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[Impact of bladder irritative symptoms and detrusor instability on the outcome of urethropexy].

OBJECTIVES: To evaluate the repercussion of irritative urinary symptoms and bladder instability on the results of urethropexy for urinary stress incontinence. METHODS: A clinical and urodynamic study was carried out in 70 adult women submitted to urethropexy (Kelly, Raz, Marshall-Marchetti-Krantz, Burch or simplified Ramirez technique). RESULTS: The urge incontinence symptom was associated with coughing incontinence is 38 (60%) of the patients submitted to urethropexy. This symptom decreased to 42% (27 patients) after urethropexy. The average score of diurnal urinary frequency was 23% less posturethropexy. The simplified Ramirez technique had the lowest diurnal urinary frequency score [1.17 +/- 1.07 (0 to 3)]. Bladder instability with urinary stress incontinence (mixed incontinence) was found in 21 (30%) patients before urethropexy. The incidence of bladder instability after urethropexy was significantly greater in this group (52%) than in the patients with isolated urinary stress incontinence (17%). However, urethropexy also corrected bladder instability in 30% of the women with mixed incontinence. The Kelly technique produced the lowest incidence of bladder instability after urethropexy (14%). CONCLUSIONS: Urethropexy significantly decreases the irritative urinary symptoms associated with stress urinary incontinence. In some cases, bladder instability associated with stress incontinence (mixed incontinence) may disappear following urethropexy. In most cases bladder instability continues after urethropexy.

Adult↗

The heterogeneity of microsatellite instability in multiple gastric cancers.

To obtain a better understanding of the role of genetic instability in developing gastric cancer, it is of great interest to examine microsatellite alterations in synchronous multiple gastric cancers that are thought may have the same genetic background and the same microenvironment of the stomach. We report our experience with two patients with synchronous multiple gastric cancers; patient 1 showed two carcinomas in the stomach, whereas patient 2 showed two carcinomas and two adenomas in the stomach. We examined the DNAs from the two cases for microsatellite instability and expected that the status of microsatellite instability in each tumor from the same stomach would be the same. However, patient 2 revealed heterogeneity in the microsatellite instability, i.e., an early cancer that showed some apparent alterations, whereas the other advanced cancer and two adenomas did not. On the other hand, neither of the two carcinomas in patient 1 showed microsatellite instability. To our knowledge, there has been no previous report of microsatellite instability in multiple gastric cancers. In this report, we describe a case that revealed such a heterogeneity of the microsatellite instability, in which the carcinogenic process of each tumor may undergo different genetic alterations even under the same genetic conditions and background.

Aged↗

Occurrence of microsatellite instability in gastric carcinoma is associated with enhanced expression of erbB-2 oncoprotein.

To investigate the molecular mechanism of gastric carcinogenesis, we examined simultaneously the frequency of microsatellite instability and the immunoreactivities to ras, erbB-2, and p53 in 42 gastric adenocarcinoma tissues. Microsatellite instability, measured by DNA replication error, was detected in 33.3% (14/42) of patients with gastric carcinoma while positive immunostaining was demonstrated in 3.1% (1/32) for ras, 40.5% (17/42) for erbB-2, and 28.6% (12/42) for p53. There was no statistical difference between the intestinal type and the diffuse type of carcinoma with respect to microsatellite instability, ras, or erbB-2 expression. The expression of p53 occurred more frequently in the intestinal type of carcinoma (41.7%, 10/24) than in the diffuse type of carcinoma (11.1%, 2/18; P < 0.01). There was no association between microsatellite instability and ras or p53 expression, while enhanced expression of erbB-2 occurred more frequently in carcinomas with microsatellite instability (64.3%, 9/14) than in those without microsatellite instability (28.6%, 8/28; P < 0.05). Such a strong association between microsatellite instability and erbB-2 oncogene may be responsible for the increase of other oncogenic mutations and tumor progression in gastric carcinogenesis.

DNA, Neoplasm↗

Microsatellite instability occurs frequently and in both diploid and aneuploid cell populations of Barrett's-associated esophageal adenocarcinomas.

