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PubMed1976

[Dimer-X in the intracranial subarachnoid space--its toxicity (author's transl)].

The reaction of the rats to injection of Dimer-X into the intracranial subarachnoid space or the cerebrum was examined. When 28% iodine Dimer-X was injected into the subarachnoid space, 7 of 10 rats showed agitation, which is the most severe complication, and all died within one hour. All of the reactions were reduced with the lower concentrations of Dimer-X. The rats which were premedicated with Valium and/or Decadron revealed fewer and less severe complications. It is believed that the intracerebral injection method has many disadvantages, the results of its experiment are therefore reported without further elaboration. From the results of the experiment it is concluded as follows: 1) Dimer-X should not be injected into the intracranial subarachnoid space. 2) Dimer-X of low concentration in the subarachnoid space reduces the complications. 3) Complications from the subarachnoid application of Dimer-X can be reduced by premedication with Valium and Decadron.

Animals↗
PubMed2000

[A clinical evaluation of three different quantitative fibrin D-dimer analyses in the diagnosis of deep venous thrombosis].

The trial included ninety-five consecutive outpatients admitted with symptoms and signs suggesting deep venous thrombosis. Blood samples were collected on admission and analysed when the trial was ended. The three different D-dimer methods were BC D-dimer, Tinaquant D-dimer (both quantitative latex agglutination methods) and VIDAS D-dimer, based on the ELISA principle. Ultrasound was used as the reference method, but the outcome evaluated at three month follow up was the gold standard. The sensitivities of the three different methods were 66% (95% confidence interval 55-75%), 93% (88-98%) and 98% (94-100%) respectively. The negative predictive values were respectively 71% (62-80%), 88% (81-95%) and 95% (91-99%). This trial confirms that VIDAS D-dimer has a high sensitivity and negative predictive value that makes it suitable for clinical use. The same conclusion can be drawn for the Tinaquant D-dimer. The trial also emphasizes the importance of testing new methods under routine clinical conditions.

Adult↗
PubMedDate not supplied

[D-dimer in the year 2000: current data and new perspectives].

D-dimer is a product of cross-linked fibrin degradation by the fibrinolytic system. It has been shown to be highly sensitive and moderately specific for venous thromboembolic disease. Thus, the most common clinical use of D-dimer relates to its negative predictive value for deep vein thrombosis and pulmonary embolism. Diagnosis, however, should not be based solely on this parameter, and an integrated strategy that combines clinical approach (pre-test probability), a non-invasive test (ultrasonography or lung scan) and D-dimer assay is highly recommended. Over the last years a number of studies have demonstrated that D-dimer may also enable the prediction of the complications of atherothrombosis inasmuch as the data available suggest a significant association of D-dimer with the risk of coronary artery disease independent of classic risk factors. Moreover, elevated plasma D-dimer seems to be a marker of a systemic prothrombotic state, and anticoagulation can normalize its levels. However, further studies are needed to assess whether or not this parameters is of clinical value to predict or prevent arterial thrombotic events in the single patient.

Algorithms↗
PubMed2001

Exclusion of pulmonary embolism using quantitative plasma D-dimer assays.

Recent quantitative studies using pulmonary angiography as reference method have indicated that the overall accuracy of quantitative D-dimer assays for the exclusion of pulmonary embolism (PE) in patients suspected of PE is poorer than was reported in earlier studies in which the same D-dimer assays were used (90-94% vs 98-100%). An explanation can be found in the fact that the earlier studies are hampered by the fact that the reference method was a compilation of clinical data and non-invasive diagnostic tests rather than a true gold standard. Furthermore, in those studies no discrimination was made between the milder cases of subsegmental PE and the more severe cases of segmental and larger PE. The lack of a true gold standard and preselection leading to reduced proportions of cases of subsegmental PE in the earlier studies rather than differences in the storage conditions of plasma samples or treatment with heparin, appear to have caused the discrepancies in the reported accuracy of D-dimer assays. It is concluded that the sensitivity and negative predictive values obtained with different quantitative D-dimer assays are in close agreement with each other, that is poor for subsegmental PE and excellent for segmental and larger PE. In diagnostic algorithms D-dimer can reliably exclude acute segmental and/or massive PE. Further work-up within 48 hours is still necessary in negative D-dimer outcomes to exclude subsegmental PE.

Antifibrinolytic Agents↗
PubMed2001

[Role of D-dimer in diagnosis of venous thrombosis and embolism].

