Dependency of prescribed CT dose on table height,patient size,and localizer acquisition for one clinical MDCT

PurposeThe purpose of this study was to quantify the effect that table height, patient size, and localizer acquisition order may have on AEC prescribed dose.Method and materialsThree phantoms were used for this study: the Mercury Phantom, acrylic sheets, and an anthropomorphic phantom. A lateral (LAT) and a posterior-anterior (PA) localizer was acquired for each phantom at different table heights on a MDCT scanner (GE Discovery CT750 HD). AEC scan acquisitions were prescribed for each combination of phantom, localizer orientation, and table height ±4 cm with the center position; the displayed CTDI_vol was recorded. Based on the institutional dose monitoring program, the relationship between change in CTDI_vol and change in table height were studied for LAT and AP localizers for clinical exams.ResultsFor all phantom scans based on the PA localizer, the percent change in ranged between −18% and 42% for table heights 4 cm below and above proper centering; while for the LAT localizer, the percent change in CTDI_vol from ideal were no greater than 12% different for ±4 cm differences in table height. Change in CTDI_vol and change in table height displayed a strong linear relationship for AP localizer exams (P = 0.002), and weak correlation for LAT localizer exams (P = 0.12).ConclusionsSince uncertainty in vertical patient positioning is inherently greater than lateral positioning, the LAT localizer should be utilized to precisely and reproducibly deliver the intended amount of radiation prescribed by CT protocols.     

CT dose reduction using Automatic Exposure Control and iterative reconstruction: A chest paediatric phantoms study

PurposeTo evaluate the impact of Automatic Exposure Control (AEC) on radiation dose and image quality in paediatric chest scans (MDCT), with or without iterative reconstruction (IR).MethodsThree anthropomorphic phantoms representing children aged one, five and 10-year-old were explored using AEC system (CARE Dose 4D) with five modulation strength options. For each phantom, six acquisitions were carried out: one with fixed mAs (without AEC) and five each with different modulation strength. Raw data were reconstructed with Filtered Back Projection (FBP) and with two distinct levels of IR using soft and strong kernels. Dose reduction and image quality indices (Noise, SNR, CNR) were measured in lung and soft tissues. Noise Power Spectrum (NPS) was evaluated with a Catphan 600 phantom.ResultsThe use of AEC produced a significant dose reduction (p < 0.01) for all anthropomorphic sizes employed. According to the modulation strength applied, dose delivered was reduced from 43% to 91%. This pattern led to significantly increased noise (p < 0.01) and reduced SNR and CNR (p < 0.01). However, IR was able to improve these indices. The use of AEC/IR preserved image quality indices with a lower dose delivered. Doses were reduced from 39% to 58% for the one-year-old phantom, from 46% to 63% for the five-year-old phantom, and from 58% to 74% for the 10-year-old phantom. In addition, AEC/IR changed the patterns of NPS curves in amplitude and in spatial frequency.ConclusionsIn chest paediatric MDCT, the use of AEC with IR allows one to obtain a significant dose reduction while maintaining constant image quality indices.     

Automatic exposure control at single- and dual-heartbeat CTCA on a 320-MDCT volume scanner: Effect of heart rate,exposure phase window setting,and reconstruction algorithm

PurposeTo investigate whether electrocardiogram (ECG)-gated single- and dual-heartbeat computed tomography coronary angiography (CTCA) with automatic exposure control (AEC) yields images with uniform image noise at reduced radiation doses.Materials and methodsUsing an anthropomorphic chest CT phantom we performed prospectively ECG-gated single- and dual-heartbeat CTCA on a second-generation 320-multidetector CT volume scanner. The exposure phase window was set at 75%, 70–80%, 40–80%, and 0–100% and the heart rate at 60 or 80 or corr80 bpm; images were reconstructed with filtered back projection (FBP) or iterative reconstruction (IR, adaptive iterative dose reduction 3D). We applied AEC and set the image noise level to 20 or 25 HU. For each technique we determined the image noise and the radiation dose to the phantom center.ResultsWith half-scan reconstruction at 60 bpm, a 70–80% phase window- and a 20-HU standard deviation (SD) setting, the imagenoise level and -variation along the z axis manifested similar curves with FBP and IR. With half-scan reconstruction, the radiation dose to the phantom center with 70–80% phase window was 18.89 and 12.34 mGy for FBP and 4.61 and 3.10 mGy for IR at an SD setting SD of 20 and 25 HU, respectively. At 80 bpm with two-segment reconstruction the dose was approximately twice that of 60 bpm at both SD settings. However, increasing radiation dose at corr80 bpm was suppressed to 1.39 times compared to 60 bpm.ConclusionAEC at ECG-gated single- and dual-heartbeat CTCA controls the image noise at different radiation dose.     