Alterations of microsatellites consisting of extra or missing copies of these sequences occur at relatively high frequencies in sporadic and hereditary colorectal adenocarcinomas, gastric and pancreatic cancers, and at lower frequencies in endometrial, bladder, ovarian, and other carcinomas. We determined the prevalence of microsatellite instability in esophageal adenocarcinoma, Barrett's esophagus, and squamous cell carcinoma of the esophagus. Assays were performed on 105 patients, including 28 subjects with Barrett's metaplasia, 36 with Barrett's-associated adenocarcinoma, and 42 with primary esophageal squamous cell carcinoma. Flow cytometric nuclear sorting based on DNA content was performed on 25 of the adenocarcinomas prior to DNA extraction. Specimens from 11 of the 106 patients (10%) showed instability at 1 or more chromosomal loci. Instability was seen in 2 of 28 patients (7%) with Barrett's metaplasia alone, in 8 of 36 (22%) with adenocarcinoma, and in 1 of 42 (2%) with squamous cell carcinoma. Among the 25 flow cytometrically sorted adenocarcinomas, instability occurred in 8 (32%); sorted diploid nuclei from these tumors showed instability in 4 of 8 cases (50%). These data indicate that microsatellite instability occurs frequently in Barrett's-associated esophageal adenocarcinoma. They also suggest that in esophageal adenocarcinomas, microsatellite instability can develop as an early event in metaplasia and in diploid tumor cells, before aneuploidy occurs.

Adenocarcinoma↗

Microsatellite instability in the progression of gastric carcinoma.

Seventy-six gastric carcinomas were analyzed with regard to whether or how microsatellite instability was associated with the development of the carcinoma. Microsatellite instability occurred as a late genetic alteration, with an incidence significantly higher in the advanced stage (17 of 51) than in the early stage (3 of 25; P < 0.05). Chromosomal losses on 5q and 17p, detected by polymerase chain reaction-restriction fragment length polymorphism, more frequently accompanied microsatellite instability (9 of 15 and 8 of 11, respectively), compared with carcinomas which lacked instability (5 of 28 and 9 of 30, respectively; P < 0.01 and P < 0.05, respectively). Epstein-Barr virus was observed in only 8 of 76 carcinomas, none of which was associated with microsatellite instability. No significant correlation was found between instability and the familial tendency to develop gastric carcinomas. Our results suggest that microsatellite instability might play a role in the progression of gastric carcinomas but not in Epstein-Barr virus-associated gastric carcinomas.

Adult↗

Microsatellite instability analysis of primary human brain tumors.

Microsatellite instability, as shown by the presence of additional alleles or shifts of electrophoretic mobility at simple sequence tandem repeat loci, has been demonstrated in hereditary and sporadic colorectal tumors and many other tumor types. To study microsatellite instability in human brain tumors, we examined a total of 144 sporadic neoplasms. These included 33 astrocytic tumors, 23 oligodendrogliomas, six gangliogliomas, 41 meningiomas, 10 vestibular schwannomas and 31 pituitary adenomas. Di-, tri- and tetranucleotide repeat microsatellite markers localized on chromosome 4 and 9, X, 13 and 22, respectively, were used to assess whether instability was a significant aspect of their abnormal chromosomal pattern. Instability of microsatellite markers was detected in four oligodendrogliomas (17.4%), one pituitary adenoma (3.2%), one meningioma (2.4%), one astrocytic tumor (3.0%) and not at all in gangliogliomas and schwannomas. Therefore, our results suggest that the microsatellite instability which occurs in colorectal cancers with defective mismatch repair is infrequent in many types of human brain tumors and that the lower level of instability observed in brain tumors may be reflective of other mechanisms of genetic instability.

Base Sequence↗

Microsatellite instability in preinvasive and invasive head and neck squamous carcinoma.

