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PubMedDate not supplied

The development and evaluation of a disease-specific quality of life measurement tool for shoulder instability. The Western Ontario Shoulder Instability Index (WOSI).

The purpose of this study was to develop a valid, reliable, and responsive disease-specific quality of life measurement tool for patients with shoulder instability. Development included 1) identification of a specific patient population; 2) generation of issues specific to the "disease" ("items") from reviewing the literature, interviewing health caregivers, and interviewing patients representing all demographics, disease type and severity, and treatments; 3) item reduction using patient-generated frequency-importance products and correlation matrices; and 4) pretesting the prototype instrument on 2 groups of 10 patients. The final instrument, the Western Ontario Shoulder Instability Index, has 21 items representing 4 domains. The instrument attributes (validity, reliability, and responsiveness) were evaluated. Construct validation demonstrated that this index correlated predictably with other measures. Reliability was very high at 2 weeks and 3 months, and the index was more responsive (sensitive to change) than five other shoulder measurement tools (the Disabilities of the Arm, Shoulder and Hand scale; The American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form; the UCLA Shoulder Rating Scale; the Constant Score; and the Rowe Rating Scale), a global health instrument (the SF12), and range of motion. Since the patient's perception of changes in health status is the most important indicator of the success of a treatment, we suggest that this measurement tool be used as the primary outcome measure to evaluate treatments in this patient population, although it can also be used for monitoring patients' progress in clinical practice.

Demography↗
PubMed2000

Genetic instability in myelodysplastic syndrome: detection of microsatellite instability and loss of heterozygosity in bone marrow samples with karyotype alterations.

Using a polymerase chain reaction (PCR)-based approach, we examined the prevalence of loss of heterozygosity (LOH) and microsatellite instability (MSI) in relation to chromosomal imbalances in myelodysplastic syndrome (MDS). Two of 26 patients displayed MSI (8%), one of them at five loci. LOH was detected in six out of 26 cases (23%), predominantly involving markers IRF1 [5q31] and WT1 [11p]. Two patients displayed a corresponding chromosomal deletion by conventional cytogenetics. Supporting the mutator phenotype hypothesis, a significant coincidence of LOH, MSI and chromosome abnormalities was observed (P < 0.025). Moreover, our data suggest that LOH represents an initial rather than a secondary genetic event in MDS, promoting genetic instability in a subset of patients.

Aged↗
PubMed2000

Genetic instability and aberrant DNA methylation in chronic hepatitis and cirrhosis--A comprehensive study of loss of heterozygosity and microsatellite instability at 39 loci and DNA hypermethylation on 8 CpG islands in microdissected specimens from patients with hepatocellular carcinoma.

A study was conducted to examine the significance of genetic instability and aberrant DNA methylation during hepatocarcinogenesis. Genomic DNA was extracted from 196 microdissected specimens of noncancerous liver tissue that showed no marked histologic findings or findings compatible with chronic hepatitis or cirrhosis, and 80 corresponding microdissected specimens of hepatocellular carcinoma (HCC) from 40 patients. Loss of heterozygosity (LOH) and microsatellite instability (MSI) were examined by polymerase chain reaction (PCR) using 39 microsatellite markers, and DNA methylation status on 8 CpG islands was examined by bisulfite-PCR. In noncancerous liver tissues, LOH, MSI, and DNA hypermethylation were found in 15 (38%), 6 (15%), and 33 (83%) of 40 cases, respectively. The incidence of DNA hypermethylation in histologically normal liver was similar to that in chronic hepatitis and cirrhosis, although neither LOH nor MSI was found in histologically normal liver. In cancerous tissues, LOH, MSI, and DNA hypermethylation were found in 39 (98%), 8 (20%), and 40 (100%) of 40 cases, respectively. CpG islands of the p16 gene and methylated in tumor 1, 2, 12, and 31 clones were frequently methylated in cancerous tissues, although neither the thrombospondin-1 nor the human Mut L homologue (hMLH1) gene was methylated. Absence of silencing of the hMLH1 gene by DNA hypermethylation is consistent with the low incidence of MSI in HCCs. The results of this study indicate that LOH and aberrant DNA methylation contribute to hepatocarcinogenesis; DNA hypermethylation in particular, which precedes or may even cause LOH, is as an early event during hepatocarcinogenesis.

Adult↗
PubMed2001

SMAD4 mutations in colorectal cancer probably occur before chromosomal instability, but after divergence of the microsatellite instability pathway.

