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1.
Nuklearmedizin ; 47(3): 97-103, 2008.
Article in German | MEDLINE | ID: mdl-18493688

ABSTRACT

UNLABELLED: Distant metastases at primary diagnosis are a prognostic key factor in breast cancer patients and play a central role in therapeutic decisions. To detect them, chest X-ray, abdominal ultrasound, and bone scintigraphy are performed as standard of care in Germany and many centers world-wide. Although FDG PET detects metastatic disease with high accuracy, its diagnostic value in breast cancer still needs to be defined. The aim of this study was to compare the diagnostic performance of FDG PET with conventional imaging. PATIENTS, METHODS: A retrospective analysis of 119 breast cancer patients who presented for staging was performed. Whole-body FDG-PET (n = 119) was compared with chest X-ray (n = 106) and bone scintigraphy (n = 95). Each imaging modality was independently assessed and classified for metastasis (negative, equivocal and positive. The results of abdominal ultrasound (n = 100) were classified as negative and positive according to written reports. Imaging results were compared with clinical follow-up including follow-up imaging procedures and histopathology. RESULTS: FDG-PET detected distant metastases with a sensitivity of 87.3% and a specificity of 83.3%. In contrast, the sensitivity and specificity of combined conventional imaging procedures was 43.1% and 98.5%, respectively. Regarding so-called equivocal and positive results as positive, the sensitivity and specificity of FDG-PET was 93.1% and 76.6%, respectively, compared to 61.2% and 86.6% for conventional imaging. Regarding different locations of metastases the sensitivity of FDG PET was superior in the detection of pulmonary metastases and lymph node metastases of the mediastinum in comparison to chest x-ray, whereas the sensitivity of FDG PET in the detection of bone and liver metastases was comparable with bone scintigraphy and ultrasound of the abdomen. CONCLUSIONS: FDG-PET is more sensitive than conventional imaging procedures for detection of distant breast cancer metastases and should be considered for additional staging especially in patients with high risk primary breast cancer.


Subject(s)
Abdomen/diagnostic imaging , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/secondary , Fluorodeoxyglucose F18 , Positron-Emission Tomography/methods , Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Neoplasm Metastasis/diagnostic imaging , Radiography, Thoracic , Retrospective Studies , Ultrasonography
2.
Ann Oncol ; 19(7): 1249-1254, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18356138

ABSTRACT

BACKGROUND: The presence, extent and localization of distant metastases are key prognostic factors in breast cancer patients and play a central role in therapeutic decision making. The aim of this study was to compare the diagnostic performance of positron emission tomography using 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG-PET) with that of computed tomography (CT) and conventional imaging including chest radiography, abdominal ultrasound and bone scintigraphy. PATIENTS AND METHODS: A total of 119 consecutive patients with newly diagnosed locally advanced disease (n = 69) or previous history of breast cancer (n = 50) who had clinical suspicion of metastatic disease underwent FDG-PET, CT and conventional imaging procedures. Imaging results were retrospectively compared with histopathology and clinical follow-up which served as a reference standard. RESULTS: FDG-PET detected distant metastases with a sensitivity of 87% and a specificity of 83%. In contrast, the sensitivity and specificity of combined conventional imaging procedures were 43% and 98%, respectively. CT revealed a sensitivity of 83% and a specificity of 85%. CONCLUSIONS: In breast cancer, FDG-PET is superior to conventional imaging procedures for detection of distant metastases. Although FDG-PET and CT provided similar diagnostic accuracy, the information was often found to be complementary. With increasing availability of FDG-PET/CT, prospective studies are needed to determine whether it could potentially replace the array of conventional imaging procedures used today.


Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Diagnostic Imaging/methods , Fluorodeoxyglucose F18 , Positron-Emission Tomography/methods , Tomography, Emission-Computed/methods , Adult , Aged , Aged, 80 and over , Female , Fluorine Radioisotopes , Humans , Middle Aged , Neoplasm Metastasis/diagnostic imaging , Neoplasm Metastasis/pathology , Neoplasm Staging , Radiopharmaceuticals , Sensitivity and Specificity
3.
Eur Arch Otorhinolaryngol ; 262(6): 459-64, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15942798

ABSTRACT

In vitro studies show that sodium selenite is a potential radioprotector in normal cultural cells, but not in tumor cells. The aim of this study was to evaluate the cytoprotective potency of sodium selenite during a conventional fractioned irradiation of the salivary glands of rats. The head and neck area of male WAG/RijH rats was irradiated with (60)Co-gamma rays (60 Gy/30 fractions/6 weeks). Sodium selenite (15 microg/kg body weight) was applied through a venous port 30 min before irradiation. Rats of a control group were treated in the same manner with an equal volume of physiologic sodium chloride. In the course of treatment, the salivary glands were resected at different stages and examined histopathologically. The evaluation of gland function was performed prior to and after radiotherapy by sialoscintigraphy. The irradiation caused dose-dependent damage in the salivary glands. Intra- and intercellular edema (16 Gy), vacuolization (30 Gy), degranulation (46 Gy) and necrosis of the acinar cells (60 Gy) occurred. Sodium selenite delayed the development of the described damage; additionally, the number of necrotic acinar cells after the application of 60 Gy was reduced (control, 75% vs. sodium selenite, 30%). The sialoscintigaphical results confirmed these results: the loss in gland function in the control group was 74 vs. 44% (P < 0.05) in the sodium selenite group. Based on the morphological and sialoscintigraphical findings, a cytoprotective effect on the acute toxicity of the salivary glands of rats could be detected during irradiation with synchronous application of sodium selenite.


Subject(s)
Dose Fractionation, Radiation , Radiation-Protective Agents/pharmacology , Salivary Glands/radiation effects , Sodium Selenite/pharmacology , Animals , Gamma Rays/adverse effects , Male , Rats , Salivary Glands/drug effects , Salivary Glands/pathology
4.
HNO ; 52(12): 1067-75, 2004 Dec.
Article in German | MEDLINE | ID: mdl-15597168

ABSTRACT

BACKGROUND: In vitro studies show that sodium selenite is a potential radioprotector in normal cell cultures, but not tumor cells. The aim of this study was to evaluate the cytoprotective potency of sodium selenite during conventional fractionated irradiation of rat salivary glands, but also on tumor response and metastasis frequency of rhabdomyosarcomas R1H. METHOD: The head-neck area of male WAG/RijH rats and the tumor in the flank were irradiated with (60)Co-gamma-rays (60 Gy/30 fractions/6 weeks). Sodium selenite (15 microg/kg body weight) was applied through a venous port 30 min before irradiation. Rats of a control group were treated in the same manner with an equal volume of physiologic sodium chloride. In the course of treatment the salivary glands were extirpated at different stages and examined histopathologically. The evaluation of the gland function was performed prior to and after radiotherapy by sialoscintigraphy. Tumor volume was measured during irradiation and plotted in tumor-volume curves. Rat body weight was determined sequentially to estimate the general constitution of the animal during the treatment. RESULTS: Irradiation caused dose-dependent damage in the salivary glands. Intra- and intercellular edema (16 Gy), vacuolization (30 Gy), degranulation (46 Gy), and necrosis of the acinar cells (60 Gy) occurred. Sodium selenite delayed the development of the described damage, and the amount of necrotic acinar cells after the application of 60 Gy was reduced (control: 75% vs sodium selenite 30%), confirmed by the sialoscintigraphic results. The loss in gland function in the control group was 44% vs 74% (p<0.05) in the sodium selenite group. Sodium selenite had no influence on the response of R1H tumors to radiation and general constitution. CONCLUSIONS: Based on morphological and sialoscintigraphic findings, a cytoprotective effect on acute toxicity of rat salivary glands could be detected under irradiation with synchronous application of sodium selenite. In addition, no effects on tumor response and metastasis frequency were observed. The general animal constitution was not affected by additional medication with sodium selenite during irradiation.


