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The high incidence of deep venous thrombosis requires for successful therapy a timely and accurate diagnosis. We report early clinical results with a 99mTc-labelled anti-platelet antibody (BW 4) for the diagnosis of thrombosis or for studying platelet kinetics. 10 patients were studied of whom 7 were imaged for the detection of thrombi. 3 deep venous thromboses were diagnosed. 3 patients were sent for diagnosing pathological platelet kinetics; 2 demonstrated a markedly changed platelet biodistribution (increased spleen uptake compared to thrombosis patients). The simple and safe handling of the labelling kit enables early studies (within 30 min). The short physical half-life of 99mTc allows a favourable target (thrombus) to non-target (blood-pool) ratio for diagnosis within 2-6 h after injection. Human anti-mouse antibodies were not found in the serum of 4 patients (blood drawn until 4 weeks after administration). There were no side effects.

Left ventricular systolic and diastolic performance was evaluated by radionuclide angiography in 17 patients following cardiac transplantation and compared with normal persons. Both groups performed supine bicycle exercise during the investigation, the control group at 102 +/- 73 W and the transplanted patients at 61.2 +/- 15 W. The ejection fraction increased in the normal persons from 61 +/- 8 to 69 +/- 10% whereas in the transplanted patients it did not increase significantly. There were no relevant changes in systolic parameters during exercise in the transplant recipients. The changes in diastolic parameters were significantly smaller in transplant patients than in normals. After correction for heart rate-induced changes a significantly different time course of the systolic-diastolic sequence during the cardiac cycle became evident in the transplanted group at rest. During exercise the systolic-diastolic sequence during the cardiac cycle became similar in both groups. It is concluded that the reduced exercise capacity of patients in the late phase after cardiac transplantation is partially due to the absence of an EF increase and a limitation of diastolic reserve during exercise.

Fifty-one patients with muscle-infiltrating bladder carcinoma (T2-T4, N0-3, M0-1) were studied with a new imaging technique using murine monoclonal antibody directed against the carcinoembryonic antigen (CEA). A total number of 67 investigations were performed. The intact 111indium-labelled antibody (BW 431/26, Behringwerke Marburg) detected 86% of primary tumours, 93% of local and 75% of distant metastases whether there was an elevated CEA level in serum or not. Immunohistologically (avidin-biotin-peroxidase method) positive frozen tissue sections from tumour biopsies stained with the same monoclonal anti-CEA antibody, thus confirming the presence of the CEA antigen in vitro. The method was of much higher sensitivity in detecting even very small metastases than X-ray computed tomography (86% versus less than 30%). The specificity was in the region of 90%. The response to chemotherapy (MVEC regimen) was shown by repeated studies demonstrating reduced uptake (partial remission) or no accumulation (complete remission) in the second immunoscan. We suggest immunoscintigraphy of bladder tumours and their metastases as an additional method in preoperative staging and postoperative care.

Using the intact monoclonal IgG1 anti-CEA antibody BW 431/26 (Behringwerke Marburg, FRG) labelled with 99mTc by a new labelling procedure (Schwarz method), 72 patients suspected of tumour recurrences (colorectal cancer, n = 59) and with rising serum carcinoembryonic antigen (CEA) levels were studied. Sixty-nine of 72 studies had a positive result by immunoscintigraphy of which 52 have since been proven histologically/clinically. In six patients only immunoscintigraphy revealed a tumour recurrence while all other diagnostic modalities were negative. Of 52 studies 46 were true positive (diagnostic sensitivity 88%). In this series there was one false positive result. About one-third of all patients injected with the antibody developed a human anti-mouse response (HAMA), but no severe side effects were seen even after four applications. For the follow-up of colorectal and other CEA positive adenocarcinomas this 99mTc-labelled monoclonal antibody seems to be very promising in patients with rising serum CEA, especially if conventional diagnostic imaging procedures remain negative.

