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In the last 3 years, Lutetium-177 prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA-RLT) has received increasing attention in nuclear medicine as a new form of treatment for castration-resistant metastatic prostate cancer. This therapy combines the radionuclide Lutetium-177, which has been therapeutically used in nuclear medicine for many years, with a molecular target of the transmembrane prostate-specific membrane antigen expressed by prostate cancer cells. Since there are no prospective randomized studies on Lu-177-PSMA-RLT and the question of reimbursement has repeatedly been the subject of review by the MDK Nordrhein (Medischenische Dienst der Krankenversicherung), there was a desire because of the increasing number of patients being treated to clarify under which circumstances Lu-177-PSMA-RLT can be reimbursed by German statutory health insurance. The goals of this article are to help treating physicians understand how this new therapy option works, to integrate it in the overall therapy concept for castration-resistant metastatic prostate cancer, and, above all, to use Lu-177-PSMA-RLT-based on the current data-at the right place in the therapy sequence of castration-resistant metastatic prostate cancer.
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Custos de Cuidados de Saúde , Reembolso de Seguro de Saúde , Seguro Saúde , Lutécio/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/radioterapia , Radioisótopos/uso terapêutico , Antígenos de Superfície , Consenso , Alemanha , Hospitais Universitários , Humanos , Ligantes , Lutécio/efeitos adversos , Lutécio/economia , Masculino , Neoplasias de Próstata Resistentes à Castração/metabolismo , Radioisótopos/efeitos adversos , Radioisótopos/economia , Resultado do TratamentoRESUMO
The ball-pen probe (BPP) technique is used successfully to make profile measurements of the electron temperature on the ASDEX Upgrade (Axially Symmetric Divertor Experiment), COMPASS (COMPact ASSembly), and ISTTOK (Instituto Superior Tecnico TOKamak) tokamak. The electron temperature is provided by a combination of the BPP potential (ΦBPP) and the floating potential (Vfl) of the Langmuir probe (LP), which is compared with the Thomson scattering diagnostic on ASDEX Upgrade and COMPASS. Excellent agreement between the two diagnostics is obtained for circular and diverted plasmas and different heating mechanisms (Ohmic, NBI, ECRH) in deuterium discharges with the same formula Te = (ΦBPP - Vfl)/2.2. The comparative measurements of the electron temperature using BPP/LP and triple probe (TP) techniques on the ISTTOK tokamak show good agreement of averaged values only inside the separatrix. It was also found that the TP provides the electron temperature with significantly higher standard deviation than BPP/LP. However, the resulting values of both techniques are well in the phase with the maximum of cross-correlation function being 0.8.
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PURPOSE: Dopamine (DA), which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA), nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT) binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [(123)I]FP-CIT to the DAT should be decreased due to competition at the receptor. METHODS: Rats were administered 3 mg/kg IN-DA and vehicle (VEH), with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming) were assessed for 30 min in an open field prior to administration of [(123)I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT 2 h following administration of the radioligand. RESULTS: (1) After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered DA had central action and increased DA levels comparable to that found previously with L-DOPA administration; and (2) DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased) the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant drugs. THE RESULTS: (a) demonstrate a direct central action of intranasally applied DA on the DAT in the dorsal striatum, indicating enhanced DA availability; and (b) provide first evidence of a Pavlovian conditioned DA response at the DAT. The latter results have relevance to understanding neurochemical mechanisms that underlie placebo action in the treatment of Parkinsonian patients.
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In a wide variety of natural and laboratory magnetized plasmas, filaments appear as a result of interchange instability. These convective structures substantially enhance transport in the direction perpendicular to the magnetic field. According to filament models, their propagation may follow different regimes depending on the parallel closure of charge conservation. This is of paramount importance in magnetic fusion plasmas, as high collisionality in the scrape-off layer may trigger a regime transition leading to strongly enhanced perpendicular particle fluxes. This work reports for the first time on an experimental verification of this process, linking enhanced transport with a regime transition as predicted by models. Based on these results, a novel scaling for global perpendicular particle transport in reactor relevant tokamaks such as ASDEX-Upgrade and JET is found, leading to important implications for next generation fusion devices.
