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1.
Nucl Med Biol ; 52: 63-69, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28648984

ABSTRACT

The endocannabinoid system participates in many processes in the body, including memory, reward, pain, motor activity, food intake, energy metabolism, and gastrointestinal functions. [18F]MK-9470 is a positron emission tomography (PET) ligand that binds with high affinity and selectivity to the cannabinoid type 1 receptor. In order to fully characterize ligand behavior, tracer uptake measured using in vivo microPET was compared with results from ex vivo tissue dissection. Twelve male Sprague-Dawley rats were divided into three subgroups and scanned over time periods of 10min, 30min and 90min using PET. Afterwards, a number of the animals' organs were dissected. Uptake of radioactivity was expressed in terms of %ID/ml and %ID/(g tissue). For comparison of in vivo and ex vivo methods, Bland-Altman plots were computed. The highest uptake of [18F]MK-9470 was found in the liver and small intestine; the brain showed less uptake, while low and unspecific binding was observed in tissue of the heart, lung, kidney and bone. In the brain, normalized uptake of [18F]MK-9470 was on average 0.25%ID/ml (range: 0.16 to 0.28%ID/ml). Bland-Altman plots revealed the best agreement between methods for the 90min acquisition protocols. High hepatic accumulation and metabolism of [18F]MK-9470 occur with mainly enteral excretion, which may vary considerably over time - a finding which may be of relevance in metabolite determination in quantitative brain studies. Comparisons between in vivo and ex vivo methods showed that whole-body distribution of [18F]MK-9470 using positron emission tomography is a preferable alternative to ex vivo biodistribution, and requires a significantly smaller number of animals.


Subject(s)
Pyridines/pharmacokinetics , Receptor, Cannabinoid, CB1/metabolism , Animals , Ligands , Male , Positron-Emission Tomography , Pyridines/metabolism , Rats , Rats, Sprague-Dawley , Tissue Distribution
2.
Chemosphere ; 159: 619-627, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27344605

ABSTRACT

The multimedia model SimpleTreat, evaluates the distribution and elimination of chemicals by municipal sewage treatment plants (STP). It is applied in the framework of REACH (Registration, Evaluation, Authorization and Restriction of Chemicals). This article describes an adaptation of this model for application to industrial sewage treatment plants (I-STP). The intended use of this re-parametrized model is focused on risk assessment during manufacture and subsequent uses of chemicals, also in the framework of REACH. The results of an inquiry on the operational characteristics of industrial sewage treatment installations were used to re-parameterize the model. It appeared that one property of industrial sewage, i.e. Biological Oxygen Demand (BOD) in combination with one parameter of the activated sludge process, the hydraulic retention time (HRT) is satisfactory to define treatment of industrial wastewater by means of the activated sludge process. The adapted model was compared to the original municipal version, SimpleTreat 4.0, by means of a sensitivity analysis. The consistency of the model output was assessed by computing the emission to water from an I-STP of a set of fictitious chemicals. This set of chemicals exhibit a range of physico-chemical and biodegradability properties occurring in industrial wastewater. Predicted removal rates of a chemical from raw sewage are higher in industrial than in municipal STPs. The latter have typically shorter hydraulic retention times with diminished opportunity for elimination of the chemical due to volatilization and biodegradation.


Subject(s)
Environmental Monitoring/methods , Models, Chemical , Waste Disposal, Fluid , Water Pollutants, Chemical/analysis , Biodegradation, Environmental , Biological Oxygen Demand Analysis , Models, Theoretical , Sewage/chemistry , Volatilization , Wastewater/chemistry , Water Pollutants, Chemical/chemistry
3.
Am J Transplant ; 15(8): 2256-60, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25872800

ABSTRACT

Lung transplantation (LTx) may be denied for children on extracorporeal membrane oxygenation (ECMO) due to high risk of cerebral hemorrhage. Rarely has successful LTx been reported in children over 10 years of age receiving awake or ambulatory veno-venous ECMO. LTx following support with ambulatory veno-arterial ECMO (VA ECMO) in children has never been reported to our knowledge. We present the case of a 4-year-old, 12-kg child with heritable pulmonary artery hypertension and refractory right ventricular failure. She was successfully bridged to heart-lung transplantation (HLTx) using ambulatory VA ECMO. Initial resuscitation with standard VA ECMO was converted to an ambulatory circuit using Berlin heart cannulae. She was extubated and ambulating around her bed while on VA ECMO for 40 days. She received an HLTx from an oversized marginal lung donor. Despite a cardiac arrest and Grade 3 primary graft dysfunction, she made a full recovery without neurological deficits. She achieved 104% force expiratory volume in 1 s 33 months post-HLTx. Ambulatory VA ECMO may be a useful strategy to bridge very young children to LTx or HLTx. Patient tailored ECMO cannulation, minimization of hemorrhage, and thrombosis risks while on ECMO contributed to a successful HLTx in our patient.


