Shorter and sweeter: the 16-item version of the SRS questionnaire shows better structural validity than the 20-item version in young patients with spinal deformity.

PURPOSE: In patients with adult spinal deformity, it was previously shown that 16 of the non-management items of the SRS-instrument showed a better fit to the theoretical four-factor model (pain, function, self-image, mental health) than did all 20 items. Whether the same phenomenon is observed in data from younger (< 20y) patients, for whom the questionnaire was originally designed, is not currently known. METHODS: Confirmatory factor analysis was used to evaluate the factor structure of the 20 non-management items of the SRS-instrument completed by 3618 young patients with spinal deformity (75.5% female; mean age, 15.0 ± 2.0 years) and of its equivalence across language versions (2713 English-speaking, 270 Spanish, 264 German, 223 Italian, and 148 French). The root mean square error of approximation (RMSEA) and comparative fit index (CFI) indicated model fit. RESULTS: Compared with the 20-item version, the 16-item solution significantly increased the fit (p < 0.001) across all language versions, to achieve good model fit (CFI = 0.96, RMSEA = 0.06). For both 16-item and 20-item models, equivalence across languages was not reached, with some items showing weaker item-loading for some languages, in particular German and French. CONCLUSION: In patients with adolescent idiopathic scoliosis, the shorter 16-item version showed a better fit to the intended 4-factor structure of the SRS-instrument. The wording of some of the items, and/or their equivalence across language versions, may need to be addressed. Questionnaire completion can be a burden for patients; if a shorter, more structurally valid version is available, its use should be encouraged.

A Population Dose-Response Model for Inhaled Technosphere Insulin Administered to Healthy Subjects.

Technosphere insulin (TI), an inhaled insulin with a fast onset of action, provides a novel option for the control of prandial glucose. A euglycemic glucose clamp study was performed to compare the effects of TI and regular human insulin (RHI) on the induced glucose infusion rate (GIR) in healthy volunteers. Generation of a dose-response relationship between insulin dose and effect (expressed as AUC of GIR) was not possible from the clinical data directly. The GIR recording time was too short to capture the full effect and higher doses were not tested. Thus, a pharmacokinetic-GIR model was developed to simulate GIR for a sufficient time window of 20 h and for higher doses. A dose-response model was then generated from the simulated GIR profiles. The resulting model provides an ED50 for TI that is 5-fold higher than for RHI, a ratio that can be used as conversion factor for equivalent doses of RHI and TI.

Water-fat Dixon sequences in the evaluation of breast implants: proposal of a time effective rapid approach in the clinical practice.

AIM: To evaluate the diagnostic accuracy achieved from a fat-water Dixon sequence alone compared to a combination of a silicone-specific magnetic resonance imaging (MRI) sequence and a water-specific MRI sequence in the assessment of breast implants. MATERIALS AND METHODS: In this institutional review board (IRB)-approved study the integrity of breast implants was assessed retrospectively in 27 patients undergoing breast MRI at 3 T. A qualitative evaluation of (set 1) a silicon-selective water-saturated short tau inversion recovery (STIR) sequence in combination with a water-only Dixon dataset (total acquisition time 7 minutes 17 seconds), and of (set 2) fat-only and water-only Dixon datasets (4 minutes 8 seconds) was performed by two readers independently evaluating the following features: margin definition of the implant, water suppression homogeneity, image quality, presence of artefacts and their effects on the imaging interpretation, and diagnostic confidence. Diagnostic accuracy in implant rupture detection was determined and either surgical confirmation or diagnosis from the radiological report was used as a standard of reference. RESULTS: In both sequences, margin definition of the implant wall, water suppression homogeneity, and overall image quality were rated good-excellent in most of cases. Water suppression homogeneity was moderate-poor in a greater number of cases in set 1. Movement artefacts were more frequent in set 1 whereas five cases (18.5%) exhibited swap artefacts between silicone and water in set 2. Diagnostic confidence was rated high-very high with both sequences in most of cases. Diagnostic accuracy was 100% for both readers using set 1 and 96.2% and 100% using set 2. CONCLUSION: A single Dixon sequence allows an accurate diagnostic evaluation of breast implants and concomitant shortening of the overall acquisition time.

Whole-Body Diffusion Imaging Applying Simultaneous Multi-Slice Excitation.

