Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 33
Filter
1.
J Child Fam Stud ; 29(4): 1044-1054, 2020 Apr.
Article in English | MEDLINE | ID: mdl-33456296

ABSTRACT

OBJECTIVES: Adolescent girls with emotional and behavioral difficulties (EBDs) have a heightened risk of negative sexual health, including HIV, other sexually transmitted infections (STIs), and unplanned pregnancy. Few evidence-based sexual health interventions are available for adolescent girls with EBDs. This study tested the feasibility, acceptability, and efficacy of a brief, online sexual health program called HEART (Health Education and Relationship Training). METHODS: Forty-seven participants (M-age = 15.79; SD = 1.71; 62% Black, 23% Hispanic) recruited from community-based organizations in the southeastern U.S. were compared to a non-equivalent comparison group who received an attention-matched intervention. RESULTS: Findings support the feasibility of participant recruitment and program administration in community-based settings. Participants completed HEART in 44 minutes and experienced few technological difficulties. HEART was highly acceptable: most participants liked, learned from, and were engaged with the program. Further, 92% would recommend HEART to a friend and 98% would use what they learned in the future. At posttest, intervention participants had significantly higher communication intentions, communication skills, STI/HIV knowledge, sexual self-efficacy, condom attitudes, and condom norms than the comparison group (ps < .003; effect size ds = .38-1.65). Significant improvement in condom intentions was observed when comparing pretest to posttest scores among intervention participants only, t(46) = -3.21, d = 0.47. CONCLUSIONS: Findings support the feasibility, acceptability, and efficacy of HEART among adolescent girls with EBDs in community-based settings. This study also addresses the growing need for research into the transferability of sexual health interventions to facilitate evidence-based decision-making about program dissemination and implementation.

2.
Psychol Med ; 47(7): 1179-1191, 2017 May.
Article in English | MEDLINE | ID: mdl-27998319

ABSTRACT

BACKGROUND: The public health, public safety and clinical implications of violent events among adults with mental illness are significant; however, the causes and consequences of violence and victimization among adults with mental illness are complex and not well understood, which limits the effectiveness of clinical interventions and risk management strategies. This study examined interrelationships between violence, victimization, psychiatric symptoms, substance use, homelessness and in-patient treatment over time. METHOD: Available data were integrated from four longitudinal studies of adults with mental illness. Assessments took place at baseline, and at 1, 3, 6, 9, 12, 15, 18, 24, 30 and 36 months, depending on the parent studies' protocol. Data were analysed with the autoregressive cross-lag model. RESULTS: Violence and victimization were leading indicators of each other and affective symptoms were a leading indicator of both. Drug and alcohol use were leading indicators of violence and victimization, respectively. All psychiatric symptom clusters - affective, positive, negative, disorganized cognitive processing - increased the likelihood of experiencing at least one subsequent symptom cluster. Sensitivity analyses identified few group-based differences in the magnitude of effects in this heterogeneous sample. CONCLUSIONS: Violent events demonstrated unique and shared indicators and consequences over time. Findings indicate mechanisms for reducing violent events, including trauma-informed therapy, targeting internalizing and externalizing affective symptoms with cognitive-behavioral and psychopharmacological interventions, and integrating substance use and psychiatric care. Finally, mental illness and violence and victimization research should move beyond demonstrating concomitant relationships and instead focus on lagged effects with improved spatio-temporal contiguity.


