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The impact of the particle size and wettability on the orientation and order of assemblies obtained by self-organization of functionalized microscale polystyrene cubes at the water/air interface is reported. An increase in the hydrophobicity of 10- and 5-μm-sized self-assembled monolayer-functionalized polystyrene cubes, as assessed by independent water contact angle measurements, led to a change of the preferred orientation of the assembled cubes at the water/air interface from face-up to edge-up and further to vertex-up, irrespective of microcube size. This tendency is consistent with our previous studies with 30-μm-sized cubes. However, the transitions among these orientations and the capillary force-induced structures, which change from flat plate to tilted linear and further to close-packed hexagonal arrangements, were observed to shift to larger contact angles for smaller cube size. Likewise, the order of the formed aggregates decreased significantly with decreasing cube size, which is tentatively attributed to the small ratio of inertial force to capillary force for smaller cubes in disordered aggregates, which results in more difficulties to reorient in the stirring process. Experiments with small fractions of larger cubes added to the water/air interface increased the order of smaller homo-aggregates to values similar to neat 30 μm cube assemblies. Hence, collisions of larger cubes or aggregates are shown to play a decisive role in breaking metastable structures to approach a global energy minimum assembly.

Metal-halide perovskites are a class of solution processed materials with remarkable optoelectronic properties such as high photoluminescence quantum yields and long carrier lifetimes, which makes them promising for a wide range of efficient photonic devices. In this work, we demonstrate the first successful integration of a perovskite laser onto a silicon nitride photonic chip. High throughput, low cost optical lithography is used, followed by indirect structuring of the perovskite waveguide. We embed methylammonium lead tri-iodide (MAPbI 3 ) in a pre-patterned race-track microresonator and couple the emitted light to an integrated photonic waveguide. We clearly observe the build-up of spectrally narrow lasing modes at room temperature upon a pump threshold fluence of 19.6 µJcm -2 . Our results evidence the possibility of on-chip lasers based on metal-halide perovskites with industry relevance on a commercially available dielectric photonic platform, which is a step forward towards low-cost integrated photonic devices.

Cerebral ischemia induces a complex transcriptional response with global changes in gene expression. It is essentially regulated by transcription factors as well as epigenetic players. While it is well known that the inhibition of transcriptionally repressive histone deacetylases leads to neuroprotection, the role of histone methyltransferases in the postischemic transcriptional response remains elusive. We investigated the effects of inhibition of the repressive H3K9 histone methyltransferases SUV39H1 and G9a on neuronal survival, H3K9 promoter signatures and gene expression. Their inhibition either with the specific blocker chaetocin or by use of RNA interference promoted neuronal survival in oxygen glucose deprivation (OGD). Brain-derived neurotrophic factor (BDNF) was upregulated and BDNF promoter regions showed an increase in histone marks characteristic for active transcription. The BDNF blockade with K252a abrogated the protective effect of chaetocin treatment. In conclusion, inhibition of histone methyltransferases SUV39H1 and G9a confers neuroprotection in a model of hypoxic metabolic stress, which is at least in part mediated by BDNF.

The Pliocene lignite hypothesis is an environmental hypothesis that has been proposed to explain the etiology of Balkan endemic nephropathy (BEN). Aqueous leaching experiments were conducted on a variety of coal samples in order to simulate groundwater leaching of organic compounds, and to further test the role of the Pliocene lignite hypothesis in the etiology of BEN. Experiments were performed on lignite coal samples from endemic BEN areas in Romania and Serbia, and lignite and bituminous coals from nonendemic regions in Romania and the USA. Room temperature, hot water bath, and Soxhlet aqueous extraction experiments were conducted between 25 and 80 °C, and from 5 to 128 days in duration. A greater number of organic compounds and in higher concentrations were present in all three types of leaching experiments involving endemic area Pliocene lignite samples compared to all other coals examined. A BEN causing molecule or molecules may be among phenols, PAHs, benzenes, and/or lignin degradation compounds. The proposed transport pathway of the Pliocene lignite hypothesis for organic compound exposure from endemic area Pliocene lignite coals to well and spring drinking water, is likely. Aromatic compounds leached by groundwater from Pliocene lignite deposits in the vicinity of endemic BEN areas may play a role in the etiology of the disease. A better understanding of organic compounds leached by groundwater from Pliocene lignite deposits may potentially lead to the identification and implementation of effective strategies for the prevention of exposure to the causative agent(s) for BEN, and in turn, prevention of the disease.

Background: Development of biosimilars requires physicochemical and biologic characterization to show comparability with a reference product. Zarzio (filgrastim) is a biosimilar recombinant human granulocyte colony-stimulating factor (G-CSF) that has been approved in the EU using Neupogen as its reference product., Objective: The aim of this study was to compare the drug identity, purity, and bioactivity of Zarzio (300 and 480 μg/0.5 mL solution) with Neupogen, using a broad range of standard and advanced analytical methods., Methods: Peptide mapping with UV detection and mass determination, circular dichroism (CD) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry and liquid chromatography electrospray ionization (LC-ESI) mass spectrometry were among the analyses used to compare primary and higher-order protein structure. Cation-exchange chromatography (CEX) and reversed-phase high-performance liquid chromatography (RP-HPLC) were used to compare polarity and charge. Biologic characterization included comparison of G-CSF receptor binding affinity by surface plasmon resonance spectroscopy, an in vitro cell proliferation assay, and Western blot immunologic binding., Results: The primary structures of Zarzio and Neupogen were shown to be identical by peptide mapping and other tests. CD and NMR spectroscopy demonstrated that the two products have comparable secondary and tertiary structures. RP-HPLC and other methods showed that the products have similar purity profiles. Comparable affinity with the G-CSF receptor GCSFR/CD114 was obtained using surface plasmon resonance spectroscopy, and comparable in vitro bioactivity was shown in a cell proliferation assay., Conclusion: These results show the physicochemical and biologic comparability of Zarzio and its reference product, Neupogen.

