Occupancy of striatal D(2)-like dopamine receptors after treatment with the sigma ligand EMD 57445, a putative atypical antipsychotic.

RATIONALE: EMD 57445 (panamesine) is a high affinity sigma ligand with the profile of an atypical antipsychotic in animal studies. It has been reported recently to have antipsychotic activity in schizophrenia. However, its metabolite, EMD 59983, binds also to D(2) and D(3) dopamine (DA) receptors. OBJECTIVES: The aim of this study was to test, using single photon emission computed tomography (SPECT) and [(123)I]iodobenzamide (IBZM) as the radiotracer, whether EMD 59983 would pass the blood-brain barrier and to what extent it would contribute to the effects of EMD 57445 in schizophrenia. METHODS: Two IBZM SPECT-scans were performed in five neuroleptic-free schizophrenic patients (DSM IV), one before and one after treatment with 60 mg panamesine daily for a treatment duration of 12-26 days. RESULTS: A high occupancy of striatal D(2)-like DA receptors similar to that induced by typical neuroleptics was observed in all patients treated with EMD 57445. CONCLUSIONS: Our results suggest that a possible antipsychotic activity of EMD 57445 in schizophrenia is not necessarily attributable to its affinity for sigma receptors, but could be simply due to the potent antidopaminergic effects of EMD 59983, its main metabolite.

[Automatic setting of the contrast range of whole body scintigrams using a histogram method]. / Automatische Kontrasteinstellung von Ganzkörperszintigrammen mit einer Histogramm-Methode.

AIM: To get standardised results on the display of whole body scintigrams regarding an optimal contrast setting (using linear scaling), an algorithm was developed, which can be used for an automatic setting of an upper intensity truncation value. METHODS: From the integral of the gray level histogram of 30 randomly selected whole body images upper threshold values LA were defined, where a certain area percentage A (80% < or = A < or = 99.5%) of all pixels with intensity > 0 are contained in the intensity range. Independently an interactive upper level Lvis of the contrast range was determined by two observers to get an optimal visual appearance of the image. RESULTS: For the threshold levels with an area percentage A of 92% ... 98% (L92 ... L98) a very close linear correlation (r > 0.9) was found to the visual levels. Levels resulting to area percentages A < 92% or A > 98% correlated worse to the interactive values. Based on our results we propose as a good definition for an upper threshold on whole body scintigrams with dual intensity ranges: Range 1 (high activities): Upper threshold = min (2.5 x L95, 100%), Range 2 (low activities): Upper threshold = min (1.25 x L95, 100%). CONCLUSION: The procedure is well suited for an automatic definition of the contrast settings of whole body scintigrams. It can be implemented easily; its use gives a substantial contribution to the standardisation of the documentation of scintigrams.

[Imaging of metastases from thyroid carcinomas using 111In-pentetreotide scintigraphy]. / Darstellung von Metastasen eines Schilddrüsenkarzinoms mittels 111In-Pentetreotide-Szintigraphie.

There is little experience with imaging of thyroid carcinoma tissue by somatostatin receptor scintigraphy. Our case report describes an acromegalic patient, in whom 111In pentetreotide scintigraphy did not only demonstrate a receptor-positive pituitary tumor but also visualized metastases from a papillary thyroid carcinoma which had no correlate in radioiodine scintigraphy carried out under hypothyroid conditions. The possible role of this radiopharmaceutical in dedifferentiating thyroid carcinoma is discussed for its usefulness in tumor localisation and its predictive value for the outcome of an octreotide therapy.

Assessment of ventricular function with first-pass radionuclide angiography using technetium 99m hexakis-2-methoxyisobutylisonitrile: a European multicentre study.

In the context of a multicentre study on the use of technetium 99m hexakis-2-methoxyisobutylisonitrile (99mTc-Sestamibi), we evaluated the accuracy of the ventricular function assessed at rest by means of first-pass radionuclide angiocardiography acquired during the injection of the tracer for myocardial perfusion scintigraphy. The results were compared with first-pass studies performed using reference tracers sodium pertechnetate Tc 99m or technetium 99m diethylene triamine penta-acetic acid or with gated radionuclide angiocardiography. A total of 66 patients of the 105 enrolled in the study could be evaluated. The comparison of the first-pass studies was possible in 33 subjects with regard to the left ventricular ejection fraction, yielding r = 0.909 (P less than 10(-6)), and in 22 cases with regard to the right ventricular ejection fraction, yielding r = 0.712 (P less than 0.001). The comparison between the first-pass study using 99mTc-Sestamibi and the equilibrium gated radionuclide angiocardiography was possible for the left ventricular ejection fraction in 26 cases, with r = 0.937 (P less than 10(-6)), and for the right ventricular ejection fraction in 15 subjects, with r = 0.783 (P less than 0.001). In conclusion, the assessment of ventricular function performed by acquiring a first-pass radionuclide angiocardiograph during the injection of 99mTc-Sestamibi for perfusion myocardial scintigraphy can be considered reliable and accurate, when compared with the usually employed techniques. This result confirms the feasibility of a combined evaluation of perfusion and function at rest and during stress testing, which represents one of the most interesting advantages offered by the use of 99mTc-Sestamibi.

