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PubMed2005

Latex-enhanced immunoassay d-dimer and blood gases can exclude pulmonary embolism in low-risk patients presenting to an acute care setting.

BACKGROUND: Pulmonary embolism (PE) is common, and diagnosis is often difficult. Investigation has traditionally required expensive imaging procedures that are frequently nondiagnostic. Consequently, current practice favors noninvasive diagnosis of PE using algorithms combining risk assessment and d-dimer. Despite the proven safety of this approach, concern persists about such strategies to exclude PE, largely due to variable d-dimer sensitivity. The aim of this study was to prospectively assess the safety of a new algorithm combining a novel, rapid d-dimer test (IL Test; Instrumentation Laboratory; Lexington, MA), Pa(O2) measurement, and risk factor assessment in excluding PE in subjects presenting to an acute care setting. METHODS: All patients aged 18 to 60 years presenting to the emergency department of Christchurch Hospital with suspected PE underwent measurement of d-dimer (IL Test latex-enhanced immunoassay) and Pa(O2), and were assessed for the presence of major clinical risk factors. Those with no risk factors, normal d-dimer findings, and Pa(O2) > or = 80 mm Hg (study arm A) were discharged and followed up by telephone questionnaires over 12 months. Those with elevated d-dimer levels, Pa(O2) < 80 mm Hg, or one or more risk factors (study arm B) were managed as per hospital guidelines. Outcome data were collected on these patients. Our primary outcome was incidence of PE in group A during the first 3-month follow-up period. RESULTS: Three hundred twenty-eight patients were enrolled, of whom 149 were assigned to group A and 179 were assigned to group B. In none of the group A patients was PE diagnosed over the subsequent 3-month period (0%; 95% confidence interval, 0 to 2.1%). PE was diagnosed in 37 group A patients (21%). CONCLUSIONS: The latex-enhanced immunoassay d-dimer and normal arterial oxygen pressure levels can safely exclude PE in a low-risk population presenting to an acute care setting. While these results cannot be extrapolated to all patients with suspected PE, they do confirm the safety of this approach in a population with a low underlying risk of PE.

Blood Gas Analysis↗

PubMed1982

Preparation and properties of covalently linked insulin dimers.

The synthesis of six isomeric insulin dimers, linked through selected amino groups of the monomers by a dicarboxylic acid, is described. Symmetrical dimers were obtained by direct crosslinking of N,N-bis(methylsulfonyl-ethoxycarbonyl)insulins with the bis(p-nitrophenyl) esters of dicarboxylic acids. The synthesis of asymmetrical dimers was achieved by use of Msc-protected insulin active ester intermediates. N epsilon-B29,N epsilon B29'-Insulin dimers containing oxalyl, suberoyl and dodecanedioyl crosslinks were produced. N alpha B1,N epsilon B29'-Insulin dimers were suberoyl and dodecanedioyl crosslinks were synthesized; all other dimers were synthesized with suberoyl crosslinks. The positions of crosslinks were determined by sulfitolysis, tryptic digestion, electrophoresis and quantitative end-group determination. The dimers showed potencies between 1-60% that of insulin on a weight basis in stimulating lipogenesis in isolated fat cells. The potencies are considerably lower than the relative binding affinities determined with isolated fat cells.

Adipose Tissue↗

PubMed1990

Characterization of dimeric forms of human pituitary growth hormone by bioassay, radioreceptor assay, and radioimmunoassay.

Seven highly purified dimeric forms of human pituitary growth hormone, composed of the monomeric forms 20 K hGH, 22 K hGH and 24 K hGH linked together by noncovalent or covalent bonds, have been characterized by an in vitro bioassay (the Nb2 assay), a radioreceptor assay and a radioimmunoassay. Considerable differences in the ability to displace labelled recombinant hGH were observed in the radioreceptor assay. The seven dimeric forms varied over a range between 22 K hGH (most effective) and 20 K hGH. The three covalently-linked dimeric forms had nearly identical affinity constants. The mitogenic action of all but one of the hGH dimers in the Nb2 assay was in the same mutual order as the receptor binding activity in the radioreceptor assay. In the RIA, all dose-response curves were parallel except for those obtained with 20 K hGH and with the dimeric form (20 K-20 K)hGH. In this assay, dimeric variants of the constituents 22 K hGH and 24 K hGH were approximately twice as active as 22 K hGH on a molar basis, suggesting about the same affinity between the antibodies and each of the monomeric forms. Determination of the amino acid compositions of the dimeric forms provided support for their content of monomeric constituents as established earlier by electrophoretic analysis.