Subject(s)
Crime Victims/statistics & numerical data , Hospitalization/statistics & numerical data , Ill-Housed Persons/statistics & numerical data , Mental Disorders/epidemiology , Violence/statistics & numerical data , Adult , Humans , Mental Disorders/therapy
3.
J Thromb Haemost ; 13(3): 398-408, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25495610

ABSTRACT

BACKGROUND: Post-thrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT). OBJECTIVE: In the BioSOX study, we investigated whether inflammation markers predict the risk of PTS after DVT. METHODS: We measured C-reactive protein (CRP), ICAM-1, interleukin (IL)-6, and IL-10, at baseline, and 1 month and 6 months after a first proximal DVT, among 803 participants in the SOX trial. Participants were prospectively followed for 24 months for development of PTS. RESULTS: Median CRP levels at 1 month, ICAM-1 levels at baseline, 1 month and 6 months, IL-6 levels at 1 month and 6 months and IL-10 levels at 6 months were higher in patients who developed PTS than in those who did not. Multivariable regression with the median as a cutoff showed risk ratios (RRs) for PTS of 1.23 (95% confidence interval [CI] 1.05-1.45) and 1.25 (95% CI 1.05-1.48) for ICAM-1 at 1 month and 6 months, respectively, and 1.27 (95% CI 1.07-1.51) for IL-10 at 6 months. Quartile-based analysis demonstrated a dose-response association between ICAM-1 and PTS. ICAM-1 and IL-10 were also associated with PTS severity. Analysis of biomarker trajectories after DVT demonstrated an association between the highest-trajectory group of ICAM-1 and PTS. CONCLUSIONS: In this prospective study, ICAM-1 over time was most consistently associated with the risk of PTS. Further study is required to confirm these findings and assess their potential clinical relevance.


Subject(s)
Inflammation Mediators/blood , Intercellular Adhesion Molecule-1/blood , Postthrombotic Syndrome/etiology , Venous Thrombosis/blood , Adult , Aged , Biomarkers/blood , C-Reactive Protein/metabolism , Canada , Chi-Square Distribution , Female , Follow-Up Studies , Humans , Interleukin-10/blood , Interleukin-6/blood , Linear Models , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Postthrombotic Syndrome/diagnosis , Postthrombotic Syndrome/prevention & control , Prospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Stockings, Compression , Time Factors , Treatment Outcome , United States , Venous Thrombosis/complications , Venous Thrombosis/diagnosis , Venous Thrombosis/therapy
4.
Thromb Haemost ; 112(6): 1137-41, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25183442

ABSTRACT

Acute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30-40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.


Subject(s)
Acute Pain/therapy , Lower Extremity/blood supply , Stockings, Compression , Venous Thrombosis/therapy , Acute Pain/diagnosis , Acute Pain/etiology , Adult , Aged , Canada , Equipment Design , Female , Humans , Male , Middle Aged , Pain Measurement , Postthrombotic Syndrome/etiology , Postthrombotic Syndrome/prevention & control , Severity of Illness Index , Time Factors , Treatment Outcome , United States , Venous Thrombosis/complications , Venous Thrombosis/diagnosis
5.
J Thromb Haemost ; 9(12): 2397-405, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21951970

ABSTRACT

BACKGROUND: Few studies have evaluated the long-term economic consequences of deep vein thrombosis (DVT). None of them have incorporated prospectively collected clinical data to ensure accurate identification of incident cases of DVT and DVT-related health outcomes of interest, such as post-thrombotic syndrome (PTS). OBJECTIVES: To prospectively quantify medical and non-medical resource use and costs related to DVT during 2 years following diagnosis, and to identify clinical determinants of costs. METHODS: Three hundred and fifty-five consecutive patients with acute DVT were recruited at seven Canadian hospital centers. Resource use and cost information were retrieved from three sources: weekly patient-completed cost diaries, nurse-completed case report forms, and the Quebec provincial administrative healthcare database (RAMQ). RESULTS: The rate of DVT-related hospitalization was 3.5 per 100 patient-years (95% confidence interval [CI] 2.2-4.9). Patients reported a mean (standard deviation) of 15.0 (14.5) physician visits and 0.7 (1.2) other healthcare professional visits. The average cost of DVT was $5180 (95% CI $4344-6017) in Canadian dollars, with 51.6% of costs being attributable to non-medical resource use. Multivariate analysis identified four independent predictors of costs: concomitant pulmonary embolism (relative increase in cost [RIC] 3.16; 95% CI 2.18-4.58), unprovoked DVT (RIC 1.65; 95% CI 1.28-2.13), development of PTS during follow-up (RIC 1.35; 95% CI 1.05-1.74), and management of DVT in the inpatient setting (RIC 1.79; 95% CI 1.33-2.40). CONCLUSIONS: The economic burden of DVT is substantial. The use of measures to prevent the occurrence of PTS and favoring outpatient care of DVT has the potential to diminish costs.


