RESUMEN
Background: All-trans-retinoic acid (ATRA) is a differentiating agent used in the treatment of acute-promyelocytic-leukemia (APL) and it is under-exploited in other malignancies despite its low systemic toxicity. A rational/personalized use of ATRA requires the development of predictive tools allowing identification of sensitive cancer types and responsive individuals. Materials and methods: RNA-sequencing data for 10 080 patients and 33 different tumor types were derived from the TCGA and Leucegene datasets and completely re-processed. The study was carried out using machine learning methods and network analysis. Results: We profiled a large panel of breast-cancer cell-lines for in vitro sensitivity to ATRA and exploited the associated basal gene-expression data to initially generate a model predicting ATRA-sensitivity in this disease. Starting from these results and using a network-guided approach, we developed a generalized model (ATRA-21) whose validity extends to tumor types other than breast cancer. ATRA-21 predictions correlate with experimentally determined sensitivity in a large panel of cell-lines representative of numerous tumor types. In patients, ATRA-21 correctly identifies APL as the most sensitive acute-myelogenous-leukemia subtype and indicates that uveal-melanoma and low-grade glioma are top-ranking diseases as for average predicted responsiveness to ATRA. There is a consistent number of tumor types for which higher ATRA-21 predictions are associated with better outcomes. Conclusions: In summary, we generated a tumor-type independent ATRA-sensitivity predictor which consists of a restricted number of genes and has the potential to be applied in the clinics. Identification of the tumor types that are likely to be generally sensitive to the action of ATRA paves the way to the design of clinical studies in the context of these diseases. In addition, ATRA-21 may represent an important diagnostic tool for the selection of individual patients who may benefit from ATRA-based therapeutic strategies also in tumors characterized by lower average sensitivity.
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Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/genética , Tretinoina/uso terapéutico , Neoplasias de la Mama/patología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Línea Celular Tumoral , Femenino , Regulación Leucémica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/patología , Humanos , Leucemia Promielocítica Aguda/patología , Aprendizaje Automático , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/patología , Modelos Teóricos , Análisis de Secuencia de ARN , Neoplasias de la Úvea/tratamiento farmacológico , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/patologíaRESUMEN
The BRAVISSIMO study is a prospective, non-randomized, multi-center, multi-national, monitored trial, conducted at 12 hospitals in Belgium and 11 hospitals in Italy. This manuscript reports the findings up to the 12-month follow-up time point for both the TASC A&B cohort and the TASC C&D cohort. The primary endpoint of the study is primary patency at 12 months, defined as a target lesion without a hemodynamically significant stenosis on Duplex ultrasound (>50%, systolic velocity ratio no greater than 2.0) and without target lesion revascularization (TLR) within 12 months. Between July 2009 and September 2010, 190 patients with TASC A or TASC B aortoiliac lesions and 135 patients with TASC C or TASC D aortoiliac lesions were included. The demographic data were comparable for the TASC A/B cohort and the TASC C/D cohort. The number of claudicants was significantly higher in the TASC A/B cohort, The TASC C/D cohort contains more CLI patients. The primary patency rate for the total patient population was 93.1%. The primary patency rates at 12 months for the TASC A, B, C and D lesions were 94.0%, 96.5%, 91.3% and 90.2% respectively. No statistical significant difference was shown when comparing these groups. Our findings confirm that endovascular therapy, and more specifically primary stenting, is the preferred treatment for patients with TASC A, B, C and D aortoiliac lesions. We notice similar endovascular results compared to surgery, however without the invasive character of surgery.
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Arteria Ilíaca , Enfermedad Arterial Periférica/terapia , Stents , Adulto , Anciano , Anciano de 80 o más Años , Aleaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/patología , RecurrenciaRESUMEN
AIM: Although several randomized trial and monocentric study reported good results EVAR of abdominal aortic aneurysm (AAA), the long-term results of EVAR is still debated for the incidence of complication and the necessity of reintervention and or surgical conversion. The aim of the present study was to generate a score to grade the risk of reintervention/conversion after EVAR. METHODS: We present a five-year prospective study. All patients with AAA and treated by EVAR were inserted in the study. Patients with ruptured AAA or treated with fenestrated-graft or chimney technique were excluded from the analysis. The rates of reintervention, surgical conversion and aneurysm-related death were recorded at 6 months after the procedure. Complication predictors were analyzed and was generated a numeric score for all the variables to predict the patient individual risk. RESULTS: During the study period 976 EVAR procedures were successfully performed. No patients were lost during follow-up. We report 23 reinterventions (2.35%), the majority were performed electively. In six cases (0.61%) was performed conversion to surgical repair (1 graft infection, 3 for continuous growing of the aneurysmal sac and 2 cases for a ruptured AAA). In our experience, we report 4 deaths (0.4%) due to aneurysm rupture (1 case), acute myocardial infarction (2 cases) and colon cancer (1 case). The procedures were defined at low, moderate or high risk, respectively, according to whether the Siena EVAR Score was defined as EVAR1 (score <3), EVAR2 (3-6) or EVAR3 (>6). CONCLUSION: Our Score could be an useful tool to predict patients individual risk after EVAR but, to be validated, needs to be analyzed in independents cohorts in different Center.