PURPOSE: The purpose of this study was to examine the feasibility of a fast protocol for whole-body diffusion-weighted imaging (WB-DWI) using a slice-accelerated echo-planar sequence, which, when using comparable image acquisition parameters, noticeably reduces measurement time compared to a conventional WB-DWI protocol. MATERIALS AND METHODS: A single-shot echo-planar imaging sequence capable of simultaneous slice excitation and acquisition was optimized for WB-DWI on a 3 T MR scanner, with a comparable conventional WB-DWI protocol serving as the reference standard. Eight healthy individuals and one oncologic patient underwent WB-DWI. Quantitative analysis was carried out by measuring the apparent diffusion coefficient (ADC) and its coefficient of variation (CV) in different organs. Image quality was assessed qualitatively by two independent radiologists using a 4-point Likert scale. RESULTS: Using our proposed protocol, the scan time of the WB-DWI measurement was reduced by up to 25.9 %. Both protocols, the slice-accelerated protocol and the conventional protocol, showed comparable image quality without statistically significant differences in the reader scores. Similarly, no significant differences of the ADC values of parenchymal organs were found, whereas ADC values of brain tissue were slightly higher in the slice-accelerated protocol. CONCLUSION: It was demonstrated that slice-accelerated DWI can be applied to WB-DWI protocols with the potential to greatly reduce the required measurement time, thereby substantially increasing clinical applicability. KEY POINTS: •Whole-body diffusion-weighted imaging (WB-DWI) using simultaneous multi-slice and blipped-CAIPIRINHA reduces the measurement time strongly without having a significant impact on image quality. •The reduction in measurement time might strongly contribute to the clinical applicability of WB-DWI. •However, further refinement of the slice-accelerated EPI sequence, and the WB-DWI protocol applying this sequence type seems necessary; and the value of such WB-DWI protocols for assessment of systemic oncological diseases needs to be investigated in further clinical studies.

Quantitative in vivo analysis of small bowel motility using MRI examinations in mice--proof of concept study.

Small bowel motility analyses using magnetic resonance imaging (MRI) could reduce current invasive techniques in animal studies and comply with the 'three Rs' rule for human animal experimentation. Thus we investigated the feasibility of in vivo small bowel motility analyses in mice using dynamic MRI acquisitions. All experimental procedures were approved by the institutional animal care committee. Six C57BL/6 mice underwent MRI without additional preparation after isoflurane anaesthetization in the prone position on a 4.7 T small animal imager equipped with a linear polarized hydrogen birdcage whole-body mouse coil. Motility was assessed using a true fast imaging in a steady precession sequence in the coronal orientation (acquisition time per slice 512 ms, in-plane resolution 234 × 234 µm, matrix size 128 × 128, slice thickness 1 mm) over 30 s corresponding to 60 acquisitions. Motility was manually assessed measuring the small bowel diameter change over time. The resulting motility curves were analysed for the following parameters: contraction frequency per minute (cpm), maximal contraction amplitude (maximum to minimum [mm]), luminal diameter (mm) and luminal occlusion rate. Small bowel motility quantification was found to be possible in all animals with a mean small bowel contraction frequency of 10.67 cpm (SD ± 3.84), a mean amplitude of the contractions of 1.33 mm (SD ± 0.43) and a mean luminal diameter of 1.37 mm (SD ± 0.42). The mean luminal occlusion rate was 1.044 (SD ± 0.45%/100). The mean duration needed for a single motility assessment was 185 s (SD ± 54.02). Thus our study demonstrated the feasibility of an easy and time-sparing functional assessment for in vivo small bowel motility analyses in mice. This could improve the development of small animal models of intestinal diseases and provide a method similar to clinical MR examinations that is in concordance with the 'three Rs' for humane animal experimentation.

Dynamic MR urography in children with uropathic disease with a combined 2D and 3D acquisition protocol--comparison with MAG3 scintigraphy.

