Glucagon-like peptide-1 receptor imaging for the localisation of insulinomas: a prospective multicentre imaging study

BACKGROUND Small benign insulinomas are hard to localise, leading to difficulties in planning of surgical interventions. We aimed to prospectively assess the insulinoma detection rate of single-photon emission CT in combination with CT (SPECT/CT) with a glucagon-like peptide-1 receptor avid radiotracer, and compare detection rates with conventional CT/MRI techniques. METHODS In our prospective imaging study, we enrolled adults aged 25-81 years at centres in Germany, Switzerland, and the UK. Eligible patients had proven clinical and biochemical endogenous hyperinsulinaemic hypoglycaemia and no evidence for metastatic disease on conventional imaging. CT/MRI imaging was done at referring centres according to standard protocols. At three tertiary nuclear medicine centres, we used whole body planar images and SPECT/CT of the abdomen up to 168 h after injection of (111)In-[Lys40(Ahx-DTPA-(111)In)NH2]-exendin-4 ((111)In-DTPA-exendin-4) to identify insulinomas. Consenting patients underwent surgery and imaging findings were confirmed histologically. FINDINGS Between Oct 1, 2008, and Dec 31, 2011, we recruited 30 patients. All patients underwent (111)In-DTPA-exendin-4 imaging, 25 patients underwent surgery (with histological analysis), and 27 patients were assessed with CT/MRI. (111)In-DTPA-exendin-4 SPECT/CT correctly detected 19 insulinomas and four additional positive lesions (two islet-cell hyperplasia and two uncharacterised lesions) resulting in a positive predictive value of 83% (95% CI 62-94). One true negative (islet-cell hyperplasia) and one false negative (malignant insulinoma) result was identified in separate patients by (111)In-DTPA-exendin-4 SPECT/CT. Seven patients (23%) were referred to surgery on the basis of (111)In-DTPA-exendin-4 imaging alone. For 23 assessable patients, (111)In-DTPA-exendin-4 SPECT/CT had a higher sensitivity (95% [95% CI 74-100]) than did CT/MRI (47% [27-68]; p=0·011). INTERPRETATION (111)In-DTPA-exendin-4 SPECT/CT could provide a good second-line imaging strategy for patients with negative results on initial imaging with CT/MRI. FUNDING Oncosuisse, the Swiss National Science Foundation, and UK Department of Health.

Diagnostic Accuracy of Full-Body Linear X-Ray Scanning in Multiple Trauma Patients in Comparison to Computed Tomography

Purpose: The purpose of this study was to evaluate the diagnostic accuracy of full-body linear X-ray scanning (LS) in multiple trauma patients in comparison to 128-multislice computed tomography (MSCT). Materials and Methods: 106 multiple trauma patients (female: 33; male: 73) were retrospectively included in this study. All patients underwent LS of the whole body, including extremities, and MSCT covering the neck, thorax, abdomen, and pelvis. The diagnostic accuracy of LS for the detection of fractures of the truncal skeleton and pneumothoraces was evaluated in comparison to MSCT by two observers in consensus. Extremity fractures detected by LS were documented. Results: The overall sensitivity of LS was 49.2 %, the specificity was 93.3 %, the positive predictive value was 91 %, and the negative predictive value was 57.5 %. The overall sensitivity for vertebral fractures was 16.7 %, and the specificity was 100 %. The sensitivity was 48.7 % and the specificity 98.2 % for all other fractures. Pneumothoraces were detected in 12 patients by CT, but not by LS. 40 extremity fractures were detected by LS, of which 4 fractures were dislocated, and 2 were fully covered by MSCT. Conclusion: The diagnostic accuracy of LS is limited in the evaluation of acute trauma of the truncal skeleton. LS allows fast whole-body X-ray imaging, and may be valuable for detecting extremity fractures in trauma patients in addition to MSCT. Key Points: • The overall sensitivity of LS for truncal skeleton injuries in multiple-trauma patients was < 50 %.• The diagnostic reference standard MSCT is the preferred and reliable imaging modality.• LS may be valuable for quick detection of extremity fractures. Citation Format: • Jöres APW., Heverhagen JT, Bonél H et al. Diagnostic Accuracy of Full-Body Linear X-Ray Scanning in Multiple Trauma Patients in Comparison to Computed Tomography. Fortschr Röntgenstr 2016; 188: 163 - 171.

Research lines in Hyperthermia at the Bioinstrumentation Laboratory of the Centre for Biomedical Technology

The Bioinstrumentation Laboratory belongs to the Centre for Biomedical Technology (CTB) of the Technical University of Madrid and its main objective is to provide the scientific community with devices and techniques for the characterization of micro and nanostructures and consequently finding their best biomedical applications. Hyperthermia (greek word for “overheating”) is defined as the phenomenon that occurs when a body is exposed to an energy generating source that can produce a rise in temperature (42-45ºC) for a given time [1]. Specifically, the aim of the hyperthermia methods used in The Bioinstrumentation Laboratory is the development of thermal therapies, some of these using different kinds of nanoparticles, to kill cancer cells and reduce the damage on healthy tissues. The optical hyperthermia is based on noble metal nanoparticles and laser irradiation. This kind of nanoparticles has an immense potential associated to the development of therapies for cancer on account of their Surface Plasmon Resonance (SPR) enhanced light scattering and absorption. In a short period of time, the absorbed light is converted into localized heat, so we can take advantage of these characteristics to heat up tumor cells in order to obtain the cellular death [2]. In this case, the laboratory has an optical hyperthermia device based on a continuous wave laser used to kill glioblastoma cell lines (1321N1) in the presence of gold nanorods (Figure 1a). The wavelength of the laser light is 808 nm because the penetration of the light in the tissue is deeper in the Near Infrared Region. The first optical hyperthermia results show that the laser irradiation produces cellular death in the experimental samples of glioblastoma cell lines using gold nanorods but is not able to decrease the cellular viability of cancer cells in samples without the suitable nanorods (Figure 1b) [3]. The generation of magnetic hyperthermia is performed through changes of the magnetic induction in magnetic nanoparticles (MNPs) that are embedded in viscous medium. The Figure 2 shows a schematic design of the AC induction hyperthermia device in magnetic fluids. The equipment has been manufactured at The Bioinstrumentation Laboratory. The first block implies two steps: the signal selection with frequency manipulation option from 9 KHz to 2MHz, and a linear output up to 1500W. The second block is where magnetic field is generated ( 5mm, 10 turns). Finally, the third block is a software control where the user can establish initial parameters, and also shows the temperature response of MNPs due to the magnetic field applied [4-8]. The Bioinstrumentation Laboratory in collaboration with the Mexican company MRI-DT have recently implemented a new research line on Nuclear Magnetic Resonance Hyperthermia, which is sustained on the patent US 7,423,429B2 owned by this company. This investigation is based on the use of clinical MRI equipment not only for diagnosis but for therapy [9]. This idea consists of two main facts: Magnetic Resonance Imaging can cause focal heating [10], and the differentiation in resonant frequency between healthy and cancer cells [11]. To produce only heating in cancer cells when the whole body is irradiated, it is necessary to determine the specific resonant frequency of the target, using the information contained in the spectra of the area of interest. Then, special RF pulse sequence is applied to produce fast excitation and relaxation mechanism that generates temperature increase of the tumor, causing cellular death or metabolism malfunction that stops cellular division

