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At least 19 recordsLinked to original sources
PubMed2006

Circulating MMP2 and MMP9 in breast cancer -- potential role in classification of patients into low risk, high risk, benign disease and breast cancer categories.

Matrix metalloproteinase (MMP) 2 and 9 are involved in cancer invasion and metastasis, and increased levels occur in serum and plasma of breast cancer (BC) patients. It is, however, unclear whether changes in serum levels can be exploited for early detection or classification of patients into different risk/disease categories. In our study, we measured concentration and activity of MMP2/9 in sera of 345 donors classified as low risk (Gail score <1.7), high risk (HR) (Gail score > or =1.7), benign disease or BC. Kruskal-Wallis and Mann-Whitney nonparametric tests showed that total-MMP2 concentration is higher in HR compared to control (p = 0.012), benign (p = 0.001) and cancer (p = 0.007). Active MMP2 (aMMP2) concentration is higher in control than benign and cancer (p < 0.001, respectively). Total and aMMP9 concentrations are higher in cancer than benign (p < 0.001, p = 0.002, respectively). Total-MMP2 and total-MMP9 activities are lower in control than benign (p < 0.001, p = 0.002, respectively) and cancer (p < 0.001, respectively). Total-MMP2 and MMP9 activities are also higher in cancer than benign (p = 0.004, p < 0.001) and HR (p = 0.008, p = 0.007, respectively). These results were not affected by age or inclusion/exclusion of donors with noninvasive cancer or atypical hyperplasia. Linear discriminant analysis revealed that HR donors are characterized by lower total-MMP2 and higher aMMP2. Overall group classification accuracy was 64.5%. Independent validation based on the leave-one-out cross validation approach gave an overall classification of 63%. Our study provides evidence supporting the potential role of serum MMP2/9 as biomarkers for breast disease classification.

Adult↗
PubMed2006

High risk plaque, high risk patient or high risk procedure?

SAPPHIRE, a randomised trial of endarterectomy versus angioplasty in 'high-risk' patients, concluded that angioplasty was 'not inferior' to surgery. This has subsequently been translated to mean that angioplasty was 'preferable' or 'advisable' in patients considered high-risk for surgery, with no further discrimination between symptomatic and asymptomatic individuals. Moreover, there have been suggestions that the accepted procedural risks may have to be increased in these patients. In fact, 71% of patients in SAPPHIRE were asymptomatic in whom there was an average 6% 30-day death/stroke rate. At this level of risk, neither surgery nor angioplasty could ever prevent long-term stroke. The concept of identifying high-risk patients is laudable, but they should be high risk for stroke (i.e. symptomatic). There is currently little systematic evidence to include asymptomatic patients within this definition.

Angioplasty↗
PubMed2003

Non-traditional drug targets: high risk, high reward.

Genomics and proteomics have unveiled a plethora of protein-protein interactions that may control cellular processes involved in disease development. Many of these interactions involve non-traditional candidate targets (i.e., neither enzymes nor cell surface receptors/channels). To date, non-traditional targets have largely been ignored by the pharmaceutical industry or have failed to lead to drugs. This review focuses on the use of transdominant genetically encoded agents and specialized small-molecule drugs to explore this void.

Amino Acid Sequence↗
PubMed2001

Low risk and high risk human papillomaviruses (HPVs) and cervical cancer in Zimbabwe: epidemiological evidence.

OBJECTIVE: To establish the prevalence of detectable low-risk and high-risk, oncogenic HPV types in cervical swabs of women with histologically proven cancer of the cervix. DESIGN: Cross sectional study. SETTING: Harare Central and Parirenyatwa Hospitals. SUBJECTS: 119 women with histologically proven cervical cancer of whom 63 had the degree of differentiation of the tumour reported. MAIN OUTCOME MEASURES: Frequency of infection with high and low-risk human papillomaviruses. RESULTS: The presence of HPV DNA was demonstrated in 63% (75/119) of cases. Low risk HPVs were present in 26% (31/119) and high-risk HPVs were demonstrated in 51% (61/119) of samples tested. Co-infection with both low-risk and high-risk HPVs was observed in 14% (17/119) of the specimens. High-risk HPVs were detected in 55% (21/38) of poorly differentiated tumours while 60% (15/25) of moderately and well-differentiated tumours showed the presence of high-risk HPVs. CONCLUSION: High-risk human papillomaviruses are associated with cervical cancer. There was no significant difference in the frequency of high-risk HPV types in women with moderately to well-differentiated tumours and those with poorly-differentiated tumours.

