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Biomedical subjects

H Vosberg

Publications and source records attributed to H Vosberg.

At least 19 recordsLinked to original sources

[Diagnosis, radioiodine and radiotherapy of thyroid carcinomas].

The long-term prognosis of differentiated thyroid carcinoma depends on early diagnosis and treatment of metastases and local recurrences and is modulated by several factors, age and histology being the most relevant. This article summarizes current trends in the use of radioactive iodine (131J) and gives explicit advice on its use in the treatment of these cancers. Complications of therapy are discussed in detail. We currently recommend that all patients undergoing a subtotal or total thyroidectomy are followed up by 131J thyroid scanning approximately 4 weeks after surgery. The combined use of three diagnostic modalities (measurement of serum thyroglobulin, neck ultrasonography with ultrasound-guided biopsy for detecting recurrences of carcinoma in the neck region and 131J whole-body scintigraphy) appears to give the best results in the follow up of patients with differentiated thyroid carcinoma. If any residual uptake is detected in the neck or if the tumor extends beyond the thyroid, we recommend routine thyroid ablation with 1,5-3 GBq of radioactive 131J. External radiotherapy is always indicated in papillary and folliculary carcinoma in the pT4 stage of pTNM classification but not in those in pT1-3 pN0 stage. In the presence of lymph-node metastases and distant metastases, an individual treatment concept is recommended regarding all risk factors, especially the age and sex of the patient, the histology and grading of the tumor and the completeness of tumor resection. Finally, radiotherapy is usually not indicated in medullary carcinoma, whereas it is always indicated in anaplastic carcinoma.

Follow-Up Studies

[Positron emission tomography with [18 F]-2-fluoro-2-deoxy-D-glucose (18FDG-PET) in diagnosis of retroperitoneal lymph node metastases of testicular tumors].

In 1991, this prospectively designed study was started to assess the potentials of positron emission tomography with 18FDG in the diagnostic workup for the detection of lymph node metastases in testicular cancer, since there were no data available concerning this subject at this time. In 54 patients (27 patients with pure seminoma, 27 patients with non-seminomatous tumors) 18FDG-PET results were compared with the findings obtained with abdominal computed tomography, serum level of tumor markers (AFP, beta-HCG), and the histopathological findings after primary or post-chemotherapy retroperitoneal lymph node dissection. In 21 patients with pure seminoma (clinical stage I according to the Lugano classification) 18FDG-PET results were identical with those of the abdominal computed tomography, so PET does not add relevant informations in this group of patients. In 7 patients presenting with non-seminomatous testicular cancer (stage I), PET was not able to detect the existing micrometastases in 4 patients. In 1/7 case PET examination showed a suspicious focal lesion, this lymph node had 2 micrometastases within inflammatory changes. In 1/7 patient 18FDG-PET definitely revealed metastatic lesions, while the CT scans where judged to be unobtrusive and tumor marker levels were within the normal range. In the 4 patients with pure seminomas stage II B and II C (N = 6), that have undergone retroperitoneal lymph node dissection following chemotherapy, 18FDG-PET correctly predicted absence of tumor in 3 out of these 4, and in 1/4 patient the benign nature of a persistent large tumor after two cycles of polychemotherapy was correctly identified which eventually turned out to be a ganglioneuroma. This lesion falsely was classified as malignant tumor with abdominal computed tomography, and in 2/4 patients post-chemotherapy residual retroperitoneal lesions in the CT scans could not be assessed exactly whether or not malignant tumor was present. In 20 patients presenting with non-seminomatous testicular cancer (stage II and III) 18FDG-PET was able to demonstrate therapeutic effects of chemotherapy by showing decreasing tracer activity in those regions, that had hypermetabolic foci prior to chemotherapy. It became evident in testicular cancer that there is a single entity which is not characterized by increased glucose metabolism, the mature teratoma. In lesions detected by abdominal computed tomography which do not present increased 18FDG uptake, mature teratoma as well as scar/necrosis or rare other tumors with normal glucose metabolism can be supposed, but additional characteristics based on different 18FDG uptake were not observed. In 1/20 case post-chemotherapy PET scan detected a hypermetabolic lesion, which was suspicious for metastatic spread, but in the histopathological examination this lesion was identified as inflammatory tissue reaction. Based on the data reported here in 18FDG-PET cannot be considered a standard diagnostic tool in the staging examinations in testicular cancer. It is of clinical relevance in patients who present residual tumor after chemotherapy. In this situation 18FDG-PET is helpful in deciding whether or not a residual mass post-chemotherapy contains active tumor. 18FDG-PET can not replace retroperitoneal lymph node dissection for staging purposes.