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Aneurisma de la Aorta Abdominal/cirugía , Prótesis Vascular , Procedimientos Endovasculares/métodos , Anciano , Anciano de 80 o más Años , Angiografía , Aneurisma de la Aorta Abdominal/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Italia/epidemiología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Estudios Prospectivos , Reoperación/estadística & datos numéricos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de Tiempo , Tomografía Computarizada por Rayos X , Insuficiencia del TratamientoRESUMEN
All-trans retinoic acid (ATRA) is the only clinically useful differentiating agent, being used in the treatment of acute promyelocytic leukemia (APL). The use of ATRA in other types of acute myelogenous leukemia (AML) calls for the identification of novel strategies aimed at increasing its therapeutic activity. Here, we provide evidence that pharmacological inhibition of the mitogen-activated protein kinase, p38α, or silencing of the corresponding gene sensitizes APL and AML cell lines, as well as primary cultures of AML blasts to the anti-proliferative and cyto-differentiating activity of ATRA and synthetic retinoids. P38α inhibits ligand-dependent transactivation of the nuclear retinoic acid receptor, RARα, and the derived chimeric protein expressed in the majority of APL cases, PML-RARα. Inhibition is the consequence of ligand-independent binding of p38α, which results in stabilization of RARα and PML-RARα via blockade of their constitutive degradation by the proteasome. The inhibitory effect requires a catalytically active p38α and direct physical interaction with RARα and PML-RARα. Ser-369 in the E-region of RARα is essential for the binding of p38α and the ensuing functional effects on the activity of the receptor.
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Antineoplásicos/farmacología , Leucemia Mieloide Aguda/metabolismo , Proteína Quinasa 14 Activada por Mitógenos/metabolismo , Receptores de Ácido Retinoico/metabolismo , Retinoides/farmacología , Animales , Antineoplásicos/uso terapéutico , Diferenciación Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Chlorocebus aethiops , Regulación Leucémica de la Expresión Génica , Silenciador del Gen , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Ligandos , Ratones , Proteína Quinasa 14 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 14 Activada por Mitógenos/genética , Proteínas de Fusión Oncogénica/genética , Unión Proteica , Estabilidad Proteica , Receptores de Ácido Retinoico/genética , Receptor alfa de Ácido Retinoico , Retinoides/uso terapéutico , Transcripción GenéticaRESUMEN
All-trans retinoic acid (ATRA), the only clinically available cyto-differentiating agent, has potential for the therapy/chemoprevention of breast carcinoma. Given the heterogeneous nature of this tumor, a rational use of ATRA and derivatives (retinoids) in the clinic requires the identification of patients that would benefit from retinoid-based protocols. Here, we demonstrate that 23-32% of the human ERBB2(+) breast cancers show coamplification of retinoic acid receptor alpha (RARA), encoding the retinoic acid receptor, RARα. This represents a novel subtype of breast cancer characterized by remarkable sensitivity to ATRA and RARα agonists, regardless of positivity to the estrogen receptor, a known modulator of retinoid sensitivity. In estrogen-receptor-negative cellular models showing coamplification of ERBB2 and RARA, simultaneous targeting of the corresponding gene products with combinations of lapatinib and ATRA causes synergistic growth inhibition, cyto-differentiation and apoptosis. This provides proof-of-principle that coamplification of ERBB2 and RARA can be exploited for the stratified and targeted therapy of a novel subtype of breast cancer patients, with an approach characterized by tumor cell selectivity and low predicted toxicity. The available cellular models were exploited to define the molecular mechanisms underlying the antitumor activity of combinations between lapatinib and ATRA. Global gene expression and functional approaches provide evidence for three components of the antiproliferative/apoptotic responses triggered by lapatinib+ATRA. Induction of the retinoid-dependent RARRES3 protein by ATRA stabilizes the effect of lapatinib inhibiting ERBB2 phosphorylation. Upregulation and activation of the transcription factor FOXO3A integrates ATRA-dependent transcriptional and lapatinib-dependent posttranscriptional signals, controlling the levels of effector proteins like the antiapoptotic factor, BIRC5. Stimulation of the TGFß pathway by ATRA mediates other components of the apoptotic process set in motion by simultaneous targeting of ERBB2 and RARα.