Nine hyperthyroid patients (FT4 greater than or equal to 20 ng/L; FT3 greater than or equal to 6 ng/L) were given 1 X 10 mg bisoprolol/day p.o. for a period of 7 days. Pharmacokinetic data were derived from measurements of plasma bisoprolol concentrations after the first dose and at steady state after 7 days treatment. The thyroid hormones FT4, FT3, and rT3 were determined in the serum before and after bisoprolol treatment. In addition, subjective and objective parameters of thyroid function were recorded during the course of the therapy. The maximum bisoprolol concentrations measured after the first dose and after 7 days were 54.3 +/- 2.1 and 70.3 +/- 3.8 ng/ml, respectively, the minimum concentrations being 9.6 +/- 1.0 ng/ml and 11.9 +/- 1.7 ng/ml, respectively. This yields an accumulation factor of 1.2. At steady state, the plasma elimination half-life of bisoprolol was 9.8 +/- 0.9 h. No significant changes in serum thyroid hormones were observed during bisoprolol treatment. There was, however, an improvement in the subjective and objective clinical symptoms of hyperthyroidism. In comparison with the findings in healthy volunteers, the pharmacokinetics of bisoprolol remained unaltered in mild to moderate hyperthyroid patients. After oral application of bisoprolol, only small variations in the plasma concentration were observed inter- and also intraindividually in the course of treatment. This finding reflects the high absolute bioavailability of bisoprolol.

Twenty patients aged 32-76 years (median 56 years) with various primary cancers or tumor recurrences (colorectal n = 14; lung, breast, medullary thyroid carcinoma n = 2, each) were studied with a technetium-99m labeled anti-CEA antibody. Intact monoclonal antibody BW 431/26 (Scintimum CEA-Tc-99m, Behringwerke AG, Marburg) was successfully labeled (Schwarz Method) by an instant 2-vial kit (labeling efficiency greater than 95% (TLC, HPLC), preserved immunoreactivity). The most frequent clinical indications were (1) the detection of tumor recurrences in patients with a steadily increasing serum CEA level (at a mean 2.3 years after complete removal of the primary tumor) but normal findings by conventional imaging modalities, (2) the search for extrahepatic tumor involvement in patients with known liver metastases scheduled for regional chemotherapy. Gamma camera scintigrams (planar and ECT) were performed 6-12 h and 18-26 h postinjection yielding a sensitivity of 95% (positive tumor contrast in 19/20 patients) with a specificity of 90% (positive predictive value 95%). Immunoscintigraphy successfully depicted tumor recurrences in 4/6 patients with elevated serum CEA values where all conventional imaging modalities had failed. The successful labeling of monoclonal antibodies with 99mTc represent an important step in clinical progress for the more practically orientated use of immunoscintigraphy and also opens new diagnostic fields.

Echography of the thyroid gland is a non-invasive and simple method without contraindications. The method is reliable, inexpensive and of high diagnostic efficiency. The structural information provided by the ultrasound technique complements the results of laboratory tests and other in-vivo techniques. Normal echogenicity can be observed in health persons as well as in diffuse goiters. An echofree area with enhanced echogenicity is a typical sonogram of a cystic structure. Circumscript enhanced echogenicity is usually due to a benign lesion. Areas of diminished echogenicity may be benign or malignant. In patients with Graves' disease or patients suffering from lymphocytic thyroiditis, diffuse diminished echogenicity is found in a high percentage. CT of thyroid masses allows an exact measurement of the volume of the organ to be made together with its retrosternal parts. CT examinations can locate the spread into the frontal and posterior mediastinum, thus providing optimal operative access to retrosternal goiters. Remnants of thyroid malignancies, lymph-node metastasis, infiltration into the sternum and occlusions of larger vessels due to tumour growth are visible in the CT-Scan. It is not possible to differentiate between malignant tumours or benign masses, if there is no infiltration into the surrounding organs. Also hyperthyroidism and thyreoiditis cannot be differentiated. In our opinion ultrasound examinations should immediately follow the patient's history and physical examination. Additional in-vivo methods should be performed according to the specified problems.

The available noninvasive cardiac investigational methods allow an accurate diagnosis in patients with acquired valvular defects and, in most cases, a decision on timing of surgery. Retrospective studies showed that cardiac catheterizations in 45 of 111 consecutively investigated patients were superfluous. Thus, in 40% of these patients noninvasive methods were sufficient for a reliable decision on whether to proceed with surgery or conservative measures and for a satisfactory objective assessment of preoperative haemodynamics and morphology. Invasive methods should only be used when there are insufficient or discrepant noninvasive findings or when accompanying coronary heart disease must be excluded.