Subject(s)
Cost of Illness , Venous Thrombosis/economics , Adult , Aged , Canada , Female , Health Care Rationing , Humans , Male , Middle Aged , Prospective Studies
6.
J Thromb Haemost ; 8(10): 2169-75, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20670369

ABSTRACT

BACKGROUND: The pathophysiology of post-thrombotic syndrome (PTS) is postulated to involve persistent venous obstruction and venous valvular reflux. OBJECTIVE: To study the association between D-dimer level, valvular reflux and the PTS in a well-defined cohort of deep vein thrombosis (DVT) patients. METHODS: Consecutive patients with acute symptomatic DVT were recruited at eight centers and were followed for 24months. D-dimer was measured at 4months. A standardized ultrasound assessment for popliteal valvular reflux was performed at 12months. Using the Villalta scale, patients were assessed for PTS during follow-up by evaluators who were unaware of D-dimer or reflux results. RESULTS: Three hundred and eighty-seven patients were recruited; of these, 305 provided blood samples for D-dimer and 233 had a 12-month reflux assessment. PTS developed in 45.1% of subjects. Mean D-dimer was significantly higher in patients with vs. without PTS (712.0 vs. 444.0µgL(-1) ; P=0.02). In logistic regression analyses adjusted for warfarin use at the time of D-dimer determination and risk factors for PTS, D-dimer level significantly predicted PTS (P=0.03); when stratifying for warfarin use at the time of blood draw, adjusted odds ratio (OR) for developing PTS per unit difference in log D-dimer was 2.33 (95% CI 0.89, 6.10) in those not on warfarin vs. 1.25 (95% CI 0.87, 1.79) in those on warfarin. Ipsilateral reflux was more frequent in patients with moderate-to-severe PTS than in patients with mild PTS (65% vs. 40%, respectively; P=0.01) and was independently associated with moderate-to-severe PTS in logistic regression analyses (P=0.01). CONCLUSION: D-dimer levels, measured 4months after DVT in patients not on warfarin, are associated with subsequent development of PTS. Venous valvular reflux is associated with moderate-to-severe PTS.


Subject(s)
Fibrin Fibrinogen Degradation Products/biosynthesis , Postthrombotic Syndrome/blood , Venous Insufficiency/blood , Venous Insufficiency/complications , Venous Thrombosis/blood , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Odds Ratio , Postthrombotic Syndrome/complications , Prospective Studies , Risk Factors , Venous Thrombosis/complications
7.
Prev Vet Med ; 93(2-3): 201-10, 2010 Feb 01.
Article in English | MEDLINE | ID: mdl-19926150

ABSTRACT

Healthcare research recognizes that 'satisfaction' is an important health outcome of the medical encounter. As a result, many healthcare professions have pursued the development and validation of instruments for measuring patient satisfaction. However, veterinary medicine has developed and properly validated few instruments for measuring client satisfaction. This paper describes the development and psychometric assessment of an instrument for measuring appointment-specific client satisfaction in companion-animal practice. We developed the Client Satisfaction Questionnaire (CSQ) in four main phases. Phase I relied on a series of six pet-owner focus groups (n=32) to explore clients' expectations of veterinary care to provide a basis for constructing items for the CSQ. Phase II involved developing items for a first draft of the CSQ, using the content and themes taken from the pet-owner focus groups. In phase III we pre-tested the first draft with six veterinarians in companion-animal practice and a convenience sample of their clients (n=129). Data from the pre-test were used to test the initial psychometric characteristics of each item. Together with participant feedback, these findings were used to design the final, 15-item CSQ. Phase IV involved psychometrically testing the final, 15-item CSQ as part of a larger observational study involving 20 veterinarians and 344 of their clients. We used data from this sample to assess the reliability and validity of the CSQ in companion-animal practice. Assessment was based on descriptive statistics, principal-component analysis, generalizability theory and linear mixed modeling. Findings demonstrate excellent reliability (G-coefficient for internal consistency=0.96) and support the face, content and construct validity of the CSQ as a measure of appointment-specific client satisfaction in companion-animal practice.


