RESUMEN
BACKGROUND: A decreased longitudinal strain in basal segments with a base-to-apex gradient has been described in patients with cardiac amyloidosis (CA). OBJECTIVES: Aim was to investigate the left ventricular (LV) regional distribution of early-phase 99mTc-Hydroxymethylene diphosphonate (99mTc-HMDP) uptake in patients with transthyretin-related cardiac amyloidosis (TTR-CA). METHODS: All patients underwent a whole-body planar 99mTc-HMDP scintigraphy acquired at 10-min post-injection (early-phase) followed by a thorax SPECT/CT. The segmental uptake (expressed as % of maximal myocardial HMDP uptake) was investigated on the AHA 17-segment model and 3-segment model (basal, mid-cavity, apical). RESULTS: Sixty-one TTR-CA patients were included of whom 29 were wild-type (wt-TTR-CA) and 32 had hereditary TTR-CA (m-TTR-CA). Early myocardial 99mTc-HMDP uptake occurred in all TTR-CA. In all patients, segmental analysis of the LV myocardial distribution of 99mTc-HMDP uptake showed an increased median uptake (interquartile range) in basal/mid-cavity segments compared to the lowest median uptake of apical segments (respectively, 79% [72%-86%] vs. 72% [64%-81%]; P < 10-6). This pattern was similar in wt-TTR-CA group (78% [70%-84%] vs. 70% [61%-81%]; P < 10-6), in m-TTR-CA group (80% [74%-86%] vs. 73 [66%-82%]; P < 10-7) and remained constant independently of the TTR mutation subtype with P ranging 10-5 to 0.03. CONCLUSIONS: Early-phase myocardial scintigraphy identified regional distribution of 99mTc-HMDP uptake characterized by a base-to-apex gradient, corroborating echocardiographic, and cardiac magnetic resonance findings. This apical sparing pattern was similar across TTR-CA and TTR mutation subtypes.
Asunto(s)
Neuropatías Amiloides Familiares/diagnóstico por imagen , Miocardio/metabolismo , Radiofármacos/farmacocinética , Medronato de Tecnecio Tc 99m/análogos & derivados , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Mutación , Medronato de Tecnecio Tc 99m/farmacocinéticaRESUMEN
BACKGROUND: This study sought to compare the intensity of early-phase myocardial uptake of two phosphonate-based radiotracers, 99mTc-hydroxymethylene diphosphonate (HMDP) and 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), in patients with hereditary transthyretin-related cardiac amyloidosis (TTR-CA). METHODS: Six patients with biopsy-proven diagnosis of TTR-CA and characteristic amyloid fibril composition underwent early-phase 99mTc-HMDP myocardial scintigraphy as part of their routine workup; they were later assessed by 99mTc-DPD scintigraphy after having signed informed written consent. Heart-to-mediastinum-ratio was measured at both time points as well as regional distribution on 17-segment analysis. RESULTS: All patients had an H/M ratio >1.28 on both imaging. 99mTc-DPD uptake was slightly higher than 99mTc-HMDP uptake in 3 patients, but no statistical difference was found (P = 0.13). Regional distribution of the two radiotracers was well correlated on bull's eyes analysis, with only slight underestimation of 99mTc-DPD uptake in the anterior/apical segments, compared with 99mTc-HMDP. CONCLUSION: 99mTc-HMDP and 99mTc-DPD show comparable myocardial uptake intensity on early-phase scintigraphy and can be used alternatively for the diagnosis of TTR-CA.
Asunto(s)
Neuropatías Amiloides Familiares/diagnóstico por imagen , Difosfonatos/farmacocinética , Corazón/diagnóstico por imagen , Compuestos de Organotecnecio/farmacocinética , Medronato de Tecnecio Tc 99m/análogos & derivados , Anciano , Anciano de 80 o más Años , Biopsia , Europa (Continente) , Femenino , Humanos , Masculino , Miocardio/metabolismo , Cintigrafía , Análisis de Regresión , Medronato de Tecnecio Tc 99m/farmacocinéticaAsunto(s)
Neuropatías Amiloides Familiares/diagnóstico por imagen , Cardiomiopatías/diagnóstico por imagen , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/diagnóstico por imagen , Cintigrafía/métodos , Radiofármacos/administración & dosificación , Medronato de Tecnecio Tc 99m/análogos & derivados , Neuropatías Amiloides Familiares/genética , Cardiomiopatías/genética , Diagnóstico Diferencial , Predisposición Genética a la Enfermedad , Humanos , Mutación , Prealbúmina/genética , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medronato de Tecnecio Tc 99m/administración & dosificaciónRESUMEN
Cardiac amyloidosis must be suspected in all cases of hypertrophic cardiomyopathy with preserved left ventricular ejection fraction to allow specific management. Final diagnosis needs pathological evidence, but bone scintigraphy may be an alternative for TTR amyloidosis. Invasive samplings are limited by new tools. Amyloidosis typing is required to start specific therapies if possible. Main specific treatments that are available are chemotherapy for AL; transthyretin stabilizer or gene therapy, studied for TTR-related cardiac amyloidosis.