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Antineoplásicos/farmacología , Neoplasias de la Mama/genética , Amplificación de Genes/efectos de los fármacos , Quinazolinas/farmacología , Receptor ErbB-2/genética , Receptores de Ácido Retinoico/genética , Tretinoina/farmacología , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Sinergismo Farmacológico , Proteína Forkhead Box O3 , Factores de Transcripción Forkhead/metabolismo , Humanos , Lapatinib , Fosforilación/efectos de los fármacos , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/metabolismo , Receptores de Ácido Retinoico/metabolismo , Receptor alfa de Ácido Retinoico , Proteína smad3/metabolismo , Transcripción Genética/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
OBJECTIVE: Reduced circulating adiponectin levels contribute to the aetiology of insulin resistance. Adiponectin circulates in three different isoforms: high molecular weight (HMW), medium molecular weight (MMW) and low molecular weight (LMW) isoforms. The genetics of adiponectin isoforms is mostly unknown. Our aim was to investigate whether and to which extent circulating adiponectin isoforms are heritable and whether they share common genetic backgrounds with insulin resistance-related traits. METHODS: In a family-based sample of 640 nondiabetic White Caucasians from Italy, serum adiponectin isoforms concentrations were measured by ELISA. Three single nucleotide polymorphisms (SNPs) in the ADIPOQ gene previously reported to affect total adiponectin levels (rs17300539, rs1501299 and rs677395) were genotyped. The heritability of adiponectin isoform levels was assessed by variance component analysis. A linear mixed effects model was used to test the association between SNPs and adiponectin isoforms. Bivariate analyses were conducted to study genetic correlations between adiponectin isoforms levels and other insulin resistance-related traits. RESULTS: All isoforms were highly heritable (h(2) = 0.60-0.80, P = 1.0 x 10(-13)-1.0 x 10(-23)). SNPs rs17300539, rs1501299 and rs6773957 explained a significant proportion of HMW variance (2-9%, P = 1.0 x 10(-3)-1.0 x 10(-5)). In a multiple-SNP model, only rs17300539 and rs1501299 remained associated with HMW adiponectin (P = 3.0 x 10(-4) and 2.0 x 10(-2)). Significant genetic correlations (P = 1.0 x 10(-2)-1.0 x 10(-5)) were observed between HMW adiponectin and fasting insulin, homeostasis model assessment of insulin resistance, HDL cholesterol and the metabolic syndrome score. Only rs1501299 partly accounted for these genetic correlations. CONCLUSION: Circulating levels of adiponectin isoforms are highly heritable. The genetic control of HMW adiponectin is shared in part with insulin resistance-related traits and involves, but is not limited to, the ADIPOQ locus.
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Resistencia a la Insulina/genética , Polimorfismo de Nucleótido Simple , Adiponectina/sangre , Adiponectina/química , Adiponectina/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Genotipo , Homeostasis , Humanos , Insulina/sangre , Italia/etnología , Masculino , Persona de Mediana Edad , Modelos Biológicos , Peso Molecular , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Población Blanca/genética , Adulto JovenAsunto(s)
Enfermedad de la Arteria Coronaria/genética , Diabetes Mellitus Tipo 2/genética , Angiopatías Diabéticas/genética , Proteínas Tirosina Fosfatasas Clase 2 Similares a Receptores/genética , Anciano , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo GenéticoRESUMEN
Several studies have indicated that proteasome inhibitors (PIs) are promising anticancer agents. We have discovered that PIs have the unique ability to activate effector caspases through a mitochondrial Bcl-2 inhibitable but caspase-9 independent pathway. Stabilization of released Smac induced by blockade of the proteasome could explain the apoptosome-independent cell death induced by PIs. In fact, Smac/DIABLO critically supports this PIs-dependent caspase activation. By using a new assay, we confirm that at a single cell level both Smac and PIs can activate caspases in the absence of the apoptosome. Moreover, we have observed two PIs-induced kinetics of caspase activation, with caspase-9 being still required for the rapid caspase activation in response to mitochondrial depolarization, but dispensable for the slow DEVDase activation. In summary, our data indicate that PIs can activate downstream caspases at least in part through Smac/DIABLO stabilization.
