Dopamine transporter binding in Gilles de la Tourette syndrome.

Preliminary studies in patients with Gilles de la Tourette syndrome (TS) provided evidence of presynaptic dopaminergic dysfunction, demonstrating increased reuptake sites. Therefore we investigated striatal dopamine transporter binding in 12 TS patients and 9 control subjects using single photon emission computed tomography and 123I-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane. In TS patients we found significantly higher relative striatal activity ratios (mean +/- SD 12.33 +/- 3.58) than in controls (9.36 +/- 1.35, P< 0.05). Only five patients, however, showed striatum/occipital cortex ratios more than 2 SD above the normal means. Seven patients had activity ratios within the average ratio of the control group plus 2 SD. Regarding the relationship between clinical parameters and striatum/occipital cortex ratios, we found an association between binding ratios and "self-injurious behavior" and "lack of impulse control." This study corroborates previous data suggesting an involvement of the dopaminergic system in TS pathology. Our results demonstrate that an increase in dopamine transporter capacity is a possible but not a necessary alteration, and which appears more likely when self-injurious behavior and lack of impulse control are associated.

Dopamine D2 receptor imaging in Gilles de la Tourette syndrome.

OBJECTIVES: To examine postsynaptic dopamine D2 receptors in Tourette syndrome (TS). MATERIAL AND METHODS: Seventeen patients and a control group were investigated using single photon emission computed tomography (SPECT) and iodobenzamide (123I-IBZM). RESULTS: In neuroleptic treated patients (n = 7) 123I-IBZM-binding was significantly reduced compared to both normal controls (P < 0.0001) and unmedicated patients (P < 0.001). In unmedicated patients (n = 10) mean binding ratio did not differ from that of control group. Patients in advanced stages of the disease, however, revealed significantly reduced relative striatal binding compared to patients in the early stages (P<0.005) and normal controls (P<0.0001). CONCLUSION: The results lend further support to the hypothesis that the dopamine receptor is involved in TS pathology. During the natural course of the disease tics often improve in early adulthood. It is suggested that this spontaneous recovery from tics may be associated with reduced receptor binding capacity.

Prostaglandin E1 in peripheral vascular disease: a PET study of muscular blood flow.

BACKGROUND: Increase of blood flow in the ischaemic leg is believed to represent the main action of prostaglandin E1 (PGE1) in the therapy of peripheral vascular disease (PVD). There is no reliable data in man concerning the amount of increase in muscular blood flow (MBF) of the calf, and the difference between intra-arterial and intravenous application. PATIENTS AND METHODS: We conducted a positron emission tomography (PET) study of MBF with 15O-water as flow tracer. Fifteen patients with PVD and three healthy volunteers were given 5 micrograms PGE1 intra-arterially over 50 min; PET scans were taken at 0, 25 and 50 min. Additionally, eight of the patients were investigated during an intravenous infusion of 40 micrograms PGE1 over 120 min; PET scans were taken at 0, 30, 60 and 120 min. RESULTS: Increase of muscular blood flow by intra-arterial PGE1 averaged 80%. A steal phenomenon was not observed. The amount of flow enhancement depended on whether or not the femoral artery was patent. During intravenous PGE1, muscular blood flow remained unchanged. CONCLUSIONS: In man, the pharmacodynamic profile of intra-arterial PGE1 differs clearly from intravenous PGE1. The flow-enhancing property is lost during metabolization in the lung. Since no difference exists between the therapeutic efficacy of intraarterial and intravenous PGE1, the impact on muscular blood flow is not as important as suggested previously.

[18F]fluoride PET indicates reduced bone formation in severe glucocorticoid-induced osteoporosis.

A 61-year-old female patient presenting with mixed connective tissue disease (Sharp syndrome), underwent a long-term high dose glucocorticoid treatment because of multiple organ manifestations. Under steroid therapy she developed severe osteoporosis resulting in multiple fractures. A dynamic [18F]fluoride PET study in this patient revealed reduced fluoride influx in non-fractured vertebrae. This finding corresponds to pathogenetic concepts which propose an inhibition of bone formation as major cause of glucocorticoid-induced osteoporosis. In the light of the presented case it seems to be promising to evaluate the diagnostic benefit of [18F]fluoride PET in osteoporosis.