To investigate the extent and significance of microsatellite instability in head and neck carcinogenesis we analyzed DNA extracted from normal squamous epithelium, severe dysplasia, and corresponding carcinoma specimens from 20 patients by multiplex polymerase chain reaction. Loci on chromosomes 3p, 5p, 5q, 8p, 9p, 9q, 11q, 17p, 17q, 18p, 18q were selected for analysis. Our results show that three of the dysplasias (15.0%) and six of the invasive carcinoma (30.0%) manifested instability at multiple loci. Two of the dysplastic lesions had identical alterations in the corresponding carcinomas and one showed instability differences in only two of eight loci. Normal squamous epithelium lacked microsatellite instability. No apparent association between smoking, alcohol use, or family history of cancer and instability was found in this small cohort. Invasive carcinomas with instability were relatively more poorly differentiated and had a higher stage and a high proliferative fraction. Our study indicates that microsatellite instability is 1) noted in a small subset of dysplastic lesions of head and neck squamous epithelium and 2) present in approximately one-third of invasive lesions, usually with aggressive characteristics, and may clinically be a late event associated with tumor progression.

Aged↗

Regional differences of somatic CAG repeat instability do not account for selective neuronal vulnerability in a knock-in mouse model of SCA1.

Expression of unstable translated CAG repeats is the mutational mechanism in nine different neurodegenerative disorders. Although the products of genes harboring these repeats are widely expressed, a subset of neurons is vulnerable in each disease accounting for the different phenotypes. Somatic instability of the expanded CAG repeat has been implicated as a factor mediating the selective striatal neurodegeneration in Huntington disease. It remains unknown, however, whether such a mechanism contributes to the selective neurodegeneration in other polyglutamine diseases or not. To address this question, we investigated the pattern of CAG repeat instability in a knock-in mouse model of spinocerebellar ataxia type 1 (SCA1). Small pool PCR analysis on DNA from various neuronal and non-neuronal tissues revealed that somatic repeat instability was most remarkable in the striatum. In the two vulnerable tissues, cerebellum and spinal cord, there were substantial differences in the profiles of mosaicism. These results suggest that in SCA1 there is no clear causal relationship between the degree of somatic instability and selective neuronal vulnerability. The finding that somatic instability is most pronounced in the striatum of various knock-in models of polyglutamine diseases highlights the role of trans-acting tissue- or cell-specific factors in mediating the instability.

Animals↗

A gene expression signature of genetic instability in colon cancer.

Genetic instability plays a central role in the development and progression of human cancer. Two major classes of genetic instability, microsatellite instability (MSI) and chromosome instability (microsatellite stable; MSS), are best understood in the context of colon cancer, where MSI tumors represent approximately 15% of cases, and compared with MSS tumors, more often arise in the proximal colon and display favorable clinical outcome. To further explore molecular differences, we profiled gene expression in a set of 18 colon cancer cell lines using cDNA microarrays representing approximately 21,000 different genes. Supervised analysis identified a robust expression signature distinguishing MSI and MSS samples. As few as eight genes predicted with high accuracy the underlying genetic instability in the original and in three independent sample sets, comprising 13 colon cancer cell lines, 61 colorectal tumors, and 87 gastric tumors. Notably, the MSI signature was retained despite genetically correcting the underlying instability, suggesting the signature reflects a legacy of the tumor having arisen from MSI, rather than sensing the ongoing state of MSI. Our findings support a model in which MSI and MSS preferentially target different genes and pathways in cancer. Further, among the MSI signature genes, our findings implicate a role of elevated metallothionein expression in the clinical behavior of MSI cancers.

Adaptor Proteins, Signal Transducing↗

The death-inducing effect and genomic instability.