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UNLABELLED: Impairment of GABA(A) receptor function is increasingly recognized to play a major role in the pathophysiology of neuropsychiatric diseases including anxiety disorder (AD), major depressive disorder (MDD) and schizophrenia (SZ). PATIENTS, METHOD: We conducted a PUBMED search, which provided a total of 23 in vivo investigations with PET and SPECT, in which GABA(A) receptor binding in patients with the primary diagnosis of AD (n = 14, 160 patients, 172 controls), MDD (n = 2, 24 patients, 28 controls) or SZ (n = 6, 77 patients, 90 controls) was compared to healthy individuals. RESULTS: A retrospective analysis revealed that AD, MDD and SZ differed as to both site(s) and extent(s) of GABAergic impairment. Additionally, it may be stated that, while the decline of GABA(A) receptor binding AD involved the whole mesolimbocortical system, in SZ it was confined to the frontal and temporal cortex. CONCLUSION: As GABA is known to inhibit dopamine and serotonin, GABAergic dysfunction may be associated with the disturbances of dopaminergic and serotonergic neurotransmission in neuropsychiatric disorders.
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Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Transtorno Depressivo Maior/metabolismo , Receptores de GABA-A/metabolismo , Esquizofrenia/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/epidemiologia , Biomarcadores/metabolismo , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Incidência , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/epidemiologia , Sensibilidade e Especificidade , Tomografia Computadorizada de Emissão/estatística & dados numéricosAssuntos
Regeneração Nervosa , Sistema Nervoso/patologia , Cicatrização , Animais , Axônios/efeitos dos fármacos , Axônios/metabolismo , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Humanos , Imunidade/efeitos dos fármacos , Regeneração Nervosa/genética , Sistema Nervoso/efeitos dos fármacos , Sistema Nervoso/imunologia , Sistema Nervoso/fisiopatologia , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Pesquisa Translacional Biomédica , Cicatrização/efeitos dos fármacos , Cicatrização/genéticaRESUMO
Magnetically confined plasmas in the high confinement regime are regularly subjected to relaxation oscillations, termed edge localized modes (ELMs), leading to large transport events. Present ELM theories rely on a combined effect of edge current and the edge pressure gradients which result in intermediate mode number (nâ 10-15) structures (filaments) localized in the perpendicular plane and extended along the field lines. By detailed localized measurements of the magnetic field perturbation associated to type-I ELM filaments, it is shown that these filaments carry a substantial current.
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Central dopaminergic (DA) systems are affected during human immunodeficiency virus (HIV) infection. So far, it is believed that they degenerate with progression of HIV disease because deterioration of DA systems is evident in advanced stages of infection. In this manuscript we found that (a) DA levels are increased and DA turnover is decreased in CSF of therapy-naïve HIV patients in asymptomatic infection, (b) DA increase does not modulate the availability of DA transporters and D2-receptors, (c) DA correlates inversely with CD4+ numbers in blood. These findings show activation of central DA systems without development of adaptive responses at DA synapses in asymptomatic HIV infection. It is probable that DA deterioration in advanced stages of HIV infection may derive from increased DA availability in early infection, resulting in DA neurotoxicity. Our findings provide a clue to the synergism between DA medication or drugs of abuse and HIV infection to exacerbate and accelerate HIV neuropsychiatric disease, a central issue in the neurobiology of HIV.