Validation and aplication of Bioelectrical Impedance (BIA) method to determine body and carcass composition and nutrient retention of growing rabbits = Validación y aplicación de la técnica de la Impedancia Bioeléctrica (BIA) para determinar la composición corporal, de la canal y la retención de nutrientes de conejos en crecimiento

Los objetivos de esta tesis fueron 1) obtener y validar ecuaciones de predicción para determinar in vivo la composición corporal y de la canal de conejos en crecimiento de 25 a 77 días de vida utilizando la técnica de la Impedancia Bioeléctrica (BIA), y 2) evaluar su aplicación para determinar diferencias en la composición corporal y de la canal, así como la retención de nutrientes de animales alimentados con diferentes fuentes y niveles de grasa. El primer estudio se realizó para determinar y después validar, usando datos independientes, las ecuaciones de predicción obtenidas para determinar in vivo la composición corporal de los conejos en crecimiento. Se utilizaron 150 conejos a 5 edades distintas (25, 35, 49, 63 y 77 días de vida), con un rango de pesos entre 231 y 3138 g. Para determinar los valores de resistencia (Rs,) and reactancia (Xc,) se usó un terminal (Model BIA-101, RJL Systems, Detroit, MI USA) con cuatro electrodos. Igualmente se registró la distancia entre electrodos internos (D), la longitud corporal (L) y el peso vivo (PV) de cada animal. En cada edad, los animales fueron molidos y congelados (-20 ºC) para su posterior análisis químico (MS, grasa, proteína, cenizas y EB). El contenido en grasa y energía de los animales se incrementó, mientras que los contenidos en proteína, cenizas y agua de los animales disminuyeron con la edad. Los valores medios de Rs, Xc, impedancia (Z), L y D fueron 83.5 ± 23.1 , 18.2 ± 3.8 , 85.6 ± 22.9 , 30.6 ± 6.9 cm y 10.8 ± 3.1 cm. Se realizó un análisis de regresión lineal múltiple para determinar las ecuaciones de predicción, utilizando los valores de PV, L and Z como variables independientes. Las ecuaciones obtenidas para estimar los contenidos en agua (g), PB (g), grasa (g), cenizas (g) and EB (MJ) tuvieron un coeficiente de determinación de (R2) de 0.99, 0.99, 0.97, 0.98 y 0.99, y los errores medios de predicción relativos (EMPR) fueron: 2.79, 6.15, 24.3, 15.2 y 10.6%, respectivamente. Cuando el contenido en agua se expresó como porcentaje, los valores de R2 y EMPR fueron 0.85 and 2.30%, respectivamente. Al predecir los contenidos en proteína (%MS), grasa (%MS), cenizas (%MS) y energía (kJ/100 g MS), se obtuvieron valores de 0.79, 0.83, 0.71 y 0.86 para R2, y 5.04, 18.9, 12.0 y 3.19% para EMPR. La reactancia estuvo negativamente correlacionada con el contenido en agua, cenizas y PB (r = -0.32, P < 0.0001; r = -0.20, P < 0.05; r = -0.26, P < 0.01) y positivamente correlacionada con la grasa y la energía (r = 0.23 y r = 0.24; P < 0.01). Sin embargo, Rs estuvo positivamente correlacionada con el agua, las cenizas y la PB (r = 0.31, P < 0.001; r = 0.28, P < 0.001; r = 0.37, P < 0.0001) y negativamente con la grasa y la energía (r = -0.36 y r = -0.35; P < 0.0001). Igualmente la edad estuvo negativamente correlacionada con el contenido en agua, cenizas y proteína (r = -0.79; r = -0.68 y r = -0.80; P < 0.0001) y positivamente con la grasa y la energía (r = 0.78 y r = 0.81; P < 0.0001). Se puede concluir que el método BIA es una técnica buena y no invasiva para estimar in vivo la composición corporal de conejos en crecimiento de 25 a 77 días de vida. El objetivo del segundo estudio fue determinar y validar con datos independientes las ecuaciones de predicción obtenidas para estimar in vivo la composición de la canal eviscerada mediante el uso de BIA en un grupo de conejos de 25 a 77 días, así como testar su aplicación para predecir la retención de nutrientes y calcular las eficacias de retención de la energía y del nitrógeno. Se utilizaron 75 conejos agrupados en 5 edades (25, 35, 49, 63 y 77 días de vida) con unos pesos que variaron entre 196 y 3260 g. Para determinar los valores de resistencia (Rs, ) y reactancia (Xc, ) se usó un terminal (Model BIA-101, RJL Systems, Detroit, MI USA) con cuatro electrodos. Igualmente se registró la distancia entre electrodos internos (D), la longitud corporal (L) y el peso vivo (PV) del cada animal. En cada edad, los animales fueron aturdidos y desangrados. Su piel, vísceras y contenido digestivo fueron retirados, y la canal oreada fue pesada y molida para posteriores análisis (MS, grasa, PB, cenizas y EB). Los contenidos en energía y grasa aumentaron mientras que los de agua, cenizas y proteína disminuyeron con la edad. Los valores medios de Rs, Xc, impedancia (Z), L y D fueron 95.9±23.9 , 19.5±4.7 , 98.0±23.8 , 20.6±6.3 cm y 13.7±3.1 cm. Se realizó un análisis de regresión linear múltiple para determinar las ecuaciones de predicción, utilizando los valores de PV, L and Z como variables independientes. Los coeficientes de determinación (R2) de las ecuaciones obtenidas para estimar los contenidos en agua (g), PB (g), grasa (g), cenizas (g) and EB (MJ) fueron: 0.99, 0.99, 0.95, 0.96 y 0.98, mientras que los errores medios de predicción relativos (EMPR) fueron: 4.20, 5.48, 21.9, 9.10 y 6.77%, respectivamente. Cuando el contenido en agua se expresó como porcentaje, los valores de R2 y EMPR fueron 0.79 y 1.62%, respectivamente. Cuando se realizó la predicción de los contenidos en proteína (%MS), grasa (%MS), cenizas (%MS) y energía (kJ/100 g MS), los valores de R2 fueron 0.68, 0.76, 0.66 and 0.82, y los de RMPE: 3.22, 10.5, 5.82 and 2.54%, respectivamente. La reactancia estuvo directamente correlacionada con el contenido en grasa (r = 0.24, P < 0.05), mientras que la resistencia guardó una correlación positiva con los contenidos en agua, cenizas y proteína (r = 0.55, P < 0.001; r = 0.54, P < 0.001; r = 0.40, P < 0.005) y negativa con la grasa y la energía (r = -0.44 y r = -0.55; P < 0.001). Igualmente la edad estuvo negativamente correlacionada con los contenidos en agua, cenizas y PB (r = -0.94; r = -0.85 y r = -0.75; P < 0.0001) y positivamente con la grasa y la energía (r = 0.89 y r = 0.90; P < 0.0001). Se estudió la eficacia global de retención de la energía (ERE) y del nitrógeno (ERN) durante todo el periodo de cebo (35-63 d), Los valores de ERE fueron 20.4±7.29%, 21.0±4.18% and 20.8±2.79% en los periodos 35 a 49, 49 a 63 y 35 a 63 d, respectivamente. ERN fue 46.9±11.7%, 34.5±7.32% y 39.1±3.23% para los mismos periodos. La energía fue retenida en los tejidos para crecimiento con una eficiencia del 52.5% y la eficiencia de retención de la energía como proteína y grasa fue de 33.3 y 69.9% respectivamente. La eficiencia de utilización del nitrógeno para crecimiento fue cercana al 77%. Este trabajo muestra como el método BIA es técnica buena y no invasiva para determinar in vivo la composición de la canal y la retención de nutrientes en