific survival in sporadic stage C colorectal carcinoma.

BACKGROUND: Colorectal cancers (CRCs) may be categorised according to the degree of microsatellite instability (MSI) exhibited, as MSI-high (MSI-H), MSI-low (MSI-L), or microsatellite stable (MSS). MSI-H status confers a survival advantage to patients with sporadic CRC. AIMS: To determine if low levels of MSI are related to the clinicopathological features and prognosis of sporadic stage C CRC. PATIENTS: A total of 255 patients who underwent resection for sporadic stage C CRC were studied. No patient received chemotherapy. Minimum follow up was five years. METHODS: DNA extracted from archival malignant and non-malignant tissue was amplified by polymerase chain reaction using a panel of 11 microsatellites. MSI-H was defined as instability at > or =40% of markers, MSS as no instability, and MSI-L as instability at >0% but <40% of markers. Patients with MSI-H CRC were excluded from analysis as they have previously been shown to have better survival. RESULTS: Thirty three MSI-L and 176 MSS CRCs were identified. There was no difference in biological characteristics or overall survival of MSI-L compared with MSS CRC but MSI-L was associated with poorer cancer specific survival (hazard ratio 2.0 (95% confidence interval 1.1-3.6)). CONCLUSIONS: Sporadic MSI-L and MSS CRCs have comparable clinicopathological features. Further studies are required to assess the impact of MSI-L on prognosis.

Adult↗