Constraints on Elastic Neutrino Nucleus Scattering in the Fully Coherent Regime from the CONUS Experiment.

We report the best limit on coherent elastic scattering of electron antineutrinos emitted from a nuclear reactor off germanium nuclei. The measurement was performed with the CONUS detectors positioned at 17.1 m from the 3.9 GW_{th} reactor core of the nuclear power plant in Brokdorf, Germany. The antineutrino energies of less than 10 MeV assure interactions in the fully coherent regime. The analyzed dataset includes 248.7 kg d with the reactor turned on and background data of 58.8 kg d with the reactor off. With a quenching parameter of k=0.18 for germanium, we determined an upper limit on the number of neutrino events of 85 in the region of interest at 90% confidence level. This new CONUS dataset disfavors quenching parameters above k=0.27, under the assumption of standard-model-like coherent scattering of the reactor antineutrinos.

The broken circle method: a novel technique that enhances detection of Hill-Sachs lesions on internal rotation shoulder radiographs.

AIM: To describe and test a new method that increases the conspicuity of a Hill-Sachs lesion on internal rotation (IR) radiographs. MATERIALS AND METHODS: This study had institutional review board approval. A retrospective search for patients with a prior shoulder dislocation and a Hill-Sachs lesion documented on magnetic resonance imaging (MRI) was performed over a 10-year period identifying 256 test patients. In Part 1, the IR radiographs from test cases were randomised with controls, and three readers scored them independently for the defect. The readers were then taught the Broken Circle (BC) method and re-scored the radiographs. In Part 2, 15 cases of Hill-Sachs lesions that were missed by all readers in Part 1 were randomised with controls, and were shown to 25 radiology residents before (pre-test) and after (post-test) learning the BC method. A paired t-test was used to compare the differences in sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: In Part 1, the sensitivity increased 19.7% (54.1%-73.8%; p<0.05) and NPV increased 10.8% (62.5%-73.3%; p<0.01). In Part 2, post-test sensitivity for residents increased 16.3% (55.2%-71.5%; p<0.0001), accuracy increased 13.4% (64%-77.4%; p<0.0001), and NPV increased 13.3% (40.8%-54.1%; p<0.0001) independent of the level of training. The change in accuracy was also statistically significant for every individual class. CONCLUSION: The BC method was an effective technique that facilitated detection of a Hill-Sachs lesion at all levels of training, and was useful as a teaching tool.

Detection and localisation of hip fractures on anteroposterior radiographs with artificial intelligence: proof of concept.

AIM: To investigate the feasibility of applying a deep convolutional neural network (CNN) for detection/localisation of acute proximal femoral fractures (APFFs) on hip radiographs. MATERIALS AND METHODS: This study had institutional review board approval. Radiographs of 307 patients with APFFs and 310 normal patients were identified. A split ratio of 3/1/1 was used to create training, validation, and test datasets. To test the validity of the proposed model, a 20-fold cross-validation was performed. The anonymised images from the test cohort were shown to two groups of radiologists: musculoskeletal radiologists and diagnostic radiology residents. Each reader was asked to assess if there was a fracture and localise it if one was detected. The area under the receiver operator characteristics curve (AUC), sensitivity, and specificity were calculated for the CNN and readers. RESULTS: The mean AUC was 0.9944 with a standard deviation of 0.0036. Mean sensitivity and specificity for fracture detection was 97.1% (81.5/84) and 96.7% (118/122), respectively. There was good concordance with saliency maps for lesion identification, but sensitivity was lower for characterising location (subcapital/transcervical, 84.1%; basicervical/intertrochanteric, 77%; subtrochanteric, 20%). Musculoskeletal radiologists showed a sensitivity and specificity for fracture detection of 100% and 100% respectively, while residents showed 100% and 96.8%, respectively. For fracture localisation, the performance decreased slightly for human readers. CONCLUSION: The proposed CNN algorithm showed high accuracy for detection of APFFs, but the performance was lower for fracture localisation. Overall performance of the CNN was lower than that of radiologists, especially in localizing fracture location.