Objective: The Multicentre Study Differentiated Thyroid Cancer (MSDS) collective represents a well-defined group of patients with thyroid carcinomas with extrathyroidal extension. The aim of the present study was to evaluate the relationship of the primary tumour size with clinicopathological features as well as the outcome of patients with minimum and extensive extrathyroidal growth (pT3b- and pT4a-tumours; UICC 2002/2003, 6th ed)., Methods: The tumour diameter was available in 324 out of 351 MSDS patients (244 females, 80 males). Mean age of patients was 47.7±12.0 years (range, 20.1-69.8 years), and the median follow-up was 6.2 years. The relationship between primary tumour size and the following clinicopathological data was investigated: age, gender, histological tumour type (papillary thyroid carcinomas (PTC) versus follicular thyroid carcinomas (FTC)) and UICC/AJCC TNM classification. In addition, the correlation between primary tumour size and event-free and overall survival was assessed., Results: The FTC of our series were significantly larger than PTC (3.46 vs 1.84 cm; P<0.001). Patients suffering from pT3b-tumours presented with significantly smaller tumour size than those with extensive extrathyroidal growth (pT4a-tumours) (1.9 vs 3.0 cm; P<0.01). All patients with distant metastases suffered from tumours >2 cm. Furthermore, event-free and overall survival were significantly correlated with increasing tumour size (P<0.05). Using multivariate analysis, a pT4a-category and a tumour diameter >2 cm remained independent predictors of survival., Conclusions: In patients suffering from differentiated thyroid carcinoma with extrathyroidal growth (pT3b and pT4a), the tumour size is an independent predictor of event-free and overall survival.

Objective: During a subcutaneous injection with commonly used pen needles, the safety of drug administration plays an essential role. Today short needles with a length of 5.0 mm are increasingly being used. However, so far it is unresolved whether short needles of <5.0 mm affect the safety of insulin injections because of an increased backflow to the skin surface. We examined the influence of needle length and administered insulin dosage on the insulin backflow and the distribution of human insulin in the tissue by a quantitative determination of the amount of backflow of insulin to the skin surface. For the first time a new 4.5-mm pen needle was examined for its administration safety., Research Design: Human insulin was radioactively marked. By means of an insulin pen different insulin dosages with pen needles of different lengths into fresh pork rind (ex vivo model) were administered. The amount of the marked insulin leaking from the tissues at the injection site was covered and absorbed immediately into a cotton swab. The amount of leakage was calculated by means of the radioactivity taken up by the swab., Results: The amount of leakage for each measurement was less than 1% of the total dosage administered. The amount of leakage increased with increased dosage administered in absolute terms, but expressed as a percentage of the increased dosage administered the leakage decreased., Conclusion: The needle length (between 12 mm and 4.5 mm) did not have a meaningful influence on the amount of leakage; however, significant differences with different needle lengths could be observed.

Background: Needlestick injuries are always associated with a risk of infection, because these types of punctures may expose healthcare workers to a patient's blood and/or body fluids., Objective: To compare the efficacy of 4 different types of surgical gloves for preventing exposure to blood as a result of needlestick injury., Methods: For simulation of needlestick injury, a circular sample of pork skin was tightened onto a bracket, and a single finger from a medical glove was stretched over the sample. First, a powder-free surgical glove with a gel coating was used to test blood contact. Second, a glove with a patented puncture indication system was used to test blood contact with a double-gloved hand. Third, 2 powder-free latex medical gloves of the same size and hand were combined for double gloving, again to test blood contact. Finally, we tested a glove with an integrated disinfectant on the inside. The punctures were carried out using diverse sharp surgical devices that were contaminated with (99)Tc-marked blood. The amount of blood contact was determined from the transmitted radioactivity., Results: For the powder-free surgical glove with a gel coating, a mean volume of 0.048 microL of blood (standard error of the mean [SEM], 0.077 microL) was transferred in punctures with an automated lancet at a depth of 2.4 mm through 1 layer of latex. For the glove with an integrated disinfectant on the inside, the mean volume of blood transferred was 0.030 microL (SEM, 0.0056 microL) with a single glove and was 0.024 microL (SEM, 0.003 microL) with 2 gloves. For the glove with the patented puncture indication system, a mean volume of 0.024 microL (SEM, 0.003 microL) of blood was transferred., Conclusions: Double gloving or the use of a glove with disinfectant can result in a decrease in the volume of blood transferred. Therefore, the use of either of these gloving systems could help to minimize the risk of bloodborne infections for medical staff.

Background: Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance characterised by excessive tachycardia of unknown aetiology. Whether this condition involves abnormal cardiac sympathetic innervation or function remains elusive. Meta-iodobenzylguanidine (MIBG) resembles guanethidine and is a pharmacologically inactive analogue of norepinephrine, which is similarly metabolised in noradrenergic neurons. MIBG myocardial scintigraphy is used clinically to estimate local myocardial sympathetic nerve damage in some forms of heart disease and autonomic neuropathy. The objective of this study was to evaluate cardiac sympathetic innervation in patients with POTS., Methods: 20 patients with POTS were studied using (123)I-MIBG-single photon emission computed tomography, standardised autonomic testing, assessment of catecholamine plasma levels and sympathetic skin response., Results: In four POTS patients (20.0%), myocardial MIBG uptake was markedly decreased. The mean heart to mediastinum ratio was reduced to 1.22+/-0.08 compared with the normal range of >1.7. No correlation was found between myocardial MIBG uptake and degree of postural tachycardia, baroreflex sensitivity, catecholamine plasma levels or other autonomic parameters. Sympathetic skin responses were normal in all patients., Conclusions: These findings suggest that POTS may be, in part, a manifestation of autonomic cardiac neuropathy. MIBG myocardial scintigraphy may be helpful to distinguish patients with neuropathic POTS from patients with orthostatic intolerance of other origin.

Indoor air pollution has been identified as a major risk factor for acute and chronic respiratory diseases throughout the world. In the sovereign Navajo Nation, an American Indian reservation located in the Four Corners area of the USA, people burn coal in their homes for heat. To explore whether/how indoor coal combustion might contribute to poor respiratory health of residents, this study examined respiratory health data, identified household risk factors such as fuel and stove type and use, analyzed samples of locally used coal, and measured and characterized fine particulate airborne matter inside selected homes. In twenty-five percent of homes surveyed coal was burned in stoves not designed for that fuel, and indoor air quality was frequently found to be of a level to raise concerns. The average winter 24-hour PM₂.₅ concentration in 20 homes was 36.0 μg/m³. This is the first time that PM₂.₅ has been quantified and characterized inside Navajo reservation residents' homes.

Patients with idiopathic Parkinson's disease (PD) have impaired sympathetically mediated neurocirculatory innervation. Here we analyzed the correlation between cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake, orthostatic hypotension and heart rate variability in treated patients with PD. Orthostatic hypotension (OH) as a hallmark of sympathetic neurocirculatory failure was found with a high prevalence in PD. PD is known to affect cardiac innervation, resulting in a suppressed heart rate variability and a postganglionic noradrenergic lesion. We measured continuous arterial blood pressure in rest and 70 degrees head-up tilt for at least 20 min, heart rate variability in the supine position, standing, deep respiration and Valsalva manoeuvre in 58 patients with PD (27 male, 31 female; mean age 71 years, mean PD duration 5.1 years, Hoehn and Yahr 3.1+/-0.8). Sympathovagal balance was estimated by the low-frequency (LF: 0.04-0.15Hz) and high-frequency bands (HF: 0.15-0.4Hz) ratio in the analysis of heart rate variability in each condition. Myocardial adrenergic function was analyzed by imaging MIBG using the single-photon emission computed tomography technique. MIBG uptake expressed as heart-to-mediastinum ratio was reduced in all PD patients (H/M-ratio: 1.14+/-0.16). We found no correlation between myocardial MIBG uptake and sympathovagal balance, blood pressure or other autonomic findings. The LF/HF ratio in tilt-table testing was significantly more reduced in PD with OH than without OH (2.18 vs. 1.49, p=0.022). MIBG uptake did not differ. It is concluded that scintigraphy with MIBG appears to be a highly sensitive and useful tool to demonstrate sympathetic postganglionic cardiac nerve disturbances. Loss of sympathetic innervation of the heart seems to occur early and independent of orthostatic hypotension, baroreflex failure and impaired heart rate variability in PD.