Dose-related effect of intravenous L-arginine on muscular blood flow of the calf in patients with peripheral vascular disease: a H215O positron emission tomography study.

1. Endothelium-derived nitric oxide (NO) contributes to the regulation of vascular tone and blood pressure. Infusion of L-arginine produces systemic vasodilatation via stimulation of endogenous NO formation. Vasodilatation is accompanied by an increase in peripheral arterial blood flow. However, it is not known whether capillary nutritive blood flow increases as well. The time course and dose-response pattern of this effect remain to be elucidated. 2. Two groups of ten patients with peripheral vascular disease (PVD) received an intravenous infusion of 8 g or 30 g of L-arginine over a period of 40 min. Blood pressure and heart rate were monitored non-invasively. Muscular blood flow (MBF) of the calf was determined at 0, 20, 40, 60, 80 min by positron emission tomography with H215O as flow tracer. Plasma L-arginine and cyclic GMP (cGMP) levels were determined at the same time points. 3. L-arginine induced a dose-related decrease in blood pressure during the infusion period. MBF and plasma cGMP levels during and after the infusion of 8 g of L-arginine did not change significantly. In the patients receiving 30 g of L-arginine, MBF was enhanced significantly from 1.56 +/- 0.14 to 2.09 +/- 0.21 ml min-1 100 ml-1 at 40 min and 2.23 +/- 0.15 ml min-1 100 ml-1 after 80 min (+43.0%). The increase in MBF was paralleled by an increase in plasma cGMP from 4789.8 +/- 392.2 nmol/l at baseline to 9223.2 +/- 1233.6 nmol/l at 40 min. 4. We conclude that intravenous L-arginine enhances nutritive capillary MBF in patients with PVD via the NO-cGMP pathway in a dose-related manner. This effect might be therapeutically beneficial in patients with PVD.

[Genetic risk after high dose radioiodine therapy with regard to gonadal dose]. / Zum genetischen Risiko nach hochdosierter Radiojodtherapie unter Berücksichtigung der Gonadendosis.

AIM: The genetic risk for the offspring of patients treated with high doses of radioiodine was to be assessed with special regard to the gonadal dose caused by diagnostic and therapeutic procedures. METHODS: 41 young females (aged between 19 and 39 years) and four young males (aged 26 to 36 years) treated with radioiodine because of a thyroid carcinoma were interviewed by use of a questionnaire. The course of pregnancy and birth history could be documented as well as the congenital and developmental conditions of 56 children. RESULTS: The amount of radioactivity applied for therapy and whole body scans ranged over 4.144 and 35.15 GBq 1-131; the individual gonadal dose was calculated based on the MIRD model and ranged over 0.2 and 2.2 Sv (0.51 Sv at a mean). The period of time between the last radioiodine application and confinement was at least 9 months, not exceeding 14 years. As to the course of pregnancy and birth two early abortions, one extrauterine gravidity and one premature birth due to an insufficiency of the placenta were stated. In one case a chromosomal translocation 7/14 occurred as a genetic defect which lead to an interruption. The children's development was unconspicuous except of two cases of neurodermatitis as well as multiple allergies and an early closure of the anterior fontanelle in one child each. CONCLUSION: Although the genetic risk is supposed to increase with the gonadal dose achieved (doubling dose 1 Sv) and the increased risk of any congenital anomaly was calculated as about 13% at a mean in our patients, the rate of genetic determined diseases was not elevated (1.8% or 1/57). Thus, no increase of genetic defects or congenital malformations was reported in a total of 408 children described in the literature and in our group.

[Low-risk thyroid carcinoma--therapy, follow-up and prognosis]. / Das Low-risk-Schilddrüsenkarzinom--Therapie, Nachsorge und Prognose.

