[Clinical relevance of I-123/I-131-MIBG scintigraphy in intestinal carcinoid tumors]. / Klinische Relevanz der I-123/I-131-MIBG-Szintigraphie bei intestinalen Karzinoiden.

AIM: Of this retrospective study was to determine the value of MIBG-scintigraphy in patients with intestinal carcinoids dependent on histological, clinical, and biochemical parameters. METHODS: In 15 patients uptake in carcinoid tumors and metastasis was correlated with location of the primary tumor, intra- and extrahepatic tumor masses, histology, immunhistochemistry, neuroendocrinological markers, and clinical symptoms. RESULTS: High uptake was to be seen almost only in tumor masses of primary tumors located in the terminal ileum. There also was a positive correlation with clinical symptoms for carcinoids and urinary 5-HIAA level. No correlation between MIBG uptake and tumor masses, histology, and most of the immunhistochemical and neuroendocrinological markers could be found. CONCLUSION: There is a limited indication for MIBG-scintigraphy in follow up of intestinal carcinoids. In patient with proven uptake MIBG scintigraphy is suitable for long-term follow up and therapy monitoring.

[Early detection of morphologic-functional changes in the airways using a simple method of inhalation scintigraphy]. / Früherkennung von morphologisch-funktionellen Veränderungen der Atemwege durch eine einfache Methode der Inhalationsszintigraphie.

In order to validate a method of inhalation scintigraphy with 99mTc-labeled human serum albumin in the early diagnosis of morphologic-functional changes of the airways 35 volunteers and patients (12 healthy non-smokers and smokers each, 11 patients with bronchitis) were studied. Deposition of the aerosol immediately after inhalation was calculated quantitatively by a ROI technique and qualitatively (scoring of central deposition, homogeneity, and recognizability of lung outline). Additionally, the regional clearance of the inhaled aerosol was determined by continuous lung imaging up to 60 min (mainly regional mucociliary removal rates). Discrimination between healthy volunteers and patients with bronchitis was possible by means of deposition patterns immediately after inhalation. On the other hand, no differences could be recognized in this way between healthy non-smokers and smokers. Regional mucociliary removal was higher in non-smokers than in smokers, but there was no difference between smokers and patients with bronchitis.

[The weighting of SE, IE and GE sequences in tumors of the head and neck]. / Wertigkeit von SE-, IE- und GE-Sequenzen bei Tumoren im Kopf-Hals-Bereich.

In a review of 82 patients having different benign and malignant head and neck tumours we studied the value of spin echo (SE), inversion echo (IE) and gradient echo (GE) sequences. The strong T1 weighted IE mode is highly sensitive to demonstrate pathological tissue. Tumour diagnosis was in 20% and lymph node diagnosis in 29% better than T2 weighted SE sequences. According to this experience we choose the IE mode as the first one for all patients examined for tumour staging. All other sequences and orientations are planned on this tomograms knowing the location of the tumour and lymph nodes. T1 weighted SE mode is indispensable and should be recorded in transversal orientation, covering the whole head and neck region. This mode has the best imaging of anatomical structures as the known fatty limitations. The best differentiation of the tumour is usually obtained after contrast enhancement by i.v. Gd-DTPA. The highest contrast enhancement is seen on T1 weighted GE tomograms, which we prefer. T2 weighted SE sequences are less sensitive than IE sequences and T1 weighted tomograms after Gd-DTPA to show the tumour. The T2 weighted SE mode cannot be replaced by the T2 weighted GE mode having a better signal to noise ratio. To minimise the scan-time of T2 weighted SE mode, only one measurement is performed; the quality of the tomograms is satisfactory.

The efficacy of nifedipine and acebutolol in coronary artery disease assessed by radionuclide ventriculography.

The efficacy of a fixed combination of 10 mg nifedipine and 100 mg acebutolol was tested in 21 patients with angiographically proven coronary artery disease (CAD). Ejection fraction (EF), emptying and filling rate (VS and VD), and end-systolic volume (ESV) were assessed by means of radionuclide ventriculography at rest and during exercise prior to as well as 1 hour and 5 hours following oral drug application. Whereas exercise-induced worsening of cardiac function had been documented in all the patients prior to medication, EF and ESV improved significantly after drug administration.