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Apoptosis , Inhibidores Enzimáticos/farmacología , Inhibidores de Proteasoma , Animales , Proteínas Reguladoras de la Apoptosis , Western Blotting , Proteínas Portadoras , Caspasa 9 , Caspasas/metabolismo , Muerte Celular , Citocromos c/metabolismo , Citosol/metabolismo , Activación Enzimática , Etopósido/farmacología , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Procesamiento de Imagen Asistido por Computador , Péptidos y Proteínas de Señalización Intracelular , Cinética , Potenciales de la Membrana , Microscopía Confocal , Microscopía Fluorescente , Mitocondrias/metabolismo , Proteínas Mitocondriales , Plásmidos/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Interferente Pequeño/metabolismo , Retroviridae/genética , Factores de Tiempo , TransfecciónRESUMEN
Mammalian caspases are a family of cysteine proteases that plays a critical role in apoptosis. We have analyzed caspase-2 processing in human cell lines containing defined mutations in caspase-3 and caspase-9. Here we demonstrate that caspase-2 processing, during cell death induced by UV irradiation, depends both on caspase-9 and caspase-3 activity, while, during TNF-alpha-dependent apoptosis, capase-2 processing is independent of caspase-9 but still requires caspase-3. In vitro procaspase-2 is the preferred caspase cleaved by caspase-3, while caspase-7 cleaves procaspase-2 with reduced efficiency. We have also demonstrated that caspase-2-mediated apoptosis requires caspase-9 and that cells co-expressing caspase-2 and a dominant negative form of caspase-9 are impaired in activating a normal apoptotic response and release cytochrome c into the cytoplasm. Our findings suggest a role played by caspase-2 as a regulator of the mitochondrial integrity and open questions on the mechanisms responsible for its activation during cell death.
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Apoptosis/fisiología , Caspasas/genética , Caspasas/metabolismo , Muerte Celular/fisiología , Regulación Enzimológica de la Expresión Génica/efectos de la radiación , Factor de Necrosis Tumoral alfa/farmacología , Rayos Ultravioleta , Sustitución de Aminoácidos , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Caspasa 2 , Caspasa 3 , Caspasa 7 , Caspasa 9 , Muerte Celular/efectos de los fármacos , Muerte Celular/efectos de la radiación , Línea Celular , Femenino , Fibroblastos , Técnica del Anticuerpo Fluorescente Indirecta , Regulación Enzimológica de la Expresión Génica/fisiología , Biblioteca de Genes , Humanos , Mamíferos , Mutagénesis Sitio-Dirigida , Proteínas Recombinantes/metabolismo , TransfecciónRESUMEN
Gas2 is a caspase-3 substrate that plays a role in regulating microfilament and cell shape changes during apoptosis. Here we provide evidence that overexpression of Gas2 efficiently increases cell susceptibility to apoptosis following UV irradiation, etoposide and methyl methanesulfonate treatments, and that these effects are dependent on increased p53 stability and transcription activity. To investigate possible pathways linking Gas2 to p53, a yeast two-hybrid screen swas performed, indicating m-calpain as a strong Gas2- interacting protein. Moreover, we demonstrate that Gas2 physically interacts with m-calpain in vivo and that recombinant Gas2 inhibits calpain-dependent processing of p53. Importantly, the Gas2 dominant-negative form (Gas2171-314) that binds calpain but is unable to inhibit its activity abrogates Gas2's ability to stabilize p53, to enhance p53 transcriptional activity and to induce p53-dependent apoptosis. Finally, we show that Gas2 is able to regulate the levels of p53 independently of Mdm2 status, suggesting that, like calpastatin, it may enhance p53 stability by inhibiting calpain activity.
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Apoptosis/fisiología , Calpaína/metabolismo , Proteínas de Microfilamentos/metabolismo , Transcripción Genética , Proteína p53 Supresora de Tumor/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Calpaína/genética , Línea Celular , Supervivencia Celular , Etopósido/farmacología , Genes Reporteros , Humanos , Luciferasas/genética , Metilmetanosulfonato/farmacología , Ratones , Ratones Endogámicos BALB C , Osteosarcoma , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae , Eliminación de Secuencia , Transfección , Células Tumorales Cultivadas , Rayos UltravioletaRESUMEN
After a brief introduction about carotid body tumor's etiopathogenesis and clinical presentation, four clinical cases observed between January 1996 and December 1998 are described. Three of them have been classified as I and the last as III type according to Shamblin's classification. The diagnostic trial and surgical option needed by each patient are presented. The surgical treatment and the possibility of alternative or complementary techniques such as endovascular embolization and/or irradiation are discussed. The conclusion is drawn that surgical option for carotid body tumor is the best choice. Embolization, some hours before surgical treatment, can be a very useful procedure in order to reduce intraoperative risks and bleeding. Nevertheless surgery of carotid body tumor must be performed by surgical teams experienced in supra-aortic vessel treatment.