Adult

[Antimyosin scintigraphy for diagnosis and follow-up of patients with clinically suspected myocarditis].

Antimyosin-scintigraphy is believed to have a high specificity but a low sensitivity for the diagnosis of myocarditis when histological analysis of endomyocardial biopsy is used as the reference method. However, the histological evaluation itself seems to have a low sensitivity for the diagnosis of myocarditis. Therefore, immunohistological techniques have been developed for the detection of lymphocytic infiltrates and increased expression of HLA antigens in the myocardium. The present study compares the results of antimyosin-scintigraphy with histological and immunohistological analysis of the endomyocardial biopsy. 65 patients with clinically suspected myocarditis underwent antimyosin-scintigraphy and histological and immunohistological analysis of the endomyocardial biopsy. Myocarditis could be diagnosed histologically in only 9/36 (25%) patients with a positive antimyosin scan but additional immunohistological analysis revealed lymphocytic infiltrates in 31 (86%) of these patients. In 29 patients with a normal antimyosin scan, histological analysis showed evidence of myocarditis in 3 (10%) patients; additional immunohistological evaluation disclosed lymphocytic infiltrates in 17 (59%) patients. With immunohistological analysis of the endomyocardial biopsy as the reference method, antimyosin-scintigraphy has a high sensitivity but a lower specificity for the diagnosis of myocarditis. Detection of autoantibodies against human cardiac myosin in patients with myocarditis is associated with a significantly lower incidence of positive antimyosin scans in these patients. Antimyosin-scintigraphy was repeated after six months in 14 patients with myocarditis. Histological and immunohistological evaluation of the endomyocardial biopsy now showed persistent myocarditis in 3/8 patients with a positive antimyosin scan and in 5/6 patients with a normal antimyosin scan.

Adult

Antimyosin scintigraphy and immunohistologic analysis of endomyocardial biopsy in patients with clinically suspected myocarditis--evidence of myocardial cell damage and inflammation in the absence of histologic signs of myocarditis.

OBJECTIVES: This study compares the results of antimyosin scintigraphy in patients with clinically suspected myocarditis with histologic and immunohistologic findings in the endomyocardial biopsy. BACKGROUND: In patients with clinically suspected myocarditis, antimyosin scintigraphy often demonstrates myocardial cell damage but histologic evaluation of the endomyocardial biopsy often fails to show evidence of myocarditis. Recently developed immunohistologic techniques appear to be more sensitive for the detection of myocardial inflammation than histologic analysis alone. Studies comparing antimyosin scintigraphy and immunohistologic analysis of the endomyocardial biopsy in patients with clinically suspected myocarditis are not yet available. METHODS: Sixty-five patients with clinically suspected myocarditis underwent antimyosin scintigraphy. Antimyosin antibody uptake was correlated with histologic and immunohistologic findings in the endomyocardial biopsy. RESULTS: Antimyosin scintigraphy showed evidence of myocardial cell damage in 36 (55%) of the 65 patients and was negative in 29 (45%) patients. Histologic analysis of the endomyocardial biopsy revealed myocarditis in nine patients: six had a positive and three had a negative antimyosin scan, respectively. Thirty (83%) of 36 patients with evidence of myocardial cell damage on antimyosin scintigraphy were histologically negative for myocarditis. Immunohistologic analysis showed evidence of myocarditis in 31 (86%) of 36 patients with a positive antimyosin scan and also in 17 (59%) of 29 patients with a normal scan (p < 0.047). CONCLUSIONS: Antimyosin scintigraphy often shows myocyte injury in patients with clinically suspected myocarditis. Histologic analysis of the endomyocardial biopsy alone is often negative, but additional immunohistologic analysis of the endomyocardial biopsy frequently provides evidence of myocardial inflammation in these patients. With immunohistologic analysis as the reference method, antimyosin scintigraphy has a high specificity but a lower sensitivity for the detection of myocarditis.

