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Biomedical subjects

E Bernardi

Publications and source records attributed to E Bernardi.

At least 37 records · Page 2Linked to original sources

Accuracy of two newly described D-dimer tests in patients with suspected deep venous thrombosis.

Accumulating evidence suggests that the ELISA determination of D-Dimer might be a useful tool for the exclusion of deep vein thrombosis (DVT) of lower extremities, because of its high sensitivity and negative predictive value. However, conventional ELISA assay is time-consuming and, therefore, is not suitable for emergency use. To evaluate the accuracy of two rapid assays recently described, 126 consecutive outpatients with the clinical suspicion of DVT underwent the NycoCard D-Dimer and the Instant I.A. D-Dimer determination, using venography as the reference test. In all patients, the conventional ELISA assay was also performed. Venography confirmed the presence of DVT in 30 patients (23.8%), and ruled out the diagnosis in the remaining 96. Instant I.A D-Dimer was positive in 28 patients with DVT (sensitivity, 93.3%), and negative in 90 subjects free from thrombosis (specificity, 93.8%). Nycocard D-Dimer correctly identified 27 patients with DVT (sensitivity 90.0%), and was negative in 77 subjects free from thrombosis (specificity, 80.2%). Sensitivity, specificity, negative and positive predictive values of both tests did not differ from those found with the classic ELISA method. In conclusion, both Instant I.A. D-Dimer and Nycocard D-Dimer assays show a great potential for clinical use.

Adult↗

Upper-extremity deep vein thrombosis. Risk factors, diagnosis, and complications.

BACKGROUND: Little is known about the clinical, diagnostic, and prognostic aspects of upper-extremity deep vein thrombosis (UEDVT). OBJECTIVES: To identify the clinical and laboratory parameters associated with this disease, to assess the diagnostic accuracy of ultrasonographic methods for its detection, and to establish the frequency of both early and late complications. PATIENTS AND METHODS: After a careful history was taken, 58 consecutive patients with signs and symptoms that were clinically suggestive of UEDVT underwent the determination of antithrombin III and protein C and S levels and resistance to activated protein C and lupuslike anticoagulants. Compression ultrasonography, color flow Doppler imaging, and Doppler ultrasonography were performed prior to venography. Patients with confirmed UEDVT underwent objective tests to detect a pulmonary embolism and were followed up prospectively to record recurrent thromboembolic events and postthrombotic sequelae. RESULTS: Findings from venography confirmed UEDVT in 27 patients (47%). Central venous catheters, thrombophilic states, and a previous leg vein thrombosis were statistically significantly associated with UEDVT. Sensitivity and specificity of compression ultrasonography (96% and 93.5%, respectively) and color flow Doppler imaging (100% and 93%, respectively) were comparable and better than those of Doppler ultrasonography (81% and 77%, respectively). Objective findings suggestive of a pulmonary embolism were recorded in 36% of the patients with UEDVT. After a mean follow-up of 2 years, 2 patients with UEDVT experienced recurrent thromboembolic events, and 4 had postthrombotic sequelae. CONCLUSIONS: Symptomatic UEDVT is associated with central venous catheters, thrombophilic states, and a previous leg vein thrombosis. Both compression ultrasonography and color flow Doppler imaging are accurate methods for its detection. A pulmonary embolism is a common complication of the disease. Finally, this disorder may recur and may be followed by postthrombotic sequelae.

Adult↗

A complementarity-determining region peptide of an anti-desmosome autoantibody may interact with the desmosomal plaque through molecular mimicry with a cytoplasmic desmoglein 1 sequence.

The sera of patients with pemphigus, a group of autoimmune blistering skin diseases, contain autoantibodies directed against components of adhering junctions termed desmosomes. F12, a human monoclonal antibody derived from a pemphigus patient, recognizes an unknown polypeptide of the desmosomal and hemidesmosomal plaques. The third complementarity-determining region of the F12 heavy chain (VH-CDR3) was shown to share a four-amino-acid sequence (GSSG) with the intracellular domains of desmoglein 1 and bullous pemphigoid antigen 2 which interact with components of, respectively, the desmosomal and hemidesmosomal plaques. Computer modeling of F12 showed that the GSSG sequence protudes inside the antigen-combining site and thus might be involved in antigen interactions. The GSSG sequence is essential to F12 function, since a peptide containing the VH-CDR3 inhibited its binding to target antigens while VH-CDR3 peptides with specific modifications of the GSSG sequence did not. These data allow us to hypothesize that certain autoantibodies produced during the course of an autoimmune disease can behave as adhesion molecules, through the molecular mimicry of the motif involved in protein/protein adhesion, and to propose a new self-antigen binding mechanism for some autoantibodies.