Subject(s)
Extracorporeal Membrane Oxygenation , Heart Transplantation , Lung Transplantation , Child, Preschool , Female , Humans
4.
Can J Cardiol ; 29(12): 1535-1552, dec. 2013.
Article in English | BIGG - GRADE guidelines | ID: biblio-965277

ABSTRACT

Pediatric heart failure (HF) is an important cause of morbidity and mortality in childhood. This article presents guidelines for the recognition, diagnosis, and early medical management of HF in infancy, childhood, and adolescence. The guidelines are intended to assist practitioners in office-based or emergency room practice, who encounter children with undiagnosed heart disease and symptoms of possible HF, rather than those who have already received surgical palliation. The guidelines have been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and are accompanied by practical Recommendations for their application in the clinical setting, supplemented by online material. This work does not include Recommendations for advanced management involving ventricular assist devices, or other device therapies.


Subject(s)
Humans , Infant , Child, Preschool , Child , Heart Defects, Congenital , Heart Failure , Vasodilator Agents , Algorithms , Vasopressins , Angiotensin-Converting Enzyme Inhibitors , Echocardiography , Biomarkers/blood , Cardiotonic Agents , Catecholamines/therapeutic use , Electrocardiography, Ambulatory , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Diuretics , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/therapy , Myocarditis , Myocardium/pathology
6.
Pharmacopsychiatry ; 46(4): 130-6, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23364872

ABSTRACT

Negative mood states after alcohol detoxification may enhance the relapse risk. As recently shown in healthy volunteers, dopamine storage capacity (V d) in the left amygdala was positively correlated with functional activation in the left amygdala and anterior cingulate cortex (ACC) during an emotional task; high functional connectivity between the amygdala and the ACC, a region important for emotion regulation, was associated with low trait anxiety. Based on these findings, we now tested whether detoxified alcohol-dependent patients have a disrupted modulation of the anterior cingulate cortex activation in response to aversive stimuli by amygdala dopamine. Furthermore, we asked whether disrupted functional coupling between amygdala and ACC during aversive processing is related to trait anxiety.We used combined 6-[18F]-fluoro-l-DOPA positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and Spielberger's state-trait anxiety questionnaire (STAI) in 11 male detoxified alcohol-dependent patients compared to 13 matched healthy controls.Unlike healthy controls, patients showed no significant correlation between our PET metric for dopamine storage capacity (FDOPA V d), in left amygdala and activation in left ACC. Moreover, the functional connectivity between amygdala and ACC during processing of aversive emotional stimuli was reduced in patients. Voxel-based morphometry did not reveal any discernible group differences in amygdala volume.These results suggest that dopamine-modulated corticolimbic circuit function is important for responding to emotional information such that apparent functional deficits in this neuromodulatory circuitry may contribute to trait anxiety in alcohol-dependent patients.


Subject(s)
Affect/physiology , Alcoholism/psychology , Dopamine/physiology , Emotions/physiology , Adult , Alcoholism/diagnostic imaging , Alcoholism/metabolism , Amygdala/diagnostic imaging , Amygdala/physiology , Anxiety/psychology , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/physiology , Diagnostic and Statistical Manual of Mental Disorders , Dopamine/analogs & derivatives , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Photic Stimulation , Positron-Emission Tomography , Radiopharmaceuticals , Smoking/psychology
7.
Recent Results Cancer Res ; 194: 395-423, 2013.
Article in English | MEDLINE | ID: mdl-22918772