AIM AND METHODS: A retrospective study was performed to determine the frequency of local recurrences and distant metastases as well as potential risk factors in patients with low-risk differentiated thyroid carcinoma. In addition, the efficiency of our follow-up programme and the diagnostic value of the procedures administered was to be evaluated. RESULTS: 41/740 (8%) patients developed 62 recurrences at a mean 4.7 years after the onset of the disease. In 14 cases the tumor marker thyroglobulin was the first diagnostic sign. 13 recurrences were diagnosed by chest x-ray and/or CT. In 12 cases recurrences/metastases were detected by iodine-131 whole body scan, and 8 cases by ultrasound of the neck. A good prognosis was found if patients were under 45 years of age when the tumor was first diagnosed, and if the tumor did not exceed 20 mm in diameter. The prognosis was not statistically significant influenced by histology, gender and surgical methods. The 10-year survival rate for papillary carcinomas was 91% and for follicular carcinomas 84%. CONCLUSIONS: We recommend yearly follow-up examinations with selective use of other diagnostic methods in order to provide best patient care.

Use of sequential bone scintigraphy for monitoring onlay grafts to grossly atrophic jaws.

OBJECTIVES: To evaluate the capability of sequential bone scintigraphy for assessing the viability of avascular onlay grafts in combination with primary or secondary implant placement. METHODS: Forty-six patients with severe alveolar ridge atrophy received full-arch onlay grafts from the iliac crest. Twenty patients received primary insertion of endosseous implants, while secondary implant placement was performed in 26 patients after an average interval of 95 days. In cases of primary implant placement, bone scintigraphy was performed after grafting and before abutment connection. In patients with secondary insertion, bone scans were performed after grafting, before and after implant placement and before abutment connection. For bone scintigraphy, 8 MBq 99mTc-MDP/kg body weight were administered intravenously and anterior views of the skull were obtained 3 h later. Regions of interest were drawn over the grafted area and over the calvarium as a reference area. Ratios of count densities between jaw and calvarium were calculated as a measure of tracer uptake. RESULTS: Bone grafts with primary insertion of implants showed a significant decrease (P = 0.0001) in ratios calculated for the whole graft from a mean of 3.53 after grafting to 2.35 before abutment connection. In cases of secondary implant placement, ratios decreased significantly after grafting from 4.04 to 2.78 before implant placement (P = 0.0001). After implant placement, there was a significant increase to 3.28 (P = 0.0062), which was followed again by a significant decrease to a mean ratio of 2.58 (P = 0.0437). CONCLUSIONS: Sequential bone scintigrams can provide information about the viability of the graft at the time of implant insertion and may thus indicate the ability of the grafted bone to accomplish osseointegration.

Oxygen-15-water PET assessment of muscular blood flow in peripheral vascular disease.

UNLABELLED: To assess quantitatively regional nutritive muscular blood flow in patients with peripheral vascular disease (PVD), we evaluated the utility of PET with 15O-water. METHODS: Eight healthy volunteers and 16 patients with angiographically proven PVD were studied. Regional blood flow of the calf was measured with 15O-water PET during rest, after intra-arterial infusion of prostaglandin E1 and during ergometry. The studies were quantified using a one tissue compartment model. RESULTS: Normalized mean tracer uptake from 15-60 sec correlated closely (r = 0.98) with absolute blood flow. Scan times longer than 90 sec were required to determine blood flow reliably. The flow values were overestimated by 2% if arterial blood volume was neglected or if the input function delay was corrected globally for parametric imaging. Mean blood flow of calf muscles at rest did not differ significantly between patients (0.017 +/- 0.006 ml/min/ml) and control subjects (0.018 +/- 0.010 ml/min/ml). In PVD patients, blood flow increased by 100% after intra-arterial infusion of PGE1 in the respective leg. In the control subjects, average flow increased by a factor of six during exercise. The increase was more pronounced in the extensor muscles (0.182 +/- 0.031 ml/min/ml) than in flexor muscles (0.121 +/- 0.045 ml/min/ml). Due to the specific type of ergometry, superficial flexors exhibited higher flow values than the profound ones. CONCLUSION: PET with 15O-water enables reliable determination of regional nutritive skeletal muscle blood flow for research and clinical applications in patients with PVD.

