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At least 883 records · Page 49Linked to original sources
PubMed2005

Genomic instability in multiple myeloma: evidence for jumping segmental duplications of chromosome arm 1q.

Multiple myeloma (MM) is a malignant plasma cell disorder characterized by complex karyotypes and chromosome 1 instability at the cytogenetic level. Chromosome 1 instability generally involves partial duplications, whole-arm translocations, or jumping translocations of 1q, identified by G-banding. To characterize this instability further, we performed spectral karyotyping and fluorescence in situ hybridization with probes for satII/III (1q12), BCL9 (1q21), and IL6R (1q21) on the karyotypes of 44 patients with known 1q aberrations. In eight patients, segmental duplication of 1q12-21 and adjacent bands occurred on nonhomologous chromosomes. In five cases, the 1q first jumped to a nonhomologous chromosome, after which the 1q12-21 segment again duplicated itself 1-3 times. In three other cases, segmental duplications occurred after the 1q first jumped to a nonhomologous chromosome, where the proximal adjacent nonhomologous chromosome segment was duplicated prior to the 1q jumping or inserting itself into a new location. These cases demonstrate that satII/III DNA sequences are not only associated not only with the duplication of adjacent distal chromosome segments after translocation, but are also associated with the duplication and jumping/insertion of proximal nonhomologous chromosome segments. We have designated this type of instability as a jumping segmental duplication.

Adult↗
PubMed2005

Telomere dysfunction drives chromosomal instability in human mammary epithelial cells.

The development of genomic instability is an important step toward generating the multiple genetic changes required for cancer. Telomere dysfunction is one of the factors that contribute to tumorigenesis. Telomeres shorten with each cell division in the absence of telomerase. Human mammary epithelial cells (HMECs) obtained from normal human tissue demonstrate two growth phases. After an initial phase of active growth, HMECs exhibit a growth plateau termed selection. However, some cells can emerge from this growth plateau by spontaneously losing expression of the p16(INK4a) protein. These post-selection HMECs are capable of undergoing an additional 20-50 population doublings in culture. Continued proliferation of these post-selection HMECs leads to further telomere erosion, loss of the capping function, and the appearance of end-to-end chromosome fusions that can enter bridge-fusion-breakage (BFB) cycles, generating massive chromosomal instability before terminating in a population growth plateau termed agonescence. We have found that the chromosome arms carrying the shortest telomeres are those involved in telomere-telomere type rearrangements. In addition, we found that the risk of a particular chromosome being unstable differs between individuals. Most importantly, we identified sister chromatid fusion as a first event in generating genomic instability in HMECs. During post-selection HMEC growth, double strand breaks are generated by both fused chromosomes as well as individual chromosomes with fused chromatids entering BFB cycles. These broken chromosome extremities are able to join other broken ends or eroded telomeres, producing massive chromosomal instability at the later passages of the cell culture. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

Blotting, Western↗
PubMed2006

Genomic instabilities in squamous cell carcinoma of head and neck from the Indian population.

Intrinsic genomic instability of an incipient tumor cell drives the development of cancer. In colorectal cancer, an inverse relationship between microsatellite instability (MIN) and chromosomal instability (CIN) has been reported. The relationship between MIN and CIN in head and neck squamous cell carcinoma (HNSCC) is uncertain. In the present study, we examined these two types of instabilities in HNSCC using microsatellite markers and arbitrary primed PCR (APPCR) technique. HNSCC tumors showed high frequency of MIN and loss of heterozygosity (LOH). We observed that, in contrast to colorectal tumors, the frequency of LOH increased with the increase in MIN. There was no significant difference between MIN- and MIN+ groups of HNSCC tumors in the extent of overall genomic alterations; rather higher MIN+ tumors exhibited higher incidence of deletion. Thus, in sporadic HNSCC, both MIN and CIN pathways operate simultaneously to drive tumor formation.

Carcinoma, Squamous Cell↗
PubMed1990

Postero-lateral rotatory instability in osteoarthritis of the knee.