Automatic exposure control at MDCT based on the contrast-to-noise ratio: Theoretical background and phantom study

PurposeTo develop a new automatic exposure control (AEC) technique based on the contrast-to-noise ratio (CNR) and provide constant lesion detectability.MethodsLesion detectability is affected by factors such as image noise, lesion contrast, and lesion size. We performed ROC analysis to assess the relationship between the optimum CNR and the lesion diameter at various levels of lesion contrast. We then developed a CNR-based AEC algorithm based on lesion detectability. Using CNR- based AEC algorithm, we performed visual evaluation of low-contrast detectability by 5 radiologists on a low-contrast module of the Catphan phantom, a contrast-difference level of 1.0% (difference in the CT number = 10 HU), and objects 3.0–9.0 mm in diameter.ResultsOn step-and-shoot scans the mean detection fraction with CNR-based AEC remained almost constant from 88 to 99 % regardless of the lesion size. We observed the same trend on helical scans, the mean detection fraction with CNR-based AEC exhibited a high score from 91 to 100%. Although CNR-based AEC maintains higher CNR for smaller size or lower contrast lesion, radiation dose on 3 mm lesion resulted in about 13 times larger than that of 9 mm lesion size. CTDI_vol for the CNR-based AEC technique changed dramatically with the SD_Z from 7.5 to 100.0 mGy for step-and-shoot scans and from 9.1 to 121.5 mGy for helical scans.ConclusionsFrom the viewpoint of ROC analysis-based CNR for lesion detection, CNR-based AEC potentially provide image quality advantages for clinical implementation.     

Effects of various generations of iterative CT reconstruction algorithms on low-contrast detectability as a function of the effective abdominal diameter: A quantitative task-based phantom study

PurposeTo investigate how various generations of iterative reconstruction (IR) algorithms impact low-contrast detectability (LCD) in abdominal computed tomography (CT) for different patient effective diameters, using a quantitative task-based approach.MethodsInvestigations were performed using an anthropomorphic abdominal phantom with two optional additional rings to simulate varying patient effective diameters (25, 30, and 35 cm), and containing multiple spherical targets (5, 6, and 8 mm in diameter) with a 20-HU contrast difference. The phantom was scanned using routine abdominal protocols (CTDI_vol, 5.9–16 mGy) on four CT systems from two manufacturers. Images were reconstructed using both filtered back-projection (FBP) and various IR algorithms: ASiR 50%, SAFIRE 3 (both statistical IRs), ASiR-V 50%, ADMIRE 3 (both partial model-based IRs), or Veo (full model-based IR). Section thickness/interval was 2/1 mm or 2.5/1.25 mm, except 0.625/0.625 mm for Veo. We assessed LCD using a channelized Hotelling observer with 10 dense differences of Gaussian channels, with the area under the receiver operating characteristic curve (AUC) as a figure of merit.ResultsFor the smallest phantom (25-cm diameter) and smallest lesion size (5-mm diameter), AUC for FBP and the various IR algorithms did not significantly differ for any of the tested CT systems. For the largest phantom (35-cm diameter), Veo yielded the highest AUC improvement (8.5%). Statistical and partial model-based IR algorithms did not significantly improve LCD.ConclusionIn abdominal CT, switching from FBP to IR algorithms offers limited possibilities for achieving significant dose reductions while ensuring a constant objective LCD.     