OBJECTIVE: The aim of this study was to evaluate combined two-dimensional (2D) and three-dimensional (3D) dynamic MR urography with respiratory compensation in children with anomalies of the genitourinary tract, allowing for computation of split renal function and assessment of urinary tract obstruction. METHODS: Dynamic MR urography was performed in 53 children (3 months-16 years of age) with anomalies of the urinary tract. A protocol for dynamic MR urography and nephrography was implemented at 1.5 T using a navigator-triggered 2D TurboFLASH sequence. Split renal function and contrast-medium excretion were assessed after the bolus injection of 0.05 mmol kg(-1) body weight of gadolinium dimeglumine. In the excretory phase, a 3D gradient-echo data set with high spatial resolution was acquired. In all patients, mercaptoacetyltriglycine (MAG3) scintigraphy was obtained as a reference standard. RESULTS: In all children, dynamic MR nephrography and urography could be performed with excellent compensation of breathing artefacts providing region of interest analysis in nearly identical kidney positions. The assessment of contrast-medium excretion into the ureter allowed for discrimination of functional from non-functional stenosis. Split renal function assessed by MRI showed an excellent agreement with the MAG3 reference standard with a correlation coefficient r = 0.95. Additionally recorded 3D data sets offered good depiction of anatomical anomalies in all patients. CONCLUSION: The proposed protocol provides a robust technique for assessment of ureteral obstruction and split renal function with compensation of breathing artefacts, short post-processing time and excellent 3D spatial resolution. ADVANCES IN KNOWLEDGE: The combined protocol of 2D and 3D MR urography is an efficient technique for assessment of renal morphology and function.

First Report of Meloidogyne javanica Parasitizing Duboisia sp. in Paraná State, Brazil.

Duboisia sp. is a small tree belonging to the family Solanaceae originating from the rainforest areas of the eastern coast of Australia. Dried leaves are used for the extraction of pharmaceutical alkaloids, making this a commercially viable crop. The root-knot nematode Meloidogyne incognita has been reported parasitizing Duboisia myoporoides (5); however, no information of other root-knot nematode species associated with this plant was found. Duboisia sp. is cultivated at Solana Farm, near Arapongas (23°25'08″ S, 51°25'26″ W), Paraná State, Brazil. During the renovation of a production field in this municipality, galled roots were observed on plants and samples were submitted to the Nematology Laboratory at Instituto Agronômico do Paraná, IAPAR, on December 2013. Plants did not exhibit any above-ground symptoms. The specimens were identified through perineal patterns and esterase phenotypes of 20 adult females extracted from dissected roots (2,3) and morphometrics of 10 second-stage juveniles extracted from roots using the blender-sieving method (1). Morphological characteristics were consistent with those described for M. javanica (4). Females had rounded perineal patterns with low, trapezoid shape dorsal arch, striae smooth interrupted by a pair of incisures on both sides, corresponding to lateral fields, clearly demarcated from striae by more or less parallel lines, tail whorl often distinct (4). The juvenile mean body length was 459.9 ± 28.7 µm and tail length averaged 51.6 ± 5.1 µm, with 10 to 16 µm long hyaline region and finely rounded tail tip (4). Results from the esterase electrophoresis were typical of M. javanica (2) with the J3 (Rm = 1.0, 1.3, and 1.4) phenotype being obtained. To our knowledge, this is the first report of M. javanica on Duboisia sp. in Brazil. This finding has great importance for Brazilian production since this nematode may damage plants, reduce yields, and control of this nematode on Duboisia sp. is difficult (5). Additional work is necessary in order to elucidate the losses caused by M. javanica on Duboisia sp. References: (1) J. I. Bonetti and S. Ferraz. Fitopatol. Bras. 6:533, 1981. (2) P. R. Esbenshade and A. C. Triantaphyllou. J. Nematol. 22:10, 1990. (3) K. M. Hartman and J. N. Sasser. Page 115 in: An Advanced Treatise on Meloidogyne. Volume II Methodology. K. R. Barker et al., eds. North Carolina State University Graphics, Raleigh, 1985. (4) D. J. Hunt and Z. A. Handoo. Page 55 in: Root-Knot Nematodes. R. N. Perry et al., eds. CABI International, Wallingford, UK, 2010. (5) A. M. Mello et al. Nematol. Bras. 22(2):12, 1998.

PET/CT versus body coil PET/MRI: how low can you go?

