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1.
Colorectal Dis ; 15(11): e627-33, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24192263

RESUMEN

AIM: Treatment of locally advanced rectal cancer (LARC) includes preoperative radiation therapy with or without chemotherapy followed by radical surgery, but the clinical outcome is uncertain. A systemic review was carried out to determine the predictive value of (18)F-fluoro-2-deoxyglucose positron emission tomography ((18)FDG-PET) for assessing disease-free (DFS) and overall survival (OS) in LARC. METHOD: A literature search (PubMed/MEDLINE, EMBASE, Cochrane) up to January 2012 to identify full papers with sequential (18)FDG-PET and survival data, using indexing terms and free text words. The inclusion criteria were: a study of at least 10 patients, having sequential (18)FDG-PET imaging before and after adjuvant chemoradiation and a minimal follow-up of 24 months. Studies were selected by two of the authors. A meta-analysis was performed for DFS and OS using the hazard ratio (HR) as the primary outcome. RESULTS: Five eligible studies were identified including 330 patients (mean age 63 years, 64% men), in which PET-CT or PET imaging was used. The American Joint Committee on Cancer stage distribution was as follows: Stage I, 2%; Stage II, 44%; Stage III, 52%; Stage IV, 1%. The pooled HRs for complete metabolic response versus partial or no response were 0.39 (95% CI 0.18-0.86; P = 0.02) for OS and 0.70 (95% CI 0.16-3.14; P = 0.64) for DFS. The lack of significance for DFS might be explained by different follow-up characteristics. There was also clinical heterogeneity among the different studies. CONCLUSION: This systematic review indicates that complete metabolic response on sequential (18)FDG-PET data after preoperative chemoradiation of LARC is predictive of OS, but not of DFS.


Asunto(s)
Tomografía de Emisión de Positrones , Neoplasias del Recto/terapia , Quimioradioterapia Adyuvante , Supervivencia sin Enfermedad , Fluorodesoxiglucosa F18 , Humanos , Estimación de Kaplan-Meier , Terapia Neoadyuvante , Valor Predictivo de las Pruebas , Radiofármacos
2.
Med Phys ; 37(4): 1826-39, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20443505

RESUMEN

PURPOSE: Radioactive atoms attached to monoclonal antibodies are used in radioimmunotherapy to treat cancer while limiting radiation to healthy tissues. One limitation of this method is that only one radioactive atom is linked to each antibody and the deposited dose is often insufficient to eradicate solid and radioresistant tumors. In a previous study, simulations with the Monte Carlo N-Particle eXtended code showed that physical doses up to 50 Gy can be delivered inside tumors by replacing the single radionuclide by a radioactive nanoparticle of 5 nm diameter containing hundreds of radioactive atoms. However, tumoral and normal tissues are not equally sensitive to radiation, and previous works did not take account the biological effects such as cellular repair processes or the presence of less radiosensitive cells such as hypoxic cells. METHODS: The idea is to adapt the linear-quadratic expression to the tumor model and to determine biological effective doses (BEDs) delivered through and around a tumor. This BED is then incorporated into a Poisson formula to determine the shell control probability (SCP) which predicts the cell cluster-killing efficiency at different distances "r" from the center of the tumor. BED and SCP models are used to analyze the advantages of injecting radioactive nanoparticles instead of a single radionuclide per vector in radioimmunotherapy. RESULTS: Calculations of BED and SCP for different distances r from the center of a solid tumor, using the non-small-cell lung cancer as an example, were investigated for 90Y2O3 nanoparticles. With a total activity of about 3.5 and 20 MBq for tumor radii of 0.5 and 1.0 cm, respectively, results show that a very high BED is deposited in the well oxygenated part of the spherical carcinoma. CONCLUSIONS: For either small or large solid tumors, BED and SCP calculations highlight the important benefit in replacing the single beta-emitter 90Y attached to each antibody by a 90Y2O3 nanoparticle.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Hipoxia , Neoplasias Pulmonares/radioterapia , Nanopartículas/química , Neoplasias/patología , Neoplasias/radioterapia , Radioinmunoterapia/métodos , Carcinoma de Pulmón de Células no Pequeñas/patología , Relación Dosis-Respuesta en la Radiación , Humanos , Modelos Lineales , Neoplasias Pulmonares/patología , Método de Montecarlo , Nanomedicina/métodos , Distribución de Poisson , Radiometría/métodos , Planificación de la Radioterapia Asistida por Computador , Programas Informáticos
3.
Cancer Radiother ; 22(5): 384-392, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30055933

