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PubMed2001

Assessment of instability of the long head of the biceps tendon by MRI.

OBJECTIVE: To determine whether MRI can identify instability of the long head of the biceps tendon (LBT) in the rotator interval. DESIGN AND PATIENTS: A retrospective review was carried out of 19 patients, all arthroscopically examined, nine of whom had surgically confirmed instability of the LBT. RESULTS: A LBT perched on the lesser tuberosity correctly indicated all nine cases of instability with one false positive. In six of seven cases where the LBT was oval in shape, no instability of the biceps tendon existed, whereas LBT instability was present in eight of 12 patients with a flat long head of the biceps tendon. In seven of eight acutely angled intertubercular sulci there was no instability of the LBT while eight of 11 obtusely angled sulci were associated with LBT instability. By consensus impression, instability of the LBT could be determined with 67% sensitivity, 90% specificity, 86% positive predictive value, and 75% negative predictive value. CONCLUSIONS: A flat LBT perched on the lesser tuberosity with an obtusely angled intertubercular sulcus suggests the diagnosis of instability of the LBT in the correct clinical setting.

Adult↗
PubMedDate not supplied

A new method to calculate the beat-to-beat instability of QT duration in drug-induced long QT in anesthetized dogs.

INTRODUCTION: Instability of QT duration is a marker to predict Torsade de Pointes (TdP) associated with both congenital and drug-induced long QT syndrome. We describe a new method for the quantification of instability of repolarization. METHODS: Female, adult beagle dogs anesthetized with a potent morphinomimetic were treated with either solvent (n=7) or dofetilide (n=7). Poincaré plots with QT(n) versus QT(n+1) were constructed to visualize the beat-to-beat variation in QT intervals from the lead II ECG. Short-term instability (STI), long-term instability (LTI) and total instability (TI) were quantified by calculating the distances of 30 consecutive data-points from the x and y-coordinate to the "centre of gravity" of the data cluster. Dofetilide at 0.0025 to 0.04 mg/kg i.v. (plasma concentrations of 4+/-0.6 to 41+/-2.7 ng/ml), dose-dependently prolonged QT and QTcV (at 0.04 mg/kg i.v.: QT: 280+/-ms versus 236+/-5 ms with solvent; p<0.05 and QTcV: 290+/-9 ms versus 252+/-4 ms with solvent; p<0.05). Concomitantly, the compound induced an increase in the instability parameters in a similar dose-dependent manner (at 0.04 mg/kg i.v.: TI: 6.8+/-0.9 ms versus 1.7+/-0.3 ms; p<0.05, LTI: 3.6+/-0.5 ms versus 1.0+/-0.2 ms; p<0.05 and STI: 4.2+/-0.6 ms versus 1.0+/-0.2 ms; p<0.05). The increases induced by dofetilide were associated with a high incidence of early afterdepolarizations (EADs) in the endocardial monophasic action potential (in 6 out of the 7 compound-treated animals versus 0 out of the 7 solvent animals; p<0.05). CONCLUSION: Quantification of beat-to-beat QT instability by our method clearly detects changes in short-term, long-term and total instability induced by dofetilide, already at pre-arrhythmic doses. Dofetilide administration to anesthetized dogs prolongs ventricular repolarization, concomitantly increases beat-to-beat QT instability and induces early after depolarizations (EADs). As such, the use of these parameters in this in vivo model shows clear potential for risk identification in cardiovascular safety assessment.

Anesthesia↗
PubMed2002

Instability of repeated DNAs during transformation in Escherichia coli.