Rotatory instability is well recognized following trauma to the knee, but it may also be seen in degenerative disease. The presence of chronic instability may affect the results of operative treatment of the osteoarthritic knee, as has been shown with postero-lateral rotatory instability in patients with varus deformity secondary to osteoarthritis. Recognition of these often subtle clinical entities is essential in order to improve patient selection when considering the various options for operation. An understanding of the pathomechanics of rotational instability in combination with abnormality of alignment in the joint will enable better classification of the changes which occur in osteoarthritis of the knee.

Female↗
PubMed1997

Pathogenetic relevance of the pregnancy hormone relaxin to inborn hip instability.

The etiology of inborn hip dysplasia is unknown. In general, a multifactorial genesis is assumed. The influence of hormones on the development of the fetal hip joint and its stability is discussed as well as mechanical influences. This study was carried out with the intention to examine the correlation between the concentration of the pregnancy hormone relaxin and the stability of the hip joint in newborns. Both hips of 90 newborn children were examined clinically and sonographically. In 25 hips (13.9%), pathological sonograms according to the classification of Graf were found. The relaxin concentration was measured in cord blood using a heterologous radioimmunoassay. Statistical evaluation revealed an insignificant decrease of relaxin concentration with increasing sonographic hip instability. The results indicate that hip instability frequently occurs with decreasing relaxin concentration. These facts contradict the earlier assumption that hip instability coincides with increased relaxin concentrations in newborns. We assume that there is a worse preparation of the pelvis and the birth canal during pregnancy due to the lower relaxin concentration and thus that there could be a higher pressure on the fetus in the perinatal phase. A decreased relaxin concentration seems to have no direct effect on the hip joint tissue, but indirectly there is consequent rigidity of the tissue in mother and child, which can further promote the development of hip instability.

Female↗
PubMed1986

When is surgery indicated in anterior knee instability? Considerations on operative and functional treatment.

Rupture of the ACL may result in chronic anterior knee instability. However, in the majority of patients the secondary stabilizers of the joint such as collateral ligaments, menisci, and the capsule will compensate for this instability. We recommend surgical reconstruction of the acute rupture of the ACL only in the young, active athlete. Concomitant ruptures of capsuloligamentuous structures do not indicate surgical treatment: they may be treated by a plaster cast or a splint with good results. Chronic symptomatic anterior knee instability should first be treated by a vigorous muscle-training program. Surgery is performed only for those patients who cannot compensate for their instability after this rehabilitation program.

Acute Disease↗
PubMed1996

Transpedicular reduction and stabilization for postlaminectomy lumbar instability.

This study retrospectively reviewed the outcomes of 17 patients with postlaminectomy lumbar instability treated by transpedicular reduction and stabilization. The criteria of instability were defined strictly by both the clinical symptom of "instability catch" and the radiological findings that fulfilled Nachemson's criteria. Low back pain and/or sciatica that interfered largely with the patients' work or quality of life were the indications for this treatment. All the operations were performed by one surgeon with the same spinal instrumentation system-"AO internal fixator". The follow-up period was between 16 and 36 months (mean 24 months). Face to face questionnaire revealed that this treatment modality is encouraging. Fourteen patients (82%) had complete or nearly complete relief from all the pre-operative symptoms. Two (12%) had partial relief of the symptoms that required a subsequent discectomy or wider laminectomy. Only one case (6%) with osteoporosis remained unchanged after the operation. On the follow-up radiographs, sixteen patients (94%) showed good alignment and solid arthrodesis of the treated motion segment. These radiological findings correlated quite well with the absence of the clinical symptom of "instability catch". A common, but acceptable, complication found in this series was a variable degree of low back stiffness secondary to the instrumentation. Fracture of the screw was found in one patient and pull out of the screw was found in another patient. However, they did not elicit detectable symptoms. Osteoporosis, concomitant disc herniation and persistent spinal stenosis at/or adjacent to the operated level were the three main factors that may contribute to unsatisfactory results secondary to this treatment. These problems remain to be resolved in the future.

Adult↗
PubMed1994

Factors of patellar instability: an anatomic radiographic study.