Asunto(s)
Amiloidosis/diagnóstico , Amiloidosis/terapia , Cardiomiopatías/diagnóstico , Cardiomiopatías/terapia , Árboles de Decisión , HumanosRESUMEN
BACKGROUND: Aortic stenosis (AS) and transthyretin cardiac amyloidosis (TTR-CA) are both frequent in elderly. The combination of these two diseases has never been investigated. AIMS: To describe patients with concomitant AS and TTR-CA. METHODS: Six cardiologic French centres identified retrospectively cases of patients with severe or moderate AS associated with TTR-CA hospitalized during the last 6 years. RESULTS: Sixteen patients were included. Mean ± SD age was 79 ± 6 years, 81% were men. Sixty per cent were NYHA III-IV, 31% had carpal tunnel syndrome, and 56% had atrial fibrillation. Median (Q1;Q4) NT-proBNP was 4382 (2425;4730) pg/mL and 91% had elevated cardiac troponin level. Eighty-eight per cent had severe AS (n = 14/16), of whom 86% (n = 12) had low-gradient AS. Mean ± SD interventricular septum thickness was 18 ± 4 mm. Mean left ventricular ejection fraction and global LS were 50 ± 13% and -7 ± 4%, respectively. Diagnosis of TTR-CA was histologically proven in 38%, and was based on strong cardiac uptake of the tracer at biphosphonate scintigraphy in the rest. Eighty-one per cent had wild-type TTR-CA (n = 13), one had mutated Val122I and 19% did not had genetic test (n = 3). Valve replacement was surgical in 63% and via transcatheter in 13%. Median follow-up in survivors was 33 (16;65) months. Mortality was of 44% (n = 7) during the whole follow-up period. CONCLUSIONS: Combination of AS and TTR-CA may occur in elderly patients particularly those with a low-flow low-gradient AS pattern and carries bad prognosis. Diagnosis of TTR-CA in AS is relevant to discuss specific treatment and management.
Asunto(s)
Neuropatías Amiloides Familiares , Estenosis de la Válvula Aórtica , Anciano , Femenino , Humanos , Masculino , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Prealbúmina , Volumen Sistólico , Resultado del TratamientoRESUMEN
Cardiac amyloidosis (CA) is recognized as a common cause of restrictive cardiomyopathy and heart failure due to the deposition of insoluble proteins in the myocardial interstitium. We emphasize the role of [18F]-sodium fluoride (NaF) PET/CT as a potential noninvasive tool to identify and differentiate the transthyretin-related cardiac amyloidosis from the light-chain cardiac amyloidosis. We report cases of a 73-year-old man and a 75-year-old woman followed in our center for congestive heart failure with marked alteration of the left ventricular ejection fraction due to familial transthyretin Val122Ile cardiac amyloidosis and light-chain cardiac amyloidosis, respectively, confirmed on endomyocardial biopsy.