Subject(s)
Consumer Behavior , Surveys and Questionnaires/standards , Veterinary Medicine/standards , Adult , Aged , Animals , Cats , Dogs , Female , Focus Groups , Humans , Linear Models , Male , Middle Aged , Psychometrics , Reproducibility of Results , Sensitivity and Specificity , Young Adult
8.
J Thromb Haemost ; 6(7): 1105-12, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18466316

ABSTRACT

BACKGROUND/OBJECTIVES: We prospectively measured change in quality of life (QOL) during the 2 years after a diagnosis of deep vein thrombosis (DVT) and evaluated determinants of QOL, including development of the post-thrombotic syndrome (PTS). PATIENTS/METHODS: Consecutive patients with acute DVT were recruited from 2001 to 2004 at eight hospitals in Canada. At study visits at baseline, and 1, 4, 8, 12 and 24 months, clinical data were collected, standardized PTS assessments were performed, and QOL questionnaires were self-completed. Generic QOL was measured using the Short-Form Health Survey-36 (SF-36) questionnaire. Venous disease-specific QOL was measured using the Venous Insufficiency Epidemiological and Economic Study (VEINES)-QOL/Sym questionnaire. The change in QOL scores over a 2-year follow-up was assessed. The influence of PTS and other characteristics on QOL at 2 years was evaluated using multivariable regression analyses. RESULTS: Among the 387 patients recruited, the average age was 56 years, two-thirds were outpatients, and 60% had proximal DVT. The cumulative incidence of PTS was 47%. On average, QOL scores improved during follow-up. However, patients who developed PTS had lower scores at all visits and significantly less improvement in QOL over time (P-values for PTS*time interaction were 0.001, 0.012, 0.014 and 0.006 for PCS, MCS, VEINES-QOL and VEINES-Sym). Multivariable regression analyses showed that PTS (P < 0.0001), age (P = 0.0009), proximal DVT (P = 0.01) and inpatient status (P = 0.04) independently predicted 2-year SF-36 PCS scores. PTS alone independently predicted 2-year VEINES-QOL (P < 0.0001) and VEINES-Sym (P < 0.0001) scores. CONCLUSIONS: Development of PTS is the principal determinant of health-related QOL 2 years after DVT. Our study provides prognostic information on patient-reported outcomes after DVT and emphasizes the need for effective prevention and treatment of the PTS.


Subject(s)
Quality of Life , Venous Thrombosis/complications , Venous Thrombosis/psychology , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postthrombotic Syndrome/diagnosis , Postthrombotic Syndrome/etiology , Prognosis , Prospective Studies , Surveys and Questionnaires , Venous Thrombosis/drug therapy
9.
Osteoarthritis Cartilage ; 16(10): 1183-91, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18403221