TIRADS for sonographic assessment of hypofunctioning and indifferent thyroid nodules.

AIM: To test the feasibility of the Thyroid Imaging Reporting And Data System (TIRADS) according to Horvath and Kwak for the assessment of thyroid nodules. PATIENTS, METHOD: Retrospective analysis of patients with thyroid nodules applying the following inclusion criteria: B-mode-ultrasound, surgery and histological results. Thyroid nodules were classified as TIRADS 2, 3, 4A, 4B, 4C, 5 and 6. RESULTS: A total of 172 patients were included (133 women, 48 ± 13 years, 39 men, 49 ± 11 years) with 222 thyroid nodules (24.9 ± 11.5 mm). Final histological diagnosis revealed 203 benign nodules (91%) and 19 malignant nodules (9%; 18 papillary thyroid carcinoma, PTC, and one medullary thyroid carcinoma, MTC). One hundred and sixty thyroid nodules were hypofunctioning in 99mTc-pertechnetate-scintigraphy, 14 nodules were hyperfunctioning and 46 nodules were classified as indifferent. In two cases with small carcinoma < 1 cm 99mTc-pertechnetate-scintigraphy was not performed. According to Horvath, the prevalence of malignancy was 6.7% in TIRADS 2, 0% in 3, 1.9% in 4A, 33% in 4B, 12.5% in 5 and 100% in 6; 73 nodules (39%) were not clearly classifiable, including 3 carcinoma (4.1%). According to Kwak, the prevalence of malignancy was 6.9% in TIRADS 2, 0% in 3, 2% in 4A, 4.1% in 4B, 23.1% in 4C, and 100% in 5 and 6, respectively. Notably, in the subgroup of hot nodules, 11 (79%) were graded as TIRADS 4A or higher, and thus advisable for fine-needle aspiration biopsy in both TIRADS. CONCLUSION: The TIRADS described by Horvath is not practicable due to numerous unclassifiable nodules. The revised TIRADS published by Kwak is feasible and suitable to assess the prevalence of malignancy, but it cannot replace scintigraphic imaging. Fine-needle-biopsy is not necessary in nodules categorized as (K)TIRADS 3, 4A and 5.

[99mTc-MIBI scintigraphy of hypofunctional thyroid nodules. Comparison of planar and SPECT imaging]. / 99mTc-MIBI-Szintigraphie hypofunktioneller Schilddrüsenknoten. Vergleich von planarer und tomographischer Technik.

UNLABELLED: 99mTc-MIBI-scintigraphy allows to assess the dignity of hypofunctional thyroid nodules. A concordant pattern in MIBI- and pertechnetate-scintigraphy excludes malignancy with high accuracy. For increased MIBI-uptake histological evaluation is advised. The assessment of MIBI-isointense nodules is discussed controversially. Objective of our study was to analyse the prevalence of malignancy for isointense nodules and the diagnostic accuracy of image acquisition in SPECT-technique. PATIENTS, METHODS: MIBI-scintigraphies were analysed retrospectively. Imaging was performed 60 min after intravenous injection of 510 MBq 99mTc-MIBI. Thyroid nodules were assessed as hypo-, iso- or hyperintense compared to the paranodular tissue. RESULTS: 83 of 225 patients underwent thyroid surgery (age 48.6 ± 12.6 years, 72% women). In 12 (14.5%) cases a papillary carcinoma was diagnosed. In planar imaging 12, 34 and 37, in tomographical imaging 16, 21 and 46 nodules, respectively, were classified as hypo-, iso- oder hyperintense. Among hypo-, iso- and hyperintense nodules in planar imaging 1, 5 and 6 carcinomas were found, resp. In tomographical imaging no, 4 and 8 carcinomas were found, respectively. Classification of iso- and hyperintense nodules as "suspicious for malignancy" showed for planar imaging a sensitivity, specificity, NPV and PPV of 91.7, 15.5, 91.7 and 15.6%, for tomographical imaging of 100, 22.5, 100 and 17.9%, respectively. CONCLUSION: Hypofunctional thyroid nodules with iso- and hyperintense MIBI-Uptake have a comparable prevalence of malignancy. Image acquisition in SPECT-technique results in improved diagnostic sensitivity and negative predictive value.