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Dopamina/metabolismo , Infecções por HIV/metabolismo , Infecções por HIV/patologia , Transmissão Sináptica/fisiologia , Ácido 3,4-Di-Hidroxifenilacético/líquido cefalorraquidiano , Adulto , Benzamidas , Antígenos CD4/metabolismo , Estudos de Casos e Controles , Quimiocina CCL2/metabolismo , Galactosefosfatos/metabolismo , HIV/genética , Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/imunologia , Ácido Homovanílico/líquido cefalorraquidiano , Humanos , Masculino , Pessoa de Meia-Idade , Pirrolidinas , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tropanos , Carga Viral/métodosRESUMO
OBJECTIVE: To evaluate high-resolution multi-pinhole single photon emission computed tomography (MPH-SPECT) for the detection of bony alterations in early rheumatoid arthritis (ERA), early osteoarthritis (EOA) of the fingers and healthy controls. METHODS: The clinically dominant hands of 27 patients (13 ERA, nine EOA, five healthy controls) were examined by MPH-SPECT and bone scintigraphy. Additionally, magnetic resonance imaging (MRI) was performed in the ERA patients. Number of affected joints, localisation, pattern of tracer distribution and joint involvement were scored. Quantitative analysis was achieved by measurement of the region of interest (ROI) in all patients. The MPH-SPECT and MR images were fused in the ERA group. RESULTS: Bone scintigraphy detected fewer joints (26 joints,13/22 patients) with increased tracer uptake than did MPH-SPECT (80 joints, 21/22 patients). Bone scintigraphy did not show recognisable uptake patterns in any group of patients. With MPH-SPECT central tracer distribution was typical in ERA (10/13 patients, EOA 2/9). In contrast, an eccentric pattern was found predominantly in EOA (7/9, ERA 2/13). Normalised counts were 4.5 in unaffected joints and up to 222.7 in affected joints. The mean uptake values in affected joints were moderately higher in the EOA patients (78.75, and 62.16 in ERA). The mean tracer uptake in affected joints was approximately three-times higher than in unaffected joints in both groups (ERA 3.64-times higher, EOA 3.58). Correlation with MR images revealed that bone marrow oedema and erosions matched pathological tracer accumulation of MPH-SPECT in 11/13. MPH-SPECT demonstrated increased activity in 2/13 patients with normal bone marrow signal intensity and synovitis seen on MR images. CONCLUSION: MPH-SPECT is sensitive to early changes in ERA and EOA and permits them to be distinguished by their patterns of uptake.
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Artrite Reumatoide/diagnóstico , Artrite/diagnóstico , Articulações dos Dedos/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Idoso , Artrite/diagnóstico por imagem , Artrite Reumatoide/diagnóstico por imagem , Feminino , Articulações dos Dedos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , RadiografiaRESUMO
AIM: Comparison of MRI with a newly developed high-resolution multi-pinhole single photon emission computed tomography (MPH-SPECT) regarding the detection of bony pathologies of the metacarpophalangeal (MCP) joints in patients with early rheumatoid arthritis (ERA). MATERIALS AND METHODS: The clinically dominant hand of 15 patients with ERA (disease duration 6 months) was examined using MRI and MPH-SPECT. The evaluation of MRI was achieved according to RAMRIS criteria and for the MPH SPECT regarding pathological tracer uptake and distribution. Image fusions of MRI and MPH-SPECT were provided and the two methods were compared. RESULTS: In MRI 12 of 15 patients showed arthritic joint pathologies, while 8 patients exhibited soft tissue and bony changes. 4 patients had only soft tissue inflammation (synovitis) with a normal bone signal. In MPH-SPECT 10 of 15 patients showed pathologically increased bone metabolism. The fusion images presented a high agreement of the pathological changes in both methods, while areas with increased bone metabolism were not only present in the case of erosions, but also in the case of bone edema. In 2 patients increased bone metabolism was detectable in areas of MR tomographic normal bone, while a clear surrounding synovitis was present in each case here. CONCLUSION: The comparison of MPH-SPECT with MRI proves that the latter is a sensitive procedure for the detection of bony pathologies of MCP joints in ERA. A normal bone signal in MRI does not exclude early changes in bone metabolism in cases of severe synovialitis.