Escherichia coli has provided an important model system for understanding the molecular basis for genetic instabilities associated with repeated DNA. Changes in triplet repeat length during growth following transformation in E. coli have been used as a measure of repeat instability. However, very little is known about the molecular and biological changes that may occur on transformation. Since only a small proportion of viable cells become competent, uncertainty exists regarding the nature of these transformed cells. To establish whether the process of transformation can be inherently mutagenic for certain DNA sequences, we used a genetic assay in E. coli to compare the frequency of genetic instabilities associated with transformation with those occurring in plasmid maintained in E. coli. Our results indicate that, for certain DNA sequences, bacterial transformation can be highly mutagenic. The deletion frequency of a 106 bp perfect inverted repeat is increased by as much as a factor of 2 x 10(5) following transformation. The high frequency of instability was not observed when cells stably harboring plasmid were rendered competent. Thus, the process of transformation was required to observe the instability. Instabilities of (CAG).(CTG) repeats are also dramatically elevated upon transformation. The magnitude of the instability is dependent on the nature and length of the repeat. Differences in the methylation status of plasmid used for transformation and the methylation and restriction/modification systems present in the bacterial strain used must also be considered in repeat instability measurements. Moreover, different E. coli genetic backgrounds show different levels of instability during transformation.

DNA Replication↗
PubMed2001

Favorable survival associated with microsatellite instability in endometrioid endometrial cancers.

OBJECTIVE: To determine whether microsatellite instability in endometrioid endometrial cancer is associated with favorable survival. METHODS: Microsatellite instability analysis was performed in 131 patients with endometrioid endometrial cancer using three polymorphic markers in paired cancer and normal DNA. Logistic regression and multivariable analyses calculated the relation between microsatellite instability, clinical features, and survival. RESULTS: Microsatellite instability was detected in 29 of 131 (22%) endometrioid endometrial cancers. There was no correlation between microsatellite instability and age, race, grade, stage, or depth of myometrial invasion. Microsatellite instability was associated with better survival in univariate and multivariable analyses after controlling for confounding influences (P =.03). The 5-year survival rate of those with microsatellite instability was 77% (95% confidence interval 55%, 90%) compared with only 48% (95% confidence interval 39%, 57%) in other cases. Microsatellite instability was associated with other molecular features that predict favorable outcome including PTEN mutation (P =.002) and the absence of p53 overexpression (P =.01). CONCLUSION: Microsatellite instability is a molecular alteration associated with favorable outcome in endometrioid endometrial cancers, even when accounting for other prognostic factors. This association might be explained by the finding that the pathway of molecular carcinogenesis characterized by loss of DNA mismatch repair favors alteration of genes that result in a less virulent clinical phenotype.

Adult↗
PubMed2001

Genomic instability: potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy.

PURPOSE: Induced genomic instability generally refers to a type of damage which is transmissible down cell generations, and which results in a persistently enhanced frequency of de novo mutations, chromosomal abnormalities or lethality in a significant fraction of the descendant cell population. The potential contribution of induced genomic instability to tumour and normal tissue response, and second tumours, after radiotherapy, is explored. RESULTS: The phenomenon of spontaneous genomic instability is well known in some rare genetic diseases (e.g. Gorlin's syndrome), and there is evidence in such cases that it can lead to a greater propensity for carcinogenesis (with shortened latency) which is enhanced after irradiation. It is unclear what role induced genomic instability plays in the response of normal individuals, but persistent chromosomal instability has been detected in vivo in lymphocytes and keratinocytes from irradiated normal individuals. Such induced genomic instability might play some role in tumour response in a subset of tumours with specific defects in damage response genes, but again its contribution to radiocurability in the majority of cancer patients is unclear. In normal tissues, genomic instability induced in wild-type cells leading to delayed cell death might contribute to more severe or prolonged early reactions as a consequence of increased cell loss, a longer time required for recovery, and greater residual injury. In tumours, induced genomic instability reflected in delayed reductions in clonogenic capacity might contribute to the radiosensitivity of primary tumours, and also to a lower incidence, longer latency and slower growth rate of recurrences and metastases. CONCLUSIONS: The evidence which is reviewed shows that there is little information at present to support these propositions, but what exists is consistent with their expectations. Also, it is not yet clear to what extent mutations associated with genomic instability, particularly gene polymorphisms, or other low penetrant gene mutations, contribute to the recognized spectrum of normal tissue radiosensitivity amongst cancer patients, or in the general population. Tests for such genetic modifications may help in the search for more accurate prognostic markers of response, which hopefully could be used in addition to other strategies to further improve the outcome for cancer patients given radiotherapy.