ABSTRACT

OBJECTIVE: Cartilage degradation in osteoarthritis (OA) generates the type II collagen fragments, Helix-II and CTX-II that can be used as clinical biological markers. Helix-II and C-telopeptide of type II collagen (CTX-II) levels are associated independently with progression of OA suggesting that they may be generated through different collagenolytic pathways. In this study we analyzed the release of Helix-II and CTX-II from human cartilage collagen by the proteinases reported to play a role in cartilage degradation. METHODS: In vitro, human articular cartilage extract was incubated with activated human recombinant cathepsins (Cats) and matrix-metalloproteases (MMPs). Next, we analyzed the spontaneous release of Helix-II and CTX-II from cartilage sections of patients with knee OA who were immediately deep frozen after joint replacement to preserve endogenous enzyme activity until assay. Cartilage sections were then incubated for up to 84 h in the presence or absence of E-64 and GM6001, inhibitors of cysteine proteases and MMPs, respectively. RESULTS: In vitro, Cats K, L and S generated large amount of Helix-II, but not CTX-II. Cat B generated CTX-II fragment, but destroyed Helix-II immunoreactivity. Cat D was unable to digest intact cartilage. MMPs-1, -3, -7, -9, and -13 efficiently released CTX-II, but only small amount of Helix-II. Neither CTX-II nor Helix-II alone was able to reflect accurately the collagenolytic activity of Cats and MMPs as reflected by the release of hydroxyproline. In OA cartilage explants, E-64 blunted the release of Helix-II whereas the release of CTX-II could be completely abrogated by GM6001 and only partly by E-64. CONCLUSION: These in vitro and ex vivo experiments of human cartilage suggest that Helix-II and CTX-II could be released in part by different enzymatic pathways. Helix-II and CTX-II alone reflect only partially overall cartilage collagen degradation. These findings may explain why these two biological markers could provide complementary information on disease progression in OA.


Subject(s)
Cartilage, Articular/pathology , Cathepsins/metabolism , Collagen Type II/metabolism , Matrix Metalloproteinases/metabolism , Osteoarthritis, Knee/pathology , Biomarkers/metabolism , Humans , Predictive Value of Tests
11.
Arch Sex Behav ; 29(4): 323-34, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10948722

ABSTRACT

Self-report measures of sexual violence that ask women whether they have experienced threats of physical violence have attracted criticism in recent years; detractors claim that these measures lead researchers to overestimate the prevalence of sexual violence. Our study explored this issue by collecting data on the prevalence of threats versus force in the context of sexual aggression. Female undergraduates at two universities (n1 = 69; n2 = 111) were asked about their experiences with sexual coercion using a revised version of the Sexual Experiences Scale (Koss and Gidycz, 1985). Four of the original items were modified to distinguish between sexual contact that occurred as a result of a perpetrator using physical force and sexual contact that occurred because a perpetrator threatened physical violence. Analyses of the revised items revealed that the use of physical force was at least as likely as threats and that for some types of sexual acts, physical force was actually more likely than verbal threats. Furthermore, prevalence figures for three of the four types of sexual acts considered were not significantly altered by collapsing threat of force with use of force. Implications for future research on women's experiences of sexual coercion are discussed.


Subject(s)
Coercion , Rape/statistics & numerical data , Sexual Behavior/psychology , Violence/psychology , Violence/statistics & numerical data , Adolescent , Adult , Coitus , Female , Humans , Male , Prevalence , Rape/psychology
12.
Electrophoresis ; 21(11): 2196-208, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10892730

ABSTRACT

Our preliminary results are reported in the investigation of the tyrosine phosphorylation cascade triggered by the stimulation of the insulin receptor in the adipocyte cell line 3T3-L1 using a mini two-dimensional gel electrophoresis approach. The minigel format, 8 x 10 cm, was found sufficiently resolving and reproducible to study complex biological samples while considerably increasing throughput and lowering costs compared to larger gel formats. Consequently, we used the minigel format to rapidly screen a large number of samples, of which only the most relevant were then analyzed by optimized, preparative two-dimensional gels. The accurate localization and relative quantification of tyrosine-phosphorylated proteins was performed using a nonradioactive triple labeling method. After transfer onto polyvinylidene difluoride (PVDF) membranes, proteins were stained with Sypro Ruby to verify the separation quality and to localize the general region of interest for immunostaining. The membranes were subsequently blocked with polyvinylpyrrolidone-40 and probed with the relevant antibodies for visualization of the phosphorylated proteins by chemiluminescence. Finally, membranes were stained with colloidal gold to obtain a pattern reminiscent of the silver staining of a polyacrylamide gel. We believe that the presented strategy can be generalized for any gel application in which a protein has to be detected and identified based on its immunoreactivity.