Asunto(s)
Amiloidosis/diagnóstico por imagen , Técnicas de Imagen Cardíaca/métodos , Cardiopatías/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluoruro de Sodio , Anciano , Diagnóstico Diferencial , Femenino , Radioisótopos de Flúor , Humanos , Masculino , Radiofármacos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Amyloidosis is characterized by extracellular deposits of insoluble proteins that cause tissue damage. The three main types are monoclonal light chain (AL), wild-type transthyretin (wt-TTR) and mutated transthyretin (m-TTR) amyloidosis. Cardiac amyloidosis (CA) raises diagnostic challenges. OBJECTIVE: To assess the diagnostic accuracy of (99m)Tc-HMDP-scintigraphy for typing CA, differentiating CA from non-amyloid left ventricle hypertrophy (LVH), and predicting outcomes. METHODS: 121 patients with suspected CA underwent (99m)Tc-HMDP-scintigraphy in addition to standard investigations. RESULTS: CA was diagnosed in all AL (n = 14) and wt-TTR (n = 21). Among m-TTR (n = 34), 26 had CA, 4 neuropathy without CA and 4 were asymptomatic carriers. Of the 52 patients with non-amyloid heart disease, 37 had LVH and served as controls. (99m)Tc-HMDP cardiac uptake occurred in all wt-TTR, in m-TTR with CA except two and in one AL. A visual score ≥ 2 was 100% specific for diagnosing TTR-CA. Among TTR-CA, heart-to-skull retention (HR/SR) correlated with CA severity (LVEF and NT-proBNP). Median follow-up was 111 days (50;343). In a multivariate Cox model including clinical, echocardiographic and scintigraphic variables, NYHA III-IV and HR/SR > 1.94 predicted acute heart failure and/or death. CONCLUSIONS: This preliminary study suggests that (99m)Tc-HMDP-scintigraphy may aid differentiation between transthyretin and AL-CA as well as CA from other LVHs. (99m)Tc-HMDP-scintigraphy appears to provide prognostic information in CA.
Asunto(s)
Amiloidosis/diagnóstico por imagen , Cardiopatías/diagnóstico por imagen , Radiofármacos/administración & dosificación , Medronato de Tecnecio Tc 99m/análogos & derivados , Anciano , Amiloidosis/patología , Ecocardiografía , Femenino , Cardiopatías/patología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Cintigrafía , Medronato de Tecnecio Tc 99m/administración & dosificaciónRESUMEN
A 71-year-old African man without history of cardiac disease was referred to our center for dyspnea. Transthoracic echocardiogram and cardiac MRI were suggestive of cardiac amyloidosis (CA). The diagnosis of the light-chain cardiac amyloidosis (AL-CA) was made after a first endomyocardial biopsy. Accordingly chemotherapy was started. Systematic 99mTc-HMDP scintigraphy showed moderate cardiac uptake (visual score of 2), unusual for AL-CA, and permitted to rectify the diagnosis. Hereditary transthyretin cardiac amyloidosis was confirmed by a second endomyocardial biopsy with a positive Congo-red and anti-transthyretin antibody stainings, mass spectrometry and genetic analysis (Val122Ile mutation).
Asunto(s)
Amiloidosis Familiar/diagnóstico por imagen , Amiloidosis Familiar/genética , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/genética , Errores Diagnósticos/prevención & control , Medronato de Tecnecio Tc 99m/análogos & derivados , Anciano , Diagnóstico Diferencial , Humanos , Masculino , Cintigrafía , RadiofármacosRESUMEN
GABAA receptors shape synaptic transmission by modulating Cl(-) conductance across the cell membrane. Remarkably, animal toxins that specifically target GABAA receptors have not been identified. Here, we report the discovery of micrurotoxin1 (MmTX1) and MmTX2, two toxins present in Costa Rican coral snake venom that tightly bind to GABAA receptors at subnanomolar concentrations. Studies with recombinant and synthetic toxin variants on hippocampal neurons and cells expressing common receptor compositions suggest that MmTX1 and MmTX2 allosterically increase GABAA receptor susceptibility to agonist, thereby potentiating receptor opening as well as desensitization, possibly by interacting with the α(+)/ß(-) interface. Moreover, hippocampal neuron excitability measurements reveal toxin-induced transitory network inhibition, followed by an increase in spontaneous activity. In concert, toxin injections into mouse brain result in reduced basal activity between intense seizures. Altogether, we characterized two animal toxins that enhance GABAA receptor sensitivity to agonist, thereby establishing a previously unidentified class of tools to study this receptor family.