Cell Division↗
PubMed1998

Anticipatory postural adjustments in conditions of postural instability.

OBJECTIVES: The purpose of this study was to investigate anticipatory postural adjustments (APAs) in standing subjects who performed a standard motor action triggering a standard postural perturbation (releasing a 2.2 kg load from extended arms) in conditions of different stability requirements. METHODS: The degree of stability was varied either by balancing on special boards with long and narrow support beams or by instructions to the subjects. In the first series of experiments 13 subjects stood on the board facing either perpendicular to the beam (instability in a sagittal plane) or along the beam (instability in frontal plane); different widths of the beam were used to vary the degree of instability. During the second series of experiments (6 subjects) inclined and one-legged postures were used to induce instability in sagittal and frontal planes respectively. EMG activity of rectus abdominis, erector spinae, rectus femoris, biceps femoris, tibialis anterior, and soleus muscles were recorded. Statistical methods included repeated measures analysis of variance (ANOVA) with direction of instability and level of instability being major factors, descriptive statistics, and post hoc Student's t tests. RESULTS: The integral measure of changes in the background electromyographic activity of postural muscles during APAs depended on two factors related to the postural task: (1) standing on a platform with a narrow support area led to an attenuation of the APAs; and (2) these effects were stronger when instability was in a sagittal rather than in the frontal plane. The anticipatory component in the displacement of the center of pressure did not show a clear attenuation that would depend on the direction of instability. CONCLUSIONS: We suggest a hypothesis that, in conditions of high stability demands, the central nervous system may suppress APAs as a protection against their possible destabilizing effects. These effects are more pronounced when the direction of an expected perturbation is in the plane of instability.

Adult↗
PubMed1997

Prognostic significance of microsatellite instability in patients with gastric carcinoma.

A proportion of gastric adenocarcinomas exhibit replication errors manifested as microsatellite instability. The clinicopathological and prognostic significance of this abnormality remains uncertain. This study aimed to determine the importance of microsatellite instability by analysing a large series of gastric carcinomas from an English population. Using a novel fluorescent polymerase chain reaction technique, we amplified 11 microsatellite sequences from paired normal and carcinoma DNA from 101 patients who underwent a potentially curative resection for gastric carcinoma. Overall, 21% of cases demonstrated microsatellite instability in at least one locus. At least four loci were examined in each case. A replication error positive phenotype (minimum of 29% of loci affected) was detected in 9% of cases. There was no statistically significant association between the presence of microsatellite instability or replication error positive phenotype and the patient's age, sex, tumour site, stage, node status, histological subtype or grade. Carcinomas confined to the mucosa or submucosa (T1) showed a significantly higher frequency of instability and replication error positive phenotypes than T3 lesions (P = 0.03 and P = 0.05, respectively). A larger proportion of patients who were microsatellite instability or replication error positive were alive at 5 years compared with those who were negative but this did not reach statistical significance (P = 0.15 and P = 0.16, respectively). We identified a subset of gastric carcinomas from a relatively low-risk population which showed evidence of microsatellite instability. There were no statistically significant 5-year survival advantages in cases demonstrating microsatellite instability or replication error positive phenotypes. The detection of microsatellite instability is of limited prognostic value in gastric carcinoma.

Adult↗
PubMed2000

Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer.

