Whole-body [18F]-FDG-PET/MRI for staging of pediatric non-Hodgkin lymphoma: first results from a single-center evaluation.

AIM: In 2015, the revised International Pediatric Non-Hodgkin Lymphoma Staging System was published. It mentions [18F]-FDG-PET/MRI as the latest method to perform whole-body imaging. However, supporting data are pending. Our aim was to investigate the performance of whole-body [18F]-FDG-PET/MRI in pediatric non-Hodgkin lymphoma patients by using a limited number of MRI sequences. MATERIALS AND METHODS: Ten pediatric patients with histologically proven non-Hodgkin lymphoma underwent whole-body [18F]-FDG-PET/MRI at staging. The retrospective analysis included three steps: First, [18F]-FDG-PET and MR scans were evaluated separately by a nuclear medicine physician and a pediatric radiologist. Nineteen nodal and two extranodal regions as well as six organs were checked for involvement. Second, discrepant findings were reviewed together in order to reach consensus. Third, [18F]-FDG-PET/MRI findings were correlated with the results of other clinical investigations. RESULTS: Of the 190 lymph node regions evaluated, four were rated controversial. Consensus was reached by considering metabolic, functional and morphologic information combined. Concordantly, [18F]-FDG-PET and MRI detected Waldeyer's ring involvement in two patients whose Waldeyer's ring was negative on clinical assessment. In four patients MRI showed pleural effusion. However, in only two of them an increased glucose metabolism as a reliable sign of pleural involvement was detectable. In six patients [18F]-FDG-PET and MRI detected skeletal lesions although bone marrow biopsy was positive in only one of them. CONCLUSION: Despite the small number of cases evaluated, whole-body [18F]-FDG-PET turned out to be a valuable tool for staging of pediatric non-Hodgkin lymphoma.

Complexation of Trivalent Lanthanides (Eu) and Actinides (Cm) with Aqueous Phosphates at Elevated Temperatures.

In this study, the complexation of Eu(III) and Cm(III) with aqueous phosphates was investigated using laser-induced luminescence spectroscopy. Experiments at 25 °C and different ionic strengths (0.6-3.1 mol·L-1 NaClO4) established the formation of EuH2PO42+ and CmH2PO42+. From the conditional stability constants, the respective values at infinite dilution as well as the ε(Me(H2PO4)2+;ClO4-) (Me = Eu or Cm) ion interaction coefficients (using the specific ion interaction theory - SIT) were derived. Further experiments (at constant ionic strength of 1.1 mol·L-1) showed that upon increasing the temperature (25-80 °C), the formation of both EuH2PO42+ and CmH2PO42+ was favored. Using the van't Hoff equation, the molal enthalpy Δ R H m° and molal entropy Δ R S m° of these reactions were derived, corroborating an endothermic and entropy driven complexation process. This work contributes to a better understanding of the coordination chemistry of both trivalent lanthanides and actinides with phosphate ions.

Favorable outcome in children and adolescents with a high proportion of advanced phase disease using single/multiple autologous or matched/mismatched allogeneic stem cell transplantations.

We determined the indication, outcome, and risk factors of single and multiple hematopoietic stem cell transplantation(s) (HSCT) in children and adolescents mostly with advanced disease. Forty-one out of 483 patients (8.5 %; median age 9 years) diagnosed at the University of Leipzig with hematological and oncological diseases required HSCT from 1999 to 2011. Patients had overall survival (OS) of 63 ± 10 and 63 ± 16 %, event-free survival (EFS) of 57 ± 10 and 42 ± 16 %, relapse incidence (RI) of 39 ± 10 and 44 ± 18 % and nonrelapse mortality (NRM) of 4 ± 4 and 13 ± 9 % at 10 years after one or more allogeneic and autologous HSCT, respectively. One patient in CR1 and five with advanced disease received two HSCT. Four of the six patients maintained/achieved CR for a median of 13 months. Three died of progression and one of NRM. Two patients had a third HSCT and one survived in CR +231 days after HSCT. Risk factors for OS and EFS were disease stage at HSCT and EBMT risk score. Center (pediatric or JACIE accredited pediatric/adult) was not a determinant for survival. Pediatric single and multiple HSCT are important curative approaches for high-risk malignant diseases with low NRM. Efforts to reduce high RI remain the major aim.