[Scintigraphic method to test the function of intraperitoneal draining catheters for regional intraabdominal chemotherapy]. / Szintigraphische Uberprüfung der Funktion intraperitoneal liegender Katheter zur regionalen intraabdominellen Chemotherapie Scintigraphic Method to Test the Function of Intraperitoneal Draining Catheters for Regional Intraabdominal Chemotherapy.

AIM: Intraoperative peritoneal chemohyperthermia (IPCH) followed by one or more courses of closed intraperitoneal chemotherapy via peritonealdialysis-catheter (Zellermann) is a promising concept for treatment of peritoneal carcinomatosis. METHODS: To prove the functionality of the catheter a scintigraphic method is introduced using a liquid solution of sodium chloride-- Tc-99m-Diethylenetriaminepentaacetic acid (Tc-99m-DTPA) (500 ml). This study was aimed to look for problems over the period of application and to measure the intraperitoneal distribution and resorption of the fluid. RESULTS: One leakage and 3 revisible obstructions occured in 26 applications done in 20 patients. The upper right and the central abdomen was not reached as extensive as the other regions. The abdomen was divided into 9 regions of equal size. In 4 out of 19 patients (20%) the fluid tracer was missed in more than 3 regions (up to 40% of the total area). CONCLUSIONS: It is to early to decide whether methological modifications are necessary in these cases, but closed chemotherapies in patients with maldistribution may not be indicated. This will be in particular necessary if there is a relation between the maldistribution and the location of recurrencies. The demonstrated simple scintigraphic method, however, is able to recognize patients at risk.

A compartmental model for alveolar clearance of pertechnegas.

UNLABELLED: The washout of an inhaled water soluble radiotracer from the lungs is a measure of alveolar integrity. Data evaluation of 99mTc-DTPA studies were previously performed mainly with monoexponential fitting with or without background subtraction. The introduction of 99mTc-pertechnegas for the assessment of alveolar permeability necessitates the investigation of adequate data evaluation schemes for this radiotracer. METHODS: We developed a three-compartmental model to describe 99mTc-pertechnegas kinetics after inhalation. Monoexponential fitting of the first 5 min was investigated as simplification for clinical use. Different background corrections based on blood samples or representative regions of interest were compared. RESULTS: Correction of intra- and extravascular background by subtraction of calibrated curves, which are derived from blood or background areas, resulted in monoexponential washout curves. Clearance rates based on the three-compartmental model were nearly the same as those derived from a monoexponential fit after blood-activity subtraction (r = 0.96). A monoexponential analysis of the first 5 min without any background correction correlates well with the first component of the biexponential analysis (r = 0.97). CONCLUSION: A dynamic study of more than 45 min allows quantitative determination of the transfer rate of 99mTc-pertechnegas from the alveoli into the blood using compartmental analysis. A simplified monoexponential analysis of the first 5 min allows assessment of lung clearance without any background correction.

[Bone SPECT of the jaws after fracture, onlay osteoplasty of insertion of implants]. / Knochen-SPECT des Kiefers nach Fraktur, Auflagerungsosteoplastik oder Implantatinsertion.

AIM: The aim of this study was early differentiation between uncomplicated and complicated processes of healing in the jaw using bone SPECT. METHODS: Investigations were performed in 40 mandibular fractures and 26 jaws after onlay osteoplasty as well as secondary insertion of implants. Bone SPECT was carried out within 1-2 months and after approximately 4-5 months. The uptake in the jaw was assessed semi-quantitatively using ROI analysis. RESULTS: Fractures with uncomplicated healing showed a decrease of uptake in follow-up, whereas fractures with an infection in the later course showed an increase, resulting in a significantly higher uptake at the follow-up investigation for the latter group. 1-2 months after onlay osteoplasty significantly lower uptake was found in regions with later occurrence of sequestration. In regions with implants in which osseointegration failed, there was significant reduction of uptake initially and significant elevation at the follow-up investigation. CONCLUSION: These results indicate a prognostic relevance of bone SPECT in the evaluation of processes of healing in the jaw.

Completion thyroidectomy in 131 patients with differentiated thyroid carcinoma.