Amino Acid Sequence↗

Investigating synthetic P-regions from voltage-gated sodium channel at the conformational and functional levels.

Four peptides mimicking the four P-regions of the electric eel sodium channel were chemically synthesized to characterize their secondary structure and their contribution to the channel selectivity. Circular dichroism spectra of these peptides in trifluoroethanol demonstrate an important beta-sheet conformational component. This beta-sheet content is much enhanced upon interaction with phosphatidylcholine small unilamellar vesicles. As expected (and except for P of domain III), no significant voltage-dependence is revealed in either macroscopic or single-channel conductance experiments. The concentrations-dependences of macroscopic conductances suggest that tetramers are the membrane conducting aggregates. In asymmetric ionic conditions, these channels made up of P-peptides were mostly specific for sodium over chloride whilst caesium was largely excluded. Single-channel conductance analysis discloses a moderate selectivity for sodium over potassium for PI and PII. This selectivity is larger with PIII but inverted for PIV. Finally, a control random peptide of the same length and with a comparable mean hydrophibicity was also tested. Its conformation in TFE is mainly unordered and no activity was detected in planar lipid bilayers. The data suggest that the presumed selectivity filter may not assume a circular symmetry and that molecular recognition between the different P-regions has to be taken into account.

Amino Acid Sequence↗

The long-term clinical course of acute deep venous thrombosis.

BACKGROUND: In patients who have symptomatic deep venous thrombosis, the long-term risk for recurrent venous thromboembolism and the incidence and severity of post-thrombotic sequelae have not been well documented. OBJECTIVE: To determine the clinical course of patients during the 8 years after their first episode of symptomatic deep venous thrombosis. DESIGN: Prospective cohort study. SETTING: University outpatient thrombosis clinic. PATIENTS: 355 consecutive patients with a first episode of symptomatic deep venous thrombosis. MEASUREMENTS: Recurrent venous thromboembolism, the post-thrombotic syndrome, and death. Potential risk factors for these outcomes were also evaluated. RESULTS: The cumulative incidence of recurrent venous thromboembolism was 17.5% after 2 years of follow-up (95% CI, 13.6% to 22.2%), 24.6% after 5 years (CI, 19.6% to 29.7%), and 30.3% after 8 years (CI, 23.6% to 37.0%). The presence of cancer and of impaired coagulation inhibition increased the risk for recurrent venous thromboembolism (hazard ratios, 1.72 [CI, 1.31 to 2.25] and 1.44 [CI, 1.02 to 2.01], respectively). In contrast, surgery and recent trauma or fracture were associated with a decreased risk for recurrent venous thromboembolism (hazard ratios, 0.36 [CI, 0.21 to 0.62] and 0.51 [CI, 0.32 to 0.87], respectively). The cumulative incidence of the post-thrombotic syndrome was 22.8% after 2 years (CI, 18.0% to 27.5%), 28.0% after 5 years (CI, 22.7% to 33.3%), and 29.1% after 8 years (CI, 23.4% to 34.7%). The development of ipsilateral recurrent deep venous thrombosis was strongly associated with the risk for the post-thrombotic syndrome (hazard ratio, 6.4; CI, 3.1 to 13.3). Survival after 8 years was 70.2% (CI, 64.7% to 75.6%). The presence of cancer increased the risk for death (hazard ratio, 8.1; CI, 3.6 to 18.1). CONCLUSION: Patients with symptomatic deep venous thrombosis, especially those without transient risk factors for deep venous thrombosis, have a high risk for recurrent venous thromboembolism that persists for many years. The post-thrombotic syndrome occurs in almost one third of these patients and is strongly related to ipsilateral recurrent deep venous thrombosis. These findings challenge the widely adopted use of short-course anticoagulation therapy in patients with symptomatic deep venous thrombosis.