RESUMEN

It is now well demonstrated that (18F)-fluorodeoxyglucose PET/CT is the most accurate imaging method for determining disease extent in Hodgkin lymphoma. Thus, up-front PET/CT is mandatory for involved node radiation therapy design. For a proper use of this new imaging modality for radiotherapy, some adaptations should be made to the PET/CT acquisition as well as to the report. Initial PET/CT should be performed in the radiotherapy treatment position. Nuclear medicine physicians should report to the radiation oncologist the precise location of each involved lymph node, for which the use of a common atlas of upper diaphragmatic nodal stations could be useful. All these new procedures have to be implemented in close collaboration among the different medical specialists providing care to Hodgkin lymphoma patients. We report here the usual procedures of PET/CT acquisition in the radiotherapy environment and propose a more sophisticated description of the different lymph nodes for a more efficient nuclear medicine report to the radiation oncologist.


Asunto(s)
Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/radioterapia , Ganglios Linfáticos/diagnóstico por imagen , Irradiación Linfática/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radioterapia Guiada por Imagen , Documentación , Fluorodesoxiglucosa F18 , Humanos , Exposición Profesional , Posicionamiento del Paciente , Dosis de Radiación , Radiofármacos
4.
Cancer Radiother ; 22(5): 393-400, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30033076

RESUMEN

Fluorodeoxyglucose (FDG) positons emission tomography (PET)-computed tomography (CT) is used in many ways at baseline and during the treatment of patients with Hodgkin lymphoma. Many properties of the technique are used in the different steps of patient's management. Initial staging with PET-CT is more accurate than conventional imaging and PET-CT also became the gold standard imaging at the end of treatment with a negative PET-CT mandatory for reaching a complete remission. Early assessment of response by PET-CT is one of the most powerful prognostic factors for progression-free survival of patients with localized and advanced stages and allows guiding treatment. Conversely, previous studies showed that there is no role of FDG PET-CT for the patient's follow-up.


Asunto(s)
Toma de Decisiones Clínicas , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/terapia , Ganglios Linfáticos/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Antineoplásicos/uso terapéutico , Fluorodesoxiglucosa F18 , Trasplante de Células Madre Hematopoyéticas , Humanos , Irradiación Linfática , Estadificación de Neoplasias/métodos , Neoplasia Residual/diagnóstico por imagen , Pronóstico , Radiofármacos , Radioterapia Guiada por Imagen
5.
Med Phys ; 34(11): 4504-13, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18072516

RESUMEN

Radioimmunotherapy uses monoclonal antibodies that are still labeled with only one radioactive atom. The aim of this paper is to assess, by means of MCNPX simulations, the doses delivered around and throughout a solid tumor when the radioactive atom linked to each antibody is replaced by a 5 nm diameter nanoparticle composed of numerous radionuclides. A new model for a spherical vascularized tumor has been developed in which the antibody distributions inside the tumor can be uniform or heterogeneous. It is also possible to simulate a central necrotic core inside the tumor where the concentration of radiolabeled antibodies is assumed to be zero. Dosimetry calculations have been performed for the beta-emitting radionuclide (90)Y2O3. Preliminary results show that the irregularity of vasculature and the presence of a necrotic core have a noticeable influence on the deposited dose profiles. Moreover, with a total activity of 5 and 34 MBq for tumor radii of 0.5 and 1.0 cm, respectively, viable tumor cells can receive doses of up to 50 Gy, even if high nonuniformity of the total activity is observed in the tumor. These simulations still require accurate information about antibody characteristics and necrosis sizes but clearly confirm that the use of monoclonal antibodies conjugated to nanoparticles could lead to a considerable enhancement of treatment efficacy against cancer.


Asunto(s)
Nanopartículas/química , Neoplasias/patología , Neoplasias/radioterapia , Radioinmunoterapia/instrumentación , Radioinmunoterapia/métodos , Radiometría/métodos , Animales , Anticuerpos/química , Anticuerpos Monoclonales/química , Simulación por Computador , Humanos , Método de Montecarlo , Necrosis/patología , Neoplasias/metabolismo , Neovascularización Patológica , Programas Informáticos
6.
Comput Math Methods Med ; 2015: 284360, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26136812

RESUMEN

Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like (131)I or (90)Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of (90)Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as (90)Y, (177)Lu, (131)I, (124)I, and (188)Re are used. Tumour control probability (TCP) and normal tissue complication probability (NTCP) curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody) distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC)). (90)Y and (188)Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases.