Amino Acids↗

PubMed2000

Effect of FSH and cell localization on dimeric inhibin-A secretion from bovine granulosa cells in culture.

We tested the hypotheses that the secretion of dimeric inhibin-A from cultured bovine granulosa cells is stimulated by FSH, and that antral cells secrete more inhibin-A than do mural cells. Cells from the antral or mural compartment of follicles were cultured in defined medium in two culture systems, and dimeric inhibin-A was measured by two-site ELISA or by Western immunoblotting. In the first culture system, dimeric inhibin-A secretion declined with time in culture, but was significantly (P<0.05) higher from antral than from mural cells (as was total inhibin-alpha measured by RIA). The secretion of dimeric inhibin-A and inhibin-alpha from antral but not mural cells was responsive to FSH. In the second culture system, dimeric inhibin-A secretion increased with time in culture, and was significantly stimulated by FSH, but FSH responsiveness was dependent on the concentrations of insulin in the culture medium. The major forms of inhibin-A secreted had molecular masses of approximately 58, 62, 103-116 and >116 kDa; the 32 kDa form was barely detectable. These different forms were all stimulated by FSH, but the >116 and 62 kDa forms were most responsive to FSH. We conclude that (i) FSH stimulates dimeric inhibin-A secretion from bovine granulosa cells, (ii) the 62 kDa form of inhibin-A may be more responsive to FSH than the 58 kDa form, and (iii) the spatial differentiation of granulosa cell function within the follicle previously observed for oestradiol secretion was also observed for inhibin-alpha and dimeric inhibin-A secretion.

Animals↗

PubMed2006

IgG dimers in multidonor-derived immunoglobulins: aspects of generation and function.

Immunoglobulin G (IgG) concentrates for therapeutic purposes, like passive immunotherapy, supplementation in inherited or acquired deficiencies or immunomodulation, are prepared from multidonor-derived plasma pools. They usually contain varying amounts of dimeric IgG. The essential factor influencing dimer formation is the pool size; in addition, molecular properties of IgG and a variety of production process- and formulation-specific parameters are important. Numerous experimental findings suggest that dimers are predominantly generated by interactions of idiotypic and anti-idiotypic antibodies (Ids, anti-Ids). Ab-inherent crossreactivity, frequency distribution of both the affinities for particular Id-anti-Id interactions and the corresponding dimer concentrations still have to be elucidated. All these parameters influencing molecular features and functional activity of IgG dimers hamper the assay-dependent measurement of biological efficacy and correlation of total IgG content. A more detailed understanding may help to better control the dual nature of dimer-dependent biological activity comprising both undesirable (e.g., hypotension) and desirable effects of dimeric IgG (blockade of the reticuloendothelial system, RES, in immune thrombocytopenic purpura, ITP). These effects are detectable in in vitro and in vivo models and are thought to be of relevance for humans.

Animals↗

PubMed2004

False-positive D-dimer result in a patient with Castleman disease.

In suspected cases of disseminated intravascular coagulation, concurrent elevation of both fibrin(ogen) degradation products (FDPs) and D-dimer levels aids in confirming the diagnosis. This pattern of results reflects the action of plasmin proteolysis of cross-linked fibrin polymers as well as fibrinogen. We report the case of a patient with human immunodeficiency virus (HIV) and Castleman disease who presented with a high-positive D-dimer level and a negative FDP level in the course of a workup for disseminated intravascular coagulation. This finding suggested the possibility of either a false-positive D-dimer or a false-negative FDP level. To investigate the former, a Western blot was performed on the patient's serum to determine the presence of the D-dimer. No D-dimer band was visualized on the Western blot, confirming the false-positive nature of the D-dimer result. Insufficient quantity of patient serum, however, prevented further investigation into the etiology of this result. The false-positive D-dimer result is likely attributable to interference caused by the patient's Castleman disease-associated monoclonal gammopathy, a phenomenon that has been reported in other immunoassays. As the development of lymphoproliferative disorders is especially common within the HIV population, and hypergammaglobulinemia in Castleman disease is particularly common, clinicians should be aware of this phenomenon when the laboratory findings do not fit the clinical picture. Although it is rare, recognition of potential paraprotein interference in immunoassays will help avoid undertreatment or overtreatment of patients based on erroneous laboratory results.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Combination of D-dimer and amino-terminal pro-B-type natriuretic Peptide testing for the evaluation of dyspneic patients with and without acute pulmonary embolism.

