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Biomedical subjects

M N Wasser

Publications and source records attributed to M N Wasser.

34 records · Page 2Linked to original sources

Hemodynamic significance of renal artery stenosis: digital subtraction angiography versus systolically gated three-dimensional phase-contrast MR angiography.

PURPOSE: To compare digital subtraction angiography with three-dimensional phase-contrast magnetic resonance (MR) angiography in detection of significant renal artery stenosis. MATERIALS AND METHODS: Sixteen patients underwent digital subtraction angiography and systolically gated three-dimensional phase-contrast MR angiography within 1 week. Scoring of stenosis on MR angiograms was based on presence and length of a flow void and quality of flow signal intensity in the distal part of the artery. Intraarterial pressure measurement was the reference standard for hemodynamically significant renal artery stenosis. RESULTS: MR angiography depicted two of five patent accessory arteries. Comparison of digital subtraction angiography and MR angiography with intraarterial pressure measurements was possible in 25 main renal arteries. In 13 arteries, a pressure gradient of more than 15 mm Hg was found. Digital subtraction angiography depicted 10 of these stenoses (sensitivity, 77%; specificity, 92%). A flow void was present at MR angiography in eight stenoses (sensitivity, 62%; specificity, 83%). In 12 of the stenosed vessels, distal flow signal intensity was impaired at MR angiography (sensitivity, 92%; specificity, 75%). There was no difference between the two modalities (P > .05) in grading hemodynamic significance of renal artery stenosis. CONCLUSION: Systolically gated MR angiography and digital subtraction angiography are equally effective in depicting hemodynamically significant stenoses in the main renal arteries. MR angiography, however, is not adequate in depiction of accessory renal arteries.

Adult↗

Doppler sonography evaluation of superior mesenteric artery flow to assess Crohn's disease activity: correlation with clinical evaluation, Crohn's disease activity index, and alpha 1-antitrypsin clearance in feces.

OBJECTIVE: This study was undertaken to investigate the value of Doppler flow measurements of the superior mesenteric artery (SMA) as a marker for disease activity in patients with Crohn's disease. SUBJECTS AND METHODS: Duplex Doppler sonography measurements of SMA blood flow volume were obtained in 29 consecutive patients with suspected Crohn's disease. We prospectively sought a correlation between the independent assessment of Doppler flow measurements and markers for disease activity: Crohn's disease activity index and fecal alpha 1-antitrypsin clearance and our reference standard based on clinical history, physical examination, laboratory values, endoscopy, surgery, and follow-up. RESULTS: In 27 of 29 patients, adequate measurements of SMA blood flow were obtained. In 15 patients no disease activity was judged to be present or no Crohn's disease (n = 2) was found at follow-up (group 1). In 12 patients, activity of Crohn's disease was diagnosed (group 2) on the basis of the reference standard. In group 2 the Doppler SMA blood flow values were significantly higher (p < .05) than those for group 1 (826 +/- 407 ml/min versus 323 +/- 103 ml/min). Of the other parameters investigated, only the alpha 1-antitrypsin value correlated with the reference standard but to a lesser degree than the values for SMA blood flow measurement. CONCLUSION: This prospective study shows that SMA Doppler blood flow measurements can be used to assess disease activity in patients with Crohn's disease. This approach may be of value in the diagnosis and follow-up of patients with Crohn's disease, providing directly available, quantifiable, noninvasive information on disease activity.

Adult↗

Activity of Crohn disease assessed by measurement of superior mesenteric artery flow with Doppler US.

PURPOSE: To test the hypothesis that increased blood flow in the superior mesenteric artery (SMA) reflects disease activity in patients with Crohn disease. MATERIALS AND METHODS: Duplex Doppler sonographic measurements of SMA blood flow volume were obtained in 10 patients with active Crohn disease, 10 patients with chronic inactive Crohn disease, and 10 healthy volunteers. Disease activity was determined with clinical and laboratory indicators. RESULTS: Interstudy reproducibility of repeated SMA flow volume measurements was good (r = .98). A marked increase in SMA flow volume was noted in patients with active disease compared with patients with inactive disease and healthy volunteers: 1,588 mL/min +/- 576 versus 288 mL/min +/- 113 and 417 mL/min +/- 147, respectively (P < .05 for both comparisons). CONCLUSION: Activity of Crohn disease causes a substantial increase in SMA flow volume. Measurement of SMA blood flow may be an important noninvasive, readily available, inexpensive tool that can be used to monitor Crohn disease objectively.

Adolescent↗

Effects of an antifibrin monoclonal antibody and fragments thereof on some properties of fibrin.