AIM: To analyze efficiency of semi-quantitative fast D-dimer test in diagnosis of deep vein thrombosis (DVT) and thromboembolism of pulmonary artery (TPA). MATERIAL AND METHODS: The study enrolled 42 patients (26 males and 16 females) aged 25 to 86 years. 30 and 12 of them were suspected to have DVT and TPA, respectively. DVT was verified at ultrasound dopplerography and radionuclide phlebography in 16 of 30 suspects. TPA was verified by x-ray, perfusion scintigraphy of the lungs and at autopsy (one case) in 7 of 12 suspects. D-dimer levels in the blood were measured by latex parts agglutination reaction. The parts were covered with monoclonal antibodies to D-dimer. The reagents were provided by the kit Roche/Diagnostica Stago. RESULTS: The D-dimer test was positive in 20 of 23 DVT patients and negative in 3 cases (13%). Of 19 patients with rejected diagnosis of DVT/TPA the test was negative in 17(89.4%) and positive in 2 patients (10.6%). Thus, sensitivity and specificity of the D-dimer test was 87% and 89.4%, respectively. CONCLUSION: High sensitivity of the test allows to use it in screening for DVT/TPA. Negative D-dimer test rejects DVT, while positive test needs verification by other methods.

Adult↗
PubMedDate not supplied

[Value of D-dimer measurement in the exclusion diagnosis of pulmonary embolism].

Diagnosis of pulmonary embolism, a common and potentially fatal disease, is first based on clinical probability assessment, and often requires invasive testing such as pulmonary angiography. However, it often represents a diagnosis challenge. The measurement of D-dimer, a specific fibrin degradation product, was recently introduced in the diagnosis strategy. Even if D-dimer levels are highly sensitive in the diagnosis of pulmonary embolism, they are not specific of an on-going venous thromboembolic process. Its high negative predictive value enables to validly exclude diagnosis of pulmonary embolism, particularly in outpatients, in the case of D-dimer levels below a well-defined cut-off value. Prospective management studies confirmed that D-dimer measurement could be validly used as an initial screening test in patients with clinically suspected pulmonary embolism. Using such a diagnosis strategy, imaging tests would be performed only in the case of high D-dimer levels i.e. above the cut-off level. Even if they constitute the gold standard, conventional Elisa are not useful as a routine emergency test. New rapid and automated assays based on various principles (Elisa-derived or micro-latex agglutination) are now available. All demonstrated both high sensitivity (about 100%) and negative predictive value (over 98%), using a well-defined cut-off level (usually defined to be 500 ng/mL). Finally, with the increasing number of new D-dimer assays currently available, a lack of standardization was pointed out. As the result, both the clinical significance and the cut-off level have to be defined in prospective clinical trials, for each individual assay.

Fibrin Fibrinogen Degradation Products↗
PubMed2002

D-dimer as a risk factor for deep vein thrombosis: the Leiden Thrombophilia Study.

We studied the association of D-dimer with the risk of deep vein thrombosis (DVT). D-dimer was measured in 474 patients more than 6 months after diagnosis of a first DVT and in 474 age- and sex-matched controls. For D-dimer above the 70th percentile (130.5 ng/ml), the odds ratio (OR) for DVT was 2.2 (95% CI, 1.6-2.9). The association was unchanged with adjustment for other risk factors. Excluding participants with Factor V Leiden, prothrombin 20210A, or factors VIIIc or IX above the 90th percentile, the OR was 1.6 (95% CI, 1.1-2.3). The risks of DVT with the joint presence of high D-dimer and either factor V Leiden or prothrombin 20210A were increased 12.4-fold (95% CI 5.6-27.7) and 7.2-fold (95% CI 2.1-25.1), respectively. Higher D-dimer concentration was associated with the risk of DVT, and was supra-additive to the risks associated with factor V Leiden and the prothrombin 20210A variant. Persistence of this association in the absence of other hemostatic risk factors for DVT suggests that high D-dimer may be related to other, as yet unknown, risk factors for venous thrombosis. Confirmation of these findings is desirable.

3' Untranslated Regions↗
PubMed2001

[Relationship between the level of plasma D-dimer and diabetic microangiopathy].