CONTEXT: D-dimer concentration can be used to exclude a diagnosis of acute pulmonary embolism. However, clinicians frequently order unnecessary supplemental testing in patients with low concentrations of D-dimer. Elevations in natriuretic peptides have also been described in the setting of pulmonary embolism. OBJECTIVE: We investigated the integrative role of D-dimer with amino-terminal pro-B-type natriuretic peptide for the evaluation of patients with and without acute pulmonary embolism. DESIGN: Patients were selected for analysis from a previous study in which levels of D-dimer and amino-terminal pro-B-type natriuretic peptide were measured. The presence of pulmonary embolism was determined by computed tomographic angiography. RESULTS: The median levels of D-dimer were significantly higher in patients with acute pulmonary embolism. Similarly, the median levels of amino-terminal pro-B-type natriuretic peptide were higher in patients with pulmonary embolism. CONCLUSIONS: The Roche Tina-quant D-Dimer immunoturbidimetric assay provides a high negative predictive value and can be used to exclude acute pulmonary embolism in patients with dyspnea. Measurement of amino-terminal pro-B-type natriuretic peptide in addition to D-dimer improves specificity for acute pulmonary embolism without sacrificing negative predictive value. A combination of both markers may offer reassurance for excluding acute pulmonary embolism, and thus avoid redundant, expensive confirmatory tests.

Acute Disease↗

PubMed1996

Dimerization of A82846B, vancomycin and ristocetin: influence on antibiotic complexation with cell wall model peptides.

The thermodynamics of glycopeptide antibiotic dimerization have been studied by means of sedimentation equilibrium, using A82846B, vancomycin, ristocetin and complexes formed with several cell wall model peptides. These results indicate that vancomycin dimerization can be strongly promoted in two ways: i) stabilization of the antibiotic conformation in which the carbonyl group of residue three is on the back face of the molecule and ii) preferential interaction of the dimer with the lysine residue of N,N'-diacetyl-lysyl-D-alanyl-D-alanine. This effect was not found in ristocetin. A82846B forms stable dimers at very low antibiotic concentration. Two conformational forms have been found for complexed A82846B by 1H NMR. However, calorimetric binding experiments have shown that all its binding sites are thermodynamically equivalent. The affinity of the A82846B dimer for the tripeptide has been estimated to be about 3kJ x mol-1 higher than that of the vancomycin monomer and about -2.6kJ x mol-1 lower than that of dimeric vancomycin. The possible role of dimerization in the biological activity of glycopeptide antibiotics is discussed further on the basis of present thermodynamic data.

Amino Acid Sequence↗

PubMed1998

Sensitivity and specificity of a rapid whole-blood assay for D-dimer in the diagnosis of pulmonary embolism.

BACKGROUND: Patients with suspected pulmonary embolism often have nondiagnostic lung scans and may present in circumstances where lung scanning is unavailable. Levels of D-dimer, a fibrin-specific product, are increased in patients with acute thrombosis; this may simplify the diagnosis of pulmonary embolism. OBJECTIVE: To determine the sensitivity and specificity of a whole-blood D-dimer assay in patients with suspected pulmonary embolism and in subgroups of patients with low pretest probability of pulmonary embolism or nondiagnostic lung scans. DESIGN: Prospective cohort. SETTING: Four tertiary care hospitals. PATIENTS: 1177 consecutive patients with suspected pulmonary embolism. MEASUREMENTS: All patients underwent an assessment of pretest probability by use of a standardized clinical model, a D-dimer assay, ventilation-perfusion lung scanning, and bilateral compression ultrasonography. Patients in whom pulmonary embolism was not initially diagnosed were followed for 3 months. Accordingly, patients were categorized as positive or negative for pulmonary embolism. RESULTS: Of the 1177 patients, 197 (17%) were classified as positive for pulmonary embolism. Overall, the D-dimer assay showed a sensitivity of 84.8% and a specificity of 68.4%. In 703 patients (3.4%) with a low pretest probability of pulmonary embolism, the likelihood ratio associated with a negative D-dimer test result was 0.27, resulting in a posterior probability of 1.0% (95% CI, 0.3% to 2.2%). In 698 patients with nondiagnostic lung scans (previous probability, 7.4%), the likelihood ratio associated with a negative D-dimer test result was 0.36, resulting in a posterior probability of 2.8% (CI, 1.4% to 4.8%). CONCLUSIONS: A normal D-dimer test result is useful in excluding pulmonary embolism in patients with a low pretest probability of pulmonary embolism or a nondiagnostic lung scan.