Asunto(s)
Venenos Elapídicos/farmacología , Elapidae/metabolismo , Péptidos/farmacología , Receptores de GABA-A/metabolismo , Secuencia de Aminoácidos , Animales , Venenos Elapídicos/química , Células HEK293 , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Activación del Canal Iónico/efectos de los fármacos , Cinética , Masculino , Ratones , Datos de Secuencia Molecular , Mutación/genética , Red Nerviosa/efectos de los fármacos , Red Nerviosa/fisiología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Péptidos/química , Unión Proteica/efectos de los fármacos , Subunidades de Proteína/química , Subunidades de Proteína/metabolismo , Ratas , Receptores de GABA-A/química , Receptores de GABA-A/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacología , Sinaptosomas/efectos de los fármacos , Sinaptosomas/metabolismo , XenopusRESUMEN
Senile systemic amyloidosis (SSA) is characterized by infiltration of amyloid transthyretin fibrils in the myocardium. SSA occurs mainly (but not always) in elderly men. SSA leads to hypertrophic and/or restrictive cardiomyopathy complicated by conduction disturbances, atrial arrhythmia and systemic embolization (stroke ). That is why SSA needs a special care and to be diagnosed. Cardiac SSA diagnosis needs to exclude two other forms of cardiac amyloidosis: AL amyloidosis (light chain) and hereditary transthyretin amyloidosis (genetic testing). Scintigraphic 99mTc-DPD heart retention is observed in cardiac amyloidosis. DPD heart retention is more frequent in cardiac transthyretin amyloidosis than in cardiac AL amyloidosis. Specific treatments of cardiac TTR amyloidosis are in development.
Asunto(s)
Amiloidosis/diagnóstico , Cardiopatías/diagnóstico , Factores de Edad , Anciano , Amiloidosis/terapia , Árboles de Decisión , Cardiopatías/terapia , HumanosRESUMEN
The venom of the North African scorpion Androctonus amoreuxi (Aam) was analyzed using a combination of gel filtration, C18 reverse phase HPLC together with mass spectrometry analysis and bioassays. Three novel Birtoxin-like (BTX-L) peptides of 58 amino acid residues comprising three disulfide bridges were isolated and chemically characterized. One peptide, AamBTX-L3, induced serious toxic symptoms in mice and was lethal at nanogram quantities using intracerebroventricular injection. The three BTX-L peptides were tested in competition experiments on rat brain synaptosomes against the (125)I-labeled "classical" α- and ß-toxins of reference, as well as with the (125)I-KTX, a voltage-gated potassium channel blocker. Only AamBTX-L3 was able to prevent the equilibrium binding of the ß-toxin (125)I-Css IV to its receptor site 4 with a IC(50) value of 189 nM. Even if previous electrophysiological data allowed the classification of other BTX-L peptides among the ß-type toxins, this report clearly shows that AamBTX-L3 is pharmacologically a ß-toxin, which recognizes the voltage-gated Na(+) (Na(v)) channels from central mammalian neurons. In order to uncover the residues functionally essential for interaction between the AamBTX-L3 with the putative receptor site of (125)I-Css IV on Na(v)1.2, molecular models of the three novel Aam BTX-L molecules were made and their surfaces were compared to the already described Css IV biologically interactive surfaces. A hypothesis is given that in BTX-L3, three residues found in the α-helix play a key role during target binding.
Asunto(s)
Venenos de Escorpión/química , Venenos de Escorpión/metabolismo , Secuencia de Aminoácidos , Animales , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Masculino , Espectrometría de Masas , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Filogenia , Ratas , Homología de Secuencia de Aminoácido , Membranas Sinápticas/efectos de los fármacosRESUMEN
Scorpion venoms are very complex mixtures of molecules, most of which are peptides displaying different kinds of biological activity. Indeed, these peptides specifically bind to a variety of pharmacological targets, in particular ionic channels located in prey tissues, resulting in neurotoxic effects. Toxins modulating Na+, K+, Ca2+ and Cl(-) currents have been described in scorpion venoms. In this work, we have used several specific antibodies raised against the most lethal scorpion toxins already described to screen the Moroccan scorpion Androctonus mauretanicus mauretanicus venom in order to characterize new compounds. This immunological screening was also implemented by toxicity tests in mice and with mass spectrometry study, providing new informations on the molecular composition of this venom. In fine, we were able to determine the molecular masses of 70-80 different compounds. According to the immunological data obtained, many toxins cross-react with three sera raised against the most lethal alpha-toxins found in North African scorpion venoms, but not at all with those raised against the main beta-toxins from South and North American venoms. Some of the previously described toxins from Androctonus mauretanicus mauretanicus venom could thus be detected by combining immunological tests, toxicity in mice and molecular masses. Among these toxins, one of them, which showed a mild cross-reaction with the serum raised against AaH I (a highly potent toxin from the venom of Androctonus australis), was identified as Amm III and fully sequenced.