OBJECTIVES: The purpose of this study was to evaluate if positron emission tomography (PET)/magnetic resonance imaging (MRI) with just one gradient echo sequence using the body coil is diagnostically sufficient compared with a standard, low-dose non-contrast-enhanced PET/computed tomography (CT) concerning overall diagnostic accuracy, lesion detectability, size and conspicuity evaluation. METHODS AND MATERIALS: Sixty-three patients (mean age 58 years, range 19-86 years; 23 women, 40 men) referred for either staging or restaging/follow-up of various malignant tumours (malignant melanoma, lung cancer, breast cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, CUP, gynaecology tumours, pleural mesothelioma, oesophageal cancer, colorectal cancer, stomach cancer) were prospectively included. Imaging was conducted using a tri-modality PET/CT-MR set-up (full ring, time-of-flight Discovery PET/CT 690, 3 T Discovery MR 750, both GE Healthcare, Waukesha, WI). All patients were positioned on a dedicated PET/CT- and MR-compatible examination table, allowing for patient transport from the MR system to the PET/CT without patient movement. In accordance with RECIST 1.1 criteria, measurements of the maximum lesion diameters on CT and MR images were obtained. In lymph nodes, the short axis was measured. A four-point scale was used for assessment of lesion conspicuity: 1 (>25 % of lesion borders definable), 2 (25-50 %), 3 (50-75 %) and 4 (>75 %). For each lesion the corresponding anatomical structure was noted based on anatomical information of the spatially co-registered PET/CT and PET/MRI image sections. Additionally, lesions were divided into three categories: "tumour mass", "lymph nodes" and "lesions". Differences in overall lesion detectability and conspicuity in PET/CT and PET/MRI, as well as differences in detectability based on the localisation and lesion type, were analysed by Wilcoxon signed rank test. RESULTS: A total of 126 PET-positive lesions were evaluated. Overall, no statistically significant superiority of PET/CT over PET/MRI or vice versa in terms of lesion conspicuity was found (p = 0.095; mean score CT 2.93, mean score MRI 2.75). A statistically significant superiority concerning conspicuity of PET/CT over PET/MRI was found in pulmonary lesions (p = 0.016). Additionally, a statistically significant superiority of PET/CT over PET/MRI in "lymph nodes" regarding lesion conspicuity was also found (p = 0.033). A higher mean score concerning bone lesions were found for PET/CT compared with PET/MRI; however, these differences did not achieve statistical significance. CONCLUSION: Overall, PET/MRI with body coil acquisition does not match entirely the diagnostic accuracy of standard low-dose PET/CT. Thus, it might only serve as a back-up solution in very few patients. Overall, more time needs to be invested on the MR imaging part (higher matrix, more breath-holds, additional surface coil acquired sequences) to match up with the standard low-dose PET/CT. MAIN MESSAGES: • Evaluation of whether PET/MRI with one sequence using body coil is diagnostically sufficient compared with PET/CT • PET/MRI with body coil does not match entirely the diagnostic accuracy of standard low-dose PET/CT • PET/MRI might only serve as a backup solution in patients.

Crohn's disease: small bowel motility impairment correlates with inflammatory-related markers C-reactive protein and calprotectin.

BACKGROUND: To evaluate the correlation between the levels of C-reactive protein (CRP), calprotectin, and small bowel motility in patients with Crohn's disease assessed with MRI. METHODS: This prospective institutional review board approved study included magnetic resonance imaging enterography (MRE) and analyses of inflammatory markers in blood (C-reactive protein) and feces (calprotectin). For cine MRE, a coronal 2D-T2w sequence was used on a 1.5 T MRI system. Small bowel motility was analyzed in 13 patients using dedicated magnetic resonance MR-motility assessment software (Motasso). Contraction frequency, amplitude, amplitude diameter ratio, and luminal diameter were determined as well as the blood levels of CRP (mg L(-1) ) and fecal levels of calprotectin (ug g(-1) ). Statistics were calculated using Pearson's correlation coefficient. KEY RESULTS: A significant inverse linear correlation was found between the contraction frequency and both the level of CRP (r = -0.701, P = 0.008) and calprotectin (r = -0.805, P = 0.001). Dilatation of small bowel diameter significantly correlated with calprotectin levels (r = 0.857, P =< 0.001) but not with CRP (r = 0.447, P = 0.126). The absolute amplitude of the contractions did not correlate neither with the level of CRP (r = -0.527, P = 0.064) nor with calprotectin (r = -0.612, P = 0.026). The ratio describing the contraction amplitude relatively to the individual luminal diameter significantly correlated with calprotectin (r = 0.736, P = 0.004) and with CRP (r = 0.577, P = 0.039). CONCLUSIONS & INFERENCES: Alterations of small bowel motility during CD flares significantly correlate with the level of calprotectin and CRP indicating that they represent inflammatory activity.