Myocardial 123I-Meta-iodobenzylguanidine uptake was markedly reduced in a patient with postural tachycardia syndrome (POTS). This finding suggests that loss of sympathetic autonomic neurons in the heart may play a role in the etiology of POTS.

Current research has shown relationships between the environment (eg, parks and trails) and levels of physical activity participation. This study was designed to implement and evaluate a communications based worksite campaign to promote awareness of an existing local walking path and to increase walking. Promotional materials were distributed for 1 month via flyers, email, website postings, and during bi-weekly information booths. Evaluations were conducted at baseline, during, and following the promotional campaign. Borderline statistically significant increases in walking activity from baseline were observed midway through the campaign (p = 0.069) and following the campaign (p = 0.075). Counts observed during the intervention were almost triple those at baseline and increased in the post-campaign phase to approximately three and a half times those at baseline. Sign recognition surveys revealed at baseline, 51% of the participants correctly identified the walking path signs, which increased to 65% during the campaign (p = .0674). Familiarity with physical activity messages around the workplace increased from 64.6% at baseline to 75.5% during the campaign (p = .097). This study shows initial promise of a theoretically based communications intervention to increase knowledge of physical activity and to promote walking.

Aim and Method: Scientific publications in the journal of Nuklearmedizin Molecular Imaging and Therapy during 2004/2005 were retrospectively examined for their potential classification to molecular imaging or molecular guided therapy, functional imaging and therapy, and were compared to earlier analyses., Results: Of the 57 original papers examined, 36 (63%) were assigned to the category of molecular imaging/molecular guided therapy. Within this category, the number of original papers on molecular guided therapy increased by 19% compared to preceding periods. There was a general overall increase in the proportion of experimental papers and more frequent inclusion of basic background subjects., Conclusion: The development of molecular imaging as a direct instrument in therapy planning leads to further promotion of molecular guided therapy. The structural advantage of nuclear medicine, uniting method-lead diagnosis and therapy within one specialist subject, predestines it to advance molecular imaging and molecular guided therapy.

Unlabelled: AIM, METHOD: The scientific publications in the 2003 and 2004 issues of the journal Nuklearmedizin were analyzed retrospectively with regard to the proportion of medical technology research., Results: Out of a total of 73 articles examined, 9 (12%) were classified as medical technology research, that is, 8/15 of the original papers (16%) and one of the case reports (5%). Of these 9 articles, 44% (4/9) focused on the combination of molecular and morphological imaging with direct technical appliance or information technology solutions., Conclusion: Medical technology research is limited in the journal's catchment area. The reason for this is related to the interdependency between divergent development dynamics in the medical technology industry's locations, the many years that the area of scintigraphic technology has been underrepresented, research policy particularly in discrepancies in the promotion of molecular imaging and a policy in which health is not perceived as a predominantly good and positive economic factor, but more as a curb to economic development.

Unlabelled: AIM, METHOD: The scientific publications in the 2002 and 2003 issues of the journal Nuklearmedizin. Journal of Functional and Molecular Imaging were analyzed retrospectively with regard to the development of information technology methods., Results: Out of a total of 72 original papers and case reports 9 (11%) were classified having information technology as their subject, 5 (56%) of them the fusion of molecular and morphological imaging. Researchers from medical specialities other than nuclear medicine were co-authors in 7 (78%) of the 9 articles, out of the 8 original papers 4 (50%) were prospective studies. Of the 59 original papers, 28 (47%) were predominantly dedicated to methodological development; 46/59 (78%) of them were clinical studies and 2 (3%) experimental research., Conclusion: Although a high proportion of the papers were dedicated to methodological development, the proportion dedicated to development of information technology methods was relatively low.

Objective: The main objective of this study was to evaluate a clinically suspected renovascular hypertension (RVH) by means of MRI. It was to find out if functional MRI (fMRI) is able to provide adequate results with regard to MAG3 captopril scintigraphy and if contrast-enhanced MR angiography (MRA) is able to provide adequate results in the stenosis grading compared with the nonselective digital subtraction angiography (DSA)., Methods: This open, monocentric, prospective, phase 3 study included patients with a clinically suspected RVH. For fMRI a dynamic TurboFLASH sequence and for MRA a single-shot breath-hold flash 3D sequence was performed. Gadodiamide was injected as contrast medium., Results: Sixty patients were included in the study. The correlation between fMRI and scintigraphy had an accuracy, a sensitivity, and a specificity of 69%, 5%, and 92%, respectively, and correlations between MRA and DSA of 95%, 92%, and 96%., Conclusion: The noninvasive MRA can replace DSA in the diagnosis of renal artery stenosis. However, fMRI can not replace renal scintigraphy.

Aim and Method: The scientific publications in the 2001 and 2002 issues of the journal Nuklearmedizin. Journal of Functional and Molecular Imaging were analyzed retrospectively with regard to molecular imaging/therapy content criteria., Results: Out of a total of 82 original papers and case reports 83% were based on molecular or functional methods, 91% of them using commercially available tracers, 57% were categorized as molecular imaging, 11% as molecular therapy, 12% as functional imaging and 2% as functional therapy. 3% of the studies were categorized as experimental research. Researchers from medical specialties other than nuclear medicine were co-authors in 71% of the articles, they were rooted in basic medical sciences in 16%. Of the 65 original papers 51% were predominantly dedicated to methodological development; 49% of them were prospective studies., Conclusion: The subtitle Journal of Functional and Molecular Imaging describes the current practice of publishing in Nuklearmedizin. The number of authors from other specialties shows that multidisciplinary integration within the field of molecular imaging is performed. Nevertheless, more integration of basic medical sciences is needed. Nuklearmedizin contributes to the insight of molecular imaging and to its clinical application in humans.