Exposure to ionizing radiation can induce a heritable change in the unirradiated progeny of irradiated cells. This non-targeted effect of ionizing radiation manifests as genomic instability, and although there is some debate as to the role of genomic instability in the carcinogenic process, it is thought by some to be an early step in radiation carcinogenesis. Although the mechanism of induction of genomic instability is not clearly understood, evidence suggests that secreted factors from irradiated cells may be involved. We have previously identified another non-targeted effect of ionizing radiation, the death-inducing effect. Exposure of unirradiated GM10115 cells to medium from chromosomally unstable clones was generally found to be cytotoxic. However, occasionally cells will survive in medium from unstable clones and can be clonally expanded. The absolute yield of survivors is independent of the initial number of cells plated when cell densities reached 5,000 or more cells/dish. After cytogenetic analysis of the surviving colonies, we found chromosomal instability in three of 40 clones analyzed, while some clones exhibited increased micronucleus frequency and HPRT mutation frequency. These data suggest that our chromosomally unstable GM10115 cells secrete factors that are cytotoxic to the majority of stable, parental cells but are also capable of inducing a heritable change in some of the survivors that can manifest as delayed genomic instability. These results suggest a mechanism whereby instability can be perpetuated through the influences of potentially cytotoxic factors produced by genomically unstable clones.

Animals↗

Factors associated with physiotherapists' confidence during assessment of clinical cervical and lumbar spine instability.

BACKGROUND AND PURPOSE: Physiotherapists commonly encounter patients with complaints of vague, indistinguishable neck and back pain, such as clinical spine instability. Since confidence is a component of expert clinical practice, we were interested in measuring expert clinicians' confidence in diagnosing and assessing clinical spine instability. The aims of the present study were to factor out the common 'identifiers' associated with physiotherapists' objective, physical diagnosis and assessment of clinical spine instability, and to determine the association of reported diagnostic confidence to these identifiers. METHOD: The study used data from a Delphi instrument for the factor analysis and a survey of APTA Board-certified orthopaedic specialists for report of confidence. Using an ologit regression analysis, the identifier themes and clinical background characteristics were associated with confidence in diagnosis of clinical spine instability. RESULTS: Only clinical cervical spine instability obtained significant findings. The identifier 'observable or palpable abnormalities of motion during movement assessment in clinical practice' was positively associated with reported confidence in diagnosis, as was the influence of manual therapy background models: Cyriax, Maitland, McKenzie, NAIOMPT, Osteopathic, Paris and other. Male gender yielded negative association with reported confidence. No factors were associated with reported lumbar confidence. CONCLUSIONS: Multiple backgrounds of physiotherapists demonstrate confidence in detecting clinical spine instability using observable or palpable methods to detect abnormal movements.

Adult↗

Standardized ultrasound examination for evaluation of instability of the acromioclavicular joint.

Anteroposterior X-ray views of both acromioclavicular (AC) joints with 10-kg weights held in each hand are the generally accepted procedure for diagnosis of Tossy I-III grades of AC joint separation. An analogous diagnosis can be made by standardized ultrasound examination. Ten individuals with Tossy-I, 11 with Tossy-II and 8 with Tossy-III instability were examined both radiographically and by B-mode ultrasound. The degree of AC joint separation was uniformly determined on the basis of a calculated index (AC Index = AC joint width of uninjured side/AC joint width of injured side). The mean AC Index for Tossy-I instability determined by ultrasound was 1.0; mean indices of 0.49 and 0.5 were determined for Tossy-II injury by ultrasound and X-ray, respectively, and of 0.21 and 0.2, respectively, for Tossy-III instability. Statistical analysis showed significant differences between the mean AC indices of all three groups (P < 0.0001). We conclude that the reliability of ultrasound examination of AC joint instability is equal to that of radiographic measurement. Standard X-rays of the shoulder remain mandatory only to exclude fracture. The indication for operative stabilization of the AC joint can be established on the basis of the grade of AC joint instability measured by the side-effect-free and cost-effective method of ultrasound examination (AC Index < 0.3 equivalent to Tossy-III instability).

Acromioclavicular Joint↗

Surgical treatment of ligamentous instability after total knee arthroplasty.

During the period of January 1, 1972 through October 31, 1982 seven knees in seven patients had ligamentous reconstructions for instability following total knee arthroplasty. The type of ligamentous instability included severe medial instability in six and a combined severe medial and mild lateral instability in one patient. The surgical technique utilized to reconstruct the ligaments included proximal and distal advancement of the medial collateral ligament. In five of the seven, additional soft tissue surgery was combined with tightening of the medial collateral ligament. Unfortunately, ligamentous reconstruction failed to restore stability to the knee in any of the seven patients. Four patients required revision total knee arthroplasty. Instability of the knee necessitated full-time support with a brace and the seventh patient manages his instability without a brace. Ligamentous reconstruction without component revision is inappropriate in the treatment of the unstable knee following total knee arthroplasty.