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Artrite Reumatoide/diagnóstico , Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Articulação Metacarpofalângica/patologia , Técnica de Subtração , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Diagnóstico Precoce , Humanos , Processamento de Imagem Assistida por Computador/instrumentação , Imageamento por Ressonância Magnética/instrumentação , Restrição Física/instrumentação , Sensibilidade e Especificidade , Membrana Sinovial/patologia , Sinovite/diagnóstico , Tomografia Computadorizada de Emissão de Fóton Único/instrumentaçãoRESUMO
BACKGROUND: Genital Chlamydia trachomatis infection is a worldwide public health burden. A screening program for C. trachomatis was therefore initiated by the public health insurers in Germany ("Gemeinsamer Bundesausschuss", GBA) in April 2008. OBJECTIVES: To estimate C. trachomatis prevalence from screening 115,766 asymptomatic females and 20,033 female patients with unspecific abdominal pain. STUDY DESIGN: Urine samples (pooled by five for the asymptomatic screening subjects) and cervical swabs were analyzed using semi-automated real-time PCR. Infection prevalence was determined separately in four categories of women, defined by health status (asymptomatic screening vs. non-screening with unspecified symptoms) and test material used. Comparative analyses were stratified by age and pregnancy status. RESULTS: Experimental evaluation of the assay used revealed a detection limit of 379 genome copies/ml urine. For pooled urine samples, the positive predictive value was 100% whereas the negative predictive value equaled 98.1%. The observed infection prevalence was higher for cervical swabs than for urine samples. Prevalence estimates also differed significantly between pregnant and non-pregnant adolescents (< or = 20 years), irrespective of the test material used (10.2% vs. 7.3% for cervical swabs, 10.9% vs. 6.1% for pooled urine samples). CONCLUSIONS: Our retrospective study, based upon a very large number of females from all parts of Germany, revealed a high infection prevalence in adolescents, particularly in pregnant adolescents, thereby justifying the screening directive of the German GBA.
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Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis , Programas de Rastreamento , Adolescente , Adulto , Fatores Etários , Automação Laboratorial , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/urina , Chlamydia trachomatis/genética , Chlamydia trachomatis/isolamento & purificação , DNA Bacteriano/genética , DNA Bacteriano/urina , Feminino , Alemanha/epidemiologia , Humanos , Limite de Detecção , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/urina , Prevalência , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esfregaço VaginalRESUMO
The transition of toxic or nodular goiter to Graves' disease is known as a rare side effect of (131)I therapy. Here, we report the case of a 46-year-old German female with posttherapeutical Graves' disease after surgery of a multinodular goiter. Although the major part of the thyroid was excised the patient suffered from manifest Graves' disease including typical clinical and laboratory findings. Prior to surgery, no TSH receptor antibodies were found, although low TPO antibody titres could already be detected. It may thus be assumed that the therapeutic manipulation elicited the key change towards a TSH receptor antibody production in a predisposed organ or alternatively deteriorated a mild unapparent pre-existing Graves' disease. It might be concluded that the possibility of posttherapeutical Graves' disease should be considered in the presence of TPO antibodies prior to the surgical intervention.
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Bócio Nodular/cirurgia , Doença de Graves/patologia , Feminino , Doença de Graves/imunologia , Humanos , Pessoa de Meia-IdadeRESUMO
At the moment autologous nerve grafting remains the only reasonable technique for reconstruction of peripheral nerve defects. Unfortunately, this technique has a lot of complications and disadvantages. These problems are related to the autologous nerve that is harvested for this procedure. Donor site morbidity with loss of sensitivity, painful neuroma formation and of course the restricted availability of autologous nerves stimulates the idea for alternative techniques on that field. In this paper we describe our experience with different graft materials for reconstruction of a 2 cm nerve gap in a median nerve model in rats. After implantation of various materials (biological/synthetic) the main experiments were conducted with a synthetic, biodegradable nerve conduit seeded with autologous Schwann cells. With this material we were able to reconstruct successfully a 2 cm gap in the rat median nerve. Regeneration with this material was found to be equally to an autologous nerve graft.