Subject(s)
Electrophoresis, Gel, Two-Dimensional/methods , Phosphoproteins/metabolism , Tyrosine/metabolism , 3T3 Cells , Animals , Mice , Phosphorylation , Signal Transduction
13.
Arch Intern Med ; 160(4): 512-6, 2000 Feb 28.
Article in English | MEDLINE | ID: mdl-10695691

ABSTRACT

BACKGROUND: In patients with a low clinical probability of pulmonary embolism (PE) and a nondiagnostic lung scan, the prevalence of PE is theoretically very low. We assessed the safety and usefulness of this association for ruling out PE. METHODS: We analyzed data from 2 consecutive cohort management studies performed in 2 university hospitals (Geneva University Hospital, Geneva, Switzerland, and Hospital Saint-Luc, Montreal, Quebec), which enrolled 1034 consecutive patients who came to the emergency department with clinically suspected PE. All patients were submitted to a sequential diagnostic protocol of lung scan, D-dimer testing, lower-limb venous compression ultrasonography (US), and pulmonary angiography in case of inconclusive results of noninvasive workup. RESULTS: The prevalence of PE was 27.6%. Empirical assessment was accurate for identifying patients with a low likelihood of PE (8.2% prevalence of PE in the low clinical probability category). One hundred eighty patients had a low clinical probability of PE and a nondiagnostic lung scan. Among these patients, US showed deep vein thrombosis in 5. Hence, PE could be ruled out by a low clinical probability, a nondiagnostic lung scan, and a normal US in 175 patients (21.5%). The 3-month thromboembolic risk in these patients was low (1.7%; 95% confidence interval, 0.4%-4.9%). CONCLUSIONS: Anticoagulant treatment could be safely withheld in patients with a low clinical probability of PE and a nondiagnostic lung scan, provided that the US is normal. This combination of findings avoided pulmonary angiography in 21.5% of patients with suspected PE in this series.


Subject(s)
Pulmonary Embolism/diagnosis , Adult , Aged , Angiography , Blood Gas Analysis , Cohort Studies , Diagnosis, Differential , Electrocardiography , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Physical Examination , Predictive Value of Tests , Pulmonary Embolism/blood , Pulmonary Embolism/diagnostic imaging , Risk , Risk Factors , Switzerland , Ultrasonography
15.
Biochem Pharmacol ; 58(12): 1859-67, 1999 Dec 15.
Article in English | MEDLINE | ID: mdl-10591140

ABSTRACT

We have shown previously that bis(N,N-dimethylhydroxamido)hydroxooxovanadate (DMHV) is an excellent reversible inhibitor of protein tyrosine phosphatase (PTP) in vitro. DMHV does not carry a charge under physiological pH conditions and is anticipated to permeate cell membranes more easily than vanadate. In the present study, the efficacy of DMHV as a PTP inhibitor in intact cells was compared with that of vanadate by measuring phosphotyrosine levels in various cells treated with these compounds. DMHV was more effective in increasing both the phosphotyrosine levels of various proteins in 3T3L1 fibroblasts and the level of insulin-receptor phosphorylation in CHO cells overexpressing the human insulin receptor. DMHV was about 10- to 20-fold more effective than vanadate in increasing glucose transport and glycogen synthesis in 3T3L1 adipocytes. DMHV, unlike vanadate, also inhibited PTP in Jurkat cells. The implications of these observations are discussed.