conejos en crecimiento de 25 a 77 días de vida. En el tercer estudio, se llevaron a cabo dos experimentos con el fin de investigar los efectos del nivel de inclusión y de la fuente de grasa, sobre los rendimientos productivos, la mortalidad, la retención de nutrientes y la composición corporal total y de la canal eviscerada de conejos en crecimiento de 34 a 63 d de vida. En el Exp. 1 se formularon 3 dietas con un diseño experimental factorial 3 x 2 con el tipo de grasa utilizada: Aceite de Soja (SBO), Lecitinas de Soja (SLO) y Manteca (L) y el nivel de inclusión (1.5 y 4%) como factores principales. El Exp. 2 también fue diseñado con una estructura factorial 3 x 2, pero usando SBO, Aceite de Pescado (FO) y Aceite de Palmiste como fuentes de grasa, incluidas a los mismos niveles que en el Exp. 1. En ambos experimentos 180 animales fueron alojados en jaulas individuales (n=30) y 600 en jaulas colectivas en grupos de 5 animales (n=20). Los animales alimentados con un 4% de grasa añadida tuvieron unos consumos diarios y unos índices de conversión más bajos que aquellos alimentados con las dietas con un 1.5% de grasa. En los animales alojados en colectivo del Exp. 1, el consumo fue un 4.8% más alto en los que consumieron las dietas que contenían manteca que en los animales alimentados con las dietas SBO (P = 0.036). La inclusión de manteca tendió a reducir la mortalidad (P = 0.067) en torno al 60% y al 25% con respecto a las dietas con SBO y SLO, respectivamente. La mortalidad aumentó con el nivel máximo de inclusión de SLO (14% vs. 1%, P < 0.01), sin observarse un efecto negativo sobre la mortalidad con el nivel más alto de inclusión de las demás fuentes de grasa utilizadas. En los animales alojados colectivo del Exp. 2 se encontró una disminución del consumo (11%), peso vivo a 63 d (4.8%) y de la ganancia diaria de peso (7.8%) con la inclusión de aceite de pescado con respecto a otras dietas (P < 0.01). Los dos últimos parámetros se vieron especialmente más reducidos cuando en las dietas se incluyó el nivel más alto de FO (5.6 y 9.5%, respectivamente, (P < 0.01)). Los animales alojados individualmente mostraron unos resultados productivos muy similares. La inclusión de aceite pescado tendió (P = 0.078) a aumentar la mortalidad (13.2%) con respecto al aceite de palmiste (6.45%), siendo intermedia para las dietas que contenían SBO (8.10%). La fuente o el nivel de grasa no afectaron la composición corporal total o de la canal eviscerada de los animales. Un incremento en el nivel de grasa dio lugar a una disminución de la ingesta de nitrógeno digestible (DNi) (1.83 vs. 1.92 g/d; P = 0.068 en Exp. 1 y 1.79 vs. 1.95 g/d; P = 0.014 en Exp. 2). Debido a que el nitrógeno retenido (NR) en la canal fue similar para ambos niveles (0.68 g/d (Exp. 1) y 0.71 g/d (Exp. 2)), la eficacia total de retención del nitrógeno (ERN) aumentó con el nivel máximo de inclusión de grasa, pero de forma significativa únicamente en el Exp. 1 (34.9 vs. 37.8%; P < 0.0001), mientras que en el Exp. 2 se encontró una tendencia (36.2 vs. 38.0% en Exp. 2; P < 0.064). Como consecuencia, la excreción de nitrógeno en heces fue menor en los animales alimentados con el nivel más alto de grasa (0.782 vs. 0.868 g/d; P = 0.0001 en Exp. 1, y 0.745 vs. 0.865 g/d; P < 0.0001 en Exp.2) al igual que el nitrógeno excretado en orina (0.702 vs. 0.822 g/d; P < 0.0001 en Exp. 1 y 0.694 vs. 0.7999 g/d; P = 0.014 en Exp.2). Aunque no hubo diferencias en la eficacia total de retención de la energía (ERE), la energía excretada en heces disminuyó al aumentar el nivel de inclusión de grasa (142 vs. 156 Kcal/d; P = 0.0004 en Exp. 1 y 144 vs. 154 g/d; P = 0.050 en Exp. 2). Sin embargo, la energía excretada como orina y en forma de calor fue mayor en el los animales del Exp. 1 alimentados con el nivel más alto de grasa (216 vs. 204 Kcal/d; P < 0.017). Se puede concluir que la manteca y el aceite de palmiste pueden ser considerados como fuentes alternativas al aceite de soja debido a la reducción de la mortalidad, sin efectos negativos sobre los rendimientos productivos o la retención de nutrientes. La inclusión de aceite de pescado empeoró los rendimientos productivos y la mortalidad durante el periodo de crecimiento. Un aumento en el nivel de grasa mejoró el índice de conversión y la eficacia total de retención de nitrógeno. ABSTRACT The aim of this Thesis is: 1) to obtain and validate prediction equations to determine in vivo whole body and carcass composition using the Bioelectrical Impedance (BIA) method in growing rabbits from 25 to 77 days of age, and 2) to study its application to determine differences on whole body and carcass chemical composition, and nutrient retention of animals fed different fat levels and sources. The first study was conducted to determine and later validate, by using independent data, the prediction equations obtained to assess in vivo the whole body composition of growing rabbits. One hundred and fifty rabbits grouped at 5 different ages (25, 35, 49, 63 and 77 days) and weighing from 231 to 3138 g were used. A four terminal body composition analyser was used to obtain resistance (Rs, ) and reactance (Xc, ) values (Model BIA-101, RJL Systems, Detroit, MI USA). The distance between internal electrodes (D, cm), body length (L, cm) and live BW of each animal were also registered. At each selected age, animals were slaughtered, ground and frozen (-20 ºC) for later chemical analyses (DM, fat, CP, ash and GE). Fat and energy body content increased with the age, while protein, ash, and water decreased. Mean values of Rs, Xc, impedance (Z), L and D were 83.5 ± 23.1 , 18.2 ± 3.8 , 85.6 ± 22.9 , 30.6 ± 6.9 cm and 10.8 ± 3.1 cm. A multiple linear regression analysis was used to determine the prediction equations, using BW, L and Z data as independent variables. Equations obtained to estimate water (g), CP (g), fat (g), ash (g) and GE (MJ) content had, respectively, coefficient of determination (R2) values of 0.99, 0.99, 0.97, 0.98 and 0.99, and the relative mean prediction error (RMPE) was: 2.79, 6.15, 24.3, 15.2 and 10.6%, respectively. When water was expressed as percentage, the R2 and RMPE were 0.85 and 2.30%, respectively. When prediction of the content of protein (%DM), fat (%DM), ash (%DM) and energy (kJ/100 g DM) was done, values of 0.79, 0.83, 0.71 and 0.86 for R2, and 5.04, 18.9, 12.0 and 3.19% for RMPE, respectively, were obtained. Reactance was negatively correlated with water, ash and CP content (r = -0.32, P < 0.0001; r = -0.20, P < 0.05; r = -0.26, P < 0.01) and positively correlated with fat and GE (r = 0.23 and r = 0.24; P < 0.01). Otherwise, resistance was positively correlated with water, ash and CP (r = 0.31, P < 0.001; r = 0.28, P < 0.001; r = 0.37, P < 0.0001) and negatively correlated with fat and energy (r = -0.36 and r = -0.35; P < 0.0001). Moreover, age was negatively