In vivo demonstration of focal fibrinolytic activity in abdominal aortic aneurysms.

Disseminated intravascular coagulation in association with arterial aneurysm has been reported in several cases. Reports have suggested a continuous deposition of fibrin and/or platelets at the site of the aneurysm followed by fibrinolysis as responsible for this disorder. To further investigate this theory we studied the in vivo binding of an indium-111-labelled monoclonal antibody against human tissue plasminogen activator (t-PA), a proteolytic enzyme involved in the fibrinolysis. Six patients admitted to the hospital for elective resection of an abdominal aortic aneurysm with a mural thrombus were examined. One day before the operation the antibody was injected intravenously. Scintigrams acquired just prior to operation and tissue samples obtained at the operation revealed an increased t-PA accumulation in the wall of the aneurysm. The study demonstrates in vivo, focally increased fibrinolytic activity in the aneurysm, explaining the coagulopathy observed in these patients.

Esophageal scintigraphy: reproducibility and normal ranges.

Esophageal scintigraphy has been rather widely used, but much debated as a simple screening method of esophageal dysfunction. However, reports of normal ranges, age dependence and reproducibility are very limited. We studied 60 healthy subjects with a mean age of 43 yr (26, 19, 15 subjects aged 20-39, 40-59, and 60-79 yr) to establish normal ranges and variations of esophageal mean transit time and residual activity measured by a radionuclide method using [99mTc] pertechnetate labeled water. Mean transit time was calculated by Zierler's formula. The median values and 95% percentiles of single measurements of MTT and residual activity in the supine position were 6.1 (3.2-11.5) sec and 11.5 (3.0-50)%, respectively. The coefficients of variation (CV) were 20%-35% for mean transit time and 85%-120% for residual activity in the sitting and supine positions. When double measurements were used, the CVs were reduced to 10% for MTT and 40% for residual activity in the supine position. The values did not change with age except for a higher frequency of spikes in subjects over 40 yr. The study has demonstrated that mean transit time for radiolabeled water in the esophagus of healthy subjects, measured by double determinations, has rather low, age-independent, interobserver and intersubject variabilities. In contrast, measurements of residual activity shows unacceptably high variations.

Biological background subtraction improves immunoscintigraphy by subsequent injection of antigen.

We have developed an 111In-labeled antibody for in vivo use directed against tissue plasminogen activator demonstrating focal fibrinolytic activity. However, a major problem in immunoscintigraphy is the low signal-to-noise ratio due to circulating antibody. The hepatic clearance of t-PA is very rapid. The effect of a subsequent injection of a small amount of t-PA shortly after the antibody administration to increase the blood clearance rate of the formed antigen-antibody complexes was examined in six rabbits. More than 99% of the circulating antigen-antibody complexes were eliminated by the liver within 10 min. This technique could make immunoscintigraphy a first line diagnostic tool in acute medicine including imaging of thromboembolic lesions in organs with high blood volumes such as the lungs, the heart, and the brain.

Fallacy in direct cystourethrography.

Voiding cystourethrography is widely used in children to detect vesicoureteral reflux disease. A case of radionuclide voiding cystourethrography is reported, where the initial location of the catheter tip in an open ureter ostium might have lead to erroneous interpretation. Recommendations for catheter technique and control of imaging in voiding cystourethrography are given.

[Production of human antimurine antibody after in vivo use of radioisotope labelled murine antibodies]. / Produktion af humant antimurint antistof efter in vivo anvendelse af radioaktivt maerkede murine antistoffer.

In vivo employment of monoclonal antibodies of murine origin (MoAb) with the object of immunotherapy or immunoscintigraphy may result in formation of human antimouse antibodies (HAMA) in a number of the persons exposed. HAMA is of IgG and also IgM types. Allergic reactions may occur but only few are of serious nature (less than 0.3 per thousand). In cases where MoAb is administered on repeated occasions, HAMA forms complexes with the injected which results in resuced quality of immunescintigraphic examinations, increased clearance of MoAb and reduced effect of immunetherapy. "Sandwich" type of immune analyses on blood samples which contain HAMA must be planned so that HAMA interference is eliminated.

Detection of deep venous thrombosis with indium 111-labelled monoclonal antibody against tissue plasminogen activator.

The administration of a radiolabelled monoclonal antibody against tissue plasminogen activator allows detection of areas with increased fibrinolytic activity, i.e. those with an active thrombotic lesion. Eight patients with phlebographically verified deep venous thrombosis were examined. At the time of immunoscintigraphy study they were examined receiving anticoagulant therapy. Some 75-85 MBq indium 111-labelled antibody were injected, and scintigrams were obtained after 30 min and after 24 h. The precise site of the thrombus could not be visualized after 30 min due to high background activity, whereas after 24 h it was detectable in all patients. The thrombus/background ratios achieved are twice as high as those observed in a human antifibrin antibody study. These preliminary data suggest a high sensitivity of our t-PA-specific antibody for the detection of active deep venous thrombosis in man, and our antibody seems to offer theoretical advantages over both platelet and fibrin-specific antibodies.

Effects of heavy hyperventilation on transcutaneous and arterial oxygen tensions in healthy adults.

Transcutaneous pO2 on thorax and the volar part of the forearm was measured in six healthy volunteers during heavy hyperventilation, and the values compared with simultaneously measured arterial blood pO2. We found a significant rise in arterial pO2 during hyperventilation with a lesser increase in thoracic transcutaneous pO2. When measured on arm the transcutaneous pO2 did not even rise significantly. After hyperventilation pO2 fell to values below the resting level. The transcutaneous/arterial pO2 index, fell significantly during hyperventilation with the greatest reduction in the arm index. After hyperventilation the arm index returned to the control values, whereas the thoracic index remained low. We suggest, that the significant fall in transcutaneous/arterial blood pO2 index during hyperventilation is caused primarily by skin vasoconstriction, whereas the fall in pO2 after hyperventilation is caused by hypoxia. When measured on areas with increased muscular activity transcutaneous pO2 might depend on the local blood flow and skin oxygen consumption also, causing problems in interpretation with certain patient groups.

Persistent impairment of liver function caused by a pendulated accessory liver lobe.

A large pendulated accessory liver lobe and complete absence of the left lobe were discovered by liver scintigraphy and ultrasound scanning in a patient suspected of having an ovarian tumor. The patient had a history of fluctuating impaired liver function tests for many years, probably caused by intermittent torsion of the peduncle. Pedunculated accessory liver lobes are extremely rare and seldom diagnosed in vivo. Our patient seems to be the 11th published case, and the only 1 in which longstanding fluctuating impaired liver function tests have been observed.

A prospective study of antisperm antibody development in acute epididymitis.

The association between acute epididymitis and development of antisperm antibodies was investigated by the gelatin agglutination technique in prospectively collected serum samples from 27 patients. Agglutinating antisperm antibodies, mainly of the IgG class, were detected in seven men (27 per cent), a significantly increased frequency compared to prevalences previously found among blood donors and men from infertile couples. The antibodies developed de novo in four patients (15 per cent). The increased incidence of positive sera and the kinetics of the antibody responses strongly indicate a causal link between acute epididymitis and autoimmunization against spermatozoa. In the majority of the patients the antibody titers were low, being of only theoretical importance in respect to later fertility.