The genus Anaedus Blanchard, 1842 in China with description of two new species (Coleoptera: Tenebrionidae: Goniaderini)

The genus Anaedus Blanchard, 1842 from China is revised. Anaedus serratus sp. nov. (Yunnan) and Anaedus nonedgus sp. nov. (Anhui, Hubei, Zhejiang) are described and illustrated. In addition to, a key to Chinese Anaedus species is given, and their geographical locations have been mapped.www.zoobank.org/urn:lsid:zoobank.org:pub:479055B1-08F6-4A35-8D45-999D46B0AEC9     

Evaluating the accuracy of geometrical distortion correction of magnetic resonance images for use in intracranial brain tumor radiotherapy

AimDetermine the 1) effectiveness of correction for gradient-non-linearity and susceptibility effects on both QUASAR GRID^3D and CIRS phantoms; and 2) the magnitude and location of regions of residual distortion before and after correction.BackgroundUsing magnetic resonance imaging (MRI) as a primary dataset for radiotherapy planning requires correction for geometrical distortion and non-uniform intensity.Materials and MethodsPhantom Study: MRI, computed tomography (CT) and cone beam CT images of QUASAR GRID^3D and CIRS head phantoms were acquired. Patient Study: Ten patients were MRI-scanned for stereotactic radiosurgery treatment. Correction algorithm: Two magnitude and one phase difference image were acquired to create a field map. A MATLAB program was used to calculate geometrical distortion in the frequency encoding direction, and 3D interpolation was applied to resize it to match 3D T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) images. MPRAGE images were warped according to the interpolated field map in the frequency encoding direction. The corrected and uncorrected MRI images were fused, deformable registered, and a difference distortion map generated.ResultsMaximum deviation improvements: GRID^3D, 0.27 mm y-direction, 0.07 mm z-direction, 0.23 mm x-direction. CIRS, 0.34 mm, 0.1 mm and 0.09 mm at 20-, 40- and 60-mm diameters from the isocenter. Patient data show corrections from 0.2 to 1.2 mm, based on location. The most-distorted areas are around air cavities, e.g. sinuses.ConclusionsThe phantom data show the validity of our fast distortion correction algorithm. Patient-specific data are acquired in <2 min and analyzed and available for planning in less than a minute.     

Effect of age and Gender on Fasting and Food-Stimulated Levels of Calcitonin,Parathyroid, and Gastrin Hormones in Healthy Adults

Objective: To investigate the effect of age and gender on basal and food-stimulated serum calcitonin (CT), parathyroid hormone (PTH), and gastrin levels among healthy adults.Methods: Ninety-six healthy adults (76 men and 20 women) aged between 21 and 43 years were recruited. Serum CT, PTH, and gastrin levels were measured after a 9-hour overnight fast, and 1 and 3 hours postprandially.Results: PTH levels decreased early and increased late after feeding. This change was significant in men but not in women. CT levels increased in response to food intake in men but not in women. Gastrin levels were significantly increased after feeding in both men and women. Mean basal and food stimulated CT, PTH, and gastrin levels did not significantly differ between genders. Fasting and post-prandial PTH levels were higher while gastrin levels were lower in older subjects (>30 years old) compared to younger subjects (≤30 years old). Fasting and postprandial CT levels were not significantly different between age groups.Conclusion: Age had a significant effect on fasting and food-stimulated PTH and gastrin hormone levels. The effect of age on PTH levels was independent of baseline vitamin D levels. Men showed significant changes in CT and PTH levels in response to feeding compared to women, although the mean hormone levels were not significantly different between men and women.Abbreviations: CT = calcitonin; MTC = medullary thyroid carcinoma; PTH = parathyroid hormone; SD = standard deviation     

Prognostic Value of Lymph Node Uptake on Pretreatment F-18 FDG PET/CT in Patients with N1B Papillary Thyroid Carcinoma