correlated with water, ash and CP content (r = -0.79; r = -0.68 and r = -0.80; P < 0.0001) and positively correlated with fat and energy (r = 0.78 and r = 0.81; P < 0.0001). It could be concluded that BIA is a non-invasive good method to estimate in vivo whole body composition of growing rabbits from 25 to 77 days of age. The aim of the second study was to determine and validate with independent data, the prediction equations obtained to estimate in vivo carcass composition of growing rabbits by using the results of carcass chemical composition and BIA values in a group of rabbits from 25 to 77 days. Also its potential application to predict nutrient retention and overall energy and nitrogen retention efficiencies was analysed. Seventy five rabbits grouped at 5 different ages (25, 35, 49, 63 and 77 days) with weights ranging from 196 to 3260 g were used. A four terminal body composition analyser (Model BIA-101, RJL Systems, Detroit, MI USA) was used to obtain resistance (Rs, ) and reactance (Xc, ) values. The distance between internal electrodes (D, cm), body length (L, cm) and live weight (BW, g) were also registered. At each selected age, all the animals were stunned and bled. The skin, organs and digestive content were removed, and the chilled carcass were weighed and processed for chemical analyses (DM, fat, CP, ash and GE). Energy and fat increased with the age, while CP, ash, and water decreased. Mean values of Rs, Xc, impedance (Z), L and D were 95.9±23.9 , 19.5±4.7 , 98.0±23.8 , 20.6±6.3 cm y 13.7±3.1 cm. A multiple linear regression analysis was done to determine the equations, using BW, L and Z data as parameters. Coefficient of determination (R2) of the equations obtained to estimate water (g), CP (g), fat (g), ash (g) and GE (MJ) content were: 0.99, 0.99, 0.95, 0.96 and 0.98, and relative mean prediction error (RMPE) were: 4.20, 5.48, 21.9, 9.10 and 6.77%, respectively. When water content was expressed as percentage, the R2 and RMPE were 0.79 and 1.62%, respectively. When prediction of protein (%DM), fat (%DM), ash (%DM) and energy (kJ/100 g DM) content was done, R2 values were 0.68, 0.76, 0.66 and 0.82, and RMPE: 3.22, 10.5, 5.82 and 2.54%, respectively. Reactance was positively correlated with fat content (r = 0.24, P < 0.05) while resistance was positively correlated with water, ash and protein carcass content (r = 0.55, P < 0.001; r = 0.54, P < 0.001; r = 0.40, P < 0.005) and negatively correlated with fat and energy (r = -0.44 and r = -0.55; P < 0.001). Moreover, age was negatively correlated with water, ash and CP content (r = -0.97, r = -0.95 and r = -0.89, P < 0.0001) and positively correlated with fat and GE (r = 0.95 and r = 0.97; P < 0.0001). In the whole growing period (35-63 d), overall energy retention efficiency (ERE) and nitrogen retention efficiency (NRE) were studied. The ERE values were 20.4±7.29%, 21.0±4.18% and 20.8±2.79%, from 35 to 49, 49 to 63 and from 35 to 63 d, respectively. NRE was 46.9±11.7%, 34.5±7.32% and 39.1±3.23% for the same periods. Energy was retained in body tissues for growth with an efficiency of approximately 52.5% and efficiency of the energy for protein and fat retention was 33.3 and 69.9%, respectively. Efficiency of utilization of nitrogen for growth was near to 77%. This work shows that BIA it’s a non-invasive and good method to estimate in vivo carcass composition and nutrient retention of growing rabbits from 25 to 77 days of age. In the third study, two experiments were conducted to investigate the effect of the fat addition and source, on performance, mortality, nutrient retention, and the whole body and carcass chemical composition of growing rabbits from 34 to 63 d. In Exp. 1 three diets were arranged in a 3 x 2 factorial structure with the source of fat: Soybean oil (SBO), Soya Lecithin Oil (SLO) and Lard (L) and the dietary fat inclusion level (1.5 and 4%) as the main factors. Exp. 2 had also arranged as a 3 x 2 factorial design, but using SBO, Fish Oil (FO) and Palmkernel Oil (PKO) as fat sources, and included at the same levels than in Exp. 1. In both experiments 180 animals were allocated in individual cages (n=30) and 600 in collectives cages, in groups of 5 animals (n=20). Animals fed with 4% dietary fat level showed lower DFI and FCR than those fed diets with 1.5%. In collective housing of Exp. 1, DFI was a 4.8% higher in animals fed with diets containing lard than SBO (P = 0.036), being intermediate for diet with SLO. Inclusion of lard also tended to reduce mortality (P = 0.067) around 60% and 25% with respect SBO and SLO diets, respectively. Mortality increased with the greatest level of soya lecithin (14% vs. 1%, P < 0.01). In Exp. 2 a decrease of DFI (11%), BW at 63 d (4.8%) and DWG (7.8%) were observed with the inclusion of fish oil with respect the other two diets (P < 0.01). These last two traits impaired with the highest level of fish oil (5.6 and 9.5%, respectively, (P < 0.01)). Animals housed individually showed similar performance results. The inclusion of fish oil also tended to increase (P = 0.078) mortality (13.2%) with respect palmkernel oil (6.45%), being mortality of SBO intermediate (8.10%). Fat source and level did not affect the whole body or carcass chemical composition. An increase of the fat sources addition led to a decrease of the digestible nitrogen intake (DNi) (1.83 vs. 1.92 g/d; P = 0.068 in Exp. 1 and 1.79 vs. 1.95 g/d; P = 0.014 in Exp. 2). As the nitrogen retained (NR) in the carcass was similar for both fat levels (0.68 g/d (Exp. 1) and 0.71 g/d (Exp. 2)), the overall efficiency of N retention (NRE) increased with the highest level of fat, but only reached significant level in Exp. 1 (34.9 vs. 37.8%; P < 0.0001), while in Exp. 2 a tendency was found (36.2 vs. 38.0% in Exp. 2; P < 0.064). Consequently, nitrogen excretion in faeces was lower in animals fed with the highest level of fat (0.782 vs. 0.868 g/d; P = 0.0001 in Exp. 1, and 0.745 vs. 0.865 g/d; P < 0.0001 in Exp.2). The same effect was observed with the nitrogen excreted as urine (0.702 vs. 0.822 g/d; P < 0.0001 in Exp. 1 and 0.694 vs. 0.7999 g/d; P = 0.014 in Exp.2). Although there were not differences in ERE, the energy excreted in faeces decreased as fat level increased (142 vs. 156 Kcal/d; P = 0.0004 in Exp. 1 and 144 vs. 154 g/d; P = 0.050 in Exp. 2). In Exp. 1 the energy excreted as urine and heat production was significantly higher when animals were fed with the highest level of dietary fat (216 vs. 204 Kcal/d; P < 0.017). It can be concluded that lard and palmkernel oil can be considered as alternative sources to soybean oil due to the reduction of the mortality, without negative effects on performances or nutrient retention. Inclusion of fish impaired animals´ productivity and mortality. An increase of the dietary fat level improved FCR and overall protein efficiency retention.