Effects of fructose and glucose overfeeding on hepatic insulin sensitivity and intrahepatic lipids in healthy humans.

OBJECTIVE: To assess how intrahepatic fat and insulin resistance relate to daily fructose and energy intake during short-term overfeeding in healthy subjects. DESIGN AND METHODS: The analysis of the data collected in several studies in which fasting hepatic glucose production (HGP), hepatic insulin sensitivity index (HISI), and intrahepatocellular lipids (IHCL) had been measured after both 6-7 days on a weight-maintenance diet (control, C; n = 55) and 6-7 days of overfeeding with 1.5 (F1.5, n = 7), 3 (F3, n = 17), or 4 g fructose/kg/day (F4, n = 10), with 3 g glucose/kg/day (G3, n = 11), or with 30% excess energy as saturated fat (fat30%, n = 10). RESULTS: F3, F4, G3, and fat30% all significantly increased IHCL, respectively by 113 ± 86, 102 ± 115, 59 ± 92, and 90 ± 74% as compared to C (all P < 0.05). F4 and G3 increased HGP by 16 ± 10 and 8 ± 11% (both P < 0.05), and F3 and F4 significantly decreased HISI by 20 ± 22 and 19 ± 14% (both P < 0.01). In contrast, there was no significant effect of fat30% on HGP or HISI. CONCLUSIONS: Short-term overfeeding with fructose or glucose decreases hepatic insulin sensitivity and increases hepatic fat content. This indicates short-term regulation of hepatic glucose metabolism by simple carbohydrates.

Simultaneous PET/MR imaging in a human brain PET/MR system in 50 patients--current state of image quality.

OBJECTIVES: The present work illustrates the current state of image quality and diagnostic accuracy in a new hybrid BrainPET/MR. MATERIALS AND METHODS: 50 patients with intracranial masses, head and upper neck tumors or neurodegenerative diseases were examined with a hybrid BrainPET/MR consisting of a conventional 3T MR system and an MR-compatible PET insert. Directly before PET/MR, all patients underwent a PET/CT examination with either [18F]-FDG, [11C]-methionine or [68Ga]-DOTATOC. In addition to anatomical MR scans, functional sequences were performed including diffusion tensor imaging (DTI), arterial spin labeling (ASL) and proton-spectroscopy. Image quality score of MR imaging was evaluated using a 4-point-scale. PET data quality was assessed by evaluating FDG-uptake and tumor delineation with [11C]-methionine and [68Ga]-DOTATOC. FDG uptake quantification accuracy was evaluated by means of ROI analysis (right and left frontal and temporo-occipital lobes). The asymmetry indices and ratios between frontal and occipital ROIs were compared. RESULTS: In 45/50 patients, PET/MR examination was successful. Visual analysis revealed a diagnostic image quality of anatomical MR imaging (mean quality score T2 FSE: 1.27±0.54; FLAIR: 1.38±0.61). ASL and proton-spectroscopy was possible in all cases. In DTI, dental artifacts lead to one non-diagnostic dataset (mean quality score DTI: 1.32±0.69; ASL: 1.10±0.31). PET datasets of PET/MR and PET/CT offered comparable tumor delineation with [11C]-methionine; additional lesions were found in 2/8 [(68)Ga]-DOTATOC-PET in the PET/MR. Mean asymmetry index revealed a high accordance between PET/MR and PET/CT (1.5±2.2% vs. 0.9±3.6%; mean ratio (frontal/parieto-occipital) 0.93±0.08 vs. 0.96±0.05), respectively. CONCLUSIONS: The hybrid BrainPET/MR allows for molecular, anatomical and functional imaging with uncompromised MR image quality and a high accordance of PET results between PET/MR and PET/CT. These results justify the application of this technique in further clinical studies and may contribute to the transfer into whole-body PET/MR systems.

Pulmonary function over 2 years in diabetic patients treated with prandial inhaled Technosphere Insulin or usual antidiabetes treatment: a randomized trial.