Loss of chromosome 18q21 is well documented in colorectal cancer, and it has been suggested that this loss targets the DCC, DPC4/SMAD4, and SMAD2 genes. Recently, the importance of SMAD4, a downstream regulator in the TGF-beta signaling pathway, in colorectal cancer has been highlighted, although the frequency of SMAD4 mutations appears much lower than that of 18q21 loss. We set out to investigate allele loss, mutations, protein expression, and cytogenetics of chromosome 18 copy number in a collection of 44 colorectal cancer cell lines of known status with respect to microsatellite instability (MSI). Fourteen of thirty-two MSI(-) lines showed loss of SMAD4 protein expression; usually, one allele was lost and the other was mutated in one of a number of ways, including deletions of various sizes, splice site changes, and missense and nonsense point mutations (although no frameshifts). Of the 18 MSI(-) cancers with retained SMAD4 expression, four harbored missense mutations in the 3' part of the gene and showed allele loss. The remaining 14 MSI(-) lines had no detectable SMAD4 mutation, but all showed allele loss at SMAD4 and/or DCC. SMAD4 mutations can therefore account for about 50-60% of the 18q21 allele loss in colorectal cancer. No MSI(+) cancer showed loss of SMAD4 protein or SMAD4 mutation, and very few had allelic loss at SMAD4 or DCC, although many of these MSI(+) lines did carry TGFBIIR changes. Although SMAD4 mutations have been associated with late-stage or metastatic disease, our combined molecular and cytogenetic data best fit a model in which SMAD4 mutations occur before colorectal cancers become aneuploid/polyploid, but after the MSI(+) and MSI(-) pathways diverge. Thus, MSI(+) cancers may diverge first, followed by CIN(+) (chromosomal instability) cancers, leaving other cancers to follow a CIN(-)MSI(-) pathway.

Adenocarcinoma↗
PubMed2003

Induction of genetic instability and chromosomal instability by nickel sulfate in V79 Chinese hamster cells.

Nickel compounds are known to be carcinogenic to humans and show genotoxicity, including the ability to induce chromosome aberrations and neoplastic transformation in vitro. The mutagenicity of nickel compounds is, however, equivocal and the mechanisms of carcinogenesis are still not clear. In this study, the possibility that nickel compounds induce genetic or chromosomal instability was examined, because recent studies in cancer research show that these conditions are critically involved in carcinogenesis. V79 Chinese hamster cells were treated with 320 microM nickel sulfate for 24 h at low cell density (100 cells/100 mm diameter dish) and clones derived from single cells surviving Ni treatment were isolated. When cells grew up to 23-25 population doublings post-treatment, mutation frequency at the HPRT locus and the chromosome aberration frequency of each clone were examined. Five out of 37 clones (13.5%) derived from Ni-treated cells showed a remarkably increased frequency of HPRT mutations (>or=1 x 10(-4)), while only one out of 37 control clones (2.7%) showed this high mutation rate. In addition, 17 out of 37 clones (45.9%) from Ni-treated cells showed structural chromosomal aberrations in 10% or more of cells (up to 45.5%), while only three out of 31 control clones (9.7%) showed this high aberration rate. Out of 37 clones derived from Ni-treated cells, eight (21.6%) and 11 (29.7%) clones showed an increased frequency (>or=5%) of aneuploid and polyploid cells, respectively, while only a few control clones showed such an increase in aneuploid and polyploid cells. These results indicate that nickel sulfate can induce genetic and chromosomal instability in V79 cells.

Aneuploidy↗
PubMed1988

Detrusor instability and bladder outflow obstruction. Evidence for a correlation between the severity of obstruction and the presence of instability.

Forty patients with bladder outflow obstruction due to benign prostatic hypertrophy were assessed by means of symptom analysis, rectal examination, intravenous urography and/or cystoscopy, medium-fill water cystometry and pressure flow study. No significant correlation was found between the severity of obstruction and the degree of instability, but the occurrence of instability did correlate with the degree of obstruction. This latter conclusion, though logical, had not been proved before, and was achieved by means of a new urodynamic parameter.

Aged↗
PubMed2001

Single nucleotide instability without microsatellite instability in rat mammary carcinomas.