Asunto(s)
Neoplasias/inmunología , Neoplasias/radioterapia , Radioinmunoterapia/instrumentación , Radioinmunoterapia/métodos , Radioisótopos/uso terapéutico , Algoritmos , Anticuerpos Monoclonales/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Simulación por Computador , Humanos , Radioisótopos de Yodo/uso terapéutico , Pulmón/efectos de la radiación , Neoplasias Pulmonares/radioterapia , Lutecio/uso terapéutico , Modelos Estadísticos , Método de Montecarlo , Nanomedicina/métodos , Neumonitis por Radiación/diagnóstico , Planificación de la Radioterapia Asistida por Computador/métodos , Renio/uso terapéutico , Radioisótopos de Itrio/uso terapéutico
7.
J Cereb Blood Flow Metab ; 16(6): 1288-99, 1996 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8898703

RESUMEN

(+)-alpha-[11C]Dihydrotetrabenazine (DTBZ) binds to the vesicular monoamine transporter (VMAT2) located in presynaptic vesicles. The purpose of this work was to evaluate various model configurations for analysis of [11C]DTBZ with the aim of providing the optimal measure of monoamine vesicular transporter density obtainable from a single dynamic PET study. PET studies on seven young normal volunteer subjects, ages 20-35, were performed following i.v. injection of 666 +/- 37 MBq (18 +/- 1 mCi) of (+)-alpha-[11C]DTBZ. Dynamic acquisition consisted of a 15-frame sequence over 1 h. Analysis methods included both creation of pixel-by-pixel functional images of transport (K1) and binding (DVtot) and nonlinear least-squares analysis of volume-of-interest data. Pixel-by-pixel calculations were performed for both two-compartment weighted integral calculations and slope-intercept estimations from Logan plots. Nonlinear least-squares analysis was performed applying model configurations with both two-compartments, estimating K1 and DVtot and three compartments, estimating K1-k4. For the more complex configuration, we examined the stability of various binding-related parameters including k3 (konBmax'), k3/k4 (Bmax'/Kd), DVsp[(K1/k2)(k3/k4)], and DVtot [K1/k2(1 + k3/k4)]. The three-compartment model provided significantly improved goodness-of-fit compared to the two-compartment model, yet did not increase the uncertainty in the estimate of the DVtot. Without constraining parameters in the three-compartment model fits, DVtot was found to provide a more stable estimate of binding density than either k3, k3/k4, or DVsp. The two-compartment least-squares analysis yielded approximately 10% underestimations of the total distribution. However, this bias was found to be very consistent from region to region as well as across subjects as indicated by the correlation between two- and three-compartment DVtot estimates of 0.997. We conclude that (+)-alpha-[11C]DTBZ and PET can provide excellent measures of VMAT2 density in the human brain.


Asunto(s)
Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana , Neuropéptidos , Tetrabenazina/análogos & derivados , Adulto , Sitios de Unión , Transporte Biológico , Humanos , Cinética , Modelos Teóricos , Ensayo de Unión Radioligante , Tetrabenazina/metabolismo , Tetrabenazina/farmacología , Tomografía Computarizada de Emisión , Proteínas de Transporte Vesicular de Aminas Biógenas , Proteínas de Transporte Vesicular de Monoaminas
8.
J Med Chem ; 39(1): 191-6, 1996 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-8568807

RESUMEN

Tetrabenazine is a high-affinity inhibitor of the vesicular monoamine transporter in mammalian brain. As part of a program to develop in vivo imaging agents for these transporters in human brain, a series of 2-alkylated dihydrotetrabenazine ligands was synthesized and evaluated in vitro and in vivo for binding to the brain vesicular monoamine transporter. Additions of organometallic reagents to tetrabenazine produced 2-methyl, 2-ethyl, 2-n-propyl, 2-isopropyl, and 2-isobutyl derivatives of dihydrotetrabenazine. The stereochemistry and conformation of the addition products were thoroughly verified by two-dimensional NMR techniques. All of these alkyl derivatives displayed in vitro affinity for the vesicular monoamine transporter binding site in rat brain using competitive assays with the radioligand [3H]methoxytetrabenazine. Except for the isopropyl derivative, all compounds when tested at 10 mg/kg iv showed an ability to inhibit in vivo accumulation of the radioligand [11C]methoxytetrabenazine in the mouse brain striatum. Derivatives with small alkyl groups (methyl, ethyl) were more effective than those with large groups (propyl, isobutyl). These studies suggest that large groups in the 2-position of the benzisoquinoline structure will significantly diminish both in vitro and in vivo binding of these compounds to the vesicular monoamine transporter.