Subject(s)
Enzyme Inhibitors/pharmacology , Protein Tyrosine Phosphatases/antagonists & inhibitors , Vanadates/pharmacology , 3T3 Cells , Animals , Biological Transport/drug effects , CHO Cells , Cricetinae , Glucose/metabolism , Glycogen/biosynthesis , Humans , Jurkat Cells , Mice , Phosphotyrosine/metabolism , Receptor, Insulin/genetics , Receptor, Insulin/metabolism
16.
Lancet ; 353(9148): 190-5, 1999 Jan 16.
Article in English | MEDLINE | ID: mdl-9923874

ABSTRACT

BACKGROUND: We designed a simple and integrated diagnostic algorithm for acute venous thromboembolism based on clinical probability assessment of deep-vein thrombosis (DVT) or pulmonary embolism (PE), plasma D-dimer measurement, lower-limb venous compression ultrasonography, and lung scan to reduce the need for phlebography and pulmonary angiography. METHODS: 918 consecutive patients presenting at the emergency ward of the Geneva University Hospital, Geneva, Switzerland, and Hôpital Saint-Luc, Montreal, Canada, with clinically suspected venous thromboembolism were entered into a sequential diagnostic protocol. Patients in whom venous thromboembolism was deemed absent were not given anticoagulants and were followed up for 3 months. FINDINGS: A normal D-dimer concentration (<500 microg/L by a rapid ELISA) ruled out venous thromboembolism in 286 (31%) members of the study cohort, whereas DVT by ultrasonography established the diagnosis in 157 (17%). Lung scan was diagnostic in 80 (9%) of the remaining patients. Venous thromboembolism was also deemed absent in patients with low to intermediate clinical probability of DVT and a normal venous ultrasonography (236 [26%] patients), and in patients with a low clinical probability of PE and a non-diagnostic result on lung scan (107 [12%] patients). Pulmonary angiography and phlebography were done in only 50 (5%) and 2 (<1%) of the patients, respectively. Hence, a non-invasive diagnosis was possible in 866 (94%) members of the entire cohort. The 3-month thromboembolic risk in patients not given anticoagulants, based on the results of the diagnostic protocol, was 1.8% (95% CI 0.9-3.1). INTERPRETATION: A diagnostic strategy combining clinical assessment, D-dimer, ultrasonography, and lung scan gave a non-invasive diagnosis in the vast majority of outpatients with suspected venous thromboembolism, and appeared to be safe.


Subject(s)
Leg/blood supply , Pulmonary Embolism/diagnosis , Venous Thrombosis/diagnosis , Acute Disease , Algorithms , Ambulatory Care , Enzyme-Linked Immunosorbent Assay , Fibrin Fibrinogen Degradation Products/analysis , Humans , Lung/diagnostic imaging , Prospective Studies , Pulmonary Embolism/diagnostic imaging , Radionuclide Imaging , Risk Factors , Ultrasonography , Venous Thrombosis/diagnostic imaging
17.
Biochem J ; 337 ( Pt 2): 219-23, 1999 Jan 15.
Article in English | MEDLINE | ID: mdl-9882618

ABSTRACT

Peptides containing the non-hydrolysable phosphotyrosine analogue 4-[difluro(phosphono)methyl]phenylalanine [Phe(CF2P)] were synthesized and tested as inhibitors of the protein tyrosine phosphatases (PTPs) PTP1B, CD45, PTPbeta, LAR and SHP-1. We have identified peptides containing two adjacent Phe(CF2P) residues as potent inhibitors of PTPs. The tripeptide having the sequence Glu-Phe(CF2P)-Phe(CF2P) is a potent and selective inhibitor of PTP1B. This peptide inhibits PTP1B with an IC50 of 40 nM, which is at least 100-fold lower than with other PTPs. A second tripeptide, Pro-Phe(CF2P)-Phe(CF2P), is most potent against PTPbeta, with an IC50 of 200 nM, and inhibits PTP1B with an IC50 of 300 nM. These data suggest that it is possible to develop selective, active-site-directed, reversible, potent inhibitors of PTPs.