Tumores indutores de osteomalácia: diagnóstico, caracterização tumoral e avaliação evolutiva em longo prazo de nove pacientes

INTRODUÇÃO: Tumores indutores de osteomalácia (TIOs) são raros, geralmente apresentam origem mesenquimal, têm produção excessiva de fosfatoninas sendo a mais comum o FGF23 (Fibroblast Growth Factor 23) que, em níveis elevados, provoca osteomalácia hipofosfatêmica. A cura dos TIOs envolve a remoção completa do tumor, o que torna essencial sua localização. OBJETIVOS: (1) caracterizar nove pacientes com TIO ao diagnóstico e avaliá-los evolutivamente em longo prazo; (2) avaliar a eficácia da cintilografia com Octreotida (Octreoscan®) e a da cintilografia de corpo inteiro com Mibi (MIBI) na detecção dos TIOs. MÉTODOS: O acompanhamento dos pacientes consistiu na avaliação clínica, na avaliação laboratorial com ênfase no metabolismo ósseo e na realização de exames de imagem para caracterização das deformidades esqueléticas. Para a localização dos TIOs, os pacientes foram submetidos a exames de Octreoscan®, MIBI, ressonância magnética (RM) e tomografia computadorizada (TC). RESULTADOS: O período de observação dos pacientes variou de dois a 25 anos. Ao diagnóstico, todos exibiam fraqueza muscular, dores ósseas e fraturas de fragilidade. Em relação à avaliação laboratorial, apresentavam: hipofosfatemia com taxa de reabsorção tubular de fosfato reduzida, fosfatase alcalina aumentada e níveis elevados de FGF23. O Octreoscan® permitiu a identificação dos TIOs nos nove pacientes e o MIBI possibilitou a localização dos TIOs em seis pacientes, sendo que ambos os exames foram concordantes entre si e com os exames topográficos (RM ou TC). Os achados histopatológicos das lesões dos nove pacientes confirmaram tratar-se de oito tumores mesenquimais fosfatúricos (PMTs) benignos e um PMT maligno. Após a primeira intervenção cirúrgica para a remoção dos TIOs, quatro pacientes encontram-se em remissão da doença e cinco evoluíram com persistência tumoral. Dos cinco, quatro foram reoperados e um aguarda nova cirurgia. Dos que foram reoperados, um paciente se mantém em remissão da doença, um foi a óbito por complicações clínicas, uma teve doença metastática e o último apresentou recidiva tumoral três anos após a segunda cirurgia. Deformidades ósseas graves foram observadas nos pacientes cujo diagnóstico e/ou tratamento clínico foram tardios. O tratamento da osteomalácia foi iniciado com fosfato e perdurou até a ressecção tumoral, tendo sido reintroduzido nos casos de persistência/recidiva tumoral. Quatro pacientes que fizerem uso regular desse medicamento por mais de seis anos evoluíram com hiperparatireoidismo terciário (HPT). CONCLUSÕES: O estudo revelou que tanto o Octreoscan® como o MIBI foram capazes de localizar os TIOs. Por isso, incentivamos a realização do MIBI nos locais onde o Octreoscan® não for disponível. Uma equipe experiente é indispensável para o sucesso cirúrgico visto que os tumores, embora benignos, costumam ser infiltrativos. Recomendamos o seguimento por tempo indeterminado em função do risco de recidiva tumoral. Assim como o FGF23, consideramos o fósforo um excelente marcador de remissão, persistência e recidiva dos TIOs. O diagnóstico e o tratamento precoce são fundamentais para a melhora dos sintomas podendo minimizar as deformidades esqueléticas e as sequelas ósseas. O uso prolongado do fosfato no tratamento da osteomalácia hipofosfatêmica foi associado ao desenvolvimento do HPT