Antifibrin monoclonal antibody Y22, of IgG1-subclass, has its epitope in the D-domain of fibrin. In a thrombin time assay, Y22 and its F(ab)2 fragments interfere with clotting of citrated plasma. Transmission and scanning electronmicroscopic studies show that clotting of citrated blood or plasma in the presence of Y22 results in formation of thin, short fibrin fibres. The (smaller) Fab fragments of Y22 did not have an anti-clotting effect. This suggests that the anticoagulant effect of Y22 is due to steric hindrance of the association of fibrin monomers. A control antibody and its F(ab)2 and Fab fragments have no effect on fibrin formation. In a parabolic rate assay, Y22 Fab fragments interfered strongly with the fibrin-induced enhancement of the t-PA-catalyzed plasminogen activation, whereas intact Y22 and a control antibody did not. In contrast with their effects on the fibrin assembly, the effects of Y22, Y22-F(ab)2 and Y22-Fab on the capacity of fibrin to act as a rate-enhancer in the plasminogen activation by t-PA appears to decrease with the size of the immunoreactive entity. As is discussed, this may be due to the differential accessibility of sites involved in stimulation and polymerization which are located in the fibrin D-domain.

Amino Acid Sequence↗

Thrombus detection using a Tc-99m labeled antifibrin monoclonal antibody (MoAb). Experiments in vitro and in animals.

This paper describes the production and characterization of an antifibrin monoclonal antibody, produced by immunizing mice with fibrinogen degradation fragment Y. The antibody (designated Y22) is directed against a conformation dependent epitope in the D-domain of fibrin Y22 was labeled with the radionuclide Tc-99m. Experiments in vitro and in rats are presented which show the potential of scintigraphic detection of thrombi with Tc-99m-Y22. Preliminary results show that immunoscintigraphy of thrombi may also have potential for the monitoring of thrombolytic therapy (eg with t-PA).

Animals↗

An antifibrin monoclonal antibody useful in immunoscintigraphic detection of thrombi.

Balb/c mice were immunized with human plasmin-generated fibrinogen degradation product Y. Spleen cells were fused with P3X63-Ag8.653 myeloma cells. A clone (Y22) was found that produces monoclonal antibodies (MoAbs) with a strong reactivity with human fibrin and only a weak reactivity with fibrinogen in an enzyme immunoassay (EIA). Y22 also reacts with fibrin of rabbits, rats, sheep, and dogs. The antibodies are of the IgG1 kappa-type and appear to be directed against a conformation-dependent epitope in the D-domain of fibrin. Experiments with 99mTc-labeled Y22 in vitro show that Y22 binds rapidly to forming clots. 99mTc-Y22 also binds to preformed plasma clots in a plasma milieu, even in the presence of high concentrations of heparin. Clot localization experiments in rabbits and rats confirm the high fibrin specificity and the potential of 99mTc-Y22 for thrombus imaging in vivo.

Abdomen↗

A new method for protein labeling with 99mTc.

A method is described for labeling proteins with 99mTc, the radionuclide of choice in diagnostic nuclear medicine. Labeling efficiency, stability of label attachment and retained biological behaviour, e.g. immunoreactivity of monoclonal antibodies after radiolabeling are demonstrated. An application of a 99mTc-labeled anti-fibrin monoclonal antibody in radioimmunoimaging of thrombi is presented.

Albumins↗

An in vitro model for the scintigraphic detection of thrombi using a 99Tcm-labelled antifibrin monoclonal antibody.

Because of their specific targeting properties, monoclonal antibodies have found widespread use in nuclear medicine. In this paper, a method is described for the evaluation of immunoscintigraphic parameters for the detection of thrombi, using a 99Tcm-labelled antifibrin monoclonal antibody (designated as Y22). An in vitro model was developed to evaluate the effects of various environmental conditions on uptake by plasma clots of 99Tcm-Tc-Y22 in circulating plasma on a gamma camera. The clots became visible as hotspots after approximately 1 h of circulation of 99Tcm-Y22 containing citrated plasma at 37 degrees C. Circulation of 99Tcm-fibrinogen, 99Tcm-HSA or 99Tcm-control MoAb did not show visible uptake by the clots under the same conditions. At 37 degrees C, 99Tcm-Y22 accumulated approximately four times faster than at 20 degrees C. Heparin did not affect binding of the antibody to clots. To assess the feasibility of thrombus detection in vivo, an extracorporeal rat thrombus model was used. A thrombus in a shunt between a carotid artery and a jugular vein became visible 1 h after injection of the labelled Y22 and, more clearly, after 3 h.

Animals↗

The effect of fresh versus stored blood on post-operative bleeding after coronary bypass surgery: a prospective randomized study.

In a prospective study, 237 patients undergoing a primary coronary bypass operation were randomized to receive 2 units of fresh whole blood (study group) or stored (2-5 d) blood (control group) at the end of the extracorporeal circulation. Serious post-operative bleeding necessitating a re-thoracotomy occurred in 4.2% of all patients with an equal distribution over the two groups. Post-operative haemoglobin content and platelet counts were higher in the study group, but the differences were small and clinically not important. There were no differences in transfusion requirements, post-operative blood losses and haemostatic parameters between the trial groups. At low post-operative platelet counts (below 120 X 10(9) platelets/l) however, patients in the control group lost significantly more blood and had increased transfusion requirements compared with patients in the study group (7.1 versus 4.8 units). These differences must be attributed to qualitative platelet defects in the transfused units of stored blood. The small, clinically insignificant, differences in two laboratory parameters between the study and control groups, and the increased transfusion requirements of a subpopulation of patients with low platelet counts in the control group do not justify giving fresh blood or prophylactic platelet transfusions to coronary bypass patients.