OBJECTIVE: To study the relationship between the level of plasma D-dimer and microangiopathy of the type 2 diabetes mellitus. METHODS: The level of plasma D-dimer and blood viscosity were measured in 52 cases with type 2 diabetes mellitus, and these patients were divided into three groups according to the level of urinary albumin excretion (UAE) together with 15 age-matched healthy volunteers as the control (NC group). RESULTS: In the cases with higher urinary albumin excretion rate, including 28 cases with trace albuminuria (EDN group) and 10 cases with clinical albuminuria (CDN group), plasma D-dimer and blood viscosity were increases than 14 cases without albuminuria (SDM group) and NC group. D-dimer was positively correlated with diabetic retinopathy, Serum insulin and diabetic durations, but not correlated with blood viscosity and fibrinogen. CONCLUSION: The type 2 diabetes mellitus complicated with microangiopathy had a higher level of plasma D-dimer. As a marker of thrombus formation, D-dimer may play an important role in the pathogenesis of diabetic microangiopathy.

Adult↗
PubMed1992

[Clinical evaluation of serum levels of monomeric dimeric and tetrameric pseudocholinesterases in patients with various liver diseases].

Serum levels of monomeric, dimeric and tetrameric pseudocholinesterases were measured by means of enzyme-linked immunosorbent assay in patients with various liver diseases and normal controls in order to evaluate their clinical significance. In patients with liver cirrhosis, serum levels of monomeric, dimeric and tetrameric were significantly lower than those in normal controls, patients with fatty liver and chronic hepatitis. The ratio of monomeric and dimeric to tetrameric in patients with liver cirrhosis was also significantly lower than that in normal controls, patients with fatty liver and chronic hepatitis. Serum levels of tetrameric, dimeric and monomeric were not significantly higher in the patients with fatty liver than in normal controls, but the ratio of monomeric and dimeric to tetrameric was significantly higher in patients with fatty liver than that in normal controls, patients with chronic hepatitis and liver cirrhosis. These findings suggest that the selective determinations of serum levels of monomeric, dimeric and tetrameric pseudocholinesterases are useful to estimate the metabolism of fat and protein in various liver diseases.

Adult↗
PubMed2003

D-dimer test: diagnostic role in clinical and sub-clinical DIC.

D-dimer test is used as a diagnosis test for acute disseminated intravascular coagulation (DIC). This study was undertaken to find out its sensitivity and specificity in the diagnosis of acute DIC and its role in diagnosis of sub-clinical DIC, as there is limited data available on the subject. Of the 29 patients of clinically acute DIC, all had positive D-dimer test, and markedly prolonged PT, APTT and TT were seen in 24 (83%) of these patients. D-dimer test was found to be highly specific but less sensitive for the diagnosis of acute DIC. Of the 29 patients predisposed to sub-clinical DIC. D-dimer was positive is 26 (90%) patients and PT, APTT and TT were mildly prolonged in 11 patients. It is suggested that D-dimer positivity for the diagnoses of sub-clinical DIC need to be considered with caution and to be supplemented by other coagulation test including serial follow up with d-dimer and coagulation tests.

Disseminated Intravascular Coagulation↗
PubMed2004

[Role of fibrin D-dimer in acute coronary syndrome. Prospective study of 22 cases].

Fibrin D-dimer are the consequence of an excess of fibrinolysis. The raise of their level in coronary heart disease seems to be helpful to enhance the diagnosis of coronary ischemia. Prospective study over 4 months, including 22 patients (16 male, 6 female) divided in 2 subgroups: Group I: 10 patients investigated for stable angina Group II: 12 patients investigated for ACS without ST elevation. All patients underwent fibrin D-dimer dosage and coronarography. Fibrin D-dimer levels were higher in group II (924.5 ng/ml vs 703.9 ng/ml; p < 0.0001). In group II, 6 patients had ST depression with a level of fibrin D-dimer 879.5 ng/ml vs 969.6 ng/ml in the other 6 patients. We found a positive correlation between level of fibrin D-dimer and complexity of coronary lesions (1007 ng/ml in type C vs 675 ng/ml in type A lesions; p < 0.0001). Fibrin D-dimer seems highly implicated in coronary disease and if these results are confirmed by larger studies their routine dosage will be helpful in ACS.

Adult↗
PubMed2005

Calcium-binding calmyrin forms stable covalent dimers in vitro, but in vivo is found in monomeric form.