Post-mortem CT and MR brain imaging of putrefied corpses

INTRODUCTION Putrefaction of the brain is a challenge to a forensic pathologist because it may lead to considerable organ alterations and restrict documenting reliable autopsy findings. OBJECTIVES This study aims to present a new and systematic evaluation of possible benefits of post-mortem MR Neuroimaging (1.5 Tesla, sequences: T1w, T2w) in putrefied corpses in comparison to PMCT and autopsy. METHODS A post-mortem MRI brain examination was conducted on 35 adult, putrefied corpses after performing a whole body CT scan prior to a forensic autopsy. Imaging data and autopsy findings were compared with regard to brain symmetry, gray and white matter junction, ventricular system, basal ganglia, cerebellum, brain stem, and possible pathological findings. RESULTS At autopsy, a reliable assessment of the anatomical brain structures was often restricted. MR imaging offered an assessment of the anatomical brain structures, even at advanced stages of putrefaction. In two cases, MR imaging revealed pathological findings that were detectable neither by CT scans nor at autopsy. CONCLUSIONS Post-mortem MR imaging of putrefied brains offers the possibility to assess brain morphology, even if the brain is liquefied. Post-mortem MR imaging of the brain should be considered if the assessment of a putrefied brain is crucial to the evaluation of a forensic autopsy case.

Changes in body water distribution during treatment with inhaled steroid in pre-school children

Primary objective: The study aimed to examine the changes in water distribution in the soft tissue during systemic steroid activity. Research design: A three-way cross-over, randomized, placebo-controlled, double-blind trial was used, including 4 weeks of fluticasone propionate pMDI 200 mug b.i.d. delivered via Babyhaler(R), budesonide pressurized metered dose inhaler (pMDI) 200 mug b.i.d. delivered via Nebuchamber(R) and placebo. Spacers were primed before use. In total, 40 children aged 1-3 years, with mild intermittent asthma were included. Twenty-five of the children completed all three treatments. At the end of each treatment period body impedance and skin ultrasonography were measured. Methods and procedures: We measured changes in water content of the soft tissues by two methods. Skin ultrasonography was used to detect small changes in dermal water content, and bioelectrical impedance was used to assess body water content and distribution. Main outcomes and results: We found an increase in skin density of the shin from fluticasone as measured by ultrasonography (p = 0.01). There was a tendency for a consistent elevation of impedance parameters from active treatments compared to placebo although overall this effect was not statistically significant (0.1< p <0.2). However, sub-analyses indicated a significant effect on whole-body and leg impedance from budesonide treatment (p <0.05). Conclusion: Decreased growth during inhaled steroid treatment seems to partly reflect generalized changes in body water.

Magnetic resonance microscopy of the equine hoof wall: a study of resolution and potential

Reasons for performing study: Obtaining magnetic resonance images of the inner hoof wall tissue at the microscopic level would enable early accurate diagnosis of laminitis and therefore more effective therapy. Objectives: To optimise magnetic resonance imaging (MRI) parameters in order to obtain the highest possible resolution of the structures beneath the equine hoof wall. Methods: Magnetic resonance microscopy (MRM) was performed in front feet from 6 cadaver horses using T-2-weighted fast spin echo (FSE-T-2), and T-1-weighted gradient echo (GRE-T-1) sequences. Results: In T-2 weighted FSE images most of the stratum medium showed no signal, however the coronary, terminal and sole papillae were visible. The stratum lamellatum was clearly visible and primary epidermal lamellae could be differentiated from dermal lamellae. Conclusion: Most structures beneath the hoof wall were differentiated. Conventional scanners for diagnostic MRI in horses are low or high field. However this study used ultra-high field scanners currently not available for clinical use. Signal-to-noise ratio (SIN) increases as a function of field strength. An increase of spatial resolution of the image results in a decreased SIN. SIN can also be improved with better coils and the resolution of high field MRI scanners will increase as technology develops and surface array coils become more readily available. Potential relevance: Although MR images with microscopic resolution were obtained ex vivo, this study demonstrates the potential for detection of lamellar pathology as it occurs. Early recognition of the development of laminitis to instigate effective therapy at an earlier stage and may improve the outcome for laminitic horses. Clinical MR is now readily available at 3 T, while 4 T, 7 T and 9 T systems are being used for human whole body applications.