Asunto(s)
Monoaminas Biogénicas/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana , Neuropéptidos , Vesículas Sinápticas/metabolismo , Tetrabenazina/análogos & derivados , Tetrabenazina/farmacología , Inhibidores de Captación Adrenérgica/farmacología , Animales , Unión Competitiva , Transporte Biológico/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Técnicas In Vitro , Ligandos , Espectroscopía de Resonancia Magnética , Ratones , Conformación Molecular , Estructura Molecular , Ratas , Vesículas Sinápticas/química , Tetrabenazina/antagonistas & inhibidores , Tetrabenazina/síntesis química , Tetrabenazina/química , Tetrabenazina/metabolismo , Proteínas de Transporte Vesicular de Aminas Biógenas , Proteínas de Transporte Vesicular de Monoaminas
9.
Neuroscience ; 68(3): 955-62, 1995 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8577387

RESUMEN

The properties as well as the distribution of high specific activity alpha-[O-methyl-3H]methyoxytetrabenazine binding to the synaptic vesicular monoamine transporter were studied autoradiographically in rat brain sections. Saturation analysis revealed [3H]methoxytetrabenazine interaction with a homogeneous population of striatal sites (Hill coefficient 1.00 +/- 0.05), with an apparent equilibrium dissociation binding constant of 3.9 +/- 0.4 nM and a maximal binding capacity of 1.2 +/- 0.1 fmol/micrograms protein. Highest levels of [3H]methoxytetrabenazine binding sites were observed in regions richly innervated by the monoamine systems. In the presence of 1 microM concentrations of a variety of competing drugs, only reserpine significantly inhibited [3H]methoxytetrabenazine binding. The presynaptic nigrostriatal location of [3H]methoxytetrabenazine binding was demonstrated by unilateral lesion of the median forebrain bundle with 6-hydroxydopamine. The resulting decrease of striatal [3H]methoxytetrabenazine binding showed an excellent correlation with tyrosine hydroxylase-positive neuron density in the substantia nigra pars compacta (r2 = 0.96; P < 0.001). The present studies demonstrate that in vitro [3H]methoxytetrabenazine binding is a reliable, quantitative marker of the synaptic vesicular monoamine transporter. Further, it is indicated that [3H]methoxytetrabenazine binding provides an accurate assessment of monoamine neuronal losses and may thus be of great value in future studies of neurodegenerative diseases.


Asunto(s)
Monoaminas Biogénicas/fisiología , Neuronas/efectos de los fármacos , Tetrabenazina/análogos & derivados , Animales , Autorradiografía , Unión Competitiva/efectos de los fármacos , Cinética , Ligandos , Haz Prosencefálico Medial/citología , Haz Prosencefálico Medial/enzimología , Haz Prosencefálico Medial/fisiología , Oxidopamina/toxicidad , Ratas , Tirosina 3-Monooxigenasa/metabolismo
10.
J Nucl Med ; 35(6): 974-82, 1994 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8195884

RESUMEN

METHODS: To assess the potential of thymidine for imaging brain tumors, 20 patients with untreated (n = 14) and recurrent (n = 6) supratentorial intracranial tumors were studied with PET by using 2-[11C]thymidine (Tdr), and the results were compared with [18F]fluorodeoxyglucose (FDG) PET data. RESULTS: Blood analysis consistently revealed a rapid clearance of the intact Tdr together with the appearance of CO2/HCO3- that, with time, accounted for approximately 70% of the total blood activity. As soon as 10 min after tracer injection, brain images showed a low and homogeneous Tdr distribution over the normal brain structures (cortex-to-blood ratio approximately 1). Visual and quantitative analysis revealed increased Tdr uptake (tumor-to-cortex ratio > or = 1.2) in 11 of 14 untreated tumors and in 5 of 6 recurrent tumors. No correlation was found between Tdr uptake and tumor grade. In 12 of the 14 untreated tumors, FDG uptake was low (tumor-to-cortex ratio: 0.83 +/- 0.79), but a FDG hot spot was visualized in 8 of 10 high-grade and in none of the 4 low-grade tumors. FDG uptake was consistently low in recurrent tumors (tumor-to-cortex ratio: 0.49 +/- 0.19), and PET-FDG was negative in 3 of the 6 cases. CONCLUSION: These data indicate the feasibility of brain tumor imaging with Tdr and suggest the potential clinical usefulness of the method in the detection of tumor recurrences. The specificity of the method remains, however, to be investigated.