We analyzed the radiographs and computed tomography (CT) scans of 143 knees operated on for symptomatic patellar instability and 67 contralateral asymptomatic knees, together with 190 control knee radiographs and 27 control knee scans, to determine the factors affecting patellar instability. Four factors were relevant in knees with symptomatic patellar instability: (1) Trochlear dysplasia (85%), as defined by the crossing sign (96%) and quantitatively expressed by the trochlear bump, pathological above 3 mm or more (66%), and the trochlear depth, pathologic at 4 mm or less. (2) Quadriceps dysplasia (83%), defined a present when the patellar tilt in extension is more than 20% on the CT scans. (3) Patella alta (Caton-Deschamps) index greater than or equal to 1.2 (24%). (4) Tibial tuberosity-trochlear groove, pathological when greater than or equal to 20 mm (56%). The factors appeared in only 3%-6.5% of the control knees. The etiology of patellar instability is multifactorial. Determination of the factors permits an effective elective therapeutic plan which aims at correcting the anomalies present.

Adolescent↗
PubMed1993

[Rehabilitation of fresh, surgically managed anteromedial knee instabilities].

In between 1983 and 1988, 33 patients suffering from an acute antero-medial instability of the knee were operated on for the anterior cruciate ligament. The reconstruction of the ligament was performed by transcondylar fixation. 25 of these patients took part in a retrospective examination. The postoperative treatment had been carried out according to various concepts of rehabilitation. Our investigations were supposed to measure the restoration of the muscular efficiency of the knee-extensor and -flexor by isokinetic training arrangements. The results revealed that by the operation a sufficient stabilization of the knee had not been achieved. 18 of 25 patients once more showed an antero-medial instability of the knee. Twelve of these 25 patients had an extended anterior instability. Only in seven cases the muscular system was completely restored with average isokinetic muscle efficiency. The high rate of postoperative knee-instability proves the persistent sports-incapacity. We must draw the conclusion that the after-treatment of ligamentous injuries about the knee must focus on the muscular rehabilitation.

Adult↗
PubMed1997

[Biomechanics of lumbar instability].

Several authors have tried to define segmental lumbar instability. Their definitions: increased antero-posterior translation, pathologic coupled motion, increased neutral zone, pathologic instantaneous center of rotation describe some mechanic findings occurring in the aging spine. However, there is no evidence that they help to differentiate the pathologic entity of segmental lumbar instability from the normal aging process. Dynamic explanation models are promising but at the moment they cannot be used clinically for diagnosis of instability as well. The most important structure to maintain lumbar stability is the intervertebral disc. In the third and fourth decade, more than 50 percent of specimen show peripheral tears of the anulus. It was shown in animal experiments that these tears develop to radial tears, which are accompanied by nuclear volume loss and decreased height. The facets degenerate one or two decades later. Corresponding with the loss of discal function, they increasingly contribute to spinal stability. In conclusion, the concept of lumbar segmental instability is not very helpful in clinical practise. It is recommended to base the decision of lumbar fusion on a painful degenerated disc, and additional findings promising a good result.

Animals↗
PubMed1999

[Scapholunate instability. Diagnosis--classification--treatment].

Scapholunate instability is more or less caused by injury. The ligament instability between lunate and scaphoid is not easily to be identified even there is only a little widening of this space between both bones. The instability may be proved by physical examination, by x-ray and by arthroscopy. The scapholunate instability may occur in a different manner. It is divided in three stages. In stage I a none operative treatment is sufficient. For the other stages an operative treatment is necessary: The operative treatment begins with suture of the ligament, continues with ligamentoplasty and ends with intracarpal fusions. At least a total arthrodesis of the wrist is necessary.

Arthrodesis↗
PubMed2000

Total knee arthroplasty in femorotibial instability.