OBJECTIVE: To evaluate the prognostic factors that influence survival and recurrence after "completion" thyroidectomy (removal of the total thyroid remnant after diagnosis of carcinoma has been made in a specimen that was incompletely excised for a benign condition). DESIGN: Open study. SETTING: Teaching hospital, Germany. SUBJECTS: 131 Patients (65 with papillary and 66 with follicular thyroid cancer) who underwent completion thyroidectomy after primary subtotal resection. INTERVENTIONS: Indications for further operation were: tumour stage worse than pT1 ( n = 116), tumour stage pT1 and the suspicion of persistence of the tumour (n = 13), and incompletely resected tumour (n = 2). Multivariate analysis by Cox's proportional hazards model. MAIN OUTCOME MEASURES: Recurrence, development of metastases, and length of survival. RESULTS: Patients who underwent their completion thyroidectomies within six months of the primary operation had significantly fewer recurrences, fewer lymph node metastases, fewer haematogenous metastases and survived significantly longer than those in whom the second operation was delayed for longer than six months. The age at the time of diagnosis and the stage of the tumour influenced survival, whereas sex and type of tumour did not. CONCLUSION: Completion thyroidectomy as soon as possible after incomplete resection of the tumour may improve prognosis in differentiated thyroid cancers the stage of which is worse than pT1 or in patients whose recurrent tumour is diagnosed at follow-up.

A kinetic model for cardiac PET with [1-carbon-11]-acetate.

UNLABELLED: Carbon-11-labeled acetate is a unique tracer for noninvasive assessment of myocardial oxidative metabolism with PET. Because adequate kinetic models have been missing, data evaluation in the past was performed mostly with phenomenological approaches such as mono- or biexponential fitting which cannot account for the influence of finite input duration and blood volume encountered in noninvasive PET investigations. METHODS: To investigate to what extent the current data evaluation schemes are justified, we developed a comprehensive model of [1-11C]-acetate kinetics in the myocardium which incorporates five tissue compartments: free acetate, activated acetate, CO2 precursors, amino acids and CO2. We derived the analytical solution of the model equations which is used for simulations and data fitting. RESULTS: The five-compartment model can reproduce in detail known experimental data. The resulting values of the eight model parameters compare favorably with existing biochemical facts. We have established the relation between parameters of the detailed model and one- and two-compartment models used for the evaluation of PET investigations. CONCLUSION: The kinetics of [1-11C]-acetate are adequately described by a five-compartment model. One- and two-compartment models are sufficient for simultaneous quantitative assessment of myocardial oxidative metabolism and perfusion with [1-11C]-acetate and PET.

Evaluation of the incorporation of bone grafts used in maxillofacial surgery with [18F]fluoride ion and dynamic positron emission tomography.

This study investigates the incorporation of bone grafts used in maxillofacial surgery by means of [18F]fluoride ion and positron emission tomography (PET). It considers patients who received pedicle grafts for mandibular reconstruction or onlay grafts for alveolar ridge augmentation. Dynamic PET images and arterialized venous blood samples were obtained within a 1-h period after i.v. injection of [18F]fluoride. Assuming a three-compartment model and applying multilinear least squares fitting, bone blood flow (K1) and fluoride influx (Kmlf) were determined. Additionally Patlak plot analysis was used to calculate fluoride influx (Kpat). In cervical vertebral bodies as the reference region, mean values for flow of K1 = 0.1162 +/- 0.0396 ml/min/ml and influx of Kmlf = 0.0508 +/- 0.0193 and Kpat = 0.0385 +/- 0.0102 ml/min/ml were found. Essentially these figures are comparable with physiological values in animal and man reported in the literature. Early after surgery a significant increase in flow and influx compared to vertebral bodies was observed in the regions of osteosyntheses between grafts used for reconstruction and recipient bone (K1 = 0.2181, Kmlf = 0.1000 and Kpat = 0.0666 ml/min/ml) and in onlay grafts (K1 = 0.2842, Kmlf = 0.1637 and Kpat = 0.0827 ml/min/ml). At the same time pedicle grafts showed a significant increase in flow but not in influx (K1 = 0.2042, Kmlf = 0.0774 and Kpat = 0.0529 ml/min/ml). Furthermore Kpat was significantly lower in pedicle grafts than in onlay grafts. In follow-up studies a significant decrease in flow occurred in pedicle grafts and the regions of osteosyntheses. Moreover the latter showed a significant decrease in Kmlf as well. It is concluded that [18F(-)] PET depicted increased blood flow and osteoblastic activity in onlay grafts and regions of osteosyntheses, indicating bone repair in the graft and adjacent host bone early after surgery. For the regions of osteosyntheses the decrease in both parameters corresponded to uncomplicated healing. The lack of increased influx, although flow was increased in pedicle grafts, most likely indicates that some necrosis occurred in these grafts despite patency of anastomoses. It may be concluded that [18F(-)] PET provides further insight into the biology of graft incorporation.