Objective: The aim of this study was to investigate the prognostic value of metabolic characteristics of metastatic lymph node (LN) using pretreatment F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for patients with papillary thyroid carcinoma (PTC) and metastatic lateral LN (N1b).Methods: Ninety-six PTC patients (female:male = 72:24; median age, 44.5 years) with pathologic N1b who underwent pretreatment FDG PET/CT, total thyroidectomy, and radioactive iodine ablation were retrospectively reviewed. To predict responses to initial therapy and recurrence, clinicopathologic factors and metabolic parameters were reviewed, such as sex, age, tumor size, extranodal extension, number and ratio of metastatic LNs, serum thyroglobulin, and maximum standardized uptake value (SUVmax).Results: Among the 96 PTC patients, 81 (84.4%) were classified into the acceptable response (58 excellent; 23 indeterminate) and 15 (15.6%) into the incomplete response (8 biochemical incomplete; 7 structural incomplete) by the 2015 American Thyroid Association management guideline for differentiated thyroid carcinoma. The multivariate analysis showed that SUVmax of N1b (P = .018), pre-ablation stimulated thyroglobulin level (P = .006), and the ratio of metastatic LNs (P = .018) were related to incomplete response. The cutoff value of each variable was determined by receiver operating characteristic analysis. Nine (9.4%) patients experienced recurrences (median follow-up: 50 months). The Kaplan-Meier analysis revealed that SUVmax of N1b (cutoff value: 2.3; P = .025) and ratio of metastatic LNs (cutoff value: 0.218; P = .037) were significant prognostic factors for recurrence.Conclusion: High SUVmax of N1b cervical LN on pretreatment FDG PET/CT could predict incomplete responses to initial therapy and recurrence in patients with N1b PTC.Abbreviations: ATA = American Thyroid Association; DTC = well-differentiated thyroid carcinoma; FDG = F-18 fluorodeoxyglucose; IQR = interquartile range; LN = lymph node; N1b = metastatic lateral cervical lymph node; PET/CT = positron emission tomography/computed tomography; PTC = papillary thyroid carcinoma; RAI = radioactive iodine; ROC = receiver operating characteristic; SUVmax = maximum standardized uptake value; Tg = thyroglobulin; USG = ultrasonography     

Geometric inaccuracy and co-registration errors for CT,DynaCT and MRI images used in robotic stereotactic radiosurgery treatment planning

PurposeTo measure the combined errors due to geometric inaccuracy and image co-registration on secondary images (dynamic CT angiography (dCTA), 3D DynaCT angiography (DynaCTA), and magnetic resonance images (MRI)) that are routinely used to aid in target delineation and planning for stereotactic radiosurgery (SRS).MethodsThree phantoms (one commercial and two in-house built) and two different analysis approaches (commercial and MATLAB based) were used to quantify the magnitude of geometric image distortion and co-registration errors for different imaging modalities within CyberKnife’s MultiPlan treatment planning software. For each phantom, the combined errors were reported as a mean target registration error (TRE). The mean TRE’s for different intramodality imaging parameters (e.g., mAs, kVp, and phantom set-ups) and for dCTA, DynaCTA, and MRI systems were measured.ResultsOnly X-ray based imaging can be performed with the commercial phantom, and the mean TRE ± standard deviation values were large compared to the in-house analysis using MATLAB. With the 3D printed phantom, even drastic changes in treatment planning CT imaging protocols did not greatly influence the mean TRE (<0.5 mm for a 1 mm slice thickness CT). For all imaging modalities, the largest mean TRE was found on DynaCT, followed by T2-weighted MR images (albeit all <1 mm).ConclusionsThe user may overestimate the mean TRE if the commercial phantom and MultiPlan were used solely. The 3D printed phantom design is a sensitive and suitable quality assurance tool for measuring 3D geometric inaccuracy and co-registration errors across all imaging modalities.     