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Tumor del Cuerpo Carotídeo/patología , Adulto , Arteria Carótida Común/diagnóstico por imagen , Tumor del Cuerpo Carotídeo/complicaciones , Tumor del Cuerpo Carotídeo/diagnóstico , Tumor del Cuerpo Carotídeo/cirugía , Terapia Combinada , Diagnóstico Diferencial , Embolización Terapéutica , Femenino , Humanos , Hipertensión/etiología , Complicaciones Intraoperatorias , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , RadiografíaRESUMEN
We have identified phosphodiester oligonucleotides composed of G and T bases, named GTn, which are able to inhibit the cellular growth of human cancer cell lines by recognising specific nuclear proteins. We demonstrated that GTn oligonucleotides require a length of at least 20 nucleotides in order to exert a significant cytotoxic effect and to retain the specific protein binding ability. In addition, we found that GTn cytotoxicity was lost when A or C bases were introduced at either 3' and 5' end or within the GTn sequences.
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Proteínas Nucleares/metabolismo , Oligonucleótidos/metabolismo , Biopolímeros , Humanos , Células Tumorales CultivadasRESUMEN
We have demonstrated previously that the GT triplex-forming oligodeoxyribonucleotide (TFO) d(TGTGTTTTTGTTTTGTTGGTTTTGTTT), named TFO ID, targeted to a polypyrimidine-polypurine coding sequence located within human multidrug-resistance mdrl gene, specifically and significantly reduced mdrl mRNA levels in the drug-resistant T-leukemic CEM-VLB100 cell line. In this article, we demonstrate that TFO 1D is effective at inhibiting not only transcription but also replication of mdrl genes, leading to a loss of amplified gene copies in the drug-resistant colon adenocarcinoma LoVo DX cell line. In contrast, TFO ID does not alter replication of the constitutive mdrl gene copy in the corresponding parental sensitive LoVo 109 cell line. A specific reduction in mdrl gene amplification levels was also obtained with the pyrimidine TFO d(CTTTTTCTTTTCTTCCTTTTCTTT), named TFO 24TC, directed against the same polypyrimidine-polypurine sequence of the mdrl gene. We suggest that triple helix-forming oligonucleotides might affect the replication of unstable chromosomal elements as amplicons in actively replicating cells by causing a local impairment of DNA polymerase activity. This study lends support to the notion that TFO may be used to reduce gene amplification aiming to control neoplastic progression in cancer cells bearing amplified oncogenes.
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ADN/biosíntesis , Resistencia a Múltiples Medicamentos/genética , Genes MDR , Oligodesoxirribonucleótidos/farmacología , Secuencia de Bases , Southern Blotting , Humanos , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células Tumorales CultivadasRESUMEN
The authors analyze their experience of surgical treatment of post-mastectomy lympho-edemas of the upper arm. They have performed 14 operations, each upon patients with praecox or later oedema, following Cariati's classification, and with median age of 56.5 years. Seven patients were present at the follow-up in 6 has been performed microsurgical lympho-venous anastomosis, in 1 a fasciotomy of the forearm and in 1 patient some silastic tubes were positioned in her subcutaneous tissue. An improvement of the subjective symptoms has been recorded in 57.14% of the patients, while the objective ones have improved in 50% of the patients. The authors think that the microsurgical treatment of the lymphedema post-mastectomy of the upper arm is the first choice nowadays.
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Brazo , Linfedema/cirugía , Mastectomía/efectos adversos , Adulto , Anciano , Drenaje , Fasciotomía , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Elastómeros de Silicona , Factores de TiempoAsunto(s)
Cateterismo Venoso Central/métodos , Electrocardiografía , Diálisis Renal/métodos , Femenino , Humanos , MasculinoRESUMEN
A case of open segmental fracture of the right lower leg treated with an Ilizarov external fixator in emergency surgery is presented. Approximately two months after operation, swelling in the anterior compartment of the tibia and repeated episodes of bleeding from one of the Kirschner wire holes led the authors to perform an angiography, which revealed the presence of a false aneurysm of the anterior tibial artery. The intraoperative finding of a double lesion in the anterior tibial artery confirmed the iatrogenous nature of the injury.