Adult↗

Clinical instability of the lumbar spine after microdiscectomy.

A total of 190 patients treated microsurgically for a virgin single level lumbar disc herniation were examined physically after a mean follow-up period of 3 years (range 21-68 months). Included were 99 (52%) men and 91 (48%) women with a mean age of 42 years. During the observation period, sciatica had completely recovered or markedly diminished in 172 (90%) patients, and 142 (75%) patients had returned to work. However, as many as 29% of the patients occasionally suffered from low back pain. Clinical examination revealed various signs and symptoms of segmental instability of the lumbar spine in 22% of the surgical patients. There was a significant association between postoperative instability and unsatisfactory long-term outcome: of the 42 patients with instability, 62% suffered from low back pain and 45% were on sick leave or retired because of the back, while the corresponding numbers for those patients without instability were 20% and 8%, respectively (p < 0.0001). Moreover, the mean value of the Oswestry index in instability patients was as high as 34% (SD 12), indicating moderate disability, whereas a significantly (p = 0.0001) lower Oswestry Index 16% (SD 13), indicating minimal disability, was detected in patients without instability.

Activities of Daily Living↗

[Chronic instability after posterior cruciate ligament injury. Tactics, techniques, and results].

This article reviews the surgical treatment of chronic posterior knee instability. The treatment rationale includes exact definition of the instability pattern ("envelope-of-motion" of the tibia) by clinical examination, arthrometry and stress radiography. Exact evaluation of the osseous anatomy is mandatory to identify an eventual varus morphotype. This osseous variant in combination with posterior/posterolateral instability should be treated by an osteotomy in every case. The technique of additive osteotomy to correct varus and increase the sagittal tilt of the proximal tibia is described. Ligament reconstruction in chronic posterior knee instability must address the posterior cruciate ligament and the lateral/posterolateral structures in many cases. Patellar tendon grafts, quadriceps tendon grafts or hamstrings can be used for posterior cruciate ligament replacement. Arthroscopic or mini-open techniques may be used for graft placement, direct posterior fixation of the graft via a posterior incision is an option for patellar tendon grafts. Bousquet's biceps plasty or Clancy's biceps tenodesis may be used for posterolateral stabilization; a biceps tendon strip can also be used for lateral collateral ligament reconstruction. Results of surgery are still moderate. In the author's series of chronic posterior/posterolateral instability, 26 cases were treated with posterior cruciate ligament reconstruction and biceps tenodesis. Follow-up at 18 months demonstrated increased stability (mean residual posterior drawer 8 mm at 70 degrees and 20 lb force) and improved knee function (33 % IKDC B, 67 % IKDC C). Presently, surgical treatment of chronic posterior knee instability should be restricted to centers devoted to this problem.

Arthroscopes↗

[Posterior shoulder joint instability. Classification, pathomechanism,diagnosis, conservative and surgical management].

The posterior instability of the shoulder is a more difficult diagnostic and therapeutic challenge than the anterior instability. There are many etiologies and causes of posterior instability. Most studies in the literature are retrospective and yield a great variation in therapeutic recommendations. Generally it has to be separated in traumatic and atraumatic instabilities. Most of the traumatic dislocations are impaction fractures of the humeral head against the dorsal glenoid. Therapy is depending on the size of the humeral defect, the duration of dislocation and the functional demand of the patient. Therapeutic possibilities are closed reduction and fixation with a cast, open reduction and the transfer of the lower tubercule (McLaughlin's procedure), lifting of the defect and supporting with cancellous bone, subcapital rotational osteotomy or arthroplasty. The therapy of choice for atraumatic instability is a individualized rehabilitation program with strengthening and balancing of rotator cuff muscles and scapular stabilizers. Psychologic abnormalities and emotional problems have to be recognized prior to any operative procedure. These patients are no operative candidates. Operative treatment of choice is the posterior capsular shift addressing the causative redundancy or laxity of the postero-inferior capsule. Posterior bony procedures as glenoid osteotomy or bone block transfers are indicated, if the pathologic geometry of the glenoid is primarily responsible for posterior instability. It is strongly recommended to combine them with a capsular shift to address the secondary capsular redundancy.