Algorithms↗

PubMed2001

Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer.

BACKGROUND: The limitations of the current diagnostic standard, ventilation-perfusion lung scanning, complicate the management of patients with suspected pulmonary embolism. We previously demonstrated that determining the pretest probability can assist with management and that the high negative predictive value of certain D -dimer assays may simplify the diagnostic process. OBJECTIVE: To determine the safety of using a simple clinical model combined with D -dimer assay to manage patients presenting to the emergency department with suspected pulmonary embolism. DESIGN: Prospective cohort study. SETTING: Emergency departments at four tertiary care hospitals in Canada. PATIENTS: 930 consecutive patients with suspected pulmonary embolism. INTERVENTIONS: Physicians first used a clinical model to determine patients' pretest probability of pulmonary embolism and then performed a D -dimer test. Patients with low pretest probability and a negative D -dimer result had no further tests and were considered to have a diagnosis of pulmonary embolism excluded. All other patients underwent ventilation-perfusion lung scanning. If the scan was nondiagnostic, bilateral deep venous ultrasonography was done. Whether further testing (by serial ultrasonography or angiography) was done depended on the patients' pretest probability and the lung scanning results. MEASUREMENTS: Patients received a diagnosis of pulmonary embolism if they had a high-probability ventilation-perfusion scan, an abnormal result on ultrasonography or pulmonary angiography, or a venous thromboembolic event during follow-up. Patients for whom the diagnosis was considered excluded were followed up for 3 months for the development of thromboembolic events. RESULTS: The pretest probability of pulmonary embolism was low, moderate, and high in 527, 339, and 64 patients (1.3%, 16.2%, and 37.5% had pulmonary embolism), respectively. Of 849 patients in whom a diagnosis of pulmonary-embolism had initially been excluded, 5 (0.6% [95% CI, 0.2% to 1.4%]) developed pulmonary embolism or deep venous thrombosis during follow-up. However, 4 of these patients had not undergone the proper diagnostic testing protocol. In 7 of the patients who received a diagnosis of pulmonary embolism, the physician had performed more diagnostic tests than were called for by the algorithm. In 759 of the 849 patients in whom pulmonary embolism was not found on initial evaluation, the diagnostic protocol was followed correctly. Only 1 (0.1% [CI, 0.0% to 0.7%]) of these 759 patients developed thromboembolic events during follow-up. Of the 437 patients with a negative D -dimer result and low clinical probability, only 1 developed pulmonary embolism during follow-up; thus, the negative predictive value for the combined strategy of using the clinical model with D -dimer testing in these patients was 99.5% (CI, 99.1% to 100%). CONCLUSION: Managing patients for suspected pulmonary embolism on the basis of pretest probability and D -dimer result is safe and decreases the need for diagnostic imaging.

Adolescent↗

PubMed2004

D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review.

BACKGROUND: Despite extensive literature, the diagnostic role of d-dimer for deep venous thrombosis (DVT) or pulmonary embolism (PE) remains unclear, reflecting multiple d-dimer assays and concerns about differing sensitivities and variability. PURPOSE: To systematically review trials that assessed sensitivity, specificity, likelihood ratios, and variability among d-dimer assays. DATA SOURCES: Studies in all languages were identified by searching PubMed from 1983 to January 2003 and EMBASE from 1988 to January 2003. STUDY SELECTION: The researchers selected prospective studies that compared d-dimer with a reference standard. Studies of high methodologic quality were included in the primary analyses; sensitivity analysis included additional weaker studies. DATA EXTRACTION: Two authors collected data on study-level factors: d-dimer assay used, cutoff value, and whether patients had suspected DVT or PE. DATA SYNTHESIS: For DVT, the enzyme-linked immunosorbent assay (ELISA) and quantitative rapid ELISA dominate the rank order for these values: sensitivity, 0.96 (95% confidence limit [CL], 0.91 to 1.00), and negative likelihood ratio, 0.12 (CL, 0.04 to 0.33); and sensitivity, 0.96 (CL, 0.90 to 1.00), and negative likelihood ratio, 0.09 (CL, 0.02 to 0.41), respectively. For PE, the ELISA and quantitative rapid ELISA also dominate the rank order for these values: sensitivity, 0.95 (CL, 0.85 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.03 to 0.58); and sensitivity, 0.95 (CL, 0.83 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.02 to 0.84), respectively. The ELISA and quantitative rapid ELISA have negative likelihood ratios that yield a high certainty for excluding DVT or PE. The positive likelihood values, which are in the general range of 1.5 to 2.5, do not greatly increase the certainty of diagnosis. Sensitivity analyses do not affect these findings. LIMITATIONS: Although many studies evaluated multiple d-dimer assays, findings are based largely on indirect comparisons of test performance characteristics across studies. CONCLUSION: The ELISAs in general dominate the comparative ranking among the d-dimer assays for sensitivity and negative likelihood ratio. For excluding PE or DVT, a negative result on quantitative rapid ELISA is as diagnostically useful as a normal lung scan or negative duplex ultrasonography finding.