Subject(s)
Dose Fractionation, Radiation , Parotid Gland/radiation effects , Radiation Injuries, Experimental/prevention & control , Radiation-Protective Agents/pharmacology , Radioisotope Teletherapy , Rhabdomyosarcoma/radiotherapy , Salivary Glands/radiation effects , Sodium Selenite/pharmacology , Soft Tissue Neoplasms/radiotherapy , Animals , Cell Death/radiation effects , Cell Line, Tumor/radiation effects , Cell Survival/radiation effects , Dose-Response Relationship, Radiation , Infusions, Intravenous , Male , Necrosis , Neoplasm Transplantation , Parotid Gland/pathology , Radiation Injuries, Experimental/pathology , Rats , Rats, Inbred Strains , Rhabdomyosarcoma/pathology , Salivary Glands/pathology , Soft Tissue Neoplasms/pathology
5.
HNO ; 52(1): 25-32, 2004 Jan.
Article in German | MEDLINE | ID: mdl-14740111

ABSTRACT

INTRODUCTION: The aim of this study was to correlate structural, histomorphological damage of the salivary gland with scintigraphic findings during fractioned radiotherapy. METHODS: The head and neck area of 27 WAG/RijH rats was irradiated with (60)Co-gamma-rays (60 Gy/30f/6 weeks). A port-system was implanted and (99m)Tc-pertechnetat applied at different stages of irradiation (0, 16, 30, 46, 60 Gy and 6 months post irradiation). RESULTS: After the application of 16 Gy an intra- and extra-cellular oedema developed in the salivary glands. The progressive vacuolisation (30 Gy) passed over into lipomatosis (46 Gy) and necrosis (60 Gy) in the parotid and mandibular glands. Six months after irradiation treatment, the chronic histomorphological damage corresponded to stage II according to Seifert. The corresponding loss in gland function was 13% (16 Gy); 26% (30 Gy); 57% (46 Gy); 75% (60 Gy) and 66.5% (6 months post irradiation). CONCLUSION: This animal model demonstrates the correlation between histomorphological and scintigraphic findings.


Subject(s)
Disease Models, Animal , Dose Fractionation, Radiation , Radiation Injuries, Experimental/diagnostic imaging , Radiation-Protective Agents/pharmacology , Radioisotope Teletherapy/adverse effects , Radionuclide Imaging , Salivary Glands/radiation effects , Animals , Cobalt Radioisotopes , Dose-Response Relationship, Radiation , Lipomatosis/pathology , Male , Parotid Gland/diagnostic imaging , Parotid Gland/pathology , Parotid Gland/radiation effects , Radiation Injuries, Experimental/pathology , Rats , Rats, Inbred Strains , Salivary Glands/diagnostic imaging , Salivary Glands/pathology , Sodium Pertechnetate Tc 99m , Statistics as Topic , Submandibular Gland/diagnostic imaging , Submandibular Gland/pathology , Submandibular Gland/radiation effects
6.
Eur Arch Otorhinolaryngol ; 260(9): 513-7, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12761639

ABSTRACT

Xerostomia is the most debilitating side effect induced by irradiation of head and neck tumours and is caused by irradiation damage to the salivary glands. The aim of this study was to correlate structural histomorphological damages and sialoscintigraphical findings during fractioned radiotherapy. The head and neck area of 27 WAG/RijH rats was irradiated with 60Co-gamma rays (60 Gy/30f 6 weeks). To evaluate salivary gland function, a port system was implanted, and 99mTc-pertechnetate was applied at different stages of irradiation (0, 16, 30, 46, 60 and 6 months post-irradiation). In the course of treatment the parotid glands were examined histopathologically. Rat salivary glands developed a dose-dependent radiosialadenitis. After a dose of 16 Gy an intra- and extra-cellular oedema developed in the salivary glands. Progressive vacuolisation (30 Gy) developed into lipomatosis (46 Gy) and necrotic changes (60 Gy) in the parotid glands. Six months after irradiation treatment, the chronic histomorphological damages corresponded to stage II according to Seifert. The corresponding loss in gland function investigated by measurement of the 99mTc-pertechnetate uptake of the salivary glands was 13% (16 Gy), 26% (30 Gy), 57% (46 Gy), 75% (60 Gy) and 66.5% (6 months post-irradiation). The presented animal model is suitable to demonstrate the correlation of histomorphological and sialoscintigraphical findings.