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Bioprótese , Regeneração Tecidual Guiada/métodos , Nervo Mediano/cirurgia , Próteses e Implantes , Engenharia Tecidual/métodos , Animais , Colágeno , Feminino , Lactonas , Nervo Mediano/fisiopatologia , Regeneração Nervosa , Poliésteres , Polímeros , Ratos , Ratos Endogâmicos Lew , Silício , Veias/transplanteRESUMO
A radially movable probe has been developed for studies of filamentary transport in ASDEX Upgrade during edge localized modes (ELMs) by means of Langmuir tips and magnetic pickup coils. The probe is permanently installed at the low field side in the ASDEX Upgrade vacuum vessel and is not subject to limitations in probe size, as, for example, probes on a shared manipulator are. The probe is moved by a magnetic drive, which allows for easy installation in the vessel, and has moderate machine requirements, as it will only require an electric feedthrough and an external power supply. The drive gives a linear motion with a radial range of 5 cm within 50 ms, where range and velocity can be largely scaled according to experimental requirements. The probe has been installed in the outer midplane of the ASDEX Upgrade vessel, where ELM filaments are expected to have their maximum amplitude. Filaments are coherent substructures within an ELM, carrying a fraction of the ELM released energy towards the wall. The new probe allows to measure the structure of these filaments, in particular, parameters such as filament rotation (by time delay measurements) and size (by peak width analysis). Activating the drive moves the probe from a safe position behind the limiter to a position in front of the limiters, i.e., exposes the Langmuir pins to the scrape-off layer plasma.
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Magnetismo/instrumentação , Termografia/instrumentação , Transdutores , Desenho de Equipamento , Análise de Falha de Equipamento , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Termografia/métodosRESUMO
We used functional magnetic resonance imaging to explore the brain mechanisms of changing point of view (PoV) in a visuospatial memory task in 3D space. Eye movements were monitored and BOLD signal changes were measured while subjects were presented with 3D images of a virtual environment. Subjects were required to encode the position of a lamp in the environment and, after changing the PoV (angular difference varied from 0 degrees to 180 degrees in 45 degrees steps), to decide whether the lamp position had been changed too or not. Performance data and a scan-path analysis based on eye movement support the use of landmarks in the environment for coding lamp position and increasing spatial updating costs with increasing changes of PoV indicating allocentric coding strategies during all conditions (0 degrees - to 180 degrees -condition). Subtraction analysis using SPM revealed that a parieto-temporo-frontal network including left medial temporal areas was activated during this 3D visuospatial task, independent of angular difference. The activity of the left parahippocampal area and the left lingual gyrus (but not the hippocampus) correlated with increasing changes of the PoV between encoding and retrieval, emphasizing their specific role in spatial scene memory and allocentric coding. The results suggest that these areas are involved in a continuous matching process between internal representations of the environment and the external status quo. In addition, hippocampal activation correlated with performance was found indicating successful recall of spatial information. Finally, in a prefrontal area comprising, the so-called "deep" frontal eye field, activation was correlated with the amount of saccadic eye movements confirming its role in oculomotor processes.
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Memória de Curto Prazo/fisiologia , Percepção Espacial/fisiologia , Percepção Visual/fisiologia , Adulto , Mapeamento Encefálico , Córtex Cerebral/fisiologia , Gráficos por Computador , Interpretação Estatística de Dados , Movimentos Oculares/fisiologia , Feminino , Humanos , Masculino , Rede Nervosa/fisiologia , Oxigênio/sangue , Estimulação Luminosa , Movimentos Sacádicos/fisiologia , Campos Visuais/fisiologiaRESUMO
AIM: In the context of presurgical localisation of parathyroid adenomas in primary hyper-parathyreoidism (pHPT) using (99m)Tc-sestamibi scintigraphy, subtraction- and dualphase technique are compared with each other and with the surgical findings. PATIENTS, METHODS: Prospectively, 126 patients with pHPT were investigated presurgically. For visualisation of parathyroid adenomas, an image of the thyroid ((99m)Tc-pertechnetat) was subtracted from a perfusion image ((99m)Tc-sestamibi) and 2 h p. i. another image was acquired for identification of retention of activity. Considering both techniques the clinical findings were reported promptly. Retrospectively, the evaluations were presented separately to four experienced raters. RESULTS: In clinical routine for 109 patients correct findings were reported presurgically (87%). From 129 resected parathyroid adenomas 118 were localised correctly (sensitivity 91%, positive predictive value 94%). Concerning the retrospective analysis, in 75% of the cases both techniques provided the correct site, in 14% only the dual-phase technique and in 7% only the subtraction-technique was correct. With the help of the dual-phase technique significantly more investigations were correctly rated than with the help of the subtraction technique (88.7 +/- 3.2% vs. 81.6 +/- 1.2%, p < 0.01, two-sided t-test). CONCLUSION: The presurgical scintigraphic localisation of hyperactive parathyroid glands in pHPT assists minimal invasive surgery serving a high rate of correct findings. According to our data the dual-phase technique seems to be more sensitive than the subtraction technique. In some cases, however, the correct site may only be found using the subtraction technique. For an optimal surgical strategy we suggest the combination of both techniques.