Acute Disease↗

PubMed2004

Negative D-dimer result to exclude recurrent deep venous thrombosis: a management trial.

BACKGROUND: All of the available diagnostic tests for deep venous thrombosis (DVT) have limitations for excluding acute recurrent DVT. Measurement of plasma d-dimer by using an automated quantitative assay may be useful as a rapid exclusion test in patients with suspected recurrent DVT. OBJECTIVE: To test the safety of withholding additional diagnostic testing and heparin treatment in patients who have a negative d-dimer result at presentation (using the automated quantitative assay STA-Liatest D-di), regardless of their symptoms. DESIGN: Prospective cohort study. SETTING: Academic medical center in the United States. PATIENTS: 300 consecutive patients with suspected recurrent DVT. INTERVENTION: Patients underwent d-dimer testing at presentation. In patients with negative D-dimer results, heparin therapy was withheld, and no further diagnostic testing for DVT was done as part of the initial evaluation. Patients with positive D-dimer results underwent compression ultrasonography. MEASUREMENTS: The primary outcome measure was a diagnosis of new symptomatic venous thromboembolism confirmed by diagnostic testing during the 3-month follow-up period. RESULTS: Of the 300 study patients, the d-dimer result was negative at presentation in 134 patients (45%; negative cohort) and positive at presentation in 166 patients. Of the 166 patients, compression ultrasonography documented new DVT in 54 patients. Compression ultrasonography findings were normal in 79 patients and were inconclusive in 33 patients. After 3 months of follow-up, 1 of 134 patients in the negative cohort had confirmed venous thromboembolism (0.75% [95% CI, 0.02% to 4.09%]). Venous thromboembolism on follow-up could not be definitively excluded in 5 patients with recurrent leg symptoms and in 1 patient who died. If these patients are considered to have venous thromboembolism, the incidence during the 3-month follow-up period would be 6.0% (CI, 2.6% to 11.4%) (8 of 134 patients). LIMITATIONS: There is no accepted diagnostic reference standard for recurrent DVT. The precision of the estimate of the incidence of venous thromboembolism on follow-up and the generalizability to settings other than an academic health center should be evaluated. CONCLUSIONS: Measurement of plasma d-dimer by using the automated quantitative assay STA-Liatest D-di seems to provide a simple method for excluding acute recurrent DVT in symptomatic patients.

Fibrin Fibrinogen Degradation Products↗

PubMed2005

A randomized trial of diagnostic strategies after normal proximal vein ultrasonography for suspected deep venous thrombosis: D-dimer testing compared with repeated ultrasonography.