Decision Making↗

Recurrent shoulder instability among athletes: changes in quality of life, sports activity, and muscle function following open repair.

BACKGROUND: Recurrent anterior shoulder instability is a disabling condition in young athletes with possibly underestimated impact on quality of life and sports activity. Commonly used clinical scoring systems do not reflect the impairment of quality of life and sports activity. It was our aim to assess the return to preinjury levels of quality of life and sports activity as well as the changes in muscle function among competitive and recreational athletes. HYPOTHESIS: Patients suffering from post-traumatic recurrent shoulder instability have to adopt their participation in sports and therefore discover a reduction in quality of life. Open stabilization procedures are able to improve shoulder function and to reduce recurrence rates. However, return to preinjury shoulder function is not guaranteed. STUDY DESIGN: Retrospective longitudinal cohort study on 19 consecutive athletes with recurrent, post-traumatic shoulder instability. All patients were treated with an open, capsulo-labral repair. The minimum follow-up was 24 months. METHODS: Life quality (SF12) and sports activity data (Athletic Shoulder Outcome Scoring System) were retrospectively collected for the time before injury (time 1) and for the time with recurrent instability (time 2). Two years after surgical stabilization (time 3), we followed our patients with different clinical outcome scores, rotator surface EMG measurement, isokinetic muscle strength testing, and a radiological evaluation. This design of a three-step follow-up allowed for calculating the impact on quality of life and sports activity following the injury. RESULTS: Two years after surgery, the clinical scoring systems revealed good-to-excellent results in all patients. Quality of life physical component summary remained diminished by 9.2% despite the surgical procedure and was therefore significantly lower as compared to preinjury levels (p < 0.05). Sports activity was also significantly lower at the time of follow-up (p < 0.05). In this specific procedure, external rotation was not impaired postoperatively. EMG testing showed an overall reduction of muscle activity, however not significant. Isokinetic muscle strength was significantly diminished for external rotation and shoulder abduction. CONCLUSIONS: Open reconstruction procedures for recurrent shoulder instability can restore shoulder function and stability to near-normal values. Despite good-to-excellent clinical results, there is a significant impairment of quality of life and sports activity 2 years after surgery. Muscle activity and muscle strength are diminished. Recurrent shoulder instability remains a disabling condition to the young athlete. Future strategies have to emphasize restoration of quality of life, sports activity, and muscle function.

Adolescent↗

Electromyographic analysis in patients with multidirectional shoulder instability during pull, forward punch, elevation and overhead throw.

Multidirectional shoulder joint instability alters the role of dynamic stabilizers, as a result of which the motion patterns of the muscle around the shoulder joint are also changed. The aim of this study was to compare the muscle activity of patients with multidirectional shoulder instability and the control group during pull, forward punch, elevation and overhead throw. Fifteen subjects with multidirectional shoulder instability and fifteen control subjects with normal, healthy shoulders participated in the study. Both shoulders were tested in all subjects. Signals were recorded by surface EMG from eight different muscles during pull, forward punch, elevation and overhead throw. The mean and standard deviation of MVE% for the different movement types and time broadness values during overhead throw were determined for each muscle in both groups and compared with each other. Test results suggest that in case of patients with multidirectional shoulder instability the various motions are performed in a different way. The results give rise to the assumption that the centralization of the glenohumeral joint and the reduction of instability are attempted to be ensured by the organism through increasing the role of rotator cuff muscles and decreasing the role of the deltoid, biceps brachii and pectoralis maior muscles. The analysis of time broadness shows that in patients with multidirectional shoulder instability, the time difference between the peaks of normalized voluntary electrical activity is significantly greater than in the control group.

Adult↗