ABSTRACT

Pulmonary imaging using ventilation/perfusion (V/P) single-photon emission tomography (V/P scan) with Tc-99m-labeled radiotracers is a well-established diagnostic tool for clinically suspected pulmonary embolism (PE). Ga-68 aerosol (Galligas) and Ga-68-labeled macroaggregated albumin (MAA) are potential tracers for positron emission tomography (PET) lung V/P imaging and could display an advantage over conventional V/P scans in terms of sensitivity and specificity. After radiochemical and animal studies, the clinical applicability of Ga-68 aerosol (Galligas) and Ga-68-labeled MAA was investigated in an exploratory study in patients with clinical suspicion of PE. PET scans were acquired using a 16-slice Gemini TF positron emission tomography/computed tomography (PET/CT) scanner. The acquisition protocol included low-dose computed tomography (CT) for attenuation correction (AC). Dosimetry calculations and continuative phantom measurements were performed. Structural analyses showed no modification of the particles due to the labeling process. In addition, in vitro experiments showed stability of Ga-68 MAA in various media. As expected, Ga-68-labeled human serum albumin microspheres (HSAM) were completely retained in the lung of the animals. In clinical use, PET lung ventilation and perfusion imaging using Ga-68 aerosol (Galligas) and Ga-68-labeled MAA was successful in all cases. In one case a clinically suspected PE could be detected and verified. The administered activity of Ga-68 aerosol (Galligas) and Ga-68-labeled MAA may be reduced by more than 50%, resulting in comparable radiation exposure to conventional V/P scans. In conclusion, Ga-68 aerosol (Galligas) and Ga-68-labeled MAA are efficient substitutes for clinical use and could be an interesting alternative with high accuracy for lung V/P imaging with Tc-99m-labeled radiotracers, especially in times of Mo-99 shortages and increasing use and spread of PET/CT scanners and Ga-68 generators, respectively.


Subject(s)
Gallium Radioisotopes , Positron-Emission Tomography/methods , Ventilation-Perfusion Ratio , Aerosols , Aged , Aged, 80 and over , Animals , Female , Humans , Male , Microspheres , Radiometry , Rats , Rats, Sprague-Dawley , Serum Albumin
8.
Nuklearmedizin ; 51(3): 101-10, 2012.
Article in English | MEDLINE | ID: mdl-22446512

ABSTRACT

PURPOSE: To evaluate the calibration of an adaptive thresholding algorithm (contrast-oriented algorithm) for FDG PET-based delineation of tumour volumes in eleven centres with respect to scanner types and image data processing by phantom measurements. METHODS: A cylindrical phantom with spheres of different diameters was filled with FDG realizing different signal-to-background ratios and scanned using 5 Siemens Biograph PET/CT scanners, 5 Philips Gemini PET/CT scanners, and one Siemens ECAT-ART PET scanner. All scans were analysed by the contrast-oriented algorithm implemented in two different software packages. For each site, the threshold SUVs of all spheres best matching the known sphere volumes were determined. Calibration parameters a and b were calculated for each combination of scanner and image-analysis software package. In addition, "scanner-type-specific" calibration curves were determined from all values obtained for each combination of scanner type and software package. Both kinds of calibration curves were used for volume delineation of the spheres. RESULTS: Only minor differences in calibration parameters were observed for scanners of the same type (Δa ≤4%, Δb ≤14%) provided that identical imaging protocols were used whereas significant differences were found comparing calibration parameters of the ART scanner with those of scanners of different type (Δa ≤60%, Δb ≤54%). After calibration, for all scanners investigated the calculated SUV thresholds for auto-contouring did not differ significantly (all p>0.58). The resulting sphere volumes deviated by less than -7% to +8% from the true values. CONCLUSION: After multi-centre calibration the use of the contrast-oriented algorithm for FDG PET-based delineation of tumour volumes in the different centres using different scanner types and specific imaging protocols is feasible.