BACKGROUND: With suspected deep venous thrombosis and normal results on proximal vein ultrasonography, a negative d-dimer result may exclude thrombosis and a positive D-dimer result may be an indication for venography. OBJECTIVE: To evaluate and compare the safety of 2 diagnostic strategies for deep venous thrombosis. DESIGN: Randomized, multicenter trial. SETTING: Four university hospitals. PATIENTS: 810 outpatients with suspected deep venous thrombosis and negative results on proximal vein ultrasonography. INTERVENTIONS: Erythrocyte agglutination D-dimer testing followed by no further testing if the result was negative and venography if the result was positive (experimental) or ultrasonography repeated after 1 week in all patients (control). MEASUREMENTS: Symptomatic deep venous thrombosis diagnosed initially and symptomatic venous thromboembolism during 6 months of follow-up. RESULTS: Nineteen of 408 patients (4.7%) in the D-dimer group and 3 of 402 patients (0.7%) in the repeated ultrasonography group initially received a diagnosis of deep venous thrombosis (P < 0.001). During follow-up of patients without a diagnosis of deep venous thrombosis on initial testing, 8 patients (2.1% [95% CI, 0.9% to 4.0%]) in the D-dimer group and 5 patients (1.3% [CI, 0.4% to 2.9%]) in the repeated ultrasonography group developed symptomatic venous thromboembolism (difference, 0.8 percentage point [CI, -1.1 to 2.9 percentage points]; P > 0.2). Venous thromboembolism occurred in 1.0% (CI, 0.2% to 2.8%) of those with a negative D-dimer result. LIMITATIONS: Seventy patients (8.6%) deviated from the diagnostic protocols, and 9 patients (1.1%) had inadequate follow-up. CONCLUSION: In outpatients with suspected deep venous thrombosis who initially had normal results on ultrasonography of the proximal veins, a strategy based on D-dimer testing followed by no further testing if the result was negative and venography if the result was positive had acceptable safety and did not differ from the safety of a strategy based on withholding anticoagulant therapy and routinely repeating ultrasonography after 1 week.

Female↗

PubMed2000

Rapid ELISA assay for plasma D-dimer in the diagnosis of segmental and subsegmental pulmonary embolism. A comparison with pulmonary angiography.

STUDY OBJECTIVE: To assess the accuracy of a rapid ELISA D-dimer assay for the exclusion of pulmonary embolism (PE) in patients suspected of PE, using pulmonary angiography alone as reference method rather than a diagnostic strategy including lung scintigraphy and leg vein ultrasonography. METHODS: In 342 patients who were examined by pulmonary angiography to diagnose or exclude PE, the accuracy of the quantitative rapid VIDAS D-dimer test for the exclusion of PE was evaluated retrospectively. D-dimer levels were assayed in frozen samples collected during the diagnostic work-up at the time of pulmonary angiography while on treatment with unfractionated heparin for 1-2 days. RESULTS: Mean plasma D-dimer concentrations were increased in patients with angiographic evidence of PE (P <0.0001). The sensitivity of D-dimer for segmental PE was 98%, its accuracy in excluding segmental PE was 99%, higher than the respective figures for subsegmental PE (76% and 94%; P <0.01, both). For both forms of PE combined the sensitivity was 90% and the negative predictive value 94%. DISCUSSION: The sensitivity and negative predictive values reported here, are low compared with previous studies using the same rapid ELISA D-dimer assay. This probably reflects an overlooking of mild cases of subsegmental PE in previous studies, although a reduction of D-dimer levels by the heparin pretreatment may have contributed to part of the discrepancy. Prospective studies are needed to clarify this issue.

Adult↗

PubMed1975

Repair of UV-induced DNA damage and survival in yeast. I. Dimer excision.

The amount of pyrimidine dimer UV photoproduct lost from the DNA of irradiated yeast cells during dark incubation has been measured in various conditions. It was found that no dimers were lost when cells were incubated in saline. When the cells were incubated, with aeration, in a full growth medium, dimers were lost, most excision being complete within 4 h. Not all dimers were lost and the number lost was a function of UV dose. Maximum loss, amounting to 50 000 dimers per genome was observed after 4000 or 6000 erg/mm2 of UV. At higher doses, the number excised declined. Making the assumptions that dimers are the principal lethal product of UV, that a single dimer remaining in its genome is enough to prevent a cell from multiplying and that excision is the principal dark-repair process in yeast, these data were incorporated into the repair term of an expression relating survival to repair8 and it was found that the survival of yeast at doses up to 2000 erg/mm2 of UV could be quite accurately predicted. This is the first time it has been possible to account for survival in terms of measured repair. It is suggested that the divergence of the predicted and observed curves at higher doses is due to other processes known to exist in yeast.

DNA Repair↗

PubMed2000

Preliminary evaluation of two new rapid immunoturbidimetric D-dimer assays in patients with clinically suspected venous thromboembolism (VTE).