Cerebrotendinous xanthomatosis with bradyphrenia and psychiatric disorders: a case with 18F-FDG PET imaging and a literature review

Background and Objectives: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid-storage disease caused by mutations in the CYP27A1. The purpose of this study is to determine the clinical characteristics, neuroimaging and mutation detect in a family with CTX systematically. Methods: Collecting history materials and detecting the routine clinical biochemical tests and imaging examination, and for the first time taking the whole body positron emission tomography (PET)-CT examination for probed in the world to research abnormal metabolism activities in CTX. To observe the effect of treatment with chenodeoxycholic acid (CDCA) and stains before and after the intervention, using serum lipid level detection and neuropsychological evaluation. Genetic testing was carried out to screen the nine exons and exon-intron boundaries about 200-300bq of CYP27A1. Results: A 37-year-old woman with typical clinical characteristics of CTX. Magnetic resonance imaging (MRI) of brain showed bilateral lesions in the dentate nucleus of the cerebellum, then, PET images revealed multiple abnormal hypermetabolism areas at distal tendon, and multifocal areas of hypometabolism in bilateral sides of cerebellar hemispheres, the frontal lobe and temporal lobe. Histopathology reveals accumulation of xanthoma cells and dispersed lipid crystal clefts in xanthomas. In genetic analysis, it shown an insertion of cytosine (77-78insC) located in the first exon of CYP27A1 in the proband. Conclusions: We found that a Chinese patient presented a typical clinical feature of CTX along with clear correlation on both structural and functional imaging had a novel mutation in the CYP27A1 gene.

Comparison of two field methods for estimating body fat in different Spanish Dance disciplines

The purpose of the present study was to investigate percentage body fat (%BF) differences in three Spanish dance disciplines and to compare skinfold and bioelectrical impedance predictions of body fat percentage in the same sample. Seventy-six female dancers, divided into three groups, Classical (n=23), Spanish (n=29) and Flamenco (n=24), were measured using skinfold measurements at four sites: triceps, subscapular, biceps and iliac crest, and whole body multi-frequency bioelectrical impedance (BIA). The skin-fold measures were used to predict body fat percentage via Durnin and Womersley's and Segal, Sun and Yannakoulia equations by BIA. Differences in percent fat mass between groups (Classical, Spanish and Flamenco) were tested by using repeated measures analysis (ANOVA). Also, Pearson's product-moment correlations were performed on the body fat percentage values obtained using both methods. In addition, Bland-Altman plots were used to assess agreement, between anthropometric and BIA methods. Repeated measures analysis of variance did not found differences in %BF between modalities (p<0.05). Fat percentage correlations ranged from r= 0.57 to r=0.97 (all, p<0.001). Bland-Altman analysis revealed differences between BIA Yannakoulia as a reference method with BIA Segal (-0.35 ± 2.32%, 95%CI: -0.89to 0.18, p=0.38), with BIA Sun (-0.73 ± 2.3%, 95%CI: -1.27 to -0.20, p=0.014) and Durnin-Womersley (-2.65 ± 2,48%, 95%CI: -3.22 to -2.07, p<0.0001). It was concluded that body fat percentage estimates by BIA compared with skinfold method were systematically different in young adult female ballet dancers, having a tendency to produce underestimations as %BF increased with Segal and Durnin-Womersley equations compared to Yannakoulia, concluding that these methods are not interchangeable.

Body composition changes assessed by bioelectrical impedance and their associations with functional class deterioration in stable heart failure patients

Background: Heart failure (HF) patients develop important changes in body composition, but only a small number of studies have evaluated the associations between these changes and functional class deterioration in a prospective manner. Objective: The aim of this study was to evaluate whether changes in bioimpedance parameters were associated with NYHA functional class deterioration over six months. Methods: A total of 275 chronic stable HF patients confirmed by echocardiography were recruited. Body composition measurements were obtained by whole body bioelectrical impedance with multiple frequency equipment (BodyStat QuadScan 4000). We evaluated functional class using the New York Heart Association (NYHA) classification at baseline and after six months. Results: According to our results, 66 (24%) subjects exhibited functional class deterioration, while 209 improved or exhibited no change. A greater proportion of patients exhibited higher extracellular water (> 5%), and these patients developed hypervolemia, according to location on the resistance/reactance graph. A 5% decrease in resistance/height was associated with functional class deterioration with an OR of 1.42 (95% CI 1.01-2.0, p = 0.04). Conclusions: Body composition assessment through bioelectrical impedance exhibited a valuable performance as a marker of functional class deterioration in stable HF patients.

Ethnic differences in the BMI-%BF relationships between young Japanese and Australian-Caucasian males living in Australia using dual-energy X-ray absorptiometry

The Body Mass Index (BMI) has been used worldwide as an indicator of fatness. However, the universal cut-off points by the World Health Organisation (WHO) classification may not be appropriate for every ethnic group when consider the relationship with their actual total body fatness(%BF). The application of population-specific classifications to assess BMI may be more relevant to public health. Ethnic differences in the BMI%BF relationship between 45 Japanese and 42 Australian-Caucasian males were assessed using whole body dual-energy X-ray absorptiometry (DXA) scan and anthropometry using a standard protocol. Japanese males had significantly (p<0.05) greater %BF at given BMI values than Australian males. When this is taken into account the newly proposed Asia-Pacific BMI classification of BMI 23 as overweight and 25 as obese may better assess the level of obesity that is associated increased health risks for this population. To clarify the current findings, further studies that compare the relationships across other Japanese populations are recommended.