Adult↗
PubMed2002

Development of a method to identify seniors at high risk for high hospital utilization.

BACKGROUND: A small percentage of older persons account for most Medicare costs. If persons at high risk for high health care utilization can be identified, resources can be directed to improve their health care and reduce utilization. OBJECTIVE: To develop an efficient and economical approach to identifying older persons at risk for high future health care utilization. DESIGN: Validation cohort. SETTING: Three communities. SUBJECTS: Five thousand one hundred thirty-eight community-dwelling persons aged 71 years or older. MAIN OUTCOME MEASURES: High utilization (defined as >or=11 hospital days during 3 years) and overall Part A Medicare hospital costs during 3 years. RESULTS: Predictive multivariable models were created that relied on prior hospitalization only, self-report only, and combined self-report and physical examination/lab data. Ten self-report items (hospitalizations in prior year and year before that, male gender, fair/poor health, not working, infrequent religious participation, needing help bathing, unable to walk 1/2 mile, diabetes, and taking loop diuretics) and two lab tests (low serum albumin and iron) remained as independent predictors of high utilization. Based upon these variables, approximately 1/4 of the population was identified as being at high risk (>or=0.28 probability) for high health care utilization and those identified accounted for approximately half of all Medicare Part A costs for the entire population. Finally, a two-phase strategy was developed in which tests are only administered to individuals whose risk cannot be adequately determined by self-report variables (approximately 1/4 of subjects). CONCLUSIONS: Simple questions and laboratory tests can accurately and efficiently identify seniors at high risk for high health care utilization.

Aged↗
PubMed1998

Prognostic risk factors that identify patients with clinical stage I nonseminomatous germ cell tumors at low risk and high risk for metastasis.

BACKGROUND: The purpose of this study was to develop a reliable model to identify clinical Stage I nonseminomatous germ cell tumors (NSGCTs) associated with low risk or high risk for occult retroperitoneal metastasis, so that the model could be used to customize the therapeutic approach for patients with these tumors. The model was to be based on pathohistologic parameters and immunohistochemical expression of proliferation markers, proteases, and adhesion molecules in the primary tumor. METHODS: One hundred forty-nine patients with clinical Stage I NSGCTs underwent retroperitoneal lymphadenectomy and were included in the study. Three to five paraffin embedded, formalin fixed tissue blocks were available from each patient and were analyzed for the following histopathologic features associated with pathologic Stage I or II disease: the presence or absence of vascular invasion (VI), the presence or absence of tunic invasion, and the percentage of each histologic type present in the primary tumor. Immunohistochemical expression of MIB-1, p53, bcl-2, cathepsin D, and E-cadherin was evaluated using a semiquantitative scoring system. Statistical analysis was performed with univariate and multivariate logistic regression models. RESULTS: The percentage of embryonal carcinoma (%EC, P < 0.001) and the presence of VI (P < 0.0001) and tunic invasion (P < 0.002) were the most significant independent risk factors associated with pathologic Stage II disease. A combination of %EC and VI allowed correct prediction of final pathologic stage for 88% of clinical Stage I patients. Cutoff values including both variables identified the correct pathologic stage for 131 of 149 patients (88%). Less than 45% EC and the absence of VI correctly identified pathologic Stage I disease in 91.5% of patients; more than 80% EC and the presence of VI correctly predicted pathologic Stage II in 88%. In univariate analysis, only p53 (P < 0.03) and E-cadherin (P < 0.001) expression were significantly different in the embryonal carcinoma component of pathologic Stage I and II NSGCT. To evaluate prospectively the clinical utility of the new derived cutoff points, the data were applied to 10 consecutive patients with clinical Stage I NSGCT who underwent retroperitoneal lymphadenectomy; pathologic Stage I and II were correctly predicted for 5 of 6 Stage I and 4 of 4 Stage II patients, respectively. CONCLUSIONS: %EC and the presence or absence of VI appear to be reliable prognosticators to identify patients at high risk and low risk for occult retroperitoneal disease. In cases of clinical Stage I NSGCT, p53, bcl-2, MIB-1, cathepsin D, and E-cadherin did not appear to be of prognostic significance. The authors recommend that all patients with clinical Stage I NSGCT have their primary orchiectomy specimens evaluated for %EC and the presence of VI to determine their risk for occult retroperitoneal metastasis.