Subject(s)
Head and Neck Neoplasms/radiotherapy , Radiation Injuries/pathology , Salivary Glands/pathology , Sialadenitis/pathology , Xerostomia/pathology , Animals , Cobalt Radioisotopes/adverse effects , Disease Models, Animal , Dose Fractionation, Radiation , Dose-Response Relationship, Radiation , Gamma Rays/adverse effects , Male , Radiation Injuries/diagnostic imaging , Radiation Tolerance , Radionuclide Imaging , Radiotherapy, Adjuvant/adverse effects , Rats , Salivary Glands/radiation effects , Sialadenitis/diagnostic imaging , Sialadenitis/etiology , Sodium Pertechnetate Tc 99m , Xerostomia/diagnostic imaging , Xerostomia/etiology
7.
HNO ; 50(9): 822-8, 2002 Sep.
Article in German | MEDLINE | ID: mdl-12425136

ABSTRACT

Clinical studies show that amifostine can reduce xerostomia and mucositis during radiotherapy of head and neck cancers. The aim of this study was to evaluate the radioprotective potency of amifostine with respect to late toxicity of salivary glands of rats. The head-neck-area of 8 male WAG/RijH rats (295 +/- 7 g) were irradiated with 60Co-gamma-rays (60 Gy/30 f/6 weeks). Amifostine (250 mg/m2 body surface) was applied via a venous port 15 min before each irradiation. Rats of a control group were irradiated with the same schedule with equal volumes of physiological saline. The morphological and sialoscintigraphical findings clearly demonstrate that amifostine has a remarkable cytoprotective effect on the late toxicity of irradiated salivary glands.


Subject(s)
Amifostine/pharmacology , Dose Fractionation, Radiation , Radiation Injuries, Experimental/prevention & control , Radiation-Protective Agents/pharmacology , Salivary Glands/radiation effects , Animals , Cobalt Radioisotopes/toxicity , Dose-Response Relationship, Radiation , Male , Radiation Injuries, Experimental/pathology , Rats , Rats, Inbred Strains , Submandibular Gland/pathology , Submandibular Gland/radiation effects
8.
Orthopade ; 31(9): 921-9, 2002 Sep.
Article in German | MEDLINE | ID: mdl-12232712

ABSTRACT

The purpose of this study was to assess the value of F-18 FDG whole body positron emission tomography in the primary and follow-up diagnosis of musculoskeletal tumors. Between May 1994 and January 2000, 79 patients [36 females, 43 males; mean age: 44 years (9-78)] suffering from different musculoskeletal tumors were additionally examined with PET. In total, 100 whole body PET examinations (48 for primary staging, 52 for follow-up) were performed using a PET scanner [ECAT EXACT 47 (921)] with an axial field of view of 16.2 cm. The tracer was 370 MBq F-18 FDG. The results were compared to those achieved with conventional diagnostic tools such as CT, MRT, bone scan, and histology. In the primary staging, PET exhibited a sensitivity of 100% and a specificity of 50% (two false-positive results). In examinations for follow-up purposes, we found a sensitivity of 88.9% and a specificity of 92.0%. In the diagnosis of skeletal and extraskeletal metastases (100 PET inspections), the sensitivity was 87.5% and the specificity 89.7%. Besides this, PET was compared with standard diagnostic tools used in the follow-up procedures of those patients who had received chemo- and/or radiotherapy. In addition, the procedure was used to search for the unknown primary tumors in cases of secondary metastases in the skeleton and compared as well.PET with F-18 FDG as tracer has become an important additional method in the diagnosis of musculoskeletal tumors. It can be used for primary staging, search for metastases, and post therapeutic control. Negative results were seen when PET was used to search for metastases when the tumor was smaller than 5 mm, in cases of inflammatory diseases, and the differentiation of low-grade malignant tumors from benign lesions.