Adult

Left-right asymmetry of striatal dopamine D2 receptors.

Brain functions may be lateralized to the right or the left hemisphere. However, the biochemical characteristics accompanying these functions are largely unknown. To test possible lateralization of striatal dopamine D2 receptors, we examined 18 volunteers using 123I-iodobenzamide and single photon emission tomography. The striatum-to-cerebellum D2 binding ratio was 1.93 +/- 0.22 (mean +/- S.D.) on the right side and 1.85 +/- 0.19 on the left side. In 14 subjects, D2 binding was higher in the right compared to the left striatum (P < 0.05). These results are supported by a meta-analysis performed on 15 studies reported in the literature. We conclude that side differences of striatal dopamine D2 receptors exist. We propose that motor activity could be responsible for our findings.

Adult

Differential accumulation of iodine-123-iodobenzamide in melanotic and amelanotic melanoma metastases in vivo.

UNLABELLED: Iodine-123-iodobenzamide (IBZM) is a specific antagonist of dopamine D2 receptors and usually is used to study neuropsychiatric disorders. It also has a substantial affinity for malignant melanomas. This has been attributed to specific dopamine D2 receptor binding on melanoma cells because melanocytes and dopaminergic neurons share the same ectodermal origin and are both able to produce melanin. However, IBZM binding to melanoma metastases occurs predominantly 24 hr after injection, which is much later than maximal specific D2 receptor binding is expected. Furthermore, IBZM binding is not consistent in melanoma patients. This points to another mechanism of IBZM binding to melanoma cells. The aim of this study was to characterize IBZM-binding metastatic melanoma patients clinically and histologically to shed light on the nature of this mechanism. METHODS: Twenty-one patients with proven or suspected metastases of a malignant melanoma entered this prospective study after surgical removal of the primary tumor. Whole-body scans, planar scintigrams and SPECT scans were performed 2-5 hr and 1 day after intravenous injection of 185 MBq IBZM. RESULTS: The suspected diagnosis of metastatic cancer was later confirmed in 17 patients by histology, clinical follow-up, x-ray, CT or other radiologic methods. Four patients were free of tumor tissue at the time of investigation and remained stable for 2 yr thereafter. Twelve of the 17 patients had a melanotic and 5 had an amelanotic subtype of the tumor. Iodine-123-IBZM accumulation occurred in the metastases of 10 of the 12 patients with melanotic melanoma and in 0 of the 5 patients with the amelanotic tumor type (p < 0.01; chi-square test). Furthermore, IBZM accumulation occurred in 0 of the 11 amelanotic metastases but in 20 of the 25 melanotic metastases (p < 0.001). The sensitivity is, thus, 83% for the detection of melanotic melanoma metastases on a patient basis and 80% on a lesion basis. Iodine-123-IBZM scintigraphy demonstrated one previously unknown metastasis. Six initially suspected lesions were not due to melanoma metastases and were IBZM-negative. No false-positive IBZM accumulations occurred in our patients. CONCLUSION: Iodine-123-IBZM binds to melanotic malignant melanomas with high specificity and moderate sensitivity but not to amelanotic melanomas. Our data suggest that the tracer does not bind to membrane dopamine receptors of the tumor but is built in or closely bound to intracellular melanin.

Adult

[Pathogenetic differentiation of the bone superscan using bone marrow scintigraphy].

The case of a 54 year old patient suffering from a prostatic carcinoma is presented. At the time of diagnosis multiple bone metastases were detected by bone scintigraphy. An initial improvement was observed following antiandrogenic therapy. After three years the patient presented with increasing bone pain, which was most prominent in the knee joints. A "superscan" was found in bone scintigraphy with an unusually high uptake in the peripheral skeleton. Bone marrow scinitgraphy showed a nearly complete metastatic displacement of central bone marrow and a peripheral marrow extension as explanation for the bone scan findings.

Androgen Antagonists

In vivo evidence for the involvement of dopamine-D2 receptors in striatum and anterior cingulate gyrus in major depression.