Subject(s)
Algorithms , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/radiotherapy , Positron-Emission Tomography/instrumentation , Positron-Emission Tomography/standards , Radiotherapy Planning, Computer-Assisted/standards , Calibration , Equipment Failure Analysis/standards , Germany , Humans , Radiotherapy Dosage , Reference Standards , Reproducibility of Results , Sensitivity and Specificity
10.
Neurology ; 75(2): 129-36, 2010 Jul 13.
Article in English | MEDLINE | ID: mdl-20625165

ABSTRACT

OBJECTIVE: Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by sensory, motor, and autonomic symptoms. It develops after limb trauma and may be associated with relevant psychiatric comorbidity. As there is evidence for central pathophysiology which might be related to an altered opioidergic neurotransmission, we investigated the cerebral opioid receptor status under resting conditions in this patient population. METHODS: In this case-control study, 10 patients with CRPS and 10 age- and gender-matched healthy subjects underwent a PET scan using the subtype-nonselective opioidergic radioligand [(18)F]fluoroethyl-diprenorphine. As a surrogate for regional cerebral opioid receptor availability, the opioid receptor binding potential (OR-BP) was assessed by means of the modified Logan plot with reference region input for categorical group comparison and correlation with clinical data in the patient group. RESULTS: Patients with CRPS showed reduced OR-BP in contralateral amygdala and parahippocampal gyri and increased OR-BP in contralateral prefrontal cortical areas. When OR-BP in the midcingulate cortex and the ipsilateral temporal cortex was low, the McGill pain rating index was high. In general, when anxiety and depression scales were high, contralateral temporal OR-BP was high as well. In addition, the anxiety scale decreased with increasing OR-BP in the contralateral parahippocampal cortex. CONCLUSIONS: These results demonstrate altered central opioidergic neurotransmission in CRPS. The correlation of regional opioid receptor availability to measures of pain, anxiety, and depression underlines the clinical importance of these findings.


Subject(s)
Brain/metabolism , Complex Regional Pain Syndromes/metabolism , Pain/metabolism , Receptors, Opioid/metabolism , Adult , Affect , Anxiety/psychology , Brain/diagnostic imaging , Brain/physiopathology , Brain Mapping , Case-Control Studies , Complex Regional Pain Syndromes/diagnostic imaging , Complex Regional Pain Syndromes/physiopathology , Complex Regional Pain Syndromes/psychology , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Neurons/diagnostic imaging , Neurons/metabolism , Neuropsychological Tests , Pain/diagnostic imaging , Pain/physiopathology , Pain Measurement , Pain Threshold/psychology , Radionuclide Imaging , Synaptic Transmission/physiology
11.
Eur J Neurosci ; 31(11): 2101-11, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20529117

ABSTRACT

Thermoregulation enables adaptation to different ambient temperatures. A complex network of central autonomic centres may be involved. In contrast to the brainstem, the role of the cortex has not been clearly evaluated. This study was therefore designed to address cerebral function during a whole thermoregulatory cycle (cold, neutral and warm stimulation) using 18-fluordeoxyglucose-PET (FDG-PET). Sympathetic activation parameters were co-registered. Ten healthy male volunteers were examined three times on three different days in a water-perfused whole-body suit. After a baseline period (32 degrees C), temperature was either decreased to 7 degrees C (cold), increased to 50 degrees C (warm) or kept constant (32 degrees C, neutral), thereafter the PET examination was performed. Cerebral glucose metabolism was increased in infrapontine brainstem and cerebellar hemispheres during cooling and warming, each compared with neutral temperature. Simultaneously, FDG uptake decreased in the bilateral anterior/mid-cingulate cortex during warming, and in the right insula during cooling and warming. Conjunction analyses revealed that right insular deactivation and brainstem activation appeared both during cold and warm stimulation. Metabolic connectivity analyses revealed positive correlations between the cortical activations, and negative correlations between these cortical areas and brainstem/cerebellar regions. Heart rate changes negatively correlated with glucose metabolism in the anterior cingulate cortex and in the middle frontal gyrus/dorsolateral prefrontal cortex, and changes of sweating with glucose metabolism in the posterior cingulate cortex. In summary, these results suggest that the cerebral cortex exerts an inhibitory control on autonomic centres located in the brainstem or cerebellum. These findings may represent reasonable explanations for sympathetic hyperactivity, which occurs, for example, after hemispheric stroke.