Subject(s)
Bone Neoplasms/diagnostic imaging , Postoperative Complications/diagnostic imaging , Soft Tissue Neoplasms/diagnostic imaging , Tomography, Emission-Computed , Adolescent , Adult , Aged , Bone Neoplasms/drug therapy , Bone Neoplasms/radiotherapy , Bone Neoplasms/surgery , Chemotherapy, Adjuvant , Child , Combined Modality Therapy , Female , Fluorodeoxyglucose F18 , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/diagnostic imaging , Radiotherapy, Adjuvant , Sensitivity and Specificity , Soft Tissue Neoplasms/drug therapy , Soft Tissue Neoplasms/radiotherapy , Soft Tissue Neoplasms/surgery
9.
Nucl Med Commun ; 23(9): 857-64, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12195090

ABSTRACT

The presence of distant metastases is the main prognostic factor in patients with breast cancer and has a significant influence in the choice of therapy. Therefore, chest X-ray, bone scintigraphy and ultrasound of the abdomen are performed to detect distant metastases at diagnosis and follow-up. Fluorodeoxyglucose positron emission tomography (FDG PET) has been shown to provide sensitive detection of primary tumour and metastases for many tumour entities, but little information is available about the diagnostic value for breast cancer patients. This study retrospectively compared FDG PET for detection of metastatic disease with chest X-ray, bone scintigraphy and ultrasound of the abdomen, referred to as "conventional diagnostic procedures" (CDPs), in 50 breast cancer patients. Imaging procedures were analysed in a blinded fashion with the results classified as "no evidence of metastases", "equivocal" and "evidence of metastases". Clinical follow-up and the results of other imaging modalities including computed tomography and magnetic resonance imaging were used to determine if metastases were present. FDG PET identified metastatic disease with a sensitivity and specificity of 86% and 90% as compared to 36% and 95% for CDPs, respectively. Regarding "equivocal" and "evidence of metastases" as positive, the sensitivity of CDPs increased to 57% with a corresponding specificity of 81%, whereas sensitivity and specificity of FDG PET remained unchanged. Regarding different localities of metastases the sensitivity of FDG PET was superior in the detection of pulmonary metastases and especially of lymph node metastases of the mediastinum in comparison to chest X-ray, whereas the sensitivity of FDG PET in the detection of bone and liver metastases was of the same magnitude as compared with bone scintigraphy and ultrasound of the abdomen.


Subject(s)
Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Ductal, Breast/secondary , Carcinoma, Lobular/diagnosis , Carcinoma, Lobular/secondary , Diagnostic Imaging/methods , Tomography, Emission-Computed , Adult , Aged , Aged, 80 and over , False Negative Reactions , False Positive Reactions , Female , Fluorodeoxyglucose F18 , Humans , Lymphatic Metastasis , Middle Aged , Radiopharmaceuticals , Retrospective Studies , Sensitivity and Specificity , Single-Blind Method
10.
Onkologie ; 25(2): 178-80, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12006770

ABSTRACT

The implantation of a small port system for repeated intravenous applications of drugs in rats is described. The system basically consists of a Teflon catheter which is inserted into the right internal jugular vein. The open end of the catheter under the right foreleg is subcutaneously carried through to the back and closed by a small port. The port then is implanted into a skin pocket on the back of the rat. The advantage of this method is that repeated intravenous injections of drugs into rats can easily be applied with high accuracy. Complications were rarely observed (7%) and could be mastered successfully in all cases.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Catheterization, Central Venous/instrumentation , Catheters, Indwelling , Animals , Equipment Design , Jugular Veins , Male , Rats , Rats, Inbred Strains
11.
Nuklearmedizin ; 40(5): 143-7, 2001 Oct.
Article in German | MEDLINE | ID: mdl-11727626