Understanding hind limb lameness signs in horses using simple rigid body mechanics.

Hind limb lameness detection in horses relies on the identification of movement asymmetry which can be based on multiple pelvic landmarks. This study explains the poorly understood relationship between hind limb lameness pointers, related to the tubera coxae and sacrum, based on experimental data in context of a simple rigid body model. Vertical displacement of tubera coxae and sacrum was quantified experimentally in 107 horses with varying lameness degrees. A geometrical rigid-body model of pelvis movement during lameness was created in Matlab. Several asymmetry measures were calculated and contrasted. Results showed that model predictions for tubera coxae asymmetry during lameness matched experimental observations closely. Asymmetry for sacrum and comparative tubera coxae movement showed a strong association both empirically (R(2)≥ 0.92) and theoretically. We did not find empirical or theoretical evidence for a systematic, pronounced adaptation in the pelvic rotation pattern with increasing lameness. The model showed that the overall range of movement between tubera coxae does not allow the appreciation of asymmetry changes beyond mild lameness. When evaluating movement relative to the stride cycle we did find empirical evidence for asymmetry being slightly more visible when comparing tubera coxae amplitudes rather than sacrum amplitudes, although variation exists for mild lameness. In conclusion, the rigidity of the equine pelvis results in tightly linked movement trajectories of different pelvic landmarks. The model allows the explanation of empirical observations in the context of the underlying mechanics, helping the identification of potentially limited assessment choices when evaluating gait.

Adaptive responses of calcium and phosphate homeostasis in goats to low nitrogen intake: renal aspects.

In a previous study, in goats, we showed that apart from variations in dietary calcium (Ca) and phosphorus intake, also low dietary nitrogen (N) intake altered plasma concentrations of hormones, which regulate Ca and phosphate (Pi ) homeostasis. These hormonal responses in goats were in accordance with findings in monogastric animals and humans with low protein intake. In the aforementioned studies, alterations of electrolyte transport in the kidneys were also observed. However, whether renal electrolyte transport in goats is also involved in the adaptation of Ca and Pi homeostasis to low N intake remains unknown. Thus, the aim of the present study was to investigate whether in addition to the hormonal changes, as observed in our former study, renal Ca transport and renal Pi transport were also altered by low N intake in goats. Therefore, in kidney samples from the goats used in our former study, the protein expression of Ca and Pi transporters and of related regulatory proteins was examined. Furthermore, the uptake of Pi into isolated brush border membrane vesicles (BBMV) was detected. The results showed that the protein amount of the renal sodium-dependent Pi transporter NaPi IIa was elevated, and concomitantly, protein expression of its upstream regulators, the parathyroid hormone receptor and the extracellular signal-regulated kinases 1 and 2 was decreased. However, Pi uptake into renal BBMV was not enhanced. Furthermore, protein expression of the renal Ca channel, the transient receptor potential cation channel subfamily V member 5 (TRPV5) and of the vitamin D receptor was not influenced by dietary N reduction. We conclude that regulation of renal Pi transporter expression in goats is involved in the adaptation of electrolyte homeostasis to low N intake.

Species-specific responses of N homeostasis and electrolyte handling to low N intake: a comparative physiological approach in a monogastric and a ruminant species.

In our former studies low crude protein (LCP) intake influenced N homeostasis and electrolyte handling in goats. We hypothesised that due to rumino-hepatic nitrogen (N) recycling adaptation of N homeostasis and adjustment of electrolyte handling to LCP intake differs between goats and monogastric animals. Therefore, an experiment similar to that with goats was conducted with rats. Two feeding groups received a diet either containing 20 or 8 % crude protein (as fed basis) for 5 weeks and intake and excretion of N, calcium (Ca) and phosphorus (P) were determined. To detect systemic and endocrine adaptation to LCP intake plasma concentrations of urea, Ca, phosphate (Pi), insulin-like growth factor 1 (IGF-1), 1,25-dihydroxyvitamin D3 (calcitriol), parathyroid hormone (PTH) and cross-linked telopeptide of type I collagen (CTX) were measured. Adjustment of renal electrolyte transport was assessed by detecting protein expression of key proteins of renal Pi transport. All data were compared with the data of the goat experiment. LCP intake decreased plasma urea concentration stronger in goats than in rats. In both species urinary N excretion declined, but faecal N excretion decreased in goats only. Furthermore, in goats urinary Ca excretion decreased, but in rats urinary Ca concentration increased. Decreased plasma IGF-1 and calcitriol concentrations were found in goats only. Thus, renal Ca excretion appears to be a common target in adaptation of electrolyte homeostasis in both species, but is regulated differently.