Curative radioimmunotherapy of human mammary carcinoma xenografts with iodine-131-labeled monoclonal antibodies.

The radioiodinated monoclonal antibody BW 495/36 showed an exceptionally high uptake and long residence time in human ductal mammary carcinoma xenografts in nude mice. There was a mean tumor uptake of 82%/g 24 hr p.i., decreasing with a biologic half-life of approximately 6 days, to 15%/g by Day 16. The tumor-to-blood ratio increased from 2.8 to 21.4 and the percentage of the whole-body retention recovered in the tumor from 47% to 80% during the same time interval. The therapeutic efficiency of two injections of 7.4 MBq 131I-BW 495/36 was evaluated by comparing the tumor size with that in mice injected with either the same amount of the unlabeled MoAb, the same radioactivity of an 131I-labeled nonspecific MoAb, or with saline only. The high tumor accumulation of 131I-BW 495/36 led to a total tumor dose of 77 Gy resulting in a mean reduction in tumor diameter of 50%, corresponding to a reduction in tumor volume of 88% within 42 days p.i. Unlabeled MoAb had no effect on tumor growth compared with controls, whereas 131I nonspecific antibody caused a slight inhibition of tumor growth. Histologic tumor sections showed large areas of necrosis and a pronounced vacuolation of the tumor cell cytoplasm between Days 7 and 30 p.i. By Day 42 all remaining tissue in the tumor was identified as mouse connective tissue.

[Age-related heart function in patients with healthy hearts]. / Altersabhängigkeit der Herzfunktion bei Herzgesunden.

Left ventricular function was investigated at rest and during submaximal exercise in 191 healthy subjects, including 46 women, by means of radionuclide ventriculography (RNV). As global parameters of heart function, ejection fraction (EF) and maximal rates of volume change during systole (VS) and diastole (VD) as well as endsystolic volume (ESV) were determined. These parameters were calculated for four age groups with mean ages of 32, 45, 55, and 64 years, respectively. At rest, heart rate (HR), EF, VS, and ESV were not significantly different in all age groups, whereas VD decreased with increasing age from 3.3 +/- 0.6 s-1 to 2.6 +/- 0.6 s-1. During exercise, HR, EF, VS, and VD increased in all groups, but less in the elderly. The smaller increase of EF and VD could be accounted for by HR alone. VS was both HR- and age-dependent. The age dependence of VD (at rest) and VS (under exercise) may reflect a reduction of myocardial compliance with increasing age. Differences of EF and VS with respect to sex were not observed, whereas VD was slightly lower in males.

[Dual-photon absorptiometry: a new method of determining bone mineral content. I. Basic principles]. / Doppelphotonen-Absorptiometrie: Eine neue Methode zur Bestimmung des Knochen-mineralgehaltes. I. Grundlagen.

Today dual-photon absorptiometry (DPA) is recommended as the best procedure for diagnosing osteoporosis at an early stage considering its low cost, low radiation exposure and reasonable reliability. Cortical (neck of femur) and trabecular (L 2-4) bone mass has been determined repeatedly with DPA using 153Gd (NOVO Lab 22 a) in 545 females and 112 males with no evidence of bone diseases. Measured "normal" (age- and sex-related average) values for bone mineral content (BMC) differed significantly (p less than 0.01) from those of US inhabitants determined by the same equipment, i.e., they were on average about 30% lower, but matched well with corresponding results from Belgium. BMC-area was found the most suitable parameter both for cross-sectional and longitudinal studies, since it is independent of height and weight. But there is still need to reduce the overlap and improve accuracy and reproducibility for making decisions after shorter intervals. Assessment of the individual mineral loss and fracture risk by comparison with average values remains problematical due to the wide range of "normal" BMC values, and in women additionally due to the variable onset of menopause. For estimations of the individual fracture risk of elderly patients BMC should not be normalized on age, because at the age of 65 half of the women had "pathologic" values, i.e. were below the so-called "osteoporosis threshold". Comparison of the individually measured postmenopausal BMC with average values of premenopausal women and with BMC values normalized to their menopausal age may be helpful approaches to overcoming these difficulties.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-linear correlation of basal serum TSH and TRH-stimulated TSH response: new aspects in pituitary-thyroid regulation.