Regarding the reasons for failure of conventional knee arthroplasty a lot of work has be done on loosening and polyethylene wear, often leading to recurrent deformation and osteolysis. But there are only few reports concerning femorotibial instability. This instability is related to failure of the collateral ligaments which can often be found in cases of important frontal deformity both in the varus and valgus knee or in rheumatoid arthritis. Femorotibial instability has been reported in the literature as reason of failure of knee replacement in 10 to 30% of all cases. This complication may be avoided by a precise preoperative analysis including unipodal standing view and stress X-Rays. Encouraged by the good long-term results published by the Endo-Klinik we started to use the ENDO-Model rotational knee system in patients with suspected femorotibial instability in order to resolve the problems of resurfacing the patella restoring mobility correcting the deformity stabilising the knee In fact, the rotating or hinge prosthesis is actually transforming the anatomical joint in a mechanical joint in which the pivot is acting as a ligament should act.

Adult↗
PubMed2004

Telomeres and chromosomal instability.

Telomeres are distinctive structures, composed of a repetitive DNA sequence and associated proteins, which enable cells to distinguish chromosome ends from DNA double-strand breaks. Telomere alterations, caused by replication-mediated shortening, direct damage or defective telomere-associated proteins, usually generate chromosomal instability, which is observed in senescence and during the immortalization process. In cancer cells, this chromosome instability could be extended by their ability to 'repair' chromosomes and terminate in break-fusion-bridge cycles. Dysfunctional telomeres can be healed by activation of telomerase or by the 'alternative mechanism' of telomere lengthening. Activation of such telomere maintenance mechanisms may help to preserve the integrity of chromosomes even if they play a role in chromosomal instability. This review focuses on molecular processes involved in telomere maintenance and chromosomal instability associated with dysfunctional telomeres in mammalian cells.

Animals↗
PubMed2006

Hypoxia-induced genetic instability--a calculated mechanism underlying tumor progression.

The cause of human cancers is imputed to the genetic alterations at nucleotide and chromosomal levels of ill-fated cells. It has long been recognized that genetic instability-the hallmark of human cancers-is responsible for the cellular changes that confer progressive transformation on cancerous cells. How cancer cells acquire genetic instability, however, is unclear. We propose that tumor development is a result of expansion and progression-two complementary aspects that collaborate with the tumor microenvironment-hypoxia in particular, on genetic alterations through the induction of genetic instability. In this article, we review the recent literature regarding how hypoxia functionally impairs various DNA repair pathways resulting in genetic instability and discuss the biomedical implications in cancer biology and treatment.

DNA Repair↗
PubMed1998

[Diagnosis of anterior knee instability. Comparison between the Lachman test, the KT-1,000 arthrometer and the ultrasound Lachman test].

We reviewed 45 patients on average 14.7 years after surgery for rupture of the anterior cruciate ligament. The aim of the study was to compare the reliability of the Lachman test to evaluation of knee laxity with the KT 1000 arthrometer and the ultrasound-assisted Lachman test. Forty-five knees were examined with the Lachman test: 12 knees showed no sign of instability; 20 had a + positive Lachman test with a hard end point; 6 with a + positive test had no end point and were rated as unstable; a +2 Lachman test was found in 7 knees. With the KT 1000 Arthrometer 44 knees were examined: 30 knees were graded as stable according to the criteria of Daniel; 14 knees were unstable. We used the ultrasound-guided Lachman test in 44 knees. Taking only the side-to-side difference into account, 37 knees were stable and 7 unstable. According to Gruber, a single translation greater than 4 mm is also a sign of instability. Therefore, 12 knees were unstable, although 6 of these knees were rated as stable, taking the side-to-side difference into account. Comparing the two instrument measurements, all knees with ultrasound-rated instability on the basis of side-to-side measurements were also rated as unstable with the KT 1000 arthrometer. Only half of the knees rated as unstable because of a single translation greater than 4 mm with the ultrasound technique were rated as unstable with the KT 1000 arthrometer. Our results show that the accuracy of the Lachman test is as good as the instrument evaluation if the end point is taken into consideration. A positive Lachman test indicating anterior knee laxity is one where the soft end point is as described by Torg et al. Both instrument measurements are accurate in indicating anterior knee laxity, but only if they are used by an experienced examiner. Using the side-to-side measurements, the sensitivity of the KT 1000 arthrometer is higher. If only single translations greater than 4 mm without a significant side-to-side difference with the ultrasound technique are interpreted as anterior knee instability, then some knees will be rated as unstable, although both the clinical and KT 1000 arthrometer examinations prove them to be stable. We believe that only a side-to-side difference with the instrument techniques should be interpreted as knee laxity. Borderline positive measurements should only be used together with the clinical findings. Both instrument measurements can help to improve the quality of the clinical examination if the examiners are inexperienced. If instrument measurements are required, we believe that the ultrasound technique is easy and cheap to perform. Nevertheless, we believe that instrument measurements of anterior knee laxity are not necessary if a thorough clinical examination is performed, taking the end point of the Lachman test into consideration.