Purpose: With conventional planar imaging, preoperative anatomic localization of a sentinel lymph node is possible in only two dimensions. To improve spatial localization of sentinel lymph nodes, a dual-head camera equipped with a transmission source was used to create combined transmission-emission SPECT images in a patient with a malignant melanoma of the left forearm., Methods: Lymph node scintigraphy was performed after injection of Tc-99m-labeled nanocolloid around the tumor site 1 day before operation. SPECT was performed using a gamma camera equipped with a transmission collimator system originally designed to correct attenuation. Transmission and emission images were created simultaneously, matched, and displayed in three dimensions., Results: In the combined emission-transmission images, the sentinel lymph node was clearly located in the left axilla. The lymph nodes could be identified during operation at the same location as that detected by SPECT. Based on preoperative information, the sentinel lymph node was identified rapidly and the extent and duration of the operation were minimized., Conclusions: This method provides better anatomic information, especially in deep structures such as the axilla or pelvis. With accurate three-dimensional preoperative information, intraoperative access is quicker and less invasive for the patient.

Aim: The paper reviews current scientific publishing practice in the journal Nuklearmedizin., Method: The scientific publications in the 2000 and 2001 issues of the journal were analyzed retrospectively with regard to their authors, formal content criteria and citation practice., Results: 102 articles (69 original papers, 29 case reports, 4 review articles) were published. Of a total of 561 authors, 80 first authors came from Germany, 9 from Austria, 3 from Switzerland, and 10 from other countries. In 58 out of the 102 publications, researchers from other medical specialties were co-authors. The first authors were based at university hospitals or research centers in the case of 88 out of 102 publications. The author of one article had his own practice. Of the 102 first authors, 24 were female with a statistically significantly (p = 0.04) higher proportion in case reports compared to original papers. A total of 88/98 original papers and case reports were categorized as clinical research, 2 out of 69 original papers as experimental research, and 8 as management, health policy and radiation protection. 36 out of 102 articles were in English. The 69 original papers included a median of 48 investigated patients (range 4-991). A total of 2555 other papers with a median of 19 (range 3-230) was cited, comprising 212 citations of the journal Nuklearmedizin, i.e. 8.3% (range 0-56%)., Conclusion: The number of authors per paper documents the tendency to team work with a major participation of other specialties; university hospitals and research centers are represented more often. There is a predominance of clinical research with a high average number of patients per study. The percentage of first female authors are proportionate to their percentage membership in the learned societies. The relatively high percentage of papers in English raises the potential to increase the scientific response to publication of the content.

Objective: In recent in vivo studies using positron emission tomography (PET) our group demonstrated that the myocardial beta adrenoceptor (betaAR) density is reduced in arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic right ventricular outflow tract tachycardia (RVO-VT) associated with an increased presynaptic catecholamine washout. It was hypothesised that the reduction of myocardial betaAR density is secondary to an increase of local catecholamines in the myocardium resulting from the presynaptic dysfunction since circulating plasma catecholamines were demonstrated to be unchanged in these conditions. To further prove this hypothesis of an organ-limited adrenergic nervous dysfunction of the heart, this study aimed to investigate betaAR density in another thoracic organ, the lung., Methods: Pulmonary and myocardial betaAR density was measured in 7 ARVC patients, 8 RVO-VT patients and in a group of healthy controls (n = 13) using the non-selective beta-blocker [11C]-CGP 12177 and PET., Results: Pulmonary betaAR density was similar in controls (12.4 +/- 1.7 pmol/g tissue), ARVC (11.6 +/- 1.7 pmol/g tissue, p = ns) and RVO-VT (12.8 +/- 2.0 pmol/g tissue, p = ns), whereas myocardial betaAR density was significantly reduced in ARVC (6.3 +/- 1.1 pmol/g tissue, p = 0.006) and RVO-VT (6.8 +/- 1.2 pmol/g tissue, p=0.02) as compared to controls (8.8+/-1.5 pmol/g tissue)., Conclusion: The unchanged pulmonary betaAR density in the presence of a previously described significant reduction in myocardial betaAR density in the same patient principally supports our pathophysiological hypothesis that the myocardial betaAR density may be reduced in ARVC and RVO-VT because of an increase in local synaptic catecholamine levels due to an organ-limited presynaptic adrenergic dysfunction of the heart. Since in the present study only pulmonary betaAR density was measured, future functional studies excluding pulmonary betaAR desensitisation are required to finally prove the unchanged pulmonary sympathetic innervation in ARVC and RVO-VT.

Objective: To perform a comparative analysis of 1) intravenous Ig (IVIG)-bound Fab fragments from a patient with autoimmune thrombocytopenia that had progressed to systemic lupus erythematosus (SLE) and 2) IVIG-selected Fabs from an SLE patient without thrombocytopenia., Methods: IVIG preparations have been successfully used to treat certain cases of autoimmune thrombocytopenia and SLE. Specific interactions of IVIG with the components of the immune system are not well characterized. To investigate these, we had previously cloned a large number of phage-displayed IgG Fab fragments, derived from 3 patients with autoimmune thrombocytopenia, that were specifically bound by IVIG molecules during panning. Many of these Fabs reacted with platelets. Sequencing revealed that the most frequently used VH germline gene segments of all IVIG-bound Fabs were 3-23 and 3-30/3-30.5. One patient's autoimmune thrombocytopenia had progressed to SLE. Using the same cloning and panning procedures, we performed a comparative analysis of this patient's IVIG-bound Fab fragments and the IVIG-selected Fabs from an SLE patient without thrombocytopenia., Results: We observed an exclusive selection of antibodies derived from 3-23 and 3-30/3-30.5 germline segments. In contrast to the Fab fragments from the autoimmune thrombocytopenia patient who developed SLE, none of the IVIG-selected Fabs from the SLE patient without thrombocytopenia bound to thrombocytes., Conclusion: Our results suggest a preferential interaction of a subfraction of IVIG-representative of normal Ig repertoires-with antibodies and B cell receptors derived from these 2 gene segments. Importantly, these are the most frequently rearranged VH germline genes among human B cells. This kind of interaction is characteristic of a B cell superantigen, since light chains, antigen specificity, and the high variation in the third complementarity-determining region 3 showed little influence on the selection of 3-23- or 3-30/3-30.5-derived Fabs by IVIG. However, at least some of the contact residues on Fabs for IVIG appear to be different from those for staphylococcal protein A and human immunodeficiency virus gp 120. The IVIG-selected Fabs may now be used to clone antibodies representative of this IVIG subfraction to study their possible regulatory influence on the B cell repertoire during normal development and disease.