Risk of malignancy in follicular thyroid neoplasm: predictive value of thyrotropin.

UNLABELLED: The cytological diagnosis of follicular neoplasm is a common finding in fine needle aspiration cytology (FNAC) of thyroid nodules and includes benign disease as well as differentiated thyroid cancer. The aim of the study is to determine if thyrotropin is a predictive factor for a malignant nature of follicular neoplasm. PATIENTS, METHODS: The records of 119 patients with follicular neoplasm on FNAC, who underwent surgery for final diagnosis, were reviewed retrospectively. The predictive value of serum parameters including thyrotropin, thyroglobulin, and anti-thyroid antibodies, ultrasonographic criteria and clinical variables was evaluated by univariate analysis and logistic regression analysis. RESULTS, DISCUSSION: Patients with malignant nodules showed a higher thyrotropin concentration compared to patients with benign nodules (median 1.6 mU/l, interquartile range 1.4-3.0 mU/l vs. median 1.2 mU/l, interquartile range 0.8-1.6 mU/l, p < 0.01). ROC-analysis of thyrotropin revealed an optimal cut off value to differentiate benign and malignant nodules of 1.34 mU/l. The incidence of malignancy was 30.3% for a thyrotropin concentration higher than 1.34 mU/l compared to 6.4% for a thyrotropin concentration lower than or equal to 1.34 mU/l. On univariate analysis thyroglobulin higher than 300 ng/ml, positive anti-thyroid antibodies, hypoechogenicity, and ill-defined margins, respectively, were also significantly associated with malignancy. On logistic regression analysis higher thyrotropin concentrations, ill-defined margins, and thyroglobulin higher than 300 ng/ml, respectively, were independent predictive factors for malignancy (OR 20.0, 10.7, and 22.7, respectively). CONCLUSION: Higher thyrotropin concentrations are predictive for a malignant nature of follicular neoplasm.

[Spectrometric assessment of thyroid depth within the radioiodine test]. / Spektrometrisches Verfahren zur Tiefenbestimmung der Schilddrüse im Rahmen des Radioiodtests.

UNLABELLED: Aim of this study is the validation of a simple method for evaluating the depth of the target volume within the radioiodine test by analyzing the emitted iodine-131 energy spectrum. PATIENTS, METHODS: In a total of 250 patients (102 with a solitary autonomous nodule, 66 with multifocal autonomy, 29 with disseminated autonomy, 46 with Graves' disease, 6 for reducing goiter volume and 1 with only partly resectable papillary thyroid carcinoma), simultaneous uptake measurements in the Compton scatter (210 +/- 110 keV) and photopeak (364-45/+55 keV) windows were performed over one minute 24 hours after application of the 3 MBq test dose, with subsequent calculation of the respective count ratios. Measurements with a water-filled plastic neck phantom were carried out to perceive the relationship between these quotients and the average source depth and to get a calibration curve for calculating the depth of the target volume in the 250 patients for comparison with the sonographic reference data. Another calibration curve was obtained by evaluating the results of 125 randomly selected patient measurements to calculate the source depth in the other half of the group. RESULTS: The phantom measurements revealed a highly significant correlation (r = 0,99) between the count ratios and the source depth. Using these calibration data, a good relationship (r = 0,81, average deviation 6 mm corresponding to 22%) between the spectrometric and the sonographic depths was obtained. When using the calibration curve resulting from the 125 patient measurements, the overage deviation in the other half of the group was only 3 mm (12%). There was no difference between the disease groups. CONCLUSION: The described method allows on easy to use depth correction of the uptake measurements providing good results.