Antigens, Nuclear↗
PubMed1997

Maternal directive and facilitative interaction styles: associations with language and cognitive development of low risk and high risk toddlers.

The purpose of this study was to examine the relation of maternal interaction styles to the development of a sample of 56 toddlers (19 low risk, 37 high risk) seen at 12 and 24 months of age. At 12 months, videotapes of mother-child interaction were coded for directiveness, sensitivity, and elaborativeness. At 12 and 24 months, cognitive and language measures were collected. A directive maternal style was negatively correlated with sensitivity and elaborativeness, whereas sensitive and elaborative ratings were positively correlated, suggesting a facilitative style. Regression models significantly predicted receptive language and cognitive development at 24 months but not expressive language. Maternal directiveness at 12 months was negatively relative to later receptive language skills, whereas elaborativeness at 12 months was positively predictive of later cognitive development. Child status variables and maternal interactional styles contributed about equally to the prediction of later cognitive and language outcomes.

Child Language↗
PubMed1990

Lack of concordance in classification of coronary heart disease risk: high-risk HDL cholesterol less than 35 mg/dl in subjects with desirable total serum cholesterol, less than 200 mg/dl.

In using National Cholesterol Education Program guidelines (for desirable low risk, a total cholesterol level less than 200 mg/dl, and for high risk, a level of high-density lipoprotein cholesterol (HDLC) less than 35 mg/dl), our specific aim was to examine lack of concordance in classification of coronary heart disease (CHD) risk by HDLC less than 35 mg/dl in subjects with total cholesterol less than 200 and to determine whether lack of concordance increased as group CHD risk increased. We studied four cohorts ranging from putatively low to high CHD risk. These included self-referred subjects in a public urban total cholesterol screening (n = 897), hospitalized patients with depression (n = 144), Cholesterol Center referrals at presumed high CHD risk (n = 1120), and patients having coronary arteriography (n = 145) because of presumed coronary artery disease. Total cholesterol was less than 200 mg/dl in 25% of subjects from the urban sampling, in 54% of hospitalized patients with depression, in 27% of Cholesterol Center referrals, and in 41% of those undergoing cardiac catheterization. In these four cohorts, of subjects with total cholesterol less than 200, 7%, 26%, 25%, and 48%, respectively, had HDLC less than 35 mg/dl. The likelihood of having total cholesterol less than 200 and HDLC less than 35 mg/dl was 1.7% in urban public subjects, 6.8% in Cholesterol Center referrals, 13.9% in depressed patients, and 20% in cardiac catheterization patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol↗
PubMed1993

[Tumor-like and preneoplastic lesions as well as low risk and high risk urothelial tumors].

In its first part the review deals with all known hyperplastic, metaplastic as well as dysplastic urothelial changes and discusses their possible preneoplastic nature. The various changes are classified as indirect, facultative and obligatory premalignant lesions. In its second part, the review considers the tumor-like growths. In particular, it focuses on the pseudotumorous effects of various urocystitis types, postoperative spindle cell pseudosarcoma, glandular and nephrogenic metaplasias, malakoplakia and some tissue heterotopias and malformations. In its last part, the review critically compares the classification principle of the urothelial neoplasias into low-risk and high-risk tumors with other tumor classifications (superficial carcinoma/low-grade and high-grade tumors). The significance of recent study results for assessing the risk of urothelial carcinomas is discussed.