Adult↗

Chemical synthesis, structural and functional characterisation of noxiustoxin, a powerful blocker of lymphocyte voltage-dependent K+ channels.

Two forms of the Centrudoides noxius scorpion noxiustoxin, containing an amidated and an acid C-terminus, were synthesized on a solid support by using Fmoc-chemistry and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) coupling. Comparison of the two synthetic forms with the native toxin by tryptic mapping and CD spectroscopy shows that noxiustoxin possesses an amidated C-terminus and the same fold as all short scorpion toxins. Patch-clamp assays on B lymphocytes demonstrate that noxiustoxin inhibits the voltage-dependent K+ channels with 2 nM affinity, but does not affect the Ca(2+)-activated K+ channels. This toxin, because of its high affinity and specificity for voltage-gated K+ channel, may provide a powerful tool in the investigation of the role(s) of these channels in the T and B lymphocyte activation and proliferation.

Amino Acid Sequence↗

The utility of non-invasive tests for detection of previous proximal-vein thrombosis.

BACKGROUND: Despite the availability of several diagnostic methods for the detection of deep-vein thrombosis (DVT), the identification of previous episodes of DVT remains a diagnostic challenge. STUDY OBJECTIVE: To assess the reliability of a combination of a standardized clinical score with three non-invasive tests: compression ultrasonography (CUS), Doppler ultrasound (DUS), and photoplethysmography (PPG), in determining the presence or the absence of previous proximal DVT. METHODS: One hundred consecutive unselected outpatients were identified, who had undergone contrast venography six to nine years previously because of the clinical suspicion of DVT (confirmed in 43). They were blindly reinvestigated by a panel of trained operators unaware of venography results. They underwent a clinical evaluation of the lower limb, by applying a standardized score to five symptoms and six signs (grading each item from 0 to 3); a PPG test to determine the venous refilling time; a DUS test to determine the venous reflux separately in the common femoral and the popliteal vein; and a CUS test to determine vein compressibility in the same regions. RESULTS: An abnormal CUS test and/or the demonstration of venous reflux in the popliteal region and/or a high clinical score (> or = 8) identified twenty-four of the 43 (56%) DVT + patients with a specificity of 89%. The combination of normal CUS with the absence of venous reflux in both the common femoral and popliteal vein and a low clinical score excluded previous thrombosis in 45 (79%) of the 57 DVT-patients (negative predictive value, 78%). Abnormal venous reflux in the isolated common femoral vein did not reliably predict the presence or absence of previous DVT. However, this occurred in only 13 (13%) patients. The PPG determination of venous refilling time did not improve the results obtained with the other tests. CONCLUSIONS: The combination of a standardized clinical evaluation with the results of CUS and DUS can reliably diagnose or exclude previous proximal-vein thrombosis in almost 90% of patients with previous episodes of suspected DVT.

Double-Blind Method↗

Acquired risk factors for deep-vein thrombosis in symptomatic outpatients.

BACKGROUND: Epidemiologic studies on deep-vein thrombosis (DVT) have been mainly confined to the inpatient population. The aim of this study was to investigate the association between DVT and acquired risk factors in a large cohort of outpatients with clinically suspected DVT. METHODS: Consecutive outpatients with clinically suspected DVT were enrolled in the study. Before objective testing, all patients were interviewed by a trained physician for the presence of risk factors for DVT development. Subsequently, the presence or absence of DVT was assessed with venography. RESULTS: Approximately 50% of cases of DVT were considered to be secondary to a major risk factor (immobilization, trauma, and/or recent surgery). Among additional risk factors, only increased age (over 60 years), male gender, malignant neoplasm, heart failure, systemic lupus erythematosus, and arteriopathy were independently associated with the risk of acute DVT. CONCLUSION: Major risk factors for venous thromboembolism are a common cause of DVT among symptomatic outpatients; therefore, the usefulness of extending DVT prophylaxis in the outpatient setting should be tested. The role of additional risk factors in the development of DVT needs to be established by properly designed studies.

Ambulatory Care↗

Changing features of proximal vein thrombosis over time.