Impact of the axillary nodal status on sentinel node mapping in breast cancer and its relevance for technical proceeding.

OBJECTIVE: The aim of this study is to analyze whether the axillary status influences the lymphatic mapping procedure in malignant breast disease and whether clinically relevant consequences for the technique of Sentinel Node (SN) biopsy may be drawn from this information. MATERIALS AND METHODS: SN biopsy was performed in 150 consecutive patients using a combination of the radioguided and the blue-dye technique. Axillary status was compared with the number of detected nodes. In cases of numerous nodes with tracer uptake, the radioactivity of each radiolabeled node was measured separately in a dose calibrator. We analyzed whether an increased tracer uptake could possibly indicate a 'true' or 'dominant' SN. Blue dye uptake was registered and compared with radioactivity. The findings were related to the histologic results. RESULTS: In patients with a positive axillary status, significantly more radiolabeled nodes were detected than in node negative patients (median 3 vs. 2; p < 0.001). In 54/86 patients with numerous SNs a 'dominant' node with at least twice the radioactivity than other marked nodes could be identified (62.8%). From 26 cases with axillary involvement, 20 patients (76.9%) were identified by the 'dominant' and the remaining six women (23.1%) by others than the seemingly leading SN. CONCLUSION: Axillary lymph node involvement influences the drainage pattern in breast cancer. Patients with numerous SNs have an increased risk of axillary involvement. A high tracer uptake does not permit the identification of a 'true' SN. A lack of surgical accuracy may lead to pitfalls if the axilla is not screened carefully for all radioactive nodes.

Results of a standardized protocol for sentinel node imaging in breast cancer with Tc-99m labeled nanocolloidal albumin.

AIM: Of this study was to evaluate the results of a standardized protocol for sentinel node (SN) detection in breast cancer using Tc-99m labeled nanocolloidal albumin and a combined intra- and subdermal injection technique. METHODS: One hundred and fifty-five women with proven breast cancer (disease stages Tis-T2) were included. Four injections of 10 to 15 MBq of Tc-99m nanocolloid in 0.1 ml physiologic saline were administered intra- and subdermally at the 3, 6, 9 and 12 o'clock positions in the skin overlying the tumor. Planar scintigraphic images in lateral and anterior projections were obtained once between 2.5 and 18 hours after tracer administration. Guided by a gamma probe, all radioactive lymph nodes in the axilla were resected, then complete dissection followed. RESULTS: In 151 of the 155 women (97.4%), nodal tracer uptake (range 1-7 foci, average 2.2) was scintigraphically revealed. In one of these cases, drainage was only to the internal mammary lymphatic chain. Three of the 4 women with detection failure presented with histologically proven tumor infiltration of the lymphatics and axillary involvement. In 49 of the patients with visualized axillary lymph nodes (32.7%), at least one SN was metastatic. In 21 cases, this SN was the only positive node. The remaining 101 patients with negative SN included 4 cases with axillary involvement. The sensitivity of the SN with respect to the histological status of the entire axilla was thus 92.5%, the negative predictive value was 96.0%. The overall accuracy of the method was 97.3%. There was a significant difference between the number of totally detected radioactive nodes in the groups with and without nodal metastases (3.49 vs. 2.57, p < 0.01). CONCLUSION: The described protocol represents an easy reproducible and reliable method for SN detection in breast cancer that additionally allows flexible timing of surgery. Further, we found evidence that the number of scintigraphically visualized nodes also reflects the histological status of the axilla.

Development of the parafollicular cells in recurrent goiter.