The EF-hand Ca(2+)-binding protein calmyrin is expressed in many tissues and can interact with multiple effector proteins, probably as a sensor transferring Ca(2+) signals. As oligomerization may represent one of Ca(2+)-signal transduction mechanisms, we characterised recombinant calmyrin forms using non-reducing SDS/PAGE, analytical ultracentrifugation and gel filtration. We also aimed at identification of biologically active calmyrin forms. Non-reducing SDS/PAGE showed that in vitro apo- and Ca(2+)-bound calmyrin oligomerizes forming stable intermolecular disulfide bridges. Ultracentrifugation indicated that at a 220 microM initial protein concentration apo-calmyrin existed in an equilibrium of a 21.9 kDa monomer and a 43.8 kDa dimer (trimeric or tetrameric species were not detected). The dimerization constant was calculated as Ka = 1.78 x 103 M(-1) at 6 degrees C. Gel filtration of apo- and Ca(2+)-bound calmyrin at a 100 microM protein concentration confirmed an equilibrium of a monomer and a covalent dimer state. Importantly, both monomer and dimer underwent significant conformational changes in response to binding of Ca(2+). However, when calmyrin forms were analyzed under non-reducing conditions in cell extracts by Western blotting, only monomeric calmyrin was detected in human platelets and lymphocytes, and in rat brain. Moreover, in contrast to recombinant calmyrin, crosslinking did not preserve any dimeric species of calmyrin regardless of Ca(2+) concentrations. In summary, our data indicate that although calmyrin forms stable covalent dimers in vitro, it most probably functions as a monomer in vivo.

Animals↗
PubMed2005

An association between oxygen desaturation and D-dimer in patients with obstructive sleep apnea syndrome.

D-dimer, a degradation product of fibrin, is being increasingly used as a marker and prognostic factor in various thrombotic diseases. Previous reports have shown that obstructive sleep apnea is associated with platelet activation and hypercoagulability. The aim of the study was to assess the potential role of the plasma D-dimer test in patients with obstructive sleep apnea. We designed a prospective group comparison study in a tertiary-care, university-affiliated medical center. One hundred and three patients of mean age 57 years (range 50-76 years) with symptoms suggestive of obstructive sleep apnea were included. Polysomnography was performed in all cases, and blood was collected for plasma D-dimer measurement by MiniQuant turbidmetric assay. The demographic and polysomnograph data were compared between patients with normal and high (> 250 ng/ml) D-dimer levels. The group with higher D-dimer values had lower mean minimal oxygen saturation (72.1 +/- 16.4 vs. 81.7 +/- 11.6%, p = 0.008) and a longer mean period of oxygen saturation below 90% (84.1 +/- 86.2 vs. 38.5 +/- 70.8 minutes, p = 0.032). There was no correlation of respiratory disturbance index and sleep architecture with D-dimer values. We concluded that sleep apnea syndrome is associated with fibrinolytic activity. Oxygen desaturation seems to be one of the mediatory factors in the putative connection between obstructive sleep apnea and hypercoagulability state.

Aged↗
PubMed1992

D-dimer and thrombin-antithrombin III complexes in patients with clinically suspected pulmonary embolism.

One hundred and fifty-six consecutive patients with clinically suspected pulmonary embolism (PE) had blood drawn to measure levels of D-dimer and thrombin-antithrombin (TAT) complexes and underwent ventilation/perfusion (V/Q) lung scanning and bilateral impedance plethysmography (IPG); pulmonary angiography was performed in 10 patients. Patients were classified as: PE-positive (positive pulmonary angiography or high probability lung scan or non-high probability lung scan and abnormal IPG) or, PE-negative (normal lung scan or normal pulmonary angiography) or PE-unlikely (non-high probability lung scan and normal serial IPG and absence of venous thromboembolism in follow-up). Thirty patients were classified as PE-positive, 64 as PE-negative and 62 patients as PE-unlikely. PE-positive patients were treated with anticoagulants, whereas PE-negative and PE-unlikely patients were not. PE-unlikely patients were followed for 3 months with repeat IPG and clinical evaluation for the occurrence of venous thromboembolism. The sensitivities, specificities, positive predictive values and negative predictive values of the D-dimer and TAT complex assays were calculated for patients classified as PE-positive and PE-negative. In addition, the prevalences of normal D-dimer and TAT complex assays were calculated for PE-unlikely patients. Cutoffs of 300 ng/ml for D-dimer and 3.5 micrograms/ml for TAT complexes provided sensitivities of 96% for both assays, negative predictive values of 97% for D-dimer and 96% for TAT complexes and specificities of 52% for D-dimer and 51% for TAT complexes. The specificities of the assays were higher in patients without comorbid conditions and in outpatients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

[The clinical value of D-dimer in the diagnosis and treatment of thromboembolic complications and DIC syndrome in cancer patients].