AIMS: Development of inhaled insulin has increased the need to understand its pulmonary safety. This study evaluated pulmonary function changes in diabetes patients receiving inhaled Technosphere Insulin (TI) or usual antidiabetes treatment (usual care). METHODS: This randomized, open-label study was conducted at 220 sites (25 July 2005 to 29 August 2008). Pulmonary function tests [forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), total lung capacity (TLC) and lung diffusion capacity for carbon monoxide (DL(CO))] were prospectively followed over 2 years in patients with type 1 or type 2 diabetes receiving TI (n = 730) or usual care (n = 824), along with a cohort without diabetes not receiving any specific therapy (n = 145). RESULTS: Baseline demographics and pulmonary function were similar between diabetes treatment groups. Lung function declined from baseline in all groups. TI was non-inferior to usual care for mean change in FEV(1) from baseline to month 24 [mean (s.e.m.) 0.037 (0.0119) l; 95% CI 0.014 to 0.060] using mixed-model repeated-measure with a pre-specified non-inferiority margin of 50 ml/year. After a greater initial decline at month 3 with TI, rate of change (slope) in FEV(1), FVC and DL(CO) (months 3-24) was not statistically different between treatment groups. TI was well tolerated; no serious safety concerns emerged. The most common respiratory event associated with TI was mild, transient cough, occurring within minutes of inhalation. CONCLUSIONS: Observed changes in lung function with TI were small, occurred early after therapy initiation, remained non-progressive over 2 years and were unlikely to be clinically meaningful.

Methodological characteristics of the national dietary surveys carried out in the European Union as included in the European Food Safety Authority (EFSA) Comprehensive European Food Consumption Database.

In 2009 competent organisations in the European Union provided the European Food Safety Authority (EFSA) with data from the most recent national dietary survey at the level of individuals' consumption. Twenty different Member States provided EFSA with data from 22 different national dietary surveys, with consumption figures for adults and, when available, for children. Member States' dietary data were assembled into the EFSA Comprehensive European Food Consumption Database. In this paper an overview of the methodologies and protocols employed in the different national dietary surveys is provided. Specifically, details about dietary assessment methods, interview administration, sampling design, portion size estimation, dietary software, evaluation of under-reporting and non-dietary information collected are described. This information is crucial to evaluate the level of accuracy of food consumption data and to anticipate and acknowledge the utmost important sources of heterogeneity of national databases included in the Comprehensive Database. The Comprehensive Database constitutes a unique resource for the estimation of consumption figures across the European Union and represents a useful tool to assess dietary exposure to hazardous substances and nutrient intake in Europe. Nevertheless, the many substantial methodological differences that characterise the Comprehensive Database are acknowledged and critically discussed.

A new C-Peptide correction model used to assess bioavailability of regular human insulin.

The clinical assessment of new formulations of human insulin is problematic due to the inability to distinguish between endogenous insulin and exogenously administered insulin. The usual methods to surmount the problem of distinguishing between endogenous and exogenous human insulin include evaluation in subjects with no or little endogenous insulin, hyper-insulinemic clamp studies or the administration of somatostatin to suppress endogenous insulin secretion. All of these methods have significant drawbacks. This paper describes a method for C-Peptide correction based upon a mixed effects linear regression of multiple time point sampling of C-Peptide and insulin. This model was able to describe each individual's insulin to C-Peptide relationship using the data from four different phase I clinical trials involving both subjects with and without type 2 diabetes in which insulin and C-Peptide were measured. These studies used hyper-insulinemic euglycemic clamps or meal challenges and subjects received insulin or Glucagon-like peptide 1 (GLP-1). It was possible to determine the exogenously administered insulin concentration from the measured total insulin concentration. A simple statistical technique can be used to determine each individual's insulin to C-Peptide relationship to estimate exogenous and endogenous insulin following the administration of regular human insulin. This technique will simplify the assessment of new formulations of human insulin.

Pharmacokinetics and pharmacodynamics of inhaled GLP-1 (MKC253): proof-of-concept studies in healthy normal volunteers and in patients with type 2 diabetes.