ABSTRACT

AIM: The prevalence of iodine- and thyroglobulin-negative findings was evaluated in all patients with differentiated thyroid cancer (DTC) treated from 1961 until 1998 at the Department of Nuclear Medicine, University Hospital Hamburg-Eppendorf. METHODS: A total of 490 patients with papillary thyroid cancer (PCA) and 242 patients with follicular thyroid cancer (FCA) were analyzed retrospectively. Patients were divided into four groups: 1: no recurrence, 2: recurrent disease, 3: primary metastatic/progressive disease and 4: inconclusive follow-up. Results of iodine scan, serum-TG, and additional imaging modalities as well as histology were compared in all patients. RESULTS: 21/490 (4.3%) of patients with PCA and 16/242 (6.6%) with FCA suffered from recurrent disease. 62/490 (12.7%) of patients with PCA and 59/242 (24.4%) with FCA had primary metastatic/progressive disease. 12/21 patients with PCA and 12/16 with FCA showing up with recurrent disease had a negative iodinescan. 11/21 of patients with PCA and 4/16 with FCA and tumor recurrence had negative serum-TG levels. 14/62 patients with PCA and 14/59 with FCA presenting with primary metastatic/progressive disease had negative iodinescan. 14/62 patients with PCA and 6/59 with FCA had negative serum-TG. CONCLUSION: The prevalence of iodine-negative recurrent/metastatic disease is in accordance to the literature, whereas the prevalence of TG-negative recurrent/metastatic was noted higher than reported previously. Thus, the commonly used follow-up scheme of DTC is confirmed. However, iodine scan should be regularly performed in patients with high risk of recurrence.


Subject(s)
Adenocarcinoma, Follicular/diagnostic imaging , Adenocarcinoma, Papillary/diagnostic imaging , Thyroglobulin/blood , Thyroid Neoplasms/diagnostic imaging , Biomarkers/blood , Disease Progression , Humans , Iodine Radioisotopes , Neoplasm Metastasis , Radionuclide Imaging , Recurrence , Retrospective Studies
12.
Nucl Med Commun ; 22(12): 1277-85, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11711897

ABSTRACT

Resectional surgery offers a curative intent and a survival benefit for patients with hilar cholangiocarcinoma, but is associated with high morbidity. Since morphological imaging cannot solve differential diagnosis preoperatively, in order to exclude patients inappropriate to this aggressive surgery, we evaluated the impact of functional imaging using fluorodeoxyglucose positron emission tomography (FDG PET) in the detection of cholangiocarcinoma and its usefulness in the differentiation from benign Klatskin tumour-mimicking lesions. Fifteen consecutive patients aged 47-78 years underwent standardized whole-body FDG PET with attenuation correction before potentially curative surgery using a conventional full-ring PET scanner with an axial field-of-view of 16.2 cm. FDG PET was evaluated visually and semiquantitatively using tumour-to-background ratios (T/B) ratios. All lesions were evaluated histopathologically. FDG PET presumed to be indicative for carcinoma was positive in 12 of 15 patients, true positive in 10 (T/B ratio, 3.2+/-1.9) and false positive in two of them (T/B ratios, 2.1 and 2.8) with Klatskin tumour-mimicking lesions. While all true positive PET results were seen in the tubular type of cholangiocarcinoma with a high amount of tumour cells and only low production of mucus, a false negative FDG PET in three patients was observed in mucinous adenocarcinoma. Additionally, FDG PET detected locoregional lymph nodes in two patients and distant metastases in a further three patients. Due to false positive results FDG PET does not allow the differentiation of benign from malignant lesions, and FDG PET should be avoided in patients with mucinous cholangiocarcinoma. However, FDG PET may have significant influence on the treatment strategy in as much as 20% of the patients, since it may detect distant metastases.


Subject(s)
Bile Duct Neoplasms/diagnostic imaging , Bile Ducts, Intrahepatic , Cholangiocarcinoma/diagnostic imaging , Fluorodeoxyglucose F18 , Tomography, Emission-Computed , Aged , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/pathology , Cholangiocarcinoma/pathology , Cholangiocarcinoma/surgery , Diagnosis, Differential , False Negative Reactions , False Positive Reactions , Female , Humans , Male , Middle Aged , Neoplasm Metastasis/diagnostic imaging , Radiopharmaceuticals , Reproducibility of Results
14.
Nucl Med Commun ; 22(8): 889-97, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11473208