Blood Preservation↗

Anaphylaxis as a rare complication of a barium enema examination.

A patient is described who developed anaphylaxis with respiratory and circulatory arrest after a single contrast barium enema examination. Since barium sulphate is an inert substance, the reaction must have been caused by additives present in the barium suspension.

Aged↗

Alloimmunization after leukocyte-depleted multiple random donor platelet transfusions.

In a prospective study we investigated the development and the course of alloimmunization after leukocyte-depleted red cell and multiple random donor platelet transfusions in 335 patients. Of these 335 patients, who had a negative antibody screening on admission and a negative transfusion history, 69 (21%) developed either transient (n = 18) or permanent (n = 51) lymphocytotoxic antibodies, but only 31 patients (9%; 95% confidence limits 6-12%) developed multispecific alloantibodies necessitating HLA-matched platelet transfusions. There was no difference with regard to the development of antibodies and platelet refractoriness between leukemia patients receiving cytostatic treatment and patients with aplastic anemia receiving prednisone and antithymocyte globulin. Females with previous pregnancies developed platelet refractoriness with an increased incidence (Chi 2 13.38; p less than 0.001) compared to females without previous pregnancies, males, and children.

Blood Platelets↗

A new method for 99Tcm-labelling of proteins with an application to clot detection with an antifibrin monoclonal antibody.

A new method is described for labelling proteins with 99Tcm. Labelling of fibrinogen resulted in a radiochemical yield of about 80%. After clotting this 99Tcm-labelled fibrinogen with trombin, an equal percentage of the radioactivity was found in the clot illustrating the retained biological behaviour of this labile protein after our labelling procedure. Labelling of a monoclonal antibody (MoAb) directed against fibrin resulted in a labelling percentage of about 70%. Immunoreactivity of this antifibrin (Y22) is hardly affected by the procedure as demonstrated by a double-sandwich enzyme immunoassay (EIA). Perfusion experiments on a gamma camera in which a plasma clot in a glass chamber was perfused with plasma containing 99Tcm-labelled Y22 revealed an excellent uptake of activity by the clot within 2 h. Finally an animal experiment is presented which showed clear visualization of the thrombi in the jugular vein and the abdomen of a rabbit by scintigraphy after the administration of 99Tcm-labelled antifibrin (Y22).

Animals↗

Variations in blood flow waveforms in stenotic renal arteries by 2D phase-contrast cine MRI.

Waveform variations in blood flow measurements through stenotic renal arteries have been reported already with echo Doppler studies. We studied these variations with MRI in 14 patients (mean age, 60 years) with suspected renal arterial stenosis (24 patent arteries, four occluded). Flow measurements were successful in 15 arteries and unsuccessful in nine, due to practical limitations. Seven healthy younger volunteers (mean age, 28 years) and five healthy older volunteers (mean age, 58 years) were recruited for comparison purposes. In patients, the severity of stenoses was also assessed by digital subtraction angiography and intraarterially measured transstenotic pressure drops. We found flow patterns to be statistically significantly (P < 0.01) age-related. Younger healthy subjects showed shorter wave duration, higher diastolic flow, and total blood flow per minute. Also, with increasing stenosis severity, the systolic wave became more damped and the systolic wave duration became statistically significantly (P = .03) longer.

Adult↗

Systolically gated 3D phase contrast MRA of mesenteric arteries in suspected mesenteric ischemia.

OBJECTIVE: Our goal was to assess the value of MRA for detecting stenoses in the celiac (CA) and superior mesenteric (SMA) arteries in patients suspected of having chronic mesenteric ischemia, using an optimized systolically gated 3D phase contrast technique. MATERIALS AND METHODS: In an initial study in 24 patients who underwent conventional angiography of the abdominal vessels for different clinical indications, a 3D phase contrast MRA technique (3D-PCA) was evaluated and optimized to image the CAs and SMAs. Subsequently, a prospective study was performed to assess the value of systolically gated 3D-PCA in evaluation of the mesenteric arteries in 10 patients with signs and symptoms of chronic mesenteric ischemia. Intraarterial digital subtraction angiography and surgical findings were used as the reference standard. RESULTS: In the initial study, systolic gating appeared to be essential in imaging the SMA on 3D-PCA. In 10 patients suspected of mesenteric ischemia, systolically gated 3D-PCA identified significant proximal disease in the two mesenteric vessels in 4 patients. These patients underwent sucessful reconstruction of their stenotic vessels. CONCLUSION: Cardiac-gated MRA may become a useful tool in selection of patients suspected of having mesenteric ischemia who may benefit from surgery.

Adult↗