[Stomach emptying after stomach resection with and without retention of duodenal passage]. / Magenentleerung nach Magenresektion mit und ohne erhaltene Duodenalpassage.

On domestic pigs 2/3 gastrectomies with retention and elimination of the duodenal passage were carried out. Postprandial gastric emptying was measured scintigraphically for 4 h and compared with a control group (laparotomy only). For the semi-solid, 99mTc-labeled test meal delayed gastric emptying after elimination of the duodenal passage by Roux reconstruction could not be shown. There was no difference in gastric emptying between B-I and Roux-en-Y partial gastrectomy. Also alteration of the length of the jejunum loop from 40 to 20 cm after Roux-en-Y reconstruction had no influence on gastric emptying. Roux reconstruction (40 cm loop) in combination with truncal vagotomy led to a non-uniform gastric emptying, but there was a statistically proven acceleration compared with B-I resection. After 240 min the mean residual intragastric activity of the control group (n = 5) was 47.8%, 78.9% after B-I resection (n = 5), 59% after Roux reconstruction with 40 cm jejunal loop (n = 5), 38.1% after Roux reconstruction with 20 cm jejunal loop (n = 5) and 20.9% after Roux-en-Y (40 cm loop) with truncal vagotomy (n = 4).

Regional cerebral blood flow in depression: associations with psychopathology.

Regional cerebral blood flow (rCBF) was measured during rest and cognitive activation in 21 patients with a major depressive episode and 21 healthy subjects. Depressive patients had significantly lower rCBF during rest in the right global, frontal, parietal, occipital and temporal regions and in the left global and frontal regions. During mental activation patients showed significantly lower values in all right and left parietal regions. rCBF was correlated with the scores of the Brief Psychiatric Rating Scale (BPRS), the parietal regions. rCBF was correlated with the scores of the Brief Psychiatric Rating Scale (BPRS), the Bech-Rafaelsen Melancholia Scale (BRMS), the Hamilton Depression Scale (HAM-D) and the Hamilton Anxiety Scale (HAM-A). The most significant negative correlations were obtained with the BPRS. Correlation analyses between each single item of the BPRS and CBF values revealed the strongest associations between emotional withdrawal and decreased CBF. Patients with 'reactive' features had higher CBF than patients without 'reactive' symptoms. Only patients without 'reactive' symptoms had a lower CBF than controls. 'Endogenous' features had no impact on CBF.

[The place of bone scintigraphy in the diagnosis and follow-up of Ewing's sarcoma]. / Stellenwert der Skelettszintigraphie in der Diagnostik und Verlaufskontrolle des Ewing-Sarkoms.

The radiological and scintigraphic findings of 26 patients with histologically proven Ewing's sarcoma were analysed. Three-phase bone scan should be done early in patients presenting with pain and normal radiographs. Perfusion and metabolism of a bone lesion can be assessed by skeletal scintigraphy. Bone metastases are first seen on bone scan. In the follow-up of the patient bone scans at regular intervals are essential to detect bone metastases and tumour recurrence. The scintigraphic findings have to be correlated with radiographs and if these are negative a short-term control is indicated. Three-phase bone scans can assess the tumours response to therapy.

RCBF-quantification with 99mTc-HMPAO-SPECT: theory and first results.