BACKGROUND: Colorectal cancer can arise through two distinct mutational pathways: microsatellite instability or chromosomal instability. We tested the hypothesis that colorectal cancers arising from the microsatellite-instability pathway have distinctive clinical attributes that affect clinical outcome. METHODS: We tested specimens of colorectal cancer from a population-based series of 607 patients (50 years of age or younger at diagnosis) for microsatellite instability. We compared the clinical features and survival of patients who had colorectal cancer characterized by high-frequency microsatellite instability with these characteristics in patients who had colorectal cancers with microsatellite stability. RESULT: We found high-frequency microsatellite instability in 17 percent of the colorectal cancers in 607 patients, and in a multivariate analysis, microsatellite instability was associated with a significant survival advantage independently of all standard prognostic factors, including tumor stage (hazard ratio, 0.42; 95 percent confidence interval, 0.27 to 0.67; P< 0.001). Furthermore, regardless of the depth of tumor invasion, colorectal cancers with high-frequency microsatellite instability had a decreased likelihood of metastasizing to regional lymph nodes (odds ratio, 0.33; 95 percent confidence interval, 0.21 to 0.53; P< 0.001) or distant organs (odds ratio, 0.49; 95 percent confidence interval, 0.27 to 0.89; P=0.02). CONCLUSION: High-frequency microsatellite instability in colorectal cancer is independently predictive of a relatively favorable outcome and, in addition, reduces the likelihood of metastases.

Adult↗
PubMed2003

Radiation-induced genomic instability: radiation quality and dose response.

Genomic instability is a term used to describe a phenomenon that results in the accumulation of multiple changes required to convert a stable genome of a normal cell to an unstable genome characteristic of a tumor. There has been considerable recent debate concerning the importance of genomic instability in human cancer and its temporal occurrence in the carcinogenic process. Radiation is capable of inducing genomic instability in mammalian cells and instability is thought to be the driving force responsible for radiation carcinogenesis. Genomic instability is characterized by a large collection of diverse endpoints that include large-scale chromosomal rearrangements and aberrations, amplification of genetic material, aneuploidy, micronucleus formation, microsatellite instability, and gene mutation. The capacity of radiation to induce genomic instability depends to a large extent on radiation quality or linear energy transfer (LET) and dose. There appears to be a low dose threshold effect with low LET, beyond which no additional genomic instability is induced. Low doses of both high and low LET radiation are capable of inducing this phenomenon. This report reviews data concerning dose rate effects of high and low LET radiation and their capacity to induce genomic instability assayed by chromosomal aberrations, delayed lethal mutations, micronuclei and apoptosis.

Animals↗
PubMed2003

Kinetics of the shear banding instability in startup flows.

Motivated by recent light scattering experiments on semidilute wormlike micelles, we study the early stages of the shear banding instability using the nonlocal Johnson-Segalman model with a "two-fluid" coupling of flow to micellar concentration. We perform a linear stability analysis for coupled fluctuations in shear rate gamma;, micellar strain W, and concentration phi about an initially homogeneous state. This resembles the Cahn-Hilliard (CH) analysis of fluid-fluid demixing (although we discuss important differences). First, assuming the initial state to lie on the intrinsic constitutive curve, we calculate the "spinodal" onset of instability in sweeps along this curve. We then consider start-up "quenches" into the unstable region. Here the instability in general occurs before the intrinsic constitutive curve can be attained, so we analyze the fluctuations with respect to the time-dependent start-up flow. We calculate the selected length and time scales at which inhomogeneity first emerges. When the coupling between flow and concentration is switched off, fluctuations in the "mechanical variables" gamma; and W are independent of those in phi, and are unstable when the intrinsic constitutive curve has negative slope; but no length scale is selected. Coupling to the concentration enhances this instability at short length scales, thereby selecting a length scale, consistent with the recent light scattering experiments. The spinodal region is then broadened by an extent that increases with proximity to an underlying (zero-shear) CH fluid-fluid (phi) demixing instability. Far from demixing, the broadening is slight and the instability is still mechanically dominated (by deltagamma; and deltaW) with only small deltaphi. Close to demixing, instability sets in at a very low shear rate, where it is dominated instead by deltaphi. In this way, the model captures a smooth crossover from shear banding instabilities that are perturbed by concentration coupling to demixing instabilities that are induced by shear.

Journal Article↗
PubMed2000

Sporadic microsatellite instability is specific to neoplastic and preneoplastic endometrial tissues.