Monte Carlo dose in a prosthesis phantom based on exact geometry vs streak artefact contaminated CT data as benchmarked against Gafchromic film measurements

PurposeIn radiotherapy, accurate calculation of patient radiation dose is very important for good clinical outcome. In the presence of metallic implants, the dose calculation accuracy could be compromised by metal artefacts generated in computed tomography (CT) images of patients. This study investigates the influence of metal-induced CT artefacts on MC dose calculations in a pelvic prosthesis phantom.MethodsA pelvic phantom containing unilateral Ti prosthesis was CT-scanned and accurate Hounsfield unit (HU) values were assigned to known materials of the phantom as opposed to HU values produced through the artefact CT images of the phantom. Using the DOSXYZnrc MC code, dose calculations were computed in the phantom model constructed from the original CT images containing the artefacts and artefact-free images made from the exact geometry of the phantom with known materials. The dose calculations were benchmarked against Gafchromic EBT3 film measurements using 15 MeV electron and 10 MV photon beams.ResultsThe average deviations between film and MC dose data decreased from 3 ± 2% to 1 ± 1% and from about 6 ± 2% to 3 ± 1% for the artefact and artefact-free phantom models against film data for the electron and photon fields, respectively.ConclusionsFor the Ti prosthesis phantom, the presence of metal-induced CT artefacts could cause dose inaccuracies of about 3%. Construction of an artefact-free phantom model made from the exact geometry of the phantom with known materials to overcome the effect of artefacts is advantageous compared to using CT data directly of which the exact tissue composition is not well-known.     

Increased Serum Calcitonin in Sporadic Primary Hyperparathyroidism is an Uncommon Occurrence

Objective: To evaluate calcitonin (CT) levels in sporadic primary hyperparathyroidism (PHPT), which has to date rarely been considered.Methods: We evaluated serum CT levels in 290 consecutive patients with sporadic PHPT at diagnosis.Results: Mild elevations in CT levels (hyperCT) were found in 25 patients (8.6%), with no correlation among the demographic, clinical, and biochemical findings. In addition, no differences were found between patients with and without hyperCT. Follow-up data were available for 19/25 patients, but CT values were only available for 10. CT normalized in all surgically cured patients regardless of the extent of the surgery (parathyroidectomy [PTX] only in 8 and associated with partial or total thyroidectomy for benign nodular goiters in 7).Conclusion: hyperCT is an uncommon feature of sporadic PHPT and not related to biochemical or clinical features of the disease. In addition, hyperCT is reversible after PTX, regardless of whether concomitant thyroidectomies have been conducted.Abbreviations: CT = calcitonin; eGFR = estimated glomerular filtration rate; hyperCT = hypercalcitoninemia; MEN = multiple endocrine neoplasm; MTC = medullary thyroid carcinoma; PHPT = primary hyperparathyroidism; PPI = proton pump inhibitor; PTH = parathyroid hormone; PTX = parathyroidectomy     

Dose calculation accuracy of different image value to density tables for cone-beam CT planning in head & neck and pelvic localizations

PurposeWe aimed to identify the most accurate combination of phantom and protocol for image value to density table (IVDT) on volume-modulated arc therapy (VMAT) dose calculation based on kV-Cone-beam CT imaging, for head and neck (H&N) and pelvic localizations.MethodsThree phantoms (Catphan^®600, CIRS^®062M (inner phantom for head and outer phantom for body), and TomoTherapy^® “Cheese” phantom) were used to create IVDT curves of CBCT systems with two different CBCT protocols (Standard-dose Head and Standard Pelvis). Hounsfield Unit (HU) time stability and repeatability for a single On-Board-Imager (OBI) and compatibility of two distinct devices were assessed with Catphan^®600. Images from the anthropomorphic phantom CIRS ATOM^® for both CT and CBCT modalities were used for VMAT dose calculation from different IVDT curves. Dosimetric indices from CT and CBCT imaging were compared.ResultsIVDT curves from CBCT images were highly different depending on phantom used (up to 1000 HU for high densities) and protocol applied (up to 200 HU for high densities). HU time stability was verified over seven weeks. A maximum difference of 3% on the dose calculation indices studied was found between CT and CBCT VMAT dose calculation across the two localizations using appropriate IVDT curves. One IVDT curve per localization can be established with a bi-monthly verification of IVDT-CBCT.ConclusionsThe IVDT-CBCT_CIRS-Head phantom with the Standard-dose Head protocol was the most accurate combination for dose calculation on H&N CBCT images. For pelvic localizations, the IVDT-CBCT_Cheese established with the Standard Pelvis protocol provided the best accuracy.     