Subject(s)
Adrenergic Fibers/physiology , Body Temperature Regulation/physiology , Cerebral Cortex/metabolism , Cerebral Cortex/physiology , Adult , Brain Stem/diagnostic imaging , Brain Stem/metabolism , Brain Stem/physiology , Cerebral Cortex/diagnostic imaging , Fluorodeoxyglucose F18/metabolism , Glucose/metabolism , Humans , Male , Radiopharmaceuticals/metabolism , Temperature , Tomography, Emission-Computed
12.
Neuroimage ; 47(4): 1237-43, 2009 Oct 01.
Article in English | MEDLINE | ID: mdl-19497378

ABSTRACT

Transcranial ultrasound (TCS) has been shown to reveal hyperechogenicity of the substantia nigra (SN) in Parkinsonian patients and in about 10% of healthy controls. It is hypothesized that SN hyperechogenicity in healthy subjects is a vulnerability marker for idiopathic Parkinson's disease (IPD). Although there is strong evidence that the echomarker results from increased local iron content, the exact pathophysiological mechanisms remain incompletely understood. Thus, prognostic impact can only be estimated. We examined 14 subjects with SN hyperechogenicity (SN+) (7 IPD patients and 7 controls) and 7 healthy controls without the echomarker (SN-) by a magnetic resonance imaging method (MRI; T2 relaxation times) known to reveal tissue inhomogeneity following abnormal iron content and by F-Dopa PET to assess nigrostriatal function.


Subject(s)
Dihydroxyphenylalanine/analogs & derivatives , Echoencephalography/methods , Magnetic Resonance Imaging/methods , Neurons/diagnostic imaging , Neurons/pathology , Parkinson Disease/diagnosis , Positron-Emission Tomography/methods , Adult , Female , Humans , Male , Middle Aged , Radiopharmaceuticals , Reference Values , Substantia Nigra/diagnostic imaging , Substantia Nigra/pathology
13.
Auton Neurosci ; 143(1-2): 27-32, 2008 Dec 05.
Article in English | MEDLINE | ID: mdl-18723403

ABSTRACT

Although recent studies identified brain areas which are involved in short term activation of the sympathetic nervous system, little is known about brain mechanisms which generate the individual variability of basal autonomic activity. In this fluorodeoxyglucose positron emission tomography study (FDG-PET), we aimed to identify brain regions, which covary with function parameters of the autonomic nervous system at rest. Therefore, FDG-PET (Siemens, Germany) was performed twice in 14 healthy resting subjects (7 m, 7 f; mean age 29.5 years) while different parameters of autonomic function were assessed simultaneously: Blood pressure, heart rate, power spectra of heart rate variability (HF/LF ratio) and plasma catecholamines. In order to control for attention, subjects had to focus visual affective neutral presentations during the experiment. Correlation analysis was performed as a region of interest analysis using SPM2 software (p<0.001 uncorrected). Sympathetic activity at rest varied substantially between subjects. There were significant positive correlations between increase of regional cerebral glucose metabolism (rCGM) of the heads of caudate nuclei on both sides and the HF/LF ratio of heart rate variability. Furthermore, significant negative correlations between both heart rate and plasma catecholamines and rCGM decreases of caudate nuclei heads were found. In addition, there was a positive correlation between plasma catecholamines and primary motor cortex activation. Autonomic nervous system at rest seems to be partially interlocked with activity of motor brain regions - the caudate nuclei and the motor cortex. This might have clinical implications for the understanding of stress-related disorders, which are frequently accompanied by increased sympathetic activity as well as muscle tone.


Subject(s)
Brain/physiology , Fluorodeoxyglucose F18 , Positron-Emission Tomography/methods , Rest/physiology , Sympathetic Nervous System/physiology , Adult , Attention/physiology , Blood Pressure/physiology , Brain/metabolism , Chromatography, High Pressure Liquid/methods , Fluorodeoxyglucose F18/administration & dosage , Glucose/metabolism , Heart Rate/physiology , Humans , Norepinephrine/blood , Radiopharmaceuticals/administration & dosage
14.
J Clin Endocrinol Metab ; 91(12): 4786-91, 2006 Dec.
Article in English | MEDLINE | ID: mdl-16968792