The dopaminergic system is a candidate neurotransmitter system thought to be involved in the pathogenesis of depression. This study addresses the issue whether the antidepressant efficacy of serotonin reuptake inhibition is related to changes in the cerebral dopaminergic system. Cerebral dopamine-D2 receptors were characterized in 13 patients with major depression using the dopamine-D2 receptor antagonist iodobenzamide and single photon emission tomography. Dopamine receptor binding was assessed twice, before and during serotonin reuptake inhibition. An increase in dopamine-D2 receptor binding during serotonin reuptake inhibition was found in striatum and anterior cingulate gyrus in treatment responders, but not in nonresponders. The increase in dopamine-D2 receptor binding correlated significantly with clinical recovery from depression as assessed with the Hamilton depression scale (r = 0.59 for right and left striatum respectively, P < 0.05; r = 0.79 for the anterior cingulate gyrus, P < 0.05 after Bonferroni correction). Qualitatively similar correlations were observed in the precentral gyrus, the medial frontal gyrus, the inferior frontal gyrus, and the frontal part of the opercular gyrus, but these correlations failed to reach statistical significance after correction for the effects of multiple testing. No such correlations were found in the superior frontal gyrus, the orbitofrontal gyrus, the gyrus rectus, the superior parietal gyrus, or the superior temporal gyrus. The data strengthen the concept that the striatum and the anterior cingulate gyrus are involved in mood regulation. Dopamine-D2 receptors may constitute a central role in this domain.

Adult

[13C]octanoic acid breath test for non-invasive assessment of gastric emptying in diabetic patients: validation and relationship to gastric symptoms and cardiovascular autonomic function.

Since there is a need for a widely applicable non-invasive test to assess gastric emptying in diabetic patients, we evaluated the sensitivity, specificity, and reproducibility of the [13C]octanoic acid breath test as compared with scintigraphy. Moreover, we examined the relationship between the breath test indices and gastric symptoms, cardiovascular autonomic function, and metabolic parameters. Forty healthy control subjects and 34 diabetic patients were studied. Three indices of gastric emptying, assessed by the breath test, were computed: half-emptying time (t1/2breath), gastric emptying coefficient (GEC), and lag phase. Furthermore, the half-emptying time, measured by scintigraphy (t1/2scint), was calculated and gastric symptoms and cardiovascular autonomic neuropathy (CAN) were scored. The coefficients of variation of day-to-day reproducibility in 10 healthy subjects were 29.6% for t1/2breath, 7.4% for GEC, and 46.5% for lag phase. An abnormal delay for t1/2scint (> 100 min) or t1/2breath (> 200 min) was noted in 12 patients. Based on the results for t1/2scint, the sensitivity of t1/2breath and GEC was 75% and the specificity was 86%. Both t1/2breath (rs = 0.523; p < 0.05) and GEC (r2 = -0.594; p < 0.05) were significantly associated with the gastric symptom score. A significant relationship to the CAN score was demonstrated for t1/2breath (rs = 0.448; p < 0.05), GEC (rs = -0.467; p < 0.05), and t1/2scint (rs = 0.602; p < 0.05). There were no significant associations of the breath test indices with the blood glucose levels during the test, HbA1c, age, and duration of diabetes. In patients with abnormal t1/2scint (n = 12) not only was t1/2breath significantly prolonged and GEC reduced, but also the scores of CAN and gastric symptoms were significantly increased as compared with those who had a normal t1/2scint (n = 22). We conclude that the [13C]octanoic acid breath test represents a suitable measure of delayed gastric emptying in diabetic patients which is associated with the severity of gastric symptoms and CAN but not affected by the blood glucose level.

Adult

The role of bone scintigraphy in the follow-up of osteogenic sarcoma.