The relationship between basal and TRH-induced TSH in the 200 micrograms i.v. TRH test has been reinvestigated using one of the new 'supersensitive' TSH-IRMA assays. A total of 761 consecutive TRH tests (1522 sera) in unselected patients attending the Thyroid Out-patient Department was studied. The closest correlation (r = 0.962, In S.D. = 0.46787) of both TRH test parameters was found using logarithmic transformation of TSH-levels and a least squares fit based on a sixth degree polynomial approach. The resulting correlation curve revealed three points of inflection, one located in the subnormal, one in the normal and one in the high-normal range of the basal as well as the TRH-induced TSH concentrations. This indicated that 'fine-tuning' of pituitary-thyroid axis occurs according to a non-linear dose-response relationship. Consequently, the interpretation of the TRH test on the basis of delta-TSH used hitherto has to be reconsidered.

[After care of differentiated thyroid gland carcinoma with special reference to serum thyroglobulin level]. / Nachsorge des differenzierten Schilddrüsenkarzinoms unter spezieller Berücksichtigung des Serum-Thyreoglobulin-(hTg-)Spiegels.

The histories of 358 patients with carcinomas of the thyroid have been evaluated. Differentiated carcinomas of the thyroid (84.6%) were treated by means of thyroidectomy, ablative radio-iodine therapy (tissue dose 1000 Gray), TSH-suppressive thyroid hormone medication and, in special cases, external radiation. Even differentiated carcinomas showed a high recurrence rate. Metastases occurred particularly in the lungs, the skeleton and locally; low iodine uptake, particularly in distant metastases from papillary carcinomas, often made it impossible to reach a diagnosis by using radio-iodine. Some pulmonary metastases could only be demonstrated radiologically and some skeletal metastases could be shown radiologically or scintigraphically. A modified follow-up program for differentiated carcinomas is suggested, based on the highly sensitive and specific thyroglobulin determination under TSH suppression (sensitivity 97.9%, specificity 93.6%).

Improved radioimmunoscintigraphy of human mammary carcinoma xenografts after injection of an anti-antibody.

The low tumor-to-background ratio obtained after administration of radiolabeled whole monoclonal antibodies (MAbs) is one of the major problems in immunoscintigraphy and -therapy. To reduce the blood pool label caused by the circulation of radiolabeled MAb we have investigated the advantage of injecting an anti-antibody after administration of a tumor-specific MAb in nude mice bearing human mammary carcinoma xenografts. The MAb MA 10-11 of rat origin, used in these studies, had shown a high affinity to human mammary carcinoma tissue on frozen sections and low cross-reactivity with various normal human tissues. 24 h after injection of 1.5 MBq 131I-labeled MAb containing 10 micrograms IgG2a one group of mice received an additional injection of 100 micrograms anti-rat antibody. Blood taken 2 min after the second antibody injection showed nearly the whole activity bound to antibody aggregates, that cleared very rapidly from the circulation and accumulated in liver and spleen. The transitory high liver activity decreased within several hours because of rapid deiodination of the antibody-complex in this organ. The release of radioactivity from the spleen, however, was found to be much slower. The rapid excretion of the radioactivity from the blood pool combined with a nearly constant tumor activity allowed early tumor detection with tumor-to-blood ratios of 250:1 at 48 h after anti-antibody injection compared to 1.1:1 obtained for the control animals. In addition the results may explain the reported reduction of imaging quality and high uptake of radioactivity in the spleen of patients having repeated injections of mouse MAbs due to complex formation after development of human anti-mouse antibodies.

Measurement of myocardial fatty acid metabolism: kinetics of iodine-123 heptadecanoic acid in normal dog hearts.