ABSTRACT

CONTEXT: Hyperthyroidism is frequently associated with emotional distress. The underlying cerebral processes of the endocrine-induced mood changes are unclear. OBJECTIVE: The objective of this study was to investigate, for the first time, the neuronal correlates of thyrotoxicosis-associated psychic symptoms using positron emission tomography (PET). DESIGN: The study was designed as a cross-sectional trial. SETTING: The study was performed at joint nuclear medicine and thyroid clinics. PATIENTS: Twelve patients with untreated Graves' hyperthyroidism were evaluated. METHODS: Levels of emotional distress were self-rated by means of the Hospital Anxiety and Depression Scale. Both patients and 20 age- and gender-matched euthyroid controls underwent a brain fluorodeoxyglucose PET scan. Subsequently, the functional relationship between brain metabolism and the psychometric scores was analyzed. RESULTS: Compared with controls and visualized by fluorodeoxyglucose PET, hyperthyroid patients showed a decreased (P < 0.0001) glucose metabolism in the limbic system (uncus and inferior temporal gyrus). Activation foci in the posterior cingulate and in the inferior parietal lobe were correlated with both anxiety and depression scales (P < 0.001). Compared with patients with normal anxiety levels, those with increased anxiety yielded an enhanced glucose metabolism (P < 0.001) in the bilateral sensory association cortex. Serum free T3/free T4 levels negatively correlated with regional glucose metabolism in the medial posterior cingulate. CONCLUSIONS: Thyrotoxicosis and associated psychic symptoms are correlated to regional metabolic changes in the main structures of the limbic/paralimbic system.


Subject(s)
Brain/diagnostic imaging , Brain/metabolism , Graves Disease/psychology , Mood Disorders/etiology , Positron-Emission Tomography/methods , Adult , Aged , Brain Mapping/methods , Case-Control Studies , Cerebral Cortex/physiology , Female , Fluorodeoxyglucose F18/metabolism , Glucose/metabolism , Graves Disease/diagnostic imaging , Graves Disease/metabolism , Humans , Male , Middle Aged , Mood Disorders/diagnosis , Pilot Projects , Thyroid Hormones/blood
15.
Eur J Nucl Med Mol Imaging ; 32(11): 1324-8, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16133376

ABSTRACT

PURPOSE: The new beta2 radioligand (R,R)(S,S) 5-(2-(2-[4-(2-[18F]fluoroethoxy)phenyl]-1-methylethylamino)-1-hydroxyethyl)-benzene-1,3-diol ([18F]FE-fenoterol; [18F]FEFE), a fluoroethylated derivative of racemic fenoterol, was evaluated in vivo and ex vivo using a guinea pig model. METHODS: Dynamic PET studies over 60 min with [(18)F]FEFE were performed in nine Hartley guinea pigs in which a baseline (group 1, n=3), a predose (group 2, n=3; 2 mg/kg fenoterol 5 min prior to injection of [18F]FEFE) or a displacement study (group 3, n=3; 2 mg/kg fenoterol 5 min post injection of [18F]FEFE) was conducted. RESULTS: In all animal groups, the lungs could be visualised and semi-quantified separately by calculating uptake ratios to non-specific binding in the neck area. Premedication with non-radioactive fenoterol and displacement tests showed significant reduction of lung uptake, by 94% and 76%, respectively. CONCLUSION: These data demonstrate specific binding of the new radioligand to the pulmonary beta2-receptors in accordance with ex vivo measurements. Therefore, [18F]FEFE seems to be suitable for the in vivo visualisation and quantification of the pulmonary beta2-receptor binding in this animal model.


Subject(s)
Fenoterol/analogs & derivatives , Lung/diagnostic imaging , Lung/metabolism , Receptors, Adrenergic, beta-2/metabolism , Animals , Feasibility Studies , Fenoterol/pharmacokinetics , Guinea Pigs , Metabolic Clearance Rate , Models, Animal , Organ Specificity , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Tissue Distribution
16.
Exp Clin Endocrinol Diabetes ; 113(7): 388-95, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16025400

ABSTRACT

Pancreatic islet cell mass (PICM) is a major determinant of the insulin secretory capacity in humans. Currently, the only method for accurate assessment of the PICM is an autopsy study. Thus, development of a technique allowing the non-invasive quantification of PICM is of great interest. The aim of this study was to develop such a non-invasive technique featuring novel fluorine- and (99m)Tc-labelled glibenclamide derivatives. Despite the structural modifications necessary to introduce fluorine into the glibenclamide molecule, all derivatives retained insulin stimulating capacity as well as high affinity binding to human SUR1 when compared to the original glibenclamide. Contrastingly, the lipophilicity of the fluorine-labelled derivatives was altered depending on the particular modification. In the human PET-study a constant but weak radioactive signal could be detected in the pancreas using a fluorine-labelled glibenclamide derivative. However, a reliable assessment and visualisation of the PICM could not be obtained. It can be assumed that the high uptake of the fluorine-labelled tracer e.g. into the the liver and the high plasma protein binding leads to a relatively low signal-to-noise ratio. In case of the presented fluorine-labelled glibenclamide based compounds this could be the result of their invariably high lipophilicity. The development of a (99 m)Tc-labelled glibenclamide derivative with a lower lipophilicity and differing in vivo behaviour, glibenclamide based compounds for non-invasive imaging of the pancreatic islet cell mass may be possible.