The content of D-dimer was studied in 130 patients with cancer at various sites. Twenty-five patients were diagnosed as having pulmonary thromboembolism (PTE), 30 had venous thromboses, and 35 patients had acute and subacute disseminated intravascular coagulation (DIC) syndrome. A control group included 40 patients without thrombotic complications. The studies were performed on an automatic STA COMPACT analyzing device. It has been shown that there is a drastic (10-15-fold) increase in the content of D-dimer as compared with the controls. The highest level of D-Dimer was observed in patients with acute DIC who have significant clinical symptomss. The level of D-dimer was to a lesser extent increased in patients with multiple organ deficiency. The content of D-dimer decreased during therapy anticoagulant therapy. When PTE, venous thrombosis, or DIS are suspected, it is advisable to include the study of D-dimer into a coagulogram.

Disseminated Intravascular Coagulation↗
PubMed1991

Dimerization of internalized epidermal growth factor receptors.

Binding of epidermal growth factor (EGF) to cell surface EGF receptors initiates the formation of the receptor homodimers that can be detected by covalent cross-linking in intact cells or in detergent-solubilized cell extracts. Low pH dissociation of EGF from surface receptors results in immediate monomerization of receptor dimers. Using chemical cross-linking during mild permeabilization or cell solubilization, we have detected dimers of internalized EGF receptors in human carcinoma A-431 cells and transfected NIH 3T3 cells that express human EGF receptors. The percentage of internalized cross-linked receptor dimers was similar to that observed for surface EGF receptors. Furthermore, at the time of maximal accumulation of EGF-receptor complexes within the endosomal compartment (10-15 min of incubation at 37 degrees C), both the dimeric and monomeric forms of the EGF receptor are tyrosine-phosphorylated to the same extent as surface dimer and monomer species. In transfected NIH 3T3 cells, the level of dimerized and internalized kinase-negative EGF receptors was not different from that observed for wild-type receptors. These data suggest that for some time after internalization EGF does not dissociate from its receptor and indicate that a receptor conformation is preserved intracellularly that allows maintenance of receptor-receptor interactions and tyrosine kinase activity.

3T3 Cells↗
PubMed2006

[Study on vibrational spectra and structure of 4-mercaptopyridine monomer and dimer using density functional theory].

The optimized molecular structure and vibrational frequencies of 4-mercaptopyridine monomer and dimer were studied by density functional theory using B3LYP method with the 6-311++G(d, p) basis set. On the basis of the calculations, the assignments of vibrational spectra were performed on monomer and dimer, and the change in structure and vibrational spectrum of dimer as well as the intermolecular force of forming dimer were investigated. It was found that the two pyridine ring planes are vertical to each other, and the dimer was formed through H-bonding, which is between the nitrogen on one ring and the hydrogen of SH moieties on another. Furthermore, the structure and vibrational spectrum of the dimer have some changes with respect to those of the monomer.

English Abstract↗
PubMed1975

The use of hybrid molecules in a study of the equilibrium between nerve growth factor monomers and dimers.

The major protein in beta nerve growth factor preparations, beta1NGF, is a dimer in which both peptide chains have COOH-terminal arginine residues. Digestion of beta1NGF with carboxypeptidase B produced a dimer, beta3NGF, in which both chains lack these terminal arginine residues. Exposure of mixtures of beta1 and beta3NGF dimers to 8 M urea to produce monomers, followed by removal of urea to allow recombination, resulted in the formation of the hybrid beta2NGF, comprising one arginine-containing and one arginine-less chain, as well as the parent dimers. The amount of the three dimers formed was close to that expected from random association of monomers. Hybrid beta2NGF was also formed from mixtures of beta1 and beta3NGF where incubated at pH 2.6 to 4.5. The formation of beta2NGF has a half-time of 6 h at pH 4.0 and 4 degrees C. Its rate of formation decreased above pH 4.5, becoming minimal between pH 9.5 and pH 10.5, and increased with increasing temperature. The amount of beta2NGF formed was determined by the lowest pH to which the parent mixture was exposed, irrespective of its prior history. These data suggest that the hybrid is formed by the same mechanism in the absence and presence of the urea step. An approximate value for Kd, the equilibrium dissociation constant of the dimer equilibrium monomer equilibrium was derived. Its value was 3 - 10(-10) M at pH 4.0 and 4 degrees C. The alpha-subunit of 7S NGF decreased the rate of formation of beta2NGF not only at pHs where an alphabeta complex is stable, but also at an acid pH where no complex formation is observed by sedimentation analysis, suggesting that the present methodology offers a more sensitive probe of subunit interactions. In contrast, the gamma subunit and a number of indifferent proteins had little or no effect on the appearance of beta2NGF at the pHs studied.

Animals↗