OBJECTIVE: To provide more data for the discussion on whether thyroid hormones, iodide and other factors controlling the thyroid also influence the parafollicular (PF) cells, as the answer is of great importance for optimization of the medical treatment of medullary thyroid carcinoma (MTC) after surgery. DESIGN: We compared the density of the PF cells in patients who underwent surgery for the second time due to recurrent goiter with that in normal-sized thyroid glands after the first operation. METHODS: In 20 patients with only one operation, all specimens were taken from morphologically and functionally normal lobular thyroid parenchyma. The second group consisted of 30 patients who had already undergone a nearly total resection of at least one thyroid lobe several years before. Then another surgery of the same side was performed due to recurrent goiter. Immunohistochemical staining of the PF cells was performed using primary antibodies to calcitonin and chromogranin. RESULTS: An average of 78 PF cells (median 12.5) was found in the sections with the highest density of the first group. The average number of PF cells in the second group was just 5 (median 0). The Wilcoxon test revealed a highly significant difference in the total PF cell content between the groups (P < 0.001). CONCLUSIONS: Our study suggests that the stimulating factors that lead to growth of the thyroid parenchyma do not influence the PF cells. Hence a non-suppressive thyroid hormone replacement seems to be sufficient after resection of an MTC.

Lymphoscintigraphic sentinel node imaging and gamma probe detection in breast cancer with Tc-99m nanocolloidal albumin: results of an optimized protocol.

PURPOSE: The purpose of this study was to aid in the standardization of lymphoscintigraphy for detecting the sentinel node (SN) in breast cancer using Tc-99m-labeled nanocolloidal albumin. MATERIALS AND METHODS: One hundred twenty-three women with proved breast cancer were enrolled. Four injections of 10 to 15 MBq (0.27 to 0.41 mCi) Tc-99m nanocolloid in 0.1 ml physiologic saline were administered intra- and subdermally at the margin of the skin overlying the tumor. Planar scintigraphic images in the lateral and anterior projections were obtained 2.5 to 18 hours after tracer administration. With a gamma probe used as a guide, all radioactive lymph nodes in the axilla were resected. Complete dissection then followed. RESULTS: In 116 of the 123 (94%) women, axillary nodal tracer uptake was revealed. Six of the 7 women in whom detection failure occurred had histologically proved tumor infiltration of the lymphatics and axillary involvement. In 36 (31%) of the patients with visualized lymph nodes, the SN was metastatic. The remaining 80 patients with negative SN included three cases with axillary involvement. The sensitivity of the SN with respect to the histologic status of the entire axilla thus was 92.3%, and the negative predictive value was 96.3%. The overall accuracy of the method was 97.4%. The number of hot nodes in women with and without axillary involvement was significantly different. CONCLUSIONS: The described protocol represents an easily reproduced and reliable method for SN detection in breast cancer. Furthermore, the number of visualized axillary nodes reflects the histologic status of the axilla.

[Impact of serum thyroglobulin concentration in the diagnosis of benign and malignant thyroid diseases]. / Stellenwert des Serum-Thyreoglobulinspiegels bei der Diagnostik benigner und maligner Schilddrüsenerkrankungen.

UNLABELLED: AIM of this study is to evaluate new and controversially discussed indications for determining the thyroglobulin (Tg) level in different thyroid diseases to support routine diagnostics. METHODS: The following groups were included: 250 healthy subjects without goiter, 50 persons with diffuse goiter, 161 patients with multinodular goiter devoid of functional disorder (108 of them underwent surgery, in 17 cases carcinomas were detected), 60 hyperthyroid patients with autonomously functioning nodular goiter, 150 patients with Hashimoto's thyroiditis and 30 hyperthyroid patients with Graves' disease. RESULTS: The upper limit of the normal range of the Tg level was calculated as 30 ng Tg/ml. The evaluation of the collective with diffuse goiter showed that the figure of the Tg level can be expected in a similar magnitude as the thyroid volume in milliliters. Nodular tissue led to far higher Tg values then presumed when considering the respective thyroid volume, with a rather high variance. A formula for a rough prediction of the Tg levels in nodular goiters is described. In ten out of 17 cases with thyroid carcinoma, the Tg was lower than estimated with thyroid and nodular volumes, but two patients showed a Tg exceeding 1000 ng/ml. The collective with functional autonomy had a significantly higher average Tg level than a matched euthyroid group being under suppressive levothyroxine substitution. However, due to the high variance of the Tg values, the autonomy could not consistently be predicted with the Tg level in individual cases. The patients with Hashimoto's thyroiditis showed slightly decreased Tg levels. In Graves' disease, a significantly higher average Tg level was observed compared with a matched group with diffuse goiter, but 47% of all Tg values were still in the normal range (< 30 ng/ml). CONCLUSION: Elevated Tg levels indicate a high probability of thyroid diseases, such as malignancy, autonomy or Graves' disease. However, as low Tg concentrations cannot exclude the respective disorder, a routine Tg determination seems not to be justified in benign thyroid diseases.