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Glândulas Paratireoides/diagnóstico por imagem , Tecnécio Tc 99m Sestamibi , Humanos , Hiperparatireoidismo/diagnóstico por imagem , Hiperparatireoidismo/cirurgia , Cintilografia/métodos , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To image inflammatory arthritic lesions in experimental arthritis and in patients with arthritis, using a newly developed high-resolution multipinhole single-photon-emission computed tomography (MPH-SPECT) technique. METHODS: Six interleukin-1 receptor antagonist-deficient mice with arthritis of the front and back paws and 2 control BALB/c mice were imaged with MPH-SPECT and scored macroscopically for arthritis. SPECT imaging was performed with a conventional gamma camera upgraded with a pyramidal lead collimator affixed with MPH apertures. All images were reconstructed, and uptake in the paws was quantified in counts/weight and injected activity. To transfer the imaging technique to humans we examined the clinically dominant hand of 6 individuals (3 with established rheumatoid arthritis [RA], 1 with early RA, 1 with osteoarthritis, and 1 healthy control). RESULTS: MPH-SPECT images were high-resolution 3-dimensional tomographic images, which allowed exact localization and quantifiable observation of increased bone metabolism. MPH-SPECT counts of inflamed joints in mice correlated with macroscopic scoring and histologic joint analysis postmortem. In humans, MPH-SPECT images depicted a detailed visualization of tracer accumulation in bony structures of hand and finger joints, and were also capable of imaging increased bone metabolism that had appeared normal with other imaging modalities, e.g., magnetic resonance imaging. CONCLUSION: The MPH-SPECT technique represents a new diagnostic tool in the detection of bone pathology in small-animal arthritis research. Compared with macroscopic scoring, this new method provides a more objective and higher-precision quantifiable measurement of bone reaction, allowing visualization of inflammatory processes of the whole skeleton in vivo. These results suggest that MPH-SPECT may be useful as a diagnostic instrument for monitoring experimental arthritis, with further potential for use in human studies of RA.
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Artrite Reumatoide/diagnóstico por imagem , Artrite/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Animais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
BACKGROUND: In spite of considerable progress in microsurgical techniques, the treatment of long distance defects in peripheral nerves remains challenging for the surgeon. Autologous nerve grafting has been the only applicable procedure to overcome such defects in the past. Due to the known disadvantages of this procedure (neuroma formation and sensory deficits at the donor-site, limited availability of donor-material, etc.) and impaired regenerative results, different tubulisation techniques are discussed more frequently as alternatives to the autologous nerve grafts. AIM OF THE STUDY: In this work, the authors summarise their experiences and results with different synthetically developed materials, cellular and acellular tubes and venous conduits for the reconstruction of peripheral nerve defects. MATERIAL AND METHODS: To analyse peripheral nerve regeneration, we utilised a median nerve model in rats. In these studies nerve gaps up to 40 mm were induced. Guiding tubes of various materials (trimethylene carbonate-epsilon-caprolactone, polyethylene, veins, and collagen) were employed. Furthermore, we introduced Schwann cells as cellular elements into some of the trimethylene carbonate-epsilon-caprolactone tubes. The longest postoperative observation period was nine months. RESULTS: The results demonstrated that only in the case of cellular filled tubes (syngenic Schwann cells) did regeneration occur across the 20 mm gap. This regeneration was comparable to that induced after autologous grafting. Across a 40 mm gap the autologous graft demonstrated the best results.