Antihypertensive and endothelium-dependent vasodilator effects of aqueous extract of Cistus ladaniferus

Cistus ladaniferus L. (Cistaceae) is a medicinal plant originated from the Mediterranean region which exerts different pharmacological effects. In the present study, our goal was to examine whether the plant possessed antihypertensive properties. Aqueous extract of Cistus leaves (AEC, 500 mg/kg/day) reduced systemic blood pressure (SBP) in two animal models of hypertension, the l-NAME and renovascular two kidney-one clip (2K-1C) hypertensive rats. In the former, AEC prevented the increase in SBP when co-administered with l-NAME during four weeks (164 ± 3 mm Hg in l-NAME vs. 146 ± 1 mm Hg in l-NAME + AEC, p < 0.001). In the latter, AEC reversed the increase in SBP when administered during four weeks after installation of the hypertension (146 ± 5 mm Hg with AEC vs. 179 ± 6 mm Hg without, p < 0.05). AEC treatment also reversed the endothelial dysfunction observed in both animal models of hypertension. A direct effect on cardiac and vascular tissue was also tested by examining the contractile effects of AEC in rat isolated aortic rings and Langendorff perfused hearts. AEC (10 mg/L) had no effect on left ventricular developed pressure and heart rate in isolated perfused heart. However, AEC produced a strong relaxation of pre-contracted rat aortic rings (80 ± 2% relaxation, n = 25). When the rings were denuded from endothelium or were incubated with 1 mM Nω-nitro-l-arginine (l-NNA), the relaxant effect of AEC was lost. We conclude that C. ladaniferus possesses antihypertensive properties which are mainly due to an endothelium-dependent vasodilatory action.     

Mechanisms of liquid flux across pulmonary alveolar epithelial cell monolayers

Summary Active transport of sodium by pulmonary alveolar epithelial cells (AEC) is believed to be an important component of edema clearance in the normal and injured lung. Data supporting this premise have come from measurements of sodium movement across AEC monolayers or from perfused lung model systems. However, direct measurement of fluid flux across AEC monolayers has not been reported. In the present work, AEC were studied with an experimental system for the measurement of fluid flux (Jv) across functionally intact cell monolayers. Primary adult rat type II alveolar epithelial cells were cultured on 0.8 μm nuleopore filters previously coated with gelatin and fibronectin. Intact monolayers were verified by high electrical resistance (> 1000 Θ) at 4–5 d of primary culture. At the same time interval, transmission electron microscopy revealed cells with type I cell-like morphology throughout the monolayer. These were characterized by both adherens and tight junctional attachments. Fluid flux across the monolayers was measured volumetrically over a period of 2 h in the presence of HEPES-buffered DMEM containing 3% fatty acid-free bovine serum albumin. Flux (Jv) was inhibited 39% by 1 × 10⁻⁴ M ouabain (P < 0.01) and 27% by 5 × 10⁻⁴ M amiloride (P < 0.05). These data support the concept that AEC Na⁺/K⁺-ATPase and Na⁺ transport systems are important determinants of AEC transepithelial fluid movement in vitro.     

CALCITONIN SECRETORY INDEX AND UNSUSPECTED NODAL DISEASE IN MEDULLARY THYROID CARCINOMA

Objective: Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy originating from parafollicular C-cells with the potential for aggressive behavior. The extent of lymph node (LN) dissection at the time of surgery is controversial, with different schools of thought prevailing. Some systematically perform LN dissections, whereas others base their decision on radiologic evidence of disease and some with the assistance of pre-operative calcitonin (CT) levels.Methods: We retrospectively assessed the correlation between pre-operative CT levels and clinico-pathologic factors among 42 patients with MTC between 1994 and 2015. Furthermore, we refined the use of pre-operative serum CT levels and explored for the first time a test called the Calcitonin Secretory Index (CSI, ng/mL/mm).Results: Pre-operative CT levels correlated independently with tumor size (P<.0001), number of metastatic LNs (P<.01), and increased rates of distant metastasis. The CSI better predicted early LN disease (P<.045). Patients with early LN metastasis had a CSI >30 ng/mL/mm, a representative threshold above which the surgical cure declines considerably.Conclusion: In our experience, pre-operative CT levels and now the CSI appear as sensitive and specific risk stratification markers for MTC. Despite negative findings on dedicated pre-operative neck imaging in addition to total thyroidectomy, a CSI >30 ng/mL/mm would prompt bilateral central node dissection. Due to the small sample size, our study provides preliminary evidence of the value of CSI in clinical practice.Abbreviations: ANOVA = analysis of variance; ATA = American Thyroid Association; CSI = Calcitonin Secretory Index; CT = calcitonin; LN = lymph node; MTC = medullary thyroid carcinoma; ROC = receiver operating characteristic     