Unraveling photoexcited conformational changes of bacteriorhodopsin by time resolved electron paramagnetic resonance spectroscopy.

By means of time-resolved electron paramagnetic resonance (EPR) spectroscopy, the photoexcited structural changes of site-directed spin-labeled bacteriorhodopsin are studied. A complete set of cysteine mutants of the C-D loop, positions 100-107, and of the E-F loop, including the first alpha-helical turns of helices E and F, positions 154-171, was modified with a methanethiosulfonate spin label. The EPR spectral changes occurring during the photocycle are consistent with a small movement of helix C and an outward tilt of helix F. These helix movements are accompanied by a rearrangement of the E-F loop and of the C-terminal turn of helix E. The kinetic analysis of the transient EPR data and the absorbance changes in the visible spectrum reveals that the conformational change occurs during the lifetime of the M intermediate. Prominent rearrangements of nitroxide side chains in the vicinity of D96 may indicate the preparation of the reprotonation of the Schiff base. All structural changes reverse with the recovery of the bacteriorhodopsin initial state.

[Effect of iodine and thyroid hormones in the induction and therapy of Hashimoto's thyroiditis]. / Effekte von Iodid und Schilddrüsenhormonen bei der Induktion und Therapie einer Thyreoiditis Hashimoto.

AIM: The effect of an iodine prophylaxis on the induction of Hashimoto's thyroiditis as well as the influence of various therapeutic approaches on the course of antithyroglobulin (TgAb) and antiperoxidase (TPOAb) antibodies in manifest diseases are evaluated. METHOD: A collective of 375 euthyroid subjects without relevant goiter received daily doses of 200 micrograms iodide, weekly doses of 1.53 milligrams iodide, or no medication. A second group of 377 patients suffering from Hashimoto's thyroiditis was treated with a non-suppressive hormone medication, a suppressive hormone administration, a combination of a non-suppressive hormone therapy with low dose iodide (50-150 micrograms/day), mere iodide in doses of 200 micrograms/day, or received no therapy. The mean observation period in these two groups was 860 and 848 days, respectively. RESULTS: There was no significant increase of the antibody levels in the subgroup with 200 micrograms iodide/day and in the non-treated subjects of the first collective. However, the group that received 1.53 milligrams iodide/week presented a distinct increase of the TgAb as well as the TPOAb, and the incidence of Hashimoto's thyroiditis was 4-fold higher than in the two other subgroups. The patients of the second collective revealed a significant decrease of the TgAb in the subgroups treated with up to 200 micrograms iodide/day, while the reduction of the TPOAb depended on the thyrotropin level and was most significant in the suppressed group (p < 0.0001). CONCLUSION: To lower the incidence of autoimmune thyroid diseases in predisposed subjects, a daily iodine supplementation seems to be superior to high-dose weekly administrations. A hormone therapy combined with a daily, low-dose iodine medication is able to reduce the TgAb and the TPOAb levels even in patients with Hashimoto's thyroiditis.

[Hyperthyroidism in a premature infant due to transplacental passage of maternal thyrotropin receptor antibodies]. / Frühgeborenenhyperthyreose durch diaplazentar übertragene TSH-Rezeptor-Antikörper der Mutter.