Mutation frequencies (MnFs) of the lacI transgene and mutation rates (MRs) of the endogenous hprt gene were analyzed in two mammary carcinoma cell lines that we established from mammary carcinomas that had been induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in female lacI-transgenic rats. Using the lacI transgene, corrected MnF, which is the number of independent lacI mutations that occurred while 102 cells expanded into 10(7) cells and which reflect the dynamic increase of point mutations, was measured. The corrected MnFs in the two mammary carcinoma cell lines (59 x 10(-6) and 72 x 10(-6) mutations) were significantly higher than that in the primary culture of normal mammary epithelium (4.7 x 10(-6)). MRs of the hprt gene in the two mammary carcinoma cell lines (8.2 x 10(-7) and 11 x 10(-7) mutations/hprt/cell division) were also higher than the same control (1.4 x 10(-7)). A:T to C:G transversion was observed at significantly higher frequencies in the two cell lines (6 of 24 and 6 of 25 for lacI; 10 of 67 and 19 of 92 for hprt) than in the control (0 of 6 for lacI; 0 of 4 for hprt). Taking advantage of the lacI transgene, high frequencies of A:T to C:G transversion (6 of 38 and 8 of 33, respectively) was also confirmed in the primary carcinomas of the two cell lines, which indicated the presence of a common abnormality in the cell lines and in the primary carcinomas. Both the established cell lines and their primary carcinomas were negative for microsatellite instability, which is known to be caused mainly by mismatch repair insufficiency and to increase point mutations, and for p53 mutations. These findings showed that the two cell lines, and possibly their primary carcinomas, had increases in the MRs of point mutations attributable to a mechanism(s) different from mismatch repair insufficiency, and we would suggest that such a state be designated as single nucleotide instability (SNI).

Animals↗
PubMed2006

[Pelvic stabilization in cases of septic instability. Triangular osteosynthesis in case of infection related vertical pelvic ring instability].

The combination of transiliac screws and lumbopelvic distraction osteosynthesis is usually an appropriate procedure to treat vertical pelvic ring instabilities under the condition of full weight bearing. In this case, due to the extent of septic destruction of the dorsal portion of the iliac bone, the common triangular fixation method using conventional pedicle screws was not possible. Using the transiliac dorsoventral screw position with special long screws, we achieved high mechanical triangular stability sufficient for pelvic ring fusion despite the large bony defect.

Adult↗
PubMed1987

CT-functional diagnostics of the rotatory instability of the upper cervical spine. Part 2. An evaluation on healthy adults and patients with suspected instability.

Nine healthy adults and 43 patients with cervical spine injury were examined by using functional (computerized tomography) CT scanning. The ranges of axial rotation at the levels occiput C0-C1, C1-C2, and C2-C3 were measured. A rotation at C0-C1 greater than 8 degrees; at C1-C2, 56 degrees; or a right-left difference C0-C1 greater than 5 degrees and C1-2 greater than 8 degrees indicates hypermobility. A rotation at segment C1-C2 of less than 28 degrees indicates hypomobility. Surgical stabilization of rotatory instability could be considered as a possible therapeutic procedure.

Adolescent↗
PubMed2006

Comparison of the microsatellite instability analysis system and the Bethesda panel for the determination of microsatellite instability in colorectal cancers.

Microsatellite instability (MSI) analysis of colorectal cancers is clinically useful to identify patients with hereditary nonpolyposis colorectal cancer (HNPCC) caused by germline mutations of mismatch repair genes. MSI status may also predict cancer response/resistance to certain chemotherapies. We evaluated the MSI Analysis System (Promega Corp.; five mononucleotide and two pentanucleotide repeats) and compared the results to the Bethesda panel, which interrogates five microsatellite loci recommended by the 1997 National Cancer Institute-sponsored MSI workshop (three dinucleotide and two mononucleotide repeats). Thirty-four colorectal cancers were analyzed by both assays. The overall concordance between the two assays was 85% (29 of 34). There was complete concordance between the two assays for all of the MSI-high (11 of 11) and microsatellite stable (MSS; 18 of 18) cases. In the 11 MSI-high cases, all 5 of the mononucleotide loci in the MSI Analysis System demonstrated shifted alleles (100% sensitivity), and each shift resulted in products that were smaller in size than the germline alleles. All (5 of 5) of the cases interpreted as MSI-low by the Bethesda assay were interpreted as MSS by the MSI Analysis System. Our results suggest that the MSI Analysis System is generally superior and may help resolve cases of MSI-low into either MSI-high or MSS.

Case-Control Studies↗
PubMed1992

[Multi-directional instability of the shoulder; e new form of chronic shoulder instability].

This article describes multidirectional shoulder instability. This lesion is not rare and is easily overlooked. MDI is often caused by repeated minor injuries in athletic patients. The basic lesion in MDI is an enlarged joint volume. The diagnosis is based on the clinical picture. The sulcus sign is pathognomonic. Conservative treatment is the treatment of first choice. If complaints persist after one year of conservative treatment, a capsular shift as described by Neer is recommended.

Adolescent↗
PubMed2003

Low-level microsatellite instability colorectal carcinomas: do they really belong to a "gray zone" between high-level microsatellite instability and microsatellite-stable cancers?