To define the potential of iodine-123 heptadecanoic acid (IHA) for the noninvasive assessment of myocardial fatty acid metabolism with gamma camera imaging, the influence of myocardial oxygen consumption (MVO2) and blood flow (MBF) on extraction and half-times of IHA were investigated in dogs. Following IHA injection into the left circumflex coronary artery, extraction fraction and half-times were derived from the peak and slope of the IHA time activity curve, which consisted of a vascular, early, and late phase. Single-pass extraction fraction of IHA averaged 0.53 +/- 0.11 s.d. at control and was not influenced by MVO2 and MBF. The half-time of the early phase (T = 9.3 min +/- 2.8 s.d. in controls) as well as the ratio between the size of the early and late phase increased with MVO2 (r = 0.82, r = 0.87, respectively). Thus, early phase intracellular turnover of IHA increased, yet clearance of 123I activity was slowed by augmented cardiac work. Preliminary data of HPLC and electrophoretic analysis of myocardial arterial and venous blood samples over time indicate that the early phase is characterized by a decreasing washout of IHA and a relative increase of radioiodine washout. The half-time of the late phase (T = 245 min +/- 156 s.d. at control) was not related to MVO2 and MBF. In conclusion, myocardial fatty acid metabolism cannot be measured from the half-time of the early phase but might be analyzed from the ratio between the size of the early and late phase when using IHA.

Radionuclide assessment of a normal left ventricular response to exercise in patients without evidence of heart disease.

The aim of this study was to define normal left ventricular performance at rest and during supine bicycle exercise with equilibrium radionuclide ventriculography in a normal population other than young healthy volunteers. Thirty-one patients (mean age 45 years +/- 9 SD) with chest pain of varying origin and no evidence of heart disease proven by means of noninvasive and invasive techniques were studied. Left ventricular ejection fraction (LVEF) at rest averaged 0.64 +/- 0.07 SD and increased with peak exercise to 0.73 +/- 0.08 SD (P less than 0.005). Change in LVEF from rest to maximum exercise ranged within 0-0.19. Six patients (19%) failed to augment LVEF with exercise to more than 0.05; none of the patients dropped LVEF during exercise. Multivariate analysis revealed no significant predictors of LVEF response to exercise. However, there was a tendency that resting LVEF and enddiastolic volume index with exercise might influence LVEF response to exercise. Peak left ventricular ejection rate (LVER) at rest averaged 3.3 s-1 +/- 0.6 SD and increased to 5.1 s-1 +/- 1.1 SD (P less than 0.005) with exercise. Peak left ventricular early filling rate (LVFR) was 2.8 s-1 +/- 0.6 SD at rest and was measured 5.5 s-1 +/- 1.3 SD at maximum exercise (P less than 0.005). Left ventricular enddiastolic volume (EDV) did not change significantly from rest to maximum exercise, whereas left ventricular endsystolic volume (ESV) decreased to 79% +/- 19 SD (P less than 0.01) of the value at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Performance of two new solid-phase ligand assays for TSH using monoclonal antibodies.

Three ligand assays for TSH using monoclonal antibodies, an IRMA, an ELISA and a DELFIA were compared with a standard DAB RIA technique. The IRMA proved to be superior in respect to sensitivity, precision, reproducibility and practicality. The highest sensitivity yet, was achieved by DELFIA. IRMA, ELISA and DELFIA are performable on a daily routine basis. ELISA and DELFIA have the additional advantage of being non-isotopic immunoassays (NIIA). Under routine conditions IRMA reveals the best discrimination of hyperthyroid from euthyroid patients by basal TSH. This fact improves the TSH determination's clinical value considerably and may in the future--if confirmed--change the diagnostic schemes in use at present, e.g. rendering most of the TRH-tests unnecessary.

[Dissimilar course in the right and left ventricular function in a patient with dilated cardiomyopathy]. / Diskrepanter Verlauf der rechts- und linksventrikulären Funktion bei einem Patienten mit dilatativer Kardiomyopathie.

The case of a patient with severe dilative cardiomyopathy and cardiomegaly demonstrates that M-mode echocardiography and planar chest radiographs are not always sufficient to follow up the disease correctly. Using other non-invasive imaging modalities, in this case radionuclide ventriculography and NMR tomography, which provide more precise information with regard to morphology and function of both the right and the left heart, allows a more reliable follow-up of the disease.