Asunto(s)
Radioisótopos de Carbono , Neoplasias Supratentoriales/diagnóstico por imagen , Timidina , Tomografía Computarizada de Emisión , Adolescente , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Niño , Desoxiglucosa/análogos & derivados , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Supratentoriales/terapia
11.
J Nucl Med ; 36(12): 2252-60, 1995 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8523116

RESUMEN

UNLABELLED: In the search for an in vivo marker of monoamine nerve terminal integrity, we investigated methoxytetrabenazine (MTBZ) as a tracer of the brain synaptic vesicular monoamine transporter (VMAT2). METHODS: The biodistribution, metabolism and in vivo specificity of MTBZ binding were first evaluated in rodents and the human dosimetry was estimated. Subsequently, the human brain distribution of VMAT2 binding was determined in normal volunteers following administration of [11C]MTBZ. Brain regional time-activity curves were obtained, and parametric transport and binding images were calculated using arterial blood sampling and a two-compartment tracer kinetic model. RESULTS: Regional rat brain localization of [3H]MTBZ 15 min postinjection was consistent with the known monoamine nerve terminal density, which demonstrated the highest activity in the striatum, lateral septum, substantia nigra pars compacta, the raphe nuclei and the locus coeruleus. At this time, chromatography revealed over 82% of brain activity, but less than 47% of plasma activity corresponded to authentic MTBZ. In vivo [11C]MTBZ binding in the mouse brain was inhibited by coinjection of excess unlabeled dihydrotetrabenazine. In humans [11C]MTBZ had high initial brain uptake and rapid clearance from all regions, with longest retention in areas of high VMAT2 concentration. Parametric quantification of VMAT2 density revealed the highest distribution volume in the putamen and caudate with lower values in cerebral cortex and cerebellum. CONCLUSION: Carbon-11-MTBZ is a suitable ligand for PET quantification of the vesicular monoamine transporter in the human brain.


Asunto(s)
Encéfalo/diagnóstico por imagen , Glicoproteínas/análisis , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Neuropéptidos , Neurotransmisores/análisis , Tetrabenazina/análogos & derivados , Tomografía Computarizada de Emisión , Adulto , Animales , Transporte Biológico , Química Encefálica , Radioisótopos de Carbono , Femenino , Humanos , Ligandos , Masculino , Ratones , Ratas , Ratas Sprague-Dawley , Distribución Tisular , Proteínas de Transporte Vesicular de Aminas Biógenas , Proteínas de Transporte Vesicular de Monoaminas
12.
J Nucl Med ; 38(5): 797-802, 1997 May.
Artículo en Inglés | MEDLINE | ID: mdl-9170449

RESUMEN

UNLABELLED: Despite controversial clinicopathological distinctions between Parkinson's disease with dementia (PDD) and Alzheimer's disease (AD), similar patterns of metabolic reduction in the posterior brain were reported previously using PET with [18F]fluorodeoxyglucose. The current study was designed to examine more specific regional differences in cerebral glucose metabolism between PDD and AD using accurate and objective brain mapping techniques. METHODS: This study included nine normal subjects, nine PDD patients and nine AD patients. PDD and AD groups were matched carefully for age, sex and general dementia severity as measured by Mini-Mental State Examination and Clinical Dementia Rating scales. Each subject underwent [18F]fluorodeoxyglucose-PET and neuropsychological testing. After anatomic standardization of PET image sets and stereotactic data extraction, absolute and normalized cerebral metabolic rates were assessed by region of interest and pixel-by-pixel analyses. RESULTS: PDD and AD showed global glucose metabolic reduction with similar regional accentuation involving the lateral parietal, lateral temporal and lateral frontal association cortices and posterior cingulate cortex in comparison to normal controls. When comparing between PDD and AD, however, PDD showed greater metabolic reduction in the visual cortex and relatively preserved metabolism in the medial temporal cortex. CONCLUSION: Although a common feature of metabolic abnormalities in the posterior brain exists in PDD and AD, the presence of regional metabolic differences suggests different degrees and combinations of disease specific underlying pathological and neurochemical processes.


Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Desoxiglucosa/análogos & derivados , Radioisótopos de Flúor , Enfermedad de Parkinson/diagnóstico por imagen , Tomografía Computarizada de Emisión , Anciano , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/metabolismo , Mapeo Encefálico , Estudios de Casos y Controles , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Pruebas Neuropsicológicas , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/metabolismo , Técnicas Estereotáxicas
13.
Intensive Care Med ; 25(6): 574-80, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10416908

RESUMEN

OBJECTIVE: In order to prevent gastric microbial overgrowth, which may complicate nasogastric feeding, administration of nutrients more distally into the gut has been advocated in intensive care patients, as it offers the advantage of keeping the stomach empty and acid. In this study, we assessed the impact of jejunal feeding upon gastic pH in a group of mechanically ventilated, critically ill patients, with special focus on duodenogastric reflux as a possible cause of gastric alkalinization during jejunal nutrition. DESIGN: Prospective experimental study. SETTING: Multidisciplinary intensive care unit of a university hospital. PATIENTS AND METHODS: Gastric pH was recorded by continuous pHmetry over a 4-h period of fasting followed by a 4-h period of nasojejunal feeding at 100 kcal/h in 21 mechanically ventilated, critically ill patients. To determine the contribution of duodenogastric reflux to modifications of gastric acidity, the diet was traced with [(111)In] DTPA (pentetic acid) in 11 of these 21 patients; gastric contents were aspirated every 30 min, then analysed for measurement of radioactivity, glucose, and bile acid concentration. MEASUREMENTS AND RESULTS: Median intragastric pH increased slightly from 1.59 (1.20-2.73; interquartile range) (fasting) to 2.33 (1.65-4.64) (feeding) (p = 0.013), and the length of time that the pH was 4 or above increased from 1 (0-24) to 9 (0-142) min (p = 0.026). The variability of pH values and the number of acute alkalinization episodes did not change between the two phases. In 10 of 11 patients in which the diet was labeled with [(111)In] DTPA, reflux was documented at a given time of the feeding period. Bile acid concentrations in the stomach increased from 392 (61-1076) (fasting) to 1446 (320-2770) micromol/l (feeding) (p = 0.010) and mean glucose concentration increased from 59 (28-95) to 164 (104-449) mg/dl (p = 0.006). CONCLUSION: Duodenogastric reflux is common in mechanically ventilated critically ill patients with nasojejunal feeding tubes. It occurs both during fasting and during nasojejunal feeding. During nasojejunal feeding, moderate alkalinization of the gastric contents occurs as a result of bile and nutrient reflux.


Asunto(s)
Enfermedad Crítica/terapia , Reflujo Duodenogástrico/etiología , Intubación Gastrointestinal/efectos adversos , Respiración Artificial , Adulto , Anciano , Anciano de 80 o más Años , Bilis/química , Interpretación Estadística de Datos , Femenino , Determinación de la Acidez Gástrica , Contenido Digestivo/química , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Estudios Prospectivos
14.
Eur J Pharmacol ; 294(2-3): 577-83, 1995 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-8750721

RESUMEN

The number of neuronal synaptic vesicular monoamine transporters (vesicular monoamine transporter type 2; VMAT2) has been recently proposed as an index of monoamine presynaptic terminal density. The present study investigated the possible regulation of the vesicular monoamine transporter. Rats were treated for 2 weeks with drugs known to influence dopaminergic neurotransmission, including those commonly used in the treatment of Parkinson's disease. Autoradiographic assays were performed using [3H]methoxytetrabenazine, [3H]raclopride, and [3H]WIN 35,428 ([3H]2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane) to measure vesicular monoamine transporter, dopamine D2 receptor and synaptic plasma membrane dopamine re-uptake site bindings, respectively. None of the drug treatments significantly modified levels of vesicular monoamine transporter binding. In contrast, both dopamine D2 receptors and dopamine re-uptake sites were altered by some of the treatment regimens. These data extend preliminary results that suggest the vesicular monoamine transporter is not easily regulated and confirm the plasticity of dopamine D2 receptors and the dopamine re-uptake site. Measures of striatal vesicular monoamine transporter density may, thus, provide objective estimates of monoaminergic innervation in neurodegenerative diseases, unaffected by the use of symptomatic therapies.