Subject(s)
Diabetes Mellitus/diagnostic imaging , Fluorine Radioisotopes , Glyburide/analogs & derivatives , Hypoglycemic Agents , Islets of Langerhans/diagnostic imaging , Radiopharmaceuticals , Technetium , ATP-Binding Cassette Transporters/metabolism , Animals , Glyburide/chemical synthesis , Glyburide/pharmacokinetics , Humans , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/pharmacokinetics , Insulin/metabolism , Islets of Langerhans/drug effects , Islets of Langerhans/metabolism , Magnetic Resonance Imaging , Positron-Emission Tomography , Potassium Channels/metabolism , Potassium Channels, Inwardly Rectifying/metabolism , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Rats , Rats, Sprague-Dawley , Receptors, Drug/metabolism , Sulfonylurea Receptors
17.
Neurology ; 64(7): 1175-83, 2005 Apr 12.
Article in English | MEDLINE | ID: mdl-15824343

ABSTRACT

OBJECTIVE: Muscle pain differs from skin pain with respect to quality, accuracy of localization, and unpleasantness. This study was conducted to identify the brain regions associated with the affective-motivational component of tonic skin and muscle pain. METHODS: Forty healthy volunteers were investigated in three groups with different F-18 fluorodeoxyglucose PET activation scans. A verbal rating scale (VRS) was used to quantify pain intensity and unpleasantness. One group was investigated during painful infusion of an acidified phosphate buffer (pH 5.2) into either muscle or skin for 30 minutes. Muscle and skin infusions were adjusted to achieve pain intensity rating of VRS = 40. The second group received sham stimulation of muscle and skin by infusion of non-acidified phosphate buffer (pH 7.3 to 7.4, pain intensity = 0). The third group underwent only one PET scan without sensory stimulation. RESULTS: Unpleasantness ratings were higher (VRS 38.3 vs 25.5) during IM compared to intracutaneous stimulation, despite the same pain intensity (VRS = 40). Sham stimulation revealed no pain or unpleasantness. Regional cerebral glucose metabolism during sham stimulation showed similar findings for intracutaneous and IM infusions with significant activations of the bilateral anterior cingulate, bilateral frontal (premotor) cortex, and the ipsilateral parietal operculum. The comparison of pain vs sham stimulation revealed activations of the bilateral insula for IM but not intracutaneous stimulation. The unpleasantness perception in skin and muscle stimulation was positively correlated to the bilateral insular metabolism. CONCLUSION: The data suggest that the insula represents one main structure where the unpleasantness of tonic pain perception is encoded.


Subject(s)
Cerebral Cortex/diagnostic imaging , Cerebral Cortex/metabolism , Emotions/physiology , Pain/diagnostic imaging , Pain/physiopathology , Acids/adverse effects , Acute Disease , Adult , Brain Mapping , Buffers , Chronic Disease , Female , Fluorodeoxyglucose F18 , Functional Laterality/physiology , Glucose/metabolism , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/metabolism , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Muscle, Skeletal/innervation , Muscle, Skeletal/physiopathology , Nociceptors/drug effects , Nociceptors/physiology , Pain/metabolism , Pain Measurement/methods , Positron-Emission Tomography , Reference Values , Skin/innervation , Skin/physiopathology , Time Factors
18.
Int J Cosmet Sci ; 27(3): 177-89, 2005 Jun.
Article in English | MEDLINE | ID: mdl-18492185

ABSTRACT

Organic-inorganic ultraviolet (UV) active hybrid materials have been prepared by a sol-gel process from benzophenone derivatives and tetraethylorthosilicate. The silica particles are spherical in shape and have a narrow size distribution which remains unchanged up to organic chromophore concentrations of 0.2 mmol g(-1). At higher concentrations the spheres become less regular and fuse. A dependence of the material absorption properties on the particle size (at the same organic chromophore concentration) and on the concentration of surface grafted chromophores was noted. The most effective UV filter materials were found in a combination of silica incorporated chromophores and surface grafted chromophores at an overall low chromophore concentration. A comparison of the photostability of chromophores at standardized UV irradiation revealed an increase in stability for silica incorporated and surface immobilized benzophenone compared to benzophenone in a homogeneous solution.