Asunto(s)
Venenos de Escorpión/química , Escorpiones/metabolismo , Secuencia de Aminoácidos , Animales , Antígenos/inmunología , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Reacciones Cruzadas , Sueros Inmunes/inmunología , Masculino , Espectrometría de Masas , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Proteómica , Radioinmunoensayo , Venenos de Escorpión/inmunología , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
From the venom of the scorpion Androctonus australis, we have isolated a new bioactive polypeptide termed AaBTX-L1. When tested on the insect voltage-gated Na(+) channel (para) of the fruit fly, this toxin was able to induce a clear shift in activation (V(1/2)), resulting in the opening of the channel at more negative membrane potentials. Furthermore, AaBTX-L1 was totally devoid of toxicity when injected into mice intracerebroventricularly and did not compete with radiolabeled voltage-gated K(+) and Na(+) channel toxins in binding experiments on rat brain synaptosomes. Using its N-terminal amino acid sequence to design degenerate primers, several clones were amplified by PCR from the A. australis venom gland cDNA library. As a consequence, seven full oligonucleotide sequences encoding "long-chain" polypeptides with only three disulfide bridges have been cloned for the first time and are described here. Remarkably, they share high similarity with the anti-insect toxin Birtoxin from Parabuthus transvaalicus.
Asunto(s)
Oocitos/fisiología , Venenos de Escorpión/química , Venenos de Escorpión/toxicidad , Escorpiones/metabolismo , Sinaptosomas/metabolismo , Secuencia de Aminoácidos , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Ratones , Datos de Secuencia Molecular , Oocitos/efectos de los fármacos , Ratas , Venenos de Escorpión/metabolismo , Homología de Secuencia de Aminoácido , Especificidad de la Especie , Análisis de Supervivencia , Xenopus laevisRESUMEN
UNLABELLED: Assessment of perfusion defect extent is essential for determining prognosis after a myocardial infarction (MI), but quantification methods usually rely on segmental analysis, which may lack accuracy. We present an automated voxel-based and template-based approach for precise quantification of perfusion defect extent and reperfusion evolution. METHODS: Coronary angiography and stress/reinjection (201)Tl tomography were performed prospectively on 49 patients with recent MI (45 men; mean age +/- SD, 54 +/- 10 y), before and 3 mo after revascularization (40 angioplasties and 9 bypasses). Perfusion defect extent was quantified using expert 16-segment visual scoring of the slices and a 3-dimensional (3D) method with spatial normalization between times 1 and 2. Briefly, the latter automatically extracted myocardial edges, matched them to a reference template, and compared the perfusion intensity in each voxel with the intensity of the corresponding voxel in a control population of 100 healthy subjects. RESULTS: Reocclusion occurred in 12 patients within 3 mo of surgery (all had undergone angioplasty). The perfusion gain between times 1 and 2, assessed by visual analysis, was significantly higher in permeable patients than in reoccluded patients: 12.4% +/- 13.3% and 2.3% +/- 8.2% of the initial stress defect, respectively (P = 0.02). Proportional gains, measured with the quantitative 3D method, were 4.5% +/- 3.6% and 1.9% +/- 2.7%, respectively (P = 0.02). Furthermore, the 3D method allowed measurement within the initial ischemic defect (reversible part of the stress defect at time 1), the extent of myocardium whose perfusion improved at time 2 (reperfusion), and the extent of myocardium whose perfusion remained unchanged (residual ischemia). A voxel-by-voxel analysis of these regions revealed that the proportion of reperfusion was significantly higher in permeable patients than in reoccluded patients: 60.0% +/- 21.3% versus 40.0% +/- 22.5%, respectively (P = 0.008). This was cumbersome to quantify using visual analysis and did not reach statistical significance, likely because of segmental division (partial-volume effect) and absence of spatial normalization. CONCLUSION: The 3D voxel-based quantification allows satisfying assessment of reperfusion 3 mo after MI. Moreover, the automated analysis using spatial normalization should facilitate a reproducible assessment of large populations over time.