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Aneurisma Falso/etiología , Fijadores Externos/efectos adversos , Fracturas del Fémur/cirugía , Arterias Tibiales , Fracturas de la Tibia/cirugía , Anciano , Aneurisma Falso/diagnóstico por imagen , Fracturas del Fémur/diagnóstico por imagen , Humanos , Masculino , Radiografía , Arterias Tibiales/diagnóstico por imagen , Fracturas de la Tibia/diagnóstico por imagenRESUMEN
A miniaturized (3.5 F), six-electrode conductance catheter was tested in 18 anaesthetized adult rabbits (weight 3.8-4.6 kg, ethylurethane 2.5 g kg-1). In eight animals, the reference stroke volume (ref-SV) was obtained by an electromagnetic flow probe, while reference end-diastolic volume (ref-LVEDV) was computed by dividing ref-SV by undamped thermal dilution ejection fraction (ref-EF) estimates. Comparisons with conductance indexes (z-SV, z-LVEDV and z-EF) were made at baseline, subsequent levels of graded haemorrhage and reinfusion state. In 10 animals intraventricular segmental conductance was compared with echocardiographic left ventricular cross-section (5 MHz short-focus probe), in the basal state and during acute left ventricular volume changes generated by inferior vena cava balloon occlusion. In each experiment, parallel conductance due to the tissues surrounding the left ventricle (Gp) was determined by infusing a 5M NaCl solution bolus into the right ventricle. Linear regression analysis showed fairly good correlations between z-SV, z-LVEDV and z-EF and reference indexes (r = 0.84, r = 0.83, and r = 0.72, respectively; P less than 0.001 in all cases). A linear regression analysis from 17 interventions (inferior vena cava balloon occlusion) showed a good correlation between left ventricular echocardiographic cross-sectional area and conductance, and higher correlation coefficients, r ranging from 0.870 to 0.986 were obtained from continuously sampled conductance and echographic measurements. Parallel conductance Gp was correlated (r = 0.807, P less than 0.01) with the intercept of the regression line of echographic vs conductance data. The determination of Gp thus improved the accuracy of the left ventricular dimension estimate. These results add further evidence for the possibility of continuous monitoring of left ventricular dimension by means of a conductance catheter, and demonstrate the feasibility of such studies on small experimental animals.
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Cateterismo Cardíaco/métodos , Ventrículos Cardíacos/anatomía & histología , Volumen Sistólico , Animales , Cateterismo de Swan-Ganz , Ecocardiografía , Conductividad Eléctrica , Conejos , Análisis de Regresión , TermodiluciónRESUMEN
A radioisotopic method was used to evaluate the state and dynamics of the lymphatic system in 92 patients affected by chronic oedema of the limbs and in 12 control subjects. After interstitial injections of 99mTc-sulphur microcolloid, scans were obtained using a LFOV camera linked to a data processor. The quantitative indices of clearance and lymph node uptake obtained showed good correlation with lymphoedema etiology, controls and ostensibly healthy limbs of patients affected by monolateral disease. In conclusion, quantitative lymphoscintigraphy appears to be a feasible indicator of early changes in the lymph pathophysiology and supports the hypothesis that lymphoedema generally arises from a predisposing congenital pathology.
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Linfocintigrafia , Adolescente , Adulto , Anciano , Niño , Extremidades , Femenino , Humanos , Linfedema/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Azufre Coloidal Tecnecio Tc 99mRESUMEN
The aim of this work has been the study of the mechanism of lymph formation and drainage in the upper limb in patients with monolateral lymphoedema (15 limbs, L) in comparison with the apparently healthy limb (S) as well as with a control group (8 limbs, C). After interstitial injection of 99mTc sulphur micro-colloid, scans were obtained employing a LFOV camera linked to a data processor. Results were expressed as percentage of the id removed from the injection site 1 and 6 hr pi, mean T6%/h it is (T6-T1)/5 and percentage lymph nodes uptake at the same times. Mean T6%/h is significantly different between C and L, but not between L and S, while lymph node uptake at 6 hr shows a significant difference even between C and S. Quantitative lymphoscintigraphy appears to be a feasible indicator of early changes in the lymph pathophysiology and supports the hypothesis that lymphoedema generally arises from a predisposing congenital pathology.