MKC253 is glucagon-like peptide 1 (GLP-1, 7-36 amide) adsorbed onto Technosphere microparticles for oral inhalation. The pharmacokinetics of inhaled GLP-1 and the pharmacokinetic-pharmacodynamic (PK-PD) relationship between inhaled GLP-1 and insulin were analyzed in two trials, one in healthy normal volunteers and the other in patients with type 2 diabetes. Inhaled GLP-1 was absorbed quickly, with peak concentrations occurring within 5 min, and levels returned to baseline within 30 min. Inhaled GLP-1 appeared to produce plasma levels of GLP-1 comparable to those of parenteral administration and sufficient to induce insulin secretion resulting in attenuation of postmeal glucose excursions in subjects with type 2 diabetes. An E(max) (maximum effect) model described the relationship between GLP-1 concentration and insulin release. The variability in the E(max) may be due to differences in baseline glucose levels, differences resulting from genetic polymorphisms in GLP-1 receptors (GLP-1Rs), or the stage of diabetes of the patient.

Simultaneous evaluation of renal morphology and function in live kidney donors using dynamic magnetic resonance imaging.

BACKGROUND: Evaluation of potential kidney donors requires the assessment of both kidney anatomy and function. In this prospective study, we sought to expand the diagnostic yield of magnetic resonance (MR) by adding functional measurements of glomerular filtration rate (GFR) and split renal function. METHODS: Between 2007 and 2009, all potential kidney donors presenting to our facility underwent a comprehensive single-stop MR study that included an assessment of anatomy, angiography and functional measurements. GFR was measured after a bolus injection of gadobutrol (4 ml, approximately 0.05 mmol/kg) and calculated from the washout of the signal intensity obtained over the liver. Split renal function was calculated from the increase of signal intensity over the renal cortex. Values were compared to renal scintigraphy with (99m)Tc-DTPA from the same day. RESULTS: The MR investigation was successfully performed in 21 participants. The GFR derived from MR (MR-GFR) correlated well (r = 0.84) with the GFR derived from scintigraphy (DTPA-GFR). The mean value of the paired differences was 4 +/- 13 [SD] ml/min/1.73 m(2) and was not significantly different from zero. The ratio between right and left kidney function was similar with both techniques (1.01 +/- 0.17 with MR and 1.06 +/- 0.12 with scintigraphy, P = 0.20). CONCLUSIONS: We demonstrate an MR-based approach to comprehensively evaluate both kidney anatomy and function in a single investigation, thereby facilitating the evaluation of potential kidney donors.

Switching on the lights for real-time multimodality tumor neuroimaging: The integrated positron-emission tomography/MR imaging system.

A recent report of the feasibility of simultaneous PET/MR imaging of the healthy human brain has sparked excitement in the field of neuroimaging because of its potential influence and utility in clinical neuroscience research. The aim of this communication is to discuss the benefits and current drawbacks of the hybrid imaging system and to highlight some perspectives of the new technique for brain neoplasms.

Pharmacokinetics and linear exposure of AFRESA compared with the subcutaneous injection of regular human insulin.

AIM: AFRESA [Technosphere Insulin (TI); MannKind Corporation, Valencia, CA], a dry powder preparation of regular human insulin (RHI), utilizes a novel and versatile drug carrier platform that enables pulmonary administration of medications typically administered by injection. The aim of this study was to compare the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of three different inhaled doses of TI with those of subcutaneous (s.c.) RHI. METHODS: This randomized, open-label, four-way crossover study of 11 healthy, non-smoking volunteers evaluated PK and PD profiles following single inhalations of 25, 50 or 100 U TI and 10 IU RHI administered subcutaneously using a euglycaemic clamp technique. RESULTS: Following inhalation of TI, peak insulin concentrations (C(max)) were achieved approximately 2 h earlier than with RHI (12-17 min for TI vs. 134 min for RHI). Area under the insulin concentration-time curve (AUC) and insulin C(max) values increased with increasing TI dose. Insulin exposure, as measured by AUC, was found to be linear over the dose range studied. Compared with s.c. RHI, TI at doses of 25, 50 and 100 U showed a relative bioavailability of 25, 23 and 21%, respectively. The maximum bioeffect, as measured by the glucose infusion rate, occurred approximately 2 h earlier for all three TI doses (42, 50 and 58 min, respectively) than for s.c. RHI (171 min). No treatment-related adverse events were reported with TI. CONCLUSION: TI is an inhaled insulin with a more rapid absorption and a more rapid elimination than subcutaneously administered RHI, resulting in a quick onset and short duration of action. Insulin exposure following TI administration was found to be linear over the dose range of 25-100 U.