Asunto(s)
Procesamiento de Imagen Asistido por Computador , Infarto del Miocardio/diagnóstico por imagen , Isquemia Miocárdica/diagnóstico por imagen , Reperfusión Miocárdica/efectos adversos , Tecnecio Tc 99m Sestamibi , Anciano , Angiografía Coronaria , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/cirugía , Miocardio , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
The venom of the scorpion Androctonus mauretanicus mauretanicus was screened by use of a specific serum directed against AaH II, the scorpion alpha-toxin of reference, with the aim of identifying new analogues. This led to the isolation of Amm VIII (7382.57 Da), which gave a highly positive response in ELISA, but was totally devoid of toxicity when injected subcutaneously into mice. In voltage-clamp experiments with rat brain type II Na+ channel rNa(v)1.2 or rat skeletal muscle Na+ channel rNa(v)1.4, expressed in Xenopus oocytes, the EC50 values of the toxin-induced slowing of inactivation were: 29+/-5 and 416+/-14 nM respectively for AmmVIII and 2.6+/-0.3 nM and 2.2+/-0.2 nM, respectively, for AaH II interactions. Accordingly, Amm VIII clearly discriminates neuronal versus muscular Na+ channel. The Amm VIII cDNA was amplified from a venom gland cDNA library and its oligonucleotide sequence determined. It shows 87% sequence homology with AaH II, but carries an unusual extension at its C-terminal end, consisting of an additional Asp due to a point mutation in the cDNA penultimate codon. We hypothesized that this extra amino acid residue could induce steric hindrance and dramatically reduce recognition of the target by Amm VIII. We constructed a model of Amm VIII based on the X-ray structure of AaH II to clarify this point. Molecular modelling showed that this C-terminal extension does not lead to an overall conformational change in Amm VIII, but drastically modifies the charge repartition and, consequently, the electrostatic dipole moment of the molecule. At last, liquid-phase radioimmunassays with poly- and monoclonal anti-(AaH II) antibodies showed the loss of conformational epitopes between AaH II and Amm VIII.
Asunto(s)
Músculo Esquelético/metabolismo , Neuronas/metabolismo , Venenos de Escorpión/genética , Canales de Sodio/fisiología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , ADN Complementario/química , ADN Complementario/genética , ADN Complementario/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Femenino , Inyecciones Intraventriculares , Inyecciones Subcutáneas , Dosificación Letal Mediana , Potenciales de la Membrana/efectos de los fármacos , Ratones , Datos de Secuencia Molecular , Oocitos/efectos de los fármacos , Oocitos/fisiología , Venenos de Escorpión/química , Venenos de Escorpión/farmacología , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Canales de Sodio/efectos de los fármacos , Canales de Sodio/genética , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Xenopus laevisRESUMEN
UNLABELLED: Diagnosis of pulmonary embolism (PE) by visual interpretation of ventilation/perfusion (V/Q) scans is limited by the high percentages of patients classified in the intermediate- and low-probability categories. This study proposes a quantitative analysis of the distribution of V/Q ratios to better identify patients with PE. METHODS: We studied 99 consecutive patients who underwent dual-isotope (81m)Kr/(99m)Tc-macroaggregate V/Q scanning and arterial blood gas analysis within 48 h. The 8-view V/Q scans were visually analyzed by 2 observers according to the revised criteria of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) (normal scan or low, intermediate, or high probability of PE). Quantitative analysis of the posterior-view distribution histogram of V/Q ratios was performed using dedicated software. Briefly, regions of interest were drawn around the lungs on the matched V/Q images, smooth filtering was applied, normalized regional V/Q ratios were calculated within each pixel, and a distribution histogram was built. RESULTS: Patients with normal scans (n = 16) had a predominance of V/Q ratios (63.3% +/- 13.0%) between 0.8 and 1.2. They had only 9.8% +/- 5.8% of ratios > 1.2, and the remaining 26.9% +/- 7.5% of ratios were <0.8. By contrast, patients with PE (n = 34) were characterized by a significant increase (15.5 +/- 10.0%, P = 0.04) in high V/Q ratios (>1.2) and a significant increase (34.5% +/- 8.2%, P = 0.003) in low V/Q ratios (<0.8). Interestingly, a similar pattern was found in patients with a high PIOPED probability of PE, 21.3% +/- 11.0% and 37.5% +/- 9.2%, respectively. Within the nondiagnostic group (intermediate- + low-probability scans, n = 58), 17 patients were finally diagnosed with PE. Analysis of the distribution histogram in this group allowed the identification of 5 patients with PE (specificity, 78%). CONCLUSION: A quantitative approach to lung scan interpretation, based on the distribution histogram of V/Q ratios, may be helpful for categorizing patients with suspected PE.