Design of gas targets for the production of medically used radionuclides with the help of Monte-Carlo simulation of small angle multiple scattering of charged particles.

Due to scattering of protons or deuterons in the target gas the radius of beams increases with increasing penetration depth of the particles. The increase depends on the kind of beam particle, the energy, the target gas and its temperature and pressure. A Monte-Carlo program was developed for stimulation of multiple scattering. The initial beam has a particle distribution of variable sinusoidal shape behind the entrance window and may be cut off by the simulation of a collimator. The beam distribution is calculated for up to 14 planes representing energy values of the particles due to a predefined range from one plane to the next. The energy loss is calculated with the help of an integrated Bethe-Bloch routine. The distribution of the particles within the plane may be rearranged into profiles and transferred to a spreadsheet for further manipulation and graphical printout. Simulations are carried out for radionuclide production routes, commonly used for position emission tomography (PET).

[The importance of roentgenological and scintigraphic studies in patients with and without thigh pain following cementless PCA hip endoprosthesis]. / Bedeutung röntgenologischer und szintigraphischer Untersuchungen bei Patienten mit und ohne Oberschenkelschmerz nach zementfreier PCA-Hüftendoprothese.

Persisting postoperative thigh pain is a common problem in cementless total hip prostheses occurring in a rate of about 15-20% of the patients. The reason for that phenomenon has not become clear so far. In a clinical, radiological and scintigraphic study 70 patients with 81 PCA cementless total hips were randomized in groups with (n = 34) and without significant thigh pain (n = 36). All patients underwent clinical examination including a standardized questionnaire, x-ray and 3-phase bone scintigraphy. Quantitative assessment of Tc-99m-MDP uptake was made. In the group of patients with persisting thigh pain the scintigraphic analysis showed an significantly increased uptake at the tip and the medial and lateral femur. These findings could not be correlated with clinical loosening of the prosthesis. Slight or moderate uptake in the area of the greater and lesser trochanter as well as the tip was a common finding in PCA prosthesis in all patients. In the radiological analysis no difference between both groups was evident. The study showed that patients with thigh pain after cementless PCA total hip prosthesis have specific regions of significantly increased uptake in scintigraphic examination (tip, medial and lateral femur), which cannot be correllated with clinically or radiologically signs of loosening. The morphologic reasons for the thigh pain remain unclear.

Combined spatial and temporal imaging of brain activity during visual selective attention in humans.

Visual-spatial attention is an essential brain function that enables us to select and preferentially process high priority information in the visual fields. Several brain areas have been shown to participate in the control of spatial attention in humans, but little is known about the underlying selection mechanisms. Non-invasive scalp recordings of event-related potentials (e.r.ps) in humans have shown that attended visual stimuli are preferentially selected as early as 80-90 ms after stimulus onset, but current e.r.p. methods do not permit a precise localization of the participating cortical areas. In this study we combined neuroimaging (positron emission tomography) with e.r.p. recording in order to describe both the cortical anatomy and time course of attentional selection processes. Together these methods showed that visual inputs from attended locations receive enhanced processing in the extrastriate cortex (fusiform gyrus) at 80-130 ms after stimulus onset. These findings reinforce early selection models of attention.