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Lactonas , Microcirurgia/métodos , Regeneração Nervosa/fisiologia , Transferência de Nervo/métodos , Nervos Periféricos/cirurgia , Polímeros , Próteses e Implantes , Células de Schwann/transplante , Engenharia Tecidual/métodos , Animais , Feminino , Força da Mão/fisiologia , Contração Isométrica/fisiologia , Nervo Mediano/patologia , Nervo Mediano/cirurgia , Nervos Periféricos/patologia , Poliésteres , Ratos , Ratos Endogâmicos Lew , Técnicas de SuturaRESUMO
Although the ability to regenerate is evident in the nervous system, lesioned neurites are unable to cross gaps in neuronal pathways. In order to bridge gaps, guiding cues are essential to direct neurite regrowth. To overcome many of the shortcomings of polymer-based nerve guides, we developed a bioresorbable nerve guide composed of a novel trimethylene carbonate-caprolacton block copolymer (TMC-CL). Pore formation was controlled by using special solvent/precipitation media compositions in combination with the pore forming agent poly ethylene glycol (PEG). NMR spectroscopy, shear force-, compression-, and permeation assays were used for conduit characterization. The polymer conduit has a semipermeable wall with submicron pores to allow free metabolite/drug exchange. In order to investigate the principle of temporally controlled expression of therapeutic proteins in nerve guides, Neuro-2a cells were genetically engineered to express the reporter gene product green fluorescent protein (GFP) under the control of the Tet-On system. When these transduced cells were encapsulated in nerve guides, GFP expression could be induced for days by adding the antibiotic tetracycline derivative doxycycline to the nerve guide environment. Furthermore, encapsulated dorsal root ganglia (DRG) produced long neurites in vitro. In subsequent in vivo experiments, nerve guides filled with Schwann cells (SC) were implanted into lesioned spinal cords of adult rats. Regeneration of spinal cord axons into nerve guides was promoted by co-implanted Schwann cells. The data suggest that the novel TMC-CL nerve guides provide a promising tool for neuroregeneration.
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Implantes Absorvíveis , Materiais Biocompatíveis , Lactonas , Regeneração Nervosa , Polímeros , Animais , Animais Recém-Nascidos , Linhagem Celular , Feminino , Gânglios Espinais/citologia , Neuritos , Poliésteres , Ratos , Ratos Wistar , Células de Schwann/citologia , Engenharia TecidualRESUMO
AIM: Ventricular arrhythmias have been shown to originate in the myocardial peri-infarct region due to irregular heterotopic conduction. Hypoperfused but viable myocardium is often localised in those areas and may be involved in the pathogenesis of arrhythmias. We tested the hypothesis that these myocardial perfusion/metabolism mismatches (MM) are significantly associated with ventricular arrhythmias in the chronic post infarction state. PATIENTS, METHODS: 47 post infarction patients were included in the study. 33 suffered from ventricular arrhythmia whereas 14 did not. All patients underwent (99m)Tc tetrofosmin SPECT and (18)F-FDG PET. A region-of-interest(ROI)-analysis was used to assess viable myocardium based on predefined MM-criteria. Univariate analyses as well as a logistic regression model for the multivariate analysis were carried out. RESULTS: 94% of the arrhythmic patients displayed at least one MM-segment as compared to 64% of the non-arrhythmic patients. MM-segments and arrhythmia showed a statistically significant relation (p = 0.018). The logistic regression model predicted the occurrence or absence of arrhythmia in 85% of all cases. Multivariate analysis gave consistent results, after adjusting for symptomatic chronic heart failure (CHF), aneurysms and age. CONCLUSION: Our results support the hypothesis that hypoperfused but viable myocardium represents an arrhythmogenic substrate and is a relevant risk factor for developing ventricular arrhythmias following myocardial infarction. Therefore, the detection of MM-segments allows the identification of patients with a higher risk for future cardiac events.