The skin awareness study : promoting thorough skin self-examination for skin cancer among men 50 years or older

Background: Incidence and mortality from skin cancers including melanoma are highest among men 50 years or older. Thorough skin self-examination may be beneficial to improve skin cancers outcomes.--------- Objectives: To develop and conduct a randomized-controlled trial of a video-based intervention to improve skin self-examination behavior among men 50 years or older.--------- Methods: Pilot work ascertained appropriate targeting of the 12-minute intervention video towards men 50 years or older. Overall, 968 men were recruited and 929 completed baseline telephone assessment. Baseline analysis assessed randomization balance and demographic, skin cancer risk and attitudinal factors associated with conducting a whole-body skin self-examination or receiving a whole-body clinical skin examination by a doctor during the past 12 months.--------- Results: Randomization resulted in well-balanced intervention and control groups. Overall 13% of men reported conducting a thorough skin self-examination using a mirror or the help of another person to check difficult to see areas, while 39% reported having received a whole-body skin examination by a doctor within the past 12 months. Confidence in finding time for and receiving advice or instructions by a doctor to perform a skin self-examination were among the factors associated with thorough skin self-examination at baseline.---------- Conclusions: Men 50 years or older can successfully be recruited to a video-based intervention trial with the aim reduce their burden through skin cancer. Randomization by computer generated randomization list resulted in good balance between control and intervention group and baseline analysis determined factors associated with skin cancer early detection behavior at baseline.

Image acquisition and manipulation protocols for CT-PET fusion to improve the accuracy of gross tumour volume localisation for 3D conformal radiotherapy for lung cancer

Aims: To develop clinical protocols for acquiring PET images, performing CT-PET registration and tumour volume definition based on the PET image data, for radiotherapy for lung cancer patients and then to test these protocols with respect to levels of accuracy and reproducibility. Method: A phantom-based quality assurance study of the processes associated with using registered CT and PET scans for tumour volume definition was conducted to: (1) investigate image acquisition and manipulation techniques for registering and contouring CT and PET images in a radiotherapy treatment planning system, and (2) determine technology-based errors in the registration and contouring processes. The outcomes of the phantom image based quality assurance study were used to determine clinical protocols. Protocols were developed for (1) acquiring patient PET image data for incorporation into the 3DCRT process, particularly for ensuring that the patient is positioned in their treatment position; (2) CT-PET image registration techniques and (3) GTV definition using the PET image data. The developed clinical protocols were tested using retrospective clinical trials to assess levels of inter-user variability which may be attributed to the use of these protocols. A Siemens Somatom Open Sensation 20 slice CT scanner and a Philips Allegro stand-alone PET scanner were used to acquire the images for this research. The Philips Pinnacle3 treatment planning system was used to perform the image registration and contouring of the CT and PET images. Results: Both the attenuation-corrected and transmission images obtained from standard whole-body PET staging clinical scanning protocols were acquired and imported into the treatment planning system for the phantom-based quality assurance study. Protocols for manipulating the PET images in the treatment planning system, particularly for quantifying uptake in volumes of interest and window levels for accurate geometric visualisation were determined. The automatic registration algorithms were found to have sub-voxel levels of accuracy, with transmission scan-based CT-PET registration more accurate than emission scan-based registration of the phantom images. Respiration induced image artifacts were not found to influence registration accuracy while inadequate pre-registration over-lap of the CT and PET images was found to result in large registration errors. A threshold value based on a percentage of the maximum uptake within a volume of interest was found to accurately contour the different features of the phantom despite the lower spatial resolution of the PET images. Appropriate selection of the threshold value is dependant on target-to-background ratios and the presence of respiratory motion. The results from the phantom-based study were used to design, implement and test clinical CT-PET fusion protocols. The patient PET image acquisition protocols enabled patients to be successfully identified and positioned in their radiotherapy treatment position during the acquisition of their whole-body PET staging scan. While automatic registration techniques were found to reduce inter-user variation compared to manual techniques, there was no significant difference in the registration outcomes for transmission or emission scan-based registration of the patient images, using the protocol. Tumour volumes contoured on registered patient CT-PET images using the tested threshold values and viewing windows determined from the phantom study, demonstrated less inter-user variation for the primary tumour volume contours than those contoured using only the patient’s planning CT scans. Conclusions: The developed clinical protocols allow a patient’s whole-body PET staging scan to be incorporated, manipulated and quantified in the treatment planning process to improve the accuracy of gross tumour volume localisation in 3D conformal radiotherapy for lung cancer. Image registration protocols which factor in potential software-based errors combined with adequate user training are recommended to increase the accuracy and reproducibility of registration outcomes. A semi-automated adaptive threshold contouring technique incorporating a PET windowing protocol, accurately defines the geometric edge of a tumour volume using PET image data from a stand alone PET scanner, including 4D target volumes.

Throwing frame and performance of elite male seated shot-putters

Seated shot-putters rely on a customized assistive device called a throwing frame. Currently, the construction of each individual throwing frame is mainly driven by an empirical approach. One way to refine the conception is to improve the basic understanding of performance of seated shot-putters. The relationship between performance and throwing technique has been well described. Remarkably, the relationship between performance and throwing frame characteristics has received limited attention. The primary objective of this study was to present a cataloguing of characteristics of throwing frames used by seated shot-putters. This cataloguing consisted of defining and grouping 26 characteristics into three main categories (i.e., whole body, foot and upper limb specific characteristics) and seven sub-categories. The secondary objective of this study was to provide raw characterisations of the throwing frames for a group of athletes who participated in a world-class event. The characterisation consisted of describing the characteristics of each throwing frame. Potential relationships between characteristics, performance and classification were also identified. The cataloguing was achieved using a 6-step heuristic approach, involving expert opinions and the analysis of 215 attempts produced by 55 male athletes during the 2006 IPC Athletics World Championships. The distribution of samples across characteristics suggested a relevant level of comprehensiveness for the proposed cataloguing. The raw data, the profile of best athletes and the frequency of characteristics provided key benchmark information for construction of a throwing frame as well as coaching, classification and officiating. Analysis of data sets relating to characteristics, performance and classification were inconclusive.