Subject(s)
Oligopeptides/pharmacology , Phenylalanine/analogs & derivatives , Protein Tyrosine Phosphatases/antagonists & inhibitors , Catalytic Domain/drug effects , ErbB Receptors/metabolism , Oligopeptides/chemical synthesis , Peptide Fragments/metabolism , Phenylalanine/pharmacology , Recombinant Proteins/antagonists & inhibitors
18.
J Biomol Screen ; 4(6): 327-334, 1999.
Article in English | MEDLINE | ID: mdl-10838430

ABSTRACT

A highly sensitive and continuous protein tyrosine phosphatase (PTPase) assay using 3,6-fluorescein diphosphate (FDP) is described. Leukocyte phosphatase CD45 (leukocyte common antigen), protein tyrosine phosphatase-1B, and leukocyte common antigen-related protein LAR preferentially hydrolyze FDP to fluorescein monophosphate (FMP) with V(max) and K(m) values comparable with those of phosphotyrosine peptide substrates. Further hydrolysis of FMP to fluorescein was less efficient because of increased K(m) values compared with those of FDP. FMP absorbs strongly at 445 nm and fluoresces intensely near 515 nm, both of which are insensitive to pH perturbations above pH 6. Its high catalytic efficiency, coupled with the highly sensitive dual detection in the visible wavelength region and wider pH operating range, make FDP the substrate of choice for PTPase inhibitor screening in HTS format and assay miniaturization.

19.
Arch Biochem Biophys ; 354(2): 225-31, 1998 Jun 15.
Article in English | MEDLINE | ID: mdl-9637730

ABSTRACT

Sulfotyrosyl peptides corresponding to the known high-affinity substrate phosphotyrosyl peptide sequences in casein and the autophosphorylation sites of insulin receptor and EGF receptor were investigated as inhibitors of protein tyrosine phosphatases PTP1B and CD45. These peptides inhibit both PTP1B and CD45 in the micromolar range competitively and reversibly. The elements required for inhibition were investigated by truncation and substitution of these peptides. Acidic residues N-terminal to the sulfotyrosyl residues are essential for high-affinity binding to PTP1B. The recognition elements required for inhibition of PTP1B and CD45 are different and this suggests the possibility of identifying selective active-site-directed inhibitors for these enzymes.


Subject(s)
Caseins/pharmacology , Enzyme Inhibitors/pharmacology , Leukocyte Common Antigens/drug effects , Peptides/pharmacology , Protein Tyrosine Phosphatases/antagonists & inhibitors , Sulfur Compounds/pharmacology , Binding Sites , Models, Molecular , Phosphorylation , Substrate Specificity
20.
Arch Sex Behav ; 27(2): 145-53, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9562898

ABSTRACT

Although there is extensive research describing negative dating experiences and rape myth beliefs among university- and college-age women, there is little exploration of these issues among older dating women. An exploratory study that extends existing research by investigating rape myth beliefs and negative dating experiences of women ranging in age from 18 to 85 years is described. Participants (N = 115) completed a questionnaire which included a standardized measure of rape myth adherence (R-Scale; Costin, 1985), and a series of questions that assessed concerns about the potential for negative experiences while dating and actual negative dating experiences (ranging from unwanted affection to rape). There were remarkable similarities among younger and older women with respect to their dating behaviors and experiences. Women from both age groups reported being the target of negative dating experiences and being concerned about these experiences--with older women expressing slightly more concern. Older women, however, endorsed rape myths to a greater extent. This suggests that older women may be at greater risk for self-deprecation because they may be more likely to attribute the negative experiences they encounter to personal faults. Findings highlight the need for more life-span research of dating experiences and attitudes towards dating violence.


Subject(s)
Affect , Attitude , Interpersonal Relations , Rape/psychology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Self Concept
SELECTION OF CITATIONS
SEARCH DETAIL
...