The activity concentrations of 99mTc-HMPAO in brain after intravenous injection were evaluated in 25 patients using SPECT. With additional first pass studies of heart and brain with the short lived isotope 195mAu, the cardiac output and the mean cerebral transit times of the patients were measured a short time before the HMPAO injection. The time dependence of 99mTc-HMPAO activity in the brain was registered during the first 5 min after injection over both hemispheres. Using a simplified three compartment model it was possible to calculate the mean retention fraction of HMPAO in brain from the time activity curves. It could be shown that the regional cerebral blood flow in ml/min per 100 g can be calculated from the activity concentration of HMPAO in the brain, the cardiac output and the retention fraction. In 15 of the 25 cases the rCBF was measured using the planar 133Xe inhalation method as a reference. We found a significant correlation between the mean hemisphere CBF from our method and the mean hemisphere grey matter CBF from the Xenon method with a correlation coefficient of 0.73.

Intraoperative localization of malignant pheochromocytoma by 123-I-metaiodobenzylguanidine single probe measurement.

Metaiodobenzylguanidine (MIBG) imaging is a well-established method for locating intra- and extraadrenal pheochromocytomas. We investigated whether preoperative injection of 123-I-MIBG might be useful for intraoperative staging of chromaffine tumor cells. This was performed in a 46-year-old patient in whom the diagnosis of a malignant pheochromocytoma had been established by 123-I-MIBG imaging and enhanced catecholamine secretion. The rationale for intraoperative staging in this patient was a discrepancy between computed tomography (CI) of the abdomen and the radionuclide imaging, because scintigraphy revealed a mass with MIBG uptake in the right lower abdomen that could not be visualized by CT. We thus applied a preoperative dose of 4 mCi 123-I-MIBG and determined tissue activity by direct organ measurement. A right abdominal mass was thus identified with an activity of 10 x 10(4) impulses/s as compared to normal tissue (15 x 10(2)). The left-sided tumor was found to be identified correctly by prior CT and MIBG imaging. We thus conclude that intraoperative application of this single probe measurement might help to identify chromaffine tumor cells that have not been located fully by CT.

[Focal nodular hyperplasia of the liver in 930 patients]. / Fokal-noduläre Hyperplasie der Leber bei 930 Patienten.

Analysis of 930 patients with focal nodular hyperplasia of the liver (FNH), including 23 seen by the authors, showed the following results: 82.2% of patients were female, 37.8% of these had taken female steroidal hormones. There was no preference for a particular lobe of the liver. 57.7% of FNH were subcapsular, 33.7% were intrahepatic and 8.8% were pedunculated. Average size was 5.9 cm, 80.8% of the patients were asymptomatic. In 93.5% (115 out of 123) a space-occupying lesion in the liver could be demonstrated by sonography. In 13%, second or multiple tumours were missed by sonography. CT without enhancement demonstrated FNH in 90.4% (94 out of 104 patients). A rapid, marked increase in density after contrast was seen in 64 out of 68 lesions (94.1%). Colloid scintigraphy showed normal uptake in 34.9% of patients. Hepato-biliary functional scintigraphy demonstrated 32 out of 35 lesions (91.4%). In 97.3% (183 out of 188) FNH was demonstrated by angiography, in 95.4% as a highly vascular tumour.

[Difficulties in the diagnosis of osteoid osteoma]. / Schwierigkeiten bei der Diagnostik des Osteoidosteoms.

The difficulties arising in diagnosing osteoidosteoma are demonstrated by means of 30 surgically treated cases and the results are compared with those available from the literature. The value of bone scintigraphy and of tomography within the framework of a diagnostic concept is underlined. Diagnosis is confirmed and treatment is effected by the successful surgical removal of the nidus.

Echocardiographic findings in patients with proved pulmonary embolism.

Echocardiographic studies were performed in 105 patients with acute and recurrent pulmonary emboli. Pulmonary embolism was confirmed by pulmonary angiography (n = 48), autopsy (n = 6), and lung perfusion scintigraphy (n = 51). Seventy of 93 patients (75%) displayed a dilated right ventricle, 38 of 91 patients (42%) had reduced left ventricular cavity dimension, 41 of 82 patients (50%) had a decreased EF slope of the mitral valve, and 78 of 101 patients (77%) showed dilatation of the right pulmonary artery. The motion of the interventricular septum was abnormal in 41 of 93 patients (44%). Right-sided thrombi were seen in 13 patients within the right pulmonary artery (n = 11) and in the right ventricle (n = 3); in one patient they were found in the superior vena cava, in the innominate vein, and the right atrium. Two patients suffered from right-sided endocarditis. Thus echocardiographic changes were frequently found in patients with proved pulmonary emboli. The echocardiographic findings of right-sided cardiac and pulmonary artery abnormalities indicate hemodynamically active pulmonary emboli.

Balloon coronary angioplasty in patients with acute myocardial infarction.