Expression of urea transporters is affected by dietary nitrogen restriction in goat kidney.

Ruminants are known to be able to very effectively recycle urinary urea and reuse it as a source of N for ruminal microbes. It is presumed that urea recycling is accomplished by specialized urea transporters (UT) which are localized in the kidney. This could be especially important in times of increased N requirement, such as during growth or during reduced dietary N intake. The aim of our study was to characterize and to localize UT in the goat (capra hircus) kidney and to investigate its response to reduced dietary N intake in growing goats. Therefore, 12 growing, male goats were fed either a diet containing high (17% CP in complete diet) or low (9% CP in complete diet) N content for 6 wk. After harvesting, blood and kidney samples were taken and analyzed. The mRNA of the different UT isoforms, UT-A1, UT-A2 and UT-B, were detected semiquantitatively in renal tissue by Northern blot analysis. For UT-A2 and UT-B, no statistically significant effect of dietary N restriction on renal mRNA expression could be detected (UT-A2: P = 0.26, UT-B: P = 0.07). However, renal mRNA abundance of UT-A1 significantly increased in the kidney of low-N-fed goats (P = 0.01). Furthermore, protein amounts of UT-B were verified by western blotting; and the localization of UT-A2 and UT-B protein was demonstrated by immunohistochemistry. No significant differences in protein amounts of UT-B could be observed comparing the 2 feeding groups (P = 0.78). The UT-B was localized in renal medulla and papilla, whereas UT-A2 was only found in renal medulla. In addition, comparison of UT-A and UT-BAA sequences of monogastric animals and ruminants showed a high degree of homology, indicating a similar function of the transporters among these species. In summary, we conclude that in ruminants, urea reabsorption in the kidney is most likely increased in response to a low-N diet via an upregulation of UT-A1 mRNA expression. Hypothetically, the reabsorbed urea can then be returned to the rumen via the bloodstream and thus be reused as a source of N for protein synthesis of ruminal microbial community.

Proximal hindlimb flexion in the horse: effect on movement symmetry and implications for defining soundness.

REASONS FOR PERFORMING THE STUDY: Flexion tests are a common tool during the prepurchase and clinical lameness examination, yet studies quantifying the effect of flexion, apart from distal forelimb flexion in sound horses, are sparse. OBJECTIVES: To investigate the effect of proximal hindlimb flexion on perceivable and measurable changes in movement symmetry in horses with objective movement symmetry falling within the margins of 'sound'. METHODS: Thirteen horses, selected based on objective movement symmetry, were instrumented with inertial sensors on left and right tuber coxae and over the os sacrum. Vertical movement symmetry was quantified at trot before and after proximal hindlimb flexion, with a repeat of flexion after 5 min. Video recordings of the horses were assessed visually. RESULTS: Proximal hindlimb flexion introduced additive changes in movement symmetry to the individual baseline movement, with a tendency towards smaller effects with increasing stride number. The main systematic effect was a decrease in upward movement of the os sacrum following mid-stance of the flexed limb and an increase in upward movement following mid-stance of the nonflexed limb, also manifesting in a 'hip hike' of the flexed limb; these findings reflected increased movement asymmetry following flexion. Depending on individual baseline asymmetry, flexion can also increase movement symmetry. CONCLUSIONS: Proximal hindlimb flexion can exacerbate subtle asymmetry when performed carefully. Variation in measured symmetry following flexion within and between horses showed that the individual response to flexion is highly variable. POTENTIAL RELEVANCE: Proximal hindlimb flexion may elevate the asymmetry of a slightly lame limb above the threshold for visibility, thus assisting in the clinical gait examination. Further work is needed to examine the causes for a positive response to flexion and possible differences between sound and lame horses as well as horses of different athletic disciplines.