Recently, the sensitivity of impedance plethysmography (IPG) for the diagnosis of acute deep-vein thrombosis (DVT) in symptomatic outpatients has been questioned. In order to verify whether a change in the venographic pattern of DVT has occurred over years, accounting for the decreased sensitivity of IPG, the authors compared two series of consecutive venograms demonstrating proximal DVT, performed between 1984-1988 (166 patients) and 1990-1992 (140 patients). They evaluated both the extension and the occlusiveness of deep-vein thrombi in the two series. Moreover, changes in the referral characteristics of patients were investigated. In the second series of venograms a significant decrease in thrombi extension, expressed by a lower prevalence of iliac vein thrombosis (29% versus 43%; P = 0.0074) was observed; moreover, a significant increase in the prevalence of nonocclusive thrombi (22% versus 8%; P = 0.0004) was also recorded in the second series when compared with the first. During the study period, among the referral characteristics of patients, the authors observed both a significant decrease in the prevalence of proximal DVT (from 31% to 24%; P < 0.01) and a slight and not statistically significant decrease in the median time elapsed between onset of symptoms and referral for objective testing (from eight and a half to seven days). In conclusion, proximal deep-vein thrombi are currently less extensive and occlusive than observed in the past. These results might depend on earlier referral of less symptomatic patients and might explain the recently reported decrease in IPG sensitivity for proximal DVT.

Analysis of Variance↗

A simple ultrasound approach for detection of recurrent proximal-vein thrombosis.

BACKGROUND: The objective of this study was to develop a simple ultrasound method for measuring thrombus regression in patients with proximal deep-vein thrombosis (DVT) and to test its utility for the detection of DVT recurrence. METHODS AND RESULTS: The study comprised a cross-sectional survey and a prospective investigation (149 and 145 patients, respectively). In both phases, the normalization rate of a previously abnormal ultrasound test, applying the criterion of full compressibility of the common femoral and popliteal veins (C-US method), was assessed. In the prospective study, the vein diameter under maximum compression (thrombus thickness) was measured in the abnormal venous segments at scheduled times (1, 3, 6, and 12 months). In patients presenting with suspected DVT recurrence, the procedure was repeated and results were compared with those available from the previous examination. Noncompressibility of a previously normal(ized) venous segment and enlargement of thrombus thickness (> or = 2 mm) were considered diagnostic of proximal DVT recurrence. The diagnostic accuracy of the C-US method alone, as well as of the combined ultrasound methods (C-US + thrombus thickness), was assessed against contrast phlebography. C-US test normalization occurred in only 30% of patients within 1 year. A significant reduction of the thrombus mass (P < .0001) was recorded throughout the entire study period. However, a major decrease in thrombus mass (> 50%) was recorded within the first 3 months. Of 29 patients who developed a suspected recurrent DVT, phlebography confirmed diagnosis in 11. The C-US method alone showed an excellent accuracy (100%) but was applicable in only 6 patients (21%). Both the sensitivity and the specificity for proximal DVT recurrence of the combined ultrasound methods were 100% (95% confidence interval, 69% to 100% and 81% to 100%, respectively) and were applicable in all patients. CONCLUSIONS: The serial ultrasound measurement of thrombus mass after an acute episode of DVT may allow the correct identification of patients who develop a recurrent proximal-vein thrombosis.

Cross-Sectional Studies↗

Quality of parenting in alcoholics and narcotic addicts.

Alcoholics and heroin addicts were compared with a normal control group to determine whether there were differences in quality of parenting during childhood, assessed using the Parental Bonding Instrument. Maternal and paternal overprotection were reported more commonly by narcotic addicts. Maternal overprotection alone was implicated in alcoholics. Narcotic addicts seem to have more disturbed parenting than alcoholics, especially paternal parenting.

Adult↗

[Radiological study of renal injuries].

An evaluation is made of the radiological diagnosis techniques used in the classification of renal traumas. Attention is primarily directed to arteriographical pictures, since it is felt that this examination is the most meaningful for the purposes of precise classification, above all as the prelude to possible surgery. Some cases of varying degrees of seriousness are illustrated, including one of contusion in a "pancake" kidney.

Adult↗