The duration of the stimulating effect of transplacental transferred thyrotropin-receptor-antibodies (TRAb) is discussed by the example of a 23 years old woman suffering from Graves' disease with a severe hyperthyroidism. She became pregnant six weeks after the diagnosis was obtained and then discontinued her antithyroid medication on her own responsibility. On a check-up in the 20th week of pregnancy, a hyperthyroidism was once more found, leading to a therapy with propylthiouracil, which however, was again interrupted by the patient a few weeks later. In the 32nd week, she gave birth to a male child that already presented with distinct signs of thyrotoxicosis and developed a continuous deterioration of the condition, including a tachycardia with up to 190 beats per minute, fever, tremor and a respiratory disorder. Assay of the newborn serum revealed a severe hyperthyroidism. The TRAb level was 180 U/l (normal range < 15). A therapy with propranolol and prednisolone was initiated, leading to a significant improvement of the general condition. Nevertheless, after 12 days, there was still no notable decrease of the hormone levels. Therefore an antithyroid medication was started, which caused normal thyroid hormone levels within 9 days. However, after the therapy was stopped, a hyperthyroidism was again observed within one week, requiring another, low-dose antithyroid medication, which was administered for 26 days. After this period, the TRAb level was down to 25 U/l and no more hyperthyroidism was found. The biological half-life of the TRAb was 20 days in our case.

Miniaturized FRET assays and microfluidics: key components for ultra-high-throughput screening.

Assay miniaturization applicable across a wide range of target classes, along with automation and process integration, are well-recognized goals for ultra-high-throughput screening on an industrial scale. This report summarizes the implementation of fluorescence resonance energy transfer (FRET)-based biochemical and cell-based assays in 3456-well NanoWelltrade mark assay plates using key components of Aurora's ultra-high-throughput screening system.

Azide reduces the hydrophobic barrier of the bacteriorhodopsin proton channel.

The sensitivity of a nitroxide spin label to the polarity of its environment has been used to estimate the hydrophobic barrier of the proton channel of the transmembrane proton pump bacteriorhodopsin. By means of site-specific mutagenesis, single cysteine residues were introduced at 10 positions located at the protein surface, in the protein interior, and along the proton pathway. After reaction with a methanethiosulfonate spin label, the principle values of the hyperfine tensor A and the g-tensor were determined from electron paramagnetic resonance spectra measured at 170 K. The shape of the hydrophobic barrier of the proton channel is characterized in terms of a polarity index, DeltaA, determined from the variation of the hyperfine coupling constant Azz. The maximum of the hydrophobic barrier is found to be close to the retinal chromophore in the proton uptake pathway. The effect of the asymmetric distribution of charged and polar residues in the proton release and uptake pathways is clearly reflected in the behavior of the hydrophobic barrier. The presence of azide reduces the barrier height of both the cytoplasmic and extracellular channels. This finding supports the view of azide and other weakly acidic anions as catalysts for the formation of hydrogen-bonded networks in proton pathways of proteins.

Site-directed spin-labeling reveals the orientation of the amino acid side-chains in the E-F loop of bacteriorhodopsin.

Due to high temperature factors and the lack of considerable electron density, electron microscopy and X-ray experiments on the cytoplasmic E-F loop of bacteriorhodopsin result in a variety of structural models. As the experimental conditions regarding ionic strength, temperature and the presence of detergents may affect the structure of the E-F loop, we employ electron paramagnetic resonance and site-directed spin-labeling to study the structure of this loop under physiological conditions. The amino acid residues at positions 154 to 171 were replaced by cysteine residues and derivatized with a sulfhydryl-specific nitroxide spin label one by one. The conventional and power saturation electron paramagnetic spectroscopy provide the mobility of the nitroxide and its accessibility to dissolved molecular oxygen and membrane-impermeable chromium oxalate in the respective site. The results show that K159 and A168 are located at the water-lipid interface of helices E and F, respectively. The orientation of the amino acid side-chains in the helical regions from positions 154 to 159 and 166 to 171 were found to agree with published structural data for bacteriorhodopsin. In the residue sequence from positions 160 to 165 the EPR data yield evidence for a turned loop structure with the side-chains of M163 and S162 oriented towards the proton channel and the water phase, respectively.