BACKGROUND AND AIMS: Colorectal carcinomas demonstrating low-level microsatellite instability (MSI-L) may form a distinct group differing both from high-level MSI (MSI-H) and microsatellite-stable (MSS) tumors. MATERIALS AND METHODS: In a retrospective series of 172 colorectal carcinomas the microsatellite status was examined based on DNA extracted from archival blocks. Three groups - MSS ( n=100), MSI-L ( n=37), MSI-H ( n=35) - were compared with respect to clinical data, stage, histology, and immunoexpression of Ki-67, and P53. RESULTS: Compared to MSS and MSI-H carcinomas the MSI-L tumors were exceptionally rarely right-sided, and demonstrated the lowest proliferation fraction. There was a trend for less frequent high-grade histology, more frequent intermediate P53 expression, and prominent mucinous histology. CONCLUSION: Features of MSI-L colorectal carcinomas are not necessarily located between their MSS and MSI-H counterparts. The MSI-L category may contain a group of tumors belonging to a distinct carcinogenetic pathway.

Carcinoma↗
PubMed2004

Organizational instability and cardiovascular risk factors in white-collar employees: an analysis of correlates of structural instability of workplace organization on risk factors for coronary heart disease in a sample of 3,904 white collar employees in the Stockholm region.

BACKGROUND: The economic crisis in Sweden in the 1990s led to major reorganization at many workplaces, which appears to have had negative consequences for occupational and public health. METHODS: Psychosocial questionnaires and medical screening data for 3,904 white-collar employees in 15 major companies plus a large number of small-scale entrepreneurs in Stockholm were used. Subjects were part of a study of working conditions and cardiovascular risk factors (WOLF). Workplaces were categorized using interview data from managers and union representatives. Categories were compared regarding job strain, blood pressure, serum cholesterol, triglycerides, and fibrinogen among employees. RESULTS: The companies formed five categories: 'Stable', 'Changing/Growing', 'Threatened Private', 'Questioned Public', plus 'Small Firms'. Compared with the 'Stable' group, employees in 'Changing/Growing' companies had higher job strain (0.28 SD, p<0.001). In the 'Threatened Private' group, job strain (0.30 SD, p<0.001), cholesterol (0.18 mmol/l, p<0.05) and triglycerides (0.09 mmol/l, p<0.05) were elevated. The 'Questioned Public' group had higher cholesterol (0.22 mmol/l, p<0.01), triglycerides (0.10 mmol/l, p<0.01) and fibrinogen (0.13 mmol/l, p<0.05). In 'Small Firms', job strain (0.30 SD, p<0.001), cholesterol (0.28 mmol/l, p<0.001), triglycerides (0.14 mmol/l, p<0.001) and fibrinogen (0.19 mmol/l, p<0.001) were elevated. With the exception of lower systolic blood pressure (2.1 mmHg; p<0.05) in the 'Changing/Growing' category, there were no significant differences in blood pressure between the groups. CONCLUSION: In addition to traditional measures of organizational instability, such as downsizing, expansion in a favourable economic climate, appears to be adversely correlated with job strain and psychophysiology. The study also raises concerns about employees in small firms.

Adult↗
PubMed1993

Non-invasive diagnosis of bladder instability using the Bladder Instability Discriminant Index (BIDI).

The purpose of this study was to validate prospectively the BIDI index in the non-invasive diagnosis of bladder instability, as a procedure for clinical evaluation in primary health care of women. 217 patients were studied; 82 with stress incontinence, 39 with urge incontinence and 96 with both symptoms. All patients were studied by specialist physicians, who conducted a clinical evaluation, questionnaire, gynecological and urological examination, stress test, urodynamic assessment and a 7 day frequency/volume study, recording each intake and micturition; data that were used to calculate the BIDI index. The results obtained through the application of the BIDI were compared with the corresponding urodynamic diagnoses, achieving 88% sensitivity and 83% specificity. The use of the BIDI index is suggested as a non-invasive clinical diagnostic method, of low cost and simple performance. It is recommended for treatment control and for taking diagnostic and therapeutic decisions in medical centres lacking proper urodynamic equipment.

Adult↗
PubMed2001

Thermal capsulorrhaphy for instability of the shoulder: multidirectional and posterior instabilities.

Early results of thermal capsulorrhaphy appear to be favorable and the procedure seems safe when used appropriately to enhance shoulder stability, either in isolation or combination with other arthroscopic procedures. Basic science research has shown that the capsular response to thermal energy and its effect on the mechanical properties of the tissue is dependent on both time and temperature. Additional work is needed to better understand the tissue's healing response and the time required to restore its mechanical properties. Although short-term results are encouraging, longer-term follow-up and studies cited in peer-reviewed publications are needed.

Arthroscopy↗