Synthesis and cytokinin activity of (R)-(+)- and (S)-(−)-dihydrozeatins and their ribosides

(R)-(+)- and (S)-(?)-dihydrozeatins [(R)-(+)- and (S)-(?)-6-(4-hydroxy-3-methylbutylamino)purines, 1a and 1b] and their ribosides {(?)-6-[(R)-4-hydroxy-3-methylbutylamino]- and (?)-6-[(S)-4-hydroxy-3-methyl-butylamino]-9-β-D-ribofuranosylpurines, 3a and 3b} were synthesized and tested for their cytokinin activity by four bioassay systems, the growth of tobacco callus, the seed germination of lettuce, the fr. wt increase of excised radish cotyledons and the retardation of chlorophyll degradation in radish cotyledons. In tobacco callus bioassay, 1a was more active than 1b. The ribosides 3a and 3b were not less active than their corresponding aglycones 1a and 1b. In other bioassays used the activity followed the order: 1a >3a >1b >3b. In tobacco callus bioassay and lettuce seed germination, trans-zeatin [6-(4-hydroxy-3-methylbut-trans-2-enylamino)purine] showed stronger cytokinin activity than 1a.     

Synthesis of an S-(2-Aminoethyl)-L-Cysteine Conjugate in S-(2-Aminoethyl)-L-Cysteine- Resistant Adenine-Auxotrophic Cells of Datura innoxia Mill

A line of S-(2-aminoethyl)-L-cysteine-resistant adenine-auxotrophiccells (Ad^–AEC^r strain) was isolated from adenine-auxotrophiccells (Ad^– strain) of Datura innoxia Mill by a stepwiseselection method. Ad^–AEC^r and Bl cells, which were clonedfrom the original Ad^–AEC^r cells, were able to grow activelyon medium that contained 10 mM S-(2-aminoethyl)-L-cysteine (AEC),whereas the growth of Ad^– cells ceased completely in thepresence of 0.5 mM AEC. The resistant phenotype has been maintainedfor at least 10 months in culture on medium without AEC. Levels of free lysine in Ad^–AEC^r and Bl cells were similarto that in Ad^– cells. By contrast, the level of free AECin Ad^–AEC cells was 10-fold lower than in Ad^– cellsand no free AEC was detectable in Bl cells. However, acid hydrolysisof extracts from Ad^–AEC^r and Bl cells resulted in a remarkableincrease in levels of detectable AEC. This result indicatesthat conjugated AEC is synthesized and accumulated in the AEC-resistantcells. The level of the AEC conjugate in Bl cells increasedwith increases in the concentration of AEC in the culture medium,while intracellular levels of AEC were so low as not to be detectablein the case of cells grown on medium supplemented with AEC atless than 1 mM. The AEC conjugate was also detected in Ad^–cells, but at lower levels than in the AEC-resistant cells.In addition, AEC was found to be incorporated into soluble proteinsin Ad^– cells. These results suggest that the resistance of AEC-resistant cellsof Datura innoxia is accomplished via acceleration of the synthesisof the AEC conjugate which prevents any increase in intracellularlevels of free AEC. ¹Present address: Institute for Biology and Chemistry, TsumuraCo.Ltd., Inashiki, Ibaraki, 300-03 Japan. ²Present address: North Kanto Shop, Sakata Seed Co. Ltd.,Saitama,347 Japan.     