Asunto(s)
Dopamina/fisiología , Glicoproteínas de Membrana/efectos de los fármacos , Proteínas de Transporte de Membrana , Neuropéptidos , Animales , Transporte Biológico , Masculino , Glicoproteínas de Membrana/fisiología , Ratas , Ratas Sprague-Dawley , Receptores de Dopamina D2/fisiología , Sinapsis/fisiología , Tetrabenazina/análogos & derivados , Tetrabenazina/metabolismo , Proteínas de Transporte Vesicular de Aminas Biógenas , Proteínas de Transporte Vesicular de Monoaminas
15.
Eur J Pharmacol ; 278(3): 249-52, 1995 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-7589162

RESUMEN

The two enantiomers of alpha-dihydrotetrabenazine were separated using chiral high performance liquid chromatography. The (+)-isomer showed high affinity in vitro (Ki = 0.97 +/- 0.48 nM) for the vesicular monoamine transporter (VMAT2) in rat brain striatum, whereas the (-)-isomer was inactive (Ki = 2.2 +/- 0.3 microM). Each isomer was then synthesized in carbon-11 labeled form, and regional brain biodistributions in mice determined after intravenous injection. Only (+)-alpha-dihydrotetrabenazine showed selective and specific accumulations in regions of dense monoaminergic innervation (e.g., striatum, hypothalamus), which could be blocked by coinjection of unlabeled tetrabenazine. Binding of alpha-dihydrotetrabenazine to the vesicular monoamine transporter is thus stereospecific.


Asunto(s)
Glicoproteínas/metabolismo , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Neuropéptidos , Neurotransmisores/metabolismo , Tetrabenazina/análogos & derivados , Animales , Encéfalo/metabolismo , Radioisótopos de Carbono , Evaluación Preclínica de Medicamentos , Femenino , Ratones , Ratones Endogámicos , Estereoisomerismo , Tetrabenazina/química , Tetrabenazina/metabolismo , Tetrabenazina/farmacología , Proteínas de Transporte Vesicular de Aminas Biógenas , Proteínas de Transporte Vesicular de Monoaminas
16.
Nucl Med Biol ; 23(4): 467-71, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8832701

RESUMEN

The effects of various dopaminergic drug treatments on the in vivo regional brain distribution of high-affinity radioligands ([11C]dihydrotetrabenazine and [11C]methoxytetrabenazine) for the rat brain vesicular monoamine transporter (VMAT2) were determined. Acute treatments with reserpine (2 mg/kg i.p.), tetrabenazine (10 mg/kg i.v.) or related benzoisoquinolines significantly reduced radiotracer binding in vivo. In contrast, radiotracer distributions remained unchanged after treatments with other dopaminergic drugs, whether given by single injection (haloperidol, 1 mg/kg i.p., pargyline 80 mg/kg), repeatedly (pargyline, 80 mg/kg s.c., 14 days), or by continuous infusion (deprenyl, 10 mg/kg/day, 5 days; L-DOPA methyl ester 100 mg/kg/day, 5 days). Repeated injections of tetrabenazine (5 mg/kg i.p., twice daily, 3 days) did not alter in vivo radioligand binding measured after allowing drug washout from the brain. These studies support the proposal that in vivo PET imaging of VMAT2 radioligands in patients with extrapyramidal movement disorders will not be affected by concurrent use of L-DOPA or deprenyl.


Asunto(s)
Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Dopaminérgicos/farmacología , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana , Neuropéptidos , Tetrabenazina/análogos & derivados , Animales , Transporte Biológico/efectos de los fármacos , Células COS , Radioisótopos de Carbono , Interacciones Farmacológicas , Femenino , Ratones , Ratones Endogámicos , Ensayo de Unión Radioligante , Ratas , Ratas Sprague-Dawley , Tetrabenazina/metabolismo , Tetrabenazina/farmacocinética , Proteínas de Transporte Vesicular de Aminas Biógenas , Proteínas de Transporte Vesicular de Monoaminas
17.
Nucl Med Commun ; 23(11): 1107-13, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12411840

RESUMEN

Planar pulmonary scintigraphy is still regularly performed for the evaluation of pulmonary embolism (PE). However, only about 50-80% of cases can be resolved by this approach. This study evaluates the ability of tomographic acquisition (single photon emission computed tomography, SPECT) of the perfusion scan to improve the radionuclide diagnosis of PE. One hundred and fourteen consecutive patients with a suspicion of PE underwent planar and SPECT lung perfusion scans as well as planar ventilation scans. The final diagnosis was obtained by using an algorithm, including D-dimer measurement, leg ultrasonography, a V/Q scan and chest spiral computed tomography, as well as the patient outcome. A planar perfusion scan was considered positive for PE in the presence of one or more wedge shaped defect, while SPECT was considered positive with one or more wedge shaped defect with sharp borders, three-plane visualization, whatever the photopenia. A definite diagnosis was achieved in 70 patients. After exclusion of four 'non-diagnostic' SPECT images, the prevalence of PE was 23% (n =15). Intraobserver and interobserver reproducibilities were 91%/94% and 79%/88% for planar/SPECT images, respectively. The sensitivities for PE diagnosis were similar for planar and SPECT perfusion scans (80%), whereas SPECT had a higher specificity (96% vs 78%; P =0.01). SPECT correctly classified 8/9 intermediate and 31/32 low probability V/Q scans as negative. It is concluded that lung perfusion SPECT is readily performed and reproducible. A negative study eliminates the need for a combined V/Q study and most of the 'non-diagnostic' V/Q probabilities can be solved with a perfusion image obtained by using tomography.