The stereotyped pattern of veins in the Drosophila wing is generated in response to local EGF signalling. Mutations in the rhomboid (rho) gene, which encodes a sevenpass membrane protein required to enhance signalling transmitted by the EGF receptor (Egfr), inhibit vein development and disrupt the vein pattern. By contrast, net mutations produce ectopic veins in intervein regions. We have cloned the net gene and show that it encodes a basic HLH protein that probably acts as a transcriptional repressor. net and rho are expressed in mutually exclusive patterns during the development of the wing imaginal disc. Lack of net activity causes rho expression to expand, and vice versa. Furthermore, ectopic expression of net or rho results in their mutual repression and thus suppresses vein formation or generates tube-like wings composed of vein-like tissue. Egfr signalling and net exert mutually antagonising activities during the specification of vein versus intervein fate. While Egfr signalling represses net transcription, net exhibits a two-tiered control by repressing rho transcription and interfering with Egfr signalling downstream of Rho. Our results further suggest that net is required to maintain intervein development by restricting Egfr signalling, which promotes vein development, to the Net-free vein regions of the wing disc.

Intravenous immunoglobulin preparations (IVIG) have shown positive effects in the treatment of immune defects and autoimmune diseases. It is not clear how IVIG interacts with the components of the immune system. To investigate this, we cloned previously a large number of phage displayed IgG Fab fragments derived from three patients with autoimmune thrombocytopenia (AITP) that were specifically bound by IVIG molecules. Many of these Fabs reacted with platelets. Sequencing revealed that the most frequently used germ-line gene segments of all IVIG-bound Fabs were identical to those observed for many other autoantibodies. Particularly, the loci 3-30 or 3-30/3-30. 5, 3-23 and 3r, 3l, and 2a2 represented the most abundant genes used for the heavy (VH) and light chain V region (VL), respectively. This suggested a specific interaction of IVIG molecules with B cells that present B cell receptors derived from these germ-line genes. In the current study we determined the genetic origin of IVIG-reactive IgG and IgM cloned from a healthy person. A favoured selection of antibodies derived from the same germ-line origins as in AITP was observed. Because 3-30 and 3-23 are the most frequently rearranged VH germ-line gene segments among human B cells, our results suggest that this favoured anti-idiotypic interaction may have an important role for the development and control of the normal B cell repertoire.

Background: The frequent provocation of ventricular tachycardia by stress or catecholamines and the efficacy of antiarrhythmic drugs with antiadrenergic properties suggest an involvement of the cardiac adrenergic system in arrhythmogenesis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Previous studies demonstrated abnormalities of the presynaptic uptake-1 assessed by (123)I-MIBG-single-photon emission computed tomography., Methods and Results: This study investigated neuronal reuptake of norepinephrine (uptake-1) and beta-adrenergic receptor density in 8 patients with ARVC and 29 age-matched control subjects. All subjects underwent positron emission tomography with the volume of distribution (V(d)) of [(11)C]hydroxyephedrine ((11)C-HED) used to assess presynaptic norepinephrine reuptake, the maximum binding capacity (B(max)) of [(11)C]CGP-12177 ((11)C-CGP-12177) to assess postsynaptic beta-adrenergic receptor density, and [(15)O]H(2)O for quantification of myocardial blood flow. Patients with ARVC demonstrated a highly significant global reduction in postsynaptic beta-adrenergic receptor density compared with that in control subjects (B(max) of (11)C-CGP-12177: 5.9+/-1.3 vs 10.2+/-2.9 pmol/g tissue, P<0.0007), whereas the presynaptic uptake-1 tended toward reduction only (V(d) of (11)C-HED: 59.1+/-25.2 vs 71.0+/-18.8 mL/g tissue, NS). There were no differences in myocardial blood flow between the groups, and plasma norepinephrine was within normal limits in patients and control subjects., Conclusions: The findings demonstrate a significant reduction of myocardial beta-adrenergic receptor density in patients with ARVC. This may result from a secondary downregulation after increased local synaptic norepinephrine levels caused by increased firing rates of the efferent neurons or as the result of impaired presynaptic catecholamine reuptake. These findings give new insights into the pathophysiology of arrhythmogenesis in ARVC, with potential impact on diagnostic evaluation and therapeutic management.

The aim of this multicentre study was to evaluate the clinical significance of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in differentiated thyroid carcinoma and to compare the results with both iodine-131 whole-body scintigraphy (WBS) and technetium-99m 2-methoxyisobutylisonitrile (MIBI) or thallium-201 chloride (Tl) scintigraphy. Whole-body PET imaging using FDG was performed in 222 patients: 134 with papillary tumours, 80 with follicular tumours and 8 with mixed-cell type tumours. Finally, for each case an overall clinical evaluation was done including histology, cytology, thyroglobulin level, ultrasonography, computed tomography and subsequent clinical course, to allow a comparison with functional imaging results. Sensitivity of FDG-PET was 75% and 85% for the whole patient group (n = 222) and the group with negative radioiodine scan (n = 166), respectively. Specificity was 90% in the whole patient group. Sensitivity and specificity of WBS were 50% and 99%, respectively. When the results of FDG-PET and WBS were considered in combination, tumour tissue was missed in only 7%. Sensitivity and specificity of MIBI/Tl were 53% and 92%, respectively (n = 117). We conclude that FDG-PET is a sensitive method in the follow-up of thyroid cancer which should be considered in all patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases, and particularly in those with elevated thyroglobulin values and negative WBS.

Autoimmune thrombocytopenic purpura (AITP) is a severe disease in children with a still unknown aetiology. It is not known why AITP can either be transient and self limiting or become chronic. The beneficial use of intravenous immunoglobulins (IVIG) in certain groups of AITP patients has been proven. It is, however, not clear how IVIG functions. To analyse patient-derived monoclonal IgG platelet autoantibodies that interact with IVIG in an anti-idiotypic manner, the combinatorial antibody phage display system was applied. From three different patients a large number of clones specifically reacting with IVIG molecules were derived. Many of these IVIG binders also reacted strongly with platelets in ELISA and FACS, in contrast to IVIG binders derived from a healthy individual. The heavy and light chain variable regions were sequenced and compared with each other and with databases. In all three AITP patients clones with a striking complementarity-determining region (CDR) sequence homology to each other and to many of the known anti-platelet antibodies were observed. Selected Fab-phages representing the characteristic variable regions that occurred in the investigated patients with AITP may now be used to clone potentially regulatory anti-idiotypes from healthy donors by phage display.