Microsatellite instability is a frequent (13%-24%) finding in sporadic endometrial adenocarcinoma and its precursor lesions, but most studies are limited to patients who already have malignant or premalignant endometrial disease. We performed retrospective testing for microsatellite instability in women in whom cancers showing microsatellite instability developed later and prospective testing in randomly selected normal and anovular endometrial biopsy specimens. Microsatellite instability in cancer-bearing biopsy specimens accurately reflected that seen in matched malignant tissues obtained at hysterectomy. In 1 patient, microsatellite instability developed in a scanty sample of fragmented endometrial tissues 7 years before the onset of endometrial cancer. Prospective testing for microsatellite instability in the endometria of women unselected for subsequent appearance of endometrial cancer showed a very low rate of microsatellite instability. Only 1 endometrial specimen showing microsatellite instability was found among 75 anovulatory endometrial specimens, and none were found in 377 normal endometrial specimens and 46 polyps examined. Microsatellite instability may precede the onset of histologically diagnosed carcinoma but is rare in randomly sampled histologically normal endometrial tissues.

Carcinoma, Endometrioid↗
PubMedDate not supplied

Two subtypes in colorectal mucinous carcinoma in relation to microsatellite instability.

BACKGROUND/AIMS: Although some investigators have attempted to divide colorectal mucinous adenocarcinoma into two entities, there have been few reports describing microsatellite instability of each subtype. In this study, we elucidated the clinicopathological features of subtypes in mucinous carcinoma, especially the relationship between microsatellite instability and each subtype. METHODOLOGY: The present study included 33 patients with mucinous colorectal cancer. The 33 patients were classified into two groups; the papillotubular type group (n = 22) and the mucocellular type group (n = 11). The clinicopathological aspects and microsatellite instability were examined. RESULTS: Significant differences were found between the papillotubular type group and the mucocellular type group regarding the following findings such as lymphatic invasion, lymph node metastasis, peritoneal metastasis, and Dukes stage. The mucocellular type group had 2 cases with high-frequency microsatellite instability, 7 cases with low-frequency microsatellite instability and 2 cases with microsatellite stability. Conversely, the papillotubular type group included 12 cases with high-frequency microsatellite instability, 3 cases with low-frequency microsatellite instability and 7 cases with microsatellite stability. The ratio of cases with high-frequency microsatellite instability in the mucocellular type group (18.1%) was significantly lower than that of the papillotubular type group (54.5%) (P = 0.0463). The 5-year survival rate of the mucocellular type group (29.1%) was significantly lower than that of the papillotubular type group (70.3%) (P = 0.0282). CONCLUSIONS: Colorectal mucinous carcinoma needs to be classified into two groups, papillotubular type and mucocellular type, because of significant differences in microsatellite instability and patients' survival.

Adenocarcinoma, Mucinous↗
PubMed1986

Clinical significance of urethral instability.

Variations of urethral pressure were registered with microtransducers in 427 gynecologic patients with lower urinary tract symptoms during urethrocystometry. Urethral instability (variation of urethral pressure greater than 15 cm of water) was found in 16.4% of patients. The comparison of the urinary symptoms and the urodynamic data between patients with urethral instability (without previous surgery for incontinence, N = 57), and patients with stable urethra (variation of urethral pressure less than 5 cm of water, N = 269) showed that urethral instability was related to frequency, nycturia, urgency, and a history of urethral syndrome. In 27% of patients, the urethral instability was associated with a bladder instability. The comparison between patients with urethral instability and stable bladder (N = 51) and patients with bladder instability and stable urethra (N = 41) revealed that bladder instability seems to be more important than urethral instability as a factor associated with nycturia, urgency, and urge incontinence.

Adult↗
PubMed1998

Microsatellite instability and p53 mutations in sporadic right and left colon carcinoma: different clinical and molecular implications.