Asunto(s)
Interpretación de Imagen Asistida por Computador/métodos , Embolia Pulmonar/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico , Control de Calidad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Relación Ventilacion-Perfusión
18.
Acta Neurol Belg ; 101(4): 196-209, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11851026

RESUMEN

The purpose of these guidelines is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of brain perfusion SPECT studies using Tc-99m radiopharmaceuticals and brain metabolism PET studies using F-18 fluorodeoxyglucose (FDG). These guidelines have been adapted and extended from those produced by the Society of Nuclear Medicine (Juni et al., 1998) and the European Association of Nuclear Medicine by a Belgian group of experts in the field trained in neurology and/or nuclear medicine. Some indications are not universally approved (e.g. brain death), but largely supported by the literature. They have been included in these guidelines in order to provide recommendations and a standardised protocol.


Asunto(s)
Encéfalo/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/normas , Tomografía Computarizada de Emisión/normas , Acetazolamida/administración & dosificación , Adulto , Encéfalo/metabolismo , Muerte Encefálica/diagnóstico por imagen , Trastornos Cerebrovasculares/clasificación , Trastornos Cerebrovasculares/diagnóstico por imagen , Niño , Traumatismos Craneocerebrales/diagnóstico por imagen , Demencia/diagnóstico por imagen , Diagnóstico Diferencial , Epilepsia/diagnóstico por imagen , Ayuno , Fluorodesoxiglucosa F18/administración & dosificación , Humanos , Procesamiento de Imagen Asistido por Computador , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/diagnóstico por imagen , Radiofármacos/administración & dosificación , Hemorragia Subaracnoidea/diagnóstico por imagen , Tecnecio/administración & dosificación
20.
Minerva Anestesiol ; 79(5): 498-503, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23511349

RESUMEN

BACKGROUND: Mechanically ventilated patients are prone to develop ventilator associated pneumonia due to microaspirations of subglottic secretions around the endotracheal tube cuff (usually constructed of polyvinyl material). A novel polyurethane cuff has been designed to minimize these leakages. The aim of the study was to compare the tracheal sealing capacities between the two tubes. METHODS: Twenty-nine consecutive patients from whom tracheal intubation was necessary as part of their care were randomized to receive either a polyvinyl HI-LO Evac® or a polyurethane SEALGUARD Evac® endotracheal tube. Patients requiring emergency intubation, with unstable hemodynamics or history of tracheal/laryngeal disease were excluded. For the entire study, cuff pressure was set at 30 cmH2O, and ventilator parameters were adjusted for a plateau pressure ≤30 cmH2O; Patients were fasting, placed in a strict 45° position during 12 hours and sedated if needed. After injection of 74 MBq 99mTc-DTPA diluted in 5 mL 0.9% NaCl just above the cuff, tracheal radioactivity was assessed sequentially (hourly from T0 to T6, then T8 and T12 hours) using a scintillation camera. RESULTS: Sixteen polyurethane and 13 polyvinyl tubes were compared. Leakages were observed in 11/29 patients (38%) (5/16 polyurethane and 6/13 polyvinyl tubes [P=NS]). Leakages occurred more often in female (7/8) than in male patients (4/21) (P<0.001). Microaspirations were decreased with larger tubes (size 9 vs. ≤8.5: 24% vs. 75%; P=0.01), whatever the cuff membrane. CONCLUSION: These preliminary results suggest that both tubes are poorly effective in preventing microaspirations.


Asunto(s)
Intubación Intratraqueal/instrumentación , Materiales Manufacturados , Neumonía por Aspiración/prevención & control , Poliuretanos , Polivinilos , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Intubación Intratraqueal/métodos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Cintigrafía , Tráquea/diagnóstico por imagen
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