Unlabelled: Patients with idiopathic ventricular tachycardia or fibrillation have no additional structural or functional myocardial abnormalities. However, the inducibility of typical tachyarrhythmias by physical or mental stress or by catecholamine infusion suggests the involvement of the adrenergic system in the pathogenesis of these potentially life-threatening diseases., Methods: 45 patients with idiopathic right ventricular outflow tract tachycardia (RVO-VT), 25 patients with idiopathic left ventricular tachycardia (ILVT), 15 patients with idiopathic ventricular fibrillation (IVF) and 10 age-matched control patients were investigated in this study. Diagnoses were made on the basis of detailed evaluation of the results of two-dimensional echocardiography, left and right ventricular angiography, coronary angiography and endomyocardial biopsy. Local presynaptic norepinephrine re-uptake was assessed using the norepinephrine analog 1231-metaiodobenzylguanidine (MIBG), SPECT and semiquantitative 33-segment bull's-eye analysis., Results: Locally reduced 123I-MIBG uptake was found in 27 of 45 RVO-VT patients (60%), 5 of 15 ILVT patients (33%) and 17 of 25 IVF patients (68%). Unlike ILVT patients, RVO-VT and IVF patients had significantly reduced segmental 123I-MIBG uptake of the posterior wall compared with control patients., Conclusion: Patients with idiopathic tachycardia and fibrillation show abnormal 1231-MIBG uptake, which indicates presynaptic sympathetic dysfunction. RVO-VT and IVF patients exhibit significantly reduced 123I-MIBG uptake in the posterior left ventricular wall, whereas ILVT patients do not.

The beneficial use of intravenous immunoglobulins (IVIG) in certain groups of patients with autoimmune thrombocytopenic purpura (AITP) has been proven. AITP is a severe disease in children with a still unknown etiology. It is not clear how IVIG functions in this and other autoimmune diseases. To analyze and compare patient-derived monoclonal IgG antibodies that are bound by IVIG in an anti-idiotypic manner, the combinatorial antibody phage display system was applied. From three different patients with AITP, a large number of clones specifically reacting with IVIG molecules were enriched. The heavy and light chain variable regions were sequenced and compared with each other and with databases. Many variable regions showed extensive replacement mutations within the complementarity-determining regions, while two were identical to germ-line genes. Our data show that the most frequently used germ-line gene loci of these IVIG binders are identical to those observed for many other autoantibodies. This implicates a specific interaction of IVIG particularly with autoantibodies and B cell receptors derived from germ-line genes that are often used for the generation of autoantibodies.

Objectives: This study investigated the neuronal reuptake of norepinephrine (uptake-1) and the beta-adrenoceptor density in patients with idiopathic right ventricular outflow tract tachycardia (RVO-VT)., Background: Clinical findings, such as the inducibility of ventricular tachycardia by stress or catecholamine infusion, and the therapeutic efficacy of antiarrhythmic drugs with antiadrenergic properties suggest abnormalities of cardiac sympathetic innervation in patients with idiopathic RVO-VT., Methods: Eight patients with idiopathic RVO-VT and a total of 29 age-matched control subjects were investigated by positron emission tomography using [11C]hydroxyephedrine (HED) (volume of distribution of [11C]HED) to assess presynaptic norepinephrine reuptake; [11C]CGP 12177 (maximal binding capacity of [11C]CGP 12177) to measure postsynaptic beta-adrenoceptor density; and oxygen-15-labeled water for quantification of myocardial blood flow (MBF)., Results: Both myocardial catecholamine reuptake and beta-adrenoceptor density were significantly reduced in patients with idiopathic RVO-VT. The volume of distribution of [11C]HED in patients with RVO-VT was (mean +/- SD) 41.0 +/- 13.5 versus 71.0 +/- 18.8 ml/g in control subjects (p < 0.002). The maximal binding capacity of the beta-adrenoceptor antagonist [11C] CGP 12177 was 6.8 +/- 1.2 pmol/g in patients with RVO-VT versus 10.2 +/- 2.9 pmol/g in control subjects (p < 0.004). There were no significant differences in MBF at rest (0.98 +/- 0.14 vs. 0.97 +/- 0.24 ml/min per g, p = NS) between patients with RVO-VT and control subjects., Conclusions: The findings of the present study suggest that myocardial beta-adrenoceptor downregulation in patients with RVO-VT occurs subsequently to increased local synaptic catecholamine levels caused by impaired catecholamine reuptake.

Introduction: In patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin (hTg) may occur in spite of otherwise negative diagnostic procedures and in particular in spite of a negative iodine-131 scan. Positron emission tomography with F-18-deoxyglucose (FDG-PET) is a potentially useful method for the detection of metastatic lesions or the recurrence of thyroid cancer. We aimed to investigate whether FDG-PET is capable of detecting metastatic lesions or recurrence in patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin, and otherwise negative diagnostic procedures, including the iodine-131 scan., Methods: From a group of 500 patients with differentiated thyroid carcinoma, a subgroup of 32 patients had elevated serum hTg-levels, negative iodine- 131 scans, negative cervical and abdominal ultrasound, and negative X-ray of the chest. In 12 of these patients (hTg 77.8+/-94.3 ng/ml, range 1.5-277 ng/ml, median 20 ng/ml), FDG-PET was performed. All but one FDG-PET study was performed in a state of hypothyroidism (TSH 75.8+/-32.2 microIU/ml, range 31-116 microIU/ml, median 74.6 microIU/ml)., Results: In 6 of the 12 patients investigated, the FDG-PET was positive. In three of the patients, the diagnosis was confirmed by computed tomography or magnetic resonance imaging. In patients with a positive FDG-PET finding, the hTg level was 146.7+/-90.1 ng/ml (23-277 ng/ml, median 144.5 ng/ml). In contrast, in patients with a negative finding the hTg level was only 9.0+/-7.6 ng/ml (range 1.5-17 ng/ml, median 8.1 ng/ml), P=0.01., Conclusion: These preliminary results show that in patients with differentiated thyroid carcinoma, elevated hTg levels, and otherwise negative "conventional" diagnostic procedures, FDG-PET is helpful in detecting metastatic lesions.

Unlabelled: Iodine-123-alpha-methyl tyrosine (IMT) allows the investigation of amino acid transport rate in brain neoplasms. It was the aim of this study to evaluate the potential of IMT-SPECT to diagnose the recurrence of gliomas after primary therapy., Methods: Using a triple-headed SPECT camera, the cerebral uptake of IMT was determined in 27 patients 22 mo, on average, after surgical removal of a primary brain tumor. Eighteen patients had suffered from high-grade gliomas, and nine had suffered from low-grade tumors. Four patients were examined before and after surgical revision of a presumed tumor recurrence. A total of 31 studies were evaluated. The final diagnosis was based on prospective clinicopathological follow-up. Recurrence was diagnosed in 23 cases, with marked clinical deterioration occurring 3.1 mo, on average, after SPECT, and was confirmed by histopathology in 14 instances. Eight cases were free of recurrence, as evidenced by inconspicuous clinical follow-up, ranging from 6 mo to 17 mo after SPECT in seven cases, and by clinical course and histopathology in the remaining subject., Results: Patients with recurrence had significantly higher ratios of IMT uptake in the tumor area to that in a background region than did patients without recurrence (2.27 +/- 0.59 compared to 1.47 +/- 0.29; p < 0.002). The best cutoff level of the IMT uptake ratio in the differentiation between recurrence and benign posttherapeutic lesion was 1.8. Using this study-specific discrimination threshold, the sensitivity and specificity of IMT-SPECT for detecting glioma recurrence were 18 of 23 (78%) and 8 of 8 (100%), respectively. The area under the binormal receiver operating characteristic curve, fitted to the data, was 0.90 +/- 0.06., Conclusion: Iodine-123-alpha-methyl tyrosine-SPECT is a promising new tool in the follow-up of patients with gliomas after primary therapy.