BACKGROUND: Left and right colon carcinomas can display different clinical, pathologic, and genetic characteristics. The purpose of this study was to characterize multiple molecular genetic alterations in sporadic colon carcinoma and to correlate them with the location of the tumors and with lymph node metastasis. METHODS: One hundred and twenty-five cases of sporadic colon carcinoma (50 in the right colon and 75 in the left colon in patients with no family history of colon carcinoma) were studied. Status of the p53 gene was assessed by polymerase chain reaction (PCR), single strand conformation polymorphism, and sequencing at exons 5-8. Microsatellite instability was analyzed with five microsatellite markers at chromosome 18. The mismatch repair genes hMLH1 and hMSH2 were studied in tumors found to have microsatellite instability by PCR and sequencing. RESULTS: In the 125 cases studied, there were 53 tumors with mutations of the p53 gene. p53 mutations correlated with lymph node metastases from right colon carcinoma cases (61%), and all cases with p53 mutations and microsatellite instability were AJCC/UICC Stage III (Dukes Stage C). In the right colon carcinoma cases the rate of microsatellite instability was related to the tumor size (19% in tumors measuring < 4 cm, and 34% in tumors measuring > 4 cm). No correlation between microsatellite instability and p53 mutations was detected. In the left colon carcinoma cases, p53 mutations were detected in 41% of tumors and microsatellite instability in 14%; neither finding was related to the tumor size. Mutations of the hMLH1 and hMSH2 mismatch repair genes were detected in 7 of 24 cases with marked microsatellite instability. CONCLUSIONS: Microsatellite instability is prone to occur in sporadic right colon carcinoma during tumor growth and is not associated significantly with mutations in the hMLH1 and hMSH2 mismatch repair genes or in the p53 gene. Concomitant detection of microsatellite instability and p53 mutations in right colon carcinoma is associated with the presence of lymph node metastases.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Papillary thyroid cancer: high inter-(simple sequence repeat) genomic instability in a typically indolent cancer.

OBJECTIVES: The object of this study is to measure genomic instability in papillary thyroid cancer and correlate these measurements with known clinical prognosticators such as patient age, tumor size, histologic subtype, and three commonly used thyroid risk assessment indices. A secondary objective of this study was to use the measurements of genomic instability to estimate the number of mutational events present in the papillary thyroid cancer genome. METHODS: Inter-simple sequence repeat polymerase chain reaction (ISSR-PCR) is a rapid and reproducible technique for quantitation of genomic instability, or the degree of genome alteration, in solid tumors. This includes quantitation of amplifications, deletions, translocations, and insertions. Twenty-eight papillary carcinomas were evaluated by ISSR-PCR. RESULTS: Evaluation of 28 papillary carcinomas by ISSR-PCR demonstrated a wide range of genomic instability. Of the panel of clinicopathologic factors examined, only patient age was significantly associated with genomic instability. The mean genomic instability index value was greatest in the youngest age group, which was significantly different from the median value measured in the oldest age group (3.7, 2.5, respectively, p =.05). The mean value in the intermediate age group fell between the younger and older groups (3.1). By use of ISSR-PCR, we have calculated 15,000 individual genomic events as having occurred in each papillary tumor cell. CONCLUSIONS: Despite its generally indolent biologic behavior, papillary thyroid cancer exhibits a high degree of genomic instability comparable to that seen in colorectal cancer. These results suggest that elevated genomic instability, as measured by ISSR-PCR, may not be sufficient to enable thyroid tumor progression to less indolent disease and that this process is severely constrained by some additional essential factor such as the differentiated state of the tissue or the need to bring into play an additional form of genomic destabilization.

Adolescent↗
PubMed2005

Ankle function during gait in patients with chronic ankle instability compared to controls.