The role of bone scintigraphy in the follow-up of osteosarcoma patients is still controversial. It is not yet clear whether bone scintigraphy results in early detection of relapse nor whether this can improve the survival rate of relapsed patients. In this study, results of scintigraphies obtained from 78 patients treated for osteosarcoma between 1978 and 1992 were analysed. 28/78 patients presented with 61 relapse sites, including 34 lung metastases, 20 distant relapses and 7 local recurrences. More than 90% of relapses were detected within 4 years after primary diagnosis of the tumour. A total of 489 bone scintigraphies were performed routinely during follow-up of these patients. 66/489 scintigraphies showed increased uptake of tracer. In 7/66 positive scintigraphies, a relapse was detected: lung metastases (3), local recurrence (1) and distant bone or soft tissue relapses (3). These relapses occurred between 1 and 4 years after primary diagnosis. In these cases, scintigraphies showed areas with increased uptake, although these patients had neither clinical symptoms nor positive X-rays or CT scans. At an observation period of 2.5 or 3.5 years, a second or third remission was induced in 2/6 patients in whom scintigraphy allowed an early diagnosis of the relapse. In conclusion, these data show that only a small number of routinely performed bone scintigraphies indicate a relapse. However, since bone scintigraphy is able to detect relapses early, the outcome of future relapsed patients might be improved. Therefore, bone scintigraphies should be included in a follow-up programme for patients with osteosarcoma. Since most relapses detected by scintigraphy occurred during the first 4 years after initial diagnosis, bone scintigraphy should be limited to this time frame.

Adolescent

Efficacy of simultaneous determination of bone alkaline phosphatase mass concentration in serum and urinary excretion of pyridinium cross-links for detection of bone metastases.

OBJECTIVES: To examine the diagnostic validity of bone alkaline phosphatase (BAP) in serum (a marker of bone formation) and of urinary excretion of pyridinium cross-links (PYR) (a marker of bone resorption) for detection of bone metastases. DESIGN AND METHODS: Two heterogeneous immunoassays were employed for determination of BAP mass concentrations (Tandem-R Ostase) in serum and the urinary excretion of PYR (Collagen Crosslinks) in a consecutive series of 89 tumor patients examined by bone scintigraphy (with 99mTc-methylene diphosphonate). RESULTS: The discrimination power (as determined by Z score analysis) and the accuracy (as assessed by the area under the receiver-operating characteristic curve) was higher for BAP (0.84) than for PYR (0.76). Combination of both markers yielded a further increase of accuracy (0.89). There was a correlation (r = +0.422; p < 0.001) between the urinary excretion of pyridinium cross-links and bone alkaline phosphatase mass concentrations in the whole of 89 patients examined. In 14 (16%) of 89 patients bone alkaline phosphatase values were within the reference interval in spite of total alkaline phosphatase activity being increased; this indicates a higher diagnostic specificity of bone alkaline phosphatase (compared with total alkaline phosphatase) with respect to detection of bone metastases. CONCLUSION: Simultaneous assessment of bone formation by BAP and of bone resorption by PYR provides a suitable tool for detection of bone metastases.

Adult

Simultaneous assessment of bone collagen synthesis and degradation in patients with different malignant tumours. Comparison with the results of 99mTc-methylene bisphosphonate bone scintigraphy.

We report on the diagnostic validity of the serum concentrations of the C-terminal propeptide of type I procollagen (a marker of bone formation) and of the urinary excretion of deoxypyridinoline (a marker of bone resorption) in a consecutive series of 89 tumour patients who were routinely examined by 99mTc-methylene bisphosphonate bone scintigraphy for detection of bone metastases. Z score analysis reveals that the discriminating power of deoxypyridinoline is superior to that of calcium excretion whereas the discriminating power of the C-terminal propeptide concentrations is inferior to that of bone alkaline phosphatase values. Accuracy (as assessed by the area under the receiver-operating characteristic curve) was 0.75 for deoxypyridinoline and 0.82 for the C-terminal propeptide. Combination of both markers did not yield an increase of accuracy (0.82) compared with the determination of the C-terminal propeptide concentrations alone. There was a correlation (r = +0.398; p < 0.0001) between C-terminal propeptide concentrations and deoxypyridinoline excretion values in the group of 89 patients examined. Further studies should be done to elucidate whether the determination of bone collagen turnover is suitable as a screening procedure for detecting bone metastases.

Adult

[Parametric representation of kidney function using 99mTc-mercaptoacetyltriglycine (MAG3)].