Amino acid uptake is higher in high-grade than in low-grade gliomas; this is the rationale for using radioactively labelled amino acids for the non-invasive grading of brain neoplasms. We present a 14-year-old boy with a low-grade desmoplastic infantile ganglioglioma (DIG) that exhibited marked contrast enhancement on magnetic resonance imaging (MRI), but no signs of infiltration and only minimal surrounding edema. In this benign neoplasm the relative uptake of the radioactively labelled amino acid I-123-alpha-methyl tyrosine (IMT), determined using single-photon emission computed tomography (SPECT), was 3.24; it was considerably higher than that of eleven other pretherapeutic low-grade gliomas where it ranged from 1.06 to 1.94 and also markedly above that average value of 2.37 found in 20 high-grade gliomas. This case report illustrates that results from emission tomography with radioactively labelled amino acids must be interpreted with caution, particularly when rare tumor entities are considered in view of uncommon clinical or radiological findings.

Unlabelled: Amino acid transport rate in gliomas can be assessed using SPECT and the amino acid L-123I-alpha-methyl tyrosine (IMT). This study attempted to correlate the uptake of IMT by gliomas with the proliferative activity and cellular density of these neoplasms., Methods: The study used 27 patients with gliomas, including 18 patients with high-grade tumors and nine patients with low-grade neoplasms. Amino acid transport rate was determined using IMT and the triple-headed SPECT camera. Proliferative activity was immunohistochemically assessed as the relative number of cells expressing the Ki-67 nuclear antigen; cellular density was evaluated using light microscopy., Results: Relative IMT uptake correlated significantly with the proliferative fraction of tumor cells (r = 0.6, p < 0.001). There was no significant correlation between IMT uptake and cellular density (r = 0.25, p > 0.05)., Conclusion: The uptake of the SPECT radiopharmaceutical IMT is related to proliferative activity rather than to the cellular density of gliomas.

Outflow obstruction constitutes a major problem in hypertrophic obstructive cardiomyopathy (HOCM) and may be treated by transcoronary injection of ethanol into septal arteries (transcoronary ablation of septum hypertrophy, TASH). We report on myocardial perfusion and glucose metabolism in a 50 year old man in whom TASH led to a reduction of septal thickness (9 vs. 26 mm), a sustained elimination of the outflow tract obstruction (resting gradient 0 vs. 60 mmHg; post-ES-gradient 10 vs. 145 mmHg) and a substantial clinical improvement (NYHA stage II vs. II-III) without impairment of global ventricular function (left ventricular ejection fraction 0.62 vs. 0.64). After TASH, perfusion and glucose metabolism were assessed by positron emission tomography (PET) using F-18-fluorodeoxyglucose (F-18-FDG) and Tc-99m-MIBI single photon emission tomography (SPECT). TASH results in matched reduction of perfusion and glucose consumption in a circumscribed area fed by the septal branch used for ethanol injection. No remote effects were observed. TASH leads to a sharply delineated septal reduction of perfusion and metabolism with consecutive reduction of septal thickness, a sustained elimination of the outflow tract obstruction, and a substantial clinical improvement without impairment of global ventricular function.

Radioiodine scans are highly specific for detecting metastases of well-differentiated thyroid carcinomas. However, false-positive 131I whole-body scans may occur as illustrated in the following case report. In a 53-yr-old patient, abnormal 131I uptake was found in the right frontal skull 4 wk after total thyroidectomy and radioiodine therapy for papillary thyroid cancer. Bone scans and planar x-rays of the skull were unremarkable and the serum thyroglobulin level was within normal limits. X-ray CT revealed a small nodule in the right frontal sinus corresponding to the pathological focus of 131I uptake. Surgical removal and histopathological examination of this lesion yielded a mucocele, a slow-growing lesion of the paranasal sinuses accumulating mucous material. The postoperative 131I scan was unremarkable. The possibility of a false-positive finding on radioiodine scans should be considered, particularly when the serum thyroglobulin level is not elevated.

Purpose: To analyze the factors that influence survival of patients with differentiated thyroid carcinoma treated by surgical thyroidectomy, radioactive iodine, and early surgical reintervention with compartment-oriented lymphadenectomy in the case of locoregional recurrence., Methods: The survival of 500 patients with differentiated thyroid carcinoma was analyzed retrospectively with regard to mortality and survival rate (Kaplan-Meier). A total of 301 patients had papillary and 199 follicular thyroid carcinoma. The mean age of the 380 women and 120 men was 46.8 +/- 16.4 years at presentation. All patients were treated by surgical thyroidectomy, high-dose radioactive iodine, and early surgical reintervention with compartment-oriented lymphadenectomy in cases of locoregional recurrence, without routine adjuvant external radiotherapy of the neck. Patients were monitored up to 23 years, with a median follow-up time of 5.6 years., Results: Twenty-nine of 500 patients died, 19 of thyroid cancer. The corrected overall 5-year survival rate (Kaplan-Meier) was 0.92. Among patients with tumor stage pT1-3NO-1MO (low risk), none died of thyroid carcinoma (5-year survival rate, 0.97); in patients with tumor stage pT4 and/or M1 (high risk), the 5-year survival rate was 0.83. The cause of death was locoregional recurrence in eight and metastatic disease in 11. Using multivariate analysis, risk factors that significantly influence survival were local invasion (pT4), metastatic disease (M1), and age., Conclusion: In differentiated thyroid carcinoma, the use of total surgical thyroidectomy followed by high-dose radioiodine therapy and early surgical reintervention in case of locoregional recurrence yields high survival rates, even without adjuvant external radiotherapy of the neck.