BACKGROUND: Despite much research, the reasons behind the development of chronic ankle instability in individuals post ankle inversion sprain are unknown. Chronic ankle instability has not previously been investigated dynamically using 3D motion analysis during walking. We hypothesised that chronic ankle instability subjects would exhibit a different kinematic and kinetic pattern during normal walking when compared with a control group. METHODS: Gait analysis was carried out on fifty subjects (25 chronic ankle instability, and 25 age, gender, activity, and gait velocity matched controls) during walking. Kinematic and kinetic pattern differences using the 3D motion analysis system combined with a force plate were established during 100 ms pre-heel strike and 200 ms post-heel strike, between the chronic ankle instability subjects and controls during normal walking. FINDINGS: Chronic ankle instability subjects were significantly (P<0.01) more inverted in the frontal plane compared to controls from 100 ms pre-heel strike to 200 ms post-heel strike. The joint angular velocity was significantly (P<0.05) higher at heel strike in the chronic ankle instability group. During the early stance phase of gait chronic ankle instability subjects appear to be controlled by an evertor muscle moment working concentrically compared to an invertor muscle moment working eccentrically in the controls. INTERPRETATION: These changes in kinematics and kinetics which arise are likely to result in increased stress being applied to ankle joint structures during the heel strike and loading response phases of the gait cycle. This could result in repeated injury and consequent damage to ankle joint structures.

Adult↗
PubMed2006

Non-random distribution of instability-associated chromosomal rearrangement breakpoints in human lymphoblastoid cells.

Genomic instability is observed in tumors and in a large fraction of the progeny surviving irradiation. One of the best-characterized phenotypic manifestations of genomic instability is delayed chromosome aberrations. Our working hypothesis for the current study was that if genomic instability is in part attributable to cis mechanisms, we should observe a non-random distribution of chromosomes or sites involved in instability-associated rearrangements, regardless of radiation quality, dose, or trans factor expression. We report here the karyotypic examination of 296 instability-associated chromosomal rearrangement breaksites (IACRB) from 118 unstable TK6 human B lymphoblast, and isogenic derivative, clones. When we tested whether IACRB were distributed across the chromosomes based on target size, a significant non-random distribution was evident (p<0.00001), and three IACRB hotspots (chromosomes 11, 12, and 22) and one IACRB coldspot (chromosome 2) were identified. Statistical analysis at the chromosomal band-level identified four IACRB hotspots accounting for 20% of all instability-associated breaks, two of which account for over 14% of all IACRB. Further, analysis of independent clones provided evidence within 14 individual clones of IACRB clustering at the chromosomal band level, suggesting a predisposition for further breaks after an initial break at some chromosomal bands. All of these events, independently, or when taken together, were highly unlikely to have occurred by chance (p<0.000001). These IACRB band-level cluster hotspots were observed independent of radiation quality, dose, or cellular p53 status. The non-random distribution of instability-associated chromosomal rearrangements described here significantly differs from the distribution that was observed in a first-division post-irradiation metaphase analysis (p=0.0004). Taken together, these results suggest that genomic instability may be in part driven by chromosomal cis mechanisms.

B-Lymphocytes↗
PubMed2002

Sports-related injuries of the shoulder: instability.

With current technology a properly conceived imaging strategy can demonstrate instability lesions in the athlete. Plain radiographs can diagnose acute dislocations and assess successful reductions. In addition, plain radiographs can demonstrate Hill-Sachs and, more importantly for instability, osseous Bankart lesions. In the acute setting, conventional MRI nicely demonstrates labral Bankart, ligamentous. and tendonous injuries that result from dislocations and can lead to instability. In the setting of chronic instability, MR arthrography best evaluates these lesions. In the postoperative shoulder, muitislice CT arthrography may be the modality of choice, but further investigation is needed. If large series validate multislice CT arthrography for the evaluation of postoperative instability lesions, this technique may become widely used in athletes and in other populations where recurrent instability is a problem. Other imaging strategies may also find an increasing central role in evaluating shoulder instability lesions. Indirect MR arthrography, for example, may have a role in assessing these lesions in athletes . Another intriguing technology for this application is the development of high field (0.5 Tesla or greater) open magnets. In such a setting, physiological relationships in the shoulder with motion and stress may be evaluated. Such imaging may farther illuminate our understanding of the stable and unstable shoulder. Unfortunately, with all imaging modalities, whether widely used or experimental, outcomes data is Lacking. How do the various imaging modalities and strategies affect patient outcome? The answer is unknown and needs to be answered before a definitive patient work-up for shoulder instability can be established.

Athletic Injuries↗