The practical utility and diagnostic accuracy of two new rapid, automated and quantitative immunoturbidimetric D-dimer methods have been evaluated in a population of 123 randomly selected patients with suspected VTE. The STA Liatest D-dimer and MDA D-dimer methods are based on the photo-optical measurement of the rate of agglutination of antibody-coated latex particles. The VIDAS D-dimer automated Elisa was used as the reference method. Diagnosis was confirmed in 51 patients (29 PE, 19 DVT, 3 DVT+PE). The immunoturbidimetric methods compared favorably with the VIDAS Elisa as judged from the correlation coefficients of linear regression lines (r = 0.82, MDA vs VIDAS; r = 0.75, STA vs VIDAS) and areas under the curve of ROC plots (VIDAS 0.83; STA 0.83; MDA 0.81). At a discriminant value of 500 ng/mL, all three D-dimer assays showed high sensitivity (96-98%), high NPV (93-97%) and moderate specificity (39-42%). Reproducibility of results around the cut-off is an important aspect of the diagnostic utility of D-dimer assays. CV's of duplicate determinations in this critical zone showed average values of 5.4% and 17.0% for MDA and STA, respectively. These data demonstrate that such rapid and automated latex-based methods for the quantitative measurement of D-dimer hold promise as reliable and cost-efficient approaches for the exclusion of VTE. Prospective patient management studies will be required to confirm this.

Adult↗

PubMed2001

The rapid whole blood agglutination d-dimer assay has poor sensitivity for use as an exclusion test in suspected deep vein thrombosis.

AIMS: Several clinical studies have proposed using d-dimer as an initial screening test to exclude thrombosis in cases of suspected (DVT). In published series, these assays have variable sensitivity, raising concerns that they may not be sufficiently robust for clinical practice. The aim of the study was to examine the sensitivity of two commercially available d-dimer assays and to assess their value and safety as initial screening tests in suspected DVT. METHODS: In this prospective study, blood samples were collected for d-dimer measurement (SimpliRED assay and IL test d-dimer) in all patients presenting to the emergency department over a twelve month period. All patients underwent compression ultrasound scanning as the primary diagnostic procedure. RESULTS: 235 patients were included in the study. 51(22.8%) had a DVT confirmed on ultrasound. The SimpliRED assay was positive in only 33 cases, with seventeen cases of confirmed DVT giving a negative result (six cases with proximal vein thrombosis). Assay sensitivity was 66%, with a negative predictive value of 88.9%. The IL test gave three false negatives (all below knee thromboses) giving assay sensitivity and negative predictive value of 94.1% and 96.8% respectively. CONCLUSIONS: The precise role of d-dimer testing in the diagnosis of venous thrombosis has yet to be established. From our results and a review of published series, we conclude that the SimpliRED assay is too insensitive to use as a reliable exclusion test in cases of suspected DVT, however, the more sensitive automated IL test d-dimer may have a role in the initial assessment. We propose that the IL d-dimer test is used in conjunction with a pre-test probability score to identify patients at low risk of DVT and recommend that this approach is tested in a clinical study before introduction into practice.

Diagnosis, Differential↗

PubMed2002

Effect of tissue injury on D-Dimer levels: a prospective study in trauma patients.

BACKGROUND: D-Dimer measurement has been used as a simple, non-invasive test to rule out thromboembolic phenomena in patients at risk for deep venous thrombosis (DVT) and / or pulmonary embolism (PE). Elevated D-Dimer level caused by tissue injury is believed to show a trend for gradual decrease to normal within the first three days after trauma. MATERIAL/METHODS: To study the effect of tissue injury on D-Dimer levels, we conducted a prospective measurement of D-Dimer levels in severely traumatized, high-risk patients for DVT or PE, starting within 24 hours after admission until disposition of the patient or to a total of 14 days of hospitalization. Patients were observed clinically for development of thromboembolic phenomena, and were subjected to weekly surveillance using duplex scan of the lower extremities. Additional testing was done if requested by the attending trauma surgeon. RESULTS: A total of 21 patients were enrolled in the study. There were 17 males, and 4 females. Patients had a mean age of (42) with a range of (17-79), and a mean ISS score of (20) with a range of (4-50). Seven patients completed 3-9 days of testing. Fourteen patients had more than 10 days of testing. Nine patients completed 14 days of testing. In all patients, tissue injury resulted in increased levels of D-Dimer above a threshold (500 ng/ml), below which DVT or PE can be ruled out. The increased levels failed to normalize even when testing was continued for 14 days. CONCLUSIONS: In our study, the increased D-Dimer levels induced by tissue injury failed to show a trend of gradual return to normal within three days after trauma, as currently believed. This, in our opinion, may eliminate our ability to use D-Dimer testing to rule out DVT or PE in a subset of severely traumatized patients in the early post trauma period.

Adolescent↗