99mTc-mercaptoacetyltriglycine (MAG3) has recently been introduced for imaging kidney function. Due to the much lower radiation dose per MBq, the total administered activity can be much higher than in the case of 131I-ortho-iodo-hippurate (OIH). The improved counting statistics make this tracer useful for parametric imaging of the kidneys. To investigate this potential of MAG3, its kinetics was compared with that of the reference tracer OIH in 38 patients. Parameters of extrarenal tracer kinetics such as the distribution volumes, the whole-body elimination times and the clearance rates showed a good correlation; however, the clearance rate of MAG3 was always lower than that of OIH. The intrarenal kinetics was investigated using the transfer function which was calculated by deconvolution analysis of the renographic curves. Parameters of the transfer function such as the amplitude, extraction fraction and mean transport time demonstrated a high correlation between the two tracers. Since MAG3 seems to be suitable for parametric imaging of kidney function, parametric images of perfusion, uptake, extraction and transport times were calculated by deconvolution analysis of the MAG3 pixel-renograms in various renal disorders. The parameters were distributed homogeneously throughout the parenchyma of normal kidneys. In a kidney with a hemodynamically significant renal artery stenosis the perfusion parameter was decreased and the time parameter was prolonged. Further examples of a renal graft acute tubular necrosis, an obstructive uropathy, an obstructive nephropathy and of a horse-shoe kidney demonstrate that the parametric images are useful for quantitative investigation of regional renal function.

Humans

The use of gamma functions in the calculation of organ perfusion functions for non-diffusible radioactive tracers.

This paper introduces a method for quantification of mean organ perfusion by the impulse response function using the experimental time-activity curves for the organ of interest and its supplying artery. These are approximated by gamma functions and a general expression for the impulse response function is then derived. In any particular case, the impulse response function can be calculated simply by insertion of the numerical parameters. The procedure combines speed with freedom from random measurement errors. As an example of a clinical application, the impulse response function of healthy brain tissue is calculated and some clinically important parameters are tabulated.

Blood Circulation

[An experimental study of liver perfusion using non-diffusible radiotracers: differentiation of the arterial and portal venous components by deconvolution analysis of first-pass time-activity curves].

The transfer function of the liver perfusion is an idealized time-activity curve that could be registered over the liver if a non-diffusible tracer would be injected directly into the abdominal aorta and no tracer recirculation would occur. The reproducibility of the transfer function was experimentally investigated in foxhounds. Both the routes of tracer application and the modes of data evaluation were varied and the perfusion was investigated under physiological and pathological conditions. The transfer function was calculated by deconvolution analysis of first-pass time-activity curves using the matrix regularization method. The transfer function showed clearly distinguishable arterial and portal-venous components. Repeated peripheral venous and central aortic applications resulted in reproducible curves. In addition to the arterial and portal-venous components the subcomponents of the portal-venous component could also be identified in the transfer function after ligation of the appropriate vessels. The accuracy of the mathematical procedure was tested by computer simulations. The simulation studies demonstrated also that the matrix regularization technique is suitable for deconvolution analysis of time-activity curves even when they are significantly contaminated by statistical noise. Calculation of the transfer function of liver perfusion and of its quantitative parameters seems thus to be a reliable method for non-invasive investigation of liver hemodynamics under physiological and pathological conditions.

Animals

The utilization of Tc-99m-TBI as a myocardial perfusion agent in exercise studies: comparison with Tl-201 thallous chloride and examination of its biodistribution in humans.

Twenty-four patients were studied with both 201Tl-thallous chloride and 99mTc-TBI scintigraphy following exercise. Comparison of the two agents in detecting segmental myocardial ischemia and scar was made in 18 patients with evidence of coronary artery disease on 201Tl-thallous chloride scintigraphy. Agreement between the two studies was observed in 77% (125 of 162) of left ventricular segments, suggesting that 99mTc-TBI can be used as a myocardial perfusion agent. Limitations were related to early high background activity from lungs and liver. The high lung activity and early myocardial redistribution within the 1st hour contributed to the failure of 99mTc-TBI to detect 16 segmental defects seen in the immediate post-exercise thallous chloride scan. Persistently high liver activity additionally affected accurate interpretation in the left ventricular segments close to the diaphragm. Improvement in the accuracy of 99mTc-TBI stress studies might be achieved with tomographic imaging to reduce the problem of background activity or by the development of 99mTc-labeled isonitrile analogues with rapid lung and liver clearance.

Adult