19.
Br J Dermatol ; 150(2): 304-11, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14996102

ABSTRACT

BACKGROUND: Bringing up children with atopic dermatitis (AD) is widely perceived as being stressful because parenting demands considerable time and energy. There have been only a few studies to assess the extent of problems experienced by the parents. OBJECTIVE: To assess the psychosocial well-being of parents caring for a young child with AD and to examine the relationship between parental quality of life and disease-related and sociodemographic variables. METHODS: One hundred and eighty-seven parents of young children with AD attending an inpatient rehabilitation clinic participated in the study. At admission, parents completed a set of questionnaires (assessing health-related quality of life, coping with the disease, family functioning). Dermatologists assessed disease severity using the severity scoring of AD index (SCORAD). RESULTS: In general, parents cope well with their situation. Compared with normal values, high rates of psychological distress were observed in a subsample of parents of children with AD. Parents of children with a higher severity of disease reported a significantly higher impact on family functioning, a greater financial burden and a higher level of disease management. Parental disease management could be predicted by the familial situation, their personal well-being and the severity of disease of their child. Differences attributed to their child's gender or age were not observed. CONCLUSIONS: Childhood AD has a profound impact on the emotional and social well-being of many of the parents. The results underline the importance of psychological treatment approaches designed to increase parental well-being and ability to cope with stress and social strain.


Subject(s)
Adaptation, Psychological , Dermatitis, Atopic/psychology , Parents/psychology , Quality of Life , Adult , Female , Humans , Male , Regression Analysis
20.
Eur J Nucl Med Mol Imaging ; 30(5): 716-20, 2003 May.
Article in English | MEDLINE | ID: mdl-12605273

ABSTRACT

Quantitative imaging with the positron emitter (86)Y is the method of choice to determine the uptake and dosimetry of (90)Y-labelled radiopharmaceuticals. To examine the quantitative accuracy of positron emission tomography findings with (86)Y, this non-pure positron emitter was evaluated in a cylindrical phantom with rods of Teflon, water and air and measured with three different scanners: ECAT EXACT (2D/3D), ECAT HR+ (2D/3D) and PC4096+ (2D). After standard reconstruction, (86)Y radioactivity measured with the ECAT EXACT and related to the true radioactivity varied between 0.84 and 0.99 in 2D and between 0.93 and 1.20 in 3D from the first to the last acquisition (eight half-life times later). The water and Teflon rods exhibited considerable amounts of reconstructed radioactivity-21% in 2D and 67% in 3D for water and 65% and 147%, respectively, for Teflon-compared with the actual (86)Y radioactivity of the phantom. For the ECAT HR+ similar results were obtained in 3D, but there were even greater overestimations in 2D. Measurements with the PC4096+ showed rather small errors, with 10% for water and 20% for Teflon. To correct for the background of gamma-coincidences, sinograms were analysed and an experimental percentage of the background was subtracted from the sinograms. In order to minimise the errors in reconstructed radioactivity, the subtraction value had to be different for the individual scanners and modes. Our results demonstrate that (90)Y/(86)Y-based dosimetry for bone and red marrow must be regarded with caution if it is derived from regions of interest over the bone, the density of which is similar to that of Teflon. To obtain more reliable estimates, an appropriate background correction must be applied and tailored individually with respect to the scanner and acquisition mode.


Subject(s)
Algorithms , Artifacts , Image Enhancement/methods , Subtraction Technique , Tomography, Emission-Computed/instrumentation , Tomography, Emission-Computed/methods , Yttrium Radioisotopes , Background Radiation , Equipment Failure Analysis , Image Enhancement/instrumentation , Phantoms, Imaging , Radiopharmaceuticals , Reproducibility of Results , Scattering, Radiation , Sensitivity and Specificity
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