After successful thrombolysis, approximately 75% of all patients will have significant coronary stenosis, which can be dilated by means of percutaneous transluminal balloon angioplasty (PTCA). In a randomized control study, 95 of our patients (Group I) had thrombolysis alone, whereas 95 others (Group II) had thrombolysis and PTCA. Both groups were comparable with respect to age, sex, infarct location, and maximal creatine kinase (CK) value. The clinical outcome during the hospital phase was better in Group II, which had a reocclusion rate of 13%, a reinfarction rate of 5%, a lethal reinfarction rate of 2%, and a cardiac death rate of 7%, compared with respective rates of 20%, 13%, 7%, and 13% in Group I. Furthermore, in Group I, residual coronary stenosis immediately after thrombolysis (75% +/- 20%) did not improve significantly until the end of the hospital phase, when it decreased to 69% +/- 21%. In Group II, stenosis (78% +/- 16%) was improved by PTCA to 33% +/- 21%, and this improvement remained constant during the hospital phase (30% +/- 26%). In Group-II patients who had an unsuccessful PTCA, stenosis was approximately the same before dilatation (83% +/- 12%), after dilatation (80% +/- 17%), and at the control study (83% +/- 17%). The end-diastolic, end-systolic, and stroke volume indices, as well as the ejection fraction, also remained unchanged. In Group I, the number of pathologic wall segments (12.2 +/- 5.0) did not improve during the hospital phase (12.2 +/- 7.9), but in Group II, the improvement was significant (14.0 +/- 5.7 vs. 10.9 +/- 8.2) (p < 0.05). PTCA seems to improve the clinical outcome, reduce the infarction and mortality rates, and enhance myocardial perfusion and performance.

[Effect of spinal CSF dynamics on the subarachnoid diffusion of a substance applied close to the spinal cord]. / Der Einfluss der spinalen Liquordynamik auf die subarachnoidale Ausbreitung rückenmarksnah applizierter Substanzen.

In order to better understand the effects and side effects of intraspinal administration of morphine we studied the rostral spread of a comparable substance within the cerebrospinal fluid (CSF). This study was performed in connection with nuclear medical diagnostics ruling out possible rhinorrhoea or disturbances of CSF-circulation in 14 patients: Following lumbar intrathecal injection of the tracer 111-Indium-DTPA, the radioactivity over the medulla oblongata was measured continuously for 2 1/2 hours with a single probe scintillation counter; thereafter the distribution of activity over the total spinal canal was determined; finally the spread of activity was registered with the gamma scintillation camera in the 3rd, 24th and 48th hour. The diffusion of the tracer was followed in a model of the subarachnoid space. A few minutes after injection, activity over the medulla oblongata could be detected; initially it increased markedly, later less so; at the end of the 2 1/2 h observation time, approximately 8% of the total activity had reached this level. The timing of activity increase and the peak activity over the medulla oblongata varied between the individuals. Up to 48 hours the activity continued to shift from the spinal canal to the endocranium. Diffusion played a secondary role. These results are further evidence that morphine is transported cephalad within the CSF rather quickly and may act on cervical spinal cord and brainstem.

Comparison of 131I-metaiodobenzylguanidine scintigraphy with urinary and plasma catecholamine determinations in the diagnosis of pheochromocytoma.

In a retrospective study of 31 patients with suspected pheochromocytoma we examined the preoperative results of 131I-metaiodobenzylguanidine (131-I-MIBG) scintigraphy and a fluorimetric urine catecholamine determination test. An additional radioenzymatic plasma catecholamine determination test was performed in 25 patients. In 14 of the 31 patients the diagnosis of pheochromocytoma was later histologically confirmed. In the remaining 17 patients the suspected diagnosis was finally rejected after a clinical decision had been made on the basis of clinical history, symptoms, laboratory and imaging tests. 131-I-MIBG scintigraphy apparently had a very high specificity (no false-positive results among the patients with rejected diagnosis), but showed the least sensitivity (3 of 14 tumours were not detected). Urine catecholamines showed two false-negative and three false-positive results. Plasma catecholamines had the highest sensitivity and gave only one false-positive result. Because of its high pathognomonic value 131-MIBG scintigraphy can be helpful not only for localization, but also for confirmation of diagnosis when catecholamine determination tests are contradictory. On the basis of our experience with false-positive results after interfering medication therapy, urine and plasma catecholamine determination tests should only be carried out after purification with thin layer chromatography or high performance liquid chromatography.