Imaging Localization and Surgical Approach in the Management of Ectopic Parathyroid Adenomas

Objective: (1) Review the anatomy and epidemiology of ectopic parathyroid adenomas (EPAs), (2) summarize the role of relevant imaging modalities in the localization of EPAs, and (3) characterize surgical approaches for various ectopic locations.Methods: Literature review of published English-language articles from 1995 through August 2017.Results: Summary of the literature indicates that the prevalence of EPA is approximately 20% in unexplored patients with primary hyperparathyroidism, but it is as high as 66% in re-operative patients. EPAs may be located anywhere from the carotid bifurcation to the aorto-pulmonary window. Ultrasound has limited accuracy in identifying EPAs except near the thyroid and thyrothymic ligament and requires expert experience from the user. Among dual-phase ^99mTc sestamibi scintigraphy techniques, hybrid imaging with both single-photon emission computed tomography (SPECT) and computed tomography (CT) (SPECT/CT) is superior to planar scintigraphy or SPECT alone at localizing EPAs. Four-dimensional computed tomography (4DCT) precisely delineates important anatomic relationships and is highly sensitive in localizing EPAs. Although 4DCT requires radiation, intravenous iodinated contrast, and reader experience, it is well-equipped to detect lesions at various ectopic sites and guide the surgical approach. EPAs frequently require alternative surgical approaches. Re-operative parathyroidectomy may be attempted in patients having previously undergone bilateral neck exploration by an experienced surgeon once the lesion is colocalized by 2 repeat imaging modalities. Removal of nonlocalized disease requires a careful and systematic exploration of superior and inferior gland locations.Conclusion: EPAs pose challenges during both localization and surgical removal. High-volume experience and multidisciplinary care are necessary for optimal outcomes.Abbreviations: CT = computed tomography; 4DCT = 4-dimensional CT; EPA = ectopic parathyroid adenoma; EPG = ectopic parathyroid gland; PHPT = primary hyperparathyroidism; RLN = recurrent laryngeal nerve; SPECT = single-photon emission computed tomography; TE = tracheo-esophageal     

Large Adrenal Incidentalomas Require a Dedicated Diagnostic Procedure

Objective: The management of large nonsecreting adrenal tumors (at least 4 cm) is still a matter of debate as it is unclear whether imaging, especially ¹⁸F-fluorodeoxyglucose (FDG), can be used to characterize their potential malignancy. Moreover, the risk of new hypersecretion in nonoperated tumors is uncertain. Our aim was to better characterize these large adrenal incidentalomas.Methods: Patients followed in our center for a nonsecreting large (at least 4 cm) adrenal incidentaloma, with an initial computed tomography (CT) and ¹⁸F-FDG positron emission tomography (PET) CT, were retrospectively included. Patients who were not operated after initial diagnosis had to be followed with clinical, biological, and imaging evaluations for at least 3 years or until delayed surgery.Results: Eighty-one patients were included in the study: 44 patients (54.3%) had initial surgery while 37 were followed, including 21 (25.9%) who were operated after a mean of 19 months. Among the 65 operated patients, 13 (20%) had a malignant lesion (3 with metastasis, and 10 with adrenocortical carcinoma). Unenhanced CT <10 showed 85.6% sensitivity and 78.8% specificity; all had a ¹⁸F-FDG uptake ratio >1.5. Among the 24 patients who were followed for at least 3 years, 5 (20.8%) finally presented hypercortisolism (4 subclinical).Conclusion: As expected, large adrenal tumors are at a higher risk of malignancy. The combination of unenhanced CT <10 and ¹⁸F-FDG PET ratio <1.5 prove to be reassuring and might lead to a close follow-up rather than immediate surgery. Hormonal follow-up should be focused on the risk of hypercortisolism.Abbreviations: CI = confidence interval; CT = Computed Tomography; ENSAT = European Network for the Study of Adrenal Tumors; ESE = European Society of Endocrinology; FDG = fluorodeoxyglucose; HU = Hounsfield units; PET = positron emission tomography; ROI = regions of interest; SUV = standard uptake value