Anterior Cruciate Ligament↗
PubMed2004

[Corrective osteotomy in primary varus, double varus and triple varus knee instability with cruciate ligament replacement].

Osteochondral lesions and osteoarthritis in young patients are often caused by chronic knee instability in varus malaligned knees. We present the indication, operative technique, and results of 57 patients treated by simultaneous high tibial osteotomy and cruciate ligament reconstruction. The indication for simultaneous high tibial valgus osteotomy and ACL reconstruction is chronic anterior knee instability in varus knees of patients under 40 years of age. In these patients, medial meniscus deficiency secondary to prior injuries and/or chronic knee instability have frequently led to unicompartmental (medial) tibiofemoral degenerative changes. The average correction angle of the osteotomy was 7 degrees (4-10). Subjectively, all patients reported an improvement of preoperative swelling, pain, and instability. Additional cartilage surgery or meniscus implantation did not significantly alter the clinical score values. Complications occurred in four patients. Unstable varus malangulated knees can be sufficiently treated by osteotomy and cruciate ligament plasty and is suggested as cost-effective therapy with good short-term results. Performing both operations in one procedure facilitates early rehabilitation and return of the patients back to the activities of daily living and sports.

Adult↗
PubMed2004

[Ulnar instability of the carpus].

Ulnar instabilities of the carpus are rare findings depending on a dissociation of the lunotriquetral (LT-) junction. They are frequently not recognized or confused with ulnocarpal complaints of other origin due to missing typical clinical or radiological indications. The central structures are the os triquetrum and its connections to the os lunatum, the distal carpal row, radius and ulna. The most important causes are injuries, but degeneration, ulnar impaction syndrome or the ulna plus variant can also be involved. The symptoms are ulnar-sided pain, sensations of instability and weakness as well as "clunking" sensations in the ulnar wrist. Clinical examination may reveal tenderness in the LT-interval, between the ECU- and FCU-tendons, and displacement of the triquetrum on palpation. The LT-interval is rarely extended in conventional X-rays. A VISI position of the os lunatum is found in instabilities of higher degree. A distinct diagnosis is only achieved by arthroscopy. Conservative treatment consists of 4-8 weeks of arm immobilization. Diagnostic arthroscopy can be combined with débridement and/or closed reduction of the LT-interval with consecutive percutaneous k-wire fixation. If a repair of the LT-ligament is not possible, reconstructive methods are indicated. They include extrinsic tenodesis with part of the extensor carpi ulnaris tendon, ligamentoplasty or osteoligamentous autografts. The role of lunotriquetral arthrodesis is considered to be controversial, due to a high rate of non-fusions. Simple correction of the LT-dissociation does not resolve the static instability of the proximal row (VISI-position of the lunatum). In these cases, salvage procedures such as limited arthrodesis of the wrist, proximal row carpectomy or complete arthrodesis are indicated.

Arthroscopy↗
PubMed2004

[Shoulder instability. Classification and treatment].

Shoulder instability includes different degrees of instability from painful hyperlaxity to subluxation to dislocation. Different classifications of shoulder instability have been created in order to facilitate decision making for treatment. None of these, however, has gained acceptance. Subject to the indications, shoulder instability can be treated conservatively or surgically after repositioning the acute dislocation. A survey of arthroscopic and open stabilization procedures and their results are given in relation to the indications.

Arthroscopy↗