Carcinoma, Transitional Cell↗
PubMed1998

Are MAO-A deficiency states in the general population and in putative high-risk populations highly uncommon?

Lack of monoamine oxidase A (MAO-A) due to either Xp chromosomal deletions or alterations in the coding sequence of the gene for this enzyme are associated with marked changes in monoamine metabolism and appear to be associated with variable cognitive deficits and behavioral changes in humans and in transgenic mice. In mice, some of the most marked behavioral changes are ameliorated by pharmacologically-induced reductions in serotonin synthesis during early development, raising the question of possible therapeutic interventions in humans with MAO deficiency states. At the present time, only one multi-generational family and a few other individuals with marked MAO-A deficiency states have been identified and studied in detail. Although MAO deficiency states associated with Xp chromosomal deletions were identified by distinct symptoms (including blindness in infancy) produced by the contiguous Norrie disease gene, the primarily behavioral phenotype of individuals with the MAO mutation is less obvious. This paper reports a sequential research design and preliminary results from screening several hundred volunteers in the general population and from putative high-risk groups for possible MAO deficiency states. These preliminary results suggest that marked MAO deficiency states are very rare.

Adolescent↗
PubMed2002

Biological and clinical significance of cytogenetic abnormalities in low-risk and high-risk gastrointestinal stromal tumors.

We report cytogenetic findings in 19 c-Kit-positive gastrointestinal stromal tumors (GISTs) that represent a heterogenous group of mesenchymal neoplasms with respect to site, histology, and biologic behavior. All of the GISTs (5 low-risk, 11 high-risk, 3 recurrences) displayed clonal chromosomal aberrations; 15 were hypo- to near-diploid, and 4 were near-triploid and hypotetraploid. The most common abnormalities were loss of chromosomes 14 and/or 22, demonstrated in 14 GISTs irrespective of site or predominant phenotype. Ten cases (2 low-risk, 5 high-risk, 3 recurrences) were characterized by loss of both chromosomes 14 and 22, 2 cases (1 low-risk, 1 high- risk), by loss of chromosome 14; and 2 high-risk cases, by loss of chromosome 22. Additional chromosomal aberrations occurred preferentially in high-risk and recurrent GISTs, including loss of 9p and 1p in 8 cases each, loss of 15 in 6 cases, loss of 3p in 5 cases, loss of 13q and 10q in 4 cases each, loss of 19 in 3 cases, and complete or partial gains of chromosomes 5 and 4 in 2 cases each. More significantly, 5 of 6 patients with clinically aggressive GISTs, including 2 recurrences and 3 metastasing GISTs, were additionally characterized by loss of 9p; four of these had additional loss of chromosomes 1p and 15. The presented results herein indicate that loss of chromosome 14 and/or 22 is an early change in GIST tumorigenesis irrespective of site or differentiation, whereas malignant transformation and progression of GISTs appear to be associated with an increasing incidence of additional secondary aberrations.

Adult↗
PubMed1984

Guidelines for high risk or potentially high risk autopsy cases.

These excellent procedures are in use at the author's institution, and are published here for the benefit of those who have not instituted their own, which is a deficiency found frequently at CAP inspections. The CAP is in the process of developing formal recommendations which will be published at a later date.

Autopsy↗
PubMed1980

High-risk neighborhoods and high-risk families: the human ecology of child maltreatment.

Based on multiple regression analysis to identify the socioeconomic, demographic, and attitudinal correlates of neighborhood differences in the rate of child abuse and neglect, a pair of neighborhoods matched for socioeconomic level was selected, one high risk, the other low risk. Interviews with expert informants ranging from elementary school principals to mailmen were used to develop neighborhood profiles. Samples of families were drawn from each neighborhood and interviews conducted to identify stresses and supports, with special emphasis on sources of help, social networks, evaluation of the neighborhood, and use of formal family support systems. The results lend support to the concept of neighborhood "risk." Families in the high-risk neighborhood, though socioeconomically similar to families in the low-risk neighborhood, report less positive evaluation of the neighborhood as a context for child and family development. Furthermore, they reveal a general pattern of "social impoverishment" in comparison with families in the low-risk neighborhood.

Adolescent↗