ABSTRACT

The popular recreational drug, 'ecstasy', mainly contains 3,4-methylenedioxymethamphetamine (MDMA) as the psychotropic agent. MDMA is suspected of causing neurotoxic lesions to the serotonergic system as demonstrated by animal studies, examinations of human cerebrospinal fluid, and the first positron emission tomography (PET) studies using the serotonin transporter ligand [11C]-McN5652. Damage of serotonergic afferents might mediate long-lasting alterations of cerebral glucose metabolism as a secondary effect. To study a relationship between ecstasy use and long-lasting alterations, PET using 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) was performed in 93 ecstasy users and 27 subjects without any known history of illicit-drug abuse. As an index of glucose metabolism, mean normalized FDG uptake was determined in both groups using a computerized brain atlas, and was compared for a selected number of brain regions. FDG uptake was normalized in each individual by dividing local FDG uptake by the maximum FDG uptake in the individual's brain. Within the group of ecstasy users we examined the relationship between FDG uptake and cumulative ecstasy dose, time since last ecstasy ingestion at the time of PET scanning, and age at first ecstasy use, respectively. Normalized FDG uptake was reduced within the striatum and amygdala of ecstasy users when compared to controls. No statistically significant correlation of the FDG uptake and the cumulative dose of ecstasy was detected. A positive correlation was found in the cingulate between FDG uptake and the time since last ecstasy ingestion. As compared to the control group, normalized FDG uptake in the cingulate was reduced in ecstasy users who took ecstasy during the last 6 months, while it was elevated in former ecstasy users who did not consume ecstasy for more than 1 year. FDG uptake was significantly more affected in ecstasy users who started to consume ecstasy before the age of 18 years. In conclusion, ecstasy abuse causes long-lasting effects on glucose metabolism in the human brain. These effects are more severe in the case of very early abuse. However, several questions still remain to be answered, i.e. the correlation of the neuronal alterations and the history of ecstasy use (cumulative dose, and time since the last dose) and its reversibility.


Subject(s)
Brain/drug effects , Brain/metabolism , Fluorodeoxyglucose F18/pharmacokinetics , Hallucinogens/adverse effects , N-Methyl-3,4-methylenedioxyamphetamine/adverse effects , Substance-Related Disorders/metabolism , Tomography, Emission-Computed , Adolescent , Adult , Biological Transport , Brain/diagnostic imaging , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/metabolism , Carbon Radioisotopes , Female , Humans , Isoquinolines/pharmacokinetics , Kinetics , Male , Radiopharmaceuticals/pharmacokinetics , Receptors, Serotonin/metabolism , Regression Analysis , Serotonin Antagonists/pharmacokinetics , Substance-Related Disorders/diagnostic imaging , Time Factors , Tissue Distribution
16.
Int J Radiat Oncol Biol Phys ; 45(1): 181-6, 1999 Aug 01.
Article in English | MEDLINE | ID: mdl-10477022

ABSTRACT

BACKGROUND: Impairment of salivary gland function following high-dose radioiodine treatment (HDRIT) is a well-recognized side effect of the treatment. Because differentiated thyroid cancer has an excellent prognosis, reduction of long-term side-effects is mandatory. Therefore, the aim of this study was to investigate the radioprotective effect of amifostine in a rabbit animal model. METHODS: Salivary gland scintigraphy was performed in a total of 16 New Zealand White rabbits. Uptake of 99-Tc-pertechnetate was calculated in percentage of injected activity as a quantitative measure of both salivary gland and thyroid function. Reproducibility of salivary gland scintigraphy was evaluated in one rabbit without any intervention. Fifteen rabbits were studied prior to and up to 6 months after high-dose radioiodine treatment applying 2 GBq 131I. Ten animals received 200 mg/kg amifostine prior to high-dose radioiodine therapy, and 5 served as controls. Salivary glands were examined histopathologically. RESULTS: Variation coefficient of parenchymal function was less than 3.8% in salivary glands. Prior to HDRIT, thyroid uptake was 0.417+/-0.373% and 0.421+/-0.241% in control and amifostine-treated rabbits, respectively. Four weeks after HDRIT, complete ablation of the thyroid was achieved in both groups. Prior to HDRIT, uptake of 99mTc-pertechnetate in salivary glands of five control rabbits was not significantly different from ten amifostine-treated rabbits. In control rabbits 6 months after HDRIT, parenchymal function was reduced significantly (p < 0.0001) by 75.3+/-5.3% and 53.6+/-17.4% in parotid and submandibular glands, respectively. In contrast, in amifostine-treated rabbits, parenchymal function was reduced by 10.6+/-3.4% and 6.5+/-4.3% (p > 0.05) in parotid and submandibular glands, respectively. Histopathologically, marked lipomatosis was observed in control animals but was negligible in amifostine-treated animals. CONCLUSION: Parenchymal damage in salivary glands induced by high-dose radioiodine treatment can be significantly reduced by amifostine in this rabbit animal model. This corresponds to data obtained in patients with differentiated thyroid cancer.