[Individual calculation of the minimal effective levothyroxine dose in prolonged suppression tests]. / Individuelle Bestimmung der minimal erforderlichen Levothyroxindosis bei Langzeit-Suppressionstests.

AIM: A formula for calculating the minimum suppressive levothyroxine dose in prolonged suppression tests using body weight and TSH level is derived from a large number of cases. METHOD: In 1239 euthyroid patients (TSH > 0.30 mU/l) a suppression test with levothyroxine substitution for at least 6 weeks was performed. The hormone dose was primarily based on the initial TSH level using the empirical value TSH x 100, with a range between 50 and 150 micrograms per day. RESULTS: In 900 patients (73%), the TSH level was suppressed during the medication (TSH < 0.30 mU/l). Among them, we found 211 cases with an intermediate TSH suppression (TSH between 0.10 and 0.20 mU/l). Following the formula f = levothyroxine dose [microgram]/(body weight [kg] x initial TSH level [mU/l]) an average factor of 1.57 was calculated to obtain the suppressive dose in this group. As usually a complete TSH suppression (< 0.10 mU/l) is required, we recommend factor 2 for practical use. A consideration of the body weight revealed that 313 patients actually received a hormone dose equivalent to 2 x weight x TSH. In this group, a TSH suppression was found in 262 patients (84%), a factitial hyperthyreosis was not observed. When contemplating the three subgroups of this collective, who received daily doses of 50, 75 and 100 micrograms levothyroxine, respectively, we neither found a significant difference in the average body weight, nor in the value of the suppressed TSH. However, the correlation between the average initial TSH levels in these groups and the respective suppressive hormone doses clearly demonstrates their dependence on the thyroid regulation. CONCLUSION: The minimum suppressive levothyroxine dose does not only depend on the body weight, but also on the initial TSH level. It can be estimated using the formula 2 x body weight x initial TSH (range between 50 and 150 micrograms per day).

[Long-term follow-up and therapeutic control of a hepatic metastatic acinar cell carcinoma of the pancreas using FDG PET]. / Langzeitverlaufs- und Therapiekontrolle eines hepatisch metastasierenden Azinuszellkarzinoms des Pankreas mittels FDG-PET.

A 33 years old woman presented with cramp-like abdominal pain. Ultrasound examination revealed multiple lesions in the liver of hyper- and hypoechoic echogenicity which in accordance to subsequently performed computed tomography and dynamic hepatobiliary scintigraphy were considered to be a focal nodular hyperplasia (FNH). A severe increase of the serum lipase concentration, suspected to be an acute pancreatitis, was treated conservatively and led to a short improvement of symptoms. Some months later, a severe progression of the pain symptoms occurred, along with a measurable expansion of the abdominal circumference and palpable tumors of the liver. The dynamic hepatobiliary imaging and the static liver scan showed a decreased perfusion and function of the nodes as well as a reduced RES activity, respectively. A subsequently performed Positron Emission Tomography (PET) with F-18-Fluorodeoxyglucose (FDG) showed a massively increased glucose metabolism of the liver tumors. The histologic result of several biopsies of the tumors revealed metastases of an acinus cell carcinoma of the pancreas. Under systemic and local chemotherapy, a temporary remission could be obtained that was clearly detectable in a second FDG-PET. Nevertheless, during the further course of the disease, a progression occurred being detectable in an additional control PET-study by an increase in tumor size as well as in tumor glucose metabolism. The patient died in liver coma 15 months after the histologic diagnosis was obtained.