Use of iodine-123-alpha-methyl tyrosine (123I-IMT) allows investigation of the amino acid transport rate in gliomas. It was the aim of this study to compare the value of measurement of glucose metabolism with that of measurement of 123I-IMT uptake for the non-invasive grading of brain tumours. The study population comprised 23 patients with histopathologically proven primary brain tumours; 14 had high-grade gliomas, and nine low-grade brain neoplasms. Glucose metabolism was studied using an ECAT EXACT 47 positron emission tomography (PET) camera and fluorine-18 fluorodeoxyglucose (18F-FDG); 123I-IMT uptake was measured with the triple-headed single-photon emission tomography (SPET) camera, MULTISPECT 3. 18F-FDG and 123I-IMT uptake was quantified as ratios between the uptake by the tumour and contralateral regions of reference. Glucose metabolism and amino acid uptake of the brain tumours correlated significantly (r=0.71, P <0.001). Assuming discrimination thresholds between high-grade and low-grade tumours of 0.8 for 18F-FDG uptake and 1.8 for 123I-IMT uptake, the accuracy values of 18F-FDG PET and 123I-IMT SPET for differentiating between high-grade and low-grade tumours were 21/23 (91%) and 19/23 (83%), respectively. The difference in diagnostic performance was not significant on receiver operating characteristic analysis (P >0.4). It is concluded that there is no major difference between the PET investigation of glucose metabolism and the less expensive SPET measurement of amino acid uptake in terms of their accuracy in evaluating the malignancy grade of primary brain tumours. This encourages the performance of further studies to analyse the potential impact of 123I-IMT SPET on the therapeutic management of patients with brain tumours.

In the follow-up of metastatic neuroblastoma mIBG scintigraphy represents the very diagnostic method. A case report of a child with a metastatic recurrence of neuroblastoma is given. Despite clear scintigraphic visualisation serum parameters remained negative. The role of additional bone scintigraphy is inconclusive even retrospectively.

Aim: The diagnostic value of 123I-mIBG-scintigraphy, bone scintigraphy and catecholamine metabolites in the follow up of neuroblastoma stage IV will be evaluated., Methods: Nineteen children suffering from neuroblastoma were analysed retrospectively by 123I-mIBG-scintigraphy, bone scintigraphy and measurement of homovanillic acid, vanillic acid, neuronspecific enclose, lactate dehydrogenase, and ferritine. Follow up was 7-132 (median 36) months., Results and Conclusion: The significance of the methods was dependent on the time of diagnostic use. In principal, 123I-mIBG-scintigraphy has the highest diagnostic impact. For initial staging and diagnosis of recurrence a combination of all three methods can be used. On the contrary, follow up during chemotherapy is best documented by 123I-mIBG-scintigraphy, whereas bone scintigraphy is of limited and measurement of catecholamine metabolites of less diagnostic value.

Using single-photon emission tomography (SPET), the radiopharmaceutical l-3-iodine-123-alpha-methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating high-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours.

A 53-year-old woman with chronic renal failure had secondary hyperparathyroidism relapsing after undergoing a second parathyroidectomy and excision of an autologous parathyroid graft that had been implanted after her first parathyroidectomy. Double-phase scintigraphy with Tc-99m MIBI disclosed pathologic MIBI uptake in the right anterior thorax where the parathyroid transplant had been placed. Histopathologic examination of three nodules excised from this region yielded hyperplastic parathyroid tissue. This case report further illustrates the value of double-phase Tc-99m MIBI scintigraphy in atypical cases of hyperparathyroidism.

Purpose: Results of survival rates in differentiated thyroid carcinoma and comparison with a review of literature are given., Patients and Methods: Four hundred and sixty-four patients with differentiated cancer of the thyroid (354 female, 110 male, range: 6 to 84 years, median: 46.8 years; 275 patients with papillary and 190 with follicular cancer) were analyzed retrospectively. All patients were treated with ablative doses of radioiodine after thyroidectomy including compartment oriented lymphadenectomy in 27 patients. All patients passed an individual systematic follow-up according to risk: "low risk" pT < or = 3NxM0 vs. "high risk" pT4 and/or M1. Early postoperative radiation was not included even in patients with local invasion (pT4)., Results: The corrected 5- and 10-year survival rates for papillary cancer are 0.91 and 0.91, for follicular cancer 0.94 and 0.78 respectively [correction of 0.94 bzw. 0.78] (p = 0.55), age ( < or = 40 years 0.96 and 0.96, > 40 years 0.90 and 0.80; p = 0.008), gender (female 0.93 and 0.92, male 0.90 and 0.70; p = 0.06) and invasion/distant metastases (pT4 and/or M1 0.83 and 0.71, other 0.97 and 0.97; p = 0.0001)., Conclusion: A systematic follow-up with an individually adapted standardized scheme is associated with high survival rates in patients with differentiated cancer of the thyroid. Early diagnosis of recurrences, locoregional lymph node and distant metastases with early surgical treatment including compartment oriented lymphadenectomy and radioiodine therapy yield high survival even without external radiation.

Thallium-201 reinjection improves detection of hibernating myocardium in about 30%-50% of persisting defects. The main goal of cardiac revascularization techniques is amelioration of clinical symptoms such as angina and dyspnoea; however, improvement in regional and global pump function is an additional and important target. The aim of this study was to investigate whether fill-in in the reinjection study is correlated with improved contractile function after treatment (percutaneous transluminal coronary angioplasty/aortocoronary bypass surgery). We studied 32 patients with coronary heart disease and impaired regional wall motion (RWM). RWM and ejection fraction (EF) were assessed by analysing ventriculographic images using the centreline method (values in standard deviations from mean values found in a healthy control group). Three 201Tl single-photon emission tomographic studies (stress, redistribution and reinjection) were performed prior to revascularization and analysed using a bull s-eye scheme. Patients were divided into two groups (group FI-=no fill-in, n=16; group FI+=fill-in, n=16). Fifty-six percent of all patients showed persisting defects, and 56% of these defects showed fill-in after reinjection. Fill-in in our patient group was independent of the size of the persisting defects. After revascularization RWM increased significantly in group FI+ (from -1.9 to 0.0 SD, P<0.001) whereas group FI- showed no significant change (from -1.6 to -1.8 SD). EF increased from -4.3 preoperatively to -2.1 SD postoperatively in group FI+ and did not change significantly in group FI- (-2.5 to -3.2 SD). The predictive value of reinjection for improvement of RWM was 88%. It is concluded that fill-in in the 201Tl reinjection image can predict recovery of RWM and EF after revascularization and should be used in all patients with impaired RWM and persisting defects independent of their extent.

464 patients with differentiated thyroid carcinoma were scored and treated using a risk-oriented management scheme employing early surgical re-intervention including compartment-oriented lymph-node dissection in cases of lymph-node metastases or local recurrences without routine external radiotherapy. A multivariate analysis showed that there was no effect of lymph-node metastases on survival. The difference in survival between patients with (24%) and without (76%) lymph-node metastases (univariate analysis) were due to the coincidence of higher tumor stage (T4) and higher incidence of peripheral metastases (M1). Thus, provided surgery is efficient, N1 is not a risk factor influencing survival.