Subject(s)
Amifostine/therapeutic use , Radiation-Protective Agents/therapeutic use , Salivary Glands/drug effects , Animals , Disease Models, Animal , Drug Evaluation, Preclinical , Iodine Radioisotopes/pharmacology , Male , Rabbits , Radiobiology , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Reproducibility of Results , Salivary Glands/diagnostic imaging , Salivary Glands/metabolism , Salivary Glands/radiation effects , Sodium Pertechnetate Tc 99m/pharmacokinetics
17.
Cancer Biother Radiopharm ; 14(5): 337-47, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10850318

ABSTRACT

Since differentiated thyroid cancer has an excellent prognosis, reduction of long-term side effects of high-dose radioiodine treatment (HD-RIT), i.e. salivary gland impairment is important. Thus, radioprotective effects of amifostine were studied. Salivary gland function was quantified by scintigraphy both in rabbits and patients. Fifteen rabbits were studied prior to and up to 6 months after HD-RIT applying 2 GBq 131I. Ten animals received 200 mg/kg amifostine prior to HD-RIT, and five served as controls. Animals were examined histopathologically. Fifty patients with differentiated thyroid cancer were evaluated prospectively prior to and 3 months after HD-RIT with either 3 or 6 GBq 131I in a double-blind, placebo-controlled study. Twenty-five patients were treated with 500 mg/m2 amifostine intravenously prior to HD-RIT, and 25 patients receiving physiological saline solution served as controls. Complete ablation of the thyroid was achieved in all rabbits four weeks after HD-RIT. In control rabbits 6 months after HD-RIT parenchymal function was reduced significantly (p < 0.0001) by 75.3 +/- 5.3% and 53.6 +/- 17.4% in parotid and submandibular glands, respectively. In contrast, in amifostine-treated rabbits parenchymal function was not significantly reduced. Histopathologically, marked lipomatosis was observed in control animals but was negligible in amifostine-treated animals. In control patients, salivary gland function was significantly (p < 0.001) reduced by 40.2 +/- 14.1% and 39.9 +/- 15.3% in parotid and submandibular glands, respectively, three months after HD-RIT, and 11 patients developed xerostomia. In 25 amifostine-treated patients, salivary gland function was not significantly reduced (p = 0.691), and xerostomia did not occur. Thus, parenchymal damage in salivary glands induced by high-dose radioiodine therapy can be reduced significantly by amifostine. This may improve quality of life of patients with differentiated thyroid cancer.


Subject(s)
Amifostine/pharmacology , Iodine Radioisotopes/toxicity , Radiation-Protective Agents/pharmacology , Salivary Glands/drug effects , Thyroid Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Animals , Antiemetics/therapeutic use , Blood Pressure , Dose-Response Relationship, Radiation , Double-Blind Method , Female , Humans , Male , Middle Aged , Placebos , Rabbits , Radionuclide Imaging , Radiotherapy/adverse effects , Salivary Glands/diagnostic imaging , Salivary Glands/radiation effects
18.
Multivariate Behav Res ; 13(2): 215-21, 1978 Apr 01.
Article in English | MEDLINE | ID: mdl-26794018

ABSTRACT

Dawes and Corrigan have asserted that linear decision rules using random or unit coefficients "yield predictions that are superior to those of human judges." Their assertion is based on the large correlations between the decisions from random or unit rules and actual decisions. This paper reports an experiment based on the scheduling production problem in which the correlations coefficient is compared with actual costs. In spite of high correlations with the optimal decision, the unit and random rules yielded much higher costs than human judgment.

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